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  • Electronic Resource  (175)
  • 2000-2004  (175)
  • 1910-1914
  • Immunohistochemistry  (100)
  • Prognosis  (77)
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  • Electronic Resource  (175)
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  • 1
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Rejection ; ICAM-1 ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute rejection (AR) is a frequent complication following liver transplantation (LT). ICAM-1 may be involved in its pathogenesis. High doses of glucocorticoids are the standard treatment in these patients. The aim of this study was to describe corticoid effects on ICAM-1 tissue expression in liver biopsies of patients with LT and AR. The study included liver biopsies performed before and after treatment in 12 patients with LT and proven AR. In 10 patients AR was reversible and in 2, was steroid resistant. For immunohistochemistry, an indirect immunoperoxidase technique was used. Each histology section was semiquantitatively evaluated as follows: 0: 〈 10 % staining, 1: 10–25 %, 2: 25–50 %, 3: 〉 50 %. The control group comprised nine patients with LT and normal liver biopsies. In pre-treatment liver biopsy samples, ICAM-1 was markedly expressed on sinusoidal cells (2.41 ± 0.66), and there was also expression on periportal (0.66 ± 0.65) and perivenular hepatocytes (0.83 ± 0.57). By contrast, in the liver tissue from the control group, sinusoidal ICAM-1 reactivity was significantly lower (0.88 ± 0.33; P 〈 0.05), and hepatocytes showed no reliable ICAM-1 expression. After steroid treatment the intensity of ICAM-1 decreased significantly in sinusoids (1.5 ± 0.67; P 〈 0.05) and in perivenular hepatocytes (0.25 ± 0.86; P 〈 0.05). Additionally, we also observed a decreased ICAM-1 reactivity in portal hepatocytes (0.25 ± 0.62), but these differences did not reach statistical significance. Remarkably, after treatment, hepatocytes did not show ICAM-1 reactivity in resolved AR, but in corticoid-resistant patients AR did not change or increase. In conclusion, in patients with LT and AR, ICAM-1 was expressed in hepatocytes and with more intensity in sinusoid cells. Additionally, a down-regulation of the ICAM-1 tissue expression after corticoid treatment may exist, although in corticoid-resistant AR no modulation on ICAM-1 tissue expression was observed.
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  • 2
    ISSN: 1432-2307
    Keywords: Key words Nitric oxide ; Nitric oxide synthase ; Colorectal cancer ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 102-108 
    ISSN: 1432-2307
    Keywords: Key words Oral ; Squamous cell carcinoma ; Proliferation ; Apoptosis ; Tumour suppressor gene ; Oncogene ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P〈0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P〈0.001) and correlated negatively with apoptosis (P〈0.001). Proliferation (P〈0.006) and apoptosis (P〈0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.
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  • 4
    ISSN: 1432-2307
    Keywords: Key words Adhesion molecule ; Integrins ; Meningiomas ; Macrophages ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed the expression of leukocyte integrins and macrophage-associated antigens in meningiomas. Fourteen benign meningiomas, ten atypical/anaplastic meningiomas, two hemangiopericytomas and one solitary fibrous tumour (SFT) were included. Frozen sections were immunostained using antibodies directed against leukocyte integrins, CD68, CD14, CD2, CD1a, DRC1 and CD34. Their expression was evaluated semi-quantitatively. Ki67 positive cells were counted. Arachnoid membranes served as controls. Arachnoid cells expressed the β2-integrin subunit and KP1. Beta2 was detected in the tumour cells of 14 meningiomas. In nine cases, this was associated with an α-integrin subunit. There was no statistical difference in the expression of β2 between benign and atypical/anaplastic meningiomas. KP1 was constantly expressed by the tumour cells of meningiomas. It was not expressed by other meningeal tumours. CD34 was detected in the fibrous meningiomas, hemangiopericytomas and the SFT. In each tumour, macrophages were more numerous than T lymphocytes. There was no statistical difference in the density of macrophages and T lymphocytes between the benign and atypical/anaplastic meningiomas. There was no correlation between the Ki67 proliferation index and macrophage infiltration. Meningiomas, through the expression of leukocyte antigens, have a very particular phenotype. The expression of β2 integrins could play a role in the attraction of immunocompetent cells in the stroma of meningiomas.
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  • 5
    ISSN: 1432-2307
    Keywords: Key words Breast ; Adenomyoepithelioma ; Metastasis ; Thyroid ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We describe a patient who was admitted to our hospital with an enlarged left lobe of the thyroid gland. Since fine-needle aspiration showed atypical follicular cells, a surgical exploration followed. Owing to extensive tumor infiltration into the surrounding tissues curative surgery was not possible, and only an incisional biopsy was taken. Histological examination of this biopsy revealed a mixed tumor composed of epithelial and myoepithelial cells. A primary thyroid tumor, metastasis of a salivary gland, and a skin appendage tumor could be excluded based on clinical examination, conventional histology, and immunohistochemistry. A tumor of the left breast treated 12 years earlier had originally been classified as an intraductal/intracystic carcinoma with focal invasion, but was re-examined. Using immunohistochemistry, the breast tumor was reclassified as a malignant adenomyoepithelioma. The current tumor was apparently a metastasis from this primary breast tumor. An updated review of the literature is given, including current knowledge on histological and immunohistochemical features of adenomyoepithelioma of the breast, with special attention to the reported pathological characteristics of recurrent and malignant tumors. Based on the reported pathological characteristics of recurrent and metastatic tumors we offer a diagnostic tool for identifying potentially malignant and recurrent tumors.
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  • 6
    ISSN: 1432-2307
    Keywords: Key words Adenocarcinoma cell ; Mesothelial cells ; Effusions ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The detection of malignant cells in serous effusions obtained from patients diagnosed with cancer marks the presence of metastatic disease and is associated with a poor outcome. The purpose of this study was to evaluate the role of CD44s and CD44v isoforms in the distinction between mesothelial cells and malignant epithelial cells in effusions. Fifty-nine fresh pleural and peritoneal effusions were studied. These consisted of 41 specimens from patients with known gynecological neoplasms, 9 from patients diagnosed with breast adenocarcinoma, and 9 effusions from patients with various nongynecological malignancies or tumors of unknown origin. Forty-three effusions contained malignant/atypical epithelial cells, and 16 effusions were diagnosed as reactive. Three effusions contained exclusively malignant cells. Specimens were stained with anti-CD44s, v3, v5, v6, v7 and v3-10. The presence of staining in cancer cells, benign mesothelial cells and lymphocytes was evaluated. CD44s immunoreactivity was seen in 10 of 43 (23%) cases in malignant/atypical epithelial cells and in 53 of 56 (94%) cases in benign cells. In contrast, CD44v3-10 was seen in 23 of 43 (55%) cases in malignant/atypical epithelial cells and in 3 of 56 (6%) cases in benign cells. We advocate the use of CD44s and CD44v3-10 immunostaining in diagnostic evaluation of difficult serous effusions.
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  • 7
    ISSN: 1432-2307
    Keywords: Key words Clinical course ; Immunohistochemistry ; Morphology ; Primary gastric T-cell lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRγ gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5–, CD16+, CD56–, CD57–, CD25+, CD30+, CD103 (αEβ7)+, bcl-2 protein+, CD95+, CD95 ligand(L)–. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6–12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules.
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  • 8
    ISSN: 1432-2307
    Keywords: Key words Multifocal micronodular pneumocyte hyperplasia (MMPH) ; Tuberous sclerosis ; Postmenopausal woman ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a peculiar case of multifocal micronodular pneumocyte hyperplasia (MMPH) without association of pulmonary lymphangioleiomyomatosis (LAM) in a 56-year-old postmenopausal woman with tuberous sclerosis. This case is surmised to be a forme fruste of tuberous sclerosis. Computed tomography demonstrated multiple micronodules, measuring up to 5 mm in size, present in the bilateral lung fields, but no cystic changes. A proliferation of pleomorphic type-II pneumocytes lining the thickened alveolar septa in an adenomatoid pattern, with an associated increase in alveolar macrophages, was observed without typical nuclear atypia. In fully developed lesions, the ingrowth of more proliferating type-II pneumocytes into the thickened alveolar septa and macrophages filling the alveolar lumens were characteristic findings. Proliferation of immature smooth muscle cells suggesting LAM was not observed. Positive immunohistochemical stains for cytokeratin, epithelial membrane antigen, and surfactant apoproteins A and B, and negative staining for HMB45, alpha-1 smooth muscle actin, desmin, and carcinoembryonic antigen confirmed the characteristics of alveolar lining cells in each MMPH lesion. MMPH associated with tuberous sclerosis in the postmenopausal woman appears to be similar to that described in premenopausal women. The present case is familial rather than sporadic and suggests no relationship between the development of MMPH and the underlying hormonal state.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 439-448 
    ISSN: 1432-2307
    Keywords: Key words Amyloid ; Classification ; Congo red fluorescence ; Early diagnosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to find how best to diagnose amyloid deposits as early as possible, the sensitivity of three different methods that can be applied to the diagnosis of amyloid in tissue sections have been compared: the Congo red staining method (CR), the combination of CR and immunocytochemistry (CRIC) and Congo red fluorescence (CRF). Tissue blocks were available from 25 patients, including 11 with immunohistochemically distinct and 3 with chemically undefined amyloid diseases. The results revealed (a) that CRF is more sensitive than either CR or CRIC, as shown qualitatively and quantitatively, (b) that CRF can therefore be utilized to track down even minute amyloid deposits, which can be missed by the other two methods; (c) that the specificity of CRF and CRIC is secured on double-stained sections by the demonstration of green birefringence (GB) of the CRF-marked and IC-marked areas; (d) that CRF can be performed on the spot by just changing the light source; and (e) that CRF is not hampered by the congruent IC chromogen overlay, which ensures the specific classification of the amyloid deposits as applied to different amyloid classes. In conclusion, CRF was demonstrated to be the most sensitive method for direct diagnosis of amyloid in tissue sections. This method can, therefore, allow the earliest diagnosis and classification of amyloid, which is a good basis for an amyloid class-specific therapy while organ damage is still minimal.
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  • 10
    ISSN: 1432-2307
    Keywords: Key words Breast development ; Human breast ; Fetal breast ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28–32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.
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  • 11
    ISSN: 1432-2307
    Keywords: Key words CD44 ; Adhesion molecules ; Prognosis ; Soft tissue sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 602-607 
    ISSN: 1432-2307
    Keywords: Key words Thyroid ; Hashimoto thyroiditis ; Oxyphil cell ; Immunohistochemistry ; bcl-2 ; Bax ; Fas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Immunoreactivity for bcl-2, Bax and Fas was analysed in 16 cases with Hashimoto thyroiditis. Bcl-2-expression was constantly seen in regular thyrocytes and in the mantle-zone of lymphofollicular infiltrates. However, thyrocytes in the vicinity of lymphoid infiltrates and, especially, mitochondria-rich oxyphil cells exhibited reduced staining or none at all for bcl-2. Bax was found to be weakly reactive or negative in normal thyrocytes and was not up-regulated in bcl-2-deficient epithelial cells. In contrast, expression of Fas was markedly increased both in typical thyrocytes and in oxyphil cells within areas of lymphocytic infiltration. In conclusion, focal lack of bcl-2 expression together with up-regulation of Fas is a constant feature of Hashimoto thyroiditis. The reaction pattern of oxyphil cells is identical to that of affected typical thyrocytes without proliferation of mitochondria. Loss of bcl-2 with up-regulation of Fas is therefore likely to precede oncocytic change. Whether these alterations are involved in the process of oncocytic transformation remains to be clarified, however.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 628-633 
    ISSN: 1432-2307
    Keywords: Key words Prostate adenocarcinoma ; Endocrine cells ; Immunohistochemistry ; FSH ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an unusual variant of prostatic adenocarcinoma with marked endocrine differentiation (mixed endocrine-exocrine adenocarcinoma). Endocrine cells accounted for 60% of the tumour cells, were positive with silver impregnation and for chromogranin A, synaptophysin, and neuron-specific enolase, and coexpressed the exocrine antigens prostatic acid phosphatase and prostatic-specific antigen. Most of the endocrine cells were basophilic with haematoxylin-eosin and proved immunoreactive for alpha subunit of human chorionic gonadotropin and follicle-stimulating hormone. The remaining endocrine cells were represented by eosinophilic cells positive for serotonin, and by calcitonin and serotonin-immunoreactive cells not identifiable in haematoxylin-eosin-stained sections. On ultrastructural analysis, two types of endocrine cells were identified. The most frequent cell type showed abundant cytoplasmic round, electron-dense neurosecretory granules, either small (212±44 nm) or large (471±114 nm), resembling those of gonadotropic pituitary cells. The second type of endocrine cells contained irregular electron-dense granules similar to those of serotonin-storing enterochromaffin cells.
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  • 14
    ISSN: 1432-2307
    Keywords: Key words Oral cancer ; pN upgrading ; Immunohistochemistry ; Micrometastasis ; Semiserial sectioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The International Union Against Cancer (UICC) does not define the number of sections required from each regional lymph node to record pTNM classification. This study was designed to clarify the incidence of occult metastasis and to assess the pN upgrading of patients with oral cancer. Ultimately, this study led to a proposal for appropriate semiserial sectioning guidelines. Five hundred fifty-four nonmetastatic cervical lymph nodes taken from 73 patients with oral cancer were subjected to hematoxylin-eosin (HE) staining and keratin immunohistochemistry. Micrometastases, defined as foci ≤3 mm, were detected in 29 sites of 23 lymph nodes (4.2%) of 16 patients (21.9%). In 9 patients (12.3%) pN upgrading was needed: in 6 from pN0 to pN1, in 1 from pN0 to pN2b, and in 2 from pN1 to pN2b. The remaining 13 lymph nodes with occult metastasis were found in 5 pN2b and 2 pN2c patients, resulting in no pN upgrading. Occult metastasis was also detected in 6 small lymph nodes ≤5 mm in diameter. The average minor axis of the micrometastasis was 1.36±0.85 mm. We propose that the lymph nodes should be cut and examined at 1-mm intervals to detect micrometastatic foci and to evaluate the pN classification accurately.
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  • 15
    ISSN: 1432-2307
    Keywords: Keywords Small round cell tumors ; Ewing’s sarcoma ; Translocation ; Immunohistochemistry ; Differential diagnosis ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is now widely accepted that the EWS/FLI-1 fusion transcript is associated with tumors of the Ewing family. To test whether it is possible to detect the fusion transcript by means of combining polymerase chain reaction (PCR) methodology and immunohistochemistry, we investigated tumors of the Ewing family using in situ reverse transcriptase (RT)-PCR. We were able to demonstrate the t(11;22) fusion transcript in five of six cases of Ewing’s sarcoma and four of four peripheral primitive neuroectodermal tumors. These results were confirmed using fluorescence in situ hybridization in seven tumor samples. In situ RT-PCR-labeled fusion transcripts were found in virtually all tumor cells within a given sample, indicating that each cell possessed the t(11;22) transcript. We conclude from these results that in situ RT-PCR can be used for the rapid detection of EWS/FLI-1 fusion transcripts in biopsy material. The findings also suggest that all cells of the tumors of the Ewing family carry the EWS/FLI-1 fusion transcript.
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  • 16
    ISSN: 1432-2307
    Keywords: Keywords Gonadotropin-releasing hormone receptor ; Pituitary gland ; Immunohistochemistry ; Colocalization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH- and prolactin (PRL)-cell, and α-subunit (α-SU)/null-cell adenomas. The findings of this study suggest that the interaction between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and pituitary adenomas.
