[Electron microscopic studies of chromophobe pituitary adenomas in man].
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Adenoma, Chromophobe↗
Biomedical subjects
W Wechsler
Publications and source records attributed to W Wechsler.
Microscopic examination of hippocampal slices after short-term lead exposure in vitro.
By using light microscopic, electron microscopic and morphometric methods 450 microns thick slices of guinea pig hippocampus were studied after 5-hr incubation as controls in normal media and after incubation in media containing 40 microM lead acetate. Pyramidal neurons of the CA1 region and the granule cells of the fascia dentata were well preserved in the center of the slice, whereas neuronal structures in outer parts of the slice were either vacuolated or hyperchromatic and shrunken. Most of the CA4 neurons were lytic except for a few in the center of the slice. Morphometric analysis of the pyramidal layer of CA1 yielded approximately 55% well-preserved pyramidal neurons both in lead-exposed slices and in slices incubated in normal media. Electron microscopic examination of the CA1 region demonstrated no ultrastructural changes of lead-exposed slices compared to control. In conclusion, the reduction of evoked neuronal activities in the CA1 region of hippocampal slices during short-term lead exposure in vitro appears not to be linked to a specific neuropathological lesion.
Animals↗
Chemical induction of brain tumors in rats by nitrosoureas: molecular biology and neuropathology.
Nitrosourea-induced rat brain tumors are among the best investigated experimental systems for neuropathological, biochemical, diagnostic and therapeutic research in neurooncology. This review summarizes data concerning molecular biology, neuropathology, in vitro studies, transplantation models and antigen expression of experimental gliomas in inbred rat strains. Systemic application of nitroso-compounds, i.e., ENU and MNU, leads to the alkylation of DNA bases, which, due to a specific repair deficiency, persist in the nervous system remarkably longer than in other organs. The hypothesis is that alkylated bases cause base-mispairing and point mutations followed by uncontrolled expression of oncogenes and growth factor receptors, resulting in permanent cell proliferation. Thus, nitrosoureas are considered to be biological hazards, especially as potent endogenous and exogenous neurotoxins. Neuropathology and growth characteristics of these experimental tumors are comparable to human malignant gliomas. Similar to the human WHO grade III and IV tumors, they reveal cellular pleomorphism, elevated mitotic activity, proliferation of blood vessels, blood-brain barrier disturbances, necrosis and invasiveness. Nitrosourea-induced brain tumors have been used in investigations concerning glioma growth and regression, brain edema, glioma immunology, metabolism, regional biochemistry, and experimental therapy. The studies included conventional morphology, immunohistochemistry, -cytochemistry and -electronmicroscopy, morphometry, cell culture, hybridoma technology, tumor transplantation and regional imaging by autoradiography, bioluminescence, magnetic resonance and immunoscintigraphy.
Animals↗
Influence of 5-azacytidine on differentiation and growth in rat nervous system tumor cell lines.
In vitro studies with permanent cell lines derived from ENU-induced rat CNS and PNS tumors have shown that substances acting on second messenger systems as well as glucocorticoids have a cytostatic effect at high cell densities, but enhance proliferation at low densities. The nontoxic cytostatic effects are partially accompanied by the induction of differentiation monitored by immunocytochemistry with antibodies against GFAP, S-100 and PKC (alpha,beta). Cell differentiation with or without the influence of the drugs applied could be highly facilitated in some (CNS), but not all (PNS) types of tumor cells from neuroectodermal origin by pretreatment of cultures with 5-azacytidine under demethylating noncytostatic conditions. The implications of our results are relevant for molecular neurobiology and might offer new therapeutical approaches and may provide models for neurotoxicology.
Animals↗
[Immunocytochemical and biochemical studies of an Ewing sarcoma cell line: evidence for neural differentiation in vitro].
A cell line established from a Ewing's sarcoma removed from the fibula of a 19-year-old female was investigated for morphology and hormone sensitivity. Cells in culture expressed neurofilaments and showed positive immunostaining for neuron-specific enolase (NSE), Leu-7-antigen (HNK-1) and S-100 protein. The cells also contained PAS-positive, diastase-digestible cytoplasmic material, indicative of glycogen inclusions. Moreover, the cells responded to dopamine as well as to beta-adrenergic agonists and prostaglandins to stimulate cyclic AMP synthesis and 3H-glycogen hydrolysis. In conclusion, the morphological and biochemical data show evidence for a neural differentiation pattern of Ewing's sarcoma cells in vitro.
Antigens, Differentiation↗
Pleomorphic xanthoastrocytoma with desmoplastic reaction: angiomatous variant. Report of two cases.
