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  • 1985-1989  (1,734)
  • 1975-1979  (1,095)
  • 1989  (887)
  • 1986  (847)
  • 1977  (1,095)
  • Inorganic Chemistry  (2,149)
  • Ultrastructure  (272)
  • Electron microscopy
  • Immunohistochemistry
Material
Years
  • 1985-1989  (1,734)
  • 1975-1979  (1,095)
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.
    Type of Medium: Electronic Resource
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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.
    Type of Medium: Electronic Resource
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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.
    Type of Medium: Electronic Resource
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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.
    Type of Medium: Electronic Resource
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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.
    Type of Medium: Electronic Resource
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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
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 246 (1989), S. 169-179 
    ISSN: 1432-0711
    Keywords: Human fetal endometrium ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human fetal endometrium was examined by light and electron microscopy. Our study shows the following new morphological aspects: (1) Glands are already present. (2) Endometrium undergoes a maturation process during gestation and at late gestational age resembles late proliferative endometrium. (3) The nuclear bodies are present in cell nuclei throughout gestation. (4) Nucleolar channel systems (NCS) sometimes appear at a late gestational age. (5) Cells with the same morphology as that of endocrine cells are found in the basal layers of endometrium at a late gestational age. The significance of these morphological aspects is discussed.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1989), S. 113-119 
    ISSN: 1432-2307
    Keywords: Gastric mucosa ; Intestinal metaplasia ; Ciliated cell ; Ciliated metaplasia ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intestinal metaplasia of the gastric mucosa occurs commonly in aged Japanese patients and has been discussed in relation to the high incidence of gastric cancer in Japanese. Ciliated cells in the gastric mucosa have frequently been found in association with intestinal metaplasia in the pyloric gland and rarely in the cardiac gland in many Japanese patients, and exceptionally in one Chinese and in one Swedish patient. Electron microscopic examination of 12 Japanese patients has revealed that these structures are not metaplastic stereocilia, but true cilia. Ciliated cells have been found in the basal part of the gastric glands and never in the surface epithelium. The fine structure of the gastric cilia was almost the same as that of normal respiratory cilia. However, in the gastric cilia, most dynein arms were inconspicuous even after tannic acid fixation, indicating that ciliary beating of the gastric cilia is problematic. Abnormal cilia and basal bodies also were found. Ciliated cells have always occurred in association with intestinal metaplasia, therefore this phenomenon might be a type of metaplasia and is named “ciliated metaplasia” of the gastric mucosa.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2307
    Keywords: Hyperoxia ; Lung broncho-vascular reaction ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the early phenomena involved in the lung reaction to hyperoxia, twenty adult male rats were exposed to 100% oxygen at 1 ATA. Morphological pulmonary lesions were detectable after only 24 h hyperoxia, and included vasoconstriction and perivascular oedema, bronchiolar constriction, and pericyte reaction. The lesions were irregularly scattered within the lung parenchyma and occurred preferentially in areas centred on bronchiolo-vascular stems. Even at the latest stages, pulmonary heterogeneity was obvious, from the coexistence of areas damaged at different times. Neuro-epithelial-bodies were found under the bronchiolar epithelium; the morphological aspect of the neuro-endocrine cells observed was consistent with hyperoxia-induced modulation of their secretory activity. Taken together, our findings show the speed of development of hyperoxia-induced pulmonary changes and raise some pathogenic considerations.
    Type of Medium: Electronic Resource
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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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.
    Type of Medium: Electronic Resource
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  • 14
    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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  • 15
    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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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 145-149 
    ISSN: 1432-2307
    Keywords: Paracrystalline inclusion ; Microtubule ; Ciliogenesis ; Gastric ciliated cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unusual electron-dense paracrystalline inclusions were found in metaplastic ciliated cells in the stomachs of three Japanese male patients with gastric carcinoma. These patients had not been given antitumour drugs before surgery and ethrane (enflurane) was used as the anaesthetic. Ciliated cells in the gastric mucosa are found not infrequently in the pyloric glands in association with intestinal metaplasia in elderly Japanese patients. Paracrystalline inclusions were found only in the ciliated cells and never in any other types of gastric mucosal cell. These inclusions were located in the apical portion of the ciliated cells in intimate association with the basal bodies. They consisted of twisted strings about 27 nm wide with a regularly repeated spacing of about 30 nm. On highly magnified electron micrographs, granules about 4 nm in diameter were detected. These paracrystalline inclusions have never been reported previously, although their location in ciliated cells and their morphological characteristics suggest an intimate relationship with the ciliogenesis of metaplastic ciliated cells in the human stomach.