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  • 17
    ISSN: 1432-2307
    Keywords: Keywords CD99 antigen ; Neuroendocrine tumours ; Immunohistochemistry ; Cell-to-cell adhesion ; Proliferative activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although considered a specific marker for Ewing’s sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours. The present study evaluated immunohistochemically the prevalence of CD99 expression in a series of 68 neuroendocrine tumours of different gastrointestinal and pulmonary sites. We now report on membrane and/or granular cytoplasmic immunoreactivity in 25% of these tumours, independent of their anatomical sites. In lung neuroendocrine tumours, CD99 was preferentially confined to typical carcinoids (P=0.009). A statistically significant relationship was observed between the number of CD99 positive cells but not the immunostaining patterns and the presence of local invasion and/or distant metastases (P〈0.001). Moreover, there was a tendency for CD99-reactive tumours to show a reduced proliferative activity expressed by a Ki67 index of 2% (P=0.119). The number of CD99 immunoreactive cells or patterns of immunoreactivity did not correlate with the presence of associated clinical syndrome or particular hormonal immunostaining. Although the molecular basis underlying CD99 expression in neuroendocrine tumours is still poorly understood, our data suggest that CD99 may be involved in cell-to-cell adhesion of neuroendocrine tumour cells and in downregulation of their proliferative activity.
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  • 18
    ISSN: 1432-2307
    Keywords: Keywords AgNORs ; Standardised AgNOR analysis ; Parathyroid tumour ; Proliferation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 µm2; SE 0.171) through PA (3.638 µm2; SE 0.125) to PC (4.701 µm2; SE 0.179); these differences were highly significant (P〈0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P〈0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 µm2; SE 0.106) than in nonrecurrent PH (2.261 µm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 437 (2000), S. 445-449 
    ISSN: 1432-2307
    Keywords: Keywords Solitary fibrous tumour ; Adrenal gland ; Pregnancy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Solitary fibrous tumour (SFT), first described as a pleural lesion, has been reported in several extrathoracic sites over the past 10 years. We describe a SFT of the left adrenal gland incidentally discovered in a 23-year-old, 22-week pregnant woman and characterised by a rapid growth during the third trimester of pregnancy. Elevated serum and urinary levels of cortisol and elevated blood levels of delta 4 androstendione and 17-OH progesterone were observed. After spontaneous delivery, the patient underwent laparoscopic resectioning of the mass and of the left adrenal gland from which the tumour was apparently originating. The kidney was not involved, and no other abdominal tumours were found. Histological and immunohistochemical features were typical of SFT of pleura and other locations. Only one case of adrenal SFT is on record, and the adrenal gland is to be added to the long list of extrathoracic locations of SFT. The association with pregnancy was a previously unrecognised event in SFT. The focal expression of progesterone receptors in the tumour cells may be related to pregnancy. This observation prompted an analysis of steroid hormone receptors in SFT of classical sites (pleura). Two of five cases had focal progesterone receptors too, a finding which deserves further investigations in a much larger series of SFTs.
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  • 20
    ISSN: 1432-2307
    Keywords: Keywords Non-Hodgkin’s lymphoma ; Immunohistochemistry ; ALK1 ; T-cell lymphoma ; Splenic rupture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a 22-year-old male with a 10-day history of fever, painful swelling in the left groin, and abdominal complaints, emergency surgery was performed because of spontaneous splenic rupture. At histology, a cellular infiltrate of intermediate-sized atypical lymphocytes was seen in the splenic white pulp, staining for T-cell markers. In addition, CD30 and anaplastic lymphoma kinase 1 (ALK) were diffusely positive, thus, representing a case of anaplastic large cell lymphoma (ALCL), T-cell, ALK-positive, small cell monomorphic variant. ALK-positive ALCL patients generally bear a much better prognosis than patients with T-cell lymphomas, unspecified, or ALK-negative ALCL. Therefore, besides the very unusual clinical presentation, this case highlights the importance of immunostaining for CD30 and ALK in all T-cell lymphomas. This report is the first extensive description of ALK-positive ALCL involvement of the spleen.
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  • 21
    ISSN: 1432-2161
    Keywords: Key words Giant rice body ; Ultrastructure ; Immunohistochemistry ; Histogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. Design and patients: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. Results: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. Conclusion: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
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  • 22
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    Journal of cancer research and clinical oncology 126 (2000), S. 667-670 
    ISSN: 1432-1335
    Keywords: Key words Chondrosarcoma ; Heat shock protein ; Differentiation ; Diagnosis ; Immunohistochemistry ; Chondroma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Heat shock proteins (hsp) are involved in tumor immunity, and a correlation with survival, occurrence of metastases, and drug resistance has been reported. It was the aim of this study to investigate the expression of heat shock proteins in chondrosarcomas and chondromas. Methods: Hsp expression was investigated immunohistochemically on paraffin-embedded sections of 37 consecutive patients (24 male and 13 female, mean age 48 years) with chondrosarcoma and of ten patients (six male, four female, mean age 36 years) with chondroma. Results: Chondromas showed a positive staining for hsp27 in 100%, for hsp60 in 30%, for hsp72 in 80%, for hsp73 in 80%, and for hsp90 in 90%. In chondrosarcoma a decreased expression was found for hsp27 (62% positive, P 〈 0.05) and hsp72 (43% positive, P 〈 0.05), whereas no significant difference to chondromas was detected in the expression of hsp60 (49% positive), hsp73 and hsp90 (73% and 81% positive, respectively). In addition, hsp72 expression showed a correlation with differentiation of the tumors (P 〈 0.05); the lowest hsp72 expression was found in G3 chondrosarcomas (only 13% positive). No correlation with respect to differentiation was found for the expression of the other hsps. Conclusions: This study shows a different expression of hsps in chondrosarcomas and chondromas. Together with the correlation of hsp72 expression with low differentiation, this finding could lead to new experimental and diagnostic strategies.
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  • 23
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    Der Pathologe 21 (2000), S. 433-440 
    ISSN: 1432-1963
    Keywords: Schlüsselwörterα1-Antitrypsin-Mangel PiZ ; Lebermorphologie ; Immunhistochemie ; “Single-strand conformational polymorphism” ; DNA-Sequenzierung ; Keywords Alpha-1-antitrypsin deficiency PiZ ; Liver morphology ; Immunohistochemistry ; Single-strand conformational polymorphism ; DNA sequencing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Whether heterozygotes with alpha-1-antitrypsin (AAT) deficiency type PiZ bear an increased risk for chronic liver disease is controversial. On the basis of liver tissue from 1,030 autopsies (autopsy series), 1,847 biopsies (biopsy series) and 317 primary liver carcinomas (tumor series), we analysed the effect of heterozygous state PiZ for the development of liver diseases. The PiZ status was screened immunohistochemically and verified in selected cases by SSCP analysis and by sequencing DNA extracted from paraffin embedded tissue. The PiZ frequency in the biopsy series (3.4%) and tumor series (5.99%) was significantly higher than in the autopsy series (1.8%). Hepatic PiZ deposits in heterozygotes sometimes were as extensive as in homozygotes. The amount of PiZ deposits correlated positively with the inflammatory activity and stage of fibrosis, as well as with the age of patients. Patients with concurrent liver disease such as hepatitis and alcoholic liver disease showed significantly higher scores of inflammatory activity, stage of fibrosis and amount of PiZ deposits than those without additional liver disease. Cholangiocarcinomas and combined hepato-cholangiocarcinomas were seen significantly more frequently in patients with PiZ-associated liver carcinoma than in genetic healthy individuals (p=0.004). Three out of 19 PiZ-associated liver carcinomas had developed in cirrhotic liver tissue. Heterozygotes of type PiZ have an enhanced risk for chronic liver disease including primary liver carcinoma. PiZ-associated liver diseases will become clinically manifest in middle or old aged adults. Rarely this genetic defect causes liver cirrhosis even without concurrent liver disease. PiZ-associated liver carcinomas are frequently characterized by cholangiocellular differentiation and may develop often in non-cirrhotic liver tissue. Immunohistochemistry is a specific method to detect hepatic PiZ deposits.
    Notes: Zusammenfassung Bisher ist umstritten, ob heterozygote Patienten mit α1-Antitrypsin (AAT)-Mangel Typ PiZ ein erhöhtes Risiko für Lebererkrankungen aufweisen. An Leberproben von 1030 Autopsien (Autopsie-Serie), 1847 Biopsien (Biopsie-Serie) und 317 primären Leberkarzinomen (Tumor-Serie) sollte der Einfluss des heterozygoten PiZ-Status auf die Leber untersucht werden. Die PiZ-Bestimmung erfolgte immunhistochemisch, teilweise ergänzt durch SSCP-Analyse und DNA-Sequenzierung von DNA-Extrakten aus paraffineingebettetem Material. Die PiZ-Häufigkeit der Biopsie-Serie (3,4%) und der Tumor-Serie (5,99%) war signifikant höher als die der Autopsie-Serie (1,8%). PiZ-Ablagerungen waren bei manchen heterozygoten Merkmalsträgern ebenso umfangreich wie bei homozygoten. Ihr Ausmaß korrelierte positiv mit Entzündungsaktivität und Fibrosegrad der Leber sowie mit dem Patientenalter. Patienten mit konkurrierenden Lebererkrankungen wie Hepatitis oder Alkoholschädigung wiesen eine signifikant stärkere Entzündung, Fibrose und mehr PiZ-Ablagerungen auf als diejenigen ohne zusätzliche Lebererkrankungen. Cholangiokarzinome und kombinierte Hepatocholangiokarzinome traten signifikant häufiger bei Patienten mit PiZ-Mutation als bei genetisch Gesunden (p=0,004) auf. Nur 3 der 19 PiZ-assoziierten Leberkarzinome waren in einer Leberzirrhose entstanden. Patienten mit heterozygotem AAT-Mangel Typ PiZ tragen nach den hier vorgestellten Ergebnissen ein erhöhtes Risiko für chronische Lebererkrankungen einschließlich primärer Leberkarzinome. Wenn überhaupt, manifestiert sich dieser genetische Defekt erst in mittlerem oder höherem Lebensalter. Er kann in seltenen Fällen selbst ohne konkurrierende Lebererkrankung zur Zirrhose führen. PiZ-assoziierte Leberkarzinome sind häufig cholangiozellulär differenziert und entstehen mehrheitlich ohne Leberzirrhose. Hepatische PiZ-Ablagerungen lassen sich immunhistochemisch zuverlässig identifizieren.
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  • 24
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    Pediatric nephrology 14 (2000), S. 629-635 
    ISSN: 1432-198X
    Keywords: Key words Histomorphometry ; In situ hybridization histochemistry ; Molecular morphometry ; Immunohistochemistry ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Quantitative histomorphometric assessment of bone biopsies represents a powerful and informative method for the study of metabolic bone diseases. It is the gold standard against which the noninvasive ”diagnostic” markers of bone metabolism as well as newly available therapeutic modalities are tested. With the rapid progress in technology of molecular biology, identification of systemic and local biomolecules known to regulate bone metabolism can now be achieved. The study of localization, levels of expression, and synthesis of these factors in bone and its microenvironment is possible through applications of in situ hybridization histochemistry (ISHH) and immunohistochemistry (IHC). Application of ISHH allows study of specific mRNA expression. IHC determines the presence and distribution of target protein in cells. These two methodologies provide the link between the cellular processes of mRNA transcription and translation to the working protein. Combining the established bone histomorphometric techniques with ISHH and IHC elevates the study of bone to new heights, i.e., cellular and molecular mechanistic issues can now be studied.
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  • 25
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    Der Pathologe 21 (2000), S. 16-23 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Lymphknötchen ; Reaktive Infiltrate ; Maligne Lymphome ; Histotopographie ; Immunhistochemie ; Retikulinfasern ; Knochenmarkbiopsie ; Key words Lymphoid nodules ; Reactive infiltrates ; Malignant lymphomas ; Histotopography ; Immunohistochemistry ; Reticulin fibers ; Bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Differentiation of focal or extended lymphoid bone marrow infiltrates presents a diagnostic challenge and therefore warrants systematic evaluation of those features which affect this. One of the basic requirements is an appropriate technique of processing the bone marrow specimens. This includes the possibility of enzyme evaluation (naphthol-AS-D-chloroacetate esterase) and immunohistochemistry (set of monoclonal antibodies) and comparison with the corresponding lymph node histology. A number of histological parameters have emerged with a distinctive property for distinguishing between reactive focal lymphoid aggregates and malignant lymphomas. Amongst these the pattern of infiltrates, i.e., histotopography (subcortical infiltrates, paratrabcular–endosteal localization, margination, tandem-like extension between adipocytes and cribriform appearance), content of reticulin fibers, cytology (small lymphocytes versus large blast cells) and, finally, immunohistochemistry (monoclonal versus polyclonal expression of cytoplasmic immunoglobulins, uniform versus mixed population of B or T lymphocytes) are most important. In conclusion, synoptic consideration of several parameters, in particular histotopography and immunohistochemistry provides a most promising approach to differentiate neoplastic from reactive lymphoid lesions in the bone marrow.
    Notes: Zusammenfassung Die Differentialdiagnose herdförmiger oder ausgedehnter lymphoider Knochenmarkinfiltrate stellt noch immer eine diagnostische Herausforderung dar, die eine systematische Analyse entsprechender diskriminierender Faktoren erfordert. Eine der grundsätzlichen Voraussetzungen ist dabei eine Technik mit entsprechender Möglichkeit einer enzym- (Naphthol-AS-D-Chlorazetatesterase) und immunhistochemischen Aufarbeitung (monoklonale Antikörper) des Biopsiematerials und der Vergleich mit der zugeordneten Lymphknotenhistologie. Hinsichtlich der Unterscheidung zwischen reaktiven, herdförmigen lymphoiden Läsionen und malignen Lymphomen hat sich eine Anzahl histologischer Parameter als von wegleitendem diagnostischen Wert herausgestellt. Dazu gehören einmal das Infiltrationsmuster bzw. die Histotopographie (subkortikales Infiltrat, paratrabekulär-endostale Lokalisation, Abgrenzung, tandem-artige Ausbreitung zwischen den Adipozyten und kribriformes Muster), Faserdichte im Infiltrat sowie die Zytologie (kleine Lymphozyten gegenüber großen blastären Zellelementen) und schließlich die Immunhistochemie (mono-gegenüber polyklonaler Expression zytoplasmatischer Immunglobuline, uniforme gegenüber gemischtzelliger B- oder T-Lymphozytenpopulation). Zusammengefaßt verspricht eine gemeinsame Beachtung dieser verschiedenen Merkmale, insbesondere jedoch die Histotopographie und Immunhistochemie, am ehesten eine erfolgreiche Differenzierung zwischen reaktiven und neoplastischen lymphoiden Läsionen des Knochenmarks.
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  • 26
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Apoptose ; Proliferation ; Hämatopoetischer Zellumsatz ; Topoisomerase II α ; PCNA ; Chronische myeloproliferative Erkrankungen ; Prognose ; Reaktive Läsionen ; Key words Apoptosis ; Proliferation ; Hematopoietic turnover index ; Topoisomerase II α ; PCNA ; Chronic myeloproliferative disorders ; Prognosis ; Reactive lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow. Therefore, dynamics of hematopoiesis is mainly defined by these two parameters. However, since only few data are available from previous studies, we performed a retrospective analysis to elucidate some aspects of this complex pathomechanism. A total of 400 patients with chronic myeloproliferative disorders (CMPDs) and corresponding reactive bone marrow lesions were enrolled into this study. Apoptosis was detected in bone marrow tissue by the ISEL-technique and topoisomerase II α expression was demonstrated by the monoclonal antibody Ki-S1. Furthermore, by determination of the proliferating-cell nuclear antigen labeling (PCNA) index, we were able to calculate the proportion of cells in the G2/M phase, because both nuclear antigens are expressed in different phases of the cell cycle. Patients with IMF, PV, and ET revealed a normal range of apoptosis, whereas in chronic myeloid leukemia (CML) a significant increase could be observed. On the other hand, IMF and PV were characterized by a raised proliferative activity. Dynamics of hematopoiesis was assessed by calculation of the so called hematopoietic turnover index. In CML and reactive lesions no alterations of this parameter were detectable, but IMF and PV showed a significant increase. Survival analysis disclosed a relevant worsening of life expectancy for patients with reduced apoptosis and proliferation. In conclusion, our in-situ results confirm and extend previous experimental data on hematopoietic cell kinetics. In this context, a greater regenerative capacity of hematopoiesis may be reflected by an increased rate of apoptosis and/or proliferation and therefore is associated with a more favorable outcome.