Two cases of cerebral pleomorphic xanthoastrocytomas (PXA-s) with prominent vascularity and desmoplastic changes occurring in young subjects are presented. The tumors displayed the marked pleomorphism characteristic of PXA-s and had variable cellularity. The cytoplasm of many tumor cells contained an abundance of lipid droplets. Most tumor cells were positive for glial fibrillary acidic protein. The unusual feature about these tumors was the presence of very large numbers of tiny blood vessels with variable thickness of their walls. In many areas the small vessels and the neoplastic astrocytes were in close proximity to each other, with capillaries adjacent to or protruding into tumor cell cytoplasm, reminiscent of the pattern seen in highly vascularized or "angiomatous" meningiomas. In other areas extensive fibrosis was seen. We feel that the latter, as in the cases of comparably vascular meningiomas, had its origin in congelation and secondary organization of plasma proteins that have exuded through leaky walls of newly formed blood vessels. These are the first reported cases of PXA with an angiogliomatous pattern.
Adult↗
Antigen variation in a human glioblastoma: from the primary tumor to the second recurrence, permanent cell line and xenotransplantation tumors.
Antigen expression in a human glioblastoma was investigated by immunochemical methods in the primary tumor, the first and second recurrence, a permanent cell line derived from the first recurrence and in its xenotransplantation tumors. In the primary tumor, GFAP, vimentin, S100, Leu-7 and glioma-associated antigens (GAA) as defined by the monoclonal antibodies (mAbs) MUC 2-39, MUC 8-22 and MUC 2-63 were markedly expressed. In the recurrences, gradual loss of GFAP and Leu-7 could be observed, whereas S100, vimentin and GAA gave similar results to those in the primary tumor. In contrast, fibronectin and collagen IV, which were restricted to the vessel walls in the primary tumor, were represented in sarcomatous areas of the recurrences. In some of these areas, co-expression of glial cell markers was observed. In short-term cell cultures, expression of glia- and glioma-associated antigens as well as fibronectin and collagen IV was comparable to that of the recurrent tumor tissue. In long-term passages, immunoreactivity of GFAP, Leu-7 and S100 decreased, whereas GAA, vimentin and fibronectin increased. Collagen IV positive cells were not visible beyond passage 15. Transplantation tumors were only partly positive for glial cell markers, but revealed strong immunoreactivity for GAA, fibronectin and collagen IV. With these observations we confirm that the phenotypic variability of glioma cells makes it difficult to identify the origin of cells in human glioblastomas from their antigenicity.
Animals↗
Neonatal myotonic dystrophy in a premature infant: clinical and morphological findings.
We report a case of neonatal myotonic dystrophy in a premature infant of 34 weeks gestation. The striking pathological feature in muscle biopsy was severe generalized fiber hypotrophy. Histochemical stains for myofibrillar ATPase revealed a uniform fiber type of intermediate staining characteristics (Type II C). Oxidative preparations showed a light peripheral sarcoplasmic halo without enzymatic activity in most fibers. Ultrastructurally, fiber periphery consisted of a sarcoplasmic rim devoid of myofibrils and mitochondria and rich in glycogen granules and some vesicles. Satellite cells were numerous. Pathologic findings characteristic of the adult form of the disease were lacking. These morphological features were interpreted as a marked delay in fetal muscle maturation. The purpose in this paper is to present the unique pattern of myopathologic findings.
Adenosine Triphosphatases↗
Cystic changes and vascular permeability in meningiomas.
A retrospective study of 397 human meningiomas revealed microcystic and cystic changes in about 10% of tumors, predominantly meningiomas of the meningotheliomatous subtype. The biological behavior of these tumors corresponded to those of meningiomas in general, while one tumor singled out from the microcystic variant and separately described as myxomatous meningioma was characterized by a high recurrency rate. Histochemical and immunohistochemical examination with serum proteins of variable size indicated that the microcystic alterations are associated with local vascular permeability disturbances. Hyaline vascular changes and increased numbers of mast cells were further intriguing observations with respect to the pathogenesis of microcyst formation. Possible clinical implications, in particular in regard to the sometimes severe peritumoral edema, are discussed. Since surgical material is insufficient in this respect due to sampling limitations, an unoperated autopsy case is included in this study.
Adult↗
Primary malignant melanoblastosis of the meninges. Clinical, cytologic and neuropathologic findings in a case.
A 66-year-old man presented with a six-month history of neurologic symptoms suggestive of a craniospinal tumor or a diffuse inflammatory process in the subarachnoid space. Cytologic examination of cerebrospinal fluid (CSF) revealed inflammatory changes and malignant melanin-containing cells, leading to a diagnosis of meningeal spread of a melanoma. There was no history of skin excisions and no clinical evidence of primary melanoma of the eye. Neuroradiologic investigations, including CT and myelography, to confirm the diagnosis were negative. Despite intrathecal cytostatic therapy, the patient died eight months after the onset of symptoms. Autopsy disclosed diffuse meningeal melanoblastosis of the spinal cord and the base of the brain, confirming the cytologic diagnosis. In addition, two micrometastases in the liver were found as only extraneural manifestation. This case emphasizes the importance of CSF cytology in the diagnosis of diffuse infiltrating processes in the subarachnoid space.
