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  • Digitale Medien  (461)
  • 1995-1999  (461)
  • 1965-1969
  • 1890-1899
  • 1999  (461)
  • Magnetic resonance imaging  (144)
  • breast cancer  (126)
  • Immunohistochemistry  (100)
  • Apoptosis  (93)
Datenquelle
Materialart
  • Digitale Medien  (461)
Erscheinungszeitraum
  • 1995-1999  (461)
  • 1965-1969
  • 1890-1899
Jahr
Schlagwörter
  • 1
    Digitale Medien
    Digitale Medien
    Use of vector volume manometry and endoanal magnetic resonance imaging in the adult female for assessment of anal sphincter dysfunction (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 1411-1418 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Endoanal ; Magnetic resonance imaging ; Vector volume ; Manometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: This study compared conventional water-perfused and vector volume anal manometry in female patients with neurogenic fecal incontinence and chronic anal fissure and in healthy female volunteers. We used endoanal magnetic resonance (MR) imaging to measure internal and external sphincter lengths and thicknesses and contrasted these with the manometric findings in the different anorectal conditions. METHODS: One hundred thirty-three female subjects were studied over an eight-month period, including 33 control volunteers, 83 patients with neurogenic fecal incontinence, and 17 patients with chronic anal fissure. Conventional manometry was contrasted with automated vector volume-derived parameters. Endoanal magnetic resonance images were obtained using a previously described internal coil with a 0.5 T Asset™ scanner measuring quadrantal internal sphincter thickness and averaged coronal internal and external sphincter lengths. RESULTS: There was a statistically significant relationship between parameters measured by conventional manometry and those variables derived from vector volume manometry at rest and squeeze. There was no difference in sectorial vector-derived pressures within any anorectal condition and no correlation between quadrantal internal sphincter thickness measurements and sectorial pressures at rest. Patients with chronic anal fissure and neurogenic fecal incontinence had constitutionally shorter superficial and subcutaneous external sphincters than healthy control subjects (P〈0.001). CONCLUSIONS: There is no association between manometric findings and morphologic sphincter measurement; however, the shorter distal external sphincter in patients with fissure might render the lower anal canal relatively unsupported after internal sphincterotomy in the female patient.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02235038
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  • 2
    Digitale Medien
    Digitale Medien
    Gemcitabine-Induced Programmed Cell Death (Apoptosis) of Human Pancreatic Carcinoma Is Determined by Bcl-2 Content (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 279-285 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Gemcitabine ; bcl-2 ; Pancreatic cancer ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Gemcitabine is a new nucleoside analogue that produces a clinical response in 30% of patients with unresectable pancreatic carcinoma. The cytotoxic effects of many chemotherapeutic agents occur through induction of programmed cell death (apoptosis), which is controlled by the bcl-2 gene family. We determined whether induction of apoptosis by gemcitabine in pancreatic carcinoma is associated with cellular Bcl-2 content. Methods: Four pancreatic carcinoma cell lines (MIA-PaCa-2, AsPC-1, Panc-1, and Panc-48) were screened by Western blotting for Bcl-2 protein expression. Dose-response relationships for the cytotoxic effects of gemcitabine were determined using methylthiotetrazole assays, and induction of apoptosis was confirmed by fluorescence-activated cell sorting analysis. MIA-PaCa-2 cells transfected with human bcl-2 were also analyzed for gemcitabine-induced apoptosis. Results: Pancreatic cancer cell lines expressed varying amounts of Bcl-2, and the 50% lethal dose for gemcitabine-induced apoptosis was correlated with Bcl-2 content. Furthermore, Bcl-2 overexpression was associated with a significant increase in the 50% lethal dose for gemcitabine-induced apoptosis. Conclusions: Cellular Bcl-2 content was directly correlated with the cytotoxicity of gemcitabine in pancreatic carcinoma. Therefore, routine immunohistochemical analyses may be useful in predicting gemcitabine efficacy, and patients who would likely not benefit could be spared gemcitabine administration. Furthermore, the effectiveness of gemcitabine and other chemotherapeutic agents may be increased by gene therapy-mediated alteration of bcl-2 gene family members.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0279-x
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  • 3
    Digitale Medien
    Digitale Medien
    p21Waf1/Cip1 Expression Is a Prognostic Marker in Curatively Resected Esophageal Squamous Cell Carcinoma, but Not p27Kip1, p53, or Rb (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 481-488 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Esophageal cancer ; Treatment ; Prognosis ; Cell cycle ; Immunohistochemistry ; Cyclin-dependent kinases inhibitor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). Methods: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. Results: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. Conclusions: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0481-x
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  • 4
    Digitale Medien
    Digitale Medien
    Angiogenesis Correlates With Metastasis in Melanoma (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 70-74 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Angiogenesis ; Melanoma ; Metastasis ; Immunohistochemistry ; Microvessels.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Angiogenesis has been correlated with melanoma progression, but its role in melanoma metastasis is unclear. Methods: To determine whether angiogenesis correlates with the presence of melanoma metastases, we compared the number of microvessels in the primary melanomas of 12 patients presenting with metastases to those of 13 patients without metastases. Patient groups were matched for gender, age, tumor depth, and histological type and anatomical location of the primary melanoma. Microvessels were stained with factor VIII antibody and counted. Results: Microvessel counts were significantly greater for the metastatic than the nonmetastatic melanomas (51.63 ± 14.95 vs. 24.86 ± 8.415; P 〈 .0001). One hundred percent of the metastatic melanomas had a mean microvessel count of ≥ 37, whereas only 8% of the nonmetastatic melanomas had a mean microvessel count of ≥ 37 (sensitivity = 1.00, specificity = .92). Interestingly, patients with lymph node metastases had significantly lower microvessel counts than did patients with distant metastases (42.00 ± .482 vs. 58.50 ± 16.40; P 〈 .05), and significantly higher microvessel counts than did patients without metastases (42.00 ± 3.482 vs. 24.86 ± 8.415; P 〈 .001). Conclusions: An increased number of microvessels in the primary tumors of patients with melanoma correlates with the simultaneous presence of metastases. This suggests that angiogenesis may be important in the process of melanoma metastasis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0070-z
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  • 5
    Digitale Medien
    Digitale Medien
    p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 739-745 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Gastric cancer ; Intestinal/diffuse histotype ; P53 ; Immunohistochemistry ; Prognostic factors ; Multivariate analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer. Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis. Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P 〈 .05), confirmed by multivariate analysis (P 〈 .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression. Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0739-3
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  • 6
    Digitale Medien
    Digitale Medien
    Distribution of carcinoembryonic antigen and biologic behavior in colorectal carcinoma (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 640-648 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Carcinoembryonic antigen ; Colorectal neoplasms ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: Carcinoembryonic antigen is assumed from the results of several experiments to be associated with invasion of colorectal carcinoma by adhesion or contact inhibition. The patterns and the intensity of carcinoembryonic antigen distribution in colorectal carcinoma were assessed to verify whether they were correlated with malignant potential from those biologic characteristics. METHODS: Carcinoembryonic antigen distribution was tested in the archival samples of 149 colorectal carcinomas by immunohistochemistry, using three characterized anti-carcinoembryonic antigen monoclonal antibodies: T84.66, PR1A3, and PR3B10. The distribution patterns in neoplastic tissue were categorized into unstained, apicoluminal, and diffuse-cytoplasmic patterns. Tumor, invasive tumor margin, and tissue surrounding the tumor were examined. RESULTS: Although all three antibodies revealed a positive correlation, T84.66 showed better discrimination than the others. Although none of the negative staining of the tumor or invasive tumor margin showed recurrence, the apicoluminal pattern showed recurrence, and the diffuse pattern showed the most frequent recurrence (P〈0.01). Recurrence was also associated with staining intensity in the apicoluminal pattern in both the tumor and invasive tumor margin (P〈0.05). Infiltrative tumor growth and lymph node metastasis were more frequent in cases of positive staining in tissue surrounding the tumor. Patients with the apicoluminal pattern achieved longer survival than patients with the diffuse-cytoplasmic pattern in the invasive tumor margin (P=0.024) by a multivariate analysis including tumor stage and histologic differentiation. CONCLUSION: The distribution of carcinoembryonic antigen in tumors and surrounding tissue seems to be closely correlated with invasiveness and metastatic behavior in colorectal carcinoma. Carcinoembryonic antigen immune staining can be considered as an efficient tool to determine groups with risk of recurrence.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02234143
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  • 7
    Digitale Medien
    Digitale Medien
    Sentinel Node Metastasis in Patients with Breast Carcinoma Accurately Predicts Immunohistochemically Detectable Nonsentinel Node Metastasis (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 756-761 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Breast carcinoma ; Sentinel node ; Axillary lymphadenectomy ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Sentinel lymphadenectomy is highly accurate for identifying axillary metastasis from a primary breast carcinoma. Nonsentinel axillary lymph nodes (NSNs) are unlikely to contain tumor cells if the axillary sentinel node (SN) is tumor free. We previously showed that the size of the primary tumor and the size of its SN metastasis predict the risk of NSN tumor involvement detected by hematoxylin and eosin staining. This study used immunohistochemical staining (IHC) to determine the likelihood of NSN axillary metastasis in the presence of SN metastasis. Methods: Between 1991 and 1997, axillary lymphadenectomy was performed in 156 women (157 axillary basins) who had primary breast carcinoma with SN metastasis. By hematoxylin and eosin staining, we identified NSN metastasis in 55 axillae (35%). IHC was then used to re-examine all NSNs (1827 lymph nodes) from the remaining 102 axillae. The incidence of IHC-detected NSN involvement was analyzed with respect to clinical and tumor characteristics. Results: By using IHC, we identified NSN metastasis in 15 (14.7%) of the 102 axillae. By multivariate analysis, the size of the SN metastasis (P = .0001) and the size of the primary tumor (P = .038) were the only independent variables predicting NSN metastasis determined by using either hematoxylin and eosin staining or IHC. Only the number of SN metastases (1 vs. 〉1) was a significant (P = .04) predictor of IHC-detected NSN metastasis. Conclusions: Use of IHC increases the likelihood of detection of NSN metastasis, and the risk of IHC-detected metastasis increases with the size of the SN metastasis and the size of the primary tumor. If SN involvement is micrometastatic (≤2 mm) or detected by using IHC, tumor cells are unlikely to be found in other axillary lymph nodes in patients with a small primary tumor. The clinical significance of micrometastatic disease in lymph nodes is controversial, and a prospective randomized study is necessary to resolve this important issue.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0756-2
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  • 8
    Digitale Medien
    Digitale Medien
    Comparative study of transrectal ultrasonography, pelvic computerized tomography, and magnetic resonance imaging in preoperative staging of rectal cancer (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 770-775 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Rectal cancer ; Transrectal ultrasonography ; Computerized tomography ; Magnetic resonance imaging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: The preoperative assessment of rectal cancer wall invasion and regional lymph node metastasis is essential for the planning of optimal therapy. This study was done to determine the accuracy and clinical usefulness of transrectal ultrasonography, pelvic computed tomography, and magnetic resonance imaging in preoperative staging. METHODS: A total of 89 patients with rectal cancer were examined with transrectal ultrasonography (n=89), pelvic computed tomography (n=69), and magnetic resonance imaging with endorectal coil (n=73). The results obtained by these diagnostic modalities were compared with the histopathologic staging of specimens. RESULTS: In staging depth of invasion, the overall accuracy was 81.1 percent (72/89) by transrectal ultrasonography, 65.2 percent (45/69) by computed tomography, and 81 percent (59/73) by magnetic resonance imaging. Overstaging was 10 percent (9/89) by transrectal ultrasonography, 17.4 percent (12/69) by computed tomography, and 11 percent (8/73) by magnetic resonance imaging; and understaging was 8 of 89 (8.9 percent) by transrectal ultrasonography, 12 of 69 (17.4 percent) by computed tomography, and 6 of 73 (8 percent) by magnetic resonance imaging. In staging lymph node metastasis, the overall accuracy rate was 54 of 85 (63.5 percent) in transrectal ultrasonography, 39 of 69 (56.5 percent) in computed tomography, and 46 of 73 (63 percent) in magnetic resonance imaging. The sensitivity was 24 of 45 (53.3 percent) in transrectal ultrasonography, 14 of 25 (56 percent) in computed tomography, and 33 of 42 (78.5 percent) in magnetic resonance imaging; and specificity was 30 of 40 (75.0 percent) in transrectal ultrasonography, 25 of 44 (56.8 percent) in computed tomography, and 13 of 31 (41.9 percent) in magnetic resonance imaging. The accuracy in detection of positive lateral pelvic lymph nodes under magnetic resonance imaging (n=8) was 12.5 percent. The accuracy in detection of posterior vaginal wall invasion was 100 percent in transrectal ultrasonography (n=7) and 100 percent in magnetic resonance imaging (n=3), but 28.5 percent in computed tomography (n=7). CONCLUSIONS: Both transrectal ultrasonography and magnetic resonance imaging with endorectal coil exhibited similar accuracy and were superior to conventional computed tomography in preoperative assessment of depth of invasion and adjacent organ invasion. Because transrectal ultrasonography is a safer and more cost-effective modality than magnetic resonance imaging, transrectal ultrasonography is an appropriate method for preoperative staging of rectal cancer. Further efforts will be needed to provide a better staging of lymph node involvement.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02236933
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  • 9
    Digitale Medien
    Digitale Medien
    Effects of Experimental Chemoendocrine Therapy With a Combination of a Pure Antiestrogen and 5-Fluorouracil on Human Breast Cancer Cells Implanted in Nude Mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Schlagwort(e): Key Words: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s005950050376
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  • 10
    Digitale Medien
    Digitale Medien
    Wirbelsäulen- und Beckenfrakturen im Wachstumsalter (1999)
    Springer
    Trauma und Berufskrankheit 1 (1999), S. S92 
    Details
    ISSN: 1436-6274
    Schlagwort(e): Schlüsselwörter Wachstumsalter ; MRI ; Beckenfraktur ; Wirbelsäulenfraktur ; Key words Childhood ; Magnetic resonance imaging ; Pelvic fracture ; Spinal injury
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Abstract According to the literature, from 1950 to 1995 the overall risk for children of sustaining a fracture of the spinal column or the pelvic ring doubled, the main reason being the increasing incidence of high-energy trauma caused by newly popular sporting activities such as skateboarding, inline skating and mountain biking. Nonetheless, even specialized pediatric level I trauma centers in Europe and the United States of America report an incidence of below 5% for severe spinal injuries and fractures of the pelvis. Although these specific injury patters are seen relatively infrequently, whenever present they are still highly indicative of high-velocity injury mechanisms, frequently revealing a combination of injuries – each of which would be serious in itself – involving the body cavities and the soft tissues of the trunk an extremities. In summary, spinal cord injuries and pelvic ring fractures are rare but can be serious: cervical and spinal cord injuries without radiological abnormality appear to be more frequent than in adults, and the availability of nuclear magnetic imaging technologies has helped in the diagnosis of unsuspected cord injury in children. In addition, retrospective analysis of purely nonoperative management of highly unstable C-type injuries of the spine and the pelvic ring reveal some unsatisfactory results, so that specifically for these injury morphologies the alternative of an operative strategy might be considered. The purpose of this presentation is to discuss various injury patterns in which an operative concept could be considered, particularly for a multiply injured child.
