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  • Articles: DFG German National Licenses  (232)
  • 2000-2004
  • 1990-1994  (232)
  • 1985-1989
  • 1830-1839
  • 1990  (232)
  • pharmacokinetics  (125)
  • Immunohistochemistry
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  • Articles: DFG German National Licenses  (232)
Material
Years
  • 2000-2004
  • 1990-1994  (232)
  • 1985-1989
  • 1830-1839
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 10 (1990), S. 103-106 
    ISSN: 1437-160X
    Keywords: Synovium ; Synoviocytes ; Monoclonal antibody ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The functionally important lining cells of the synovium (types A and B synoviocytes) are the subjects of much study but have presented problems with their characterization and microscopical identification, particularly at the light level. Type A (macrophage-like) synoviocytes, however are more easily localized than the type B (fibroblast-like) variety because of the greater availability of antimacrophage antisera. We describe, using light and electron microscopy, a monoclonal antibody which in the synovial intimal layer is specific for type B synoviocytes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 103 (1990), S. 593-598 
    ISSN: 1437-1596
    Keywords: ABO in bones ; Putrification ; Extraction ; Immunohistochemistry ; ABO an Knochen ; Fäulnis ; Extraktion ; Immunhistochemie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Knochenteile wurden in Wasser bei Raumtemperatur 2 Jahre aufbewahrt and anschließend serologischen Untersuchungen unterzogen. Zur Anwendung kamen folgende Untersuchungsmethoden: Absorptions-Elutionstest, Extraktion von Blutgruppensubstanzen, Immunhistochemie (PAP). In frischen Knochen ergaben alle 3 Methoden im wesentlichen spezifische Ergebnisse. In faulen Knochenproben zeigten das Absorptions-Elutions-und das PAP-Verfahren unspezifische Reaktionen. Die Reaktionen in den Extrakten waren dagegen eher spezifisch, jedoch extrem schwach. Daraus wird der Schluß gezogen, daß bei der Entstehung unspezifischer Reaktionen in faulendem Knochengewebe rein physikalische Bindungen von Antikörpern mit dem durch Fäulnis veränderten Knochenmaterial eine wesentliche Rolle spielen.
    Notes: Summary Bone fragments were stored in water for 2 years at room temperature and investigated serologically using the following methods: Absorptionelution, extraction of blood group substances and immunohistochemistry (PAP). All 3 methods gave essentially specific results for fresh bone tissue but with putrid bone tissue unspecific reactions were found predominantly with the absorption-elution and PAP techniques. In contrast, more specific reactions were obtained from the extracts although they were much weaker. From this it can be concluded that pure physical binding plays a substantial role in the unspecific reaction between antibodies and bone material. It is suggested that the relevant physical properties are altered by putrifaction.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Cytomegalovirus ; Procaryotic expression ; Recombinant antigen ; Phosphorylated protein pp150 ; Monoclonal antibody ; Immunofluorescence ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Procedures for diagnostics of cytomegalovirus infections include histopathology, cell culture, serology, and direct detection of viral antigens or nucleic acids within infected cells or tissues. In order to develop a new diagnostic reagent for viral antigen detection, we generated a mouse monoclonal antibody. This antibody was raised against a recombinant antigen representing part of the large phosphorylated structural protein pp150 of human cytomegalovirus. The monoclonal antibody was shown to be useful for antigen detection by immunofluorescence and immunoenzymatic staining in infected cells from cell culture as well as from infected organs. The antibody proved to be reactive even in paraffin-embedded sections from tissue specimens.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 103 (1990), S. 593-598 
    ISSN: 1437-1596
    Keywords: ABO in bones ; Putrification ; Extraction ; Immunohistochemistry ; ABO an Knochen ; Fäulnis ; Extraktion ; Immunhistochemie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Knochenteile wurden in Wasser bei Raumtemperatur 2 Jahre aufbewahrt und anschließend serologischen Untersuchungen unterzogen. Zur Anwendung kamen folgende Untersuchungsmethoden: Absorptions-Elutionstest, Extraktion von Blutgruppensubstanzen, Immunhistochemie (PAP). In frischen Knochen ergaben alle 3 Methoden im wesentlichen spezifische Ergebnisse. In faulen Knochenproben zeigten das Absorptions-Elutions-und das PAP-Verfahren unspezifische Reaktionen. Die Reaktionen in den Extrakten waren dagegen eher spezifisch, jedoch extrem schwach. Daraus wird der Schluß gezogen, daß bei der Entstehung unspezifischer Reaktionen in faulendem Knochengewebe rein physikalische Bindungen von Antikörpern mit dem durch Fäulnis veränderten Knochenmaterial eine wesentliche Rolle spielen.
    Notes: Summary Bone fragments were stored in water for 2 years at room temperature and investigated serologically using the following methods: Absorptionelution, extraction of blood group substances and immunohistochemistry (PAP). All 3 methods gave essentially specific results for fresh bone tissue but with putrid bone tissue unspecific reactions were found predominantly with the absorption-elution and PAP techniques. In contrast, more specific reactions were obtained from the extracts although they were much weaker. From this it can be concluded that pure physical binding plays a substantial role in the unspecific reaction between antibodies and bone material. It is suggested that the relevant physical properties are altered by putrifaction.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 5 (1990), S. 110-113 
    ISSN: 1437-9813
    Keywords: Infantile hypertrophic pyloric stenosis ; Enkephalin ; Substance P ; Vasoactive intestinal polypeptide ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the recent literature it has been noted that peptidergic nerves may play an important role in infantile hypertrophic pyloric stenosis (HPS). Specimens from 20 patients with HPS were examined by immunohistochemistry with regard to the distribution of nerve cells and nerve fibers containing enkephalin (ENK), substance P (SP), and vasoactive intestinal polypeptide (VIP). Three subpopulations of peptides containing nerve cells and fibers were fairly numerous in the control specimens, but in the patients with HPS the density of the nerve fibers was markedly reduced and occasionally absent, especially the ENK- and VIP-containing fibers. In the myenteric plexus there was neither a reduction of nerve cell bodies nor of fibers. Our findings suggest that abnormalities of peptide-containing nerve fibers or impairment of neuronal function might results in HPS.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 416 (1990), S. 237-248 
    ISSN: 1432-2307
    Keywords: Neurilemoma ; Pseudosarcoma ; Electron microscopy ; Immunohistochemistry ; Cytogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of 29 cellular schwannomas is described in terms of their clinical presentation and course, light and electron-microscopic appearance, immunohistochemical properties and cytogenetics. The study indicates that cellular schwannoma can be defined as a subtype of classical schwannoma, characterized by spindle cells forming a compact fascicular, sometimes fibrosarcoma-like growth pattern, a low mitotic activity, a generally moderate nuclear and cellular polymorphism and a high degree of Schwann cell differentiation as seen by electron microscopy and immunohistochemistry. The tumour is characteristically located close to the vertebral column, in the mediastinum or retroperitoneum and has a benign course. Occasionally bone destruction and neurological symptoms develop. The clinical appearance together with the high cellularity, fascicular pattern and mitotic activity had led to the erroneous diagnosis of a soft tissue sarcoma in a few cases, and cellular schwannoma may thus be considered to be a pseudosarcoma. Immunohistochemically, cellular schwannomas appear to deviate from classical schwannomas and malignant peripheral nerve sheath tumours by their expression of glial fibrillary acidic protein. The chromosome analysis revealed a normal diploid stemline karyotype, with a variety of abnormal clones, including one with monosomy 22.
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  • 7
    ISSN: 1432-2307
    Keywords: Anaplastic large cell lymphoma ; Non-Hodgkin's lymphoma ; Immunohistochemistry ; Antigen expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this report we analyze the morphological and immunohistochemical findings observed in 5 cases of CD30/Ki-1 positive anaplastic large cell lymphoma, a recently recognized neoplastic entity. In comparison with the Ki-1 lymphomas so far described, these cases showed a fairly large number of Reed-Sternberg-like cells, often admixed with small lymphocytes and occasional eosinophils. Moreover, in all our cases immunohistochemical reactions detected the CD15/ Leu-M1 antigen, together with markers of the T-lineage and of lymphoid activation. In previous studies the CD15/Leu-M1 antigen has been found in the majority of cases of Hodgkin's disease, but has been stated to be absent typically in Ki-1 lymphomas. Our results indicate that this antigen cannot be considered a reliable tool to distinguish between Ki-1 lymphomas and Hodgkin's disease. Furthermore, the morphological and immunohistochemical findings reported suggest that in some cases Ki-1 cell lymphoma and Hodgkin's disease may be closely related. They may represent different steps in the progression of the same lymphoproliferative disorder.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 417 (1990), S. 243-246 
    ISSN: 1432-2307
    Keywords: Gallbladder ; Malignant angioendotheliomatosis ; Malignant lymphoma ; Immunohistochemistry ; Differential diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We present a case of malignant angioendotheliomatosis of the gallbladder, the first reported. Diagnostic problems connected with this rare malignancy are underlined. Immunohistochemical studies were useful in providing further evidence of the lymphoid nature of the neoplasm and avoiding possible misdiagnosis. We suggest that the term “angiotropic lymphoma” might be more appropriate to define this malignancy.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 417 (1990), S. 261-266 
    ISSN: 1432-2307
    Keywords: Stomach ; Paraganglioma ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report the second case of a malignant paraganglioma of the stomach in a 56-year-old female patient. However, our case is the first investigated by immunohistochemistry and electron-microscopy. The tumour was characterized immunohistochemically by the presence of neurofilament protein, glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, chromogranin A, ACTH, leu-enkephalin and vasoactive intestinal polypeptide, and ultrastructurally by demonstration of neurosecretory granules and paranuclear intermediate filament whorls. Despite massive metastatic spread in the abdominal cavity, the patient is still alive 4 years after initial diagnosis.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 416 (1990), S. 403-410 
    ISSN: 1432-2307
    Keywords: Langerhans cell histiocytosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunophenotypic properties of the abnormal cells in routine specimens from 16 cases of Langerhans cell histiocytosis (LCH) were examined. In five cases, cryostat sections were also available. The abnormal cells expressed a similar phenotype and were positive for HLA-DR, S-100 protein, peanut agglutinin (PNA), CD1a, CD4 and several macrophage-associated markers, including CD11c, CDw32 and CD68 (the latter detectable in routine sections with antibody KP1). Staining with CD14, CD35 (C3b receptor), and CD11b (C3bi receptor) was negative with the exception of one of the cases in which a proportion of the cells showed faint positivity with CD11b. Staining for pan-T-cell (CD2, CD3, CD5) and panB-cell (CD 19, CD22) antigens was negative in all lesions. It is concluded that LCH expresses a characteristic phenotype with some heterogeneity with regard to macrophage markers and that immunohistochemical methods in cryostat sections and routine specimens form a useful supplement to other techniques for the diagnosis of this condition.