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  • 17
    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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  • 18
    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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  • 19
    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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  • 20
    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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  • 21
    ISSN: 1432-2307
    Keywords: Human acute pancreatitis ; Zymogen granules ; Acinar cells ; Electron microscopy ; Immunocytochemistry ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study fine structural changes of acinar zymogen granules were investigated in human acute pancreatitis. Pancreatic tissue was obtained at surgery from 6 patients, prepared for ultrastructural analysis, and stained immunocytochemically for trypsinogen. Stereological parameters of zymogen granules were evaluated. The density of the immunocytochemical labelling for trypsinogen was estimated over zymogen granules, the rough endoplasmic reticulum, Golgi apparatus and the acinar lumina. In acute pancreatitis the number of zymogen granules was diminished and their size reduced. The density of the labelling for trypsinogen was unchanged over zymogen granules but showed a significant reduction over the rough endoplasmic reticulum, Golgi apparatus, and the acinar lumina. In general the integrity of zymogen granules was well preserved. Focally degenerative changes of zymogen granules and large autophagosomes were observed. From the immunogold labelling a disturbance of enzyme synthesis and secretion was suggested. Evidence is given that a disruption of the zymogen granule membranes and a fusion with lysosomal bodies might contribute to the pathogenesis of human acute pancreatitis.
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  • 22
    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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  • 23
    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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  • 24
    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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  • 25
    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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  • 26
    ISSN: 1432-2307
    Keywords: Human heart ; Papillary muscle ; Hypertrophy ; Mitochondria ; Specific staining ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biopsy material of the hypertrophied human papillary muscle has been processed according to various electron microscopical techniques in order to study the mitochondrial ultrastructure and the association between mitochondria and sarcoplasmic reticulum (SR).En bloc staining with a Cu-Pb citrate solution resulted in specifically contrasted mitochondrial and sarcotubular membranes, characterized by numerous, discrete, electron-dense particles. The differences in staining patterns between the perinuclear mitochondria and their subsarcolemmal and interfibrillar counterparts suggest differences in chemical properties and/or metabolic activities. The selectively contrasted mitochondrial particles may represent a conglomorate of extrinisic and intrinisic respiratory enzymes and other membrane-associated proteins, while the majority of the electron-dense particles of the sarcotubular membrane may represent positively stained Ca2+-pumps. Ultrastructural findings in the present study strongly indicate that the slender mitochondrial projections represent an initial stage in a process leading to the formation of large and pleomorphic mitochondria. Intimate contact between adjacent mitochondria as well as between mitochondria and SR are documented. In the contact regions some of the specifically contrasted particles of the adjacent membranes had fused with each other. It is suggested that these particles represent membrane-bound transport proteins providing a system for interorganelle exchanges of metabolites and/or ions.
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  • 27
    Electronic Resource
    Electronic Resource
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    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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  • 28
    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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  • 29
    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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  • 30
    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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  • 31
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    Virchows Archiv 415 (1989), S. 1-6 
    ISSN: 1432-2307
    Keywords: Visceral leishmaniasis ; L. donovani ; Parasitism ; Liver pathology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Liver parenchymal cell parasitism with the amastigotes form ofL. donovani was detected by electron microscopy in human visceral leishmaniasis. Endocytosis was considered to be the mechanism by which the leishmania entered the cell. Evidence of well preserved parasites within hepatocytes suggest this parasitism as a possible reservoir for recrudescence.
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  • 32
    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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  • 33
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    Virchows Archiv 415 (1989), S. 21-29 
    ISSN: 1432-2307
    Keywords: Alcoholic liver disease ; Ultrastructure ; Phagocytosis ; Cell shedding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sinusoidal macrophages were studied by light and electron microscopy in 49 liver biopsies from alcohol-abusers with a variety of alcohol-related liver lesions or with near-normal livers. Changes were related to those in nearby hepatocytes. A reduction in the number of macrophages was noted in the more severely damaged livers. Hepatocytes formed blebs at their sinusoidal poles, and these protruded into the space of Disse and into the sinusoidal lumen. It is postulated that reduced phagocytic activity in the livers of patients with severe alcohol-related liver disease leads to increased shedding of hepatocellular material into the circulation. This may promote the development of autoimmune reactions directed against hepatocytes.
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  • 34
    ISSN: 1432-2307
    Keywords: Clear cell sarcoma ; Melanosomes ; Cytochemistry ; Electron microscopy ; Nude mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the histogenesis of clear cell sarcoma of tendons and aponeuroses (CCS), two cases of human and one nude mouse-transplanted CCS line were studied using an ultrastructural and enzyme cytochemical approach. Most of the tumour cells obtained from the primary and transplanted CCS demonstrated melanosomes in various stages of development within the cytoplasm, whereas no melanosomes could be identified in the metastatic CCS. However, cholinesterase and tyrosinase activities could be demonstrated not only in the melanotic primary and transplanted CCS but also in the amelanotic metastatic CCS. The results therefore support the hypothesis that CCS is a soft tissue tumour derived from the neural crest.