    Notizen: Zusammenfassung Verletzungen des Rückenmarks und Sprengungen des knöchernen Beckenrings liegen im Kindesalter auch im Krankengut spezialisierter Zentren unter 5%. Besonders beachtenswert erscheint hierbei, daß Rückenmark- und besonders Halswirbelsäulenverletzungen v. a. beim Kind häufig keine ossäre Mitbeteiligung der Wirbelsäule zeigen und erst durch kernspintomographische Diagnostik erfaßt werden können. Desgleichen zeigt sich bei der retrospektiven Auswertung, daß ein pauschales, rein konservatives Management aller Verletzungstypen, d. h. v.a. der sog. C-Verletzungstypen an der Wirbelsäule und am Becken, z. T. unbefriedigende Behandlungsergebnisse zeigt und daher zunehmend bei bestimmten, im weiteren näher besprochenen Verletzungskonstellationen ein eher operatives Grundkonzept diskutiert wird. Neue Erkenntnisse zur Diagnostik und Therapie der Wirbelsäulen- und Beckenverletzung beim Kind liegen insofern vor, als 1. neuere epidemiologische Erhebungen heute eine präzisere, d. h. nicht nur empirisch gesicherte Unterscheidung der selten von eher regelmäßig anzutreffenden Verletzungstypen und Frakturmorphologien erlauben, 2. durch vergleichsweise „neue“ Sportarten wie „Scate-boarding“ und „Mountain-biking“ ganz generell eine statistisch belegte Zunahme von Hochrasanztraumen und komplexen Verletzungsmustern beim Kind beobachtet werden kann sowie 3. generell v.a. beim mehrfachverletzten Kind heute eine eher aggressivere Gangart, d. h. ein in bestimmten Einzelaspekten eher operatives Versorgungskonzept angestrebt wird. Gegenstand der vorliegenden Arbeit sind 1. eine Analyse der als besonders bedeutsam erkannten Verletzungsformen sowie 2. eine Darstellung der heute in Veränderung begriffenen Behandlungskonzepte v.a. beim mehrfachverletzten Kind.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00014858
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  • 11
    Digitale Medien
    Digitale Medien
    Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Schlagwort(e): chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02482240
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  • 12
    Digitale Medien
    Digitale Medien
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older (1999)
    Springer
    Annals of oncology 10 (1999), S. 397-402 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; old age ; vinorelbine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women ≥60 years old. Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent. Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008364222793
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  • 13
    Digitale Medien
    Digitale Medien
    Radiation-induced rhombencephalopathy (1999)
    Springer
    Italian journal of neurological sciences 20 (1999), S. 55-58 
    Details
    ISSN: 1126-5442
    Schlagwort(e): Key words Rhombencephalopathy ; Radionecrosis ; Magnetic resonance imaging ; Hyperbaric oxygen ; Heparin ; Buspirone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report the case of a patient who underwent radiotherapy of the neck because of an epidermoid carcinoma in Rosenmüller's fossa. Eleven months later, T1-weighted brain magnetic resonance imaging (MRI) revealed a bulbo-pontine lesion, and the clinical course and sequential MRI results led to a diagnosis of radionecrosis-induced rhombencephalopathy. At a distance of more than three years, the lesion is no longer visible on MRI images but the severe neurological deficits remain. The clinical picture has not been improved by treatment with prednisone, hyperbaric oxygen, symptomatic therapies or anticoagulants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s100720050011
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  • 14
    Digitale Medien
    Digitale Medien
    Psychiatric symptoms as late onset of Wilson's disease: neuroradiological findings, clinical features and treatment (1999)
    Springer
    Italian journal of neurological sciences 20 (1999), S. 49-54 
    Details
    ISSN: 1126-5442
    Schlagwort(e): Key words Hepatolenticular degeneration ; Affective disorders ; Magnetic resonance imaging ; Antidepressive agents ; Interpersonal psychotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We describe a case of Wilson's disease with late psychiatric onset. Major depressive disorder was the first clinical manifestation at the age of 38 years. After pharmacotherapy with antidepressive agents, a manic episode was oberseved. Extrapyramidal hand tremor and micrography were the first neurological signs. Emotional lability occurred during worsening of extrapyramidal signs. Diagnosis was based on urinary and serum copper levels, ceruloplasmin serum level, Kayser-Fleischer ring, and liver biopsy that detected cirrhosis. Magnetic resonance imaging revealed basal ganglia hyperintensity on T1-weighted images, and hypodensity in the central part and hyperintensity in the peripheral part of the lentiform nucleus on 72-weighted images. Hyperintensity on T2-weighted images was also observed in the dorsal part of the midbrain. 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) detected a normal distribution of the drug in the brain, with better signal in the right side and deficit of D2-dopaminergic receptors in the basal ganglia, Abnormal manganese erythrocyte level was observed. Treatment was based on penicillamine, zinc salts, low-copper diet, antidepressant agents, interpersonal psychotherapy and neurorehabilitation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s100720050010
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  • 15
    Digitale Medien
    Digitale Medien
    Soft-tissue signs of the upper extremity revisited: radiologic and magnetic resonance imaging correlation (1999)
    Springer
    Emergency radiology 6 (1999), S. 282-289 
    Details
    ISSN: 1438-1435
    Schlagwort(e): Key words Radiology ; Computed tomography ; Magnetic resonance imaging ; Soft-tissue sign ; Arm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract More modern imaging techniques allow us to supplement the information available on soft-tissue signs seen on radiographs. This improves our diagnostic capability, as demonstrated here in the upper extremity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101400050069
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  • 16
    Digitale Medien
    Digitale Medien
    MR imaging of a severe cervical fracture-dislocation after traumatic delivery (1999)
    Springer
    Emergency radiology 6 (1999), S. 143-145 
    Details
    ISSN: 1438-1435
    Schlagwort(e): Key words Spinal cord ; Birth injury ; Magnetic resonance imaging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We present the acute MR findings in an infant with a complicated traumatic delivery, asphyxia, spinal cord injury, and a radiographically apparent cervical spine fracture-dislocation. MRI including diffusion-weighted imaging allowed early characterization and localization of the extent of spinal cord injury.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101400050040
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  • 17
    Digitale Medien
    Digitale Medien
    Bifocal temporal ganglioglioma (1999)
    Springer
    Neurosurgical review 22 (1999), S. 112-116 
    Details
    ISSN: 1437-2320
    Schlagwort(e): Key words Ganglioma ; Brain tumor ; Magnetic resonance imaging ; Epilepsy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The authors present the case of a 33-year-old patient with a bifocal ganglioglioma located in the right superior temporal gyrus. He had a history of tonic–clonic seizures and developed intermittent nausea and vertigo later on. Magnetic resonance imaging showed two distinct, small lesions in the right temporal lobe. Both tumors were removed microsurgically with ultrasound guidance. Intraoperatively, two distinct tumors were found. Histological diagnosis of both tumors was of ganglioglioma WHO II. Postoperatively, the patient was free of symptoms. Bifocal occurrence or the coincidence of two distinct gangliogliomas is a very uncommon finding. So far, it has not yet been reported in benign gangliogliomas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101430050042
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  • 18
    Digitale Medien
    Digitale Medien
    Multiple spinal “miliary” hemangioblastomas in von Hippel-Lindau (vHL) disease without cerebellar involvement (1999)
    Springer
    Neurosurgical review 22 (1999), S. 130-134 
    Details
    ISSN: 1437-2320
    Schlagwort(e): Key words Von Hippel-Lindau disease (vHL) ; Multiple spinal hemangioblastomas ; vHL protein ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report on a 57-year-old male presenting with radicular pain in the nerve roots of L5 and S1 on the right side and dysuria. Magnetic resonance imaging (MRI) of the lumbar spine showed multiple (up to 20) small, intradural enhancing nodules attached to the cauda equina down to the sacrum, the largest 1 cm in diameter at the level Th12/ L1 compressing the conus. Additionally, small nodules in the cervico-thoracal region adjacent to the cord, but no cerebellar or cerebral abnormalities, were detected in a consecutive MRI of the remaining neuroaxis. The histology of a resected lesion at Th12/L1 revealed hemangioblastoma of the reticular type. Together with a history of left eye enucleation performed 17 years ago for angiomatosis of the retina and the immunohistochemical detection of von Hippel-Lindau (vHL) protein within the removed spinal hemangioblastoma, a diagnosis of vHL disease was established. Family history and screening for visceral manifestations of vHL disease were negative. In contrast to cerebellar or solitary spinal hemangioblastomas, multiple spinal hemangioblastomas without cerebellar involvement in vHL represent unusual manifestations. Unlike the case for solitary lesions in non-syndromic patients, a surgical cure does not seem feasible in this case. The role of treatment modalities is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101430050047
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  • 19
    Digitale Medien
    Digitale Medien
    Combining steady-state constructive interference and diffusion-weighted magnetic resonance imaging in the surgical treatment of epidermoid tumors (1999)
    Springer
    Neurosurgical review 22 (1999), S. 159-162 
    Details
    ISSN: 1437-2320
    Schlagwort(e): Key words Cerebellopontine angle ; Constructive interference in steady-state imaging ; Diffusion-weighted imaging ; Epidermoid tumor ; Magnetic resonance imaging ; Surgical treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We describe the usefulness of three-dimen-sional Fourier transformation-constructive interference in steady-state (CISS) imaging and diffusion-weighted imaging (DWI) in the pre- and postoperative magnetic resonance imaging evaluation of intracranial epidermoid tumors. Two surgically proven epidermoid tumors in the cerebellopontine (CP) angle were not identified in conventional T1- and T2-weighted images because of a signal intensity similar to that of cerebrospinal fluid (CSF). CISS images clearly demonstrated displacement of the cranial nerves and a shift caused by a lesion in the cistern, but the signal intensity of the tumor by CISS was not sufficiently different from that of CSF to demonstrate the tumor directly. Using DWI, the tumor in the cistern was shown clearly by its increased signal intensity. Together, CISS and DWI compensated for each other's disadvantages, and this combination was useful in guiding surgical treatment of epidermoid tumors in the CP cistern.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101430050055
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  • 20
    Digitale Medien
    Digitale Medien
    Solid cerebral echinococcosis mimicking a primary brain tumor (1999)
    Springer
    Neurosurgical review 22 (1999), S. 58-61 
    Details
    ISSN: 1437-2320
    Schlagwort(e): Key words Brain tumor ; Cerebral hydatidosis ; Chitinoma ; Echinococcosis ; Magnetic resonance imaging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Solitary brain affection is rare in echinococcosis. We report the case of a 35-year-old woman presenting with symptomatic grand-mal epilepsy due to a right frontal, partially cystic space-occupying lesion. Pre-operative computed tomography and magnetic resonance imaging (MRI) suggested a cystic astrocytoma. However, histological examination yielded the diagnosis of a `chitinoma', a rare subtype of solid cerebral hydatid disease (echinococcosis). It mimicked a primary brain tumor and, therefore, posed a diagnostic problem. We present the – to our knowledge – first MRI scans in a case of a histologically proven chitinoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101430050011
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  • 21
    Digitale Medien
    Digitale Medien
    Immunohistochemical and morphometrical study on the temporal expression of interleukin-1α (IL-1α) in human skin wounds for forensic wound age determination (1999)
    Springer
    International journal of legal medicine 112 (1999), S. 249-252 
    Details
    ISSN: 1437-1596
    Schlagwort(e): Key words Forensic pathology ; Wound age ; determination ; Immunohistochemistry ; Morphometrical analysis ; Interleukin-1α (IL-1α)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Notizen: Abstract An immunohistochemical and morphometrical study on the temporal expression of interleukin-1α (IL-1α) was performed on 40 human skin wounds with different wound ages. Immunohistochemically, polymorphonuclear neutrophils mainly showed positive reactions for IL-1α in wounds aged between 4 h and 1 day, but with increasing wound age, neutrophils were no longer present, and macrophages and fibroblasts were positively stained. Morphometrically, the ratio of the number of IL-1α-positive infiltrating cells to the total number of infiltrating cells was evaluated. A considerable increase in the IL-1α-positive cell ratio was observed in wound specimens aged 4 h to 1 day, and the maximum ratio was 46.5% in a 7 h-old wound. The mean value of the IL-1α-positive ratio in 10 wound specimens with different wound ages between 4 h and 1 day was 32.8 ± 9.7%. In most cases the ratio of IL-1α-positive cells gradually decreased in wounds aged between 1.5 and 21 days to less than 30%, and the mean value was 17.5 ± 7.2% (n = 27). These results suggest that ratios of IL-1α-positive cells considerably exceeding 30%, indicate a postinfliction interval of 1 day or less.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004140050244
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  • 22
    Digitale Medien
    Digitale Medien
    Neuron-specific enolase as an effective immunohistochemical marker for injured axons after fatal brain injury (1999)
    Springer
    International journal of legal medicine 113 (1999), S. 19-25 
    Details
    ISSN: 1437-1596
    Schlagwort(e): Key words Head injury ; Diffuse axonal injury ; Immunohistochemistry ; Neuron-specific enolase ; Amyloid precursor protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Notizen: Abstract Recently, it has been reported that a diagnosis of diffuse axonal injury in cases with a short survival period can be made with the use of immunolabelling for β-amyloid precursor protein (APP). We examined whether immunostaining for neuron-specific enolase (NSE) can also be a useful marker for the detection of axonal injury in its early stages. Sections of the corpus callosum from 19 cases of head injury and from 9 cases of no head injury were immunostained for NSE and stained by the standard Holmes’ silver method. For comparison, serial sections from several cases were immunostained for APP. Immunostaining for NSE as well as for APP, labelled injured axons in head injury cases with as early as 1.5 h survival where Holmes’ staining failed to detect any changes of axons. Since NSE and APP labelled only injured axons but not normal axons, the results were readily interpretable. These findings indicate that NSE should be an effective marker for the detection of axonal injury in its early stages.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004140050273
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  • 23
    Digitale Medien
    Digitale Medien
    Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 707-713 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; fibroblast growth factor ; microvasculature
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P 〈 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008303614441
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  • 24
    Digitale Medien
    Digitale Medien
    ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue (1999)
    Springer
    Annals of oncology 10 (1999), S. 903-905 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; high-dose chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008396811371
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  • 25
    Digitale Medien
    Digitale Medien
    The influence of familial and hereditary factors on the prognosis of breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1163-1170 
    Details
    ISSN: 1569-8041
    Schlagwort(e): BRCA1 ; BRCA2 ; breast cancer ; family history ; survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories.Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008301314812
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  • 26
    Digitale Medien
    Digitale Medien
    Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1451-1455 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; chemotherapy ; margins ; radiotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008371318784
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  • 27
    Digitale Medien
    Digitale Medien
    Docetaxel in the community setting: An analysis of 377 breast cancer patients treated with docetaxel (Taxotere®) in the UK (1999)
    Springer
    Annals of oncology 10 (1999), S. 205-210 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; docetaxel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were 'anthracycline resistant' and 35% among the 82 patients who were 'anthracycline refractory' (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan–Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008370930599
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  • 28
    Digitale Medien
    Digitale Medien
    Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 937-942 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; dose-intensity ; epirubicin ; G-CS/kwd〉 ; vinorelbine ; weekly schedule
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF). Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m2/week) and vinorelbine (25 mg/m2/week) with G-CSF support, for 24 consecutive weeks. Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m2 for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40). Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008324329562
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  • 29
    Digitale Medien
    Digitale Medien
    Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results (1999)
    Springer
    Annals of oncology 10 (1999), S. 403-411 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; doxorubicin ; paclitaxel-anthracycline combination ; schedule
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. Patients and methods: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713–21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. Results: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%–81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2–33.7+); the median overall survival is 20.5 months (range 5–54+). The median time to progression is 9.6 months (range 1–33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. Conclusions: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008360406322
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  • 30
    Digitale Medien
    Digitale Medien
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Schlagwort(e): 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 31
    Digitale Medien
    Digitale Medien
    Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 53-58 
    Details
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008390203340
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  • 32
    Digitale Medien
    Digitale Medien
    Effects of retinol on follicular porcine thyrocytes in culture (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 189-192 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Key words Thyroid ; Cell culture ; Retinoids ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Retinoids influence proliferation and differentiation in transformed thyroid cell lines. Retinoids are able to damage cells by destabilizing lysosomal membranes and induce apoptosis in certain cell lines. In normal thyrocytes retinol modulates iodine metabolism. At concentrations higher than 50×10–6 M retinoids are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this cytotoxicity is unknown. We studied the effect of 7–80×10–6 M retinol on porcine follicular thyrocytes in culture. In order to differentiate between membrane-destabilizing effects and apoptosis we investigated cultures after incubation with retinol by light- and electron-microscopy and by labeling of potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP mediated DNA nick end labeling. We conclude that the observed cytotoxicity is caused mainly by the induction of apoptosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001090050334