    Type of Medium: Electronic Resource
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 416 (1990), S. 437-442 
    ISSN: 1432-2307
    Keywords: Hematopoiesis ; Immunohistochemistry ; Osteomyelofibrosis ; Spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 30 spleens from patients with biopsy proven primary osteomyelofibrosis were studied by histological and immunohistochemical methods. The presence of trilinear haematopoiesis along the splenic circulatory pathway supports the theory that the spleen acquires haematopoietic precursor cells by filtration of the peripheral blood. In addition, impairment of intrasplenic circulation with subsequent red pulp congestion, pulp cord fibrosis and haemophagocytosis is of importance for the pathogenesis of both marked splenic haematopoiesis and complications due to hypersplenism.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 416 (1990), S. 535-538 
    ISSN: 1432-2307
    Keywords: Pancreatic tumour ; Immunohistochemistry ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical studies and DNA flow-cytometric investigations were performed in a case of solid-cystic tumour of the pancreas in a 35-year-old woman. All tumour cells were immunoreactive for the neuroendocrine cell markers chromogranin A and neuron-specificγ-enolase. Moreover, about 10% of tumour cells were immunoreactive for insulin, while hypoglycaemia was absent. Few tumour cells (less than 1%) were immunoreactive for somatostatin, and no cells were found to be immunoreactive for pancreatic polypeptide or glucagon. No immunoreactivity was present for duct cell marker carcino-embryonic antigen and only individual cells were reactive forα 1-antitrypsin. Nuclear DNA content of the tumour cells was diploid and the proliferative activity was low. In confirmation of some reports on neuroendocrine markers in solid-cystic tumour of the pancreas, our findings support the theory that the lesion is a hormonally inactive neuroendocrine pancreatic tumour.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-2307
    Keywords: Non-Hodgkin's lymphoma ; Brain neoplasm ; Stereotactic brain biopsy ; Histological diagnosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In establishing the histological diagnosis of primary cerebral lymphoma, stereotactic brain tumour biopsy is the method of choice as the mainstay of therapy is radiation and chemotherapy. This study describes the histopathology and diagnostic immunohistochemistry of 54 primary brain lymphomas in a mainly non-AIDS population. The stereotactic biopsies were performed using the Leksell CT stereotactic frame and a spiral needle which procured about 10-mm-long tissue cylinders. Usually, three successive biopsy cylinders were taken along the target trajectory. Histological examination revealed the prevalence of high-grade non-Hodgkin's lymphoma of the polymorphous centroblastic type. The series did not include any low-grade lymphomas or T-cell lymphomas. L-26 immunohistochemistry resulted in a positive staining of the blasts, thus confirming the B-cell origin of primary brain lymphomas. Small reactive T-lymphocytes and monohistiocytic cells were also found within and at the periphery of the lymphomas and in areas of degeneration. In the biopsies of nine patients, who had shown significant reduction of the lesions on the CT scans, after corticosteroid medication, regressive tissue changes were predominant and consisted of T-lymphocytes, macrophages, and occasionally bizarre reactive astrocytes.
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  • 14
    ISSN: 1432-2307
    Keywords: T-cell receptors ; Malignant lymphomas ; Immunohistochemistry ; Transcription ; Rearrangement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of T-cell receptors (TCR) in malignant lymphomas was examined immunohistochemically by monoclonal antibodies which react with the TCRΒ or TCRδ chain. TCRΒ was expressed in 16 out of 47 non-Hodgkin's lymphomas. These included 15 T-cell lymphomas and 1 Ki-1 lymphoma. The anti-TCRΒ chain antibody,ΒF1, did not react with 26 B-cell lymphomas, 1 Ki-1 lymphoma or 6 Hodgkin's disease. The anti-TCRδ chain antibody, TCRδ1, did not react with any type of malignant lymphoma. Although TCRΒ and CD3 were co-expressed in normal lymphoid tissues and most T-cell lymphomas, 3 cases of CD3+CD4+ CD8−T-cell lymphoma failed to express TCR0. TCRΒ and Ig JH gene configurations in malignant lymphomas were examined by Southern hybridization. Although each of 9 T-cell lymphomas had a rearranged TCRΒ locus, TCRΒ gene rearrangement in the 3 cases ofΒF1−CD3+T-cell lymphomas was demonstrated by Southern blot. No transcripts of the TCRΒ gene could be found in 2 out of the 3ΒF1−CD3+T-cell lymphomas by Northern blot, indicating the lack of TCRΒ protein expression to be due to non-transcription of the TCR gene. Loss of TCRΒ proteins in these T-cell lymphomas is thus quite likely to be associated with T-cell tumour activation and progression, since 3ΒF1−CD3+T-cell lymphomas expressed CD25 (interleukin-2 receptor) to a high degree.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 417 (1990), S. 113-118 
    ISSN: 1432-2307
    Keywords: Minute chemodectoma ; Lung ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary So-called minute pulmonary chemodectoma is a curious, small lung tumour found mainly in women. The nature and origin of the proliferating cells are still obscure. In the first report on the tumour, the component cells were described as resembling chemoreceptor cells and the tumour was named chemodectoma. However, electron microscopic studies of the tumour have revealed no evidence of neuronal characteristics and have shown a close resemblance to meningothelial cells. In this study, the electron microscopic findings were similar to those previously reported but in one of the two cases, tumour cells were filled with abundant cytofilaments, giving them an occasional dense, patch-like appearance. Immunostaining for myosin and vimentin was positive in all tumour cells, but epithelial membrane antigen staining was not seen. These findings indicate that the tumour might have its origin from muscle cells.
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  • 16
    ISSN: 1432-2307
    Keywords: Chondrosarcoma ; Chondroma ; Collagen ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunohistological distribution of collagen types I, II, III, V and VI in human benign and malignant cartilaginous tumours of bone was examined with regard to their aggressiveness. The matrix of enchondromas consisted of type II collagen distributed diffusely, and type VI predominantly localized in the immediate surroundings of the cells. Types I, III and V collagen were not found. These findings were similar to the distribution of collagenous proteins in normal hyaline cartilage where each lobule was consistently rimmed by types I and V collagen. In grade 1 chondrosarcomas, the main collagenous components of matrix were also types II and VI collagen. Type II was sometimes found in the cytoplasm of tumour cells and type VI tended to lose territorial localization. In addition, type I collagen was demonstrated consistently and type V in some cases. In grade 2 chondrosarcomas, type II collagen was demonstrated not only in the matrix but occasionally in the cytoplasm of tumour cells. Type VI was dispersed in the intercellular areas. The other collagenous proteins such as types I, III and V were also present in the matrix. In grade 3 chondrosarcomas, type II collagen was localized predominantly in the cytoplasm of tumour cells and in the adjacent matrix. Type VI was markedly decreased with complete loss of pericellular distribution, whereas types I, III and V were constantly present in the matrix. Those alterations in the distribution of collagen types correlated well with the aggressive behaviour of the tumours. The findings suggest that distribution of different collagen types in cartilaginous tumours reflects the immaturity of the tumour cells and is a useful indicator of their aggressiveness.
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  • 17
    ISSN: 1432-2307
    Keywords: Oestrogen receptor ; Progesterone receptor ; Human ovary ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemistry was used to determine the distribution of oestrogen receptors (ER) and progesterone receptors (PR) in the human ovary during folliculogenesis. Primordial and preantral follicles did not contain ER or PR. The granulosa cells of antral follicles had ER, but negligible PR, before the LH surge. In contrast, at the time of LH surge, these cells of the dominant follicle contained PR, but not ER. On the other hand, granulosa cells of the non-dominant follicles had ER, but not PR. After ovulation, the PR persisted in the luteinized granulosa cells and in the corpus luteum during early pregnancy. The theca interna and surrounding stromal cells were ER-negative and PR-positive throughout the menstrual cycle. Thus, the results show that ER and PR are not expressed simultaneously in the granulosa cells, the thecal cells, or the stromal cells during folliculogenesis. Mechanisms controlling the expression of steroid receptors during the normal menstrual cycle and in early pregnancy are discussed.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 416 (1990), S. 265-270 
    ISSN: 1432-2307
    Keywords: Pancreatic neoplasm ; Glandular epithelial neoplasm ; Child ; Alpha ; fetoprotein ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The autopsy findings in a pancreatoblastoma in a 7-year-old Japanese girl is reported. The tumour was in the head and body of the pancreas, and was associated with diffuse carcinomatous peritonitis and hepatic and pulmonary metastases. There was marked elevation (more than 10000 ng/ml) of serum alpha-fetoprotein (AFP). Histopathologically the tumour was composed of solid epithelial elements with fibrous stroma, showing acinar arrangement, squamoid clusters and tubular structures. The epithelial elements contained numerous fine PAS positive granules in the cytoplasm. Immunocytochemical results suggested epithelial differentiation with positivity to alpha-1-antitrypsin (AAT), keratin, CA19-9, and AFP. No endocrine elements were recognized. Characteristic feature of this tumour are discussed and compared with prevoius reports.
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  • 19
    ISSN: 1432-2307
    Keywords: Myofibroblast ; Cytoskeleton ; Desmoid tumour ; Desmin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The characteristics of the cytoskeleton of myofibroblasts were examined immunohistochemically in 10 extra-abdominal desmoid tumours, 3 palmar and 2 plantar fibromatoses and 5 nodular fasciites; in the cultured cells of one desmoid tumour, and also ultrastructurally in 3 desmoid tumours. Polyclonal anti-desmin antibody reacted with the cells in 7 extra-abdominal desmoid tumours, 1 palmar fibromatosis, 1 plantar fibromatosis and 3 nodular fasciites. Monoclonal antidesmin antibody reacted with cells in only 2 desmoid tumours. Desmin-positive spindle cells were scattered throughout these lesions. There were no marked ultrastructural differences between desmin-positive and desmin-negative desmoids. All specimens except one specimen of nodular fasciitis showed immunoreactivity for alpha-smooth muscle actin and vimentin. Muscle actin-positive cells were observed in all specimens. Cultured cells gave positive reactions with polyclonal desmin antibody as well as to vimentin antibodies and two preparations of actin antibodies, whereas the original tumour did not react with desmin antibody. The present studies suggested that the cytoskeleton of some myofibroblasts in both neoplastic and reactive lesions resembles that of smooth muscle cells.
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  • 20
    ISSN: 1432-2307
    Keywords: Monoclonal antibody ; Tyrosinase ; Malignant melanoma ; Metastasis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have generated monoclonal antibodies (MoAbs) against melanosomal proteins (MoAb 1C11 and MoAb HMSA-1) and a cytoplasmic protein strongly synthesized in neoplastic melanocytes but not associated with melanogenesis (MoAb 7H11). An immunohistochemical study of paraffin sections showed that nearly 90% of epidermal neoplastic melanocytes, including melanomas, expressed 1C11 antigen, whereas this antigen was poorly preserved in dermal melanocytic cells except melanomas. HMSA-1 antigen was expressed in a complementary manner to 1C11 antigen, being found in dermal naevus cells but not generally in the epidermal regions, except for dysplastic naevi and melanomas. In contrast, 7H11 antigen was distributed in nearly 90% of melanocytic tumours except solar lentigo and lentigo maligna lesions. The failure of MoAb 1C11 to react with dermal melanocytes may reflect a subtle alteration in melanogenesis during tumour evolution. Overall, the combined use of MoAbs serves as an accurate diagnosis of melanocytic tumours, the pigment-independent MoAb 7H11 being particularly useful for amelanotic and metastatic lesions.
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  • 21
    ISSN: 1432-2307
    Keywords: Cervix ; Endometrium ; Keratins ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study aimed to examine possible changes in keratin expression during neoplastic transformation of the uterine mucosa and possible differences in keratin expression between endocervical and endometrial adenocarcinomas. Routinely processed specimens with normal morphology or neoplastic changes were stained immunohistochemically using 5 commercial antibodies to keratinfilaments of molecular weight 39–58 kD: CAM 5.2, RCK 102, MCA 144, PKE and PRE. We generally found a change in keratin expression during the neoplastic transformation, consisting of pronounced heterogeneity compared with normal epithelia. In distinguishing koilocytic atypia from CIN, RCK 102 (52.5, 58 Kd) may prove helpful as it stains neoplastic cells strongly and shows no reaction in koilocytes. Staining with the antibody CAM 5.2 (reactive with 39, 43, 50 kD filaments) may aid in distinguishing between cervical and endometrial adenocarcinomas. The former is stained uniformly; the latter shows a more variable staining.
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  • 22
    ISSN: 1432-2307
    Keywords: Amyloidosis ; Immunohistochemistry ; Intervertebral disc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intervertebral discs from 82 consecutive operations on herniation and 59 autopsies (one case with generalized amyloidosis) were studied. Amyloid deposits observed in surgical and autopsy specimens increased with age in both series. Degenerative changes were related to age and to amyloid deposits in autopsy, but not in surgical cases. Calcium pyrophosphate dihydrate deposits (often in proximity to amyloid deposits) were found in autopsy discs of six patients and in surgical specimens of three patients with previous operations on herniated discs. Antisera against amyloid fibril proteins of different types including AA-, Aλ-, Aκ, AF- and AB-types showed no reaction with disc amyloid. In one case with generalized Aλ-amyloidosis the disc amyloid was not of the Aλ-type. Based on our results, we suppose that disc amyloid is a form of localized senile amyloidosis — possibly representing a new class of amyloid limited to cartilage tissue.