    Notes: Zusammenfassung Apoptose und Proliferation stellen im Rahmen einer funktionsgerechten Regelung der Hämatopoese einen integralen Bestandteil für die Aufrechterhaltung des zellulären Gleichgewichts im Knochenmark dar. Insofern ist die Dynamik des hämatopoetischen Zellumsatzes durch diese beiden Parameter gekennzeichnet. Da weiterführende Untersuchungen in dieser Hinsicht lediglich vereinzelt am Knochenmark durchgeführt worden sind, haben wir im Rahmen einer retrospektiven Analyse versucht, einige Aspekte dieses komplexen Mechanismus zu beleuchten. Insgesamt wurden 400 Patienten mit chronischen myeloproliferativen Erkrankungen (CMPE) sowie korrespondierenden reaktiven Veränderungen in die Untersuchung aufgenommen. Neben dem direkten Nachweis der Apoptose im Knochenmark durch die ISEL-Technik haben wir die Topoisomerase II α Expression mittels des monoklonalen Antikörpers Ki-S1 gemessen. Zusätzlich konnten wir durch die Bestimmung der PCNA-Markierung aufgrund der Zellzyklus-spezifischen Färbereaktion beider nukleärer Antigene den Anteil der in G2-/M-Phase befindlichen Zellen ermitteln. Während die IMF, die PV sowie die ET eine im Normbereich liegende Apoptoserate erkennen ließen, war dieser Wert bei der CML signifikant erhöht. Auf der anderen Seite wiesen IMF und PV eine deutlich gesteigerte proliferative Aktivität im Knochenmark auf. Bei der Berechnung eines hämatopoetischen Zellumsatz Index (HZI) zeigten diese beiden CMPE-Subtypen einen signifikanten Anstieg, wohingegen bei der CML sowie den reaktiven Läsionen keine relevante Verschiebung dieses Parameters festzustellen war. Im Rahmen prognostischer Analysen hatten IMF und PV Patienten mit reduzierter Proliferation und Apoptoserate jeweils eine signifikant kürzere Überlebenszeit. Unsere in-situ Ergebnisse erweitern und bestätigen vorausgegangene experimentelle Studien zur hämatopoetischen Zellkinetik. Darüber hinaus lassen sich aus unseren Daten prognostische Überlegungen ableiten, da insbesondere bei der PV und IMF Apoptose und Proliferation signifikanten Einfluß auf das Überleben der Patienten hatten. In diesem Zusammenhang spiegelt eine vermehrte Apoptose- und Proliferationsrate im Knochenmark offenbar eine größere regenerative Kapazität der Hämatopoese wieder und könnte daher für einen günstigeren Verlauf verantwortlich gemacht werden.
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  • 27
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    Der Pathologe 21 (2000), S. 456-459 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Undifferenziertes kleinzelliges Hepatoblastom ; Immunhistochemie ; Keywords Undifferentiated small-cell hepatoblastoma ; Immunohistochemistry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Undifferentiated small-cell hepatoblastoma (HB) is a rare malignant tumor of childhood. The cell of origin is supposed to be a pluripotential, probably entodermal, stem-cell. Differential diagnosis of this type of HB is difficult among the group of small round and blue cell malignant tumors of children. The immunohistochemically determined coexpression of cytokeratin 8, 18, and 19 and of vimentin and actin, regularly in the absence of α-fetoprotein expression may be diagnostically helpful. We present the case of an undifferentiated small-cell HB of a 15-month-old girl with agenesis of the right kidney. As morphological peculiarity the tumor presented disseminated histiocytic giant cells.
    Notes: Zusammenfassung Undifferenzierte kleinzellige Hepatoblastome (HB) zählen zu den seltenen malignen Tumoren der Leber im Kindesalter. Da der Tumor in der Regel kein α-Fetoprotein exprimiert, ist der Nachweis von Zytokeratin 8, 18 und 19 sowie Vimentin und Aktin diagnostisch wegweisend. Als Ausgangszelle wird eine pluripotente, wohl entodermale Stammzelle vermutet. In der Gruppe der klein-, rund- und blauzelligen malignen Tumoren des Kindesalters bietet diese Variante des HB differenzialdiagnostische Schwierigkeiten. Wir berichten über ein undifferenziertes kleinzelliges HB eines 15 Monate alten weiblichen Kleinkindes mit Agenesie der rechten Niere. Als morphologische Besonderheit des Tumors werden disseminierte histiozytäre Riesenzellen beschrieben.
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  • 28
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Gastrointestinaltrakt ; Karzinoid ; Neuroendokrine Tumoren ; DNA-Zytophotometrie ; Prognose ; Key words Gastrointestinal tract ; Carcinoid ; Neuroendocrine tumors ; DNA cytophotometry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A total of 123 manifestations (97 primary tumours and 26 metastases) of neuroendocrine tumours of the gastrointestinal tract observed in 95 patients was investigated for the prognostic value of clinical, histological and DNA cytophotometric parameters. Metastases almost exclusively occurred among ileal carcinoids, which also were responsible for all 14 cases of lethal outcome observed during the follow-up period of mean 42 months. Aneuploid DNA values could be determined significantly more frequently among ileal than in non-ileal carcinoids and showed – upon analysis of the total group of gastrointestinal neuroendocrine tumours – a significant correlation to lethal course of disease. In addition, among 18 cases with primary and secondary carcinoid manifestations available for DNA cytophotometry, an association between the DNA content of metastatic neuroendocrine tumours and prognosis came to light. When applicated to the group of ileal neoplasms, however, the parameter DNA content did not allow a better prognostic assessment.
    Notes: Zusammenfassung Untersucht wurden 123 Manifestationen (97 Primärtumoren und 26 Metastasen) von bei 95 Patienten beobachteten neuroendokrinen (NE-)Tumoren des Gastrointestinaltrakts auf die prognostische Bedeutung verschiedener klinischer, histologischer und DNA-zytophotometrischer Parameter. Metastasen traten fast ausschließlich bei ilealen Karzinoiden auf, denen auch sämtliche 14 während der durchschnittlichen Nachbeobachtungszeit von 42 Monaten aufgetretenen letalen Erkrankungsverläufe zuzuordnen waren. Aneuploide DNA-Verteilungsmuster wurden signifikant häufiger bei ilealen als bei nichtilealen Karzinoiden angetroffen und waren – bezogen auf die Gesamtgruppe – signifikant mit tödlichem Krankheitsausgang korreliert. Darüber hinaus zeigte sich bei 18 Fällen mit DNA-zytophotometrisch auswertbaren primären und sekundären Karzinoidmanifestationen eine Assoziation zwischen dem DNA-Histogrammtyp metastatischer Karzinoide und der Prognose. Innerhalb der Gruppe der Ileumtumoren erlaubte der Parameter DNA-Gehalt aber keine Verbesserung der Prognoseabschätzung.
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  • 29
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    Der Pathologe 21 (2000), S. 39-54 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Chronische myeloische Leukämie ; Megakaryozyten ; Fasern ; Erythropoese ; Makrophagen ; Klinische Befunde ; Immunhistochemie ; Knochenmarkbiopsie ; Key words Chronic myelogenous leukemia ; Megakaryocytes ; Fibers ; Erythroid precursors ; Macrophages ; Clinical findings ; Immunohistochemistry ; Morphometry ; Bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy. Following morphometry significant correlations were calculated between number of CD61+ megakaryocytes, including their precursors with fiber density. This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the complex pathomechanism of myelofibrosis. The latter was observed in about 28% of patients already at diagnosis. In a similar way, the frequency of CD68+ macrophages was correlated with the amount of Ret40f+ nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnover, hemoglobin synthesis, and degradation of the expelled nuclei from normoblasts. The (α-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens. Moreover, significant associations were calculable between reduction in erythropoiesis or increase in fibers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood, and spleen size. These variables are in keeping with more advanced stages of CML. Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out. This simplified staging system was correlated with corresponding sets of hematological data. Sequential biopsies in 173 patients with monotherapy by IFN, hydroxyurea (HU), or busulfan (BU) revealed a fibrogenic effect of IFN in contrast to a fiber-reducing property of HU. The dynamics of myelofibrosis and changes of major cell lineages during treatment were readily demonstrable by calculating corresponding indices. These included the ratios between quantitative differences of corresponding variables at repeated examinations and time. Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68+ macrophages, including activated subpopulations. Histological subgroups showed a transition from a (nonfibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subtype in about 40% of patients. This change was opposed to a numerical reduction in the myelofibrotic subtype which occurred in 17 patients (36%), but predominantly in those under HU therapy. In conclusion, the striking heterogeneity of bone marrow features in CML warrants a careful morphological evaluation of trephine biopsies and appropriate means of processing to achieve relevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.
    Notes: Zusammenfassung Bei 604 Patienten mit einer chronischen myeloischen Leukämie (CML) wurde anhand von Beckenkammbiopsien eine immunhistochemische und morphometrische Studie durchgeführt, um morphologische und klinische Befunde miteinander zu vergleichen und die Auswirkungen der Interferon- (IFN) und Chemotherapie abzuklären. Anhand der morphometrischen Analyse konnten signifikante Korrelationen zwischen der Anzahl CD61+-Megakaryozyten einschließlich ihrer Vorläuferzellen mit der Faserdichte berechnet werden. Dieser Befund spiegelt die enge funktionelle Beziehung zwischen der Megakaryopoese und den Fibroblasten im Hinblick auf den komplexen Pathomechanismus der Myelofibroseentstehung wider. Diese war bei etwa 28% der Patienten bereits zum Diagnosezeitpunkt zu beobachten. In ähnlicher Weise war die Anzahl der CD68+-Makrophagen mit der Menge an Ret40f+-kernhaltigen erythropoetischen Vorläuferzellen korreliert, was durch die Einbindung dieser Zellinie in den Eisenstoffwechsel, die Hämoglobinsynthese sowie den Abbau der ausgestoßenen Normoblastenkerne in Zusammenhang gebracht werden kann. Die (α-D-Galaktosylreste-expremierende) Pseudo-Gaucherzellen ließen sich in 30% der Biopsien vor Behandlung nachweisen. Weiterhin konnten signifikante Beziehungen zwischen einer Reduktion der Erythropoese oder einer Zunahme der Verfaserung mit klinischen Parametern wie dem Hämoglobinspiegel, dem Anteil an Myelo- und Erythro-Normoblasten im peripheren Blut und der Milzgröße berechnet werden. Diese Variablen kennzeichnen offensichtlich mehr fortgeschrittene Stadien der CML. Entsprechend unserer morphometrischen Auswertung wurde eine Klassifikation in drei unterschiedliche histologische Subgruppen vorgenommen: granulozytisch, megakaryozytisch und myelofibrotisch. Dieser vereinfachten histologischen Einteilung waren entsprechende hämatologische Daten zuzuordnen. Sequenzbiopsien an 173 Patienten, die eine Monotherapie mit IFN, Hydroxyurea (HU) oder Busulfan (BU) erhielten, zeigten einen fibrogenetischen Effekt von IFN im Gegensatz zu einer eher faserreduzierenden Eigenschaft von HU. Die Dynamik der Myelofibroseentwicklung und die entsprechende Veränderungen der hauptsächlichen Zellinien während der Behandlung ließen sich am besten durch eine Kalkulation von Indizes verdeutlichen. Diese beinhalteten das Verhältnis aus quantitativen Unterschieden der einzelnen Variablen in den wiederholt durchgeführten Entnahmen und den zugeordneten zeitlichen Differenzen. So war bei Patienten mit einer kompletten hämatologischen Remission nach IFN-Gabe die Regeneration der Erythropoese zusammen mit einem Anstieg in der Anzahl CD68+-Makrophagen einschließlich ihrer aktivierten Subpopulation auszumachen. Die histologischen Subgruppen ließen bei fortlaufenden Untersuchungen einen Übergang sowohl von einem (nicht verfaserten) granulozytären wie auch megakaryozytären Subtyp in eine myelofibrotische Gruppe bei etwa 40% der Patienten erkennen. Dieses Phänomen stand im Gegensatz zu einer anzahlmäßigen Reduzierung des myelofibrotischen Typs vor allem bei Patienten unter HU-Therapie in 17 Fällen (36%). Zusammengefaßt erfordert die auffallende Heterogenität der Knochenmarkbefunde bei der CML eine sorgfältige morphologische Auswertung von Biopsien mit geeigneten Methoden, um relevante Korrelationen zwischen klinischen Daten zu berechnen und somit einen besseren Einblick in die Dynamik der Krankheitsentwicklung zu gewinnen.
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  • 30
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Harnblase ; WHO-Klassifikation ; Flache und papilläre urotheliale Läsionen/Tumoren ; Histologie ; Immunhistochemie ; Keywords Urothelial bladder tumors ; WHO classification ; Flat and papillary urothelial lesions/tumors ; Histology ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Recently the World Health Organization published a new classification of urinary bladder tumors which is intended to take into account better the biology of the various lesions and to better distinguish between clearly benign and malignant lesions. We examine the possible diagnostic and clinical impact of the new classification, including recent immunohistochemical findings. Papillary urothelial lesions include papillomas, papillary neoplasms of low malignant potential, and papillary carcinomas. Flat urothelial lesions include hyperplasia, reactive atypia/atypia of unknown significance, dysplasia, and carcinoma in situ. Invasive patterns of papillary carcinomas are discussed, with special emphasis on lamina muscularis mucosae substaging. The most important feature of the new classification is its differentiation of two types of low-grade, noninvasive papillary urothelial lesions: papillary neoplasm of low malignant potential vs. papillary carcinoma. Long-term follow-up studies are needed to determine the clinical significance of this differentiation.
    Notes: Zusammenfassung Grund für die Aktualisierung der WHO-Klassifikation urothelialer Läsionen bzw. Tumoren der Harnblase war, der Biologie der verschiedenen Läsionen besser gerecht zu werden sowie eine schärfere Trennung zwischen benignen und malignen urothelialen Prozessen zu vollziehen. Die Bedeutung für Diagnostik und Klinik im Alltag unter Berücksichtigung aktueller immunhistochemischer Befunde wird kritisch betrachtet. Zwei Hauptgruppen werden unterschieden. Papilläre urotheliale Läsionen umfassen Papillome, papilläre urotheliale Neoplasien niedrig malignen Potentials sowie papilläre Karzinome. Flache urotheliale Läsionen umfassen flache Hyperplasien, Atypien (reaktiv oder von unklarer Bedeutung), Dysplasien sowie das Carcinoma in situ (CIS). Verschiedene Invasionsmuster papillärer Karzinome werden unter besonderer Berücksichtigung der Lamina muscularis mucosae diskutiert. Der kritischste Punkt der neuen Klassifikation sowohl für die Diagnostik als auch für die Klinik dürfte die Unterscheidung zweier Gruppen nichtinvasiver papillärer “low-grade”-Tumoren (papilläre urotheliale Neoplasie niedrig malignen Potentials vs. pTa-GI-Tumor) darstellen. Langzeit-follow-up-Studien müssen zeigen, ob diese Unterteilung ihre Berechtigung findet.
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  • 31
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    Journal of cancer research and clinical oncology 126 (2000), S. 48-52 
    ISSN: 1432-1335
    Keywords: Key words Enzyme-linked immunosorbent assay ; p53 protein ; WAF1 protein ; Lung cancer ; Prognosis ; AbbreviationsNSCLC non-small-cell lung cancer ; RR relative risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: p21WAF1, a cyclin-dependent kinase inhibitor, is an important mediator of the cell-cycle arrest and tumor suppression induced by the protein p53. Although alterations of the p53 gene and its overexpression are frequent in most malignancies, including non-small-cell lung cancer (NSCLC), and may be associated with poor patient prognosis, the clinical utility of p21WAF1 expression in NSCLC has not been established. Methods: We have used a commercial enzyme-linked immunosorbent assay (ELISA) kit for p21WAF1 to test soluble extracts of 54 NSCLC specimens with known clinicopathological properties. Results: There was no correlation between p21WAF1 and p53 concentrations, the latter being determined by a time-resolved immunofluorometric assay developed in-house. Furthermore, p21WAF1 levels were not associated with patient age, tumor/node/metastasis (TNM) stage, lymph node metastasis, histological grade or type, or smoking history, in Mann-Whitney analysis. χ2-tests, based on cutoffs equal to the 25th, 50th, or 75th percentiles of the p21WAF1 distribution, similarly did not reveal any statistically significant associations between p21WAF1 and other clinicopathological variables. Because of the small number of patients and the median follow-up of only 18 months, a meaningful survival analysis could not be performed. Conclusion: In summary, this preliminary study suggests that ELISA-quantified p21WAF1 levels in NSCLC extracts are weaker than p53 in terms of prognostic value and do not contribute to the further subclassification of patients.