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  • 33
    Digitale Medien
    Digitale Medien
    Molecular pathogenesis of chronic lymphocytic leukemia: factors and signaling pathways regulating cell growth and survival (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 282-293 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Key words Chronic lymphocytic leukemia ; Apoptosis ; Cell growth ; Signaling ; Review
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Chronic lymphocytic leukemia is a malignant disease characterized by clonal expansion of relatively mature B-lymphocytes with a high percentage of cells arrested in the nonproliferative G0/G1 cell cycle phase. Possibly reflecting the clinical heterogeneity observed in patients, various signaling pathways may become affected during the initiation and course of this disease. This review discusses frequent alterations concerning proliferative, differentiation-inducing, and apoptotic pathways elucidated in the recent years that have improved our understanding of this disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001090050351
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  • 34
    Digitale Medien
    Digitale Medien
    The prognostic significance of tumor vascularization in patients with localized colorectal cancer (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 272-276 
    Details
    ISSN: 1432-1262
    Schlagwort(e): Key words  Colorectal cancer ; Angiogenesis ; Vessel density ; Prognosis ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a ×200 field in the area of the most dense neovascularization. Vascular density was found to be 75±27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (〉75) than in those of less vessel density (〈75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003840050227
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  • 35
    Digitale Medien
    Digitale Medien
    Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 1-8 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Cell proliferation ; Apoptosis ; Cell death ; Cultured cells ; Hepatocellular carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There are conflicting results for experiments aimed at determining whether anticancer drug therapy of human hepatocellular carcinoma prolongs the survival rate effectively. The purpose of this study was to assess the effect of low concentrations of doxorubicin, mitomycin C, and ethanol on cell replication (cell number and proliferation), and cell apoptosis of cultured human hepatocellular carcinoma (Hep-G2) cells. After 1 day of exposure doxorubicin inhibited cell replication initially by 72%, but a partial recovery of the cell number was observed. Mitomycin C inhibited to the same extent but without recovery. Ethanol reduced the cell number even further, the maximum inhibition (12 days after exposure) being 96.4%. After 3 days of exposure all three agents stopped cell replication at a level of 2%–4% of the control (P 〈 0.001). Cell apoptosis was activated most strikingly by mitomycin C (5 μg/ml) after 1 day of exposure and by ethanol (150 μl/ml) after 3 days of exposure. Two-way repeated-measures analysis of variance showed statistically significant differences, with ethanol being the most significant followed by mitomycin C doxorubicin, and the control (P 〈 0.01). Thus, a low dose of ethanol combined with an exposure time of up to 3 days appears to be an effective regimen to control growth of human hepatocellular carcinoma cells in vitro. The strong induction of apoptosis by ethanol might be of additional benefit for a local application in vivo.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050235
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  • 36
    Digitale Medien
    Digitale Medien
    Basic fibroblast growth factor potentiates cisplatinum-induced cytotoxicity in MCF-7 human breast cancer cells (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 556-562 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Basic fibroblast growth factor ; Cisplatinum ; Apoptosis ; Bcl-2 ; MCF-7
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF inhibits the growth of MCF-7 human breast cancer cells. The aim of the present study was to examine the effect of bFGF on cis-diamminedichloroplatinum(cisplatin)-induced cytotoxicity in MCF-7 breast cancer cells as compared to normal endothelial cells. MCF-7/NCF cells transduced with a vector expressing the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduced with the backbone vector were incubated with a combination of bFGF and cisplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforhodamine B colorimetric cytotoxicity assay. Apoptosis was quantitatively determined by flow-cytometric analysis for DNA damage and the apoptotic death assay for DNA fragmentation, and qualitatively by electron microscopy. Reverse transcriptase/polymerase chain reaction analysis and an enzyme immunoassay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-induced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced proliferation of normal endothelial cells and did not increase cisplatin-induced cytotoxicity. This effect was accompanied by down-regulation of the anti-apoptotic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis. We suggest that the improved understanding of the role of bFGF in the differential modulation of the response of breast cancer and normal endothelial cells to chemotherapy may enable active intervention to alter the therapeutic ratio favorably in breast cancer patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050316
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  • 37
    Digitale Medien
    Digitale Medien
    Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 660-668 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Keywords Chemosensitivity ; Human gastric carcinoma ; Micrometastasis ; Apoptosis ; Circulating tumor cells ; Fluoropyrimidine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Antimetastatic effects of 5-FU and its derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU) on human gastric cancer micrometastasis and their mode of action were evaluated, using a spontaneous lung metastasis model (HY-1) in nude mice. Metastases were first detected in the lung from 4 weeks after subcutaneous transplantation, growing intravascularly and forming micrometastases at 100% incidence by 6 weeks after implantation. Lung metastasis in mice bearing subcutaneous tumors was significantly inhibited by HCFU at doses of 100–150 mg kg−1 day−1 without severe toxic side-effects, when orally administered three times per week either from week 4 or week 6 to 9 weeks after implantation. Spontaneous lung metastasis was also inhibited by the administration of 5-FU, but to lesser extent than with HCFU at equimolar low doses. Apoptosis within primary tumors and lung metastatic foci, as detected by the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling method, was found to be significantly enhanced by HCFU as well as 5-FU administration at doses of more than 100 mg kg−1 day−1 and 50 mg kg−1 day−1 respectively. However, proliferating activity of the metastatic foci, as evaluated by MIB-1 immunostaining, was not significantly suppressed by HCFU or 5-FU treatment. Furthermore, polymerase chain reaction analysis using human specific primers for the β-globin gene, which proved to be capable of detecting 10 tumor cells/ml mouse blood, revealed that circulating tumor cells in the peripheral blood of mice bearing primary tumors were reduced by HCFU or 5-FU administration. These results indicate that circulating tumor cells in blood and micrometastases in the lung are sensitive to these chemotherapeutic agents, and suggest that the anti-metastatic effect of these agents is mediated, at least in part, by enhanced apoptosis rather than by inhibition of cell proliferation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050331
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  • 38
    Digitale Medien
    Digitale Medien
    The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 166-173 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key wordsIGF ; Apoptosis ; Transformation ; Chemosensitivity ; Signaling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050259
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  • 39
    Digitale Medien
    Digitale Medien
    Subnuclear distribution of DNA topoisomerase I and Bax protein in normal and xeroderma pigmentosum fibroblasts after irradiation with UV light and c rays or treatment with topotecan (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 193-208 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Immunohistochemistry ; DNA repair ; Radiation-inducible response ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Immunohistochemical methods were used to determine abundance and subnuclear distribution of DNA topoisomerase I and the Bax protein in normal and excision-repair-deficient xeroderma pigmentosum (XP) fibroblasts after irradiation of cells with γ rays or UV light, or exposure to the topoisomerase I inhibitor topotecan. DNA topoisomerase I and Bax were monitored using antisera raised against the human proteins. In addition, topoisomerases IIα and IIβ were made visible with specific antibodies. In untreated cells, DNA topoisomerase I was found to occur in the cytoplasm and in nucleoli. Irradiation with γ rays (2–12 Gy) or UV light (0.3–1.2 mW/cm2) changed the staining pattern in nuclei such that a multitude of small topoisomerase-I-rich centers occurred, which were evenly distributed over the karyoplasm. Simultaneously nucleoli disintegrated. Treatment of fibroblasts with topotecan (6–100 μM concentrations) resulted in similar alterations although the changes were much more pronounced. Combinations of topotecan and γ irradiation caused additive effects. We conclude that the increase in the number of topoisomerase-I-positive spots and the high fluorescence intensity of the latter may reflect three biological processes: (i) enhanced transcriptional activity (e.g. of DNA damage response genes), (ii) tagging of damaged DNA sites for repair, or (iii) initiation of apoptosis. In separate assays using normal and XP cells, a dose-dependent increase in protein reacting with Bax antibody was observed in nuclei, following treatment with γ rays or topotecan. In addition, topotecan induced a netlike arrangement of this Bax protein in nuclei. The meshes of the net structure resembled vesicles. DNA staining with 4′,6-diamidino-2-phenylindole dihydrochloride revealed that the vesicle-type structures contained DNA. Upon further incubation with topotecan, cells showing the netlike Bax arrangement eventually died. We conclude that topotecan-induced changes made visible by nuclear Bax protein are associated with apoptosis. XP cells, when treated with topotecan, responded more readily than normal cells with both an increase in nuclear Bax protein and rearrangement of Bax, indicating that UV repair functions may be required to process DNA damage inflicted by topotecan. Monitoring of DNA topoisomerases IIα and IIβ in γ-irradiated cells with antibodies revealed a dramatic increase in the IIα form and a redistribution of the IIβ form representing fragmentation of nucleoli.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050263
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  • 40
    Digitale Medien
    Digitale Medien
    The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 357-360 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Colorectal neoplasms ; Apoptosis ; Chemosensitivity ; p53 gene
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose : The p53 gene is considered one of the most important in the control of apoptosis, and its mutations have a close relationship with chemosensitivity. The aim of this work was to investigate the role of p53 in the apoptosis of colorectal cancer cells in vitro, induced by 5-fluorouracil (5-FU) and hydroxy-camptothecin (HCPT). Methods : A total of 39 colorectal cancer samples from patients were treated in vitro with 5-FU (10 μg/ml), 5-FU (10 μg/ml) + leucovorin (5 μg/ml), HCPT (0.1 μg/ml) and HCPT (0.1 μg/ml) + Salvia mitorrhiza (6 μl), using an in situ terminal deoxynucleotidyltransferase assay to detect chemosensitivity. p53 gene mutations from tumor DNA were detected, after amplification by the polymerase chain reaction of exons 5–8, by non-radioactive single-strand conformation polymorphism. Results : p53 gene mutations were observed in 43.6% (17/39) of colorectal carcinomas, when the terminal deoxynucleotidyltransferase assay was used to detect the tumor apoptotic rate. Cells with mutated p53 had lower chemosensitivity than those without (p 〈 0.01). Conclusion : Routine assessment of p53 status may be helpful in selecting patients with the wild-type p53 gene, who have a predictably better response to chemotherapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050286
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  • 41
    Digitale Medien
    Digitale Medien
    Inhibition of epidermal-growth-factor-receptor-dependent signalling by tyrphostins A25 and AG1478 blocks growth and induces apoptosis in colorectal tumor cells in vitro (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 379-388 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words EGF receptor signalling ; Tyrphostin ; Apoptosis ; Colon cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Growth effects of tyrphostins A25 and AG1478 on colorectal tumor cells were studied to explore therapeutic potential. Cell number, DNA synthesis and apoptotic index were measured as growth parameters and cell-death-associated proteins Bcl-2 and Bak and protein phosphorylation were analyzed. Both tyrphostins inhibited DNA synthesis and induced apoptosis in tumor cell cultures with different patterns of activity. A25 displayed strong selectivity for the cell lines expressing high levels of epidermal growth factor (EGF), HT29/HI1 and SW480. Inhibition of DNA synthesis was efficient in all cells except T84, and the apoptotic index increased two- to fivefold. By contrast, AG1478 was highly effective in all cell lines. In addition, it caused cell loss in VACO235 adenoma cells at concentrations lower than those necessary to inhibit BrdU incorporation, reflecting preferential retention of cells actively synthesizing DNA. Induction of apoptosis was more efficient with AG1478 than with A25 (tenfold in VACO235). Insulin-like growth factor (IGF1) did not rescue cells exposed to A25 or to high concentrations of AG1478, but was effective with suboptimal amounts of AG1478. Both compounds inhibited phosphorylation of the EGF receptor as well as additional proteins. AG1478 induced expression of Bak and down-regulated Bcl-2. In summary, tyrphostins may provide alternatives for colorectal tumor treatment. Their broader range of activities and the lower susceptibility to interactions with IGF1 can be an advantage over receptor antibodies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050290
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  • 42
    Digitale Medien
    Digitale Medien
    Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 444-452 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Experimental pancreatic cancer ; Hormonal therapy ; Bombesin antagonist ; Somatostatin analog ; LH-RH antagonist ; EGF receptor ; Apoptosis ; AgNOR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 μg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of down-regulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050301
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  • 43
    Digitale Medien
    Digitale Medien
    Charakterisierung der Lymphozytensubpopulationen bei Patienten mit Ataxia teleangiectatica (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 927-931 
    Details
    ISSN: 1433-0474
    Schlagwort(e): Schlüsselwörter Ataxia teleangiectatica ; Immunfunktionsstörung ; Lymphozytensubpopulationen ; Apoptose ; CD45RO ; CD45RA ; Key words Ataxia teleangiectasia ; Immunodeficiency ; Lymphocyte subset ; Apoptosis ; CD45RO ; CD45RA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Background: Can a characterisation of the lymphocyte subset in patients with ataxia teleangiectasia offer an explanation for the cellular defect of their immunfunction? Methods: In ten patients with ataxia teleangiectasia and a corresponding control group of individuals of similar age and sex, immunophenotyping was carried out by means of flow cytometric analysis and the use of monoclonal antibodies. Results: Patients with ataxia teleangiectasia showed a reduction of the number of T-cells with a decrease in the T-helper cell subset (CD3: 990/µl, p〈0.0005 and CD4: 568/µl, p〈0.0005). The number of B-cells was low (CD19: 39/µl, p〈0.005). Moreover, there was an increase in highly activated T-lymphocytes which can be seen from a higher percentage of the HLA-DR- and CD45RO-expression in patients with ataxia teleangiectasia compared to the individuals of the control group (HLA-DR: 57%, p〈0.0005 and CD45RO: 82%, p〈0.001). At the same time, the expression of CD95 (Fas/AP01) was clearly increased (CD95: 74%, p〈0.001). Interpretation: The lymphocyte subset of the patients suffering from ataxia teleangiectasia shows a significant decrease of the B- and T-cell subsets. The reduced number of T-helper cells – caused by a CD45RA-cell loss – leads to a change in the relation „RA/RO”. It is possible that there is a link between the imbalance of „RA/RO”, the increase of highly activated T-lymphocytes and the higher expression of CD95 (Fas/APO1).
    Notizen: Zusammenfassung Fragestellung: Können durch eine Charakterisierung der Lymphozytensubpopulationen bei Patienten mit Ataxia teleangiectatica Rückschlüsse auf den zellulären Defekt der Immunfunktionsstörung gezogen werden? Methodik: Mit Hilfe der Durchflußzytometrie und des Einsatzes monoklonaler Antikörper führten wir eine Immunophänotypisierung bei jeweils 10 Patienten mit Ataxia teleangiectatica und eines bezüglich des Alters und des Geschlechts gleichverteilten Kontrollkollektivs durch. Ergebnisse: Die Patienten mit Ataxia teleangiectatica zeigten verminderte T-Zell-Zahlen mit Abnahme der T-Helferzell-Subpopulationen (CD3: 990/µl, p〈0,0005 und CD4: 568/µl, p〈0,0005). Auch die B-Zell-Zahl war erniedrigt (CD19: 39/µl, p〈0,005). Die T-Lymphozyten befanden sich darüber hinaus vermehrt im aktivierten Zustand, erkennbar an einer prozentual erhöhten HLA-DR- und CD45RO-Expression (HLA-DR: 57%, p〈0,0005 und CD45RO: 82%, p〈0,001) sowie an einer Verschiebung der Relation „RA/RO” zugunsten der „RO”-Expression. Gleichzeitig war die Expression von CD95 (Fas/APO1) deutlich gesteigert (CD95: 74%, p〈0,001). Schlußfolgerung: Die Veränderungen der Lymphozytensubpopulationen zeigen bei den Patienten mit Ataxia teleangiectatica eine verminderte B- und T-Zell-Zahl. Die CD4-Lymphopenie – verursacht durch einen CD45RA-Zellverlust – bedingt eine Verschiebung der Relation „RA/RO”. Möglicherweise besteht ein Zusammenhang zwischen der Störung der Homöostase „RA/RO” und dem erhöhten Aktivierungsgrad der Zellen sowie der vermehrten CD95(Fas/APO1)-Expression.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001120050519
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  • 44
    Digitale Medien
    Digitale Medien
    Hinweis auf zerebrale Mikroblutungen in der MRT Vergleichende histologische Befunde und mögliche klinische Bedeutung (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 1082-1087 
    Details
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Intrazerebrale Blutung ; Magnetresonanztomographie ; Hämosiderin ; Key words Intracerebral hematome ; Magnetic resonance imaging ; Hemosiderin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Increased use of gradient echo T2*- weighted gradient echo sequences in magnetic resonance imaging (MRI) of patients suffering from primary ICH called attention to foci of signal loss which were suggested to represent remnants of cerebral microbleeds. In a post mortem correlative MR and histopathological study we provide support for this notion. We found areas of signal loss on gradient echo T2*-weighted sequences in 7 out of 11 brains of patients who had died of intracerebral hematoma. Histopathologically, these areas represented hemosiderin deposits indicating previous extravasation of blood. To provide data about the prevalence of these MRI findings in a healthy elderly population a subgroup of participants of the Austrian Stroke Prevention Study was analyzed. We detected foci of signal loss on gradient echo T2*-weighted sequences in 18 out of 280 volunteers (6,4%). MR-based evidence of previous microbleeds may indicate a potentially higher risk of suffering from intracerebral bleeding which could have therapeutic implications for the treatment of acute stroke and for secondary prevention. This hypothesis will have to be tested in future prospective trials.
