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  • 1985-1989  (1,697)
  • 1989  (1,697)
  • Cell & Developmental Biology  (1,469)
  • Immunohistochemistry  (116)
  • pharmacokinetics
Material
Years
  • 1985-1989  (1,697)
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 8 (1989), S. 269-272 
    ISSN: 1437-160X
    Keywords: Activated lymphocytes ; Autoradiography ; Immunohistochemistry ; Cytotoxic lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The occurrence of MHC class I antigens and microbial antigens derived from the triggering infection of the diseased joints in reactive arthritis (ReA) seems to set the stage for local immune activation. In this report activated lymphocytes are demonstrated by using an avidin-biotin-peroxidase complex (ABC) method combined with autoradiography that identifies DNA synthesis and, thus, activation. Most of the activated T lymphocytes in reactive arthritis were found to belogn to the CD8 suppressor/cytotoxic T-lymphocyte subset. In striking contrast, the majority of the activated T lymphocytes detected in rheumatoid arthritis (RA) synovial fluid belonged to the CD4 helper/inducer subset. These findings agree well with the assumption that CD8-positive cells identify the foreign antigen in the context of class I antigens, whereas CD4-positive cells are found to be associated with the recognition of MHC locus II coded HLA antigens.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 9 (1989), S. 49-51 
    ISSN: 1437-160X
    Keywords: Synovium ; Monoclonal antibodies ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cells making up the lining of the synovium have long been known as type A and B synoviocytes, with an intermediate form sometimes also described. Accumulating evidence shows that the type A cells are macrophages and the type B cells are fibroblasts. Recently, a definite orientation of these cells within the synovial lining has been observed. The number of synovial lining cells increases in joint disease, and this now seems more likely to be due to cellular recruitment rather than local proliferation.
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  • 3
    ISSN: 1432-1440
    Keywords: Papillary thyroid carcinoma ; Transthoracic lung biopsy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distant metastases from occult papillary carcinoma of the thyroid, which is defined as a tumor less than 15 mm in diameter, are extremely rare. A 21-year-old patient with miliary micronodular densities in both lungs is described, in whom pulmonary lymphangitic spread of occult papillary thyroid carcinoma was diagnosed by thransthoracic lung biopsy.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 244 (1989), S. 193-206 
    ISSN: 1432-0711
    Keywords: Immunoscintigraphy ; Cancer of the ovary ; Tumor marker CA 125 ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Radioimmundetection (RID) using anti-CA 125 antibodies proved to be a valuable tool in the follow-up of metastasizing ovarian cancer. Sensitivity, specificity, and accuracy were high. RID had no clinical side effects. But some patients formed antibodies which interfered a) with the evaluation of the scintigram and b) with further measurement of CA 125 levels. We found 2 cm diameter metastases that were not detected by computed tomography. However, the heterogeneity of tumor metastases limits the sensitivity of this method. CA 125 serum levels, immunohistochemistry, and immunoscintigraphy did not always correlate. Monitoring serum levels of CA 125 was most valuable in clinical management of tumor spread and in the optimal use of RID.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 244 (1989), S. 103-112 
    ISSN: 1432-0711
    Keywords: CA 125 ; Immunohistochemistry ; Müllerian duct
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true “tumour marker”, but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 246 (1989), S. 61-84 
    ISSN: 1432-0711
    Keywords: Immunohistochemistry ; Uterine cervix ; Epithelial markers ; Cervical carcinogenesis ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epithelial antigen immunostaining in the uterine cervix has been claimed to be helful in the identification and classification of rare lesions, evaluation of basement membrane integrity, study of atypical condylomas, immunodetection of proliferating processes and early diagnosis of malignant transformation. The present review attempts to demonstrate the potential value of immunohistological techniques as a means of identifying normal and abnormal patterns of antigenic expression in cervical epithelium.
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  • 7
    ISSN: 1432-2307
    Keywords: Cholangitis ; Major histocompatibility complex antigen ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A longitudinal study of intra and extrahepatic bile duct injuries was performed in an animal model of secondary sclerosing cholangitis induced by formalin injection into the common bile duct. Lymphocytic infiltration inside and around the bile ducts occurred seven days after injection. The disease later evolved to a fibrous cholangitis of the small bile ducts. Septal intrahepatic and extrahepatic bile duct involvement became evident three months after formalin injection. The ductular proliferation led to a progressive biliary cirrhosis with portal to portal fibrous septa. After formalin injection, bile duct cells expressed the Ia antigen in the cytoplasm and/or on the membrane of bile duct cells. The intensity of staining did not correlate with the duration or severity of the disease. Lymphocytes infiltrating into and around the bile duct were mainly T-cells. This study suggests that a local cell-mediated immune response to the injection of a toxic agent induces pathological features similar to those of sclerosing cholangitis in man.
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  • 8
    ISSN: 1432-2307
    Keywords: Lymphatics ; Factor VIII-related antigen ; Ulex europaeus 1 lectin ; Laminin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to investigate the antigen profile in human lymphatic vessels when compared with blood vessels, postmortem retrograde lymphangiography was done via the thoracic duct on six patients. Formalin fixed, paraffin embedded tissue was stained immunohistochemically for Factor VIII-Related antigen (F VIII R:Ag), with Ulex Europaeus 1 lectin (UEA-1) and for laminin. The results show that the endothelium of blood vessels and lymphatics at all levels of the lymphatic system react positively following staining for Factor VIII-R:Ag and with UEA-1 lectin. The staining for F VIII R:Ag was generally weaker in the endothelial cells lining lymphatic vessels. Staining for the basement membrane component laminin can be used to distinguish lymphatic capillaries and smaller lymphatic collecting vessels from blood vessels.
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  • 9
    ISSN: 1432-2307
    Keywords: Brain neoplasms ; Growth fraction Ki-67 ; Epidermal growth factor receptor ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 100 tumours of the human nervous system were investigated by means of immunohistochemistry in order to determine the expression of epidermal growth factor receptor (EGFr) and the proliferative activity as evaluated by demonstration of the proliferation-associated Ki-67 antigen. Epidermal growth factor receptor immunoreactivity was present in 79% (23/29) of the high-grade malignant gliomas examined but in only 9% (2/22) of the low-grade gliomas. Besides the gliomas, EGFr-expression was detectable in smaller amounts in most (13/15) meningiomas, in one anaplastic neurinoma and in individual tumour cells of one medulloblastoma. In addition, EGFr-expression was found in 50% (6/12) of metastatic carcinomas. Seven of eight medulloblastomas, two cerebral primitive neuroectodermal tumours (PNETs), three benign neurinomas, one ganglioneuroma, one metastatic intracerebral malignant melanoma, three spinal plasmocytomas and one immunocytoma showed no detectable EGFr-expression. Our results indicate that (1) the expression of EGFr in human tumours of the nervous system depends on the histological tumour type and (2) in the glioma group is related to the grade of malignancy. A close correlation between EGFrexpression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.
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  • 10
    ISSN: 1432-2307
    Keywords: Thyroid neoplasms ; Electron microscopy ; Immunohistochemistry ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural study, both morphological and immunohistochemical, has been carried out on eight thyroglobulin-positive and nine thyroglobulin-negative medullary carcinomas of the thyroid. The morphometric analysis of granule size showed that all tumours contained cells with small granules and cells with medium size granules, whereas eight tumours had additional cells with large granules. The small granules had an electron dense core, while the medium and large sized granules were both pale-cored and dense-cored. The cells with small, medium or large secretory granules were all immunoreactive for calcitonin and CGRP. No ultrastructural differences were observed between thyroglobulin-positive and thyroglobulin-negative cases of medullary carcinoma of the thyroid.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1989), S. 459-464 
    ISSN: 1432-2307
    Keywords: Sebaceous carcinoma ; Parotid gland ; Salivary gland ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sebaceous carcinoma of salivary gland origin is extremely rare and, because of its rarity, the clinicopathological characteristics and the histogenesis are not fully understood. We present a case of sebaceous carcinoma of the parotid gland which brings the total number of reported cases to 22. The tumor showed epithelial cell nests which were mainly composed of sebaceous cells with marked cellular atypia. In most of the nests, glandular spaces lined by ductal epithelium were present. Scattered mucous cells and flattened eosinophilic cells at the periphery of the nests were also seen. Ultrastructural and immunohistochemical observations of the tumour revealed coexistence of sebaceous and glandular differentiations in some tumour cells. Tumour cells with lipid granules often participated in the formation of glandular structures or exhibited intracytoplasmic lumina, and immunohistochemical localization of lactoferrin and secretory component, the functional markers of ductal epithelium of salivary gland, was demonstrated not only in duct-forming tumour cells but also in many sebaceous tumour cells. It seems likely that sebaceous carcinoma originates from pluripotential duct cells which can differentiate into sebaceous, ductal and mucous cells.
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  • 12
    ISSN: 1432-2307
    Keywords: Granulomatous inflammation ; Inflammatory pseudotumour ; Immunohistochemistry ; Light microscopy ; Pleura ; Retroperitoneal fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inflammatory nature of a tumour-like lesion not formerly observed in the parietal pleura was confirmed histologically using immunohistochemical analysis and clinically by spontaneous regression. A study of the literature revealed that the histological picture of the lesion was consistent with that of the rarely described inflammatory pseudotumour.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 219-224 
    ISSN: 1432-2307
    Keywords: Multiple myeloma ; Ectopic amylase production ; Immunohistochemistry ; Immunoelectron microscopy ; Cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The first autopsy case of amylase-producing IgA-λ-type multiple myeloma is described. Immunohistochemically, amylase and α andλ chains of immunoglobulin were demonstrated in the cytoplasm of the myeloma cells. Secretion of amylase by cultured myeloma cells obtained from the patient's pleural effusion was clearly demonstrated by the starch film method. Immunoelectron microscopically, positive reaction products for amylase and the α chain of immunoglobulin were observed in the well developed endoplasmic reticulum. Since no secretory granules were observed, we postulated that the secretory process of amylase was not via the zymogen granules but via a mechanism similar to that for immunoglobulin.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 253-258 
    ISSN: 1432-2307
    Keywords: Epithelial markers ; Synovial sarcoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 297-300 
    ISSN: 1432-2307
    Keywords: Non-Hodgkin's lymphoma ; Electron microscopy ; Immunohistochemistry ; Intercellular junction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A rare example of pleomorphic B cell non-Hodgkin's lymphoma is described in which tumour cells possessed simple intercellular junctions.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 357-366 
    ISSN: 1432-2307
    Keywords: Paraquat poisoning ; Pulmonary fibrosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-nine autopsy cases of paraquat-induced lung injury were studied by histological and immunohistochemical methods. Two stages of injury were identified. In the early stage, the alveolar epithelium degenerates but the epithelial basement membrane remains intact. In the late stage, the epithelial basement membrane is focally disrupted, the mesenchymal cells grow into the alveolar space, and intra-alveolar fibrosis appears. In spite of these pathological changes, the original framework of the alveolar wall is preserved in many areas. Intra-alveolar fibrosis may follow as a consequence of damage to the epithelium without severe damage to the underlying basement membrane, which occurs at the stage of organization. Morphological variants of intra-alveolar fibrosis seem to occur not only to the size of the defect of the basement membrane but also to the difference in the stages of evolution at the time the lesion is studied. The epithelium regenerates along the basement membrane in the early stage of re-epithelialization, but grows over the luminal aspect of intra-alveolar fibrous tissue which has been laid on the remaining basement membrane in the late stage. It is speculated that the regeneration of epithelial cells may develop without any association with the basement membrane when a fibrous tissue covers the original basement membrane.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 429-436 
    ISSN: 1432-2307
    Keywords: Hodgkin's disease ; Immunohistochemistry ; Microenvironment ; Spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hodgkin's disease in the spleen - with the exception of its B cell variant - behaves quite differently from non Hodgkin's lymphomas with respect to both its spread and microenvironment. Each type of HD appears to create its own microenvironment by the secretion of cytokines responsible for the characteristic cellular composition of the infiltrates and thereby alters the normal immunoarchitecture of the spleen profoundly. While some histological findings seem to imply the presence of a host response against HD especially in the nodular sclerosis subtype, morphological and immunohistochemical evidence in the spleen cannot conclusively substantiate this hypothesis.
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  • 18
    ISSN: 1432-2307
    Keywords: Salivary gland ; Myoepithelioma ; Neoplasm ; Electron microscopy ; Immunohistochemistry ; Cytoplasmic filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was wide-spread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonalshaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.