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  • 32
    ISSN: 1432-1335
    Keywords: Key words erbB-3 ; Colorectal carcinoma ; Survival ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P 〈 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.
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  • 33
    ISSN: 1433-0385
    Keywords: Schlüsselwörter: Inkontinenz ; Rectumcarcinom ; Manometrie ; Prognose ; Anus. ; Keywords: Incontinence ; Rectal cancer ; Anorectal manometry ; Prognosis ; Anus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. Aim: To determine clinical and physiologic parameters enabling the prognosis of continence after protective ileostomy closure secondary to rectal resection for rectal cancer. Method: Patients who had undergone rectal resection (n = 65, of whom 24 had had radiochemotherapy) were evaluated by clinical examination, anorectal manometry and orthograde contrast enema before ileostomy closure. Continence was evaluated by clinical findings 91 ± 52 weeks after stoma closure with the help of standardized questionaires and classified according to the Wexner continence score. The relationship between findings before stoma closure and continence score was calculated with Pearson's correlation coefficient. Results: Correlations were found to be significant between the continence score and the level of anastomosis (r = –0.58, p 〈 0.001), median resting pressure (r = –0.52, p 〈 0.001), rectal compliance (r = –0.43, p 〈 0.001). Additionally, radiochemotherapy impairs continence (p = 0.0001). Correlations were not significant between continence and functional sphincter length, squeeze pressure, threshold for perception, urge and maximal tolerable volume, and continence for semiliquid contrast medium. Conclusion: Incontinence after rectum resection is multifactorial: the level of anastomosis, resting pressure, rectal compliance and radiochemotherapy all play a dominant role. Based on these findings, the continence score can be calculated before closure of a diverting ileostomy by applying multivariate analysis with the help of the following formula: Continence score = 18.23–0.94 · level of anastomosis – 0.18 · resting pressure + 3.72 · radiochemotherapy.
    Notes: Zusammenfassung. Ziel dieser Studie war eine Evaluation von klinischen und physiologischen Parametern zur Vorhersage des Kontinenzgrades nach Rückverlagerung der protektiven Loop-Ileostomie nach Rectumresektion wegen eines Carcinoms. Methode: 65 Patienten wurden klinisch mittels anorectaler Manometrie und orthograder Röntgenkontrastmitteldarstellung vor der Ileostomieresektion untersucht. Bei 24 Patienten war eine Radiochemotherapie durchgeführt worden. Der klinische Status wurden 91 ± 52 Wochen nach der Ileostomieresektion mittels eines standardisierten Fragebogens erhoben und der Kontinenzgrad nach dem Wexner-Kontinenzscore bewertet. Der postoperative Kontinenzscore wurde mit den Befunden vor Stomarückverlagerung korreliert und ein Pearson-Korrelationskoeffizient berechnet. Ergebnisse: Es ergab sich eine signifikante Korrelation des Kontinenzgrades mit der Anastomosenhöhe (r = –0,58, p 〈 0,001), dem mittleren Ruhedruck (r = –0,52, p 〈 0,001) und der rectalen Compliance (r = –0,43, p = 0,001). Die Kontinenz war nach Radiochemotherapie schlechter (p = 0,0001). Es fand sich keine signifikante Korrelation zwischen Kontinenzgrad und funktioneller Sphincterlänge, Kneifdruck, Perceptionsschwelle, Drangschwelle, maximal tolerablem Volumen und Kontinenz für semiliquides Kontrastmittel. Schlußfolgerung: Inkontinenz nach Rectumresektion ist multifaktoriell. Anastomosenhöhe, mittlerer Ruhedruck, rectale Compliance und Radiochemotherapie (RCT) spielen eine dominante Rolle. Basierend auf diesen Befunden ist über die Berechnung einer multivariaten Regressionsanalyse eine Abschätzung des Kontinenzgrades vor Ileostomieresektion mit folgender Formel möglich: Prognose-Wexner-Score = 18,23–0,94 · Anastomosenhöhe – 0,18 · Ruhedruck + 3,72 · RCT.
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  • 34
    ISSN: 1432-0533
    Keywords: Key words Bergmann glia ; Cell migration ; Cerebellar ¶dysplasia ; Immunohistochemistry ; Mutant rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cerebellar vermis defect (CVD) rat is a new neurological mutant characterized by a cerebellar vermis defect and dysplasia in the cerebellum, especially at the cerebellopontine junctions. In this study, the cytokinetics of glia in terms of the development of cerebellar dysplasia in the CVD rat was investigated using glial fibrillary acidic protein (GFAP) and vimentin immunohistochemistry. In the cerebellar hemispheres, dislocation of the Bergmann glia was observed from postnatal day 5 (P5) in lesions with abnormally aggregated external granule cells (EGCs). Rearranging Bergmann glia were often seen around the EGCs penetrating into the white matter. In the cerebellopontine junctional areas, Bergmann glia were induced after penetration of the Purkinje cells, identified with calbindin immunohistochemistry, and EGCs into the pons from P10. Bergmann fibers were frequently arranged perivascularly. In the clusters of Purkinje cells without EGC settlement in the pons, a small number of Bergmann fibers were observed and their alignment was completely disturbed. These findings suggest that morphological changes in the Bergmann glia depend on their contact with Purkinje cells, but that the orientation of their processes may be influenced by EGC settlement. These glial fibers in the CVD rat may play an important role in the aberrant migration of EGCs, resulting in the development of cerebellar dysplasia.
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  • 35
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    Acta neuropathologica 99 (2000), S. 310-316 
    ISSN: 1432-0533
    Keywords: Key words Ganglioglioma ; Ependymoma (tanycytic variant) ; Neurofibrillary tangle ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied a cystic ganglioglioma (GG) located in the right frontal lobe of the brain. Interestingly, the fibrillary spindle glial cells were often arranged in a fascicular pattern, and the generally uniform, round-to-oval delicate nuclei appeared to resemble those of ependymoma; and the neoplastic neurons often contained neurofibrillary tangles (NFTs). The glial component was positive for glial fibrillary acidic protein and occasionally contained granular or microvesicular structures positive for epithelial membrane antigen. Ultrastructural investigation revealed that the glial cells were ependymal in nature; intracytoplasmic lumina and intercellular microrosettes lined with cilia and microvilli, as well as long zonulae adherentes, were evident. In addition, chromogranin A-positive granular staining, neurosecretory-granule-like structures, and parallel arrays of microtubules were sometimes associated with the blood vessels. We considered the present case to be an unusual example of GG with an ependymoma, more precisely a tanycytic ependymoma, as the glial component; to our knowledge, the existence of ependymoma as the main glial component of this particular tumor has not been described before. The occurrence of NFTs, which has been reported in several cases of GG, was an additional, unusual feature.
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  • 36
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    Acta neuropathologica 99 (2000), S. 503-510 
    ISSN: 1432-0533
    Keywords: Key words Hamartin ; Immunohistochemistry ; Tuberin ; Tuberous sclerosis ; Western blotting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tuberous sclerosis (TSC) is caused by a mutation in either the TSC1 or TSC2 gene. The clinical manifestations of mutations of the two genes are hardly distinguishable, for reasons as yet unknown. In this study, we examined the expression of the products of these genes, hamartin and tuberin, in control and TSC tissues. Western blotting disclosed that hamartin and tuberin are both abundant in the cerebral gray matter and that they have similar subcellular distributions and developmental patterns of expression. Immunohistochemical localizations of hamartin and tuberin were also similar, with high levels of expression being localized to the cerebral neurons and glial cells, renal uriniferous and collecting tubules, and cardiac muscles. In the cerebrum with TSC, both hamartin and tuberin were simultaneously reduced in the cortical tubers and subependymal giant cell astrocytomas, and from the normal-appearing cortex. The renal angiomyolipomas and cardiac rhabdomyomas also showed a loss of both the proteins. These results provide evidence for the co-localization and interaction of hamartin and tuberin in vivo, and suggest that a mutation in one TSC gene may secondarily affect the expression of the other in some TSC lesions.
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  • 37
    ISSN: 1432-0533
    Keywords: Key words Neuronal intranuclear inclusion ; Neurodegenerative diseases ; Polyglutamine ; Ubiquitin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal intranuclear hyaline inclusion disease (NIHID) is a group of neurodegenerative disorders characterized by the presence of intranuclear inclusions in neurons (NIs). We report here clinicopathological findings of a 25-year-old female patient who died after 13 years of a clinical course characterized by progressive gait disturbance and movement disorders. Histological examination revealed widespread NIs with neuronal loss in restricted regions; neuronal loss was severe in the subthalamic nucleus, internal pallidum, substantia nigra, Edinger-Westphal nucleus and Purkinje cell layer. Quantification of the NIs combined with a graded evaluation of neuronal loss revealed an overall tendency for more severe neuronal loss to be accompanied by a lower frequency of NIs. A morphological similarity to the nuclear inclusions recently identified in several CAG repeat diseases prompted us to examine the immunolocalization of ubiquitin and expanded polyglutamine stretches, which demonstrated the presence of ubiquitin at the periphery of most NIs. An expanded polyglutamine stretch was seen in the center of limited number of NIs. These findings indicate that abnormal fragments such as expanded polyglutamine regions are incorporated into the inclusion, aggregated in its center, and thereby metabolized by a ubiquitin-dependent proteolytic pathway. Although it remains to be elucidated how the formation of NIs is related to neuronal degeneration, our findings suggest that NIs are formed in the process of sequestering or degrading abnormal protein fragments and formation of NIs may not be immediately toxic to neurons.
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  • 38
    ISSN: 1432-0533
    Keywords: Key words Dentatorubral-pallidoluysian atrophy ; Cerebellar dentate nucleus neuron ; Skein-like inclusion ; Polyglutamine ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently reported that, in addition to the widespread occurrence of ubiquitinated neuronal intranuclear inclusions (NIIs), the restricted occurrence of ubiquitinated intracytoplasmic filamentous inclusions in the neurons of the cerebellar dentate nucleus (CDN) is a characteristic feature of dentatorubral-pallidoluysian atrophy (DRPLA). Interestingly, these neuronal intracytoplasmic filamentous inclusions (NIFIs) were morphologically indistinguishable from the skein-like inclusions (SLIs) described previously in the spinal anterior horn cells in amyotrophic lateral sclerosis (ALS). In the present study, we examined immunohistochemically the CDN in ten patients with clinicopathologically and genetically confirmed DRPLA and the spinal anterior horns in five patients with sporadic ALS, using a monoclonal antibody (1C2) directed against long polyglutamine stretches. In all of the patients with DRPLA, both the NIFIs and the NIIs were visualized clearly with 1C2. Conversely, in the patients with ALS all structures, including the SLIs, were completely negative. These findings indicate that in DRPLA, the NIFIs in the CDN are an alteration that is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine) and that, from the molecular point of view, they are distinct from the SLIs in ALS.
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  • 39
    ISSN: 1432-0533
    Keywords: Key wordsα-Synuclein ; Brain tumors ; Neuronal ¶differentiation ; Immunohistochemistry ; Neuronal marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α-Synuclein is presynaptic nerve terminal protein and its immunoreactivity has been observed in such neurodegenerative structures as senile plaques of Alzheimer’s disease or Lewy bodies of Parkinson’s disease. The physiological role of α-synuclein is still unknown. It is speculated that α-synuclein may be expressed in brain tumors, especially in those showing neuronal differentiation. We examined the immunohistochemical localization of α-synuclein in 77 human brain tumors. α-Synuclein was widely distributed in the brain tumors showing neuronal differentiation. As a result, positive immunostaining for α-synuclein was observed in ganglioglioma, medulloblastoma, neuroblastoma, primitive neuroectodermal tumor, pineocytoma/pineoblastoma, and central neurocytoma. Compared with other neuronal markers, the positive ratio of α-synuclein was not as high as synaptophysin, microtubule-associacted protein 2, neuron-specific enolase and tau, but it was higher than neurofilament and chromogranin A. The expression of synaptophysin was diffusely observed in the cytoplasm, cellular processes and nucleus in tumors showing neuronal differentiation; however, the expression of α-synuclein was predominantly observed in the cytoplasm of the tumors as well as in the cellular processes. On the other hand, non-neuronal brain tumors such as astrocytic tumors or meningiomas were totally negative for α-synuclein. In conclusion, the appearance of an α-synuclein-positive structure was not limited to neurodegenerative diseases, but could also be detected in neoplastic cells showing neuronal differentiation.
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  • 40
    ISSN: 1432-0568
    Keywords: Key words α-Smooth muscle actin ; Chronological changes ; Smooth musculature ; Chick ; Ileum ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The genesis of intestinal smooth muscle layers was immunohistochemically investigated by use of an antibody to α-smooth muscle actin (α-SMA) in the developing chick ileum. Myoblast cells positive for α-SMA were already found in the presumptive circular muscle layer on E 8.5. On E 11.5 radially oriented muscle fibers were protruded from the outermost layer of the developing circular musculature and then formed a tuft-like aggregates. These radial muscle bundles were bent into an L-shape. The long distal extension of muscle bundles run parallel to the long axis of the ileal loop and developed into the longitudinal muscle layer. The obliquely oriented muscle fibers, locating at the intermuscular space of the muscularis propria, probably are to be considered a remnant of the short extension of radial muscle bundles. The muscularis mucosae was formed by the processes equivalent to the genesis of longitudinal muscle layer. On E 14.5 centripetally oriented muscle fibers emerged from the innermost layer of circular musculature. The long distal extension of centripetal fibers lay along the inner surface of developing circular musculature. On E 19.5 the longitudinal muscle layer of the muscularis mucosae was newly formed by separating from the circular musculature. The villous myoblast cells initially developed from the innermost layer of the muscularis mucosae on E 18.5, and were widely distributed in the lamina propria mucosae on E 20.5. Temporal and chronological pattern in expression of α-SMA was observed during the development of the chick intestinal smooth muscle. By E 14.5 the entire layer of the muscularis propria was intensely immunostained for α-SMA, but from E 15.5 onward the staining intensity gradually began to decrease from the outer half of the circular musculature. Finally, the immunoreactivity was localized in the inner layer of circular muscle and the longitudinal muscle layer. A possible functional role of this inner layer of circular muscle is discussed.
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  • 41
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    Anatomy and embryology 201 (2000), S. 149-156 
    ISSN: 1432-0568
    Keywords: Key words Cell differentiation ; Cell proliferation ; Collagen ; Fetal development ; Fibronectin ; Immunohistochemistry ; Keratin ; Laminin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  At gestational day 16 the epithelium of the rat stomach consists of a stratified layer of undifferentiated cells, and two days later glandular structures appear. The present study was carried out to identify extracellular matrix proteins that could be involved in the epithelial cell proliferation and differentiation processes that occur in the fetal rat stomach during this period. For comparative purposes the expression of the same components in the adult gastric mucosa was examined. Pregnant Sprague-Dawley rats received an intraperitoneal injection of 5-bromo-2’-deoxyuridine to label proliferating cells. One, 3.5, or 6 h post-injection the stomachs were excised and immediately frozen. The specimens were sectioned and stained with hematoxylin and eosin or for 5-bromo-2’-deoxyuridine, cytokeratin no. 8, H,K-ATPase, and the extracellular matrix proteins fibronectin, laminin, and collagens type I and IV. A stratified layer of proliferating cells was observed in the epithelium of the fetal stomachs, while in adult stomachs proliferating cells were detected in the isthmus/neck region of the glands. Cytokeratin, an epithelial cell marker, was sparse at gestational day 16 but abundant both at gestational day 18 and in the isthmus/neck region of gastric glands of the adult stomach. The parietal cell marker H,K-ATPase could not be detected in the fetal stomachs during this period. Fibronectin was observed in the stroma of both fetal and adult stomachs. Collagen type I could only be detected in the stroma close to the oesophagus at gestational day 16. Two days later, collagen type I was abundant in the lamina propria, the submucosa and in the serosa of the fetal stomachs. In adult tissue collagen type I was detected in the surface epithelium, the submucosa and in the serosa of the stomach. Collagen type IV and laminin were expressed in the lamina propria, the basement membranes around blood vessels, muscle cells, and nerve bundles, as well as in the serosa of both 16- and 18-day-old fetal and adult rat stomachs. In conclusion, a high cell proliferation rate was observed in the epithelium at both gestational days 16 and 18. The increased expression of cytokeratin observed during this period indicates that the epithelial character of the embryonic cells becomes more distinct, while the remarkable change in the expression of collagen type I might reflect an important role of collagen type I in the development of the gastric epithelium.