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  • 23
    ISSN: 1432-2307
    Keywords: Granulocytic sarcoma ; Immunohistochemistry ; Naphthol ASD chloroacetate reaction ; Nasal region ; Malignant lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A panel of monoclonal antibodies (anti-CD45 [common leukocyte antigen], Ki-B3, L26, MT1, UCHL1, anti-CD15 [X-hapten], anti-neutrophil granule protein elastase [NP57]), anti-lysozyme, and the naphthol-ASD-chloroacetate reaction were applied to two cases of granulocytic sarcoma (GS) for evaluation of their utility in differentiating GS from malignant lymphoma. Lysozyme and naphthol-ASD-chloroacetate esterase were found to be the most reliable markers for detection of the myeloid nature of the tumour cells. GS infiltrated solely the mucosa of the nasal cavity in one case, while in the other it involved both the nasal cavity and maxillary sinus with simultaneous eruptions on the skin of the trunk. In both cases, peripheral blood and bone marrow findings were inconspicuous at the time of diagnosis of GS.
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  • 24
    ISSN: 1432-2307
    Keywords: Arteriosclerosis ; Lipoprotein(a) ; Apoprotein (a) ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n=74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.
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  • 25
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    Virchows Archiv 417 (1990), S. 325-331 
    ISSN: 1432-2307
    Keywords: Hereditary disease ; Amyloidosis ; Skin ; Cysteine proteinase inhibitor ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinically normal skin from 47 individuals aged 9–70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17–46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker. Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in following progression of the disease.
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  • 26
    ISSN: 1432-2307
    Keywords: Streptozotocin ; Diabetes ; Syrian hamsters ; Autoradiography ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Streptozotocin (Sz) given as a single dose of 50 mg/kg body wt. caused severe diabetes in Syrian hamsters. However, the level of blood glucose decreased gradually after 21 days post-Sz and reached the near normal level at 70 days in 90% of hamsters. The recovery from diabetes was associated with the regeneration of theβ-cells of islets and a reduction in the initially increased number ofα- andδ-cells. Daily treatment of diabetic hamsters with insulin was associated with the persistence of severe diabetes, lack of or minimal tendency forβ-cell regeneration and sustained hyperplasia ofα- andδ-cells in 90% of hamsters. Insulin also inhibited DNA synthesis (as measured by incorporation of tritiated thymidine), in ductal, ductular and acinar cells in Sz-pretreated hamsters but not in normoglycemic control hamsters treated with insulin alone. The results demonstrate a deleterious effect of exogenous insulin in the course of Sz-induced diabetes in hamsters.
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  • 27
    ISSN: 1432-2307
    Keywords: Corticotroph adenoma ; Adrenocorticotropin ; Luteinizing hormone ; Immunohistochemistry ; Tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two pituitary adenomas removed from a 37-year-old woman and a 26-year-old woman with typical Cushing's disease were studied by light and electron microscopy, immunohistochemistry and radioimmunoassay of tissue culture media. Both patients had high plasma levels of cortisol and normal levels of luteinizing hormone (LH). Both tumours were monomorphous, composed of densely granulated corticotrophs; the tumour cells contained periodic acid-Schiff positivity, were arranged in a sinusoidal pattern and, ultrastructurally, contained well-developed cytoplasmic organelles. By immunohistochemistry the majority of tumour cells contained immunoreactive adrenocorticotropin (ACTH); approximately 10% of the tumour cell population contained LH immunoreactivity. The LH-positive cells tended to form clusters scattered widely throughout the tumour tissues. LH immunoreactivity was demonstrated in some ACTH-immunoreactive cells on serial sections. Large amounts of immunoreactive ACTH and smaller quantities of LH, follicle stimulating hormone and αsubunit were released into the culture media and release of the glycoprotein hormones responded in parallel to corticotropin releasing hormone stimulation or inhibition by cortisol. These findings indicate that LH can be simultaneously produced and released by ACTH-producing tumour cells of otherwise typical functioning corticotroph adenomas. The capacity for LH production may be acquired during neoplastic proliferation. This is the first detailed report of concurrent production of LH by pituitary corticotroph adenomas.
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  • 28
    ISSN: 1434-0879
    Keywords: Prostatic carcinoma ; Prostate-specific antigen ; Prostate-specific acid phosphatase ; Immunohistochemistry ; Differential expression ; Tumour architecture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of 55 randomly chosen radical prostatectomy specimens was analyzed for expression of prostate-specific antigen (PSA) by immunohistochemical techniques. Tissue sections were selected in such a manner that in addition to glandular benign prostatic hyperplasia (BPH), one or more different prostatic tumour growth patterns were present. Four monoclonal antibodies, directed against three different PSA epitopes, and one polyclonal anti-PSA antiserum were used. Expression of PSA was compared with that of prostate-specific acid phosphatase (PAP), recognized by two different polyclonal antisera. A critical dilution aimed at a maximum of staining intensity on BPH tissue sections was chosen for all antibodies. Anti-PSA and anti-PAP antisera stained essentially all BPH samples (over 90%). Irrespective of the nature of the antibodies used, PSA expression was found to be decreased in prostatic carcinoma. A clear cut relationship was found between immunoreactivity for PSA and the degree of differentiation of the tumour area. Under the experimental conditions used the PSA monoclonal antibodies stained only 1 out of 10 undifferentiated carcinomas, whereas 50% to 70% of the well- and moderately-differentiated carcinomas showed immunoreactivity. This correlation was less pronounced with the PAP staining pattern. If the PSA antibody titer was raised the percentage of clearly staining undifferentiated carcinomas could be considerably increased (up to 60%–100%), indicating that PSA expression is not absent, but lowered in most (if not all) undifferentiated carcinomas.
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  • 29
    ISSN: 1432-0533
    Keywords: Parkinson's disease ; Lewy body ; Enteric nervous system ; Immunohistochemistry ; Vasoactive intestinal polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We performed immunohistochemical analysis of specimens from three autopsied patients with Parkinson's disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinson's disease.
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  • 30
    ISSN: 1432-0568
    Keywords: Creatine kinase ; Development ; Distribution ; Rat ; Heart ; Muscle ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution pattern of creatine kinase (E.C 2.7.3.2) isozymes in prenatal rat heart and skeletal muscle was studied by immunohistochemistry. Between embryonic day (ED) 12–18, creatine kinase M (CK-M) is heterogeneously expressed in the heart: a pronounced staining of CK-M is first observed in the outflow tract and the trabeculae of the right ventricle (ED12-14), and subsequently in the venous valves, the interatrial septum and the sinoatrial node. From ED18 onwards, a homogeneous expression of CK-M is observed due to an increase in isozyme concentration in the remaining part of the myocardium. By contrast, the developmental appearance of creatine kinase B (CK-B) occurs almost homogeneously throughout the heart between ED11-14. Thereafter, a decrease of the CK-B is first observed in the inflow tract (in particular in the sinoatrial node), in the inner part of those atrial walls that are adjacent to the atrioventricular junction, and temporarily in a band in the upper part of the interventricular septum. From ED18, a selective disappearance of CK-B is found in the papillary muscle of the left ventricle. At birth, a considerable amount of CK-B remains present in the ventricular walls. Although some of the stage-dependent regional differences in expression of the creatine kinase isozymes, in particular those of the M-subunit, are shared by other mammalian and avian species, their significance for the developmental changes in the physiology of the heart is speculative at present.
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  • 31
    ISSN: 1432-0568
    Keywords: Calbindin-D28K ; Immunohistochemistry ; Habenular ganglia ; Elasmobranchs ; Scyliorhinus canicula
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using an antibody raised against a purified chick duodenal vitamin D-dependent calcium-binding protein, the presence and distribution of calbindin has been studied immunohistochemically in the habenular ganglia of the dogfish. In the more developed left ganglion, a positive reaction was clearly observed in the neurons of the medial nucleus, whereas in the lateral nucleus, only some scarce, hardly immunostained cells appeared. In the neurons of the right habenula however, no immuno-reactivity was observed. The distribution of vitamin D-dependent calcium-binding protein in the dogfish habenulae is therefore asymmetrical. This may be due to differences in the neuronal activity between the two ganglia.
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  • 32
    ISSN: 1432-0533
    Keywords: Ischemia ; Cat ; Selective vulnerability ; Immunohistochemistry ; Glial fibrillary acidic protein (GFAP)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dorsal hippocampus of cat was investigated by light microscopy and immunohistochemistry following 1 h global cerebral ischemia and various recirculation times from 1 day to 1 year. Complete ischemia was produced by combining hypotension with intrathoracic occlusion of major arteries. Postischemic resuscitation was carried out using an intensive care regimen with continuous neurophysiological monitoring. Brains of controls (n=4) and postischemic animals (n=12) were fixed in formaldehyde and prepared for histology and immunohistochemistry of glial fibrillary acidic protein (GFAP). In all post-ischemic animals the hilus and the regio superior of dorsal hippocampus which encompasses the CA1 subfield were severely damaged. Neurons in these regions exhibited the typical sequela of neuronal death. GFAP staining revealed vivid astroglial proliferation in stratum lacunosum-moleculare and stratum oriens. Changes in the regio inferior of dorsal hippocampus, i.e., CA3 subfield, and in dentate gyrus granular layer, were variable. Although most animals exhibited moderate to severe neuronal and glial alterations, groups of surviving cells were observed in the stratum oriens and in the granular layer of dentate gyrus. In one animal the majority of CA3 pyramidal cells and granule cells was preserved. These findings demonstrate that after 1 h of complete cerebral ischemia dorsal hippocampus exhibits two different types of injury: a consistent pattern of selective vulnerability in the hilus and the regio superior, and a variable pattern of non-selective injury in the regio inferior and dentate gyrus. The two patterns can be best explained by intrinsic (pathoclitic) and extrinsic (hemodynamic/edema) factors, respectively and are likely to represent basically different mechanisms of ischemic injury.
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  • 33
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    Acta neuropathologica 80 (1990), S. 12-17 
    ISSN: 1432-0533
    Keywords: Serotonin (5-hydroxytryptamine, 5-HT) ; Spinal cord trauma ; Ventral horn ; p-Chlorophenyl alanine ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possibility that serotonin (5-hydroxytryptamine, 5-HT) is involved in the early tissue reactions occurring in spinal cord trauma was examined in a rat model using an immunocytochemical technique. The injury was made in the form of a 5-mm long and 2.5-mm wide lesion of the right dorsal horn at the level of T10–11. Injured rats, pretreated with the 5-HT synthesis blocking agent, p-chlorophenyl alanine (p-CPA) were compared with untreated injured controls and the animals were allowed to survive for 5 h. The distribution of 5-HT was examined in proximal and distal cross-sections of the cord, located 2 and 5 mm away from the injury. Normal rats showed immunoreactive material in nerve cell processes and in a few nerve cell bodies of the ventral horns. The trauma to the spinal cord caused a marked increase in 5-HT immunoreactivity in the segments located 2 mm proximal and distal to the injury, particularly in the ipsilateral ventral horn. The segment located 5 mm distal to the lesion showed a similar increase in immunoreactivity but it was apparently less pronounced in the corresponding proximal segment. Treatment with p-CPA markedly reduced the trauma-induced increase in 5-HT immunoreactivity in all the segments. These immunohistochemical findings were in line with the changes in the contents of 5-HT measured biochemically in corresponding spinal cord segments. At the onset of the trauma to the spinal cord 5-HT is thus present in the tissue, mainly in the form of 5-HT-containing nerve cell processes. Biochemical determinations also revealed that there is an increased amount of 5-HT in the traumatized spinal cord. The present study indicates that this is at least partly due to an increased amount of 5-HT in neurons and nerve cell processes of the perifocal region. The pathophysiollogical significance of the observed 5-HT-reaction in spinal cord injury is not known in all its details. However, 5-HT might be implicated in such tissue reaction, such as increased microvascular permea bility and edema formation occurring in the early period after trauma.