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  • 35
    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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  • 36
    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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  • 37
    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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  • 38
    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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  • 39
    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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  • 40
    ISSN: 1432-2307
    Keywords: Collagen secretion granule ; Myofibroblast ; Spindle cell tumour ; Electron microscopy ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Collagen secretion granules, representing stages in the intracellular packaging, transport and secretion of collagen-fibril precursor, have been studied by transmission electron microscopy in non-neoplastic human myofibroblasts and in neoplastic cells from a preliminary study of tumours exclusively or partly of spindle cell type. Vesicles, newly separated from Golgi saccules and containing finely fibrillar material, were identified as early presecretory granules, the most immature type of granule. Later stages exhibited longitudinally arranged, densely fibrillar bundles. Subsequently, secretory granules developed more homogeneously dense content. Fibril-containing cisternae near the plasma membrane were interpreted as either endocytotic or lysosomal structures, or as participants in the final stages of secretion. The features by which collagen secretion granules can be distinguished from other Golgi products, in particular melanosomes, Weibel-Palade bodies and lysosomes, are pointed out. The significance of these organelles for cell identification and tumour diagnosis is discussed.
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  • 41
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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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  • 42
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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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  • 43
    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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  • 44
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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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  • 45
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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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  • 46
    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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  • 47
    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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  • 48
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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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  • 49
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    Acta neuropathologica 78 (1989), S. 555-560 
    ISSN: 1432-0533
    Keywords: Sporadic motor neuron disease ; Lewy body-like hyaline inclusions ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lewy body-like hyaline inclusions were immunocytochemically and electron microscopically investigated in a patient with sporadic motor neuron disease. The hyaline inclusions were chiefly observed within the perikarya of both normal-looking and chromatolytic anterior horn cells in the lumbar spinal cord, but some were detected in the axons and dendrites. Usually, a single inclusion was found in the perikaryon, but in rare cases two or more were observed. Immunocytochemically, these inclusions were intensely immunostained with anti-ubiquitin anti-body. Ultrastructurally, the hyaline inclusions were chiefly composed of randomly arranged linear structures associated with ribosome-like granules, varying from compactly arranged linear densities to more loosely packed ones. They contained scattered vesicles of various sizes and occasionally a focal accumulation of randomly arranged 10-nm neurofilaments or 13–25-nm filamentous structures.
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  • 50
    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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  • 51
    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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  • 52
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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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  • 53
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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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  • 54
    ISSN: 1432-0533
    Keywords: Neuronal inclusions ; Leigh disease ; Tropomyosin ; Actin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A novel type of non-viral cytoplasmic inclusion is described, which was seen in virtually every neuron in the brain and spinal cord of a child with a presumed metabolic disorder whose clinical picture and CNS pathology were compatible with Leigh Syndrome. The ovoid to round inclusions were sharply demarcated, measuring up to 11 μm in diameter. They showed no distinctive staining with a battery of routine histological techniques. The ultrastructural features are unique, comprising non-membrane-bounded aggregates of randomly oriented plate-like structures with parallel linear densities depicting a periodicity of 11–16 nm. Immunocytochemical studies revealed strong staining with antisera to tropomyosin and weaker staining with antisera to actin. There was no reactivity with antibodies against neurofilaments, microtubules and their associated proteins, paired helical filaments, ubiquitin, vinculin or alpha-actinin. It is postulated that the metabolic disorder resulted in a neurodegenerative condition which manifested pathologically with lesions compatible with those of Leigh Syndrome. Associated with the condition was the discrete accumulation of cytoplasmic proteinaceous components, including tropomyosin, in the form of neuronal cytoplasmic inclusions possibly resulting from an alteration of the neuronal cytoskeleton.
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  • 55
    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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  • 56
    ISSN: 1432-0533
    Keywords: Cerebral hypoxia ; Cerebral ischemia ; Ultrastructure ; Neocortex ; Brain isolation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The acute cortical response to surgical brain isolation and subsequent extracorporal normoxic or 30 min hypoxic (PaO2=20 mm Hg) perfusions (hypoxic hypoxia with relative ischemia) was evaluated. Cerebral blood flow, arterial pH and CO2 were maintained constant during both perfusions; only the arterial oxygen content was changed. The isolated brain model used in this and previous investigations produces no qualitative ultrastructural changes in the neocortex following brain isolation and normoxic perfusion. However, the acute cortical structural response to 30 min of hypoxic hypoxia with relative ischemia demonstrated a number of important observations. Hypoxic hypoxia produced ultrastructural responses common to cerebral ischemia such as nuclear chromatin clumping, nucleolar condensation and cytoskeletal breakdown. Although neuronal abnormalities seen after 30 min of hypoxic hypoxia were similar to those acute neuronal changes observed following complete cerebral ischemia without recirculation, they differed three ways: (a) mitochondrial swelling and microvacuolation were observed in many cortical pyramidal neurons. (b) Glycogen particles within astroglial processes were observed even after a 30-min period of hypoxic hypoxia. (c) Perivascular astroglial swelling was minimal despite considerable perineuronal swelling. In contrast, incomplete cerebral ischemia produces mitochondrial changes similar to those in hypoxic hypoxia but also causes the depletion of tissue glycogen and perivascular glial swelling. Thus, hypoxic hypoxia with relative ischemia produces a unique acute ultrastructural response compared to either complete or incomplete cerebral ischemia.