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  • 42
    ISSN: 1432-0533
    Keywords: Key words Cytosine arabinoside ; Heterotopia ; Microcephaly ; Hippocampus ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pregnant mice were injected intraperitoneally with cytosine arabinoside (Ara-C) on days 13.5 and 14.5 of pregnancy. The brains of their offspring were studied histologically and histochemically. In addition to dysgenic microcephaly, nodular structures consisting of cells with a relatively homogeneous morphology were observed in the depths of the cerebral cortex. The cell clusters were first seen around postnatal day 4, and had a cellular continuity with the disarrayed pyramidal cell layer in the CA1 region of the hippocampus. Golgi-Cox staining showed a number of pyramidal-shaped cells in the clusters. Morphologically, they resembled the pyramidal neurons of the hippocampus. Immunohistochemical examination, using anti-serotonin or anti-tyrosine hydroxylase antibodies, also indicated similarities between the cell clusters and the pyramidal cell layer. It is, therefore, proposed that the cell clusters consisted of heterotopic pyramidal cells of the hippocampus. A few synaptic structures could already be detected in the heterotopic cell clusters on postnatal day 3 by electron microscopy. This early establishment of synaptic contact with related neurons may have caused the heterotopic localization of the pyramidal cells.
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  • 43
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    Acta neuropathologica 100 (2000), S. 427-434 
    ISSN: 1432-0533
    Keywords: Key words Ependymoma ; Ganglioglioma ; Immunohistochemistry ; Intranuclear inclusions ; Tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have observed intranuclear inclusion bodies immunoreactive for the cytoskeletal protein class III β tubulin (C3βT) in neurons and ependymal cells of post-mortem human brain. The relationship of these inclusions, detected by light microscopy, to the intranuclear rodlets described by the classical microscopists is unknown. The present study was conducted to determine whether these proteinaceous inclusions (C3βT-NIIs) exist in the neoplastic counterparts of these cell types. Immunohistochemical staining for C3βT revealed intensely stained, predominantly rod-shaped intranuclear inclusions in a variable proportion of tumor cells in five of ten ependymomas. In addition, C3βT-NIIs were encountered in less than 1% of neuronal cells in two of five gangliogliomas. This study represents the first report of tubulin-containing intranuclear inclusions in brain tumors. The functional significance of these inclusions in normal human brain and in cerebral neuroepithelial neoplasms remains to be determined.
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  • 44
    ISSN: 1432-0533
    Keywords: Key words HSV ; Immunohistochemistry ; Apoptosis ; p53 ; Transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the mechanism of neuronal apoptosis induced by herpes simplex virus (HSV) infection in vivo, the distribution of viral antigen, the appearance of apoptotic bodies, and the expressions of the tumor suppressor gene p53 and several transcription factors such as c-fos, c-jun and NF-κB were examined immunohistochemically and histopathologically after corneal infection of mice with HSV type 2 strain 186. Five days after HSV infection, viral antigen was diffusely detected in the corneal epithelium, the trigeminal ganglion and the pars caudalis of the spinal trigeminal nucleus. Neuronal apoptosis was observed in the brain stem ipsilateral to the HSV-infected side with the immunoreactivities of c-fos, c-jun, NF-κB and p53. Dual-labeling immunohistochemical studies revealed that almost all of the viral antigen-positive neurons and glia in the brain stem also showed p53 immunoreactivity. On the other hand, no neuronal apoptosis but only with the expression of c-jun was found in the trigeminal ganglion. Our results suggest that the different expression of transcription factors between the brain stem and the trigeminal ganglion may influence the neuronal apoptosis induced by HSV infection.
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  • 45
    ISSN: 1432-0851
    Keywords: Key wordsαvβ3 ; Integrins ; Melanoma ; Blood vessels ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The αvβ3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of αvβ3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information is available about the clinical significance of αvβ3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that αvβ3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared αvβ3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we have examined the lesions for expression of the αv subunit to gain information on the regulation of αvβ3 expression on endothelial cells and on cells of the melanocyte lineage. αvβ3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions. However, αvβ3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The αv subunit and the αvβ3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways control their expression. This finding may account for the differential clinical significance of αvβ3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, αvβ3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of all metastatic lesions tested and its restricted distribution in normal tissues.
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  • 46
    ISSN: 1432-0843
    Keywords: Key words Monoclonal antibody ; A33 ; Gastric cancer ; Immunohistochemistry ; Tumor targeting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Murine monoclonal antibody A33 (mA33) was developed by the Memorial Sloan-Kettering Cancer Center and by the New York Branch of the Ludwig Institute for Cancer Research. It is an immunoglobulin (Ig)G2a antibody that detects a protease- and neuraminidase-resistant, periodate-sensitive epitope. Serological analysis of the antigen showed that it is expressed in a few colorectal cancer cell lines and a pancreatic cancer cell line, but is basically not reactive with other types of cell line. Normal fibroblasts and normal kidney cell lines reacted negatively to mA33. Immunohistochemical study of normal tissues identified the large and small intestinal mucosa as the principal site of A33 expression. Tests in tumor samples demonstrated that only tumors of the gastrointestinal tract are consistently A33 positive. A33 is found in 95% of primary and metastatic colorectal cancers, with uniform expression throughout the tumors in most cases. A33 is also detected in 63% of gastric cancers, with uniform expression in 45% of cases. Eighty-three percent of intestinal-type gastric cancers were positive for A33, and about 50% of the diffuse-type and mucinous cancers were mA33 positive. A33 was expressed in 50% of the pancreatic cancers but with marked heterogeneity. Other epithelial cancers, sarcomas, neuroectodermal tumors, and lymphoid neoplasms were generally A33 negative. A33 is the first example of a constitutively expressed, organ-specific epithelial membrane antigen permitting highly specific tumor targeting in patients with gastrointestinal cancer. Encouraged by the success of the biodistribution and imaging characteristic studies performed at Memorial Sloan-Kettering Cancer Center by the New York Branch of the Ludwig Institute in colorectal cancers, a new clinical study of humanized monoclonal antibody huA33 against A33 antigen-positive gastric cancers has been initiated in Japan.
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  • 47
    ISSN: 1432-0851
    Keywords: Key words IL-2 serum levels ; NSCLC ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P 〈 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P 〈 0.0001), although they were still significantly higher than controls (P 〈 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P 〈 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P 〈 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
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  • 48
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    European journal of orthopaedic surgery & traumatology 10 (2000), S. 199-202 
    ISSN: 1432-1068
    Keywords: Abscess ; Prognosis ; Spinal epidural abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five patients suffering from spinal epidural abscess associated with neurologic deficit are reported. Four patients underwent a decompressive procedure for abscess drainage, and one patient was medically treated. One of the patients showed a neurologic deterioration at the early postoperative period. The long-term follow-up showed a good outcome in all patients. It is concluded that epidural abscess associated with progressive neurologic deficit requires immediate decompression and administration of antibiotic. Postoperative neurological deterioration may be seen despite proper and immediate decompression and in such a case neurologic improvement is observed in the late postoperative period.
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  • 49
    ISSN: 1432-069X
    Keywords: Keywords Melanoma ; Immunohistochemistry ; SM5-1 ; HMB-45 ; S100
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antibodies such as HMB-45 and anti-S100 protein have been widely used as markers of malignant melanoma despite evidence that HMB-45 has a sensitivity of only 67–93% and S100 is nonspecific for melanoma. Using a subtractive immunization protocol in a mouse model of human melanoma, we have generated several monoclonal antibodies with putative specificity for melanoma. After initial screenings, the antibody SM5-1 was chosen because of its intriguing reactivity with melanocytic tumors in both frozen and paraffin sections. The immunohistochemical staining of SM5-1 was studied in paraffin-embedded specimens of 401 melanomas (n = 401; 250 primary melanomas, 151 metastases), melanocytic nevi of the skin (n = 16), nonmelanocytic neoplasms (n = 84). The results were compared with HMB-45 and anti-S100 staining. All antibodies reacted with nevi and 97–99% with primary melanomas. Whereas both SM5-1 and anti-S100 stained 96% (146/151) of melanoma metastases, HMB-45 correctly identified only 83% (126/151). All HMB-45-negative metastases were positive for SM5-1. Whereas neither SM5-1 nor HMB-45 stained any of 84 specimens from 40 different nonmelanocytic neoplasms, anti-S100 was positive in 21/84 (25%). While the staining pattern of SM5-1 was mostly homogeneous, small tumor areas in some metastases remained unstained. Staining with SM5-1 was also observed in perivascular dendritic cells, in plasma cells, some myofibroblasts and the secretion of eccrine sweat glands. Nonactivated epidermal melanocytes, keratinocytes, endothelial cells, smooth muscle cells and peripheral nerves were all negative for SM5-1. These results suggest that SM5-1 is highly specific, as well as sensitive, for melanocytic lesions and is useful in the immunohistochemical evaluation of melanoma.
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  • 50
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    Archives of gynecology and obstetrics 264 (2000), S. 13-19 
    ISSN: 1432-0711
    Keywords: Key words Fallopian tube cancer ; Radiotherapy ; Chemotherapy ; Lymph node metastasis ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To contribute toward the understanding of the therapeutic management of fallopian tube cancer. Methods: Recent studies related to the treatment of fallopian tube cancer were reviewed. Results: Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. Conclusions: This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.
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  • 51
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
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  • 52
    ISSN: 1432-119X
    Keywords: Endometrium ; Normal ; Immunohistochemistry ; Immunofluorescence ; Inhibin/activin subunits ; Inhibin-alpha ; Inhibin-beta A ; Inhibin-beta B
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractInhibins are dimeric glycoproteins composed of an alpha (α) subunit and one of two possible beta (β-) subunits (βA or βB). The aims of this study were to assess the frequency and tissue distribution patterns of the inhibin subunits in normal human endometrium. Samples from human endometrium from proliferative phase (PP; n=32), early secretory phase (ES; n=10) and late secretory phase (LS; n=12) were obtained. Immunohistochemistry, immunofluorescence and a statistical analysis were performed. All three inhibin subunits were expressed by normal endometrium by immunohistochemistry and immunofluorescence. Inhibin-α was primarily detected in glandular epithelial cells, while inhibin-β subunits were additionally localised in stromal tissue. Inhibin-α staining reaction increased significantly between PP and ES (P〈0.05), PP and LS (P〈0.01), and ES and LS (P〈0.02). Inhibin-βA and -βB were significant higher in LS than PP (P〈0.05) and LS than ES (P〈0.05). All three inhibin subunits were expressed by human endometrium varying across the menstrual cycle. This suggests substantial functions in human implantation of inhibin-α subunit, while stromal expression of the β subunits could be important in the paracrine signalling for adequate endometrial maturation. The distinct expression in human endometrial tissue suggests a synthesis of inhibins into the lumen and a predominant secretion of activins into the stroma.
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  • 53
    ISSN: 1432-1238
    Keywords: Key words Acute renal failure ; 80 years old ; Etiology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old.¶Design: Historical cohort analysis.¶Setting: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris.¶Patients and participants: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 μmol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50 % over the basal creatininemia.¶Measurements and results: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29 % of the patients received dialysis. Global mortality at the hospital was 40 %. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months.¶Conclusion: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.
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  • 54
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    Intensive care medicine 26 (2000), S. S064 
    ISSN: 1432-1238
    Keywords: Key words Bacteraemia ; Sepsis ; Septic shock ; Epidemiology ; Prognosis ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and 〉 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in 〉 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in 〉 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.
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  • 55
    ISSN: 1432-1084
    Keywords: Key words: MR imaging ; Non-small cell lung cancer ; Therapeutic effect ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The aim of this study was to evaluate the therapeutic effect more accurately and predict the prognosis of treated non-small cell lung cancer by using contrast-enhanced magnetic resonance imaging (CE-MRI). Contrast-enhanced computed tomography (CE-CT) and CE-MRI were examined 90 non-small cell lung cancer patients treated with conservative therapies. Enhancement patterns of CE-MRI were classified into three types: peripheral; mottled; and homogeneous. Reduction ratio of tumor size (RRT) based on the World Health Organization response criteria and a new response rate; reduction ratio of viable tumor size (RRVT) which evaluates not only the reduction of tumor size but also changes in necrosis and/or cavity size, were evaluated. Changes of enhancement pattern were compared and correlated with pathological diagnosis. The RRTs, RRVTs, and interobserver agreements evaluated by all modalities were compared. The RRTs and RRVTs in each subgroup were correlated and compared with prognoses. Change of enhancement pattern depended on therapy had no tendency (p = 0.06). Enhancement pattern had significant correlation with pathological diagnosis (p 〈 0.0001). Partial response (PR) case of RRVT had significant difference between imaging techniques (p = 0.04). The RRVT of other cases and RRT had no significant difference. Interobserver agreements of RRT and RRVT were almost perfect (ϰ≥ 0.93). Prognosis had better correlation with RRVT than with RRT. Differences of relapse-free survival and survival between patients considered as having no change (NC) by RRT and PR by RRVT (NC-PR) and patients considered as having NC by RRT and RRVT were significant (p = 0.03, p = 0.01). There were no significant differences of relapse-free survival and survival between NC-PR patients and patients considered as having PR by RRT and RRVT. The CE-MRI technique could accurately evaluate the therapeutic effect and predict the prognosis of treated non-small cell lung cancer.
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  • 56
    ISSN: 1279-8509
    Keywords: Acute myeloid leukemia ; Chemotherapy ; Allogenic transplantation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to assess the place of HLA-identical allogeneic bone marrow transplantation (BMT) and to compare it to other post-induction therapies, we analyzed patient outcome in intention-to-treat based on the presence or not of an HLA-identical familial donor in young adults with de novo acute myeloid leukemia (AML) in first complete remission (CR). Between 1985 and 1998, 152 consecutive AML patients aged less than 41 years old, seen in our institution, were treated according to 3 different successive protocols (LYLAM85, LAM90, AML10). 144/152 patients entered our prospective study in which they were registered at time of diagnosis for presence or absence of HLA-identical donor and analyzed in intention-to-treat. In this study, 52 patients (36%), who had at least one identical sibling donor (group 1), were offered allogeneic BMT after CR achievement. The 92 patients without donor were allocated to group 2 and were assigned to receive chemotherapy or autologous transplantation as post-remission according to the protocol they were initially included in. Patients from both groups had similar disease characteristics at diagnosis. Karyotypes at diagnosis were defined as low risk (t(8;21) or t(15;17) or chromosome 16 abnormalities(, intermediate risk (normal karyotypes), or high risk (other abnormalities). Overall, 114/152 patients (75%) achieved a CR. Of the 144 eligible patients, 46/52 (88%) with a donor and 68/92 (74%) without a donor achieved a CR. The median follow-up duration of the 144 patients was 21.2 months. The relapse rate was higher in group 2 (56%) than in group 1 (31%). However, the overall survival was not different between patients with and without donor (median survival respectively at 16.7 months and 26.6 months with estimated survival at 5 years respectively at 32% and 34%). Thirty-four patients from group 1 (65%) were actually transplanted in first CR. The probability of 5-year survival for patients receiving effectively allogeneic BMT was 44% and was not significantly better than that of patients who did not. In univariate as in multivariate analysis, karyotypic status was the main prognostic factor for CR achievement (p = 0.002), CR duration (p 〈 0.0001), and overall survival (p 〈 0.0001). There were no significant differences between group 1 and group 2 when survivals were compared with adjustment for karyotypes. We conclude that the availability of an HLA-identical sibling donor did not confer any prognostic advantage in terms of outcome for young adults with AML in first CR. These results make allogeneic BMT process questionable as systemic post-remission therapy in patients with an HLA-identical familial donor.