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  • 19
    ISSN: 1432-2307
    Keywords: Breast tumours ; Oncogene products ; Immunohistochemistry ; Lymph node metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is a matter of debate whether the amplification of c-erbB-2 oncogene or production of the oncoprotein in breast cancers correlate with the presence of lymph node metastasis and with a poor prognosis. This study was aimed at elucidating the immunohistochemical localization of oncogene products which are related to cell growth, c-erbB-2 product, epidermal growth factor receptor (EGFR), c-myc protein and estrogen receptor (ER), in benign and malignant lesions of the breast. Fresh frozen sections of 25 breast cancers and 11 fibroadenomas from Japanese women were studied by indirect immunoperoxidase method with proper fixation. C-erbB-2 product and EGFR were localized on the cell membrane whereas c-myc protein and ER were observed in the nuclei. Immunohistochemical expression of oncogene products and ER were not only observed in the mammary carcinomas but also in the fibroadenomas. However immunoreactivities of EGFR and ER were more frequently seen in the fibroadenomas (p〈0.05). In breast cancers, the incidence of immunoreactivity for c-erbB-2 was higher in the cases with lymph node metastasis than cases without nodal metastasis (p 〈 0.05) and there was reciprocal correlation between the expressions of EGFR and ER (p〈0.05). Regarding the size of the primary tumour, there was no statistically significant correlation with the expressions of c-erbB-2, EGFR, c-myc or ER. Histological grade correlated only with the expression of ER (p〈0.05).
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  • 20
    ISSN: 1432-2307
    Keywords: Papillary carcinoma of the thyroid ; Intranuclear cytoplasmic inclusions ; Immunohistochemistry ; Thyroglobulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intranuclear cytoplasmic inclusions (ICI) in 38 cases of thyroid papillary carcinoma were studied histopathologically, immunohistochemically, and ultrastructurally in order to examine the frequency of ICI and their relationship to both the histological structure and cytological findings in thyroid papillary carcinoma. The fine-structure and biochemical state of ICI were also studied. ICI occurred in all 38 cases. ICI occurrence ranged from one in several microscopic fields to more than ten per field. The number of ICI divided by the number of nuclei on the microscopic photographs ranged from 0.013 to 0.116. The frequency of ICI was strongly influenced by the state of nuclear chromatin and pleomorphism, but was not influenced by a pattern of papillary or follicular tumour growth. Immunohistochemically, 10-30% of ICI revealed strong thyroglobulin (Tg), which was ascertained by immunoelectron microscopy. Neither T3 nor T4 was detected in ICI (with some exceptions). Some ICI showed keratin and vimentin. PAS-positive ICI were observed. Ultrastructurally, enlarged r-ER, many Golgi vesicles and small vesicles (diameter of 300-500 nm) and sacs were observed in ICI. These findings suggested increased protein synthesis and/or protein accumulation Abundant secondary lysozomes, showing degradation of ICI, and bundles of condensed intermediate filaments were also detected. The character and genesis of ICI are discussed.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1989), S. 231-241 
    ISSN: 1432-2307
    Keywords: Gastric carcinoma ; Lymphoid stroma ; T lymphocytes ; HLA-DR ; Interleukin-1 ; Mucin histochemistry ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 626 surgically resected gastric carcinomas were reviewed, and 24 cases (3.8%) of “gastric carcinoma with lymphoid stroma” were identified. The tumour cells were consistently arranged in an anastomosing trabecular or alveolar pattern and were densely infiltrated by lymphoid cells. The specimens were studied using mucin histochemistry and the indirect immunoperoxidase method to determine the histochemical properties of this form of gastric carcinoma. The tumour cells were consistently positive for concanavalin A paradoxical staining, class III and almost devoid of acidic mucins, features demonstrating preferential differentiation toward pyloric glands or pseudopyloric glands. Immunohistochemically, positive reactions for Leu M1 and lysozyme, marker substances of (pseudo)pyloric gland cells, were often observed. Carcinoembryonic antigen was positive in focal areas without (pseudo)pyloric glandular patterns. Secretory component was focally positive. HLA-DR was strongly expressed in most cancer cells and 17 tumours (71%) showed positivity for interleukin 1 (IL-1). The lymphoid stroma contained a high percentage of UCHL1-reactive T cells both within and around the cancer cell nests, while SL26-reactive B cells clustered in lymphoid follicles. A considerable number of T-lymphoid cells were also reactive for IL-1. A number of plasma cells with a predominance of IgG-type were distributed around the cancer cell nests. S-100 protein-positive dendritic cells were not identified. We speculate that the prominent lymphoid stroma including intraepithelial lymphocyte-like T cells with IL-1 receptors is possibly induced by IL-1 related mediators released from the HLA-DR-positive gastric cancer cells of the (pseudo)pyloric gland-type.
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  • 22
    ISSN: 1432-2307
    Keywords: Malignant fibrous histiocytoma ; Ultrastructure ; Enzyme histochemistry ; Immunohistochemistry ; “Fibrohistiocytoid cell”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural, enzyme histochemical and immunohistochemical studies were performed on tissue obtained from eight cases of malignant fibrous histiocytoma (MFH) and five cases of sacral decubitus ulcer. The MFH was composed of two major tumour cell types: fibroblast-like and histiocyte-like cells. Both cell types demonstrated abundant branching, fragmented rough endoplasmic reticulum (rER), many free ribosomes, occasional small mitochondria, an oval, elliptical or irregularly shaped nucleus with one or two prominent nucleoli and often a few dense bodies. However, pseudopodial projections, multivesicular bodies and phagosomes, common histiocyte organelles, were not seen. With little difference between cases or selection sites, the MFH cells reacted to acid phosphatase (AcP) and α-naphtyl butyrate esterase (ANBE) by enzyme histochemistry and with ferritin (Fer), α1-antitrypsin (AT), α1-antichymotrypsin (ACT), fibronectin (FN), HLA-DR, HLA-DP, Leu 10 and OKT 9 in immunohistochemical studies. MFH tumour cells did not immunostain with monocyte/macrophage markers (Leu M1, Leu M3, Mo 1, Mo 2 and Macrophage) although non-neoplastic histiocytes did react to these markers. In addition, granulation tissue, such as that found in sacral decubitus ulcers, was examined and the existence of a specific cell type called the “fibrohistiocytoid (FH) cell” was documented. The FH cell was short, spindle shaped and elliptical. Ultrastructurally, it had fragmented rER distributed in a branching pattern, dispersed free ribosomes, small mitochondria and a few dense bodies, but lacked diverse fused lysosomes and distinct pseudopodial cytoplasmic extensions. The FH cells reacted with AcP, alkaline phosphatase and ANBE but not with peroxidase using enzyme histochemistry and with Fer, AT, ACT, FN, HLA-DR, HLA-DP, Leu 10 and OKT 9 but not with monocyte/macrophage markers, C3d receptor, C3bi receptor in immunohistochemical studies. The FH cells had morphological, enzyme histochemical and immunohistochemical characteristics intermediate between fibroblasts and histiocytes. Similarities between MFH cells and the FH cells seen in chronic inflammation are discussed.
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  • 23
    ISSN: 1432-2307
    Keywords: Barrett's oesophagus ; Mucus ; Histochemistry ; Immunohistochemistry ; Precancerous lesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Columnar cell lined lower oesophagus (CELLO), often considered to be a precancerous lesion, is characterized by a glandular mucosa with a predominance of sulphomucins in the specialized epithelium. This histochemical abnormality can be correlated with abnormal differentiation which may also be studied by anti-mucus antibodies (anti-M1, anti-M3, anti-SIMA, anti-LIMA). The purpose of this prospective study is to define the mucin profile in a large population of CELLO by immunohistochemistry and to compare it with the results of histochemistry. Biopsies of 79 patients with reflux oesophagitis were included. Thirty-eight had CELLO and 41 had a histologically normal cardia. Six surgical specimens of oesophageal adenocarcinomas were also included. The histochemical methods confirmed the preponderance (57.9%) of type III intestinal metaplasia (IM) found in 57.9% of cases. The immunohistochemical methods showed a similar antigenic profile of type II and III IM with positivity of anti-SIMA and anti-M3 antibodies in the goblet cells, and positivity of anti-LIMA antibodies in both the goblet and intermediate cells of the specialized epithelium. The mucus secreting cells of the oesophageal adenocarcinomas had the same immunohistochemical profile. These results are similar to those of Filipe et al. in type II and III IM surrounding gastric adenocarcinomas. Immunohistochemical methods allow us to subdivide type II and type III IM into 2 subgroups according to the positivity or negativity of the anti-LIMA antibodies in the intermediate cells. Among the 41 normal cardias in patients with reflux oesophagitis, 10 contain sulphomucin secreting cells positive with anti-LIMA antibodies. We suggest that this anti-LIMA positivity may be a step preceeding type III IM in specialized epithelium.
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  • 24
    ISSN: 1432-2307
    Keywords: Le a ; Le b ; Le x ; Le y ; CA 19-9 ; CA-50 ; Chronic pancreatitis ; Pancreatic carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of the blood group antigens Le a, Le b, Le x, Le y and the carbohydrate antigens CA 19-9 and CA-50 was studied in 20 ductal pancreatic carcinomas, 24 pancreases with chronic pancreatitis and 10 normal fetal and adult pancreases. CA 19-9, CA-50 and Le a showed the strongest staining intensity, the highest percentage of labelled cells, and a membrane-bound expression pattern in epithelial cells of normal pancreas, chronic pancreatitis and well differentiated (G1) carcinoma; in moderately and poorly differentiated carcinomas (G2/3) it was predominantly cytoplasmic. The staining pattern of Le b and Le x was less clearly membrane-bound but varied with cytoplasmic and Golgi-located distributions in all pancreatic specimens. Le y revealed a consistent granular antigen expression in the Golgi-region of ductal epithelial, acinar and carcinoma cells. None of the antibodies allowed a morphological differentiation by their expression pattern between hyperplastic, metaplastic and dysplastic or neoplastic cells. The differences in their staining patterns were quantitative and did not allow a qualitative differentiation between chronic pancreatitis and pancreatic carcinoma. We found coexpression of Le a and Le b antigens in 46/54 pancreatic specimens. All but 7 pancreata were CA 19-9 positive. An association between Le x, y and Le a, b antigen expression could not be noted in our material.
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  • 25
    ISSN: 1432-2307
    Keywords: Bronchial neoplasms ; Carcinoid ; Immunohistochemistry ; Inclusions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A bronchial carcinoid with globular intracytoplasmic inclusions is reported. The inclusions stain brown with Grimelius silver impregnation and some show distinct immunoreactivity for chromogranin A. Tumour cells stain positively with antisera to neuron specific enolase, chromogranin A and not with antisera against ACTH, somatostatin or S-100 protein. The cells show distinct immunoreactivity for cytokeratins and vimentin, which is particularly intense in the intracytoplasmic inclusions. Desmin and glial fibrillary acidic protein are absent. Ultrastructural analysis reveals that the inclusions are composed of aggregates of filaments of 8–10 nm of diameter, intrapping a few neurosecretory granules. Immunohistochemical and ultrastructural data support the hypothesis that the inclusions are composed of intermediate filaments, whose metabolism and synthesis have somehow been deranged.
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  • 26
    ISSN: 1432-2307
    Keywords: MHC class II antigens ; Antigen presenting cells ; Pulmonary fibrosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Major histocompatibility complex (MHC) class II antigens are essential in the presentation of antigens to T lymphocytes, and cells expressing MHC class II antigens are known to play a role as antigen presenting cells (APC). We investigated the distribution of MHC class II antigens and the reactivity of monoclonal antibodies OKM1 and OKM5 in normal and fibrotic lungs immunohistochemically. The results showed that alveolar capillary endothelial cells (ACEnd) expressed MHC class II antigens and were reactive with OKM5 in both normal lungs and the non-thickened parts of alveolar septa of pulmonary fibrosis. However, ACEnd did not express MHC class II antigens and were not reactive with OKM5 in thickened alveolar septa of pulmonary fibrosis. Type II alveolar epithelial cells (AEp) proliferating and replacing type I AEp in pulmonary fibrosis expressed MHC class II antigens strongly. Alveolar macrophages expressed MHC class II antigens strongly and reacted with OKM1 in pulmonary fibrosis, especially in alveolar spaces. These findings suggest that the phenotypic changes of ACEnd may be involved in the process of pulmonary fibrosis, and type II AEp and alveolar macrophages in the parts of thickened alveolar septa may play a role as APC.