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  • 34
    ISSN: 1432-0533
    Keywords: AIDS ; Immunohistochemistry ; gp41 ; Microglia ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among 100 brains from patients with acquired immunodeficiency syndrome (AIDS), 33 brains (21 adults and 12 children) with histological evidence of subacute AIDS encephalitis were immunostained with one of the most sensitive antibodies to HIV-1 antigen, anti-gp41. Twenty-six (20/21 adults, 6/12 children) of the 33 brains showed pg41 positivity. Brains from children had fewer gp41-positive cells than brains from adults. The distribution of gp41-positive cells was characteristic. They were frequently detected and most numerous in the globus pallidus (medial 〉 lateral). Although gp41-positive cells were prevalent, fewer were detected in the corpus striatum and thalamus. Of infratentorial areas involved, the ventral midbrain, especially the substantia nigra, and the dentate nucleus contained many positive cells. Lower levels of infections, often patchy, were noted in the cerebral and cerebellar white matter and pontine base. Gp41-positive cells were rarely seen in the cerebral cortex, medulla, spinal cord, leptomeninges, choroid plexus, ependyma, subependymal areas and endothelia. Besides immunoreactive macrophages and multinucleated cells, gp41-positive microglia with various morphological alterations were abundant in the deep cerebral gray matter, ventral midbrain and dentate nucleus. Most of these microglia were undetectable with conventional histological methods. We discuss the significance of the distribution of HIV-1-infected cells, especially microglia, with respect to cellular tropism and involvement of deep gray matter nuclei in a pattern reminiscent of a multisystem atrophy.
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  • 35
    ISSN: 1432-0533
    Keywords: Cytoplasmic body myopathy ; Immunohistochemistry ; Desmin ; Intermediate filaments ; Actin filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a fine structural and immunocytochemical study, the latter performed on semithin sections of epoxy resin embedded skeletal muscle fibers, three types of cytoplasmic bodies were identified in a case of cytoplasmic body myopathy: (1) The first type, the classical type, showed a central core and a light halo with radiating actin filaments at the periphery. (2) The second type, the spheroid body was characterized by irregularly arranged granular masses associated with intermediate filaments. Desmin immunoreactivity occurred in the central and peripheral parts, where filaments of intermediate size were visualized by electron microscopy. Desmin immunoreactivity was noted also at the Z-bands of striated annulets, within areas of disordered myofibrils, such as sarcoplasmic masses, and in atrophic muscle fibers. (3) The third type of the cytoplasmic body was composed mainly of large masses of uneven granularity and electron density. The center of this type reacted to anti-actin antibody suggesting that the 5- to 6-nm filaments, which ultrastructurally proved to be a major component, were of the actin type. By contrast, neither intermediate filaments nor actin microfilaments were found by electron microscopy in cytoplasmic bodies in a second case where no immunoreaction to desmin or actin occurred. Anti-vimentin antibody stained only the cytoplasm of endomysial cells, but not the inclusion bodies. Some other, unusual inclusions with 18- to 20-nm tubulo-filamentous structures have to be distinguished from the various types of filaments in cytoplasmic bodies. It is concluded, that pleomorphism and heterogeneity of “cytoplasmic bodies” have to be taken into consideration when classifying cytoplasmic body myopathies.
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  • 36
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    Acta neuropathologica 80 (1990), S. 453-458 
    ISSN: 1432-0533
    Keywords: Dementia ; Neuronal inclusions ; Pick's disease ; Lewy bodies ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 62-year-old man presented with memory impairment progressing over 6 years to dementia with near mutism and was diagnosed as having Alzheimer's disease. At autopsy his brain showed lobar atrophy suggestive of Pick's disease and there were spherical intracytoplasmic neuronal inclusions in the fascia dentata, hippocampal pyramidal cell layer, and temporal cortex. Unlike Pick bodies, however, the inclusions were eosinophilic with H&E stains, non-argyrophilic, and failed to react immunohistochemically with antibodies to paired helical filaments or Alz-50. They did label with antibodies to ubiquitin, however, and electron microscopy disclosed dense-cored granular structures with thin filamentous coronas which resembled brain stem-type Lewy bodies. The substantia nigra and locus coeruleus were not affected.
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  • 37
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    Acta neuropathologica 80 (1990), S. 635-641 
    ISSN: 1432-0533
    Keywords: Choroid plexus papilloma ; Choroid plexus carcinoma ; Prognosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixty-seven tumor specimens of epithelial choroid plexus neoplasms obtained by 60 biopsies and 7 autopsies from 52 patients were investigated. Diagnoses of the first operations were choroid plexus papilloma (PP; 32 cases), choroid plexus papilloma with histological atypies (atypical PP; 6 cases), and choroid plexus carcinoma (PC; 14 cases). Carcinoembryonic antigen was expressed by 2 of the 3 biopsies autoptically recognized as metastatic carcinomas and by 2 autopsy cases of PC, while it was absent in all biopsies of true choroid plexus tumors. Tumor cells positive for transthyretin (TTR, prealbumin), S-100 protein (S100), and glial fibrillary acidic protein (GFAP) were detected in 39, 46 and 13, respectively, of the 49 cases of true choroid plexus tumors. Fourth ventricle tumors expressed more S100 (number of positive tumor cells) than lateral ventricle tumors, PP more S100 and TTR than atypical PP/PC. Tumors from patients 20 years of age and older expressed more GFAP and TTR than tumors from younger patients. Of the 30 patients with complete follow-up 19 were alive 2 to 11 years after surgery, including 7 recurrencies. Eleven died from the tumor 4 months to 7 years after surgery. The following histopathologic features (in order of decreasing significance) were correlated with poor prognosis (recurrency or fatal outcome): less than 50% of the tumor cells heavily positive for S100, presence of mitoses, absence of TTR-positive cells, brain invasion by cell nests, absence of marked stromal edema, and presence of necrotic areas. Our results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.
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  • 38
    ISSN: 1432-0533
    Keywords: AIDS ; HIV encephalopathy ; Immunohistochemistry ; Cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes andRicinus communis agglutinin 1–120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter: the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.
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  • 39
    ISSN: 1432-0568
    Keywords: Immunohistochemistry ; Leu-7 ; Conduction system ; Embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution pattern of Leu-7 (HNK-1) in developing human embryonic hearts and rat hearts was studied by immunohistochemistry. Human and rat embryos at Streeter's stages XIII ∼ XX and fetus stage I were used. Leu-7, which is absent in the newborn rat heart, is expressed transiently in the embryo and fetus I stages. The earliest embryonic heart shows two incomplete circular structures with immunoreactivity in the myocardium along the primitive atrioventricular cushion and bulboventricular canal. These two structures become localized topographically in the definitive atrioventricular node and atrioventricular bundle after rearrangement and partial disappearance during embryonic development. At Streeter's stages XVIII ∼ XX, Leu-7 immunoreactivity appears to localize topographically in almost all the pathways of the conduction system, although some discontinuities are observed in the atrioventricular junction and atrial internodal tracts. Thereafter, immunoreactivity decreases gradually and differentially by site and stage. The precise nature of Leu-7 immunoreactive cells, that is, whether or not they are neurogenic or myogenic, is not revealed by this study. The present observations are discussed in connection with the hypothesis that specialized ring tissue is the primordium of the conduction system.
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  • 40
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    Anatomy and embryology 182 (1990), S. 611-616 
    ISSN: 1432-0568
    Keywords: Eye development ; Glycoconjugates ; Histochemistry ; Immunohistochemistry ; Lectins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lectin histochemical methods and immunohistochemical techniques have been utilized to investigate and partially characterize glycoconjugates in the developing eye. Peanut-lectin-binding sites associated with radial glial cells were found in the diencephalon. In the optic primordia, binding sites associated with radial glia were masked by terminal sialic acid, and only reacted with peanut lectin when pretreated with sialidase. This finding indicates that glycoconjugates associated with diencephalic radial glia contain terminal galactose-β-(1→3)N-acetyl galactosamine, but glycoconjugates associated with radial glia in the optic primordia contain sialic acid→galactose-β(1→3)N-acetyl galactosamine. The selective distribution of galactose, N-acetyl galactosamine and fucose associated with radial glial cells has also been demonstrated. We postulate that these distributions mediate the shaping of the developing eye.
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  • 41
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    Acta neuropathologica 79 (1990), S. 686-688 
    ISSN: 1432-0533
    Keywords: Transferrin receptor ; Brain injury ; Edema fluid ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies have demonstrated the presence of transferrin receptors (Tf-R) in the central nervous system. The present study of Wistar rats with experimentally induced brain injuries, using immunohistochemistry at the light microscopy level, demonstrated the presence of Tf-R in regenerated endothelial cells, reactive astrocytes and in other cells, probably macrophages. Although Tf-R were seen in proliferating cells, Tf-R were also observed in nonproliferating cells, many of them macrophages. The receptors perhaps bind transferrin in edema fluid and play an important role in lesion repair.
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  • 42
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    Acta neuropathologica 81 (1990), S. 217-218 
    ISSN: 1432-0533
    Keywords: Immunohistochemistry ; Polyglucosan bodies ; Dog ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the use of monoclonal antibodies, raised against the human polyglucosan, positive staining of polyglucosan bodies (PGB) was detected in the brain, spinal cord and cecum of aged dogs. PGB in feline brain were also positively stained with these antibodies. These findings indicate that animal PGB share common antigenicity with human PGB.
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  • 43
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    Acta neuropathologica 81 (1990), S. 228-232 
    ISSN: 1432-0533
    Keywords: Cerebral tumor ; Polar spongioblastoma ; Astrocytoma ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case is reported of a 9-year-old boy with a cerebral polar spongioblastoma. This neoplasm, first described by Russell and Cairns in 1947, is morphologically a distinct entity characterized by bipolar tumor cells with palisading nuclei. In the case under study immunoreactivity for neuron-specific enolase was found and ultrastructural features of developing neuronal elements were present. A neuro-endocrine nature was suggested by de Chadarévian et al. (1984) in a morphologically similar case. These findings are in contrast with the longheld view that the polar spongioblastoma is cytogenetically related to the embryonal radial glial cells.
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  • 44
    ISSN: 1432-0533
    Keywords: Fibroblast growth factor (FGF) ; Basic FGF ; Angiogenesis ; Brain tumors ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm-and neuroectoderm-derived cell types (e.g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections of 73 human brain tumors using immunohisto-chemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e.g., pseudopalisading or pathological vessels) could be related to FGF activity.
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  • 45
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    Acta neuropathologica 79 (1990), S. 456-460 
    ISSN: 1432-0533
    Keywords: Rosenthal fibers ; Immunohistochemistry ; Ultrastructure ; Neoplastic and reactive astrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nature of Rosenthal fibres (RF) was investigated in eight cases each of low-grade astrocytoma and reactive gliosis using immunohistochemical (IH) staining for glial fibrillary acidic protein (GFAP), electron microscopy (EM) and immunoelectron microscopy (IEM) by immunogold labelling technique. By IH under light microscopy (LM), three types of RF were seen, uniformly positive (type I), rim positive (type II) and completely negative (type III). EM showed variation in structural pattern of RF. Some RF contained large amount of glial filaments (GF) intermingled with RF while others with a large amount of electron dense material and less GF. Thus, the presence and amount of GF in RF appear to be responsible for the different types of IH staining under LM. IEM showed that all RF including the ones consisting of entirelh amorphous material possess immunoreactivity for GFAP. It is suggested that RF formation is a two-stage process, staring with excessive accumulation of GF within astrocytic processes followed by their gradual alteration into electron-dense amorphous material under the influence of some unknown metablic or other factors. The quantitative analysis of different types of RF suggests a difference in the rate of formation of RF in neoplastic and reactive conditions.
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  • 46
    ISSN: 1432-0533
    Keywords: Natural killer cells ; Immunohistochemistry ; Leu-19 antigen ; Brain tumors ; Neuroendocrine cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Leu-19 antigen is a 200–220 kDa surface glycoprotein, initially detected on natural killer (NK) cells exhibiting non-major histocompatibility complex-restricted cytotoxity. Using a monoclonal antibody (mAb) directed against the Leu-19 molecule, we were unable to identify NK cells immunohistologically in cryostat sections of neuroectodermal tumors. Instead, mAb Leu-19 cross-reacted with the surfaces of the tumor cells, except for melanomas. It stained mesodermal tumor cells less intensely and did not stain those of carcinoma metastases. In three plasmocytomas, cells were observed, most likely NK cells, which extend Leu-19-positive cell processes towards to the unstained tumor cells. Furthermore, the Leu-19 antigen was identified on physiological tissues, especially on all neuroendocrine cells analyzed. The cross-reactions observed with Leu-19 mAb were confirmed using mAb NKH-1, which is also directed against the Leu-19 molecule. Thus, the expression of Leu-19 on neuroectodermal cells is another example of antigen sharing between specialized immune cells and the nervous system.