Humans↗
Experimental carcinogenesis in the nervous system with N-nitroso-compounds.
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Animals↗
The epidermal growth factor receptor in glioblastoma: genomic amplification, protein expression, and patient survival data in a therapeutic trial.
Human glioblastomas were evaluated for overexpression of the epidermal growth factor receptor (EGFR) in a therapeutic trial with the anti-EGFR antibody EMD 55900. A total of 55 cases were examined by immunohistochemistry using 4 different monoclonal antibodies on frozen or on paraffin sections: EGFR-1 (Amersham), E 62 (Merck), E 30 (Merck), and EMD 55900 (MAB 425, Merck). Definition for inclusion in clinical trials of EMD 55900 was an immunohistochemical overexpression of grade 4+ or 3+ in a scale of 4 grades of staining quality. The use of the 4 different antibodies gave essentially equal results. In 21 cases, the immunohistochemical results were supplemented by molecular genetic analysis of EGFR amplification on the corresponding locus of chromosome 7, using frozen tissue from the same blocks after screening for vital tumor areas. Since no other material was available, the differential polymerase chain reaction technique was applied. Interferon-gamma (IFN-gamma) served as a reference gene. In a preliminary experimental series with cases of known EGFR amplification, a densitometric EGFR/IFN-gamma ratio higher than 3 was determined as indicator for amplification of the EGFR gene. With this experimental approach we were able to identify an amplified EGFR gene in 13 specimens including 2 from recurrent glioblastomas in the same patients. All of these showed an increased immunoreactivity for EGFR protein. The degree of EGFR amplification (EGFR/IFN-gamma ratio as measured by DNA densitometry) showed a positive correlation with the grade of immunohistochemical protein expression, both in regard to the fraction of positive cells and to the overall staining intensity.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.
This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.e. maturing neuroblastoma (ganglioneuroblastoma and gangliocytoma), S-100 protein-positive cells are mostly confined to the connective tissue septa dividing tumor into lobules, and are not freely interspersed with beta III-immunoreactive neoplastic neurons. Significant ensheathment of individual axon-like processes by Schwann cells occurs only in mature ganglioneuromas. beta III is localized in a full spectrum of neoplastic neuronal phenotypes, ranging from poorly-differentiated apolar neuroblasts (often signaling ensuing neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schwann cells in peripheral neuroblastomas are stroma-derived cells and not an expression of divergent neoplastic differentiation.
Adolescent↗
Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions.
We report the neuropathological and immunohistochemical findings in the brains of 14 AIDS patients with HIV-related encephalopathy. Clinically, half of the patients presented with severe AIDS dementia complex including advanced psychomotor retardation and behavioural dysfunction. These features correlated with striking cerebral atrophy and subcortical lesions visible in CT and/or MRI scans. In 7 cases early signs of impaired memory and concentration and/or psychomotor slowing were apparent accompanied by subcortical lesions in MRI scans and normal CCTs. In order to investigate the topographical distribution of HIV-1-associated features, in every case tissue samples from the frontal, temporal, parietal, occipital cortex and subcortical white matter, the hippocampus, basal ganglia, midbrain, pons, medulla oblongata and cerebellum were studied. In all patients histological examination disclosed the typical cellular constituents of HIV encephalitis (n = 12) or leukoencephalopathy (n = 2). Antibodies against lymphocyte subsets, CD68 antigen, myelin basic protein and GFAP were used to characterize the phenotype of cells and to highlight the white matter gliosis. The distribution and degree of pathological features were analysed in a semiquantitative scale, based on the number of CD68-positive cells, and disclosed great interindividual differences concerning the affected brain regions which only in part correlated with the severity of the clinical picture. It is noteworthy, that the deep gray matter, in particular putamen and thalamus, was involved in every case, independent from the stage of the disease. In addition, quantity and topographical distribution of HIV-1 core protein p24 were studied by use of two monoclonal antibodies. It is noteworthy, that the number of immunoreactive multinucleated giant cells and microglial cells decreased gradually from the deep gray matter, especially putamen and thalamus, and deep white matter to corpus callosum, cerebellar white matter and subcortical cerebral white matter. The topographical predilection of the deep gray matter even in cases with early cognitive decline indicates that the basal ganglia are affected early in the course of the disease. This observation closely resembles the results of highly sensitive quantitative neuropsychological tests which disclosed slowing and impaired coordination of rapid extremity movements indicating basal ganglia lesions even in early stages of HIV dementia.
AIDS Dementia Complex↗