    Notizen: Zusammenfassung Vermehrte Anwendung T2*-gewichteter Gradienten-Echo-Sequenzen bei Magnetresonanztomographie- (MRT-) Untersuchungen von Patienten nach einem intrazerebralen Hämatom machte auf kleine, hypointense Areale aufmerksam, von denen bisher nur angenommen wurde, daß sie abgelaufene Mikroblutungen darstellen. In einer Post-mortem-Studie mit MRT und vergleichenden histopathologischen Untersuchungen zeigen wir Daten, die diese Hypothese stützen. Bei 7 von 11 Patienten, die an primärem intrazerebralem Hämatom verstorben waren, fanden sich hypointense Areale in T2*-Gradienten-Echo-Sequenzen. Histopathologisch zeigten diese Areale Hämosiderin-Ablagerungen, welche auf abgelaufene Blutungen hinweisen. Um Aussagen über die Prävalenz dieser MRT-Befunde in einem Kollektiv klinisch unauffälliger Probanden mittleren Alters machen zu können, wurden Teilnehmer derÖsterreichischen Schlaganfall-Vorsorge-Studie untersucht. Bei 18 von 280 Probanden (6,4%) fanden sich Signalhypointensitäten in T2*-Gradienten-Echo-Sequenzen. Der MR-tomographische Nachweis abgelaufener Mikroblutungen könnte ein Hinweis auf ein erhöhtes zerebrales Blutungsrisiko sein, was therapeutische Konsequenzen für die primäre Therapie und Sekundärprophylaxe beim Schlaganfall haben könnte. Hierzu sind noch weitere prospektive Studien notwendig.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001150050542
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  • 45
    Digitale Medien
    Digitale Medien
    Knochenneubildungen in einer seltenen Raumforderung des inneren Gehörgangs (1999)
    Springer
    HNO 47 (1999), S. 563-568 
    Details
    ISSN: 1433-0458
    Schlagwort(e): Schlüsselwörter Schädelbasis ; Innerer Gehörgang ; Tumor ; Hämangiom ; Kernspintomographie ; Computertomographie ; Key words Skull-base tumors ; Internal auditory meatus ; Hemangiomas ; Magnetic resonance imaging ; Computed tomography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Hemangiomas of the skull base are rare neoplasms and are easily misdiagnosed as acoustic neuromas when occurring in the internal auditory canal. Among these tumors, ossifying hemangiomas are characterized histologically be newly formed bone tissue within their substance. We describe a 26-year old female patient who presented with left-sided sensorineural hearing loss and tinnitus. T2-weighted magnetic resonance imaging demonstrated a bright space-occupying lesion of the internal auditory canal with extension to the geniculate ganglion. Bony erosions of the internal auditory canal were proved by high-resolution computed tomography. A hemangioma was suspected preoperatively and was resected via a middle cranial fossa approach. Histologically, new bone formations were found in a cavernous hemangioma. In general, radiologic findings can suggest a hemangioma of the internal auditory canal and help to differentiate it from acoustic neuroma. Based on the histological findings of intratumoral bone formation, the hemangioma in our patient was classified as an ossifying hemangioma. However, reactive bone formation at the borders of a tumor in the internal auditory canal can also be mistaken as new intratumoral bone formation.
    Notizen: Zusammenfassung Hämangiome der Schädelbasis sind insgesamt seltene Tumoren, die im Bereich des inneren Gehörgangs insbesondere mit dem wesentlich häufigeren Akustikusneurinom verwechselt werden können. Das ossifizierende Hämangiom repräsentiert eine Sonderform in der Gruppe der Hämangiome und ist histopathologisch durch intratumorale Knochenneubildungen gekennzeichnet. Es wird von einem kavernösen Hämangiom des linken inneren Gehörgangs bei einer 26jährigen Patientin berichtet, welches zu einer progredienten sensorineuralen Hörminderung und Tinnitus geführt hatte. Bei T2-gewichteter kernspintomographischer Darstellung einer signalreichen Neubildung im inneren Gehörgang mit computertomographisch evidenten Knochendestruktionen am Gehörgangsboden war präoperativ die Abgrenzung von einem Akustikusneurinom möglich. Über einen transtemporalen Zugang konnte die vaskuläre Neubildung reseziert werden. Histopathologisch waren Knochenneubildungen in einem kavernösen Hämangiom zu erkennen. Die radiologischen Befunde ermöglichen präoperativ die Abgrenzung eines Hämangioms vom Akustikusneurinom. Aufgrund des Nachweises von Knochenneubildungen in den histologischen Schnittpräparaten des Tumors ist die Einordnung des kavernösen Hämangioms als ossifizierendes Hämangiom naheliegend. Neben der Wertung der histologisch nachgewiesenen Knochenneubildungen als intratumorale Ereignisse muß auch an die Möglichkeit einer in den Schnittpräparaten vorgetäuschten intratumoralen Knochenneubildung durch den Anschnitt reaktiver Knochenneubildungen am destruierten Gehörgangboden gedacht werden.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001060050425
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  • 46
    Digitale Medien
    Digitale Medien
    Zerebrale Effekte von Perfluorcarbonen (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 679-687 
    Details
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Perfluorcarbon-Emulsionen ; Perfluorcarbone ; Neuroprotektion ; Ischämie ; Reperfusionsschaden ; Kernspintomographie ; Tumorversorgung ; Key words Perfluorocarbon emulsions ; Perfluorochemicals ; Cerebral protection ; Ischemia ; Reperfusion injury ; Magnetic resonance imaging ; Tumor oxygenation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary For the ussage as blood substitutes perfluorocarbons (PFC) have been developed as artificial oxygen carriers. In addition they may have potency for protective use in ischemic tissue. Formulation improvement achieved higher oxygen carrying capacity and better compatibility than the first generation of PFC. Preclinical studies have been performed in animal heart and brain. Former and progressed emulsification for intravascular use have been investigated for infarction and reperfusion injury. This investigations are reviewed and the potencies for the use of PFC in neurology, neurosurgery, diagnostics today and in the future are emphasized.
    Notizen: Zusammenfassung Perfluorcarbone (PFC) sind künstliche Sauerstoffträger, die ursprünglich als Blutersatzstoffe entwickelt wurden. Auf Grund ihrer spezifischen Eigenschaften ist darüber hinaus ihr Einsatz bei ischämischen Perfusionsstörungen von potentiellen Nutzen. Neuere Perfluorcarbonpräparationen verfügen über eine höhere Sauerstofftransportkapazität und sind mit weniger Nebenwirkungen behaftet als die PFC der ersten Generation. Ältere und neuere PFC-Emulsionen, die für die intravaskuläre Applikation geeignet sind, wurden und werden im Tierversuch für den Einsatz in ischämischen Gebieten des Herzens und des Gehirns untersucht. In dieser Arbeit werden präklinische Studien bei Infarkten und Reperfusionsschaden beschrieben und potentielle Nutzungsmöglichkeiten dieser Substanzgruppe für diese Indikationsstellung diskutiert.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001150050497
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  • 47
    Digitale Medien
    Digitale Medien
    Die “Häm”-Sequenz (T2*-gewichtete Gradienten-Echo-Magnetresonanztomograpie¶Stellenwert in der Differentialdiagnose spontaner intrazerebraler Blutungen (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 714-722 
    Details
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Intrakranielle Blutung ; Magnetresonanztomographie ; T2*-gewichtete Gradienten-Echo-Sequenz ; Hypertensive zerebrale Mikroangiopathie ; Zerebrale Amyloidangiopathie ; Zerebrale Kavernome ; Key words Intracerebral hemorrhage ; Magnetic resonance imaging ; Cerebral amyloid angiopathy ; Hypertensive cerebral microangiopathy ; Cerebral cavernoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In four patients presenting with acute nontraumatic intracerebral or intraspinal hemorrhage, T2*-weighted gradient-echo MRI showed numerous residual hemosiderin deposits due to old intracerebral hemorrhages that were missed on initial CT and spin-echo MRI. The demonstration of additional chronic bleedings and their anatomical distribution provided important diagnostic information. In a hypertensive patient, the hemosiderin deposits were most pronounced within deep brain structures suggesting hypertensive cerebral microangiopathy. In a second patient, the cortico-subcortical distribution of the hemorrhages was typical of cerebral amyloid angiopathy. In a third patient, the diffuse distribution including spinal bleeding, the marked calcification, and the characteristic appearance on spin-echo MRI were consistent with multiple cavernomas. In another patient with cerebral and spinal hemorrhage, T2*-weighted gradient-echo MRI revealed new subclinical hemorrhages during follow-up. Based on these findings, we recommend that T2*-weighted gradient-echo MRI of the brain should be performed in all patients with acute intracranial and spinal bleedings.
    Notizen: Zusammenfassung Bei 4 Patienten mit akuten intrazerebralen oder intramedullären Blutungen konnte die T2*-gewichtete Gradienten-Echo-Magnetresonanztomographie (“Häm”-Sequenz) multiple intrakranielle Hämosiderinablagerungen als Beleg für in der Vergangenheit abgelaufene Hirnblutungen nachweisen. Diese klinisch stummen Blutungen waren sowohl der Computertomographie als auch der Spin-Echo-Magnetresonanztomographie entgangen. Bei 3 Patienten ermöglichte das Verteilungsmuster der als Signalauslöschungen dargestellten Hämosiderinablagerungen eine bessere Eingrenzung der Blutungsursache. Bei einem Patienten mit arterieller Hypertonie legten die vorwiegend in den tieferen Hirnstrukturen lokalisierten Blutungen eine hypertensive zerebrale Mikroangiopathie nahe. Bei einem Patienten mit rezidivierenden Lobärhämatomen sprach die kortikosubkortikale Lokalisation der Blutungen für das Vorliegen einer zerebralen Amyloidangiopathie. Bei einer Patientin mit spinaler Blutung stellten wir aufgrund des diffusen Verteilungsmusters, der starken Verkalkungstendenz und des heterogenen Signalverhaltens der Blutungsherde in der Spin-Echo-Magnetresonanztomographie die Diagnose multipler zerebrospinaler Kavernome. Bei einem Patienten mit zerebralen und spinalen Blutungen erlaubte die “Häm”-Sequenz keine diagnostische Einordnung, erwies sich aber als sensitives Instrument in der Verlaufskontrolle. Bei allen Patienten mit spontaner intrazerebraler oder intraspinaler Blutung sollte im Rahmen der bildgebenden Diagnostik eine “Häm”-Sequenz durchgeführt werden.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001150050500
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  • 48
    Digitale Medien
    Digitale Medien
    A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury (1999)
    Springer
    International journal of legal medicine 112 (1999), S. 227-232 
    Details
    ISSN: 1437-1596
    Schlagwort(e): Key words Brain injury ; Cortical contusion ; Inflammatory reaction ; Immunohistochemistry ; Wound ; age
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Notizen: Abstract The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004140050241
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  • 49
    Digitale Medien
    Digitale Medien
    Electron microscopic and immunohistochemical studies of gastrointestinal stromal tumors (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 213-220 
    Details
    ISSN: 1437-773X
    Schlagwort(e): Key words Gastrointestinal stromal tumor ; Gastrointestinal autonomic nerve tumor ; Electron microscopy ; Immunohistochemistry ; Gastrointestinal tract
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Sixteen gastrointestinal stromal tumors (GISTs) were studied by immunohistochemical analysis and an ultrastructural procedure. The tumor locations were as follows: esophagus (2), stomach (7), small intestine (3), and large intestine (4). Four of the lesions were classified as malignant, 2 as borderline, and 10 as benign. On the basis of the immunohistochemical analysis, the tumors were classified as follows: 1 as myogenic type, 2 as Schwann cell type, 8 as Cajal cell type (including 2 gastrointestinal autonomic nerve tumors, GANTs), and 5 as mixed-cell type. In each subtype the phenotype was compared to the ultrastructural findings. Myogenic and Schwann cell type revealed ultrastructurally smooth muscle differentiation and schwannian tumor. All 8 tumors of the Cajal cell type revealed interdigitating cytoplasmic processes with occasional clusters of filopodia. Two tumors were subdivided as GANT. Five tumors of mixed-cell type were composed of a mixture of cells with variable myogenic features or variable neural differentiation. We confirmed in this study that immunohistochemical analysis reflected electron microscopic findings.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s007950050005
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  • 50
    Digitale Medien
    Digitale Medien
    Altered intramuscular innervation and synapse formation in internal sphincter achalasia (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 192-194 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Keywords Internal anal sphincter achalasia ; Innervation ; PGP 9.5 ; Synapse ; Synapsin I ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Internal anal sphincter achalasia (IASA) is a condition with a clinical presentation similar to Hirschsprung's disease, but with the presence of ganglion cells on rectal biopsy. The diagnosis of IASA is made on anorectal manometry, which demonstrates the absence of a rectosphincteric reflux on rectal balloon inflation. In order to understand the nature of neuronal abnormalities in this condition, we performed immunohistochemistry using PGP 9.5 (a general neuronal marker) and synapsin I (a presynaptic marker) in IAS specimens from 10 patients with IASA and 8 normal controls. In the IAS of normal controls, there were many PGP 9.5 and synapsin I-positive nerve fibers. In IASA PGP 9.5-immunoreactive fibers were markedly reduced and synapsin I-positive fibers were either absent or markedly reduced. Our findings demonstrate that the IAS in achalasia patients has defective intramuscular innervation as well as defective innervation of the neuromuscular junction, thereby contributing to the motility dysfunction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050552
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  • 51
    Digitale Medien
    Digitale Medien
    Clinical implications of mRNA expression of KAI1 in ovarian cancer with or without metastasis (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 343-347 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words KAI1, Ovarian tumors ; PCR ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. KAI1 is a potential metastasis suppressor gene for prostate cancer. Decreased expression of KAI1 mRNA has been shown to be associated with the formation of metastasis and the progression of prostate, lung, breast, pancreatic, and bladder cancer. It has also been reported, however, that KAI1 expression is unchanged in metastatic and nonmetastatic esophageal and gastric cancer. We performed the present study to investigate the function of KAI1 in the progression and/or metastasis of ovarian cancer. Methods. We investigated the mRNA expression levels of the KAI1 gene, using quantitative polymerase chain reaction (PCR), in 29 ovarian tumors (1 adenoma, 2 low- malignant potential tumors, 9 adenocarcinomas without metastasis, and 17 adenocarcinomas with metastasis), seven ovarian cancer cell lines, and two normal ovaries. Using a thermal cycler, we found that the KAI1 gene was amplified in parallel with an internal control gene, β-Actin. The relative expression ratio (KAI1/β-Actin) as measured by densitometry was used to evaluate gene expression. Immunohistochemical localization of the KAI1 protein in ovarian cancer tissues was confirmed by the avidin-biotin peroxidase complex (ABC) method. Results. The mRNA expression levels of KAI1 were consistent in normal ovary, ovarian tumor samples, and ovarian cancer cell lines. No statistically significant difference in the KAI1 mRNA expression level was found in ovarian cancer samples with or without metastasis. Immunohistochemistry revealed that the KAI1 protein was expressed in the cell membranes of ovarian cancer cells. Conclusions. Our results suggest that reductions in KAI1 mRNA expression are not involved in either the progression or metastasis of ovarian carcinomas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050082
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  • 52
    Digitale Medien
    Digitale Medien
    Oxidation of lipoprotein in injury and repair of obstructive nephropathy (1999)
    Springer
    Clinical and experimental nephrology 3 (1999), S. 254-260 
    Details
    ISSN: 1437-7799
    Schlagwort(e): Key words Low density lipoprotein ; Apoptosis ; Malondialdehyde ; TGFβ1 ; Unilateral ureteral obstruction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. To test the hypothesis that oxidized low density lipoprotein (oLDL) is involved in the renal injury of obstructive nephropathy, male Sprague-Dawley rats weighing 125–150 g were used. Methods. Three days after arrival, the rats were randomly assigned to undergo: (1) sham operation, (2) left unilateral ureteral obstruction (UUO), or (3) reversal of the unilateral ureteral obstruction (R-UUO). Seven days after the reversal operation or 10 days after the sham or UUO procedure, all animals were killed by exsanguination under anesthesia, with blood taken from the abdominal aorta. LDL was prepared by gradient ultracentrifugation and used immedi-ately after isolation. Rat mesangial cells were utilized with an LDL concentration of 100 μg/ml/protein in the media. After 72 h, cell survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method. Cell survival was determined by comparing the optical density between the control wells and the experimental wells. In order to investigate the mechanisms of injury and repair of obstructive nephropathy, data for kidney apoptosis, malondialdehyde (MDA), and transforming growth factor β1 (TGFβ1) mRNA were obtained in the sham-operated, UUO, and R-UUO groups. Results. Our results showed that LDL malondialdehyde during UUO was increased 87% over baseline values (P 〈 0.005). With R-UUO, the oxidized LDL dropped 23% from the peak values during UUO (P 〈 0.005), but was still different from that of the baseline values (P 〈 0.025). Rat mesangial cell survival, after 72 h exposure to oLDL, inversely correlated to oLDL cytotoxicity and showed a 14% drop during UUO compared with sham-operated animals (P 〈 0.01). Cell survival increased 11% after R-UUO (P 〈 0.02) and was not different from control values (P = NS). The apoptotic counts by the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) technique showed significant increases during UUO and a noticeable reduction after R-UUO. Conclusion. Our data support the proposition that UUO stimulates oxidation of LDL. The cytotoxicity of oLDL plays a significant role in the injury of UUO. A decrease in cytotoxicity was associated with the repair in R-UUO. Our observations that apoptosis follows this same pattern, point to the importance of apoptosis in the injury and repair of obstructive nephropathy. Future studies to interrupt these processes of injury may lead to novel treatment modalities in reversing the injury and hastening the repair of obstructive nephropathy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101570050044