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  • 47
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    Acta neuropathologica 80 (1990), S. 68-71 
    ISSN: 1432-0533
    Keywords: Meningeal haemangiopericytoma ; Cerebellar haemangioblastoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical study was performed on three meningeal haemangiopericytomas and four cerebellar haemangioblastomas (paraffin embedded) in an attempt to elucidate the uncertain histogenesis of these tumours. The tumour cells of all meningeal haemangiopericytomas show no expression of α-smooth muscle actin and, thus, no immunohistochemical proof of their true pericytic nature can be obtained. The stromal cells of cerebellar haemangioblastomas show foci of positive staining for S-100 protein, neuron-specific enolase and synaptophysin, thereby clearly indicating their neuroectodermal origin. These results allow the conclusion that the present nomenclature of these tumours is at least arguable and probably incorrect.
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  • 48
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    Acta neuropathologica 80 (1990), S. 46-58 
    ISSN: 1432-0533
    Keywords: Central pontine myelinolysis ; Demyelination ; Astrocytes ; Cell adhesion molecules ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical study was performed to compare glial reactions in recent and old lesions of central pontine myelinolysis (CPM). Regions of demyelination and destruction of oligodendrocytes, showed reduced immunoreactivity of myelin basic protein (MBP), myelin-associated glycoprotein (MAG), transferrin, and carbonic anhydrase C (CA C). In addition, labeling of glial fibrillary acidic protein (GFAP) and S-100 protein revealed distinct dystrophic alterations of the astroglia. Remarkably, immunolabeling of GFAP was drastically reduced in astrocytic cytoplasm within freshly demyelinated lesions. Immunostaining of vimentin revealed a differential intracytoplasmic decoration of hypertrophic and dystrophic astrocytes in recent and old CPM lesions. Immunolabeling of desmin failed to stain glial cells. Monoclonal antibodies against HNK-1 exhibited greatly increased immunoreactivity both of persisting oligodendrocytes and of reactive fibrillary astrocytes in old CPM foci. In freshly demyelinated lesions, enhanced immunoreactivity of the X-hapten (3-fucosyl-N-acetyllactosamine) was prominent in astroglia and oligodendrocytes. Simultaneously, reactive astrocytes revealed intracytoplasmic labeling of laminin. Quantitation of GFAP+ astroglia in fresh CPM and control cases revealed an increase in the number of astrocytes within the demyelinated foci and in the surrounding nondemyelinated pontine tissue of CPM cases. The occurrence of astroglial alterations in the demyelinated foci of CPM could be interpreted as “astroglial dystrophy” which may represent a pathogenic factor in CPM. Furthermore, it is possible that changes of the glial microenvironment may influence the astroglia to revert transiently back to an immature phenotype as indicated by the enhanced expression of the X-hapten and HNK-1, and the de novo synthesis of vimentin and laminin.
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  • 49
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    Acta neuropathologica 80 (1990), S. 88-91 
    ISSN: 1432-0533
    Keywords: Huntington's disease ; Striatum ; Synaptophysin ; Calcineurin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This immunohistochemical study compares the expression of synaptophysin (SYP) in the striatum in Huntington's disease (HD) with that of calcineurin (CaN), a marker for striatal medium-sized spinous neurons. As compared to controls, in the HD striatum there was a significant loss of SYP immunoreactivity with residual staining displaying an inhomogeneous pattern, which strikingly resembled that of CaN. Our results may indicate that there is a synaptic loss in the striatum with HD and this is most likely due to loss of medium-sized spinous neurons characteristic of this disease.
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  • 50
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    Acta neuropathologica 80 (1990), S. 103-107 
    ISSN: 1432-0533
    Keywords: Brain neoplasms ; Medulloepithelioma ; Primitive neuro-ectodermal tumor ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case is reported of a boy, 3 years of age, with a large medulloepithelioma in the left cerebral hemisphere. Medulloepitheliomas are rare tumors of the primitive medullar epithelium. Histological, immunohistochemical and electron microscopical findings are presented. We discuss previously reported cases, the ontogeny of this type of tumor and the relation to the socalled primitive neuro-ectodermal tumors (PNET).
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  • 51
    ISSN: 1432-0533
    Keywords: Meningioma ; Bromodeoxyuridine ; Cell kinetics ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-six patients with intracranial meningiomas and two with hemangiopericytic variants received a 30-min intravenous infusion of bromodeoxyuridine (BrdUrd), 200 mg/m2, before tumor removal. Excised tumor specimens were stained by the indirect immunoperoxidase method to determine the BrdUrd labeling index (LI), or percentage of cells in DNA synthesis. The BrdUrd LI was 〈 1% in 63 (86.3%) of 73 nonmalignant meningiomas and 〈 1% in 20 (87%) of 23 malignant meningiomas. Of 23 malignant meningiomas 11 were recurrent tumors; 8 patients had recurrence 3 to 33 months after the study. The recurrence rate was 100% (five of five) in patients whose tumors had a BrdUrd LI 〉 5%, 44% (11 of 25) in those with a BrdUrd LI 1% to 5%, and 6.1% (4 of 66) in those with an LI 〈 1%. Thus, meningiomas with a BrdUrd LI 〉 1% may grow faster and recur more frequently. Among patients with malignant mengngiomas, the mean time to recurrence after the study was 7.5 months in those with a BrdUrd LI 〉 5% and 20.2 months for those with an LI 1% to 5%. The mean time to recurrence was 97.8 months in patients with nonmalignant meningiomas. Both hemangiopericytic variants were recurrent and showed LIs of 0.5% and 4.1%; the former tumor recurred 8 years after complete resection, while the latter recurred three times in 3.5 years. Thus, the proliferative potential of intracranial meningiomas as reflected by the BrdUrd LI appears to be a prognostic variable that can help to elucidate the biological behavior of individual meningiomas.
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  • 52
    ISSN: 1432-0533
    Keywords: Central nervous system ; Coxsackie B virus ; Encephalitis, viral ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of fatal acute encephalitis due to Coxsackie B1 virus is described. Confirmation of Coxsackie B virus as the etiological agent of encephalitis was based on identification of the virus antigen in formalin-fixed paraffin-embedded tissue sections. In the past, the diagnosis was obtained by serological studies of peripheral blood and viral isolation. This is the first report in which indirect immunofluorescent and immunoper-oxidase methods using rabbit antiserum raised against Coxsackie B types 1–6 was utilized in determining the etiology of encephalitis. It must be emphasized that these methods can be used both on biopsy or autopsy specimens, even retrospectively.
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  • 53
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Guam ; Ubiquitin ; Immunohistochemistry ; Anterior horn cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical studies with an antibody to ubiquitin revealed the presence of filamentous inclusions in spinal anterior horn cells in all of six patients with Guamanian amyotrophic lateral sclerosis (ALS) and one of six cases of parkinsonism-dementia complex (PD) on Guam. Similar ubiquitin-reactive filamentous inclusions were found in all of seven non-Guamanian sporadic ALS patients examined. No similar inclusions were seen in six normal controls or in non-ALS patients who had chromatolytic neurons. The filamentous inclusions differed from spinal neurofibrillary tangles, a characteristic feature of Guamanian ALS and PD, since they were restricted to anterior horn cells and did not react with anti-tau antibody. The chromatolytic neurons of non-ALS patients occasionally had weak diffuse immunoreactivity, but no focal inclusions were detected. These results suggest that ubiquitin-reactive focal filamentous inclusions may reflect a characteristic degenerative process of anterior horn cells of motor neuron disease.
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  • 54
    ISSN: 1432-0533
    Keywords: Neuropeptide Y ; Immunohistochemistry ; Hirschsprung's disease ; Aganglionosis ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localisation and distribution of neuropeptide Y (NPY)-like immunoreactivity were studied by use of immunohistochemical methods in gut tissues from 19 patients with Hirschsprung's disease, including 4 cases of long segment aganglionosis. In the normoganglionic segment, immunoreactive cell bodies and nonvaricose processes were seen within both myenteric and submucous plexuses. A scarce supply of varicose fibres was found in the lamina propria mucosae, muscularis mucosae and longitudinal muscle layer. NPY fibres were more frequently encountered in the circular muscle layer, although with a weakly immunostaining intensity. In addition, blood vessels in the submucosal connective tissue were surrounded by a typical plexus of varicose, NPY-positive fibres. Immunoreactive endocrine cells could be detected in the colonic epithelium. In the aganglionic segment, numerous nerve fasciculi comprising a small to moderate number of NPY fibres with varicosities were observed throughout the entire layer of the colonic wall. A few varicose, NPY-positive fibres were also contained in the relatively large, hypertrophic nerve fasciculi located in the intermuscular zone and submucosal connective tissue. NPY-immunoreactive fasciculi were more densely distributed in the distal aganglionic segment than in the proximal aganglionic one. On the other hand, the distribution of NPY-positive fibres in long segment aganglionosis was quite different from that in short segment type; in cases of long segment type, no immunoreactive nerve fibres were detected within the circular muscle layer of the proximal aganglionic segment near the oligoganglionic segment and only a few fibres were observed within the hypertrophic nerve bundle of the intermuscular zone. The present results suggest that NPY-like immunoreactive nerves in the human colon have a dual origin of intrinsic and extrinsic elements. The origin and nature of extrinsic NPY nerve fibres in the human colon are discussed.
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  • 55
    ISSN: 1432-0568
    Keywords: Synaptophysin ; Immunohistochemistry ; Pineal gland ; Pinealocytes ; Meriones unguiculatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synaptophysin (protein p38), a major integral membrane glycoprotein of small presynaptic vesicles, was localized immunohistochemically in semithin sections of the superficial pineal gland of the Mongolian gerbil (Meriones unguiculatus). Synaptophysin immunoreactivity could be detected in all pinealocytes, which were visualized with antibodies directed against neuron-specific enolase (NSE) in adjacent sections. No p38 immunoreactivity was discernible in the interstitial glial cells, which showed a heterogeneous pattern of immunostaining for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Pinealocytes exhibited considerable intercellular differences in the densities of immunostaining. The various degrees of synaptophysin immunoreactivities in pinealocytes were not correlated with the densities of NSE immunostaining. Nerve terminals and varicosities displayed stronger immunoreactivities than pinealocytes. They were particularly numerous in the perivascular spaces. It is not clear whether this distribution indicates an innervation of pineal capillaries in addition to the functionally important innervation of pinealocytes. Several highly p38-positive dots of variable size were a conspicuous feature throughout the gland. By the consecutive semithin-thin section technique, they could be identified as processes of pinealocytes, filled with accumulations of small clear vesicles. Obviously, these vesicles represent the major site of synaptophysin immunoreactivity in pinealocytes. In the gerbil, similar vesicles have been ascribed a role in the secretory activity of the gland, and/or in the transport of calcium. The intercellular differences in the degrees of p38 immunostaining may, therefore, reflect different states of a specific cellular activity. The presence of synaptophysin in pinealocytes of the normal pineal, including the deep portions of the gland, emphasizes the paraneuronal character of these cells.
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  • 56
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    Anatomy and embryology 181 (1990), S. 441-452 
    ISSN: 1432-0568
    Keywords: Development ; Pancreatic primordium ; Transplantation ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dorsal pancreatic primordia of 12.5-day-old rat embryos transplanted into the third ventricle of adult female rats were immunohistochemically examined 10, 20 and 40 days after transplantation. On day 10, the grafts grew into an epithelial sacculus (S) with a thick subepithelial tissue (ST). Tubular and vesicular structures with a single cuboidal epithelium were found within the wall of the S, but they underwent thereafter a regression without allowing the primordia to differentiate into the exocrine acinar tissues. In contrast with this, pancreatic hormone-containing cells existed in the ST, and were arranged like the islands of a mature animal. The tissue also has smooth muscle fibers and neurons. When the primordium was grafted along with its root connected to the duodenum, gut-like tubular structures differentiated, showing mucosa with villi and crypts, submucous mesenchymal tissue and muscle layers. The mucosa possesses epithelial cells immunoreactive for the pancreatic hormones, and the muscle layers have the myenteric plexuses. These findings seem to provide further evidence that in the rat pancreas, pancreatic-hormone-containing cells differ from the acinar cells in origin.