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  • 57
    ISSN: 1279-8517
    Keywords: Gastric carcinomas ; Cardiac carcinomas ; TNM-classification ; Prognosis ; Lesser and greater omenta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in « understaging » and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.
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  • 58
    ISSN: 1129-2377
    Keywords: Key words Dopamine receptors ; Pial arteries ; Immunohistochemistry ; Prejunctional receptors ; Post-junctional receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial arteries. This was done to further understand the pathophysiology of cerebrovascular dopaminergic system in migraine. The study was performed in sections of dog brain including the pia-arachnoid membrane, which were processed for indirect immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. A faint dopamine D1 receptor protein immunoreactivity was observed in smooth muscle of the tunica media of different sized pial arteries. Dopamine D2 receptor protein immunoreactivity was located in the adventitia and adventitia-media border of pial arteries. In the same area tyrosine hydroxylase immunoreactive nerve fibers were found. No dopamine D3 receptor immunoreactivity was detectable in dog pial arteries. A faint dopamine D4 receptor protein immunoreactivity was observed in dog pial arteries, with a localization similar to that of D2 receptor protein. A moderate dopamine D5 receptor protein immunostaining was observed in smooth muscle of the tunica media. These findings indicate that dog pial arteries express dopamine D1-like (D1 and D5) and D2-like (D2 and D4) receptor subtypes and display, respectively, a muscular (post-junctional) and probably prejunctional localization. These results, the first analysis of dopamine D1-D5 receptor subtype distribution in the cerebrovascular tree, suggest that dopamine is involved in the regulation of cerebral circulation. These finding may help evaluate the role of cerebrovascular dopaminergic mechanisms in the pathogenesis of migraine.
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  • 59
    ISSN: 1432-0533
    Keywords: Key words Heme oxygenase-1 ; Heat shock protein-32 ; Traumatic brain injury ; Cerebral infarction ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extracellular heme derived from hemoglobin following hemorrhage or released from dying cells induces the expression of heme oxygenase-1 (HO-1, HSP-32) which metabolizes heme to the gaseous mediator carbon monoxide (CO), iron (Fe) and biliverdin. Biliverdin and its product bilirubin are powerful antioxidants. Thus, expression of HO-1 is considered to be a protective mechanism against oxidative stress and has been described in microglia, astrocytes and neurons following distinct experimental models of pathological alterations to the brain such as subarachnoidal hemorrhage, ischemia and traumatic brain injury (TBI) and in human neurodegenerative diseases. We have now analyzed the expression of HO-1 in human brains following TBI (n = 28; survival times: few minutes up to 6 months) and focal cerebral infarctions (FCI; n = 17; survival time: 〈 1 day up to months) by ¶immunohistochemistry. Follwing TBI, accumulation of ¶HO-1+ microglia/macrophages at the hemorrhagic lesion was detected as early as 6 h post trauma and was still pronounced after 6 months. In contrast, after FCI HO-1+ microglia/macrophages accumulated within focal hemorrhages only and were absent in non-hemorrhagic regions. Further, HO-1 was weakly expressed in astrocytes in the perifocal penumbra. In contrast to experimental data derived from rat focal ischemia, these results indicate a prolonged HO-1 expression in humans after brain injury.
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  • 60
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    Acta neuropathologica 100 (2000), S. 506-512 
    ISSN: 1432-0533
    Keywords: Key words Telencephalin ; Holoprosencephaly ; Cerebral cortex ; Glomerular structure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telencephalin (TLN), a telencephalon-specific glycoprotein, is exclusively expressed in neurons of the mammalian telencephalon. In the normally developing human brain, TLN immunoreactivity appeared and increased from 35 gestational weeks (GW) in the temporal cortex, and reached adult level at 5 months of postnatal age, being strong in the molecular layer, and weak in the external and internal granular layers. TLN expression corresponded with the development of neuronal dendrites and synapses. In brains with holoprosencephaly TLN immunoreactivity was already strong from as early as 28 GW. Staining was weak in the molecular layer, but strong in the external sparse and middle cellular layers in most cases. Notably, TLN was abundant in the glomerular structures in the internal pyramidal and multiform layers of fetal brains with alobar holoprosencephaly, which disappeared with increasing age. These results indicate premature and ectopic development of the dendrites and synaptic network in holoprosencephaly.
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  • 61
    ISSN: 1432-0533
    Keywords: Key words Myotonic dystrophy ; Myotonic dystrophy protein kinase ; Immunohistochemistry ; Human brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the pathophysiologic role of myotonic dystrophy protein kinase (DMPK) in the brain in myotonic dystrophy (MD), the developmental characteristics of DMPK immunoreactivity in the central nervous system and its alteration with disease were studied. Eleven patients’ brain with MD (5 congenital form, 6 adult form) were examined by immunohistochemistry using a specific antibody against synthetic DMPK peptides, anti-peptide DM1, and compared with 30 control brains, including 16 age-matched controls. In controls, DM1-immunoreactive neurons appeared in the early fetal frontal cortex and cerebellar granule cell layer, persisting through 29 weeks of gestation and then disappearing. In contrast, immunoreactive neurons continued to persist in the cerebral cortex and cerebellar granule cell layer of MD patients. When we counted DM1-immunoreactive neurons, the increase over controls was greater in the congenital form of MD than in the adult form, and was greater in the cerebrum than in the cerebellum in both forms of MD. DM1 immunostaining was predominantly nuclear, mirroring Western blotting of subcellular fractions. Differences in DM1 expression related to development and to the two forms of MD may be closely related to the pathogenesis of mental retardation in this disease.
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  • 62
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    Annals of hematology 79 (2000), S. 455-458 
    ISSN: 1432-0584
    Keywords: Key words Anterior chamber ; Hypopyon ; Leukemia ; Extramedullary ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We encountered a patient with acute myelogenous leukemia (AML) who developed leukemic hypopyon. Leukemia initially spread into the pharynx, gingiva, lymphnode, and bone marrow. He achieved complete remission after chemotherapy but developed blurred vision and hypopyon. Anterior chamber paracentesis disclosed leukemic infiltration of the anterior chamber. Infiltration of the central nervous system also occurred. He received systemic chemotherapy, intrathecal chemotherapy, and local chemotherapy. However, he did not achieve prolonged remission. These findings suggest that these chemotherapy treatments have an inadequate effect for AML with anterior chamber infiltration. This rare complication is associated with extramedullary infiltration of leukemia.
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  • 63
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    Annals of hematology 79 (2000), S. 158-160 
    ISSN: 1432-0584
    Keywords: Key words Splenic rupture ; T-cell lymphoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pathological or spontaneous rupture of the spleen has been described in a variety of diseases affecting the spleen, with infections being cited as the cause in most cases. In hematological malignancies it is a rare event, despite the frequent involvement of the spleen in these diseases. It has, however, been described in patients with acute and chronic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma of B-cell origin, mycosis fungoides, and so-called histiocytic lymphoma. Here, we present a fatal case of splenic rupture caused by infiltration of a peripheral T-cell lymphoma, unspecified according to the REAL classification. The importance of a correct diagnosis and fast surgery is emphasized.
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  • 64
    ISSN: 1432-0533
    Keywords: Key words Aging ; Immunohistochemistry ; Inclusion body ; Neostriatum ; Ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the presence of ubiquitin-immunoreactive skein-like inclusions (SLI) in the neostriatum and spinal cord in normal individuals and patients with different neurodegenerative diseases. Ubiquitin-immunoreactive SLI in the neostriatum were observed both in the normal individuals and in the patients with a variety of neurodegenerative diseases. In particular, SLI were frequently seen in normal aged subjects and certain neurodegenerative diseases, such as progressive supranuclear palsy and myotonic dystrophy. In contrast, the occurrence rate of SLI in cases with Pick’s disease and multiple system atrophy tended to decrease. On the other hand, SLI in the spinal anterior horn were detected in cases of amyotrophic lateral sclerosis, but not in any cases with other neurodegenerative diseases. SLI in the neostriatum were also identifiable using phosphotungstic acid-hematoxylin and Gomori trichrome staining. Ubiquitin immunoelectron microscopy demonstrated that the SLI in the neostriatum corresponded to bundles of filaments. These features of SLI in the neostriatum were quite similar to those of intracytoplasmic rod-like inclusions (RLI) in the large neurons of caudate nucleus, which were first described by Kojima and Ogawa in 1974. Our findings indicate that SLI in the neostriatum are ubiquitin-related structures whose occurrence increases by aging, and less frequently accompany several neurodegenerative diseases, and are identical to at least some RLI.
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  • 65
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    Acta neuropathologica 100 (2000), S. 106-110 
    ISSN: 1432-0533
    Keywords: Key words Posterior pituitary ; Ganglion cell ; Immunohistochemistry ; Ectopia ; Transdifferentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Histologic examination revealed large ganglion cells within the posterior pituitary of an 80-year-old woman who died of myocardial infarction. Apparently fully mature, the cells were an incidental finding scattered within hyperplastic foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic examination of the pituitary obtained at autopsy. Immunocytochemistry showed staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of the glycoprotein hormones and beta-endorphin. The presence of these ganglion cells with features similar to those of magnocellular hypothalamic neurons could be considered the result of abnormal migration during the early phase of embryonic life, or differentiation/maturation of neuroblasts, presumed to occur in the embryonic neurohypophysis. Alternatively, transdifferentiation from proliferating PI cells may explain the emergence of neurons; a hypothesis supported by the proximity and shared alpha subunit, and beta-endorphin immunoreactivities of the two cell types.
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  • 66
    ISSN: 1432-0533
    Keywords: Key words Hypothermia ; Immunohistochemistry ; Microtubule-associated protein 2 (MAP2) ; Rat ; Spinal cord injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
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  • 67
    ISSN: 1432-0533
    Keywords: Key words Cell culture ; Cell line ; Glioma ; Calcium-binding proteins ; Microglia enzymology ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Allograft inflammatory factor-1 (AIF-1) is a Ca2+-binding peptide that constitutes a potential modulator of macrophage activation and function during the immune response of the brain. Peptides termed microglia response factor-1 or ionized calcium-binding adaptor molecule-1 have been reported to be identical with AIF-1. We have investigated the expression of AIF-1 in the rat C6 glioblastoma and 9L gliosarcoma tumor models and additionally assessed AIF-1 expression in a diverse range of human astrocytomas by immunohistochemistry. AIF-1 was expressed by activated microglial cells and a subset of infiltrating macrophages in areas of infiltrative tumor growth and in compact tumor areas in both rat and human gliomas. Double-labeling experiments in rats and humans characterized the nature and the functional status of AIF-1+ cells. AIF-1 expression was detected in cells expressing major histocompatibility complex class II molecules and in a subset of activated macrophages/microglial cells. All MRP-8+ cells coexpressed AIF-1. In humans, there was a strong correlation of AIF-1-expressing activated macrophages/microglial cells with tumor malignancy (P 〈 0.0001). These results suggest that AIF-1 defines a distinct subset of tumor-associated activated macrophages/ microglial cells.
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  • 68
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    Acta neuropathologica 100 (2000), S. 709-711 
    ISSN: 1432-0533
    Keywords: Key words Multiple sclerosis ; Aλ amyloid ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rare multiple sclerosis cases amyloid is deposited in demyelinated plaques. In one such case amyloid was examined immunohistochemically with a panel of antibodies directed against different amyloid types. The amyloid was classified as the Aλ type produced by a local monoclonal B cell population.
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  • 69
    ISSN: 1432-0533
    Keywords: Key words Glial cell line-derived neurotrophic factor ; Human cerebellum ; Immunohistochemistry ; Multiple system atrophy ; Purkinje cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glial cell line-derived neurotrophic factor (GDNF) has a trophic effect on various types of neurons, including cerebellar Purkinje cells. To investigate the role of GDNF in the human cerebellum, we examined the cerebella of eight control cases and eight patients with multiple system atrophy (MSA) immunohistochemically using a polyclonal anti-GDNF antibody. The antibody recognized a single band of approximately 34 kDa on Western blot analysis of human cerebellar homogenates. In the cerebella from normal subjects, the neuronal somata and dendrites of the Purkinje cells were immunostained intensely, as were some axons, including torpedoes, immunolabeled in the granular layer. Many axons and a few oligodendrocytes were also immunopositive in the white matter, and weak immunoreactivity was detected in the granule cells and neurons in the cerebellar nuclei. In the cerebella from patients with MSA, the general immunostaining pattern was similar to that observed in the normal subjects. Most of the remaining Purkinje cells showed strong immunoreactivity, and abundant GDNF-positive granular structures or dense arborizations of GDNF-positive dendrites were found in some areas of the molecular layer. These data suggest that GDNF may be mainly produced and localized in the Purkinje cells of the human cerebellum, even in patients with MSA, and that the functional impairment of the Purkinje cells of MSA patients might cause a focal accumulation of GDNF in the dendrites of some of the surviving Purkinje cells.
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  • 70
    ISSN: 1432-0533
    Keywords: Key words Cerebral aneurysm ; Immunohistochemistry ; Smooth muscle cell ; Phenotypic modulation ; Myosin heavy chain isoforms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We used immunohistochemical methods to analyze the phenotypes of smooth muscle cells (SMCs) in human cerebral arteries and aneurysmal walls. Thirty-two aneurysmal walls were studied; 31 aneurysmal walls were resected at operation and 1 aneurysm was obtained at autopsy. Seven control arteries were obtained at autopsy. Semiserial sections were subjected to immunohistochemical staining with antibodies to α-smooth muscle actin (α-SMA), desmin and smooth muscle myosin heavy chain isoforms: SM1, SM2 and SMemb. In control cerebral arteries, SMCs in the media were strongly immunostained for α-SMA, desmin, SM1 and SM2; immunoreactivity for SMemb was faint or weakly positive. SMCs in both non-ruptured and ruptured aneurysmal walls showed no staining for desmin; the expression of α-SMA was well preserved. Compared with control cerebral arteries, in 4 of 11 non-ruptured aneurysmal walls, the staining intensity of SMCs for SMemb was clearly increased. In ruptured aneurysmal walls, the expression of SM2 was lower than in control cerebral arteries and non-ruptured aneurysmal walls. Our study suggests that the phenotype of SMCs in aneurysmal walls is different from the contractile type in the media of normal cerebral arteries, at least partially changing to the synthetic type in some non-ruptured aneurysms. SMCs in ruptured aneurysmal walls may have lost both phenotypes before rupture. Phenotypic modulation of SMCs in the aneurysmal walls appears to be related to a remodeling of the aneurysmal wall and to a rupture mechanism.
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  • 71
    ISSN: 1248-9204
    Keywords: Hernia ; Strangulation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is believed that direct hernias are less likely to strangulate because, in contrast to an indirect inguinal hernia, the neck of the direct hernia is wide. For this reason, some surgeons do not repair direct hernias in I elderly patients. We analyzed all incarcerated hernias repaired on an emergency basis during a 3-year period in order to discover the extent of incarcerated direct hernias in our practice. A total of 293 patients with incarcerated hernia were evaluated; of these, 222 were inguinal (193 indirect −86.9%- and 29 direct −13.1%-). The strangulation rate for inguinal hernias was found to be 29.7%. There was a significant difference between indirect and direct inguinal hernias in respect to strangulation rate (32.6% vs 10.3% p = 0.014). However, we did not find any difference between bowel resection rates in incarcerated-strangulated indirect and direct hernias (14/193 −7.3%- vs 2/29 −6.9%-, p = 0.95). Hospitalization time was significantly longer for the patients who developed strangulation than those who did not. The side of direct hernia had no effect on strangulation (10.5% for right-sided vs 10.0% for left-sided, p = 0.97). The only prognostic factor for strangulation and resection in regression analysis was the age-group of the patients (〈 60 vs. 60 or older). At operation the average diameter of the defect in the transversalis fascia was 23.8 mm. The diameter of the defect had no effect on strangulation.