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  • 57
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    Acta neuropathologica 79 (1989), S. 168-175 
    ISSN: 1432-0533
    Keywords: Muscular ; Dystrophy ; Ovine ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initial ultrastructural changes in skeletal myofibers in ovine muscular dystrophy (MD) consisted of focal degeneration of myofibrils and the formation of Z-disc abnormalities, including nemaline rods, in adjacent sarcomeres. Peripheral and central sarcoplasmic masses, which occurred initially in large diameter fibers, contained a mixture of normal organelles and abnormal tubular and fibrillar formations. Vesiculate sarcolemmal nuclei with prominent nucleoli accumulated in central and subsarcolemmal locations in small clusters and short rows. Deformed individual nuclei were sometimes present within nuclear rows. Loss of the myofibrillar mass, increased density of small spherical nuclei, collections of fibrillar and tubular arrays, excessive folding of the sarcolemma and greatly reduced fiber diameter were seen in the end stage of the dystrophic process. Resting satellite cells were present at all stages of lesion development. The morphological progression of the lesions suggested an inherited inability to effectively replace lost myofibrils with ultimate exhaustion of the capacity for repair followed by pathological fiber atrophy.
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  • 58
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    Acta neuropathologica 79 (1989), S. 340-346 
    ISSN: 1432-0533
    Keywords: Paraganglioma ; Melanin ; Orbit ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A paraganglioma of the orbit in a 21-year-old woman is presented, containing oculo-cutaneous melanin in many tumor cells, occasionally adjacent to neurosecretory granules, and in macrophages. This tumor expands the list of neuroectodermal tumors with potential melaninization.
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  • 59
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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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  • 60
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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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  • 61
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    Anatomy and embryology 180 (1989), S. 175-178 
    ISSN: 1432-0568
    Keywords: Paratympanic organ ; Reciprocal synapses ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The innervation pattern of the paratympanic organ was studied by TEM. The paratympanic organ is a small tapering vesicle, typical of birds, situated in the medial wall of the tympanic cavity; it contains hair cells which are similar to type II receptors of the acoustic-lateral system; these cells are characterised by synapses which are not only afferent and efferent, as previously described, but also reciprocal with efferent fibers. Our observation revealed some efferent nerve fibers which form a relationship with hair cells containing synaptic bodies situated next to the plasma membrane and near the fibers themselves. Since synaptic bodies are commonly considered to be the site where the transmission of the impulse from the receptor to the nerve fiber takes place, our pictures suggest that the efferent fibers and hair cells may be either presynaptic or postsynaptic with respect to each other in the paratympanic organ. The hypothesis is formulated that reciprocal synapses allow interaction between hair cells, thus determining an increase in the contrast of information sent by the paratympanic organ to the CNS.
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  • 62
    ISSN: 1432-0568
    Keywords: Cecum ; Germ-free rat ; Microflora inoculation ; Morphometry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The structural changes of the cecal wall in germfree rats were observed at regular intervals after the inoculation of fecal microflora from conventional rats. Quantitative light microscopy showed that most of the elements in the cecal wall increased at 12 or 24 h and reached peak values at 4 days after inoculation. On the 7th day, they decreased approximately to the values for conventional rats. The crypts were bent or widely open till 24 h but were not after the 4th day. Hyperplasia of the crypt epithelial cells including mucous-type cells was observed following microbial inoculation. Electron microscopy revealed that most of the epithelial cells lining the mucosa were typical columnar cells. Desquamation of the epithelial cells and contraction of the muscle fibers were often seen on 4th day. The mucous-type cells were divided into two types, goblet and non-goblet mucous-type cells. Reduction of cecal volume after microbial inoculation may be mainly caused by muscle contraction in the early period and hyperplasia and desquamation of the epithelial cells may suggest their role as the first and non-specific defense line prior to operation of the specific immune system.