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  • 27
    ISSN: 1432-2307
    Keywords: Ageing lung ; Extracellular matrix components ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The modifications of the extracellular matrix (ExM) components in the alveolar parenchyma of elderly subjects were investigated using a panel of polyclonal antibodies. The elastic fibers showed a notable decrease along the alveolar walls while type III collagen increased when compared with that of non-elderly controls. No variations of these components were detectable in the alveolar ducts or in the respiratory bronchioli. An increase in the thickness of the alveolar basement membranes was detected in some of the subjects when antibodies against type IV collagen and laminin were used, while antibodies to fibronectin and type V collagen did not reveal any modifications compared with the controls. The modifications revealed in the lungs of the elderly can be related to the alterations of the elastic recoil and pulmonary compliance observed in these subjects.
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  • 28
    ISSN: 1432-2307
    Keywords: Breast cancer ; tumor markers ; Immunohistochemistry ; Glycolipid antigen ; Neuron-specific enolase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunocytochemical reactivity of breast cancers to antibodies raised against neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and an adenocarcinoma-associated glycolipid antigen (IR-14) was studied in relation to the long-term outcome of the neoplastic disease. The patients whose tumours exhibited reactivity with the IR-14 and anti-NSE antibodies had a considerably better 5-year and long-term survival than those without such reactivity. Assessment of DNA-ploidy of the tumour cells was also relevant for long-term prognosis, immunohistochemistry giving additional prognostic information among aneuploid tumours. Reactivity with polyclonal CEA antibodies was of no prognostic value. It is suggested that tumors carrying the IR-14 reactive epitope, which was originally isolated from circulating antigen-antibody complexes, might evoke a favourable immune response and thus improve the survival of the patient.
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  • 29
    ISSN: 1432-2307
    Keywords: MAM-3 and MAM-6 Antigens ; Human salivary gland tumour ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary MAM-3 and MAM-6 antigens of human milk fat globule membrane were detected immunohistochemically in 93 cases of salivary gland tumours as well as in normal glands. The antigens were visualized in 10% formalin-fixed paraffin sections. MAM-3 (MoAbs 115G3, 67D11) antigen was distributed in intercalated and striated duct cells of the normal salivary glands, and in luminal tumour cells and squamous metaplastic cells of pleomorphic adenomas. In pleomorphic adenomas the frequency of positive staining with MoAb 67D11 (54/67; 80.6%) was higher than that with MoAb 115G3 (36/67; 53.7%). MAM-6 (MoAbs 115D8, 115F5) antigen was expressed in luminal and lateral borders of serous acinar cells and ductal of the normal glands, and also in luminal borders of tubulo-ductal and glandular structures of salivary gland tumours. Ductal basal cells were characterized by existence of positive staining for MAM-6 antigen, in adenolymphomas MAM-6 antigen was restricted to the basal tumour cells. Some mucous cells of mucoepidermoid tumours were stained specifically with MoAb 115G3, and epidermoid cells of mucoepidermoid carcinomas manifested MAM-6 antigen staining. Immunohistochemical localization of MAM-6 antigen resembled that of epithelial membrane antigen (EMA) detected with MoAb.
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  • 30
    ISSN: 1432-2307
    Keywords: Keratin ; Mammary neoplasms ; Mouse ; Rat ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51 000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(α)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.
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  • 31
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    Virchows Archiv 414 (1989), S. 439-445 
    ISSN: 1432-2307
    Keywords: Granulosa cell tumour ; Immunohistochemistry ; Intermediate filament proteins ; Tumour markers ; Ovarian carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Paraffin-embedded material of 47 ovarian tumours primarily diagnosed as granulosa cell tumours, including 2 cases of juvenile granulosa cell tumour, were studied immunohistochemically for the presence of intermediate filament proteins, epithelial membrane antigen and tumour markers. Forty-one lesions, including the 2 juvenile granulosa cell tumours, were vimentin positive, while keratin and epithelial membrane antigen expression could not be detected. Six tumours primarily diagnosed as poorly differentiated malignant granulosa cell tumours were vimentin negative, showed a mild to moderate positivity for keratin and intense positivity with the anti-epithelial membrane antigen antibody. These latter tumours were therefore classified as undifferentiated ovarian carcinomas, corresponding to their significantly poorer prognosis and shorter survival when compared with the granulosa cell tumours. Two of these six tumours were positive for carcino-embryonic antigen. Two small cell carcinomas of the ovary studied in addition expressed keratin in a proportion of tumour cells while no epithelial membrane antigen or vimentin was detectable. None of the tumours tested for alpha-fetoprotein, human chorionic gonadotrophin, human placental alkaline phosphatase and human placental lactogen, were positive. The data indicate the value of antibodies directed against intermediate filament proteins and epithelial membrane antigen to distinguish granulosa cell tumours from poorly differentiated carcinomas, a worthwhile distinction considering the much better prognosis of granulosa cell tumours.
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  • 32
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    Virchows Archiv 414 (1989), S. 243-251 
    ISSN: 1432-2307
    Keywords: Ewing's sarcoma ; Histology ; Immunohistochemistry ; Prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histological and immunohistochemical features of 87 patients with conventionally diagnosed Ewing's sarcoma were studied retrospectively on routinely processed material and evaluated with regard to prognostic significance. 74% were convincingly positive when stained for vimentin, 13% were doubtful, and 13% were negative. A varying degree of positivity for neuron-specific enolase (NSE) was found in 15%; these cases all co-expressed vimentin. A single tumour contained scattered cytokeratin-positive cells. Positivity for the leukocyte common antigen (LCA) could be demonstrated in three cases; these were excluded from the statistical analysis of prognostic factors. Growth pattern, soft tissue invasion, monomorphic or dimorphic cell population, and PAS-, NSE- or vimentin-positivity did not influence survival significantly. However, prognosis was increasingly poor with increasing degree of necrosis: median survival was 28 months for grade I necrosis (〈10%), 16 months for grade II (10–50%), and 11 months for grade III (〉50%),p〈0.0005. A mitosis count of 〈1 per high-powerfield (HPF) was correlated to a median survival of 26 months, ≥ 1 per HPF to 12 months,p〈0.05. The findings indicate some degree of heterogeneity in Ewing's sarcoma which may be related to primitive peripheral neuroectodermal tumours (PNETs), or be a true blastoma. In future trials, diagnostic criteria (including immunohistochemistry) should be clearly defined and materials should be large enough to allow for stratification according to prognostic factors.
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  • 33
    ISSN: 1432-2307
    Keywords: Duodenal tubulo-villous adenoma ; Adenocarcinoma ; Immunohistochemistry ; Diameter of adenoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary duodenal carcinoma and duodenal adenoma are rare tumours. Duodenal carcinoma makes up about 0.3% of all malignant tumours of the gastrointestinal tract (Alwmark et al. 1980; Spira et al. 1977). The present paper describes a duodenal carcinoma arising in a mixed tubulo-villous non-Vaterian adenoma in a 68 year old male. Immunocytochemical analysis revealed evidence of neuroendocrine differentiation in both adenoma and carcinoma. In a review of the literature a correlation between the size of adenoma and the probability of concomitant carcinoma is demonstrated. Duodenal adenoma measuring more than 4 cm in diameter should be considered potentially malignant.
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  • 34
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    Virchows Archiv 414 (1989), S. 453-457 
    ISSN: 1432-2307
    Keywords: Ovarian tumours ; Tissue polypeptide antigen ; Light and electron microscopy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty specimens of benign and malignant ovarian tumours were studied for localization of tissue polypeptide antigen (TPA) at light and electron microscopic levels by an indirect immunoperoxidase technique. Of the 30 ovarian carcinomas, 23 (77%) were positive and 7 (23%) were negative for TPA, while of the 10 benign ovarian tumours 3 (30%) were positive and 7 (70%) were negative. Positive reaction did not correlate with the tumour grade. Of the 10 patients with metastasis, 8 (80%) had positive tumours. Staining for TPA was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of TPA revealed electron-dense reaction products at the cell surface and microvillous surfaces. These results provide confirmatory and supplementary evidence to support the previous findings of TPA in the serum and suggest that testing for TPA in ovarian tumors has a limited prognostic importance and a poor diagnostic value. The surface property of TPA suggests that the cell membrane is involved in secretion and probably synthesis of TPA.
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  • 35
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    Virchows Archiv 415 (1989), S. 91-95 
    ISSN: 1432-2307
    Keywords: Carcinosarcoma ; Urinary bladder ; Immunohistochemistry ; Electron microscopy ; Rhabdomyoblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of urinary bladder carcinosarcoma (UBCS) is reported with light, immunohistochemical and electron microscopical findings. The tumour consisted of a squamous cell carcinoma, variable spindle cell stromal elements compatible with fibrosarcoma, and rhabdomyoblasts. Intermediate filament co-expression of cytokeratin and vimentin was shown by immunohistochemistry. Electron microscopy (EM) confirmed the nature of the three components, and indicated some similarities between the three cell-types present. Comparisons with the previous UBCS in the literature are made.
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  • 36
    ISSN: 1432-2307
    Keywords: Trichosporon ; Candida ; Immunohistochemistry ; Autopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of disseminated trichosporonosis associated with Candida infection of the urinary bladder is presented. Coffee bean shaped or crescent shaped yeast-like elements are characteristic of Trichosporon and useful in differentiating Trichosporon fromCandida but such histological features are less efficient than the immunohistochemistry in identifing mixed fungal infection. In the present case, an application of avidin-biotin-complex (ABC) method with anti -Trichosporon antiserum and anti-Candida antiserum enabled us to diagnose a mixed infection by both fungi.
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  • 37
    ISSN: 1433-8580
    Keywords: Atrial natriuretic peptide ; ANP ; Gastrointestinal tract ; Gut ; Biopsies ; Endoscopy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The human gastrointestinal tract, important for body salt and water balance, was investigated by endoscopic biopsy for the presence of atrial natriuretic peptide (ANP). Using immunohistochemistry, ANP-immunoreactive cells were identified in the lamina epithelialis mucosae of stomach, duodenum, jejunum, colon, and rectum. The findings indicate that ANP plays a role in intestinal salt and water regulation in man. ANP measurements in tissue specimens reached by endoscopic biopsy may be of major interest for future investigations on (patho-)physiological and pharmacological aspects of ANP.
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  • 38
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    Acta neuropathologica 78 (1989), S. 258-263 
    ISSN: 1432-0533
    Keywords: Teratoma ; Microglia ; Nervous tissue ; Immunohistochemistry ; Tumor markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten human teratomas arising outside the central nervous system (CNS) were studied using a panel of immunohistochemical, and lectin histochemical stains to determine the relationship of the presence of microglia to markers of neural maturity or differentiation. Microglia, identified by silver carbonate,Ricinus communis agglutinin-1 (RCA-1), or both were found in eight out of ten cases. They were common in mature areas which also had S-100, glial fibrillary acidic protein, vimentin, neurofilament, and synaptophysin immunostaining. Microglia were distinguished from macrophages in necrotic foci. Cells which were RCA-1 positive and silver carbonate positive were found in immature neural tissues but these lacked all typical features of microglia. These observations indicate that true microglia are frequent in nonCNS teratomas and that they are found in association with other indicators of neural maturation. The presence of possible precursors in immature areas suggests that microglia undergo maturation concurrent with neural differentiation in these tumors.
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  • 39
    ISSN: 1432-0533
    Keywords: Globus pallidus ; Immunohistochemistry ; Calcineurin ; Synaptophysin ; Neuropeptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The afferent nerve terminal in the human globus pallidus, which receives the projection nerve fibers from both the striatum and the subthalamic nucleus, were clearly visualized immunohistochemically using antibodies to calcineurin, synaptophysin, Met-enkephalin (MEnk) and substance P (SP). In normal control case, MEnk and SP-like immunoreactivities were densely localized in the external and internal pallidal segments, respectively, whereas calcineurin and synaptophysin were distributed throughout the globus pallidus. Calcineurin, synaptophysin, MEnk and SP-like immunoreactive peroxidase products decorated most of the long radiating dendrites and the cell bodies of the pallidal neurons. In the cases with Huntington's disease (HD) and striatonigral degeneration (SND), marked loss of calcineurin, MEnk and SP-like immunoreactivities was seen in the globus pallidus corresponding to areas of striatal neurodegeneration, whereas synaptophysin immunoreactivity remained in areas which revealed almost complete loss of calcineurin, MEnk and SP-like immunoreactivities. Calcineurin, MEnk and SP, which show difference in their localization patterns, may provide reliable markers for the striatal efferent nerve terminals, and synaptophysin for the entire pallidal afferent nerve terminals. This report demonstrates the distribution patterns of these neurochemical molecules in the globus pallidus with HD and SND.