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  • 72
    ISSN: 1534-4681
    Keywords: Rectal cancer ; Intensive follow-up ; Local recurrence ; Reoperation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Because more than 90% of local recurrences after curative surgery for rectal cancer appear within the first 36 months after surgery, an intensive and strict follow-up program during this period could improve early diagnosis and, thus, prognosis of patients. Methods: Of the 216 patients who underwent surgery for rectal cancer, 127 entered an intensive follow-up program (median follow-up: 42 months); the clinical outcome of the remaining 89 patients was reconstructed with the help of their general practitioners. Results: Fifty eight (26.8%) of the 216 patients who were treated with curative surgery alone developed a local recurrence; pelvic recurrences were prevalent. Eleven (30.5%) of the 36 patients who had recurrence during follow-up, and 6 of the 22 who had not undergone follow-up, had a reoperation with curative intent; the median survival was 19 months vs. 8 months, respectively (P 5 ns). Four (44.4%) curative reoperations were performed on the 9 asymptomatic patients and in 13 (26.5%) of the 49 cases with symptomatic local recurrences. Median survival was 15 months vs. 14 months, respectively (P 5 n.s). All patients except one (living after 42 months from reoperation) died within 48 months. Conclusions: In our study, adherence to a strict follow-up program unfortunately proved to be ineffective for improving long-term survival for patients who underwent reoperation with curative intent.
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  • 73
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Prognosis ; Pepsinogen C ; Pepsinogen A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. Methods: Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. Results: A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P 〈 .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P 〈 .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P 〈 .001), and in 71 patients with resectable carcinomas (P 〈 .005). Multivariate analysis according to Cox’s model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P 〈 .05, for both). Conclusions: The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.
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  • 74
    ISSN: 1534-4681
    Keywords: Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival rate ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis. Methods: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1–6), Level II nodes (intermediate, No.7–9), and Level III nodes (distant, No.10–16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk. Results: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P 〈 .01), total number of positive nodes (P 〈 .01), number of positive Level I nodes (P 〈 .01), and number of positive Level II nodes (P 〈 .01), in addition to the tumor location (P 〈 .05), tumor size (P 〈 .05), gross type (P 〈 .01), and depth of wall invasion (P 〈 .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0–1 vs. ≥2) (62% vs. 19%, P 〈 .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P 〈 .01). Conclusions: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.
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  • 75
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    Strahlentherapie und Onkologie 176 (2000), S. 513-516 
    ISSN: 1439-099X
    Keywords: Key Words: Breast cancer ; Zoster ; Radiotherapy ; Prognosis ; Schlüsselwörter: Mammakarzinom ; Zoster ; Radiotherapie ; Prognose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Hintergrund: Wir haben in einer retrospektiven Analyse die Häufigkeit eines Herpes zoster bei Patientinnen mit Mammakarzinom und postoperativer Radiotherapie untersucht. Patientinnen und Methode: Von Januar 1985 bis Dezember 1993 erhielten 1 155 Patientinnen an unserer Klinik eine postoperative Bestrahlung nach Mastektomie (n = 961) oder brusterhaltende Operation (n = 194) in kurativer Intention. Das Alter betrug 34 bis 79 Jahre. 443 (38%) waren prä- und 712 (62%) postmenopausal, 21% hatten T3- bis T4-Tumoren, und 55% wiesen einen axillären Lymphknotenbefall auf. Alle Patientinnen erhielten eine Bestrahlung der Restbrust bzw. Thoraxwand bis 50 Gy, bei mastektomierten Patientinnen wurden zusätzlich die regionären Lymphknoten mit 44 Gy bestrahlt. 65% der Patientinnen erhielten eine zusätzliche Systemtherapie. Die Nachbeobachtungszeit betrug drei Monate bis 12,5 Jahre (Median 3,1 Jahre). Ergebnisse: 41/1 155 Patientinnen (3,7%) entwickelten im Nachbeobachtungszeitraum einen Herpes zoster. Alle Infektionen waren lokalisiert, eine generalisierte Hautinfektion oder systemische Infektionen traten nicht auf. Alter, Menopausenstatus, Erkrankungsstadium oder Art der Therapie (Brusterhaltung vs. Mastektomie, zusätzliche Chemotherapie) hatten keinen Einfluss auf die Frequenz von Zoster. Patientinnen mit starker akuter Hautreaktion waren ebenfalls nicht signifikant stärker betroffen als Patientinnen mit geringer Hautreaktion im Bestrahlungsfeld (5% vs. 2%). Das Auftreten eines Zosters nach Therapie hatte keinen Einfluss auf die Prognose hinsichtlich lokaler Kontrolle oder Überleben. Schlussfolgerungen: Die beobachtete Häufigkeit von Herpes zoster (etwa 4% nach drei Jahren Follow-up) lässt vermuten, dass ein Herpes zoster im untersuchten Kollektiv etwa drei- bis fünffach häufiger auftritt als anhand der Inzidenzen in der Normalbevölkerung erwartet. Dies ist nicht mit einer schlechteren Prognose assoziiert. Ob die erhöhte Frequenz auf die Radiotherapie zurückzuführen ist oder in Zusammenhang mit der Krebserkrankung steht, kann nich beurteilt werden.
    Notes: Background: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative interent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. Conclusions: The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response.
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  • 76
    ISSN: 1438-2199
    Keywords: Keywords: Amino acids ; Spinal cord injury ; Heme oxygenase ; Heat shock protein ; Carbon monoxide ; Growth factors ; BDNF ; IGF-1 ; Immunohistochemistry ; Cell injury ; Spinal cord edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The influence of brain derived neurotrophic factor (BDNF) or insulin like growth factor-1 (IGF-1) on spinal cord trauma induced carbon monoxide (CO) production and cellular stress response was examined using immunostaining of the constitutive isoform of the hemeoxygenase (HO-2) enzyme and the heat shock protein (HSP 72 kD) expression in a rat model. Subjection of rats to a 5 h spinal trauma inflicted by an incision into the right dorsal horn at T10–11 segment markedly upregulated the HO-2 and HSP expression in the adjacent spinal cord segments (T9 and T12). Pretreatment with BDNF or IGF-1 significantly attenuated the trauma induced HSP expression. The upregulation of HO-2 was also considerably reduced. These results show that BDNF and IGF-1 attenuate cellular stress response and production of CO following spinal cord injury which seems to be the key factors in neurotrophins induced neuroprotection.
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  • 77
    ISSN: 1438-2199
    Keywords: Keywords: Amino acids ; Nerve lesion ; Neuropathic pain ; Heme oxygenase ; Carbon monoxide ; Cell injury ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The influence of carbon monoxide (CO) on chronic spinal nerve lesion induced spinal cord neurodegeneration was examined using immunohistochemical expression of the constitutive isoform of its synthesising enzyme, hemeoxygenase-2 (HO-2) in a rat model. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model of neuropathic pain and rats were allowed to survive for 8 weeks. Sham operated rats, in which the spinal nerves were exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of HO-2 expression which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, morphological investigations showed distorted neurons, membrane disruption, synaptic damage and myelin vesiculation. Sham operated rats did not show an upregulation of HO-2 expression and the structural changes in the spinal cord were absent. These observations strongly suggest that spinal nerve lesion is associated with an increased production of CO which is somehow contributing to the neurodegenerative changes in the spinal cord, not reported earlier.
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  • 78
    ISSN: 1436-2813
    Keywords: Key words Methionine adenosyltransferase ; Colorectal adenocarcinoma ; Colon ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet) from ATP and L-methionine. AdoMet is the major methyl donor in most transmethylation reactions in vivo, and it is also the propylamino donor in the biosynthesis of polyamines. In the present study, we assessed MAT activity in human colons with colorectal carcinoma and the values were compared with those of morphologically normal adjacent mucosa. Higher levels of MAT activity were observed in the colorectal carcinoma than in the normal colon. The ratio of MAT activity in tumor tissue versus normal tissue seemed to be correlated well will the stage of the colorectal tumor. Furthermore, immunoblot analysis showed that the high levels of MAT activity observed in colorectal carcinoma were due to the increased amounts of MAT protein. Immunohistochemical analysis revealed that MAT was most abundant in goblet cells, particularly in granules in the supranuclear area of these cells. In the colorectal carcinoma tissues, MAT was strongly stained in the cancerous cells and localized in granules in the supranuclear region. The results of this preliminary study suggest that determination of the relative ratio of MAT activity in both normal and tumor regions in human colorectal carcinoma could be a clinically useful tool for determining the stage of malignancy of colorectal carcinomas.
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  • 79
    ISSN: 1436-3305
    Keywords: Key words Hypergastrinemia ; Carcinoid tumor ; Prognosis ; Autoimmune gastritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Gastric carcinoid tumors associated with chronic atrophic gastritis type A have been reported to show good prognosis, because invasion and metastasis are rare. We report a case of gastric carcinoid tumor associated with hypergastrinemia that showed no malignant changes for 12 years. A 15-year-old man with abdominal discomfort underwent endoscopic examination. A polypoid lesion was detected on the atrophic mucosa of the fundus, and was diagnosed as a carcinoid tumor. Serological examination revealed a high level of anti-parietal-cell antibody, suggesting that the patient had chronic atrophic gastritis type A. The tumor was treated by endoscopic mucosal resection. Follow-up examinations were performed for 12 years, but showed no recurrence. This case confirms that gastric carcinoid tumors associated with chronic atrophic gastritis type A may have a good prognosis.
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  • 80
    ISSN: 1436-3305
    Keywords: Key words Gastric cancer ; Beta-catenin ; E-cadherin ; Immunohistochemistry ; Western blot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers. Methods. The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined. Results. Beta-catenin expression was classified into two patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the latter being subclassified as overexpressed (7.3%; 6 patients) and reduced (69.5%; 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration (P = 0.0154), but was not associated with lymph node metastasis (P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression (P 〈 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis; however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival. Conclusion. Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.
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  • 81
    ISSN: 1436-3305
    Keywords: Key words Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis. Methods. The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model. Results. The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]). Conclusion. In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.
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  • 82
    ISSN: 1438-2199
    Keywords: Keywords: Amino acids ; Basal ganglia ; Dopamine ; Nitric oxide ; Excitatory amino acids ; Organotypic culture ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The nigrostriatal and mesolimbic systems of the rat have been re-constructed using the organotypic culture model, whereby neonatal brain tissue is grown in vitro for approximately one month. The nigrostriatal cultures consisted of tissue from the substantia nigra, dorsal striatum and frontoparietal cortex; while the mesolimbic cultures included the ventral tegmental area, ventral striatum and cingulate cortex. The cultures were grown at 35°C in normal atmosphere, using a tube-roller device placed in a cell incubator and changing the medium every 3–4 days. The in vitro development was evaluated with an inverted microscope equipped with a variable relief contrast function. Samples were taken directly from the medium in the culture tube and analysed for several amino acids with HPLC. After a month the cultures were fixed and processed for immunohistochemistry. High levels of glutamate and aspartate were observed every time the medium was changed, but the levels rapidly decreased reaching a steady state after approximately 24 h. A decrease in the levels was also observed along development, reaching stable values (∼2 μM and ∼0.12 μM for glutamate and aspartate, respectively) at approximately two weeks, but only when the cultures showed an apparently healthy development. The levels were approximately 10 times higher in deteriorating or apparently damaged cultures. Glutamine levels were in the mM range and remained stable along the entire experiment. No differences were observed among nigrostriatal and mesolimbic cultures. Immunohistochemistry confirmed the impressions obtained from microscopic and biochemical analysis along the in vitro development, revealing apparently healthy neuronal systems with characteristics similar to those observed in vivo, when tyrosine hydroxylase and nitric oxide synthase, markers for dopamine and nitric oxide containing neurons, respectively, were analysed. In the substantia nigra, nitric oxide synthase-positive networks surrounded tyrosine hydroxylase-positive neurons, while in the striatum nitric oxide synthase dendrites were surrounded by tyrosine hydroxylase-positive nerve terminals, suggesting a reciprocal interaction among dopamine and nitric oxide containing neurons. Thus, the organotypic model appears to capture many of the neurochemical and morphological features seen in vivo, providing a valuable model for studying in detail the neurocircuitries of the brain.
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  • 83
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    Diseases of the colon & rectum 43 (2000), S. 396-401 
    ISSN: 1530-0358
    Keywords: Colorectal carcinoma ; Cathepsin D ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although it has been suggested that cathepsin D, a lysosomal protease, is involved in tumor invasion and metastasis in human colorectal cancers, conflicting studies have also been reported recently. In addition, this issue has been only rarely studied in human colorectal tumors by use of immunohistochemical methods. The aim of the study presented here was to clarify not only the correlation between cathepsin D expression and tumor invasion or metastasis but also the correlation between the intracellular immunostaining pattern of cathepsin D and tumor invasion and metastasis in human colorectal tumors. METHODS: Thirty-four primary colorectal adenocarcinomas and 24 adenomas were immunostained by use of an anticathepsin D antibody. Both the incidence and the immunostaining patterns of cathepsin D were investigated in all tissue samples. RESULTS: Three different immunostaining patterns,i.e., supranuclear, basal, and diffuse, were observed in samples containing cathepsin D. Although the incidence of cathepsin D-positive carcinomas was not correlated with tumor progression, invasion, or metastasis, the immunostaining pattern was significantly correlated with lymphatic invasion. CONCLUSIONS: The results of this study suggest that abnormal cathepsin D immunostaining patterns (basal or diffuse) can be used to predict a potential for lymphatic invasion in colorectal carcinoma.
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  • 84
    ISSN: 1534-4681
    Keywords: Melanoma ; Sentinel node analysis ; Tyrosinase RT-PCR ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Immunohistochemistry (IHC) of serial sectioning is considered the gold standard for detection of melanoma activity in sentinel node (SN) biopsies. However, this is cost and labor intensive. In contrast, tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) is simple and quick, but it is hampered by its extreme sensitivity. This study was performed to test whether a strategy that combines the two methods, using tyrosinase RT-PCR to preselect nodes for IHC, could be accurate and cost effective. Methods: In 36 patients, SNs were identified by scintigraphy and patent blue uptake. Of each SN, one cross section was analyzed first by hematoxylin and eosin staining. Next, all nodes were examined by serial sectioning and IHC of one-half and tyrosinase RT-PCR of the other. Before comparison, all results were documented in a blinded manner. Material costs and workload estimates were noted per SN. Results: Fifty-five SNs were retrieved from the 36 patients. Hematoxylin and eosin staining of the first cross section revealed tumor positivity in 3 patients (6 SN). Tyrosinase RT-PCR was positive in 11 of the remaining 33 patients (19 of 49 SN). Of these same 11 patients, only 5 were shown to have tumor-positive SNs by using IHC on serial sections (7 SN). All these nodes had been positive for tyrosinase on PCR. For IHC, an average of 40 sections were prepared and examined per SN at a cost of $200(U.S.)/SN. In contrast, routine tyrosinase RT-PCR costs $37(U.S.)/SN, and takes 5% of the time necessary for IHC. A strategy including hematoxylin and eosin staining on the first cross section, followed by tyrosinase RT-PCR on half of each negative (half) node, could preselect nodes to be taken through serial sectioning. In these series, such a strategy would have prevented serial sectioning and IHC of 30 SN from 22 patients. Apart from a considerable gain in efficiency, this would have reduced material costs by a minimum of $6000 (U.S.). This iscrepancy would be even higher if work intensity of analysts and pathologists were considered. Conclusions: In routine analysis of SN biopsies in melanoma patients, tyrosinase RT-PCR can be used effectively to preselect nodes for further IHC of serial sections. This method seems both time and cost effective.