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  • 53
    Digitale Medien
    Digitale Medien
    Apoptosis and bcl-2 oncogene expression in Wilms' tumor (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 243-247 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Wilms' tumo ; Apoptosis ; Bcl-2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Wilms' tumor (WT) usually has a good outcome, although a poor prognosis is often related to more advanced stages and anaplastic features. Apoptosis occurs with variable frequency in malignant tumors, and may have a role in reducing their growth rate. The bcl-2 proto-oncogene inhibits apoptosis, and the consequent increase in the number of cells may play a role in the development of tumors. The aim of this study was to analyze the role of apoptosis and bcl-2 expression in WT. Twenty-six resected WT specimens were studied; 12 patients had stage I tumor, 4 stage II, 5 stage III, 3 stage IV, and 2 stage V. Twenty-three tumors were classified as favorable histology (FH) and 3 as unfavorable (UH). The mean follow-up was 34 months; 22 patients were alive and 4 were dead (2 with FH: 1 stage III and 1 stage IV, and 2 with UH stages 4). Apoptosis was detected by the in-situ end-labelling technique; bcl-2 expression was detected by immunohistochemistry. An apoptotic index (AI) was calculated as the ratio of apoptotic to normal cells in each specimen. The AI was lower in higher tumor stages, with a significant difference between stages I and IV (P 〈 0.05). In cases with UH, Al was lower than in tumors with FH (P 〈 0.01). The AI was also lower in patients who died than in those who survived (P 〈 0.01). In all specimens no correlation between AI and bcl-2 expression was observed. Progression to advanced stages of WT and a poor prognosis f anaplastic tumors may be linked with disruption of the mechanisms that control apoptosis. Bcl-2 does not play a role as a regulator of apoptosis in WT, other oncogenes and tumor-suppression genes may be more involved in inhibiting apoptosis in WT.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050567
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  • 54
    Digitale Medien
    Digitale Medien
    Localization of ladsin, a homolog of laminin-5, in normal adult human tissues: immunohistochemical and immunoelectron microscopic studies (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 25-35 
    Details
    ISSN: 1437-773X
    Schlagwort(e): Key words Basement membrane ; Ladsin ; Laminin-5 ; Immunohistochemistry ; Immunoelectron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ladsin, a homolog of laminin-5, is a large cell-adhesive protein with potent cell-scattering activity. In the present study, we investigated, by immunohistochemistry, the distribution of ladsin in a wide range of normal adult human epithelial tissues along with that of integrin subunit α3 as a marker of integrin α3β1, which is the primary receptor of ladsin. Our results demonstrated that ladsin was localized in the basement membranes of almost all the epithelial tissues with coexisting integrin subunit α3 along the cell membranes, suggesting that their interaction is important in the maintenance of normal architecture and function of these membranes. Only cytoplasmic localization of ladsin was observed in the fundic glands, hepatocytes, renal tubuli, and acini of the mammary glands, and in these tissues, integrin subunit α3 was also localized in the cytoplasm. Both ladsin and integrin subunit α3 were absent in the acini of the pancreas, major salivary glands, and bronchial glands. These tissue- and cell type-specific localizations of ladsin and integrin subunit α3 likely reflect the differences in their role and function in each tissue.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s007950050005
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  • 55
    Digitale Medien
    Digitale Medien
    Effect of cell plating density and extracellular matrix protein on cell growth of epithelial rests of Malassez in vitro (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 127-132 
    Details
    ISSN: 1437-773X
    Schlagwort(e): Key words Epithelial rest of Malassez ; Cell ; cell interaction ; Extracellular matrix ; In vitro ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study investigated how cell plating density and extracellular matrix protein influence cell survival of epithelial rests of Malassez (ERM) in vitro. ERM cells were plated on culture dishes coated with laminin (LM), type IV collagen (type IV), or fibronectin (FN), or on noncoated dishes, (Non) at a cell density of 2 × 104–1 × 105/ml in a nonserum culture medium. XTT assays were performed to calculate the number of cells attached on the substrata after 6, 24, 48, and 72 h. Mean cell numbers were calculated, and significant differences were determined using ANOVA. When epithelial cells were cultured on various matrices at a cell density of less than 2 × 104/ml, the cells did not grow and then fell into apoptotic cell death, which was confirmed by transmission electron microscopy. The cell number was significantly increased in cells plated on FN compared to those on Non at a cell density of 4 × 104/ml–8 × 104/ml. These results suggest that both extracellular matrix proteins and cell–cell interactions may contribute to prevent apoptosis of ERM in vitro. Cell–cell interactions may be a more important factor than exogenous extracellular matrix proteins for the survival of ERM cells in vitro.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s007950050019
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  • 56
    Digitale Medien
    Digitale Medien
    Carcinosarcoma of the liver with an osteosarcomatous component (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 185-188 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Hepatocellular carcinoma ; Carcinosarcoma ; Mesenchymal differentiation ; Immunohistochemistry ; Hepatectomy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report a case of hepatocellular carcinoma associated with mesenchymal differentiation, which was identified as a true carcinosarcoma based on thorough pathologic examination. A 48-year-old man presented with a giant mass in the lateral segment of the liver. It was resected by lateral segmentectomy combined with total gastrectomy. Microscopically, the tumor consisted of hepatocellular carcinoma, osteosarcoma, and undifferentiated sarcomatous components. The undifferentiated sarcomatous components were positive for cytokeratin, whereas the osteosarcomatous components were negative for cytokeratin and positive for S100. To our knowledge, this is only the second known case in which mesenchymal differentiation was immunohistochemically demonstrated in liver carcinosarcoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050051
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  • 57
    Digitale Medien
    Digitale Medien
    Effect of anticancer agents on Fas-mediated cytotoxicity against bladder cancer cells (1999)
    Springer
    Journal of infection and chemotherapy 5 (1999), S. 139-143 
    Details
    ISSN: 1437-7780
    Schlagwort(e): Key words Fas ; ADR ; Bladder cancer ; Synergy ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Fas and Fas ligand play an important role in cytotoxic T lymphocyte-mediated cytotoxicity. Like Fas ligand, anti-Fas monoclonal antibody (mAb) induces apoptosis of cells expressing Fas and mimics tumor necrosis factor-α (TNF-α) in its cytotoxic activity, but not in regard to other TNF-α-mediated activities. Since combination treatment with TNF-α and some anticancer chemotherapeutic agents results in synergistic cytotoxicity against various cancer cells, anti-Fas mAb may also synergize with anticancer agents in exerting cytotoxicity. The present study examined this hypothesis using bladder cancer cells. Cytotoxicity was examined by a 1-day microculture tetrazolium dye assay. Treatment of T24 cells with anti-Fas mAb in combination with mitomycin C, methotrexate, or 5-fluorouracil did not overcome their resistance to these agents. However, combination treatment with anti-Fas mAb and adriamycin (ADR) resulted in a synergistic cytotoxic effect on T24 cells, three other bladder cancer lines, and fresh bladder cancer cells derived from four patients. Treatment with ADR enhanced the expression of Fas on T24 cells. The expression of P-glycoprotein was not affected by the antibody-mediated sensitization. This study showed that combination treatment of bladder cancer cells with anti-Fas mAb and ADR can overcome their resistance and that the upregulation of Fas expression by ADR may play a role in the enhanced cytotoxicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101560050023
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  • 58
    Digitale Medien
    Digitale Medien
    Expression of Fas and Bcl-2 proteins and induction of apoptosis in human hepatocellular carcinoma cell lines (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 199-203 
    Details
    ISSN: 1437-773X
    Schlagwort(e): Key words Hepatocellular carcinoma ; Apoptosis ; Fas protein ; Bcl-2 protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Because the induction of apoptosis in cancer cells is very important in clinical management, it is useful to examine the association with the Fas–Fas ligand pathway and Bcl-2 protein family in apoptosis. We morphologically examined the expression of Fas and Bcl-2 proteins and induction of apoptosis by anti-Fas in four human hepatocellular carcinoma cell lines, PLC/PRF/5, Huh-6, and Huh-7, as well as OCUH-16, which was originally established in our university. Fas protein was expressed in 96% of OCUH-16 cells in cytoplasm, 24% of PLC/PRF/5 cells, 20% of Huh-6 cells, and no Huh-7 cells. Bcl-2 protein was expressed in 43%–72% of cells in cytoplasm and nuclei of the four lines examined. Administration of anti-Fas induced apoptosis in about 40% of OCUH-16 cells, but did not induce apoptosis in the other three cell lines. In conclusion, an original cell line, OCUH-16 cells, expressed Fas and Bcl-2 proteins and underwent apoptosis following treatment with anti-Fas, but the other three cell lines examined did not undergo apoptosis. OCUH-16 cells are thus very useful for the study of apoptosis and molecules related to apoptosis at the levels of cell-surface receptors and intracytoplasmic regulation of apoptosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s007950050002
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  • 59
    Digitale Medien
    Digitale Medien
    Cellular localization of CD44 correlates with cell proliferation and liver metastasis in colon cancer (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 78-83 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words CD44 ; Colon cancer ; Liver metastasis ; Cellular localization ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. The functional heterogeneity of the cell adhesion molecule family CD44 is explained by differences in its activity, which is regulated by alterations in the distribution of its cellular localization. The aim of the current study was to evaluate the functional differences in cancer cells according to variations in the cellular localization of CD44. Methods. Paraffin-embedded tissue sections of 34 colon cancers (obtained from 17 patients with liver metastasis and 17 without liver metastasis) were investigated. These tumors were classified according to the predominant pattern of cellular localization of CD44 (the isoforms CD44H, CD44v6, and CD44v9). For each CD44 isoform, the functional differences were investigated for a correlation between localization patterns and Ki-67 labeling index (to indicate cell proliferative activity), and for a correlation between localization patterns and liver metastasis. Results. On staining for CD44H, tumors displayed three localization patterns. One pattern, in which CD44H was expressed on the basal or basolateral side of the plasma membrane in cancer cells, showed a higher Ki-67 labeling index than other localization patterns (P 〈 0.01), and a higher rate of the basolateral localization pattern was observed in patients with liver metastasis than in those without (P = 0.02). On staining for CD44v6 and CD44v9, tumors showed four and three localization patterns, respectively. No significant differences in localization patterns were found in analyses of the Ki-67 labeling index and liver metastasis for either CD44v6 or CD44v9. Conclusions. A functional correlate of CD44H localization patterns was detected. In particular, cancer cells in which CD44H was localized at the basal or basolateral membranes were closely associated with high proliferative activity and high liver metastatic potential.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050031
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  • 60
    Digitale Medien
    Digitale Medien
    Effects of interleukin-6 (IL-6) on chemotherapy-induced apoptosis in human ovarian cancer cell lines (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 84-89 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Ovarian cancer ; Apoptosis ; IL-6 ; CDDP ; Taxol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Apoptosis is a cascade of events that is regulated by many factors. We studied the effects of interleukin-6 (IL-6) on chemotherapy-induced apoptosis in three human ovarian cancer cell lines (JV, GG, and NF). Methods. Cells were treated with the anticancer drugs cis-diamminedichloroplatinum (II) (CDDP) and paclitaxel (Taxol; Bristol-Myers Squibb Pharmacessticals, Noble Park, Australia) over a period of 72 h. The treatments were repeated in combination with human recombinant IL-6 or anti-IL-6 monoclonal antibody (anti-IL-6 mAb). The induction of cell death was examined by morphology and by internucleosomal DNA fragmentation. Results. Reduced cytotoxicity and fewer apoptotic cells were observed after treatment with CDDP or Taxol combined with IL-6 compared with treatment with CDDP or Taxol alone. However, treatment with CDDP or Taxol combined with anti-IL-6 mAb enhanced the cytotoxic effects of the drugs and increased the number of apoptotic cells. These findings indicated that apoptosis caused by CDDP or Taxol was influenced negatively by high doses of IL-6. Conclusion. The use of CDDP or Taxol combined with anti-IL-6 mAb may have therapeutic value for patients with ovarian cancer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050032
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  • 61
    Digitale Medien
    Digitale Medien
    Abnormalities of elastin and elastic fibers in infantile hypertrophic pyloric stenosis (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 540-542 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Infantile hypertrophic pyloric stenosis (IHPS) ; Elastic fibers ; Elastin ; Connective tissue ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle, causing pyloric-channel narrowing and elongation. The rigidity of the muscle is increased, which is characterized as an “olive.” Elastin is an insoluble protein that forms the major structural component of the elastic fibers and maintains the tensile strength of the tissues. To understand the possible histologic and molecular basis of the elasticity of the hypertrophic muscle in IHPS, we determined the distribution of the elastic fibers and elastin expression using Victoria blue van Gieson (VVG) staining and immunohistochemistry. In IHPS, the number of elastic fibers in the connective tissue was significantly increased in the thickened connective-tissue septa (CTS) compared with normal control specimens. In normal pyloric muscle, weak to moderate elastin immunoreactivity was observed in the CTS while no immunoreactivity was observed among the muscle fibers. In IHPS, strong immunoreactivity of elastin was observed in the CTS and moderate immunoreactivity among the hypertrophic smooth-muscle fibers. Our findings suggest that the increase on elastic fibers and elastin expression in the pyloric muscle in IHPS may play an important role in the development of pyloric-muscle rigidity, causing pyloric-canal obstruction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050665
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  • 62
    Digitale Medien
    Digitale Medien
    Preoperative imaging of a choledochal cyst in children: non-breath-holding magnetic resonance cholangiopancreatography (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 546-548 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Cholangiography ; Choledochal cyst ; Cholestasis ; Magnetic resonance imaging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Magnetic resonance cholangiopancreaticography (MRCP) was used to visualize the biliary tract in two children, aged 7 weeks and 10 years, with a choledochal cyst. MRCP was successful in both cases and the findings were confirmed by intraoperative cholangiography.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050667
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  • 63
    Digitale Medien
    Digitale Medien
    Posteromedial corner of the knee: MR imaging with gross anatomic correlation (1999)
    Springer
    Skeletal radiology 28 (1999), S. 305-311 
    Details
    ISSN: 1432-2161
    Schlagwort(e): Key words Joint ; Knee ; Anatomy ; Magnetic resonance imaging ; Posteromedial corner ; Intra-articular contrast
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Objective. The objective of this study was to illustrate the magnetic resonance (MR) image appearance of the structures of the posteromedial ”corner” of the knee with particular emphasis on the anatomy and differentiation between the medial collateral ligament and the posterior oblique ligament. Design. Six cadaveric knee specimens underwent MR imaging, before and following instillation of intra-articular contrast material. The knees were sectioned in the axial, coronal, and coronal oblique planes and the gross morphology of the posteromedial corner and surrounding structures was studied and correlated with the MR images. Patients. The human cadaveric specimens were from two female and four male patients (age at death, 72–86 years; average, 78 years). Results and conclusions. The contrast-enhanced sequences and the coronal oblique images allowed for improved visualization of the structures.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002560050522
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  • 64
    Digitale Medien
    Digitale Medien
    Chondrosarcoma of the foot: imaging, surgical and pathological correlation of three new cases (1999)
    Springer
    Skeletal radiology 28 (1999), S. 153-158 
    Details
    ISSN: 1432-2161
    Schlagwort(e): Key words Bone tumor ; Chondrosarcoma ; CT ; Magnetic resonance imaging ; Tumor of the ankle ; Tumor of the foot
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The foot is an uncommon location for chondrosarcoma. The presentation, diagnosis, pathological findings, surgical treatment and follow-up of three patients with chondrosarcoma in this rare location are presented. Though nonspecific, MR imaging findings were of aid in the diagnosis and treatment planning of these patients. If the diagnosis of this tumor is rapidly made, a tumor excision instead of limb amputation may be sufficient treatment at surgery.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002560050492