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  • 40
    ISSN: 1432-0533
    Keywords: Purkinje cell ; Immunohistochemistry ; Axon ; Phenytoin ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytion. Thirty male C57BI/6J mice received phenytion orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion.
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  • 41
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    Acta neuropathologica 77 (1989), S. 445-448 
    ISSN: 1432-0533
    Keywords: Ectopic meningioma ; Immunohistochemistry ; Pathogenesis ; Electron microcopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral nerve meningiomas are exceedingly rare neoplasms of controversial origin; only four cases have been reported. Proposed origins of ectopic meningiomas include extradural trapping of arachnoid cells during embryogenesis, ectopic migration of arachnoid cell nests with the developing peripheral nerve, and metaplasia of mature peripheral nerve sheath cells or a common progenitor cell. In this report of a meningioma of the brachial plexus, immunohistochemical and ultrastructural examinations of the tumor matched all the criteria of a traditional meningioma but failed to clarify the origins of such neoplasms.
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  • 42
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    Acta neuropathologica 77 (1989), S. 569-575 
    ISSN: 1432-0533
    Keywords: Monoclonal antibody ; Microglial cells ; Alzheimer's disease ; Senile plaques ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A monoclonal antibody, termed AD11/8, reactive to microglial cells, was produced by immunization of mice with partially purified amyloid fibrils of senile (neuritic) plaques. With immunoperoxidase staining on human tissues, AD11/8 also recognized macrophages in the red pulp of the spleen, Kupffer cells in the liver, and macrophages in the bone marrow. The results show that AD11/8 recognizes the antigens associated with mononuclear phagocytes lineage. In normal brains a few resting microglial cells were stained in gray matter, and less frequently in white matter. In senile dementia of the Alzheimer type numerous microglial cells were stained intensively and they often formed clusters in gray matter. By double immunostaining with AD11/8 and a polyclonal antibody against synthetic amyloid β-protein, clustered microglial cells were observed in and around senile plaques with amyloid deposits. Some amyloid plaque cores were surrounded by microglial cell processes. These results indicate that microglial cells may play an important role in senile plaque formation.
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  • 43
    ISSN: 1432-0533
    Keywords: Serotonin ; Neostriatum ; Hyperthermia ; Seizure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Changes occurring in serotonin neurons during hyperthermia and hyperthermia-induced convulsions were examined by quantiative immunohistochemistry. A marked increase in serotonin immunoreactivity was observed at the rostral and intermediate levels of the neostriatum of mice kept at high temperatures with no convulsions, and a significant reduction in serotonin immunoreactivity was verified throughout the neostiatum of mice which had hyperthermia-induced seizures. These results suggest that serotonin neurons change significantly during thermal stress and seizures, and that regional analysis is essential for an understanding of the role of serotonin neurons.
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  • 44
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    Anatomy and embryology 180 (1989), S. 143-149 
    ISSN: 1432-0568
    Keywords: Development ; Adenohypophysis ; Immunohistochemistry ; Lizard ; Gallotia galloti
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical methods have been used to study the embryonic and postnatal development of the hormone-producing cells in the adenohypophysis of the lizard Gallotia galloti. In this species, Rathke's pouch is formed between stages 30 to 32 of the embryonic development, although the first sign of immunoreactivity to antisera against adenohypophysial hormones occurs in stage 33 in the pars distalis anlage. These cells derive from the dorsal face of Rathke's pouch and are immunoreactive to anti-ACTH serum. The cytodifferentiation of ACTH and MSH cells occurs in the pars intermedia in stage 34. The TSH cells appear at stage 35 and the gonadotrope cells at stage 37. These cells derive from both the dorsal and ventral face of the Rathke's pouch. The LTH cells are revealed at stage 39 and are only originated from the dorsal face. The STH cells, which come from the dorsal as well as ventral face, are the last secretory cells differentiated just before hatching. During postnatal development an increase and also a redistribution of the immunoreactive cells occur until acquiring the adult distribution.
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  • 45
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    Anatomy and embryology 180 (1989), S. 159-163 
    ISSN: 1432-0568
    Keywords: Ontogeny ; Neuron-specific enolase ; Taste buds ; Vallate papillae ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The detailed morphology of the nerve fibers and the taste bud cells in developing vallate papillae of the rat tongue was investigated utilizing the immunoperoxidase technique to detect neuron-specific enolase (NSE). For convenience of description, five stages of development were defined: Stage 1, the fifteenth and the sixteenth embryonic day (E15–E16): NSE like immunoreactive (NSE-) nerve fibers, with some random arborization, appeared around the median lingual sulcus at the base of the tongue; Stage 2 (E16–E17): NSE-nerve fibers invading the central core of newly formed vallate papilla and underlying the apical epithelium of the papilla; Stage 3 (E18–E21): round-shaped undifferentiated NSE-taste bud cells appearing in the apical epithelium; Stage 4, the first day of postnatal age (P1): NSE-taste bud cells migrated to the side epithelium, lining the gutter beneath which the nerve plexus formed during E18–E21, and extended cytoplasmic process toward the surface and/or the basal lamina; Stage 5 (P3–P5): NSE-nerve fibers and spindle-shaped NSE-taste bud cells with a typical figure of taste bud cells appeared in newly formed taste buds in the side epithelium, lining the gutter. The sequential topographic development of nerve preceding NSE-taste bud cells in precise morphological locations, suggests that the ingress of precursor NSE-taste bud cells and their subsequent differentiation are contingent upon initial neural derived ontologic signals.
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  • 46
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    Anatomy and embryology 179 (1989), S. 387-393 
    ISSN: 1432-0568
    Keywords: Distribution pattern ; Creatine kinase isozymes ; Embryonic chicken heart ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution pattern of creatine kinase (EC 2.7.3.2) isozymes in developing chicken heart was studied by immunohistochemistry. Creatine kinase M, which is absent from adult heart, is transiently expressed between 4 and 11 days of incubation. During that period, numerous muscular cells in the roof and septum of the atrium, in the interventricular septum and on top of the trabeculae cordis and at the rim of the outflow tract stain strongly with a polyclonal antibody that is specific for the M subunit. In the ventricle and outflow tract, the M-positive cells are found mainly subendocardially and in the right half, at the transition of conducting and working myocytes. Creatine kinase B, which is the predominant adult isozyme, is initially expressed to a high concentration in a small group of disperse myocardial cells in the upstream part of the inflow tract. When compared to the expression pattern of cardiac myosin heavy chains, the observed creatine kinase expression pattern suggests that M-positive cells are mainly found in areas that participate in the formation of cardiac conductive tissue, whereas B-positive cells are first found in areas that are involved in the generation of cardiac rhythm.
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  • 47
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    Acta neuropathologica 78 (1989), S. 159-165 
    ISSN: 1432-0533
    Keywords: Encephalitis ; Encephalomyelitis ; Immunohistochemistry ; Pathogenesis ; Rabies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spread of rabies virus in the central nervous system of mice was examined after hindlimb footpad and intracerebral inoculation of the CVS strain of fixed rabies virus. All mice developed paralytic rabies. After intracerebral inoculation there was early simultaneous infection of neurons in the cerebral cortex and pyramidal neurons of the hippocampus, and later there was spread to the cerebellum. After high-dose intracerebral inoculation there was early infection ependymal cells lining the lateral ventricles and neurons adjacent to the central canal of the spinal cord, suggesting that rabies virus entry into the CNS occurs, at least in part, by a cerebrospinal fluid pathway. The sequence of involvement was different after hindlimb footpad inoculation. Infection became established in the cerebellum on day 5, in the cerebral cortex on day 6, and in the hippocampus on day 8. CA3 was initially affected, CA1 became infected 2 days later, and there was much less involvement of the dentate gyrus. Hippocampal infection occurred late relative to the rest of the brain after peripheral inoculation, but not after intracerebral inoculation. The hippocampus is not a good location for the detection of early brain infection after peripheral inoculation, although it may be involved when a natural rabies vector has the ability to transmit infection. These findings also raise questions about the mechanisms for the limbic dysfunction observed in clinical rabies.
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  • 48
    ISSN: 1432-0533
    Keywords: Protein kinase C ; Proliferative activity ; Immunohistochemistry ; Human brain neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protein kinase C (PKC), the major receptor for phorbol ester tumor promotors, is a phospholipid- and calcium-dependent phosphorylating enzyme which plays an important role in the intracellular signal transduction necessary for a variety of basic cellular functions including the control of cell proliferation. To determine the expression of PKC in human neurogenic tumors we investigated 121 tumors of the human nervous system by means of immunohistochemistry using the monoclonal antibody C5. The results were compared with immunohistochemical staining for intermediate filament proteins, desmoplakins, and the proliferation-associated nuclear antigen Ki-67. Besides strong staining of normal and reactive astrocytes, C5 immunoreactivity was consistently observed in tumor cells of all types of gliomas. However, the fraction of C5 positive tumor cells varied between the different tumor types with astrocytomas and subependymomas demonstrating the strongest immunoreactivity. In the other gliomas, especially those of higher malignancy, a considerable heterogeneity in C5 expression could be observed. There was a tendency for the percentage of C5 immunostained tumor cells being lower in high-grade gliomas compared to low-grade ones and comparison with Ki-67 staining frequently revealed an inverse relationship between proliferative activity and C5 immunoreactivity. Besides the gliomas we found 3 of 7 neurinomas and 6 of 18 meningiomas which were partially C5 positive. All other tumors investigated including medulloblastomas and metastatic carcinomas were C5 negative. Our results thus indicate that immunohistochemistry for PKC using the monoclonal antibody C5 could be an useful aid for histopathological tumor classification in neurooncology.
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  • 49
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    Acta neuropathologica 78 (1989), S. 332-335 
    ISSN: 1432-0533
    Keywords: Gliosarcoma ; Subependymoma ; Immunohistochemistry ; Factor VIII-related antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of a recurrent posterior fossa subependymoma in a 60-year-old man is reported. In the recurrent tumor, the vasculature had undergone apparent sarcomatous proliferation of the endothelial cells. The bizarre cells expanded and replaced the vessel walls, and stained for Factor VIII-related antigen. The literature on gliosarcomas arising in brain tumors other than high-grade gliomas is reviewed.
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  • 50
    ISSN: 1432-0533
    Keywords: Somatostatin ; Immunohistochemistry ; Aganglionosis ; Man ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of somatostatin-like immunoreactive (SOM-LI) nerves was elucidated immunohistochemically in the gut tissues from patients with Hirschsprung's disease and congenital aganglionosis rats. In the normoganglionic human colon, SOM-LI nerve cell bodies were found to a greater extent in the submucous plexus and to a lesser extent in the myenteric plexus. However, they were rarely observed in both the plexuses of the oligoganglionic segment. SOM-LI nerve fibres were widely distributed in the aganglionic bowel. The circular muscle layer of the distal aganglionic segment was densely innervated by SOM-LI nerve fibres which are probably derived from the extrinsic, hypertrophic nerve bundles. A decreased number of the intramuscular nerves fibres were seen in the proximal aganglionic segment. In the colon and rectum from adult and 21-day-old rats, SOM-LI cell bodies were numerous in both plexuses. On the other hand, enteric neurons were completely lacking from the colon and rectum of congenital aganglionosis rats of 21 days old. No neuronal elements staining for SOM were disclosed in these aganglionic segments of mutant rats. A possible origin and pathophysiological role of the extrinsic nerve fibres containing SOM in the diseased bowel are discussed. It is concluded that SOM-LI nerves in the human distal colon comprise both intrinsic and extrinsic elements, while SOM nerves in the rat colon and rectum are of only intrinsic origin.