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  • 63
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    Anatomy and embryology 180 (1989), S. 237-242 
    ISSN: 1432-0568
    Keywords: Perineurium ; Lanthanum ; Diffusion barriers ; In vivo ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While the perineurium as a diffusion barrier has been extensively investigated by light and electron microscopy, copy, such studies have been largely restricted to the use of protein tracers. In the present study the permeability of the perineurium to a physiologically more relevant ionic tracer has been assessed. In vivo the rat sural or tibial nerve was either microinjected with lanthanum nitrate solution for endoneurial application or bathed in the lanthanum solution for epineurial application. The findings generally demonstrated an effective barrier to the tracer which failed to penetrate the inner layers of the perineurium. Only at the highest lanthanum concentration and longest time intervals employed did trace quantities occasionally penetrate the barrier and then only in the presence of some cytopathological changes to the outermost perineurial cells. The usefulness of the microinjection method was limited by the slight but unavoidable trauma to the perineurium. The findings are related to those of other studies which have used electron dense tracers, also to studies using physiological including electrophysiological techniques and morphological including freeze-fracture methods.
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  • 64
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    Anatomy and embryology 180 (1989), S. 273-280 
    ISSN: 1432-0568
    Keywords: Wallerian degeneration ; Myelin breakdown ; Light microscopy ; Electron microscopy ; Marchi staining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphological aspects of myelin breakdown in the posterior funiculus during Wallerian degeneration were studied in kittens subjected to lumbosacral dorsal rhizotomies 6–8 days after birth. The first sign of myelin breakdown was characterized by swollen or shrunken nerve fibers. Shortly thereafter there was an increased occurrence of collapsed myelin sheaths and later of rounded myelin bodies. Myelin was clearly seen in microglial cells. Correlative observations on Marchi-stained material indicated the simultaneous and frequent appearance of Marchi-positive bodies (MPB:s) and myelin bodies. Due to the rapidity of the degeneration process in the kitten, the increase in the occurrence of Marchi-positive granules (MPG:s) seemed to start concomitantly with increased occurrence of MPB:s. However, the frequent occurrence of MPG:s outlasted that for MPB:s. The findings indicate that the MPB:s may be the counterpart to myelin bodies and the MPG:s to lipid droplets. Microglial cells may be responsible for the primary uptake of degenerating myelin and the subsequent transformation of myelin bodies to lipid droplets. The much faster breakdown of myelin and elimination of lipid material in the degenerating posteror funiculus of the kitten, as compared to the adult, seemed to be due not only to the lower myelin content in the kitten, but also to a higher density of microglia and a greater efficiency in the myelin breakdown process in the degenerating posterior funiculus of the kitten.
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  • 65
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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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  • 66
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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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  • 67
    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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  • 68
    ISSN: 1432-0533
    Keywords: Schwann cell ; Oligodendrocyte ; Electron microscopy ; Myelin ; Optic nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neonatal rats were exposed to Tellurium (Te), via the mother's milk, from the day of birth until sacrifice at 7, 14, 21, and 28 days of age. Light and electron microscopy revealed Schwann cell and myelin degeneration in the sciatic nerves at each age studied. These changes were similar to those described in weanling rats as a result of Te intoxication. In the CNS, hypomyelination of the optic nerves was convincingly demonstrated at 14, 21, and 28 days of age, accompanied by some evidence of myelin degeneration. These changes were also seen in the ventral columns of the cervical spinal cords, although less markedly, and were confirmed by quantitative methods. There was little evidence of oligodendrocyte pathology in the CNS, and it appears that degeneration of these cells is not the primary cause of the CNS hypomyelination, in contrast to the PNS where Schwann cell degeneration has been shown to precede the myelin pathology.
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  • 69
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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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  • 70
    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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    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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    Anatomy and embryology 179 (1989), S. 435-442 
    ISSN: 1432-0568
    Keywords: Ultrastructure ; In vitro fertilization ; Bovine ; Ova ; Cortical granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Heifers were superovulated by PMSG or FSH, and oestrus was induced by prostaglandin. One group of animals was ovariectomized 19–26 h after the LH peak, the content of preovulatory follicles aspirated, and the oocytes processed for in vitro fertilization. Another group was inseminated and ova were collected from the oviducts for study of in vivo fertilization. All ova were examined ultrastructurally. The developmental rate following in vitro fertilization was delayed compared to fertilization in vivo. A high proportion of the in vitro fertilized ova showed polyspermic penetration of the zona pellucida, and supernumerary spermatozoa were found in the ooplasm of some ova. In vivo fertilization was associated with release and subsequent dispersal of the cortical granule content in the perivitelline space. In contrast to this the released granule content of the in vitro fertilized ova remained undispersed close to the oolemma. This feature may account for the high incidence of polyspermic penetration of the zona pellucida. In addition, the study provided an ultrastructural visualization of the initial contact between the equatorial segment of the spermatozoon and the microvilli of the oocyte, and the subsequent internalization of the sperm head.