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  • 57
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    Archives of dermatological research 282 (1990), S. 179-182 
    ISSN: 1432-069X
    Keywords: Human malignant melanoma ; Hanganutziu-Deicher antigen ; N-Glycolylneuraminic acid ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Hanganutziu-Deicher (HD) antigen is a heterophile antigen whose immunodominant molecule is N-glycolylneuraminic acid, a sialic acid that cannot be found in normal tissues of either humans or chickens. Using biotinylated chicken anti-HD antibody purified with affinity chromatography, expression of HD antigen was immunohistochemically investigated in formalin-fixed tissues of human malignant melanoma. HD antigen-positive melanoma cells were clearly demonstrated in 7 of 11 lesions of malignant melanoma. No HD antigen-positive cells were found in 8 lesions of melanocytic nevus, and no components of normal human skin including epidermal melanocytes were stained with the antibody. This study is the first that immunohistochemically demonstrates HD antigen in tissue sections of human malignant melanoma. The expression of the HD antigen in transformed human melanocytes may have great immunological significance because the antigen is absent from normal human tissues and is immunogenic in humans.
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  • 58
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    Archives of dermatological research 282 (1990), S. 227-233 
    ISSN: 1432-069X
    Keywords: Genodermatoses ; Keratinization disorders ; Fetal cytokeratins ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathogenesis of a rare form of the ichthyotic diseases, ichthyosis hystrix Curth-Macklin, was investigated by immunohistochemistry and electron microscopy. Monoclonal antibodies (Mabs) against keratins expressed in normal basal cells (PKK2 and KA1), Mabs against keratins only present in normal fetal skin (PKK1), and Mabs against keratins 1, 2, 10, and 11 (KA5 and K8.60) were used. The Mabs reacting with normal basal cells showed an increased reaction with many cell layers. The Mab PKK1 distinctly reacted with the basal cell layer, suggesting an expression of fetal keratins. Electron microscopic study of both normal-looking and involved skin revealed the keratinization disorder characterized by tonofilament shells, perinuclear vacuoles, and binuclear keratinocytes. The results suggest that there is no prematurity of keratinization, but rather a pathological expression of specific keratin genes leading to expression of fetal keratins in this form of ichthyosis hystrix.
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  • 59
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    Experimental brain research 81 (1990), S. 257-266 
    ISSN: 1432-1106
    Keywords: Serotonin ; Area 17 ; Postnatal development ; Immunohistochemistry ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The laminar distribution and postnatal development of profiles immunoreactive to antibodies directed against serotonin (5-hydroxytryptamine, 5-HT) have been investigated in the primary visual cortex (striate cortex, area 17) of cats. In the adult cat, profiles with serotonin-like immunoreactivity consist exclusively of fibers which exhibit laminar differences in density and predominant orientation. Immunoreactive fibers are dense in layers I–III, less dense in layer V, and sparse in layers IV and VI. In layers I and VI the trajectories of these fibers are mainly tangential to the pial surface; in layers II–V they are predominantly radial and more irregular. The vast majority of immunoreactive fibers consists of fine axons with frequent small varicosities. In addition, there are a few thick axons. In 2-week-old cats, immunoreactive fibers are sparsely distributed through layers II–V. By 4 weeks, fiber density has decreased still further in layer IV and increased in layers I–III. By 6 weeks, the laminar pattern resembles that of adult cats except that fiber density is still lower than in adults. At three months of age, the mature pattern is established.
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  • 60
    ISSN: 1432-1106
    Keywords: Neuropeptide Y ; Dopaminergic mesencephalic pathway ; Nucleus accumbens ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The density of neuropeptide Y (NPY) immunostained neurons examined in the rat nucleus accumbens (NAcc) was shown to be constant across the anteroposterior extent of the nucleus and did not present any right-left hemispheric difference. Selective unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigral dopaminergic neurons induced, 15 to 21 days later, a bilateral decrease in the NPY neuron density which was, interestingly, more marked in the contralateral than in the ipsilateral NAcc. Dopamine depletion induced by α-methylparatyrosine treatment elicited a decrease in NPY neuronal density similar in amplitude to that induced by the 6-OHDA lesion in the ipsilateral NAcc suggesting that similar mechanisms underly both NPY responses. In both experimental conditions, changes in NPY immunostaining were quite homogeneous in the two antero-posterior NAcc portions arbitrarily considered. Apomorphine treatment in animals with 6-OHDA injury completely reversed the ipsilateral lesion effect in the anterior part of the NAcc but only partially the contralateral one. In contrast, no significant effect of apomorphine was observed in either side of the NAcc posterior portion. This data suggests the involvement of at least 2 components in the NPY neuron responses to the lesion. The component reversed by apomorphine treatment was presumed to be directly linked to the DA depletion, while the second component not antagonized by apomorphine was considered independant on DA transmission. These data therefore provide morphological evidence for the occurence of complex functional interactions between dopaminergic afferents and NPY-containing neurons within the NAcc.
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  • 61
    ISSN: 1432-1106
    Keywords: Neuropeptide ; Plasticity ; Nerve injury ; Spinal cord ; Immunohistochemistry ; Cat ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary By use of fluorescence immunohistochemistry it is shown that sciatic nerve section in cat and rat induces increased levels of immunoreactive calcitonin gene-related peptide (CGRP) in axotomized motoneurons. In the rat, this effect was clearly seen at 2–5 days postoperatively, but could not be demonstrated after 11–21 days. These findings are discussed in relation to previously proposed roles for CGRP in motoneurons.
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  • 62
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    Experimental brain research 82 (1990), S. 25-32 
    ISSN: 1432-1106
    Keywords: Retina ; Development ; In situ hybridization ; Gene expression ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of the synapsin I gene was studied during postnatal development of the rat retina at the mRNA and protein levels. In situ hybridization histochemistry showed that synapsin I mRNA was expressed already in nerve cells in the ganglion cell layer of the neonatal retina, while it appeared in neurons of the inner nuclear layer from postnatal day 4 onward. Maximal expression of synapsin I mRNA was observed at P12 in ganglion cells and in neurons of the inner nuclear layer followed by moderate expression in the adult. At the protein level a shift of synapsin I appearance was observed from cytoplasmic to terminal localization during retinal development by immunohistochemistry. In early stages (P4 and P8), synapsin I was seen in neurons of the ganglion cell layer and in neurons of the developing inner nuclear layer as well as in the developing inner plexiform layer. In the developing outer plexiform layer synapsin I was localized only in horizontal cells and in their processes. Its early appearance at P4 indicated the early maturation of this cell type. A shift and strong increase of labelling to the plexiform layers at P12 indicated the localization of synapsin I in synaptic terminals. The inner plexiform layer exhibited a characteristic stratified pattern. Photoreceptor cells never exhibited synapsin I mRNA or synapsin I protein throughout development.
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  • 63
    ISSN: 1432-1106
    Keywords: Immunohistochemistry ; Monoclonal antibody ; GABAA-receptors ; Tissue cultures ; Spinal cord ; Brain stem ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Explant cultures of rat spinal cord, brain stem and cerebellum were used to visualize GABAA-receptors by means of immunohistochemistry. For these studies we have incubated the cultures with the monoclonal antibody bd 17 against the β-subunit of the GABAA/benzodiazepine/chloride channel complex. In spinal cord cultures, many interneurones were immunoreactive whereas only a small number of large neurones, probably motoneurones was specifically stained. In brain stem cultures, groups of large and medium-sized neurones showed immunoreactivity. In cultures of cerebellum, a great number of neurones was specifically stained. Granule cells showed the strongest immunoreactivity whereas other neurones, presumably Purkinje cells and interneurones, were only moderately stained. The immunoreactivity was mainly confined to the cell bodies of the neurones while their processes were only weakly or not stained. In contrast to neurones, no immunoreactivity could be detected on astrocytes.
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  • 64
    ISSN: 1432-1106
    Keywords: Calcitonin gene-related peptide ; Human spinal cord ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary CGRP-immunoreactive varicose nerve fibers displayed three kinds of termination patterns in the cervical, thoracic and lumbar segments of the human spinal cord. Bundles of immunoreactive fibers formed a loose network in lamina I. A homogenous band of immunoreactive fibers filled lamina II. Multiple bundles of CGRP-positive fibers coursed through the superficial laminae towards deep portions of the grey matter. In the lumbar segments, in contrast to the cervical and thoracic segments, the bundles could be followed deep into the dorsal funiculus. Bundles of varicose immunoreactive fibers were seen to twine around the dendrites of neurons located in lamina I, in the dorsal funiculus of the lumbar segments and deep in the dorsal horn (laminae III–V). The corresponding types of large and medium-sized neurons were found in silver impregnated adjacent spinal cord sections. It is suggested that neurons in the above locations preferentially receive multiple contacts from CGRP-containing nerve fibers along their extensive dendritic arborizations (CGRP-target neurons).
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  • 65
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    European journal of clinical pharmacology 39 (1990), S. 395-397 
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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  • 66
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    European journal of clinical pharmacology 38 (1990), S. 343-346 
    ISSN: 1432-1041
    Keywords: indomethacin ; cerebrospinal fluid ; pharmacokinetics ; protein binding ; analgesic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and cerebrospinal fluid (CSF) concentrations of indomethacin have been determined in 52 patients hospitalized for nerve-root compression pain. Samples of blood and CSF were collected at the same time in each subject, 0.5 to 12 h after a single intramuscular injection of 50 mg indomethacin. Analgesic effect was assessed by the absolute and percentage variation in Huskisson's visual analogue scale between dosing and sampling. According to its high lipid solubility, indomethacin rapidly crossed the blood-brain barrier, being detected in CSF 0.5 h after administration. After attainment of equilibrium within 2 h, the CSF level exceeded the free plasma level. Since the drug was extensively bound to serum albumin (99.7±0.1%), this phenomenon may represent a slight degree of binding of indomethacin in CSF. The analgesic activity was not related to either the plasma or CSF concentration of indomethacin.
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  • 67
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    European journal of clinical pharmacology 38 (1990), S. 523-524 
    ISSN: 1432-1041
    Keywords: tolbutamide ; hydroxytolbutamide ; carboxytolbutamide ; urinary excretion ; age ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. The reason for these findings is not known at the present time and may be associated with the decrease in creatinine clearance observed in these subjects or other changes in the pharmacokinetics of tolbutamide which are currently being investigated.
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    European journal of clinical pharmacology 38 (1990), S. 499-503 
    ISSN: 1432-1041
    Keywords: 2-mercaptopropionylglycine ; body clearance ; half-life ; pharmacokinetics ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 2-mercaptopropionylglycine (2-MPG) was studied in ten healthy volunteers after a single i. v. injection of 250 mg (1532 μmol). The total and non-protein-bound concentrations versus time curves were best described by a three-exponential function with terminal half-lives of 55 and 59 h respectively. Body clearance based upon the total concentration was estimated to be 105 and 231 ml/min based on the non-protein-bound 2-MPG. The corresponding values for Vss were 99 l and Vss,n 173 l, and for Vγ485 l and Vγ,n 1121 l respectively. 75% of the dose was excreted in the urine, mainly during the first 6 h after injection. The proportion of non-protein-bound 2-MPG diminished exponentially during the first 15 h and then levelled off at about 30%. There was a nonlinear increase in the non-protein-bound fraction of 2-MPG as the total plasma concentration of the drug increased.
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    European journal of clinical pharmacology 38 (1990), S. 526-527 
    ISSN: 1432-1041
    Keywords: phenytoin ; posture ; pharmacokinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 70
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    European journal of clinical pharmacology 39 (1990), S. 487-490 
    ISSN: 1432-1041
    Keywords: sulphadimethoxine ; plasma concentration ; skin blister fluid concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-dependent concentration curves of sulphadimethoxine in plasma and cantharidin-induced skin blister fluid have been evatuated following a single oral dose of 1 g. In contrast to other drugs, sulphadimethoxine exhibited two-stage penetration into the blister fluid, the second peak concentration being higher than the first. The maximum plasma concentration of 94.1 mg·l−1 was observed after 4 h, and in skin blister fluid the first peak of 25.6 mg·l−1 was found after 7 h, and the second of 58.0 mg·l−1 occurred after 30 h. The penetration of sulphadimethoxine into skin blister fluid, defined as the ratio of the AUC there to that in plasma was 0.748. The results suggest that sulphadimethoxine penetrates into skin blister fluid to a great extent from plasma and achieves concentrations exceeding the MIC for susceptible pathogens, but it requires a relatively long time to do so.