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  • 51
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    Acta neuropathologica 78 (1989), S. 472-483 
    ISSN: 1432-0533
    Keywords: Astroblastoma ; Electron microscopy ; Immunohistochemistry ; Organ culture ; Tanycytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two examples of cerebral astroblastoma have been studied by electron microscopy and immunohistochemistry, one of them having been maintained in vitro in an organ-culture matrix system for 8 months and the explants studied by light and electron microscopy at different time intervals. The fine structural characteristics were those of a glial cell type with features intermediary between those of astrocytes and ependymocytes. They recapitulated the structure of the tanycyte, a glial precursor cell which is normally found scattered along the ependymal lining of the embryonal and neonatal mammalian brain, but is distinct from epithelial ependymocytes. The possible origin of some astroblastomas from such a cell would account for a number of characteristics in this enigmatic type of glioma.
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  • 52
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    Anatomy and embryology 180 (1989), S. 65-69 
    ISSN: 1432-0568
    Keywords: Laminin ; Basement membrane ; Avian embryos ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used immunohistochemical techniques to study laminin in quail blastoderms milked from the oviduct and the distribution of laminin in laid chicken and quail blastoderms. Laminin is a constituent of the basement membrane in both chicken and quail blastoderms. It is found at the ventral side of the upper layer cells. Laminin is first observed under individual upper layer cells in prelaid quail blastoderms 15 h post-ovulation, but is absent at the ingression site of endophyll cells. The presence of a continuous laminin layer coincides with the epithelialization of the epiblast after 5–10 h incubation. The laminin layer is discontinuous at the primitive streak and at Hensen's node. It is thinner and partly discontinuous at the median part of the neural plate. By induction, either of an ectopic primitive streak or a neural plate, we have demonstrated, using the chicken-quail nucleolar marker technique, that at these sites the laminin layer is interrupted. A laminin layer might confer rigidity onto the epiblast, whereas disruption of a laminin layer seems to be correlated with ingression of cells or bending of the neural plate.
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  • 53
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    Acta neuropathologica 78 (1989), S. 65-71 
    ISSN: 1432-0533
    Keywords: Striatonigral degeneration ; Basal ganglia ; Calcineurin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The basal ganglia (including substantia nigra) of two patients with striatonigral degeneration, who had clinical histories of Parkinson's disease, were studied immunohistochemically using a purified antibody to calcineurin (CaN). Marked loss of CaN-immunoreactive neurons in the putamen and neuromelanin-pigmented neurons in the zona compacta of the substantia nigra was seen in both cases. A small number of CaN-immunoreactive neurons remained dispersed in “clusters” or “islands” in the medial portion of the putamen. In one case there was loss of CaN-immunoreactive neurons in the caudate nucleus to a lesser degree than that in the putamen. In addition, both cases showed marked depletion of CaN-immunoreactive afferent nerve fibers in the external and internal segments of the globus pallidus and the zona reticulata of the substantia nigra. This report emphasizes the usefulness of the CaN-immunostaining technique for assessing the striatal efferents in human basal ganglia, and shows the neuropathological changes in the basal ganglia with striatonigral degeneration which were not possible to ascertain with previous techniques.
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  • 54
    ISSN: 1432-0533
    Keywords: Immunohistochemistry ; Medulloepithelioma ; Cytoskeletal proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four examples of human cerebral medulloepithelioma were studied immunohistochemically with a panel of antibodies and antisera to neuronal and glial proteins. The tumors, in addition to primitive medullary epithelium, contained areas of neuroblastic, ganglionic, astrocytic, ependymoblastic and ependymal differentiation, and, in one tumor, areas resembling polar spongioblastoma. Tumor cells throughout the primitive medullary epithelium displayed focal immunocreactivity for vimentin, glial fibrillary acidic (GFA) protein and for the neuron-associated class III β-tubulin isotype. Neuroblasts showed immunoreactivity for the class III β-tubulin isotype, microtubule-associated protein 2 and neuron-specific enolase. Immunoreactivity for neurofilament epitopes and synaptophysin was detected in areas of ganglionic differentiation and coincided with the demonstration of neurofibrils in Bielschowsky's silver impregnations. Vimentin was the only marker detected in ependymoblastic and ependymal rosettes or in areas of polar spongioblastoma, as well as in mesenchymal, cells. The results indicate that, even in very primitive neoplastic neuroepithelium, immunocytochemical evidence of early commitment of some of the cells to a neuronal or glial lineage can be demonstrated. The neuron-associated class III β-tubulin isotype appears to be one of the earliest markers indicative of neuronal differentiation in normal and neoplastic primitive neuroepithelium.
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  • 55
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    Acta neuropathologica 79 (1989), S. 305-309 
    ISSN: 1432-0533
    Keywords: Gliosarcoma ; Immunohistochemistry ; Histiocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gliosarcomas contain both neuro-ectodermal and mesenchymal elements. Its histogenesis has been much debated and endothelial and adventitial fibroblast origins have been suggested, as has a “histiocytic” origin following the demonstration of antiprotease activity. Eight gliosarcomas have been examined with a panel of ten monoclonal and polyclonal antibodies to investigate the origin of the sarcomatous element. Glial fibrillary acid protein expression showed a sharp distinction between gliomatous and sarcomatous tumour components. Contrary to some previous reports factor 8-related antigen and Ulex europeus agglutinin stained vascular luminal endothelium but no tumour cells. Vimentin and fibronectin expression was extensive and confined largely to sarcomatous areas. Desmin and neurofilament protein could not be demonstrated in any of the cases. Numerous cells, particularly in the sarcoma areas, expressed alpha-1-antitrypsin and-chymotrypsin. A proportion of these stained for the monocyte/macrophage marker MAC 387. Four cases focally exhibited a true stori-form pattern and this and the immunohistochemical results suggest analogies with the fibrous histiocytomas. These tumours contain reactive histiocytes but are now thought to be derived from fibroblasts or from pluripotent mesenchymal cells in perivascular adventitia. This resembles the pattern exhibited in the sarcomatous component of gliosarcomas.
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  • 56
    ISSN: 1432-0533
    Keywords: Glial fibrillary acidic protein ; Vimentin ; Immunohistochemistry ; Ethylnitrosourea ; Rat Gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immuno-histochemically in 104 experimental gliomas induced by transplancental application of ethylnitrosourea (ENU) in CDF rats. Immunoreactivity for vimentin was prominent in many astrocytic tumor cells and especially in small glioma cells forming anaplastic medulloblastoma-like foci in many tumors. The majority of tumor cells in oligodendroglial tumors were vimentin negative, except for some of the large polymorphous oligodendrogliomas which contained intermingled vimentin positive glioma cells. GFAP immunoreactivity was detectable only in a low fraction of tumor astrocytes and in a few exceptional cases some oligodendroglial tumor cells stained positive. Immunohistochemistry with antibodies against neurofilaments and cytokeratins revealed no staining in tumor cells of ENU-induced gliomas, while all oligoden-drogliomatous tumors stained positive for HNK-1. Immunocytological and immunoblot investigations of the two rat glioma cell clones RG2 and F98, which are both derived from ENU-induced gliomas, showed a prominent expression of vimentin in monolayer cultures and in syngeneic intracerebral transplantation tumors. F98 additionally demonstrated a fraction of GFAP positive cells especially in confluent cultures and in intracerebral tumors. RG2, on the other hand, exhibited virtually no GFAP immunoreactivity in culture but showed individual GFAP positive tumor cells in intracerebral tumors. Our results revealed a more precise picture of the cellular differentiation in ENU-induced rat gliomas and in two widely used glioma cell lines. They underline the heterogeneity of experimental rat gliomas which may comprise cells at different stages of differentiation towards the oligodendroglial or astroglial phenotype.
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  • 57
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    Acta neuropathologica 78 (1989), S. 325-328 
    ISSN: 1432-0533
    Keywords: Ependyma ; Ependymoma ; Epithelial membrane antigen ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ependyma and choroid plexus of 23 normal brains and 20 ependymal tumors were examined immunohistochemically for expression of epithelial membrane antigen (EMA) using a specific monoclonal antibody. The ependyma of normal brains showed three patterns of immunoreactivity: membrane immunoreactivity confined to the luminal surface; irregular punctate intracytoplasmic immunore-activity in the subependymal layer; and spherical and ring-like intracytoplasmic immunoreactivity in the subependymal layer. Of 13 differentiated ependymomas 11 reflected the immunoreactive patterns of normal ependyma. The anaplastic ependymomas and ependymoblastomas had no immunoreactivity. Our results indicate that EMA has a highly selective distribution in the ependyma, and is a marker for differentiated ependymoma.
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  • 58
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    Acta neuropathologica 78 (1989), S. 594-604 
    ISSN: 1432-0533
    Keywords: Neurocysticercosis ; Pathogenesis ; Histochemistry ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was based on two cases of disseminated human neurocysticercosis from India. The material availabel was examined grossly, and by light microscopy, histochemistry, immunomorphology and electron microscopy. The results showed that the parasites commonly embolized to the anatomically discernable gray-white matter junction of the brain and were located in cavities, the walls of which were dilated vascular channels. The parasite-nutrition process was through endocytosis and microtrichal activity. To camouflage themselves from the host-defense mechanisms, the parasites apparently covered themselves with host-tissue-like material. Host reactivity to the parasite was heralded morphologically by the physical anchoring of the parasite by activated endothelial cells, loss of the host-tissue-like cover and an acute polymorphonuclear leucocytic response.
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  • 59
    ISSN: 1432-0568
    Keywords: Immunohistochemistry ; Substance P ; Heart innervation ; Conduction system ; AV bundle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is limited information on the distribution of nerve fibers containing substance P (SP) in the heart conduction system. Therefore, in the present study, the various parts of the conduction system of the bovine heart were examined by the use of an SP-antiserum and immunohistochemistry. Nerve fibers showing SP-like immunoreactivity (SP-LI) occurred in the proximities of conduction cells in all parts of the conduction system, but were present in greatly larger numbers in the AV bundle than in the other parts. The nerve fibers showed a predilection for certain regions of the bundles of conduction cells (Purkinje fiber bundles) in the AV bundle and the bundle branches and their ramifications. Nerve fibers showing SP-LI also occurred in the walls of the arteries and in association with some the ganglionic cells located in the regions of the conduction system. None of the ganglionic cells exhibited SP-LI. The observations are discussed in relation to what is known of the function of SP in the heart and of the distribution of sympathetic and parasympathetic nerve fibers in the conduction system. As SP is regarded as a marker of afferent fibers the observations support the view that afferent nerve fibers are present throughout the conduction system. It is likely that the existence of a significant SP-innervation in the conduction system is of importance for the function of this part of the heart.
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  • 60
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    Annals of hematology 58 (1989), S. 129-132 
    ISSN: 1432-0584
    Keywords: Amyloidosis ; Immunoglobulin λ-light chains ; Immunohistochemistry ; Immunoperoxidase ; Anti-amyloid antibodies ; Immunologic cross-reactions ; Horse ; Nasal tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tumorous amyloid deposits in the nasal mucosa of two horses differed from generalized AA-amyloidosis with respect to clinical features, organ distribution, and resistance to KMnO4 treatment. Using a panel of antibodies directed against different human amyloid fibril proteins and employing the peroxidase-anti-peroxidase (PAP) technique, we showed the described equine amyloid to be Aλ-type, as demonstrated by immunohistochemical cross-reactivity. Consequently, we identified a second amyloid class in horses and showed that immunoglobulin light-chain-derived amyloid may also be present in animals.
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  • 61
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    Acta neuropathologica 77 (1989), S. 654-658 
    ISSN: 1432-0533
    Keywords: Melanotic neuroectodermal tumor ; Immunohistochemistry ; Ultrastructure ; Pineal origin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of a melanotic neuroectodermal tumor arising from pineal region of a 4-year-old girl is presented. The tumor had spread diffusely to the meninges, consistent with malignant behavior. Histologically, the tumor consisted primarily of epithelial elements arranged in tubules, cords and nests separated by fibrous vascular tissue in addition to a small neuroblastomatous focus. Melanin pigment was frequently observed in the epithelial tumor cells, and melanin-laden macrophages were also often observed. No teratoid elements were found. Immunohistochemically, tumor cells were positive for neuron-specific enolase but were nonreactive for S-100 protein, epithelial membrane antigen, glial fibrillary acidic protein, vimentin, α-fetoprotein and human chorionic gonadotrophin. Ultrastructurally, the epithelial nature of the tumor cells could be easily demonstrated. In addition, melanosomes in various stages in maturation were observed, indicating melanogenesis of the tumor. On the basis of the tumor location and the histological similarities previously observed for the fetal pineal body, it is very likely that this melanotic epithelial tumor could have originated from the fetal pineal gland.