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    Anatomy and embryology 179 (1989), S. 497-501 
    ISSN: 1432-0568
    Keywords: Parotid gland ; Ultrastructure ; Amylase ; Secretion ; Isoproterenol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of continuous light on ultrastructural organization and sympathetic secretory responses of the rat parotid gland are reported. After 50 days of continuous light exposure, the fine structure of the parotid gland exhibited features of enhanced secretory activity as judged by the striking development of rough endoplasmic reticulum and Golgi complexes, the depletion of secretory granules and the increased turnover of secretory cells. The secretory responses of parotid gland to isoproterenol revealed that continuous light induced a 30% increase in amylase release. This secretory hyperactivity appears to be related to a postsynaptic supersensitivity of sympathetic fibers of the autonomic nervous system.
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  • 74
    ISSN: 1432-0568
    Keywords: Sympathetic ganglion ; Binucleate cells ; Ultrastructure ; Feulgen staining ; Computerized image analysis ; DNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative proportion, ultrastructure and DNA-content of the binucleate cells in the celiac superior mesenteric ganglion of the guinea pig was studied using light and electron microscopy as well as computerized image analysis of Feulgen stained cells. The number of mono — versus binucleate cells was found to vary with stage of development with about 40% of the cells being binucleate in adult animals and 50% in late prenatal stage. No difference in ultrastructure was observed between the nuclei of the two cell types. The binucleate cells contain twice the amount of DNA found in the mononucleate cells.
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    Anatomy and embryology 179 (1989), S. 591-604 
    ISSN: 1432-0568
    Keywords: Fetus ; Membranes ; Placenta ; Green monkey ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study examined developmental changes in fetal membranes and placenta of Cercopithecus aethiops from a Carnegie developmental stage 12 embryo to nearterm fetuses. Ultrastructurally, yolk sac cells (endoderm and mesothelium) were similar to comparable stages in other primates. Endodermal cells had few apical microvilli, abundant rough-endoplasmic reticulum, electron dense mitochondria and dense bodies. In contrast, mesothelial cells were squamous with numerous microvilli, small mitochondria and a few short strands of rough endoplasmic reticulum. Amnion cells early in gestation were squamous with few microvilli, large glycogen deposits and poorly developed cytoplasmic components. Tight junctions and desmosomes held adjacent cells together. The basal surface was smooth and the basal lamina was distinct. As development proceeded the amniotic cells became cuboidal and possessed numerous microvilli. Cytoplasmic organelles were better developed and glycogen deposits increased by mid-gestation. A thick layer of microfibrils and collagen fibers was prominent below the basal lamina. Near-term, the glycogen had virtually disappeared and the amount of lipid droplets increased. Basal infoldings and podocytic processes and the extracellular matrix had increased. The smooth chorion consisted of pseudostratified columnar cells. Cells had short microvilli, numerous granules and vesicles of variable size and electron density in early gestation. With increasing age, amounts of granules and vesicles decreased, as the endoplasmic reticulum became prominent. The chorionic trophoblast was a continuous layer in mid-pregnancy and its cells had well-developed organelles and inclusions. Late in gestation, the trophoblastic layer became discontinuous and wide intercellular spaces and channels were present. In the placenta, the trophoblastic elements showed features characteristic of primate placenta.
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  • 76
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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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  • 77
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    Anatomy and embryology 180 (1989), S. 103-108 
    ISSN: 1432-0568
    Keywords: Ultrastructure ; Gut ; Endocrine cells ; Testudo graeca ; Chelonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The digestive tract of Testudo graeca (Chelonia) was investigated by means of electron microscopy using both conventional and immunocytochemical techniques. EC-, L-, D-, G-, B-, N- and EC-L-cells were detected. These cells share several common ultrastructural characteristics with the endocrine cells of mammals (i.e. clear cytoplasm, prominent Golgi apparatus, secretory granules etc.). EC and D1 cells have so far not been described in the esophagus of any animal species; in the present study these cells have been observed in the esophagus of T. graeca. Of special interest was the presence of B-cells in the intestine, suggesting that the migration of B-cells from the gut to the pancreas to constitute pancreatic islets is not concluded in T. graeca. The present study demonstrates that the gut endocrine system of T. graeca is a complex structure containing a large variety of endocrine cell types similar in morphology to those found in higher vertebrates.
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  • 78
    ISSN: 1432-0568
    Keywords: Monkey ; Ultrastructure ; Pinealocytes ; Axon terminals ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study described the normal ultrastructure of the monkey pineal gland. The gland was composed of the principal pinealocytes, intramural neurons and glial cells. The nucleus of the pinealocytes was deeply infolded with evenly distributed chromatin materials. The abundant cytoplasm was rich in organelles including the well-developed Golgi apparatuses, multivesicular bodies, dense-cored vesicles and widely scattered free and polyribosomes. A variety of axon terminals was observed and the majority of them contained pleomorphic agranular vesicles with a few large dense-cored vesicles. A few terminals showed flattened vesicles or small dense cored vesicles. Some of the axon terminals formed synaptic contacts with the cell bodies of pinealocytes. These synapses were mainly concentrated in the posterior third of the gland. The occasional intramural neurons observed were postsynaptic to axon terminals containing round agranular vesicles. The sources of the nerve fibres and terminals forming synaptic junctions with pinealocytes and intramural neurons were discussed.