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  • 71
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    European journal of clinical pharmacology 38 (1990), S. 209-211 
    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; pharmacokinetics ; pharmacodynamics ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0–8) were 6.0 ng · ml−1, 1.5 h and 15.1 h · ng · ml−1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0–8) were 3.7 ng · ml−1, 1.2 h and 12.2 h · ng · ml−1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.
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  • 72
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    European journal of clinical pharmacology 39 (1990), S. 583-586 
    ISSN: 1432-1041
    Keywords: ranitidine ; piroxicam ; interaction ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of piroxicam (40 mg) on the pharmacokinetics of ranitidine (150 mg) and of ranitidine (150 mg bid) on the pharmacokinetics of piroxicam (20 mg) were assessed in two 2-way crossover studies in two groups of 18 healthy male subjects. In the first study there were no statistically significant differences between the pharmacokinetic variables for ranitidine in the presence or absence of piroxicam. The mean maximum plasma concentration (Cmax) was 467 ng·ml−1 for ranitidine alone and 466 ng·ml−1 in the presence of piroxicam; mean area under the plasma concentration vs time curve (AUC) was 2460 h·ng ml−1 and 2551 h·ng ml−1 respectively; and the mean terminal half-life (t 1/2) was 3.6 h and 3.8 h respectively. In the second study there were no statistically significant differences between the pharmacokinetic variables for piroxicam in the presence or absence of ranitidine. The mean Cmax was 2.1 μ·ml−1 in the presence of placebo and 2.0 μg·ml−1 in the presence of ranitidine respectively; mean AUC was 133 h·μg ml−1 and 137 h·μg ml−1 respectively, and the mean t 1/2 was 53.6 h and 54.5 h respectively.
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  • 73
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    European journal of clinical pharmacology 39 (1990), S. 613-614 
    ISSN: 1432-1041
    Keywords: Thioridazine ; debrisoquine polymorphism ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 74
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    European journal of clinical pharmacology 38 (1990), S. 255-258 
    ISSN: 1432-1041
    Keywords: theophylline ; mequitazine ; drug interaction ; pharmacokinetics ; asthma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an oral anti-allergic drug, mequitazine, on the pharmacokinetics of theophylline has been investigated in seven asthmatic patients. They received chronic theophylline therapy (a sustained-release theophylline tablet 200–400 mg b.d. at 12 h intervals) and coadministered mequitazine 6 mg for 3 weeks. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of mequitazine were compared. No significant change in the pharmacokinetic parameters of theophylline or in the urinary recovery of unchanged drug and its metabolites was observed. Thus, mequitazine did not influence the pharmacokinetics of theophylline and it should be safe for coadministration to asthmatic patients on chronic theophylline therapy.
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  • 75
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    European journal of clinical pharmacology 38 (1990), S. 259-263 
    ISSN: 1432-1041
    Keywords: tacrine ; amyotrophic lateral sclerosis ; postoperative sedation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l·h−1. Volume of distribution, Vα varied 100–680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6–36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.
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  • 76
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    European journal of clinical pharmacology 38 (1990), S. 269-273 
    ISSN: 1432-1041
    Keywords: flecainide ; quinine ; pharmacokinetics ; metabolism inhibition ; drug interaction ; renal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of flecainide and its two sequential metabolites, both free and conjugated, its pharmacodynamics, and the influence of simultaneously administered quinine, have been studied in 10 healthy subjects. The study comprised two, 48-h open phases at an interval of 1 week. Flecainide acetate 150 mg was given as a 30-min i.v. infusion and quinine sulphate orally 500 mg×3 over 24 h. Quinine administration did not change the apparent volume of distribution or the renal clearance of flecainide, but it significantly reduced its systemic clearance (9.2 vs 7.6 ml · kg−1 · min−1), thus increasing the elimination half-life (9.6 vs 11.5 h). The amount of flecainide transformed to its first, meta-O-dealkylated metabolite (MODF) fell with no change in the renal excretion of the latter, either in its free or conjugated forms. This finding, in association with a fall in amount of the second, meta-O-dealkylated lactam metabolite (MODLF) recovered in its conjugated forms in the urine, suggests that quinine inhibits both the first and the second steps of the sequential metabolism of flecainide. When the subjects received quinine in addition to flecainide, the PR interval in the ECG was slightly more prolonged than with flecainide alone. Due to the study design, an effect of quinine per se and the consequence of increased serum flecainide levels could not be distinguished.
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  • 77
    ISSN: 1432-1041
    Keywords: celiprolol ; renal failure ; pharmacokinetics ; enantioselective kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the ß1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.
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  • 78
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    European journal of clinical pharmacology 38 (1990), S. S53 
    ISSN: 1432-1041
    Keywords: nitrates ; pharmacokinetics ; pharmacodynamics ; nitrate tolerance ; isosorbide-5-mononitrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Healthy male volunteers received three different dose regimens of a controlled-release form of isosorbide-5-mononitrate (IS-5-MN; 60 mg per tablet). Dose regimen I consisted of a single daily dose of 60 mg given for 5 days. Dose regimen 11 was started with a dose of 60 mg, followed by 30 mg 12 h later and thereafter every 8 h. The last dose, on the 5th day was again 60 mg. In dose regimen III60 mg followed by 30 mg 6 h later were administered every day for 5 days. The peripheral arterial and venous effects of IS-5-MN during the first and last dosing interval were followed by changes in the finger pulse curve, standing systolic blood pressure, heart rate, and venous distensibility. Plasma concentrations of IS-5-MN were measured frequently following the first and the last dose. Following dose regimen I all hemodynamic effects produced by the first dose were maintained during the study. The maximal plasma concentrations were about 400 ng/ml and the trough value, lower than 100 ng/ml. Following dose regimen II the hemodynamic effects of IS-5-MN and sublingual glyceroltrinitrate were completely abolished on the 5th day. Trough plasma concentrations were approximately 300 ng/ml during the entire study period. Following dose regimen III pronounced hemodynamic effects were seen on the 1st day. However, a significant attenuation of the hemodynamic effects was measured on the 5th day, when trough plasma concentrations were between 100 and 230 ng/ml. There was a significant negative correlation between the magnitude of hemodynamic effect remaining on the 5th day (measured by the area under the finger pulse curve) and the trough plasma concentration. Thus, the maintenance of minimum plasma concentrations of IS-5MN of 300 ng/ml or higher produces a rapid development of hemodynamic nitrate tolerance, whereas no tolerance was found when the plasma concentrations were allowed to decline below 100 ng/ml before the next dose was given. A significant attenuation of hemodynamic effects was found when minimum plasma concentrations were between 100 and 230 ng/ml. The degree of attenuation in this concentration range increased with increasing trough plasma concentrations.
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  • 79
    ISSN: 1432-0711
    Keywords: Immunohistochemistry ; Progesterone receptor ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The potential for immunohistochemical detection of progesterone receptors (PRs) in routinely formalin-fixed and paraffin-embedded cancer tissues by use of the monoclonal antibody Mi 60-10 (mPR1, Dianova GmbH, Hamburg) was evaluated. The PR content of breast cancer tissue was investigated in 170 cases. A positive reaction to Mi 60-10 was found exclusively in the nuclei of benign or malignant epithelial cells. The distribution of PRs was heterogeneous. Immunohistochemical reaction was scored by multiplying the percentage of positive tumour cells by their prevalent degree of staining (Immunoreactive Score or IRS). The IRS values of formalin-fixed tissues (n=170) were compared with those in snap frozen tissues (n=82), with the PR content assayed by a DCC (dextran-coated charcoal) method (n=170), with histopathological grading according to Bloom and Richardson and with the menopausal status of the patient. There was an acceptable ranked correlation (r=0.74) between IRS in formalin-fixed and paraffin-embedded parts and snap frozen parts of the same carcinoma. A good correlation (r=0.72) was also found, when the semiquantitative results of immunohistochemical PR detection in formalin-fixed and paraffin-embedded tissues were compared to PR concentrations measured by a DCC method in tumor cytosols. There was an 80% concordance between the two methods for qualitative discrimination of PR-negative and PR-positive carcinomas. IRS correlated significantly with the degree of histological differentiation of the tumors (P〈0.001) but not with the menopausal status of the women (P〉0.05). Storage of paraffin-embedded tissues did not impair PR detection, for up to at least 5 years. Fixation of tissues in formalin only decreased the immunohistochemical detection rate if fixative acted for more than 24 h.
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  • 80
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    European journal of clinical pharmacology 39 (1990), S. 189-190 
    ISSN: 1432-1041
    Keywords: Diltiazem ; bioinequivalence ; plasma concentration ; dissolution ; pharmacokinetics ; commercial brands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A bioequivalence study of three brands of regular diltiazem — Angizem (A), Dilzem (B) and Herbesser (C) has been carried out in 5 healthy, male volunteers. After a single oral dose of 60 mg of each preparation, the mean AUC(0–8 h) and Cmax of preparation B was significantly higher than of brands A and C. The tmax of A and B was significantly lower than of C. B had a higher dissolution rate in vitro (98.8% dissolved in 45 min) than A and C. Thus, there was bioinequivalence of the three brands of diltiazem, due partly to differences in dissolution and perhaps in part to a first pass effect.
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  • 81
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    European journal of clinical pharmacology 39 (1990), S. 199-201 
    ISSN: 1432-1041
    Keywords: netilmicin ; pharmacokinetics ; diurnal variation ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Netilmicin 1.5 mg/kg body weight was administered intravenously every 8 h for 2 days to 8 patients with normal renal function. Significant elevation of mean and trough plasma concentrations was found at 05.00 h and 09.00 h. This was considered to be due to circadian variation, with possible accumulation during the night. The clinical importance of this phenomenon in relation to the development of aminoglycoside toxicity awaits further investigation.
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  • 82
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    European journal of clinical pharmacology 39 (1990), S. 507-513 
    ISSN: 1432-1041
    Keywords: Anthracyclines ; cancer patients ; iodo-doxorubicin ; doxorubicin ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of doxorubicin (DOX), iodo-doxorubicin (I-DOX) and their metabolites in plasma has been examined in five patients each receiving 50 mg/m2 of both anthracyclines as a bolus injection. Terminal half-life, mean residence time (MRT), peak plasma concentration Cmax, and area under the curve (AUC) appeared smaller for I-DOX, whereas its plasma clearance (CLp) and volume of distribution at steady state (Vss) were larger than for DOX. The major metabolite of I-DOX was iodo-doxorubicinol (I-AOL) followed by doxorubicinol aglycone (AOLON). The AUC of I-AOL was 6-times larger than that of its counterpart AOL, which is the major metabolite of DOX. AOLON generated after I-DOX administration is a further important metabolite, as its AUC was 10-times larger than that of AOLON generated from DOX. The other aglycones, such as doxorubicin aglycone (AON) and the 7-deoxy-aglycones were only minor metabolites after either I-DOX or DOX injection. The ratio AUCI-AOL/AOL/AUCI-DOX/DOX was 27 in the case of I-DOX and 0.4 after DOX. The terminal half-lives of the cytostatic metabolites I-AOL and AOL were similar, although a longer MRT for AOL was calculated. Both metabolites had much longer MRTs than their parent drugs. The MRTs of the aglycones AOLON and AON were greater than those of the 7-deoxy-aglycones after both I-DOX and DOX. Approximately 6% DOX and less than 1% I-DOX were excreted by the kidneys during the initial 48 h. About 5% of I-DOX was excreted via the kidneys as I-AOL. Aglycones were not detected in significant amounts. The plasma concentrations of all compounds measured were highest during the first few minutes after administration of I-DOX and DOX. The I-AOL concentration was comparable to that of I-DOX immediately after the injection, due to very rapid metabolism within the central compartment (vascular space) by the aldoketo reductase system in the erythrocytes. The plasma concentration-time curves of (7d)-aglycones showed a second peak between 2 and 9 h after injection, suggesting enterohepatic circulation of metabolites lacking the daunosamine sugar moiety.