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  • 62
    ISSN: 1432-0533
    Keywords: Gangliocytoma ; Ganglioglioma ; Ultrastructure ; Immunohistochemistry ; Neuroendocrine markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied five cases of central nervous system neuronal tumor, one gangliocytoma and four gangliogliomas, both ultrastructurally and immuno-histochemically, using antibodies to neuroendocrine markers including tyrosine hydroxylase (TH), serotonin (5HT), somatostatin (SOM), met-enkephalin (MEK), leu-enkephalin (LEK), substance P (SP), gastrin, vasopressin, oxytocin, vasoactive intestinal polypeptide, adrenocorticotropic hormone and calcitonin. In all cases, the presence of dense-core vesicles (60–250 nm) in the neuronal elements was the characteristic ultrastructural finding. Synapses were observed in two cases. Immunohistochemically, variable numbers of neuronal cells showed positive staining for SOM in five cases, TH, MEK and LEK in three cases, and 5HT and SP in one case each. The others were negative. Positive immunoreactivity for multiple markers was shown in all cases. SOM, TH, 5HT and SP were present in the small- to medium-sized cells, while MEK and LEK were almost exclusively confined to the large cells. Our study clearly indicated that these tumors contained neuronal cells which were not homogeneous with regard to neuroendocrine markers.
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  • 63
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    Acta neuropathologica 77 (1989), S. 258-266 
    ISSN: 1432-0533
    Keywords: Neurofibrillary tangles ; Alzheimer's disease ; Pick bodies ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the immunohistochemical reactivity and ultrastructure of both neurofibrillary tangles (NFTs) occurring with severe neurofibrillary diseases, and Pick bodies (PBs) associated with Pick's disease. The NFTs and PBs did not react immunohistochemically with the anti-nonphosphorylated neurofilament monoclonal antibody irrespective of whether they were pretreated with alkaline phosphatase. In granular neurons of the dentate fascia of Ammon's horn in cases of dementia of the Alzheimer type (DAT), NFTs either resembled PB-like inclusion bodies (Horoupian's inclusion bodies) in form, or had a perinuclear structure. Immunohistochemically and ultrastructurally, the NFTs in the dentate fascia in cases of DAT, including Horoupian's inclusion bodies, were similar to the NFTs in the pyramidal neurons of Ammon's horn, which are found most frequently in association with severe neurofibrillary diseases. Under a light microscope, Horoupian's inclusion bodies and PBs could not be differentiated and appeared to be argyrophilic round cytoplasmic inclusions in granular neurons of the dentate fascia. There were, however, ultrastructural differences. Horoupian's inclusion bodies consisted of bundles made up of straight tubules (STs), each about 15 nm in diameter. These bundles were intermixed with a few paired helical filaments which occurred at intervals of about 80 nm. On the other hand, PBs were composed of randomly distributed 15-nm-wide STs, intermixed with a very few fibrillary structures. These fibrils had a periodicity of about 160 nm, and ranged in width from about 15 nm to 30 nm. Horoupian's inclusion bodies associated with DAT and PBs associated with Pick's disease are different in this neuropathological aspect. The NFTs, including Horoupian's inclusion bodies in the dentate fascia in cases of DAT, are considered to be a manifestation of neurofibrillary degeneration.
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  • 64
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Bromodeoxyuridine ; Cerebral endothelium ; Immunohistochemistry ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is still unknown when and in which area endothelial regeneration occurs after brain injury, and to what extent such changes depend on the severity of the injury. We have, therefore, studied bromodeoxyuridine (BrdU) uptake by regenerating endothelial cells in two different groups of rats given cold lesions using immunohistochemistry employing anti-BrdU monoclonal antibody, anti-factor VIII-related antigen antibody and anti-glial fibrillary acidic protein antibody. The earliest evidence for the presence of BrdU-positive endothelial cells (BrdU+end) was observed at 2 days after injury, the injured endothelial cells regenerating from the edge toward the center of the lesion in both groups. We considered that edema fluid could act as an important factor, since at 2 days post-injury BrdU+end were not in contact with macrophages and were always found in Evans blue-stained areas. Study of endothelial cell kinetics also confirmed that the repair of injured endothelial cells was intimately involved in the reconstruction of the blood-brain barrier, since the time of disappearance of BrdU+end coincided with the disappearance of Evans blue-stained areas. The difference in the process of endothelial regeneration was first apparent on the 3rd day, there being no difference at 2 days.
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  • 65
    ISSN: 1432-0533
    Keywords: Experimental allergic neuritis ; Monocytes ; Immunohistochemistry ; Electrophysiology ; Resident dendritic cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological, clinical and histological techniques were used to monitor the time course of events related to experimental allergic neuritis (EAN) in 48 Lewis rats. The primary lesion was found to be paranodal demyelination without cellular infiltration. Endoneural phagocytes derive from hematogenous ED1+ED2− monocytes and possibly from resident ED1− ED2+ monocytic cells, not from Schwann cells and fibroblasts. We demonstrate a population of monocytic Ia-bearing, ED1−ED2+ spindle-shaped cells residing in normal peripheral nerve and provide evidence for their transformation into macrophages in the course of EAN.
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  • 66
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    Acta neuropathologica 79 (1989), S. 27-29 
    ISSN: 1432-0533
    Keywords: Malignant lymphoma ; Non-Hodgkin lymphoma ; Brain tumor ; Tumor-infiltrating lymphocyte ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical study was performed on small lymphoid cells present in frozen tissue sections of seven cases of primary B cell malignant lymphomas of the brain by using monoclonal antibodies to T cell (Leu-1, OKT-11, Leu-3a, and Leu-2a) and B cell (BA-1 and Leu-12) surface markers. In all the seven cases, positive reaction for Leu-1 and OKT-11 was seen in the majority of the small lymphoid cells which were dispersed among the lymphoma cells or clustered around blood vessles. The large neoplastic cells were unstained by these antibodies. Staining for T cell subsets with antibodies to Leu-3a and Leu-2a showed heterogeneous staining in each case. The ratio of Leu-3a+ to Leu-2a+ cells was less than one in six cases, demonstrating a suppressor/cytotoxic phenotype predominance. Most of these small lymphoid cells were negatively stained by antibodies to BA-1 and Leu-12. From these findings, it was shown that the small lymphoid cells observed in primary B cell lymphomas of the brain were of T cell lineage, distinct from the neoplastic cells, and probably reactive in nature. The implications of these findings are discussed.
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  • 67
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Phosphorylated neurofilament ; Immunohistochemistry ; Lewy body-like inclusion ; Cord-like neurite thickening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distribution of phosphorylated neurofilament proteins within anterior horn cells in three cases of familial and six cases of sporadic amyotrophic lateral sclerosis (ALS) and ten control cases were investigated by using a monoclonal antibody. Two distinct staining patterns of perikarya were observed; (1) homogeneous pattern; either the entire or a part of the perikaryon was immunostained homogeneously (homogeneously diffuse or partial pattern); (2) focal pattern: perikarya contained very distinct, inclusion-like focal accumulation of immunoreactive products of various morphologies such as round, ring-shaped, cord-like, tube-like and more irregular shapes. The homogeneous pattern was found in all three groups but was most common in sporadic ALS. On the other hand, the focal pattern was seen almost exclusively in familial ALS. The focal accumulation of neurofilaments appears at least in part to be related to the Lewy body-like hyaline inclusion which is known to contain neurofilaments. In addition, cord-like swellings of neurites in familial ALS also showed focal neurofilament accumulation. These observations suggest that the focal accumulation of phosphorylated neurofilaments is characteristic of familial ALS, although it may not be specific to the entity. The pathological process(es) producing the neurofilamentous abnormality may play an important role in anterior horn cell degeneration in familial ALS.
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  • 68
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    Acta neuropathologica 79 (1989), S. 129-136 
    ISSN: 1432-0533
    Keywords: Ferritin ; Microglia ; Immunohistochemistry ; Scrapie-associated fibrils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical analysis of formalin-fixed, paraffin-embedded brain sections was performed with antisera against holoferritin and the light(L)-subunit of ferritin. Sections immunostained using anti-glial fibrillary acidic protein (GFAP), Ricinus communis agglutinin-1 (RCA-1) stain for microglia and iron stain (Berlin blue stain) were compared. The L-subunit of ferritin was purified from normal human spleen according to the modified scrapie-associated fibrils purification, and the antiserum was raised in a rabbit. Both ferritin antisera positively stained resting and, more markedly, reactive microglia, both of which were also stained with RCA-1 but not with GFAP. Ferritin-positive resting microglia were seen more abundantly in cerebral and cerebellar cortices than in white matter. The advantages of ferritin antisera over RCA-1 are as follows. (1) RCA-1 heavily stains blood vessels, while anti-ferritin does not, hence the microglial cells are more readily visualized with ferritin immunohistochemistry. (2) Reactive microglia and macrophages are more strongly stained with anti-ferritin. (3) The staining intensity of ferritin is independent of the length of tissue fixation in formalin. However, anti-ferritin is inferior to RCA-1 in staining resting microglia with a scanty cytoplasm, especially in the white matter, probably because the former recognizes cytoplasmic components, while the latter recognizes cell membrane. Iron stain only gave a reaction to microglial cells in brains with neurosyphilis and to hemosiderin-laden macrophages. Thus, in addition to RCA-1, ferritin antisera are useful as a microglia marker in formalin-fixed, paraffin-embedded sections.
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  • 69
    ISSN: 1432-0533
    Keywords: Neurofibromatosis 2 ; Bilateral acoustic neurofibromatosis ; Ghal hamartomas ; Immunohistochemistry ; S-100 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bilateral acoustic neurofibromatosis (neurofibromatosis 2, NF2) accounts for less than 10% of all cases of neurofibromatosis and manifests itself with bilateral acoustic schwannomas, multiple schwannomas of spinal nerve roots, meningiomas, glial tumors and hamartomatous CNS lesions. We have observed dysplastic foci of immature neuroectodermal cells in the cerebral cortex and basal ganglia of six patients afflicted with neurofibromatosis 2, ranging from occasional clusters of immature, dysplastic cells to numerous, confluent lesions. These cells, although often polymorphic and multinuclear did not show mitotic acitivity or a tendency for neoplastic transformation. To determine the histogenesis of these foci, extensive immunocytochemical reactions were carried out with antibodies to a variety of glial, neuronal and nonneural cell lineages. With the exception of S-100 protein, no immunoreactivity was detectable. S-100 was consistently expressed in these foci, irrespective of their size, location, and degree of polymorphism. On the basis of cytological appearance, distribution and immunoreactivity we tentatively designate these foci as glial micro-hamartomas. Although we did not systematically analyze the CNS of patients with von Recklinghausen neurofibromatosis (neurofibromatosis 1, NF1), the present study strongly suggests that these micro-hamartomas constitute a morphological hallmark of bilateral acoustic neurofibromatosis (NF2).
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  • 70
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    Journal of cancer research and clinical oncology 115 (1989), S. 361-365 
    ISSN: 1432-1335
    Keywords: Estrogen receptor ; Progesterone receptor ; Immunohistochemistry ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human breast carcinomas were evaluated for estrogen and progesterone receptors by immunohistochemistry using monoclonal anti-receptor antibodies (n=267) and by cytosol steroid-binding assays (n=212). The estrogen and progesterone receptor contents of the tumors correlated with histological features of differentiation, such as histological and nuclear grade, and with the amount of tumor necrosis and lymphoid infiltration. The correlation of immunohistochemically determined steroid receptor values with histological characteristics was somewhat better than that of biochemically assessed concentrations.
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  • 71
    ISSN: 1432-1106
    Keywords: Immunohistochemistry ; Coexistence ; Catecholamines ; NPY ; Peptide ; Neurotransmitters ; Brain stem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The indirect immunofluorescence technique was used to analyze the catecholaminergic neurons in the medulla oblongata of the rat for the presence of enkephalin (ENK) — and neuropeptide Y (NPY)-like immunoreactivity (LI). In colchicine pretreated animals, using a double staining technique with mouse and rabbit antibodies against ENK and tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT), it was demonstrated that both TH-and ENK-LI occurred in the same neurons, particularly in many neurons of the A1 noradrenaline cell group. In the transition zone to the C1 adrenaline cell group, a proportion of PNMT-positive cells also contained ENK-LI. In the rostral and mid portion of the C1 group only few TH/PNMT-positive cells were found to be ENK-positive. In the noradrenergic A2 region, a moderate number of cell bodies also contained TH plus ENK-LI, whereas only a few of the adrenaline cells of the C2 and C3 groups showed ENK-LI. In addition, with an elution restaining technique it was possible to demonstrate that several of the cells containing TH-and ENK-LI were also positive for NPY-LI. The present findings demonstrate that a subpopulation of the catecholaminergic neurons in the medulla oblongata of the rat is ENK positive, thereby indicating a possible co-release of the two compounds in their projection areas, for example the paraventricular nucleus and the spinal cord.