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  • 79
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    Anatomy and embryology 180 (1989), S. 243-257 
    ISSN: 1432-0568
    Keywords: Dorsal lateral geniculate nucleus ; Synapse formation ; Synaptic glomerulus ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synapse formation and maturation were examined in the rat dorsal lateral geniculate nucleus (dLGN) from birth to adulthood. Examination of animals, whose ages were closely spaced in time, showed that the maturation of the synaptic organization of the nucleus takes place chiefly during the first 3 weeks of postnatal life. This period of maturation may be divided into 3 broad stages. During the first stage, which spans the first 4 days of life, there are only a few immature synapses scattered throughout the nucleus; occasionally aggregates of 3 or 4 synapses are encountered. Dendrodendritic synapses first appear at the end of this stage. The second stage, which lasts from the end of the first stage through day 8, is characterized by intensive synaptogenesis as well as extensive growth and degeneration. For the first time, large boutons resembling retinal terminals form multiple synaptic contacts with dendrites and dendritic protrusions; these synaptic arrangements are partially covered by glial processes. A feature characteristic of the developing dLGN during the first 2 postnatal weeks, and particularly during the second stage, is the presence of membrane specializations that resemble vacant postsynaptic densities. These specializations, which may be unapposed or opposite another neuronal process, decrease in frequency as the number of synapses increases. It is not known whether these densities are converted to synapses or whether they result from loss of presynaptic elements. The third stage in the process of synaptogenesis, which spans a period between days 10 and 20, is characterized by myelination and by the diminution of growth cones, degenerating profiles and vacant postsynaptic densities. There is also a very significant increase in the number and maturation of synapses including synaptic glomeruli. However, it is not until the end of this stage that synapses appear qualitatively indistinguishable from synaptic arrangements identified in adult animals.
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  • 80
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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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  • 81
    ISSN: 1432-0533
    Keywords: 2,4-Dithiobiuret ; Thioimidodicarbonic diamide ; Motor endplate ; Neuromuscular junction ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 2,4-Dithiobiuret was given i.p. to rats for 4 days at a daily dosage of 1 mg/kg and the development of the lesion associated with neuromuscular dysfunction studied in hindlimb lumbrical muscles. The first morphological indication of neurointoxication was the appearance in some motor endplates of masses of branching tubular smooth endoplasmic reticulum (SER) on day 2 which correlated with the initial functional disturbances. By the 3rd day, most motor endplates were distended by accumulations of densecored, lucent and synaptic vesicles, abnormally swollen mitochondria, intermediate filaments and branching, tubular SER. Evidence of collateral axonal sprouting was seen first at this time. On days 4 and 5, many motor endplates were markedly enlarged and showed axoplasmic organelle congestion. A significant increase in synaptic vesicle size was noted at these times in some terminals. Interposition of Schwann cell processes between the pre- and postsynaptic membranes and terminal retraction was now evident. Some intramuscular nerves showed hydropic Schwann cell cytoplasm with separation of the outermost myelin lamellae, mitochondrial swelling and adaxonal vacuoles as early as the 1st day. Proliferation and segregation of SER around central cores of neurofilaments was seen in myelinated nerve fibres and preterminals on the 3rd day. At this and later times accumulations of SER and swollen mitochondria were found at sites of axonal varicosities and at the paranodal constrictions at nodes of Ranvier. These ultrastructural data are discussed with regard to reduced terminal Ca2+ content (demonstrated by oxalate-pyroantimonate cytochemistry) and compared with the sequelae of botulinum intoxication.
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  • 82
    ISSN: 1432-0533
    Keywords: Senile plaque-like structure ; Periodicacid methenamine silver (PAM) method ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Numerous diffuse senile plaque-like structures (SPLSs) were found in the cerebral cortex from cases with dementia of the Alzheimer type by means of the methenamine-Bodian method. SPLSs varied in shape and size. They were never recognized in the original Bodian, PAS and Congo red preparations, but were positive with anti-β-protein immunostaining and periodic-acid methenamine silver (PAM) methods, which are thought to specifically stain amyloid substance. With PAM electron microscopy, we found sparse aggregations of amorphous, often ramified, structures with fine granular silver deposits in SPLS. Routine electron microscopic examination on the same portion where SPLS were confirmed by PAM electron microscopy revealed amorphous, partially fibrous structures. These structures might be amyloid or amyloid-precursor substance. In SPLSs only a few degenerated neurites and astrocytic processes with glycogen granules were seen. We consider SPLSs to be a kind of senile plaque.