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  • 65
    Digitale Medien
    Digitale Medien
    Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells (1999)
    Springer
    Virchows Archiv 435 (1999), S. 496-500 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Tenascin-C ; Laryngeal carcinoma ; Immunohistochemistry ; In situ hybridization ; Cell proliferation ; Cell migration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Tenascin-C (TN-C) is an extracellular matrix glycoprotein upregulated in various pathological processes. In this study, we investigated its distribution in dysplasia and carcinoma of the human larynx using immunohistochemistry and in situ hybridization (ISH) techniques. In all cancer tissues, TN-C immunostaining was markedly increased in the stroma, especially around the cancer cell nests. In addition, cytoplasmic staining of cancer cells was also observed in 62.5% of the invasive cases, the cells being distributed in the periphery of the nests adjacent to the stroma. TN-C mRNA signals in cancer cells were detected in all six cases examined by ISH. Furthermore, in vitro evaluation of the roles of TN-C demonstrated an increase in the proliferating cell fraction in a dose-dependent manner. In a wound closure assay, the addition of TN-C promoted migration. We conclude that TN-C secreted by cancer cells may be involved in their proliferation and migration in an autocrine fashion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050433
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  • 66
    Digitale Medien
    Digitale Medien
    Malignant myoepithelioma of the breast metastasizing to the jaw (1999)
    Springer
    Virchows Archiv 435 (1999), S. 520-523 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Breast neoplasms ; Malignant myoepithelioma ; Metastasis ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A breast tumor in a 52-year-old female was interpreted as a malignant myoepithelioma based on morphological and immunohistochemical studies. The tumor consisted of elongated cells with clear cytoplasm and lacked glandular components. The tumor cells were stained positively for keratin, S-100 protein, glial fibrillary acidic protein (GFAP) and muscle-specific actin. Distant metastasis in the right jaw developed 8 years after the initial surgery and the metastatic deposit showed a similar morphology and immunoreactivity. Myoepithelial tumors are generally considered as benign or low-grade lesions and distant metastasis has been rarely documented. The present case presents the possibility of delayed occurrence of distant metastasis in myoepithelial tumor of the breast.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050436
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  • 67
    Digitale Medien
    Digitale Medien
    p21 Expression in colorectal carcinomas: a study on 103 cases with analysis of p53 gene mutation/expression and clinic-pathological correlations (1999)
    Springer
    Virchows Archiv 435 (1999), S. 559-565 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words p21 ; p53 ; Colon ; Immunohistochemistry ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050441
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  • 68
    Digitale Medien
    Digitale Medien
    Proliferation marker Ki-S11 – a prognostic indicator for squamous cell carcinoma of the hypopharynx (1999)
    Springer
    Virchows Archiv 435 (1999), S. 590-595 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Hypopharynx carcinoma ; Prognosis ; Proliferation ; Ki-S11 ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (〉45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050445
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  • 69
    Digitale Medien
    Digitale Medien
    Mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome: an autopsy case with a 24-year survival period (1999)
    Springer
    Virchows Archiv 435 (1999), S. 606-611 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Mixed ductal-endocrine carcinoma ; Pancreas ; Gastrinoma ; Immunohistochemistry ; Zollinger-Ellison syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We report an autopsy case of mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome. A 38-year-old Japanese male was found to have Zollinger-Ellison syndrome and pancreatic gastrinoma, and gastrectomy and resection of the pancreatic tumor were performed. However, hypergastrinemia persisted, and the patient died of disseminated carcinomatosis at 62 years of age, 24 years after the onset of Zollinger-Ellison syndrome. At autopsy, the main tumor was present in the residual pancreas, and metastases were noted in many organs. In the pancreas and other organs, ductal and endocrine carcinoma areas were mixed and there was a gradual transition between the two. No acinar differentiation was noted. The ductal elements were positive for mucins and carcinoembryonic antigen but negative for neuroendocrine markers, while endocrine elements were positive for chromogranin A and synaptophysin and to a lesser extent for gastrin, but negative for mucins and carcinoembryonic antigen. The ductal elements comprised about 30% of the tumor cells, and endocrine elements 70%. According to the revised World Health Organization classification, our case was diagnosed as mixed ductal-endocrine carcinoma. Our case is rare because the tumor manifested as gastrinoma with Zollinger-Ellison syndrome and the patient survived for 24 years. To the best of our knowledge, no such case has been reported. Our case suggests that pancreatic endocrine tumors may evolve into mixed ductal-endocrine carcinomas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050447
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  • 70
    Digitale Medien
    Digitale Medien
    Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma (1999)
    Springer
    Virchows Archiv 434 (1999), S. 153-158 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Cyclin B1 ; Esophageal squamous cell carcinoma ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9 % (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P〈0.005) and with venous invasion (P〈0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P〈0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P〈0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050319
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  • 71
    Digitale Medien
    Digitale Medien
    Myoepithelial cells and basal lamina in poorly differentiated in situ duct carcinoma of the breast (1999)
    Springer
    Virchows Archiv 434 (1999), S. 227-234 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Ductal carcinoma in situ ; Immunohistochemistry ; Myoepithelial cells ; Basal lamina ; Smooth muscle actin ; Calponin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A retrospective study was made of 38 selected brest tumours with a poorly differentiated in situ duct component. These were classified on haematoxylin and eosin (H&E) as ductal carcinoma in situ (DCIS; 10 cases), DCIS with invasion (17 cases) and DCIS with features suggestive of for stromal invasion (11 cases). The last were these lesions composed of neoplastic ducts with irregular outlines and a myoepithelial layer that was not clearly evident or large neoplastic ducts growing close together or surrounded by inflammatory desmoplastic stroma. Cases of DCIS involving areas of sclerosing adenosis were included in this category. Consecutive sections obtained from each case were studied with a panel of antibodies against myoepithelial cells (alpha smooth muscle actin and calponin) and basal lamina (BL) components (laminin and type IV collagen). It was found that in situ lesions showed well-formed basal lamina and/or an evident myoepithelial layer. These features were lacking in the invasive areas. Nine of the 11 cases with suggestive features of stromal invasion were reclassified as invasive duct carcinoma (5 cases)and DCIS (4 cases), according to the absence or presence of a continuous myoepithelial layer and/or basal lamina. In 2 such cases immunohistochemistry yielded equivocal results and the label ”suggestive of invasion” was therefore pertinent. Immunohistochemistry facilitates the diagnosis of breast DCIS; myoepithelial and basal lamina markers are useful in differentiating microinvasive from in situ ductal carcinomas of the breast.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050332
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  • 72
    Digitale Medien
    Digitale Medien
    Variable expression of heparan sulfate epitopes in crescents of human glomerulonephritis (1999)
    Springer
    Virchows Archiv 434 (1999), S. 145-151 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Carbohydrates ; N-Sulfation ; O-Sulfation ; Immunohistochemistry ; Rapidly progressive glomerulonephritis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050318
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  • 73
    Digitale Medien
    Digitale Medien
    Autonomic nerve tumour with skeinoid fibres: ultrastructure of skeinoid fibres examined by quick-freezing and deep-etching method (1999)
    Springer
    Virchows Archiv 434 (1999), S. 267-276 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Autonomic nerve tumour ; Small intestine ; Immunohistochemistry ; Quick-freezing ; Deep-etching
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A case of gastrointestinal autonomic nerve tumour with skeinoid fibres (SFs) of the jejunum in a 79-year-old Japanese man, was examined by the quick-freezing and deep-etching (QF-DE) method. The tumour consisted of spindle cells with immunohistochemical reactions for vimentin, NSE and CD34. Electron microscopically, features of the neural cells of the myenteric plexus were observed. The QF-DE method demonstrated intercellular meshwork structures, consisting of thin filaments (7–15 nm), with granular deposits. Fully developed parts of the deposits formed nodular aggregates composed of irregularly surfaced thick fibrils (30–48 nm) with a tendency to linear arrangement (SFs). We detected many interconnecting thin filaments (ICTFs) between the SFs, which were pre-existing components in the meshwork, avoiding the granular deposits. The focal thickening formed by the connection between SFs and ICTFs revealed a periodicity typical of SFs (33–45 nm). We conclude that SFs are formed by decoration of the granular deposits along pre-existing intercellular meshwork structures.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050340
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  • 74
    Digitale Medien
    Digitale Medien
    Reduced expression of CD99 and functional disturbance in anencephalic cortical thymocytes (1999)
    Springer
    Virchows Archiv 434 (1999), S. 443-449 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Anencephaly ; Thymic hyperplasia ; CD99 ; Apoptosis ; Aggregation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In a significant proportion of cases, anencephaly is associated with thymic enlargement, suggesting a possibility that anencephalic fetuses have a functional disturbance in thymocyte differentiation and development. In this report, we demonstrated that CD99 expression was consistently reduced in cortical thymocytes of all anencephalic fetuses. In addition, the CD99-dependent aggregation of immature cortical thymocytes was almost completely impaired and apoptosis of thymocytes was markedly reduced in several cases. These results are in agreement with previous findings that CD99 regulates the aggregation and apoptosis of various types of cells. These data strongly suggest that functional disturbance of thymocytes and thymic hyperplasia are related to the reduced expression of CD99 molecule in anencephalic fetuses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050364
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  • 75
    Digitale Medien
    Digitale Medien
    Immunohistochemical localization of α- and βA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system (1999)
    Springer
    Virchows Archiv 434 (1999), S. 29-36 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Activin A ; Inhibin A ; Endocrine tumors ; Digestive system ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one α-subunit and one βA-subunit (α-βA), while activin A is a homodimer of the βA-subunit (βA-βA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the α- and βA-subunits of inhibin/activin. Immunoreactivity for the βA-subunit, but not for the α-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. βA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The α-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the βA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050301
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  • 76
    Digitale Medien
    Digitale Medien
    Reconstruction of pleomorphic adenoma of the salivary glands in three-dimensional collagen gel matrix culture (1999)
    Springer
    Virchows Archiv 434 (1999), S. 137-143 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Salivary gland ; Pleomorphic adenoma ; Collagen ; Cell culture ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and α-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multi-directional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050317
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  • 77
    Digitale Medien
    Digitale Medien
    Systemic granulomatous arteritis associated with Epstein-Barr virus infection (1999)
    Springer
    Virchows Archiv 434 (1999), S. 249-254 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Systemic granulomatous arteritis ; Epstein-Barr virus ; Virus-associated haemophagocytic syndrome ; In situ hybridization ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A 61-year-old woman initially presented with symptoms and findings reminiscent of infectious mononucleosis, and her illness then took a rapidly fatal course. Autopsy revealed widespread granulomatous arteritis, with multinucleated giant cells but without eosinophils and fibrinoid necrosis, affecting small arteries and arterioles and infiltration of haemophagocytic histiocytes into many organs. In situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide probes showed positive signals in the infiltrating immune cells and epithelial and endothelial cells of the affected organs. EBV-associated haemophagocytic syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the immunophenotypes of the infiltrating immune cells, a possible role of CD4+ T-cells in the pathogenesis of this haemophagocytic syndrome and granulomatous vasculitis was suggested.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050336
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  • 78
    Digitale Medien
    Digitale Medien
    High-grade carcinoma component in epithelial-myoepithelial carcinoma of salivary glands clinicopathological, immunohistochemical and flow-cytometric study of three cases (1999)
    Springer
    Virchows Archiv 434 (1999), S. 291-299 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Epithelial myoepithelial carcinoma ; Salivary gland tumours ; Immunohistochemistry ; Flow cytometry ; MIB-1 (Ki 67) ; Proliferative markers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Three cases of epithelial-myoepithelial carcinoma (EMC) with coexisting areas of high grade carcinoma are reported. In two of the cases there was a previous recurrence, and in all three patients there had been a sudden increase in size before final surgery. The typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of wide spectrum cytokeratins, Cam 5.2 and EMA in the ductal part, and muscle-specific actin, smooth muscle actin, S-100 protein, vimentin and cytokeratins in the myoepithelial component. These areas also had a low mitotic count and low proliferation rate as measured by immunohistochemistry and by flow cytometry. Conversely, areas of high-grade tumour had the features of a large cell carcinoma, with focal mucin secretion in two cases. This high-grade component showed an epithelial immunophenotype in two cases, and was negative for all tested markers in the third one. The mitotic counts and the proliferation rates were much higher in these anaplastic areas. One of the patients died 3 months after treatment; another developed lymph node metastases 1 year later and was alive after 6 years of follow-up. The third patient was alive without evidence of disease 7 months after wide surgical resection of the tumour. The possibility of anaplastic transformation in EMC makes thorough sampling mandatory in this type of neoplasm.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050344
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  • 79
    Digitale Medien
    Digitale Medien
    Cerebrovascular involvement in systemic AA and AL amyloidosis: a clear haematogenic pattern (1999)
    Springer
    Virchows Archiv 434 (1999), S. 551-560 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Systemic amyloidosis ; Brain ; Circumventricular organs ; Choroid plexus ; Immunohistochemistry ; Aβ colocalization.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Amyloid deposits in cerebral vessels are common in β-amyloid diseases (Alzheimer’s disease, congophilic amyloid angiopathy, Down’s syndrome and hereditary cerebral amyloidosis with haemorrhage of the Dutch type). We report of 20 autopsies on patients who had died with systemic amyloidosis of the AA, Aλ and Aκ types: the brains were examined for the occurrence of amyloid. Vascular amyloid was detected in choroid plexus (in 17 of 20 cases), infundibulum (5 of 8), area postrema (6 of 11), pineal body (3 of 7) and subfornical organ (2 of 3), but not in cortical and leptomeningeal vessels. Immunohistochemical classification of the cerebral amyloid and the systemic amyloid syndrome showed identity proving the same origin of both. The distribution is indicative of a haematogenic pattern of amyloid deposition in systemic amyloidosis and is different from that in Alzheimer’s, prion, ATTR and cystatin C diseases. It corresponds to areas of the brain with a ”leaky” blood–brain barrier. Additionally, all the cases with AA amyloidosis exhibited an Aβ coreactivity in choroid plexus vessels. In one exceptional case, Aβ reactivity of AA amyloid also occurred outside of the brain.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050383
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  • 80
    Digitale Medien
    Digitale Medien
    Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations (1999)
    Springer
    Virchows Archiv 434 (1999), S. 489-495 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words E-cadherin ; Colorectal cancer ; Immunohistochemistry ; Mutation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050373
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  • 81
    Digitale Medien
    Digitale Medien
    Galectin-1 and galectin-3 expression in human prostate tissue and prostate cancer (1999)
    Springer