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  • 72
    ISSN: 1432-1106
    Keywords: Steroid receptor ; CRF ; Neurotensin ; Enkephalin ; CCK ; PHI ; VIP ; Somatostatin ; TRH ; Dopamine ; Immunohistochemistry ; Arcuate nucleus ; Hormones ; Neurosecretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against GR and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY- or TH-positive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH- and NPY-positive neurons as well as a large proportion of the SOM- and NT-immunoreactive neurons contained GR-LI. The results indicate that in the PVN, in addition to the CRF neurons, certain peptidergic neurons in the parvocellular part of the PVN, without any established role in the control of ACTH synthesis and release, may also be under glucocorticoid control. This seems to be the case also for most arcuate neurons.
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  • 73
    ISSN: 1432-1106
    Keywords: Aging ; Serotonin ; Degeneration ; 5,7-DHT ; Lesion ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent morphological observations have suggested neurotransmitter specific degeneration of amongst others, the serotonergic system in the aged rat brain. However, morphological studies can only give a static picture of the events that take place over a period of several months. In the present study we used an experimental model in which degeneration of the serotonergic system in the young adult rat brain was produced on a short time scale. Morphological changes were studied 2 h and 1 or 14 days after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT). Nonspecific damage and severe depletion of serotonergic fibers was observed in the immediate surroundings of the injection site, representing the effects of high local concentrations of 5,7-DHT. Sometime after injection swollen varicosities and dilated non-varicose fibers were observed. Fourteen days after the 5,7-DHT treatment cluster-like fibers appeared. It is argued that these swollen and crumpled fiber knots are slowly degenerating fibers. A comparison is made with the abnormal serotonergic fibers in the aged rat brain and it is concluded that these aged abnormal fibers represent axonal degeneration of the serotonergic system in the senescent rat brain.
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  • 74
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    Experimental brain research 78 (1989), S. 147-163 
    ISSN: 1432-1106
    Keywords: Glia ; GFAP ; Forebrain ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the first of two papers dealing with the distribution of glial fibrillary acidic protein-(GFAP)-immunoreactive elements in the rat brain, the localization of immunostaining in the forebrain is systematically described. While the limbic cortex was found to contain intensely stained, evenly distributed astrocytes, the neocortex showed clearly stratified GFAP-staining, with substantially less immunoreactivity occurring in the middle layers than in the areas close to the brain surface or the white matter. A remarkably regular staining pattern was observed in the hippocampus and dentate gyrus. The striatum remained unstained in sharp contrast to the pallidum. In the diencephalon, the main thalamic nuclei were poor in GFAP-labelled elements in contrast to the internuclear border zones. In the hypothalamus, nuclei were conspicuous by their GFAP-staining. A consistent differential staining pattern was obtained in the epithalamic structures. The observed distributional pattern of diencephalic GFAP-immunoreactivity is thought to be due to different regional proliferation of the embryonic neuroepithelium of the diencephalon. The uneven distribution of GFAP-immunoreactivity in the forebrain is explained on a mainly developmental basis.
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  • 75
    ISSN: 1432-1106
    Keywords: 5-hydroxytryptamine ; Opioid peptide ; Colocalization ; Ventral medulla ; Bulbo-spinal projection ; Fluoro-gold dye ; Retrograde transport ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ventral medulla oblongata of rats was analyzed with a double-labelling immunofiuorescence technique using guinea pig antibodies directed against serotonin (5-HT) and rabbit antisera directed against enkephalin (ENK). Numerous cells in the region of nucleus raphe obscurus, nucleus raphe pallidus and nucleus raphe magnus showed immuno-staining for either 5-HT or ENK. A substantial number of cells showed positive immunostaining for both 5-HT and ENK. 5-HT/ENK double-labelled cells were most frequently encountered in an area that extended from the rostral aspect of the inferior olivary nucleus to the pontomedullary border. This region corresponds anatomically to nucleus raphe magnus/nucleus paragigantocellularis. In addition, a number of the 5-HT/ENK-containing cells were retrogradely labelled with Fluoro-Gold dye that had been injected into the thoracic spinal cord several days prior to perfusion. Schematic drawings showing the anatomical distribution of 5-HT/ENK colocalization are provided.
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  • 76
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    Experimental brain research 76 (1989), S. 417-423 
    ISSN: 1432-1106
    Keywords: Choline acetyltransferase ; Cerebral cortex ; Immunohistochemistry ; Development ; Transient expression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cholinergic innervation of the rat cerebral cortex was examined in pre- and postnatal life using immunohistochemistry with a monoclonal antibody directed against choline acetyltransferase (ChAT). Our observations show that there are two separate phases in the development of the cholinergic innervation of the rat neocortex. The first, a transient phase, occurs in the late stages of gestation and in the perinatal period. During this time, ChAT-labelled cells (neuroblasts, as well as immature pyramidal and non-pyramidal neurons) are present throughout the entire rostro-caudal extent of the primordial cortex. The fate of these cells, which are not visible shortly after birth, is unknwon as is their functional role in the developing cortex. The second phase in the development of the cholinergic innervation begins in the middle of the second postnatal week. At this stage only a few faintly stained neurons and fibres appear in the cortex. Their numbers and staining intensity increase gradually until the fifth postnatal week when ChAT-labelled neurons and axonal arbours appear indistinguishable from their adult counterparts. The pattern of development observed in the second phase parallels closely that shown in a recent analysis of cortical ChAT activity during postnatal life.
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  • 77
    ISSN: 1432-1041
    Keywords: diflunisal ; pharmacokinetics ; healthy volunteers ; kidney failure ; rheumatoid arthritis ; aged subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The single-dose plasma kinetics of diflunisal was studied in healthy young and old subjects, in patients with rheumatoid arthritis, and in patients with renal failure. The plasma and urine kinetics of the glucuronidated metabolites of diflunisal were studied in the healthy elderly subjects and in the patients with renal failure. In addition, the multiple-dose plasma kinetics of diflunisal was assessed in healthy volunteers and in patients with rheumatoid arthritis. After a single dose of diflunisal the terminal plasma half-life, mean residence time and apparent volume of distribution were higher in elderly subjects than in young adults. No difference was observed in any pharmacokinetic parameter between age-matched healthy subjects and patients with rheumatoid arthritis. The elimination half-life of unchanged diflunisal was correlated with the creatinine clearance (r=+0.89) and its apparent total body clearance exhibited linear dependence on creatinine clearance (r=+0.78). In patients with renal failure, the terminal plasma half-life and mean residence time of diflunisal were prolonged. The renal and apparent total body clearances were lower, the mean apparent volume of distribution was higher and the mean area under the concentration-time curve extrapolated to infinity (AUC) was greater in the renal failure patients than in controls. The plasma concentration of the glucuronidated metabolites rapidly rose to levels above those of unchanged drug in renal patients, whereas they were lower than those of unchanged diflunisal in controls. The AUC (0–96 h) of diflunisal glucuronides in the patients was four-times that in controls, and the terminal elimination half-life of the glucuronides was prolonged in them. The renal excretion and clearance of diflunisal glucuronides were reduced when renal function was impaired. After multiple dosing, the pre-dose steady-state plasma-concentration increased with decreasing creatinine clearance (r=-0.79). When the plasma concentration exceeded 200 µmol·1−1, the elimination half-life was doubled, due to partial saturation of diflunisal conjugation. This finding suggests that lower doses could be used in long-term treatment. Thus, old age and arthritic disease appear to have little influence on the kinetics of diflunisal in the absence of renal functional impairment. Ordinary doses can be given for short term treatment of elderly patients with or without RA. In patients with renal failure, however, reduced doses of diflunisal are recommended.
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  • 78
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
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  • 79
    ISSN: 1432-1041
    Keywords: nabumetone ; rheumatoid arthritis ; pharmacokinetics ; old patients ; NSAID
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have performed a detailed pharmacokinetic study of the plasma concentrations of the major active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid (6 MNA), attained after a single dose and during chronic administration comparing the results of a group of young healthy volunteers with those of a group of elderly arthritic patients. The latter had higher peak plasma concentrations of 6MNA and slower rates of elimination but there is no tendency for the drug to accumulate unpredictably in the old. Disease activity also influences plasma concentration, those with more active disease, and lower serum albumin concentrations had lower AUC values.
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  • 80
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    European journal of clinical pharmacology 36 (1989), S. 291-297 
    ISSN: 1432-1041
    Keywords: paracetamol ; renal failure ; drug disposition ; polar metabolites ; cumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure. The mean renal clearances of paracetamol and its glucuronide and sulphate conjugates in the healthy volunteers and patients with moderate renal failure were 15.7, 137 and 172, and 5.9, 14.5 and 14.8 ml/min respectively. In the latter patients the mean renal clearances of the cysteine and mercapturic acid conjugates were much greater at 35.4 and 80.2 ml/min. In the patients with moderate renal failure the AUC's of the glucuronide and sulphate conjugates were related to the plasma creatinine and there were significant negative correlations with the renal clearances of these metabolites and total urinary recovery. Marked cumulation of the polar glucuronide and sulphate conjugates of paracetamol would seem inevitable in patients with renal failure and the parent drug is apparently regenerated to a limited extent from retained metabolites.
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  • 81
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    European journal of clinical pharmacology 37 (1989), S. 257-260 
    ISSN: 1432-1041
    Keywords: nifedipine ; propranolol ; indocyanine green ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine healthy adults were administered indocyanine green (ICG) 0.5 mg·kg−1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood pressure (MAP) were also determined. Nifedipine increased ICG clearance by 14% and decreased t1/2 by 26%. Propranolol decreased ICG clearance by 21% and increased t1/2 42%. Nifedipine and propranolol given together increased ICG clearance 63% and decreased t1/2 by 19%. All changes were statistically significant. Propranolol given after multiple doses of nifedipine did not change ICG kinetic parameters. Propranolol Cmax, tmax, oral clearance, and t1/2 did not change after nifedipine therapy. However, partial propranolol AUC values between 0–0.33, 0–0.5, 0–1.0 and 0–1.5 h were significantly larger after single and multiple doses of nifedipine indicating higher propranolol concentrations during the absorption phase. Heart rate and MAP did not change after nifedipine treatment. Similar declines in heart rate and MAP occurred after propranolol alone and propranolol after single and multiple doses of nifedipine.
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  • 82
    ISSN: 1432-1041
    Keywords: ramipril ; renal insufficiency ; hypertension ; pharmacokinetics ; ramiprilat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1–2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5–15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15–40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40–80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex. The study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) smaller doses of ramipril are required than in patients with normal or borderline renal function.
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  • 83
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    European journal of clinical pharmacology 37 (1989), S. 279-283 
    ISSN: 1432-1041
    Keywords: ketoconazole ; terbinafine ; microsomal metabolism ; caffeine ; male volunteers ; pharmacokinetics ; drug interaction ; cytochrome P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml·kg−1·min−1 in controls to 1.06 and 1.21 ml·kg−1·min−1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.
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  • 84
    ISSN: 1432-1041
    Keywords: repirinast ; theophylline ; asthma ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A possible pharmacokinetic interaction between theophylline and repirinast has been investigated in asthmatic patients. The kinetics of theophylline was studied in seven adult in-patients given theophylline 400–800 mg b.d. alone and after three weeks of co-administration of repirinast. There was no effect on the kinetics of the combined treatment.
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  • 85
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    European journal of clinical pharmacology 37 (1989), S. 309-311 
    ISSN: 1432-1041
    Keywords: pyrazinamide ; haemodialysis ; pharmacokinetics ; uraemic patients ; drug metabolites ; anti-tuberculous chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of PZA during haemodialysis were determined in 6 patients with chronic renal impairment after a single oral dose of 25.7 (1.9) mg·kg−1. The dialysis clearance of PZA and of its metabolites were: pyrazinamide 132 ml·min−1; pyrazinoic acid 121 ml·min−1; 5-hydroxy-pyrazinamide 107 ml·min−1; 5-hydroxy-pyrazinoic acid 118 ml·min−1. The average amount extracted during a dialysis session of 4.1 h was 926 mg after an oral dose of 1700 mg. The high dialysability shows that PZA can property be administered at the end of each dialysis session in the usual dose of 25 to 30 mg·kg−1.
