Biomedical subjects

W Wechsler

Publications and source records attributed to W Wechsler.

At least 37 records · Page 2Linked to original sources

PubMed1991

Immunochemistry of ethylnitrosourea-induced rat neurinomas, the RN6 neurinoma cell line and their transplantation tumors.

The expression of glial fibrillary acidic protein (GFAP), vimentin, S-100 protein (S-100), HNK-1, myelin basic protein (MBP) and fibronectin was investigated immunohistochemically in 51 ethylnitrosourea (ENU)-induced neurinomas of the rat. Additionally, 90 transplantation tumors derived from ENU-induced neurinomas and the RN6 rat neurinoma cell clone were studied. Vimentin immunoreactivity was shown in 50/51 primary neurinomas and 60/90 transplantation tumors. In contrast, GFAP was expressed in only 23/51 primary tumors and in 5/90 transplantation tumors. In the RN6 neurinoma clone, vimentin and GFAP could be demonstrated both in vivo and in vitro. GFAP expression varied depending on the tumor localization, i.e., tumors of distal portions of peripheral nerves were more frequently GFAP positive than tumors of the spinal roots or of cranial nerves. The same tendency was observed for S-100. In the series of transplantation tumors S-100 and GFAP immunoreactivity decreased with increasing numbers of transplantation passages. Only individual cells in 5 primary tumors were HNK-1 positive and no MBP-immunoreactive cells were observed. Our results demonstrate that the expression of differentiation antigens in ENU-induced experimental neurinomas parallels the results reported for human neurinomas.

Animals↗

PubMed1991

Gliomatosis cerebri: bioptical approach and neuropathological verification.

Gliomatosis cerebri is rarely encountered and its intra vitam diagnosis has remained difficult. We present biopsy and autopsy findings in three cases that are representative of diffuse glioma, gliomatosis cerebri and diffuse glioblastosis, a modification of the subclassification proposed by Zülch31. Stereotactic biopsy in conjunction with nuclear magnetic resonance tomography (MRT) is recommended as the diagnostic procedure in suspected cases. Immunohistochemical examination with a panel of neuroectodermal markers is helpful in the differential diagnosis but has to take into account that reactive astrocytes may be closely intermingled with the neoplastic glial cells.

Adult↗

PubMed1991

Morphological, immunocytochemical and growth characteristics of three human glioblastomas established in vitro.

The human glioblastoma-derived cell lines 86HG-39, 87HG-28 and 87HG-31, used for the production of monoclonal antibodies (mAbs) against glioma-associated antigens (GAA), were characterized in terms of morphology, growth behaviour, chromosomes and antigen expression. In the primary tumours, differential expression of glial fibrillary acidic protein, S100 protein, Leu-7 and GAA as defined by mAbs MUC 2-39, MUC 2-63 and MUC 8-22 was demonstrated. Receptors for epidermal growth factor (EGFr) and nerve growth factor (NGFr) were found in many cells in short-term cultures, but the transferrin receptor (Tr) was found in only a few cells of 87HG-28. In permanent cell lines, differentiation antigens and EGFr decreased and Tr increased markedly. NGFr and GAA remained stable. Transplantation tumours of 86HG-39 were partly positive for Tr and GAA. Chromosomal analysis revealed that the 86HG-39 and 87HG-28 cell lines had a hypodiploid or diploid stem line with lines in the hypotetraploid to tetraploid region for 50 in vitro passages. The 87HG-31 cell line had chromosomal patterns in the hypotriploid to triploid region. A gain of chromosomes was seen in the groups C7, C8, C10, D14, F19, F20, G21, G22. The variability of antigens in these tumours and especially during long-term cultivation probably reveals an ability to influence the growth of malignant glioma cells via the respective effector molecules.

Antibodies, Monoclonal↗

PubMed1991

Myopathy in Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a disorder of unknown aetiology. The classical features of the syndrome include a typical ('elfin') facies, mental retardation and heart defects. Myopathy has not so far been part of the spectrum of WBS. We studied six patients with WBS aged 3-25 years, five of whom showed clinical and morphological evidence of myopathy. The clinical manifestations of myopathy included hypotonia in infancy, walking delay, joint contractures, scoliosis, and increased exhaustion on exertion. These symptoms were present in variable expression but part of a typical postural pattern. Examination of muscle biopsies showed lipid storage in four patients and increased variability of fibre size in three. In one patient a muscle biopsy gave normal results. Biochemical investigation in four patients with morphological evidence of lipid storage in muscle revealed muscle carnitine deficiency in three. In addition, enzyme activities of fatty acid beta-oxidation were low in one of two specimens tested. It is concluded that a clinically relevant myopathy is part of the multi-system manifestation of WBS and a clinical trial of carnitine supplementation is justified.