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  • 85
    ISSN: 1530-0358
    Keywords: Microscopic peritoneal dissemination ; Colon-cancer ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. METHODS: Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. RESULTS: In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P=0.044 andP=0.0002), whereas immunocytology was only associated with M category (P=0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P〈0.0015/P=0.007 andP〈0.001/P=0.009, respectively). Positive immunocytology was additionally associated with pN category (P=0.05). In a univariate analysis of R0 resected patients (no residual tumor), positive immunocytology was significantly related to an unfavorable prognosis in patients with gastric cancer only (n=30). Mean survival time was significantly increased in patients with gastric cancer with negative cytology compared with positive cytology (1,205 (standard error of the mean, 91)vs. 771 (standard error of the mean, 147) days;P=0.007) but not in patients with colon cancer (1,215 (standard error of the mean, 95)vs. 1,346 (standard error of the mean, 106) days;P=0.55). CONCLUSIONS: Because microscopic peritoneal dissemination influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.
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  • 86
    ISSN: 1530-0358
    Keywords: Abdominoperineal resection ; Laparoscopy ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although laparoscopic colorectal surgery is attracting ever more attention, its use for curative treatment of colorectal carcinoma in particular continues to be controversial. The present study was an attempt to analyze the results of the perioperative course, oncologic quality, and preliminary long-term results. METHOD: The data considered here were collected within the framework of a prospective, observational study initiated on August 1, 1995, and involving a total of 18 institutions in Germany and Austria. At the end of three years, the results are now being presented selectively,i.e., focusing only on abdominoperineal resection. RESULTS: A total of 116 patients underwent laparoscopic abdominoperineal resections, 98 (84.5 percent) of which were performed with curative intent. The mean operating time was 226 (confidence interval, 140–365) minutes. Seven patients (6 percent) experienced an intraoperative complication, which in more than one-half of the cases was a vascular injury involving the presacral venous plexus; the conversion rate was 3.4 percent. Postoperatively, 40 patients developed 97 complications—including those of a very minor nature—giving an overall morbidity rate of 34.4 percent. Reoperation in six patients (5.2 percent) had to be performed for an afterbleed in one-half of the cases and ileus in the other one-half. Postoperative mortality was a low 1.7 percent. In most of the curative resections, an oncologically radical operation with high transection of the inferior mesenteric artery and a complete dissection of the pelvis down to the floor was performed. The median number of lymph nodes investigated was 11.5, and there was wide fluctuation in the numbers among the individual institutions. Tumor cell dissemination occurred intraoperatively in five patients. In the meantime, 79 patients (81 percent) underwent at least one follow-up examination, the mean follow-up period being 491 days. Seven patients developed a local recurrence, and a further six patients developed distant metastases. For recurrence-free survival rate, the Kaplan-Meier estimation calculated a probability of 71 percent. CONCLUSION: Not all of the reservations about laparoscopic abdominoperineal resection, in particular with regard to resection with curative intent, have yet been eliminated. The present study does, however, show that a laparoscopic approach can in principle meet oncologic requirements of radicality and, with regard to the postoperative course, is associated with considerable benefits to the patient.
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  • 87
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    Diseases of the colon & rectum 43 (2000), S. 1222-1226 
    ISSN: 1530-0358
    Keywords: Colorectal neoplasms ; Young age ; Case-control study ; Pathology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Colorectal adenocarcinoma before the age of 40 is uncommon, and its prognosis is controversial, with many studies reporting a worse prognosis than in older patients and others showing no difference. The current study compared two groups of patients who had surgical resection for colorectal adenocarcinoma. METHODS: The case group was composed of 34 patients younger than 40 (34 ± 4) years. Detailed pathologic prognosis factors, tumor cell proliferation measured by proliferating cell nuclear antigen, survival, family history, and predisposing conditions were analyzed. Results were compared with a control group constituted of 34 patients older than 65 (75 ± 6) years matched by gender, cancer site, and Dukes stage. RESULTS: Tumor differentiation, presence of vascular and perineural neoplastic invasion, tumor growth pattern, tumor cell proliferation measured by proliferating cell nuclear antigen count, and survival according to the Kaplan-Meier method were not significantly different between younger and older patients. The only difference between the two groups was a higher prevalence of family history and predisposing conditions for colorectal cancer in younger patients (23vs. 3 percent;P=0.03). CONCLUSION: This case-control study documents that pathologic features and prognosis of colorectal adenocarcinoma are comparable in patients younger than 40 years compared with older patients for identical stages. The higher prevalence of positive family history in younger patients suggests a different genetic background compared with older patients.
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  • 88
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Younger patients ; Elderly patients ; Comparative study ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Gastric cancer is one of the most common gastrointestinal malignancies worldwide. Some studies have suggested that it has a worse prognosis in young than in elderly patients. Methods: All young and elderly patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a tertiary referral center in Mexico City were included. Demographic, clinical, and pathologic features of young patients (less than 40 years of age) with gastric cancer were compared with those of elderly patients (70 years of age or older) with the same diagnosis. Overall survival was the main outcome measure. Results: There were 38 patients in each group. The mean age of the young and elderly groups was 33 and 77 years, respectively. Family history of gastric cancer was reported by 6 patients of the younger group and by 1 patient in the older group (P 〈 .05). Most patients in both groups were symptomatic and had an advanced stage of the disease. With a mean follow-up of 17 months, the overall median survival for all patients was 12 months. By group, the median survival was 13 and 12 months for the young and elderly patients, respectively (P = .38). Variables with significant impact on survival were the stage of the disease, possibility of surgical resection, location of the tumor, and a family history of gastric cancer. Conclusions: Young patients represent a significant proportion of patients with gastric cancer in Hispanic populations. There were no significant differences in clinicopathological characteristics and outcome of gastric adenocarcinoma between young and elderly patients. Survival was determined by the stage of the tumor and the possibility of complete surgical resection.
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  • 89
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    Annals of surgical oncology 7 (2000), S. 520-525 
    ISSN: 1534-4681
    Keywords: Proximal gastric third ; Adenocarcinoma ; Total gastrectomy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The incidence of proximal gastric third carcinoma (PGC) has been rising in recent years. Classification and surgical therapy remain controversial. Methods: Between May 1986 and October 1997, 532 patients were operated for primary gastric carcinoma. All patient data were analyzed retrospectively comparing findings in patients with PGC and those with distal gastric carcinoma (DGC). Results: Two hundred fifty patients had a PGC, and 282 patients had a DGC. The rate of R0 resections was 79.3% for PGC and 81.6% for DGC. In 93.9% of the patients with PGC total gastrectomy was performed; for DGC total gastrectomy was done in 74.5% of patients. Postoperative morbidity and mortality were 29.2% for PGC and 23.8% for DGC, and 3.2% for PGC and 3.5% for DGC, respectively. Patients with advanced tumor stages (stage III and IV) were more common in the PGC group (73.3% vs. 53.6% in DGC). After R0 resection, the 5-year survival rate was 33.2% for PGC and 59.7% for DGC. Conclusions: There was no significant difference between the rates of R0 resections for PGC and DGC. Total gastrectomy can be performed with low postoperative morbidity and mortality. PGC and DGC represent the same tumor entity, and prognosis is similar, but due to more advanced tumor stages, the long-term survival is worse for patients with PGC than for those with DGC. Left retroperitoneal lymphadenectomy may be indicated for PGC.
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  • 90
    ISSN: 1530-0358
    Keywords: Fistula-in-ano ; Surgery ; Imaging ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Magnetic resonance imaging of fistula-in-ano has been shown to predict surgical anatomy accurately and identify complex features. In addition, fistula complexity has been correlated with poor outcome after surgical intervention. We investigated whether preoperative magnetic resonance imaging could predict clinical outcome after surgery for fistulous disease better than clinical examination under anesthetic. METHODS: Seventy patients with clinically suspected fistula-in-ano underwent preoperative dynamic contrast-enhanced magnetic resonance imaging before surgical exploration. Outcome was assessed at a minimum of one year after surgical exploration and correlated in a blinded fashion with the surgical and magnetic resonance grading of the severity of the fistulous disease. RESULTS: Of 70 patients, 12 were not operated on and 6 were lost to follow-up, making 52 patients eligible for analysis. Assessment by dynamic contrast-enhanced magnetic resonance imaging more accurately predicted outcome than the findings at initial surgical exploration. Dynamic contrast-enhanced magnetic resonance imaging had a sensitivity of 81 percent, specificity of 73 percent, and positive predictive value of 75 percent; surgery had a sensitivity of 77 percent, specificity of 46 percent, and positive predictive value of 59 percent. Surgical assessment of apparent disease severity bore no relation to final outcome. Dynamic contrast-enhanced magnetic resonance imaging could accurately predict whether patients were likely to have a satisfactory or unsatisfactory outcome after surgery. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging better predicts clinical outcome of patients with fistula-in-ano than initial surgical exploration.
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  • 91
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    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
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  • 92
    ISSN: 1534-4681
    Keywords: Colorectal hepatic metastases ; Liver neoplasm ; Liver resection ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined. Methods: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed. Results: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4–20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median 5 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival. Conclusions: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.
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  • 93
    ISSN: 1436-3305
    Keywords: Key words Mucosal gastric cancer ; Micrometastasis ; Cytokeratin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Endoscopic mucosal resection is frequently used in the treatment of mucosal gastric cancer. Micrometastasis in the lymph nodes of mucosal gastric cancer remains unclear. Methods. We examined 2526 lymph nodes from 84 patients with mucosal gastric cancer. Two consecutive sections were prepared, for simultaneous staining with hematoxylin and eosin and immunostaining with CAM 5.2 monoclonal antibody against cytokeratin (CK), respectively. A clinicopathological comparison was made between patients with and without lymph node involvement. Results. Lymph node involvement was detected in 45 of 2526 (1.8%) lymph nodes. The incidence of nodal involvement was significantly increased, from 1.2% (1/84 patients) with hematoxylin and eosin staining, to 19% (16/84 patients) with CK immunostaining. Although no significant difference was found, micrometastasis to lymph nodes was more frequently detected in tumors larger than 1.0 cm (15/72 patients, 21%) than in those less than or equal to 1.0 cm (1/12 patients; 8%, P = 0.307). However, discrete CK-positive cancer cells or clusters of CK-positive cancer cells were detected only in tumors larger than 2 cm. Conclusion. Because mucosal gastric cancer of more than 1.0 cm in superficial diameter may indicate a risk of micrometastasis to lymph nodes, endoscopic mucosal resection is not recommended for these patients.
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  • 94
    ISSN: 1436-3305
    Keywords: Key words EGC ; Prognosis ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. During the 1970s, a special type of Gastric Cancer with excellent prognosis (early gastric cancer; EGC) was identified by the Japanese Research Society for Gastric Cancer. EGC has been defined as a tumor which invades the mucosa and/or submucosa, regardless of the lymph node status. Using this definition, we identified an initial phase of tumor development which could be treated both endoscopically and surgically. Methods. We examined 412 EGC patients, recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an end-point of interest for the survival analysis. Results. Submucosal tumors (P = 0.008), Pen A (see definition below) type disease (P = 0.0001), and lymph node-positive cancers (P = 0.0002) were significant prognostic factors on univariate analysis. Moreover, bivariate analysis showed that the worst prognosis, in terms of survival, was for patients with nodal involvment, submucosal invasion, and node-positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a lesion with a diameter of less than 4 cm, which invades the submucosa diffusely. Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa extensively, with nodular masses, causing the complete destruction of the muscularis mucosae. Conclusion. In our series, Pen A type was an important prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49–19.86. For this reason, we believe it is important to evaluate the infiltration into the wall in all patients with EGC, paying particular attention to the growth pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a considerably worse prognosis and this finding was reinforced when lymph node metastases coexisted. We suggest, therefore, that surgical treatment with at least a D2 lymphadenectomy is performed in all these patients, as the lesions must be considered to be advanced, no longer being EGC.
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  • 95
    ISSN: 1436-3305
    Keywords: Key words Tumor marker ; CEA ; CA19-9 ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer. Methods. During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression. Results. Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression. Conclusion. Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.
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  • 96
    ISSN: 1436-2813
    Keywords: Key Words Adenosquamous carcinoma ; Remnant stomach ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein the case of a 59-year-old man found to have adenosquamous carcinoma of the remnant stomach which demonstrated rapid progression. The patient was admitted to our hospital to undergo surgery for a papillary tumor of the remnant stomach. Total resection of the remnant stomach with lymph node dissection was performed, and pathological examination confirmed a diagnosis of adenosquamous carcinoma with invasion into the muscularis propria and lymph node metastasis around the perigastric areas. Multiple liver metastases were found 6 months after the operation, for which a right hepatectomy was performed with curative intent; however, he died 2 months later due to lymphangitis carcinomatosa of the lung.
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  • 97
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    Trauma und Berufskrankheit 2 (2000), S. S154 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Hinteres Kreuzband ; Isolierte Ruptur ; Therapie ; Prognose ; Key words ; Posterior cruciate ligament ; Isolated tears ; Treatment ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The treatment of injuries to the PCL is still controversial. There are still no answers to many questions on the biomechanics of PCL, the natural history of PCL injury, the surgical technique of PCL reconstruction and the biology of PCL healing. It is well established that primary repair of bony avulsions of the PCL provides good static and functional results. PCL tears should also be treated surgically in combined knee ligament injuries. For isolated midsubstance tears of the PCL, however, no prospective randomised long-term studies are available to date demonstrating that surgical treatment with current techniques leads to better results than nonoperative, functional treatment. Nonoperative management is advocated because the knee instability following isolated PCL midsubstance tear is only moderate, the natural history has been seen to end in acceptable functional stability, knee proprioception is preserved, and the incidence of late osteoarthritis is low.
    Notes: Zusammenfassung Die Behandlung von Rupturen des hinteren Kreuzbands wird international noch immer kontrovers diskutiert. Zahlreiche Fragen zur funktionellen Anatomie, zum Spontanverlauf nach Ruptur, zur chirurgischen Technik sowie zum Heilungsverlauf sind unbeantwortet. Gesichert ist, daß die primäre operative Versorgung von knöchernen Ausrissen des hinteren Kreuzbands zu guten Ergebnissen führt. Bei kombinierten Knieinstabilitäten sollte das verletzte hintere Kreuzband auch operativ versorgt werden. Für die isolierte, interligamentäre Ruptur des hinteren Kreuzbands konnte bisher jedoch mit keiner prospektiven, randomisierten Langzeitstudie bewiesen werden, daß die heutigen Operationsverfahren reproduzierbar zu besseren Ergebnissen führen als die konservativ-funktionelle Behandlung. Für die konservative Therapie sprechen die nur mäßige Instabilität nach isolierter Ruptur des hinteren Kreuzbands, der günstige Spontanverlauf und der Erhalt der Propriozeption des Kniegelenks sowie die im Verlauf nur geringe Arthroserate.
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  • 98
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    International journal of legal medicine 113 (2000), S. 288-292 
    ISSN: 1437-1596
    Keywords: Key words Brain injury ; Cortical contusion ; Vascular ¶reaction ; Immunohistochemistry ; Wound age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract In a total of 104 individuals who had sustained traumatic brain injury (TBI), the time-dependent vascular response was investigated at the injured cortical area during the first 30 weeks after the trauma. The immunohistochemical staining of the cerebral blood vessels was performed with antibodies against laminin, type IV collagen, tenascin, thrombomodulin and factor VIII associated antigen. Compared to the immunoreactivity in unaltered control tissue, a significantly increased vascular expression could be detected in cortical contusions after a postinfliction interval of at least 3 h for factor VIII, after 1.6 days for tenascin or after 6.8 days for thrombomodulin, whereas the immunostaining for laminin and type IV collagen was regularly positive even in the vascular endothelium of uninjured brain tissue.
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  • 99
    ISSN: 1432-1335
    Keywords: Key words Blood group antigen ; ABH isoantigens ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.
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  • 100
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    Journal of cancer research and clinical oncology 126 (2000), S. 280-284 
    ISSN: 1432-1335
    Keywords: Key words Thymoma ; Prognostic factors ; Prognosis ; DNA cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. Patients and methods: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6–164) months. Results: Masaoka's stage was predictive of aneuploidy (P 〈 0.01) and disease-free survival (P 〈 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P 〈 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. Conclusion: DNA image cytometry may provide additional information about the prognosis of resected thymoma.
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