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  • 86
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    European journal of clinical pharmacology 37 (1989), S. 375-379 
    ISSN: 1432-1041
    Keywords: dihydrocodeine ; pharmacokinetics ; young/elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Although poor renal function reduces clearance of dihydrocodeine in man, and renal impairment occurs with ageing, no significant differences occurred in the handling of single doses of dihydrocodeine between elderly patients and young, normal subjects. After multiple dosing, the maximum concentration was significantly different between the groups, being higher in the elderly. The increase in the area under the curve in the elderly was 25% greater than in the young on chronic therapy. This difference was not statistically significant, but was likely to be of clinical significance. The elderly patients' mean creatinine clearance (61.8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration. Variability in all measurements was marked in both groups, and hence no clear guidelines can be given on therapeutic dosing. The small initial dose with alterations thereafter depending on clinical effect is the best advice.
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  • 87
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    European journal of clinical pharmacology 37 (1989), S. 381-385 
    ISSN: 1432-1041
    Keywords: nicardipine ; first pass effect ; pharmacokinetics ; stable isotope assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic elimination of nicardipine has been studied by an initial oral administration of nicardipine followed 1.25 h later by intravenous injection of the deuterium-labelled molecule (D3 nicardipine). To check that intravenous kinetics was not modified by the oral administration, an i.v. injection of unlabelled nicardipine (D0 nicardipine) was also given. The study was carried out in six healthy male volunteers, aged between 24 and 27 years, according to a Latin square cross-over design. Similar values were found for each kinetic parameter after i.v. administration regardless of whether it was administered alone by that route or with an oral dose. The plasma level-time curves of nicardipine were described by a three open compartment model. The total plasma clearance was about 800 ml/min, the volume of distribution was of the order of 1 l/kg and the half-life of β-elimination ranged from 4 to 5 h. The elimination rate constant β was independent of the route of administration.
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  • 88
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    European journal of clinical pharmacology 37 (1989), S. 423-426 
    ISSN: 1432-1041
    Keywords: prednisolone ; food intake ; enteric-coated tablets ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prednisolone absorption and bioavailability of 10 mg enteric-coated (EC) and plain (uncoated) tablets were investigated after fasting and heavy meals (EC only) consumed to satiety in normal healthy volunteers. The same volunteers had also received 16 mg of prednisolone intravenously. In fasted subjects, the absolute bioavailability fraction, as normalised for intravenous doses, of prednisolone from plain tablets was 1.055 and from EC tablets was 0.996. The peak concentrations after plain and EC tablets were 309 and 249 ng/ml attained at 0.98 and 5.14 h, respectively. The means plasma elimination half-lives following the plain, EC tablets and intravenous administration in fasting conditions were 3.73, 3.89 and 3.78 h, respectively. Food interfered with both the absorption and the pharmacokinetics of prednisolone after EC tablets resulting in variability in its plasma levels. In some cases absorption of prednisolone was delayed for 12 h and remained at a measurable level for 24 h. In other cases, a normal absorption pattern was observed. This inter- and intrasubject variability of the effect of food appears to be related to its quantity, constituents and also the subjects physiological characteristics. It is concluded that enteric-coated prednisolone tablets should be administered at least 2 h between meals. However, for more predictable corticosteroid absorption (perhaps thus avoiding the therapeutic failure), plain prednisolone tablets are preferable.
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  • 89
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    European journal of clinical pharmacology 36 (1989), S. 629-632 
    ISSN: 1432-1041
    Keywords: trimethadione ; antipyrine ; metabolite formation ; drug interaction ; cytochrome P-450 ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy male volunteers were given trimethadione (TMO) 4 mg/kg and antipyrine (AP) 500 mg alone or concomitantly to determine whether the metabolism of the drugs was mediated by the same or closely related forms of cytochrome P-450. Whether administered alone or together the clearance (CL) and half-life (t1/2) of TMO and AP were the same, and there was a good correlation between the CL and t1/2 of TMO and AP (aloner=0.755 and 0.623, respectively; coadministeredr=0.771 and 0.503, respectively). Excretion of AP and its main metabolite and the clearance for production of AP metabolites after AP was administered alone were not significantly different when TMO and AP were taken together. When the two drugs were administered alone or coadministered, the correlation between the CL of TMO and the excretion of 3-hydroxymethyl-3-norantipyrine (NORA) was close (aloner=0.734, coadministeredr=0.749). The correlation between the CL of TMO and CLm of NORA when TMO and AP were given alone or concomitantly was 0.762 and 0.772, respectively. The findings suggest that TMO metabolism and the formation of NORA in healthy subjects are mediated by a closely related form(s) of the cytochrome P-450 system.
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  • 90
    ISSN: 1432-1041
    Keywords: FCE 22101 ; penem antibiotic ; pharmacokinetics ; single dose ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clinical tolerance and pharmacokinetics of FCE 22101 (sodium (5R, 6S)-6-[(1R)-hydroxyethyl]-2-carbamoyloxymethyl-2-penem-3-carboxylate), a new penem antibiotic, have been studied after giving a single i.v. dose of 4 mg·kg−1 to ten healthy male volunteers. The pharmacokinetics was estimated according to a two-compartment open model. The peak plasma concentration (Cmax) was 15.5 (1.08) µg·ml−1, mean (SEM). FCE 22101 was rapidly cleared from the systemic circulation [ $$t_{1/2\lambda _z } $$ =44.2 (4.2) min; CL=7.21 (0.47) ml·kg−1·min−1]. The mean apparent volume of distribution at steady-state was 246 (16.9) ml·kg−1. The mean residence time relative to the 10 min infusion was 39.4 (1.5)min. Urinary recovery of FCE 22101 showed wide inter-subject variation, ranging from 10.2 to 53.6% of the dose. No subject complained of adverse effects.
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  • 91
    ISSN: 1432-1041
    Keywords: zidovudine ; azidothymidine ; pharmacokinetics ; metabolism ; HIV seropositivity ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 92
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    European journal of clinical pharmacology 37 (1989), S. 487-491 
    ISSN: 1432-1041
    Keywords: almitrine ; drug absorption ; liver metabolism ; pharmacokinetics ; biliary excretion ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected. Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time. The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.
    Type of Medium: Electronic Resource
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  • 93
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 617-619 
    ISSN: 1432-1041
    Keywords: clotiazepam ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the single dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets in a cross-over study in 6 healthy volunteers (median age 28 years). The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.
    Type of Medium: Electronic Resource
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  • 94
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 101-104 
    ISSN: 1432-1041
    Keywords: theophylline ; ponsinomycin ; pharmacokinetics ; drug interactions ; macrolide antibiotic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of ponsinomycin on the pharmacokinetics of theophylline has been studied in 12 young healthy volunteers. They received 10 doses of theophylline 200 mg every 8 h p.o., successively in the absence and then in the presence of ponsinomycin. This new macrolide, structurally related to midecamycin, was given in the therapeutic dose of 800 mg b.d. for 5 days, starting 2 days before the second phase of treatment with theophylline. The pharmacokinetic parameters of theophylline, calculated from its plasma concentration at steady-state, were not affected by the co-treatment. In particular, there was no significant difference between the peak and trough plasma levels, apparent clearance or apparent elimination half-life of theophylline in the absence and the presence of ponsinomycin. Only renal clearance was slightly (27%) but significantly increased by the co-treatment. The results suggest that ponsinomycin would be a good choice if a macrolide antibiotic were needed in patients being treated with theophylline.
    Type of Medium: Electronic Resource
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  • 95
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 167-171 
    ISSN: 1432-1041
    Keywords: amiloride ; hydrochlorothiazide ; pharmacokinetics ; steady-state ; elderly ; fixed combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics. The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml·min−1, amiloride; and from 418 to 157 ml·min−1, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng·ml−1, Css,max; from 2 to 8 ng·ml−1, Css,min; and from 4 to 14 ng·ml−1, Cav; Hydrochlorothiazide: from 184 to 651 ng·ml−1, Css,max; from 31 to 121 ng·ml−1, Css,min; and from 89 to 273 ng·ml−1, Cav). The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r=0.62, young;r=0.72, elderly). As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.
    Type of Medium: Electronic Resource
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  • 96
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
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  • 97
    ISSN: 1432-1041
    Keywords: azathioprine ; 6-thiouric acid ; 6-mercaptopurine ; renal transplantation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (6-TU) and 6-mercaptopurine (6-MP), metabolites of AZA, may provide more readily measurable indices of the pharmacologic activity of AZA. In order to evaluate the utility of 6-TU and 6-MP plasma concentrations in monitoring AZA therapy, we studied their pharmacokinetics in 6 renal transplant patients, and their in vitro immunosuppressive potency in a mixed lymphocyte proliferation assay. A peak plasma 6-TU concentration of 710.7 ng/ml was observed at 3.8 h after oral dosing. Good correlation was observed between the elimination t1/2 of 6-TU and serum creatinine, and between AUC over 24 h and serum creatinine. However, we did not observe a second peak in plasma 6-TU concentration that could be attributed to the degradation of active AZA metabolites. 6-MP plasma concentrations in the patients were low (mean peak concentration 36.0 ng/ml) and rapidly disappeared within 8 h. In vitro immunosuppressive activity could not be demonstrated for 6-TU over a concentration range of 1.25 ng/ml to 0.25 mg/ml. We conclude that 6-TU is pharmacologically inert and is primarily eliminated by the kidneys. Our findings currently do not support the use of plasma concentrations of 6-TU or 6-MP to monitor AZA therapy. In order to optimize AZA therapy, analytical techniques that are technically feasible and that can directly quantify the active intracellular thiopurines are being explored.
    Type of Medium: Electronic Resource
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  • 98
    ISSN: 1432-1041
    Keywords: meptazinol ; pregnant and non-pregnant women ; pharmacokinetics ; single and repeated i.v. dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the disposition of the centrally-acting analgesic meptazinol in a group of age-matched non-pregnant and pregnant (36–38 weeks gestation) women. Ten non-pregnant and nine multiparous pregnant volunteers each received a single i.v. dose of meptazinol hydrochloride (equivalent to 25 mg base). A further group of 9 non-pregnant (including four of the original participants) and 10 multiparous pregnant subjects were given repeated i.v. doses of meptazinol hydrochloride (each equivalent to 10 mg base) at 30-min intervals for 2.5 h. Meptazinol plasma concentrations were determined by HPLC using fluorescence detection and the pharmacokinetic variables investigated. After single dosing there were no statistical differences in half-life, clearance, or apparent volume of distribution between the two groups, suggesting that the disposition of meptazinol was not altered by pregnancy. This was confirmed in the repeated dose study, in which no significant differences occurred in either the plasma concentrations achieved or in areas under the curves between the non-pregnant and pregnant subjects. Furthermore, the steady-state concentrations were comparable with those predicted from the single dose results. This indicates that there should be no requirement for dosage alteration of meptazinol during pregnancy.
    Type of Medium: Electronic Resource
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 279-282 
    ISSN: 1432-1041
    Keywords: meptazinol ; rectal and oral administration ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of the centrally-acting analgesic meptazinol after oral and rectal administration to 15 healthy men. Each subject took a standard 200 mg tablet orally and Witepsol H12 suppositories containing 75, 100, and 150 mg of the drug in a cross-over design. Meptazinol plasma concentrations were measured by HPLC using fluorescence detection and the pharmacokinetics determined. The tmax values for the 100 mg and 150 mg suppositories (median =0.5 h) were statistically significantly shorter than for the tablet (median =1.13 h), suggesting that meptazinol was more rapidly absorbed via the rectal route. Despite substantial intersubject variation in Cmax the plasma concentrations after rectal dosage were higher than after oral administration. There was a statistically significant (p〈0.001) improvement in systemic availability for each of the suppository doses (mean approximately 15.5% compared with the oral tablet (mean approximately 4.5%).
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    ISSN: 1432-1041
    Keywords: ibuprofen ; enantiomers ; stereoselective protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(−)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(−)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.
    Type of Medium: Electronic Resource
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