    Urological research 27 (1999), S. 362-367 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key words Galectin-1 ; Galectin-3 ; Human prostate ; cancer ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Galectin-1 and galectin-3, two β-galactoside-binding proteins, have been suggested to play a role in the development and progression of cancer. We have studied the expression of these molecules in normal human prostate tissue and prostate adenocarcinoma. Immunohistochemistry was used to examine formalin-fixed, paraffin-embedded sections of seven normal human prostates, eight cases of prostatic intraepithelial neoplasia (PIN), 20 primary adenocarcinomas of the prostate, and 12 prostate cancer metastases. Galectin-1 was expressed in most cases of all four histologic types. In contrast, galectin-3 expression was significantly decreased in primary carcinoma and metastatic disease compared with normal and premalignant tissue. Galectin-3 expression in primary tumors tended to be less than that of surrounding normal glands. We conclude that loss of galectin-3 expression may be associated with the progression of prostate cancer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050164
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  • 82
    Digitale Medien
    Digitale Medien
    Clinical significance of nm23 expression in renal cell carcinoma (1999)
    Springer
    Urological research 27 (1999), S. 103-107 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key wordsnm23 ; Immunohistochemistry ; Renal cell carcinoma ; Flow cytometry ; Survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In many tumors an expression of nm23 gene products is associated with a lower metastatic potential. The aim was to evaluate whether nm23 gene expression in renal cell carcinoma was associated with clinicopathological findings and survival. In 41 patients, the expression of nm23 protein was analyzed in tumor and corresponding kidney cortex tissue by immunohistochemical analysis using a monoclonal nm23-H1 antibody. In all kidney cortex samples intense nm23 staining was found. Of 41 tumors, 15 had high, 12 intermediate, 5 low nm23 expression whereas 9 tumors showed none. There were no differences in nm23 staining between different stages, grades or size of tumor. No correlation between survival and nm23 expression was observed. However, diploid tumors had significantly less nm23 staining compared with aneuploid tumors, indicating that nm23 gene inactivation might be a favorable sign. The expression of nm23 gene products seems not to be correlated to tumor progression and metastatic ability in renal cell carcinoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050095
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  • 83
    Digitale Medien
    Digitale Medien
    Hemmung der Tumorneoangiogenese und Induktion von Apoptose als Eigenschaften von Docetaxel (Taxotere®) (1999)
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 3 (1999), S. 210-212 
    Details
    ISSN: 1434-3940
    Schlagwort(e): Schlüsselwörter Plattenepithelkarzinom ; Tumorneoangiogenese ; Apoptose ; Key words Squamous cell carcinoma ; Tumor neoangiogenesis ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Paclitaxel and docetaxel are potent drugs that are effective in the treatment of malignant tumors. The cytotoxic action of these drugs is not fully understood, but it appears to be mediated mainly through mitotic arrest and subsequent apoptosis. Because no information is available on the antiangiogenesis action of docetaxel, the investigations were performed to determine whether inhibition of neoangiogenesis plays a role in docetaxel’s antitumor efficacy. Four different mouse tumors, two squamous cell carcinomas (SCC-IV; SCC-VII) and two adenocarcinomas (MCA-4; MCA-29) were assayed for angiogenic activity using the in vivo i.c. angiogenesis assay. Tumor cells (5 × 105) were injected i.c. into the skin flap over the abdominal wall, and the number of new blood vessels at the tumor cell injection site was determined 2, 4, 6, 8, 10 and 12 days later. The mice were treated with docetaxel (Taxotere – 31.3 mg/kg i.v.) 1 or 4 days after tumor cell injection. The number of new blood vessels increased with time. Docetaxel reduced the number of newly formed blood vessels in MCAs, but not in SCCs. The reduction was associated with slower tumor growth. In a separate set of experiments we observed that docetaxel’s inhibitory effect on the two MCAs was histologically associated with massive tumor cell destruction by means of both apoptosis and necrosis. This was not observed for the two SCCs. Since no reduction in blood vessels occurred in tumors unresponsive to docetaxel, the inhibition of neoangiogenesis in docetaxel-responsive tumors was likely the result of a decrease in angiogenic stimuli due to docetaxel’s destruction of tumor cells.
    Notizen: Die zytotoxische Aktivität der Taxane Paclitaxel und Docetaxel ist zum jetzigen Zeitpunkt noch nicht vollständig erklärt. Diese, zur Behandlung maligner Tumoren eingesetzten antineoplastischen Chemotherapeutika, scheinen jedoch weitgehend über die Blockierung der Mitose und die nachfolgende Induktion der Apoptose zu wirken. Über eine evtl. Hemmung der Neoangiogenese, wie sie kürzlich für Paclitaxel beschrieben wurde, liegen für Docetaxel noch keine Studienergebnisse vor. Es wurde deshalb untersucht, ob die therapeutische Aktivität von Docetaxel zur Hemmung der Neoangiogenese im Tumor beitragen kann. 4 murine Tumoren, 2 Plattenepithelkarzinome (SCC-VII; SCC-IV) und 2 Adenokarzinome (MCA-4; MCA-29), wurden in einem quantitativen intrakutanen In-vivo-Angiogenese-Assay experimentell untersucht. 5 · 10 5 Tumorzellen wurden in einen Abdominallappen der Maus injiziert. Die Anzahl neuformierter Blutgefäße und das Tumorwachstum wurden im 2tägigen Intervall über einen Zeitraum von zwischen 10 und 14 Tagen bestimmt. 2 Behandlungsgruppen wurde am 1. oder 4. Tag nach der Tumorzellinokulation Docetaxel (Taxotere – 31,3 mg/kg) i.v. injiziert. Die Plattenepithelkarzinome waren gegenüber der Therapie mit Docetaxel nicht sensibel, während die Adenokarzinome mit einer Abnahme der Gefäßzahl und einer Reduktion des Tumorvolumens reagierten. Histologisch zeigten die Adenokarzinome außerdem eine massive Tumorzelldestruktion durch Apoptose und Nekrose. Da die gegenüber Docetaxel nichtsensiblen Tumoren (Plattenepithelkarzinome) nicht mit einer Abnahme der Gefäßzahl reagierten, ist der beschriebene Effekt in den Adenokarzinomen am ehesten als indirekte Wirkung von Docetaxel zu werten. Die Tumorzelldestruktion führte in den betroffenen Tumoren zu einer verminderten Freisetzung endothelialer Mitogene wie VEGF und bFGF und zur Hemmung der Tumorneoangiogenese.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s100060050132
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  • 84
    Digitale Medien
    Digitale Medien
    Differential expression of heat shock proteins 70-1 and 70-2 mRNA after ischemia-reperfusion injury of rat kidney (1999)
    Springer
    Urological research 27 (1999), S. 306-311 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Keywords Ischemia-reperfusion ; Heat shock ; HSP70 ; Kidney ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i –HSP70-1 gene and HSP70-2 gene – is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10–60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA – which was generally expressed at a far lower level than HSP70-1 mRNA – was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050155
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  • 85
    Digitale Medien
    Digitale Medien
    Apoptosis in human embryonal cell carcinoma: preliminary results (1999)
    Springer
    Urological research 27 (1999), S. 368-375 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Keywords Testicular neoplasms ; Embryonal cell ; carcinoma ; Apoptosis ; Lymphocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Disorders in the regulation of apoptotic cell death may contribute to cancer. Furthermore, lymphocytes are supposed to play a role in counteracting tumorigenesis by inducing apoptosis in different human tumors. In this study, for the first time, tumor cell and lymphocyte apoptosis were investigated systematically in human embryonal cell carcinoma. DNA fragmentation and DNA condensation were measured simultaneously on double-fluorescence-labeled testis tumor sections using immunofluorescence microscopy. Different apoptotic indices (AIs), based either on biochemical (DNA fragmentation) or morphological criteria (DNA condensation) alone or on a combination of both, were determined in different histological regions in and around the tumor. Using morphological criteria alone, 40–75% of all apoptotic cells were not detected. Based on previous observations this finding might be related to subsets of apoptotic cells which induce the process of DNA condensation without activation of processes responsible for DNA fragmentation. Moreover, the AIs of tumor cells and lymphocytes were highest in the tumor region, compared with regions around the tumor and distant from it; these findings are discussed in the context of the Fas/FasL system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050165
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  • 86
    Digitale Medien
    Digitale Medien
    Localization and expression of Jun-like immunoreactivity in apoptotic neurons induced by colchicine administration in vivo and in vitro depends on the antisera used (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 119-128 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words c-Jun ; Jun B ; Jun D ; Apoptosis ; Colchicine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of members of the Jun family of transcription factors was examined by immunohistochemistry, Western blotting, in situ hybridization and Northern blotting in the developing and adult rat brain following colchicine administration. Apoptotic cells, as revealed by their typical morphology and positive staining with the method of in situ end-labeling of nuclear DNA fragmentation, were restricted to granule cells of the dentate gyrus and olfactory bulb, and a few cells in the upper layers of the entorhinal cortex in adult rats, whereas widespread apoptosis occurred in developing rats after colchicine administration. No modifications in the expression of Jun D and Jun B, except for a generalized and moderate Jun B expression in glial cells, were observed in colchicine-treated rats. Generalized and strong c-jun mRNA induction and c-Jun/AP-1 (Ab-1) protein expression was observed in the cerebral neocortex, entorhinal and piriform cortices, CA1 and CA3 areas of the hippocampus and granule cell layer of the dentate gyrus in adult treated rats, thus indicating a generalized c-Jun response to colchicine administration. In contrast, c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) immunoreactivity was restricted to apoptotic cells in colchicine-treated adult and developing brains. Western blots of hippocampal homogenates and total brain homogenates in adult and developing rats, respectively, demonstrated a band of 39 kDa for the c-Jun/AP-1 (Ab-1) antibody in control animals, the intensity of which increased in colchicine-treated rats. However, a band of 37 kDa, the intensity of which also increased following colchicine administration, was observed for the c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) antibodies. Selective c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) expression was also observed in apoptotic cells of the SH-SY5Y neuroblastoma line after the addition of colchicine to the culture medium. Taken together, the present in vivo and in vitro results indicate a generalized c-Jun response to colchicine in sensitive cells, whereas the antibodies c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) recognize vulnerable cells dying via apoptosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051059
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  • 87
    Digitale Medien
    Digitale Medien
    Bunina bodies in amyotrophic lateral sclerosis on Guam: a histochemical, immunohistochemical and ultrastructural investigation (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 150-156 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; Bunina body ; Guam ; Immunohistochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An investigation of Bunina bodies is important when studying the pathoetiology and pathomechanisms involved in amyotrophic lateral sclerosis (ALS). It may serve as a clue essential for the study of the pathogenesis of Guamanian amyotrophic lateral sclerosis (ALS-G), and it may provide a means of answering the question of whether ALS-G is the same disease as classical ALS or a different entity. In ALS-G, however, no precise histochemical, immunohistochemical, or detailed ultrastructural examination has been published to date. To elucidate the pathological differences/similarities of Bunina bodies between classical ALS and ALS-G, we performed histochemical, immunohistochemical, topographic and ultrastructural examinations. Histochemically, hematoxylin and eosin, Masson’s trichrome, methylgreen-pyronin, phosphotungstic acid-hematoxylin, Klüver-Barrera, Bodian and periodic acid-Schiff staining were utilized. Immunohistochemical examination was performed using antibodies for cystatin C, ubiquitin, Tau-2, Cu/Zn superoxide dismutase, phosphorylated neurofilament and glial fibrillary acidic protein. Histochemical findings were consistent with those previously described for classical ALS. The immunohistochemical study showed that in ALS-G Bunina bodies were intensely labeled by an anti-cystatin C antibody. Topographic examination demonstrated that Bunina bodies were distributed in the spinal anterior horns and Clarke’s column in the spinal cord. Ultrastructurally, Bunina bodies were composed of electron-dense amorphous/ granular material accompanied by vesicular structures and neurofilaments. The results of the present study have revealed that the pathological features of Bunina bodies in ALS-G are identical to those seen in classical ALS. These findings strongly suggest that a similar degenerative process occurs in the spinal anterior horn cells in both ALS-G and classical ALS.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051063
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  • 88
    Digitale Medien
    Digitale Medien
    Immunohistochemical study of some cytoskeletal proteins in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 177-184 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Cytoskeletal proteins ; Immunohistochemistry ; Myofibrillar myopathy ; Hereditary myopathy ; Holstein-Friesian cattle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have investigated the expression, using immunohistochemical and Western blot methods, of some cytoskeletal proteins including desmin, vimentin, actin, α-actinin, and ubiquitin in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle (the histochemical and electron microscopical aspects have been previously reported). Immunohistochemically, the expression of desmin was observed strongly in the subsarcolemmal regions, but was lacking or faint in the area corresponding to the core-like structures. Vimentin showed almost the same localization as desmin, but no activity could be observed in the core-like structures. In addition, the core-like structures showed strong immunoreactivity for actin and ubiquitin, but no immunoreactivity for α-actinin. F-actin stained with phalloidin-tetramethyl-rhodamine was strongly positive in irregular spots that corresponded to the core-like structures, but was negative for desmin-positive regions. Western blot analysis of the diseased muscles revealed a significant increase in the amount of desmin and vimentin immunoreactivities and similar amounts of actin and α-actinin compared with the control muscles. Two-dimensional electrophoresis revealed no isoforms of desmin, suggesting the absence of abnormal phosphorylated forms of desmin. Since the co-localization of desmin and vimentin and the absence of phosphorylated desmin suggest that the overexpression of desmin may be reflected in the reactive change or regenerating process, the present myopathy should be regarded as an entity separate from desmin-storage myopathy or desmin-related myopathies. We also discuss the possibility that the present myopathy could be considered as myofibrillar myopathy, a recently proposed nosological entity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050971
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  • 89
    Digitale Medien
    Digitale Medien
    Neuronal vacuolation in young Rottweiler dogs (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 192-195 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Neuronal vacuolation ; Rottweiler dog ; Bcl-2 ; Bax ; c-Jun ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neuronal vacuolation, involving the cerebellar roof nuclei, Purkinje cells, selected nuclei of the brain stem, thalamus, Clarke’s column, anterior and posterior horns of the spinal cord, visceral autonomic ganglia and myenteric plexus, as well as axonal degeneration of the white matter of the brain stem, cerebellar pedunculi, dorsolateral columns of the spinal cord and ventral roots of the spinal cord, were observed in two young Rottweiler dogs which were clinically afflicted with hind limb weakness progressing to paraparesia, ataxia, intention tremor, and difficulty in swallowing and barking. The absence of modifications in Bcl-2 and Bax immunoreactivity, a lack of strong c-Jun/AP-1 (N) immunoreactivity in vacuolated cells, and the absence of DNA breaks, as seen with the method of in situ end-labeling of nuclear DNA fragmentation, all suggest that there is no involvement of the apoptotic pathway in vacuolated cells in this new neurodegenerative disorder.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050973
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  • 90
    Digitale Medien
    Digitale Medien
    Increased lipocortin-1 (annexin-1) expression in the sciatic nerve of Lewis rats with experimental autoimmune neuritis (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 583-589 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Glucocorticosteroids ; Apoptosis ; Guillain-Barré syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Lipocortin-1 exerts a potent immunosuppressive effect on pathogenic T cells. In multiple sclerosis and experimental autoimmune encephalomyelitis levels of lipocortins are raised, suggesting their involvement in the recovery from an immunological insult or in neural regeneration. To further understand the role of lipocortins in the peripheral nervous system we have characterized lipocortin-1 levels and cellular distribution of lipocortin-1 immunoreactivity in sciatic nerves of rats with experimental autoimmune neuritis (EAN), a model of human Guillain-Barré syndrome. EAN was induced actively by immunization with bovine peripheral myelin (active EAN) or by adoptive-transfer (AT-EAN) of P2-specific T cells. Cellular infiltrates in serial and semithin cryosections were characterized by immunohistochemistry. In parallel, lipocortin-1 levels in tissue extracts were quantified by a sandwich-ELISA. Only weak lipocortin-1 immunoreactivity was found in nerves of control animals injected with non-pathogenic T cells. The majority of macrophages and lymphocytes in EAN lesions exhibited lipocortin-1 immunoreactivity. Some very heavily stained cells showed a distribution and morphology similar to ED-2-positive macrophages which were abundant during early stages of EAN. Lipocortin-1 expression in T cells and macrophages was proven by immunocytochemical studies in semithin serial sections. In tissue extracts, lipocortin-1 levels increased from 0.24 ± 0.14 μg/mg protein in controls receiving non-pathogenic T cells to a maximum of 0.55 ± 0.1 μg/mg protein in AT-EAN at the peak of disease, and then slowly decreased during clinical recovery but still remained elevated. In dose-response studies in AT-EAN, highest values of lipocortin-1 (0.71 ± 0.23 μg/mg protein) were recorded after transfer of 2 × 107 T cells. Increased levels of lipocortin-1 were also measured in active EAN but occurred during the recovery phase (0.65 ± 0.27 μg/mg protein). By analogy with other immune-mediated disorders, increased lipocortin-1 expression in the inflamed sciatic nerve in EAN may exert immunoregulatory functions in-situ and contribute to the termination of the autoimmune response.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051122