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  • 83
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    European journal of clinical pharmacology 39 (1990), S. 577-581 
    ISSN: 1432-1041
    Keywords: Benzbromarone ; elimination phenotypes ; pharmacokinetics ; metabolism ; genetic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation, 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes, 10 subjects who eliminated the drug rapidly (S1–10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0–96) of the parent drug in S11 was 145 gmg · ml−1 h, and in the other individuals it averaged 18.3 (11.4–24.5) μg · ml−1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77–5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1–10 amounted to 20.1 (11.9–41.2) h for M1, and 17.2 (12.9–30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.
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  • 84
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    European journal of clinical pharmacology 39 (1990), S. 603-605 
    ISSN: 1432-1041
    Keywords: Galanthamine ; Alzheimer's disease ; stereoselectivity ; cholinesterase inhibition ; side effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36–55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5–7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg.
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  • 85
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    European journal of clinical pharmacology 39 (1990), S. 165-167 
    ISSN: 1432-1041
    Keywords: Cyclosporin A ; ponsinomycin ; pharmacokinetics ; drug interaction ; macrolide antibiotic ; renal transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin. On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption. Ponsinomycin should be use very carefully in patients treated with cyclosporin A.
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  • 86
    ISSN: 1432-1041
    Keywords: Flurbiprofen ; sustained-release formulation ; tolerance ; pharmacokinetics ; adverse reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 μg/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1–12 μg/ml. The pre-dose/peak ranges for the young and old patients were 4–10 μg/ml and 4–8 μg/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen.
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  • 87
    ISSN: 1432-1041
    Keywords: metoprolol ; oral osmotic drug delivery system (OROS) ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the bioavailability of metoprolol from an OROS system has been investigated. No significant difference was found between OROS administration to fasting subjects or after breakfast in any of the kinetic parameters (AUC, Cmax, tmax, C24 and lag time). Therefore, metoprolol OROS can be administered with breakfast.
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  • 88
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    European journal of clinical pharmacology 39 (1990), S. 385-389 
    ISSN: 1432-1041
    Keywords: Levodopa ; Parkinson's disease ; pharmacokinetics ; pharmacodynamics ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally. The best therapeutic infusion rate in the intravenous study was used for the intraduodenal infusion of levodopa. A lag time between plasma concentration and effect following oral administration was seen in three of the five patients and this disequilibrium was estimated as the rate constant ke0 using model-independent analysis. The plasma concentration-effect relationship was similar for the three modes of administration and in all patients the therapeutic plasma concentration for full mobility was 〉4–5 μg·ml−1. The disequilibrium half-life for development of effect after oral administration was calculated to be about 30 min. The patients remained clinically stable during the period of the intraduodenal infusion.
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  • 89
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    European journal of clinical pharmacology 39 (1990), S. 569-572 
    ISSN: 1432-1041
    Keywords: Bopindolol ; cirrhosis ; antipyrine ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration-time curve of the hydrolysis product of bopindolol has been investigated in 14 patients with cirrhosis and in 15 healthy volunteers given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history and clinical examination or liver biopsy. The time to maximum concentration, maximum concentration and AUC of hydrolyzed bopindolol were similar in the patients and controls. However, the elimination half-life was 6.0 h in controls and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients with cirrhosis, but no correlation was found with the pharmacokinetic parameters of hydrolysed bopindolol. Although the AUC was not significantly altered in patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests impairment of its disposition in liver disease, which could lead to significant accumulation of drug during chronic dosing.
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  • 90
    ISSN: 1432-1041
    Keywords: digoxin ; atrial fibrillation ; infusion ; pharmacokinetics ; simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart. In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group, without any detectable difference in side effects. There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients. However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.
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  • 91
    ISSN: 1432-1041
    Keywords: benazepril ; benazeprilat ; ACE inhibitor ; pharmacokinetics ; pharmacodynamics ; elderly ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of a single oral dose benazepril·HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19–32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20–40% greater. The elimination half-life of benazeprilat during the first 24 h after doing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml·min−1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated. Three of the 15 subjects reported clinical adverse experiences judged to be possibly drug related, namely headache, abdominal pain and cold extremities.
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  • 92
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    European journal of clinical pharmacology 38 (1990), S. 489-491 
    ISSN: 1432-1041
    Keywords: irtemazole ; dose-response relationship ; pharmacokinetics ; uricosuric drugs ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Irtemazole 12.5 to 50 mg in 6 healthy, normouricaemic subjects caused a maximal decrease in plasma uric acid (after 8 to 12 h) of 46.5%. The uricosuric effect began during the first 60 min after drug administration and it lasted for 7 to 24 h. Renal uric acid excretion returned to its base line value after 8 to 16 h and uric acid clearance after 10.0 to 12.0 h. Doses of irtemazole between 12.5 and 37.5 mg produced a dose-related rise in the uricosuric effect. There was no essential difference between the uricosuric effect of 37.5 mg and 50 mg irtemazole. The D50 dose (that producing a half-maximal effect) was between 16.3 mg and 34.2 mg, (average 24.7 mg). The value of irtemazole in the management of hyperuricaemia and gout remains to be determined.
    Type of Medium: Electronic Resource
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  • 93
    ISSN: 1432-1041
    Keywords: ibuprofen ; rheumatoid arthritis ; enantiomer ; stereoselectivity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary S(+)-, R(−)- or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)-, 300 mg pure R(−)- and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)-ibuprofen was not inverted to R(−)-ibuprofen, whereas R(−)-ibuprofen was inverted to S(+)-ibuprofen to a variable degree. S(+)-ibuprofen and R(−)-ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half-lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)-ibuprofen after R(−)- and racemic ibuprofen was significantly longer than after administration of the pure S(+)-enantiomer. Judged by the AUC, the bioavailability of S(+)-ibuprofen was independent of the dose within the range tested. Administration of S(+)-ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)-ibuprofen in patients was similar to that found in volunteers. S(+)-ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.
    Type of Medium: Electronic Resource
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  • 94
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    European journal of clinical pharmacology 38 (1990), S. 547-549 
    ISSN: 1432-1041
    Keywords: piroxicam ; tenoxicam ; cholestyramine ; pharmacokinetics ; enterohepatic circulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the extent of enterohepatic recycling of piroxicam and tenoxicam, their pharmacokinetics have been compared in the absence and presence of concomitant treatment with cholestyramine. In a randomized crossover study 6 healthy volunteers received piroxicam and tenoxicam 20 mg p.o., alone or with cholestyramine 24 g/day for 4 days. Cholestyramine increased piroxicam & tenoxicam elimination approximately 2-fold (t1/2 50.3 vs 28.1 h and 73.6 vs 35.8 h, respectively). It also increased the apparent clearance (Cl/f) of piroxicam and tenoxicam by 58% and 112%. When cholestyramine was administered, the t1/2 of piroxicam & tenoxicam were correlated (r=0.89), which suggests that their hepatic biotransformation is under a common control. It is concluded that: piroxicam and tenoxicam are eliminated to a large and comparable extent through the biliary route, and the administration of cholestyramine may help to accelerate their elimination in cases of overdosage.
    Type of Medium: Electronic Resource
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  • 95
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    European journal of clinical pharmacology 38 (1990), S. 579-582 
    ISSN: 1432-1041
    Keywords: d-sotalol ; d,l-sotalol ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of d-sotalol has been studied in six healthy volunteers given single doses of 0.25, 0.50, 1, 2 mg·kg−1 i.v. and one 100 mg oral dose in comparison with the kinetics of 1 mg·kg−1 i.v. of dlsotalol. There was no significant difference in the disposition of the d-enantiomer and the racemate. The terminal half-life averaged 7.2 h, and the kinetics was linear, with a mean total clearance of 0.13 l·h−1·kg−1. Renal clearance of d-sotalol represented 56 to 77% of total clearance. The absolute systemic availability of oral d-sotalol was close to 100% and the elimination half-life of the oral-d-enantiomer was similar to that of the i.v. form (7.5 h).
    Type of Medium: Electronic Resource
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  • 96
    ISSN: 1432-1041
    Keywords: Atenolol ; metoprolol CR ; elderly subjects ; subjective symptoms ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2–4 h. All three active treatments produced significant β1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of β1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
    Type of Medium: Electronic Resource
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  • 97
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    European journal of clinical pharmacology 38 (1990), S. 587-593 
    ISSN: 1432-1041
    Keywords: prenylamine ; racemic drug ; stereoselectivity ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of S-(+)- and R-(−)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.
    Type of Medium: Electronic Resource
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  • 98
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    European journal of clinical pharmacology 38 (1990), S. 599-603 
    ISSN: 1432-1041
    Keywords: Isradipine ; cirrhosis ; systemic ; calcium antagonist ; aminopyrine breath test ; serum bile acids ; galactose elimination ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the dihydropyridine calcium antagonist isradipine has been examined in 8 healthy volunteers, 7 patients with non-cirrhotic chronic liver disease (CLD), and 8 patients with biopsy-proven cirrhosis (CIR). Isradipine was simultaneously given orally (12C 5 mg) and i.v. (13C 1 mg). Systemic availability was significantly increased from 17% and 16% in controls and CLD, respectively, to 37% in CIR. The corresponding systemic clearances averaged 1.1, 0.9 and 0.61 · min−1, the reduction in cirrhotics being significant. Both aminopyrine demethylation capcity, a measure of hepatic microsomal function, and indocyanine green disappearance, a measure of hepatic perfusion, were correlated with the reduction in systemic clearance, and the reduction in oral clearance was correlated with the reciprocal of the serum bile acid concentration. The loss of first-pass extraction should be considered when this calcium antagonist is given perorally in patients with hepatic cirrhosis.
    Type of Medium: Electronic Resource
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  • 99
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    European journal of clinical pharmacology 38 (1990), S. 595-598 
    ISSN: 1432-1041
    Keywords: flecainide ; pharmacokinetics ; absorption ; non-parenteral administration ; healthy subjects ; rectal administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption kinetics of different pharmaceutical formulations of orally and rectally administered flecainide have been assessed in a cross-over study in 7 healthy volunteers. The subjects received single doses of flecainide after a washout period of at least one week. A tablet, an oral solution, a rectal solution and a 10 min i.v. infusion during 10 min each containing 100 mg flecainide were administered to the subjects in a randomized order. The mean absolute bioavailability was 98%, 78% and 81% for the rectal and oral solutions and the tablet. The lag time after administration of the oral solution was 0.33 h and it was 0.86 h after the tablet and 0.18 h after the rectal solution. The mean time to the peak serum concentration (tmax) after the rectal solution (0.67 h) was shorter than after either the tablet (4 h) or oral solution (1 h). The maximum serum concentration (Cmax) was 0.29 mg · 1−1 after the rectal solution, 0.14 mg · 1−1 after the tablet and 0.17 mg · 1−1 after the oral solution. All the volunteers showed significantly higher serum flecainide concentrations during the first 20 min of the absorption phase after rectal administration of 100 mg flecainide as a solution compared to its oral administration. In conclusion: based on the absolute bioavailability, Cmax, tmax, and lag times, rectal administration of flecainide solution gave a better absorption profile than after oral tablet or solution.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 605-608 
    ISSN: 1432-1041
    Keywords: albendazole ; albendazole sulphoxide ; absorption ; elimination ; benzimidazole ; pharmacokinetics ; echinococcosis ; cholestasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of albendazole and its main metabolite, albendazole sulphoxide, have been examined after giving a single oral dose of 200 mg albendazole to 19 patients with either Echinococcus multilocularis or E. granulosus, 5 of whom had significant extrahepatic obstruction due to the underlying disease. The AUC of albendazole sulphoxide was increased in the latter patients (mean 122 μmol · h · l−1 compared to 17 μmol · h · l−1 in the non-obstructed group). Obstructed patients had delayed absorption, ka averaging 0.39 compared to 1.41 h−1 in non-obstructed patients. The corresponding elimination rate constant, ke was also prolonged, averaging 0.041 and 0.13 h−1 in the two groups, respectively. Four patients were restudied after complete or partial resolution of the cholestasis. The pharmacokinetic parameters in them had returned towards values comparable to those in the non-obstructed patients.
    Type of Medium: Electronic Resource
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