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  • 83
    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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  • 84
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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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  • 85
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    Acta neuropathologica 79 (1989), S. 336-339 
    ISSN: 1432-0533
    Keywords: AIDS ; Cytomembranous inclusions ; Tubuloreticular inclusions ; Ultrastructure ; Peripheral nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report finding tubuloreticular inclusions (TRI) in the endothelial cells of endo- and epineurial vessels in the sural nerve of 11 patients with AIDS. Six patients had a painful peripheral neuropathy, one a non-painful sensory neuropathy, one an acute inflammatory demyelinating polyradiculoneuropathy and one a thalidomide-related neuropathy. Two patients had no clinical evidence of neuropathy. The TRI are not specific to one neuropathy and are unlikely to contribute to the pathogenesis of peripheral nerve syndromes in AIDS.
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  • 86
    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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  • 87
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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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  • 88
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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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  • 89
    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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  • 90
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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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  • 91
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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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  • 92
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    Acta neuropathologica 77 (1989), S. 664-666 
    ISSN: 1432-0533
    Keywords: Hemimegalencephaly ; Golgi study ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pathological findings in a case of hemimegalencephaly are presented. Hemispherectomy, performed because of intractable seizures, allowed an electron microscopic and Golgi study. Glial abnormalities consisted of hyperplasia of glia cells with giant astrocytes often containing several nuclei and proliferation of numerous Rosenthal fibers. Golgi stain showed many giant neurons with a perikaryon covered by perisomatic processes, and a complex dendritic tree. Glial abnormalities could be correlated with the firmness of the hemisphere and intense hypersignal on magnetic resonance imaging. Giant neurons were associated with an increase in size of the perikaryon and dendritic tree; this pattern suggests a polyploidy.
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  • 93
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Ischemic neuronal injury ; Long-term recovery ; Mongolian gerbil ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral transient cerebral ischemia was produced in Mongolian gerbils by clipping the left common carotid artery for 1h. About 60% of the gerbils with neurological symptoms had post-ischemic seizures. The majority of those that had seizures died within a few days, and sections of their cerebral cortices contained many dark and shrunken neurons. However, the gerbils that did not have seizures survived without any severe complications. In the cerebral cortex of the latter, the neurons with diffuse or peripheral pallor of the perikarya were seen along with a small number of dark and shrunken neurons. Diffuse pallor occurred within a few hours following ischemia in layers III, V and VI, and disappeared 1 or 2 days after recirculation. Electron microscopically, these neurons showed dispersion of ribosomes, simple and elongated profiles of rough endoplasmic reticulum (r-ER), clustered vacuoles, and mild to moderate mitochondrial swelling. Occasional net-like tubulomembranous structures, probably derived from r-ER, were observed. On the other hand, peripheral pallor became apparent after 5 days following ischemia, usually involving layer II first and gradually extending to the deeper layers. Concomitantly, the amount of neuropil decreased and the dendrites exhibited tortuosity and irregularity in layer II. Electron microscopically, these neurons showed marked swelling of peripheral perikarya and polyribosomes and organelles were located peripherally to the nuclei. In addition, numerous degenerated axon terminals and distended dendrites were observed around the neurons. These observations indicate that diffuse pallor represents damage directly induced by ischemia and subsequent recirculation, while peripheral pallor is the delayed and remote effect of ischemia, probably due to degeneration of neuronal processes.
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  • 94
    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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  • 95
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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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  • 96
    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.
    Type of Medium: Electronic Resource
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  • 97
    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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  • 98
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1989), S. 10-17 
    ISSN: 1432-0533
    Keywords: Locus ceruleus ; Pick bodies ; Lewy bodies ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In classical Pick's disease with typical Pick bodies, inclusions resembling those present in the cerebral cortex are frequently found in the locus ceruleus. In three such cases Pick bodies were studied by light and electron microscopy and compared with Lewy bodies, inclusions more commonly found in this location. In contrast to the situation in the cerebral cortex, nerve cells with multiple Pick bodies were often found in the locus ceruleus, but in other respects definite light and electron microscopic differences between Pick bodies and Lewy bodies were present. Pick bodies were slightly basophilic and never had a central core or a peripheral halo. They were intensely argyrophilic. Differences in immunocytochemical reactions were especially marked with antibodies to tau and to paired helical filaments. Pick bodies displayed an intense reaction with these two antibodies, contrasting with that of Lewy bodies, which either lacked reactivity or reacted in a peripheral band. By electron microscopy the Pick bodies were composed of random filaments with smooth contour, whereas typical Lewy bodies had fuzzy deposits on filaments that radiated from a central core. Pick bodies in the locus ceruleus therefore maintained their immunocytochemical and electron microscopic characteristics and did not take on the character of Lewy bodies. Such differences point to a different pathogenesis and perhaps etiology of these two types of inclusions and attest to the marked difference clinically and pathologically between Pick's and Parkinson's diseases.
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 100
    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.
    Type of Medium: Electronic Resource
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