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  • 91
    Digitale Medien
    Digitale Medien
    Changes in serotonergic neurons in the brain of pyrithiamine-induced acute thiamine-deficient mice (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 614-621 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Serotonin ; Thiamine deficiency ; Immunohistochemistry ; Vulnerability ; Degeneration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We examined changes in 5-hydroxytriptamine (5-HT, serotonin) neurons in pyrithiamine-induced thiamine deficiency in mice immunohistochemically. Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus. Most remarkably, degenerative winding fibers were detected between the deep mesencephalic nucleus and the ventral tegmental area. Increases in intensity of 5-HT immunoreactivity in the dorsal raphe nucleus and decreases in the number of 5-HT-immunoreactive cell bodies in the dorsal and the median raphe nuclei were detected. These results demonstrated the differential vulnerability of 5-HT neurons in thiamine-deficient mice. This is the first report to demonstrate changes in 5-HT neurons immunohistochemically throughout the brain of pyrithiamine-induced thiamine deficient mouse.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051126
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  • 92
    Digitale Medien
    Digitale Medien
    Chronological study of the appearance of adenohypophysial cells in the ayu (Plecoglossus altivelis) (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 469-475 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Fish ; Pituitary gland ; Developmental biology ; Cell differentiation ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We previously reported the chronological appearance of adenohypophysial cells in freshwater teleosts using an immunocytochemical technique. The present study investigated the chronological appearance of adenohypophysial cells in the ayu, which is spawned and has its early development in brackish water, and the results were compared with those obtained in freshwater and seawater teleosts, as well as in other vertebrates. In the adult teleostean adenohypophysis, seven or eight types of secretory cells have been distinguished, each of which produce different hormones: prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), gonadotropic hormones (GTH I and GTH II), adrenocorticotropic hormone (ACTH), melanophore stimulating hormone (MSH) and somatolactin (SL). In the pituitary of adult ayu, seven distinct types of glandular cells (PRL, GH, TSH, GTH, ACTH, MSH and SL cells) were identified. Chronologically, a few immunoreactive (ir)-PRL and ir-GH cells appeared in the ventral side of the pituitary one day before hatching. Then, just after hatching, ir-GTH cells were observed in the central to dorsal portion; ir-ACTH cells were found distributed in the anterior portion and some ir-MSH and a few ir-SL cells were seen in the posterior portion of the pituitary. Finally, a small number of ir-TSH cells were identified 50 days after hatching. These results differed from those obtained in other fishes previously reported with regard to the times of appearance of the PRL and GH cells. PRL cells appeared first, followed by GH cells in the freshwater teleosts, PRL and GH cells appeared at the same time in the brackishwater teleosts, while GH cells appeared first and PRL cells appeared last in the seawater teleosts. These results reflect the fact that PRL plays a major role in osmoregulation among freshwater teleosts, as compared with GH, which plays a similar role in seawater teleosts. It seems that both PRL and GH may play important roles in osmoregulation in brackishwater fish.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050295
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  • 93
    Digitale Medien
    Digitale Medien
    Nitric oxide synthase-containing neurons in the myenteric plexus of the rat gastrointestinal tract: distribution and regional density (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 99-112 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Autonomic ; Wholemounts ; Immunohistochemistry ; Myenteric ganglia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Nitrergic (NO) neurons play crucial inhibitory roles in the control of gut motility. Variations in the density of these neurons within the gastrointestinal tract (GI) may provide useful functional information, but, most surveys available have employed limited and/or highly localized samples. It remains unclear to what extent (a) NO neurons are concentrated disproportionately in particular GI regions, or (b) variations in NO cell number merely reflect changes in overall myenteric neuron density. This experiment surveyed the distributions of neuronal nitric oxide synthase-positive (NOS+) and other myenteric neurons in the GI tract, using immunohistochemical and Cuprolinic blue counterstaining techniques. Adjustable sampling grids superimposed on wholemounts were used to investigate the topographic patterns in the stomach (90 sampling sites; 45 per side) and proximal duodenum (63 loci). We present four major findings: First, variations were detected in the number of NOS+ neurons in specific regions of the stomach (e.g., corpus〉antrum@forestomach) and along both longitudinal (oral〉anal) and circumferential (mesenteric〉antimesenteric) axes in the duodenum. Second, the variations in NOS+ neuronal counts within each organ covaried with the total number of myenteric neurons at different locations (stomach, r=0.77; duodenum, r=0.59), suggesting that local myenteric plexus density is a factor determining NOS+ cell concentrations. Third, in contrast to such a principle of covariation within each organ, NOS+ neurons constituted a consistently smaller proportion of gastric (20%) than of duodenal (28%) myenteric plexus neurons, suggesting that a second principle controls the characteristic percentages of the myenteric plexus that express NOS in different organs. Fourth, the regional samples were used to extrapolate the overall number of NOS+ and total myenteric cells in the rat stomach (43,000; 217,000) and first 3.5 cm of the small intestine (29,000; 103,000). These results, taken together, also suggest that the surveying protocol used is capable of detecting subtle differences in cellular distributions, thus providing a practical strategy for investigating patterns of chemical phenotypes within the GI tract.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050213
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  • 94
    Digitale Medien
    Digitale Medien
    Immunoelectron microscopic study of c-Fos, c-Jun and heat shock protein after transient cerebral ischemia in gerbils (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 22-30 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Immediate early gene ; Heat shock protein ; Cerebral ischemia ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The neuroprotective role of the expression of heat shock protein (HSP) and immediate early gene remains unclear. Using immunoelectron microscopy, we examined the ultrastructural integrity of the neurons with expression of c-Fos, c-Jun and HSP70 in gerbils after transient cerebral ischemia and repefusion. Induction of c-Fos and c-Jun was observed in the CA3 region resistant to ischemia, while HSP70 was expressed not only in the CA3 but also in the vulnerable CA1 region. With immunoelectron microscopy, the expression of c-Fos/c-Jun and HSP70 was observed in the neurons which retained neuronal integrity except for mitochondrial swelling and polyribosomal disaggregation. In contrast, the CA1 neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and parallel stacking of rough endoplasmic reticulum, the features associated with the process of delayed neuronal death. These findings suggested that c-Fos and c-Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up-regulated even in neurons with irreversible damage, but was more preferentially and intensely expressed in neurons with reversible damage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050951
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  • 95
    Digitale Medien
    Digitale Medien
    Nuclear DNA fragmentation in Creutzfeldt-Jakob disease: does a mere positive in situ nuclear end-labeling indicate apoptosis? (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 5-12 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Creutzfeldt-Jakob disease ; Apoptosis ; Cell death ; Prion protein ; In situ end-labeling of nuclear DNA fragmentation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The method of in situ end-labeling of nuclear DNA fragmentation was used in the study of ten patients (two biopsies, eight autopsies) with sporadic Creutzfeldt-Jakob disease (CJD). All the patients had the typical morphological lesions including neuron loss, spongiform change and astrocytosis. Four of them also showed prion protein (PrP) deposits in the cerebral cortex, and two of them kuru-like plaques in the cerebellum. A few cells with DNA breaks were found in the two biopsy cases; one of them, suffering from a panencephalopathic form of the disease, showed positive nuclei not only in the cerebral cortex but also in the subcortical white matter. Variable numbers of positive nuclei were observed in the gray and white matter in the eight autopsy cases, in which, although the distribution of positive cells roughly correlated with the distribution of neuron loss, no clear relationship was found as regards the distribution and degree of cell labeling and the degree of neuron loss. Furthermore, large numbers of positive cells were concentrated in a particular area, whereas a few cells were seen in a neighboring equally affected area. Positive glial cells in the plexiform layer of the CA1 area of the hippocampus, and in the frontal white matter were frequently encountered. Staining of the cytoplasm in a minority of cells was interpreted as the result of nuclear DNA leakage. None of the stained cells had the typical morphology of apoptosis; most particularly, peripheral chromatin condensation and formation of apoptotic bodies were not seen in any case. PrP deposits did not result in an increase of nuclear DNA breaks either within the area or in adjacent regions. Although positive cells were also observed in autopsy cases of controls which were processed in the same way, positive labeling as a whole was higher in CJD than in age-matched controls. These results show that brain nuclear DNA is vulnerable in CJD, and suggest that increased DNA vulnerability has a role in cell death and neuron loss. Since nuclear shrinkage and positive nuclear staining with the method of in situ end-labeling of nuclear DNA fragmentation are not exclusive to apoptosis, further information is needed to categorize cell death in CJD as apoptosis. Necrosis or other forms of cell death, as well as increased DNA vulnerability to agonal changes of the individuals, and to postmortem delay in the fixation of the tissues, may account for additional positive staining in cases examined at autopsy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050949
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  • 96
    Digitale Medien
    Digitale Medien
    Immunocytochemical demonstration of oncocytes in normal adenohypophysis (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 40-44 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Pituitary gland ; Immunohistochemistry ; Mitochondria ; Oncocytes ; Oncocytomas
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Immunocytochemical examination for mitochondrial protein and cytochrome oxidase was performed to demonstrate oncocytes in normal adenohypophysis obtained from 28 patients of various age. A small number of solitary large epithelial cells showed intense cytoplasmic granular immunoreactivities for mitochondrial protein and cytochrome oxidase. The proportions of the cells positive for the former and the latter ranged from 0% to 5.9% (mean ± SD; 1.5 ± 1.7%) and from 0% to 4.9% (1.4 ± 1.6%), respectively. These cells were either absent or extremely rare in young patients (under 10 years) but tended to increase in number with age (P 〈 0.0001). On the other hand, the mirror section technique showed that most of these cells were negative for adenohypophysial hormones, but a few of them were faintly positive for: α-subunit (8.0%), β-subunits of follicle-stimulating hormone (4.8%), luteinizing hormone (2.5%), thyroid-stimulating hormone (1.0%), and growth hormone (0.5%), and were negative for prolactin and adrenocorticotropic hormone. We considered that these cells represent oncocytes that exist in varying numbers in normal adenohypophysis. It was suggested that oncocytes in normal adenohypophysis share various common features with tumorous oncocytes of pituitary oncocytomas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050953
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  • 97
    Digitale Medien
    Digitale Medien
    A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 407-413 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Hemimegalencephaly ; Tuberous sclerosis ; Large neurons ; Balloon cells ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spectrum of neuronal migration disorders, but consistently includes abnormal large neurons similar to those in the cortical tubers of tuberous sclerosis. Microscopically, there are also cells with homogeneous and weakly eosinophilic cytoplasm with a single eccentric nucleus, sometimes called balloon cells (likewise prominent in tuberous sclerosis). We looked for immunohistochemical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and non-phosphorylated neurofilament and synaptophysin identify the large neurons and distinguish them from balloon cells in both entities. Balloon cells in hemimegalencephaly showed no immunoreactivity for TSC2 gene product, tuberin, and vimentin, but similar cells in tuber tissue showed consistent immunoreactivity. Balloon cells in hemimegalencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfilaments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hemimegalencephaly and tuberous sclerosis is superficial; their immunohistochemistry and electron microscopic profiles show distinct differences.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051101
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  • 98
    Digitale Medien
    Digitale Medien
    Inducible nitric oxide synthase expression in human cerebral infarcts (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 215-220 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Cerebral ischemia ; Inflammation ; Immunohistochemistry ; Nitrotyrosine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The inducible or “immunological” isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli and synthesizes toxic amounts of NO. In rodent models of focal cerebral ischemia, iNOS is expressed in neutrophils invading the injured brain and in local blood vessels. Studies with iNOS inhibitors and iNOS null mice indicate that NO produced by iNOS contributes to ischemic brain injury. In the present study, we sought to determine whether iNOS is also expressed in the human brain after ischemic stroke. Studies were conducted using immunohistochemistry on autopsy brains with neuropathological evidence of acute cerebral infarction. iNOS immunoreactivity was observed in neutrophils infiltrating the ischemic brain and in blood vessels within the ischemic territory. iNOS-positive cells also were immunoreactive for nitrotyrosine, reflecting protein nitration by NO-derived peroxynitrite and nitrites. iNOS or nitrotyrosine immunoreactivity was not detected outside the region of the infarct. These observations provide evidence that iNOS is expressed in the human brain after ischemic infarction and support the hypothesis that iNOS inhibitors may be useful in the treatment of ischemic stroke in humans.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050977
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  • 99
    Digitale Medien
    Digitale Medien
    Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 240-246 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; Advanced glycation endproducts ; Immunohistochemistry ; Superoxide dismutase ; Hyaline inclusions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N ɛ-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050980
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  • 100
    Digitale Medien
    Digitale Medien
    Immunoreactivity of β-amyloid precursor protein in amyotrophic lateral sclerosis (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 463-468 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; β-Amyloid precursor protein ; Immunohistochemistry ; Fast axonal transport ; Anterior horn neuron
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the localization and extent of β-amyloid precursor protein (β-APP695) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of 21 patients with amyotrophic lateral sclerosis (ALS), paying special attention to anterior horn neurons. Specimens from 18 patients without neurological disease served as controls. Increased β-APP immunoreactivity was frequently recognized in the anterior horns of the ALS patients with short clinical courses or with mild depletion of anterior horn cells, while no β-APP immunoreactivity was demonstrated in those with severe depletion of anterior horn neurons or with long-standing clinical courses. Increased β-APP immunoreactivity in the anterior horn neurons was mainly confined to the perikarya and no immunoreactivity was recognized in the dendrites or proximal axons directly emanating from the somata, except some spheroids (proximal axonal swellings) which showed increased immunoreactivity of β-APP. Increased β-APP immunoreactivity was spotted or focally aggregated in the perikarya of normal-looking large anterior horn neurons, while it was frequently diffuse in that of degenerative neurons such as central chromatolytic cells and or those with simple atrophy. On the other hand, the controls showed no immunostaining with β-APP in the spinal cord. These findings suggest that increased immunoreactivity of β-APP in neuronal perikarya of the anterior horn cells and in some proximal axonal swellings is an early change of ALS, and may be a response of the increased synthesis of β-APP resulting from neuronal damage, or the impairment of fast axonal transport.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051015
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