Adult↗

PubMed1990

Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction.

The expression of transferrin receptor (Tr) was investigated by means of immunohistochemistry in 101 tumours of the human central and peripheral nervous system. The results were compared with the proliferative activity of the tumours, determined by immunostaining for the proliferation-associated antigen Ki-67. In addition to immunostaining of normal and proliferated blood vessel endothelium and of a fraction of tumour infiltrating lymphocytes, we observed staining for Tr in a variable fraction of neoplastic cells of all histological tumour types. Immunoreactivity in the majority of tumour cells was found only in anaplastic tumours such as glioblastomas. Furthermore, a positive correlation between Tr expression and the Ki-67 growth fraction was established for gliomas. Non-glial tumours strongly expressing Tr included one metastatic rhabdomyosarcoma, one intracerebral malignant lymphoma, two of four plasmocytomas and seven of nine metastatic carcinomas. Our results indicate that immunohistochemistry for Tr and Ki-67 can provide additional information about the biological behaviour of nervous system tumours, thus complementing conventional histopathological criteria for anaplasia.

Antigens, Surface↗

PubMed1990

Metastatic adenocarcinoma in cerebral astrocytoma: clinicopathological and immunohistochemical study with review of the literature.

Metastatic spreading of carcinoma into a pre-existing cerebral glioma is extremely rare and only a few well-documented cases have been reported in the literature. Here we report a 53-year-old man who at the age 49 was first operated on for a frontal astrocytoma (WHO-grade II). This tumour was completely resected and no post-operative radio- or chemotherapy was applied. About five years later the patient presented again with a large partially cystic space-occupying lesion at the same site, which pre-operatively appeared as a recurrence of the astrocytoma. Histologically, however, this tumour proved to be a metastatic adenocarcinoma into a recurrent astrocytoma. Further clinical examinations revealed a bronchial carcinoma as the primary lesion responsible for this unusual metastatis. The clinical and neuropathological findings of this interesting case including immunohistochemistry are presented and discussed.

Adenocarcinoma↗

PubMed1990

Enhanced immunocytochemical staining sensitivity in formalin-fixed and paraffin-embedded material by simultaneous use of PAP and ABC.

The simultaneous use of two immunoperoxidase (IP) methods; e.g. the PAP (Peroxidase-antiperoxidase) and ABC (Avidin-Biotin) to localize a single antigen enhances the sensitivity of polyclonal antibodies (FVIII/RAg and laminin) or monoclonal antibodies (MABs) (against human B-, T-cells and macrophages) in routinely formalin fixed and in paraffin embedded material. The increased sensitivity was not accompanied by loss of specificity. With antibodies against Factor VIII related antigen (FVIII/RAg) and laminin the increased staining intensity of blood vessels were demonstrated in experimental rat transplantation tumors. The similar enhancement of immunocytochemical reactions was observed with biopsies of human brain tumors, where the monoclonal antibodies against white blood cells were used. The staining results were of comparable intensity as in snapfrozen tissue or after special embedding procedure for immunocytochemical purposes acc. to Bolton and Mesnard formol sucrose gum, sucrose paraffin; FSGSP).

Animals↗

PubMed1990

Pathology of tumours in laboratory animals. Tumours of the rat. Tumours of the peripheral nervous system.

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Animals↗

PubMed1990

Quantitative analysis of experimental peritumoral edema in cats.

Cat brain tumors were produced by stereotactical xenotransplantation of rat glioma clone F98 into the internal capsule of the left hemisphere. Two to four weeks after implantation, the tissue content of water, sodium, potassium, calcium, magnesium, serum albumin, serum immunoglobulin, and hemoglobin was measured in samples taken from the tumor, from peritumoral white and gray matter, and from homotopic regions of the opposite hemisphere. Extravasated serum protein content was determined by subtracting intravascular from total tissue protein, using the hemoglobin content as a marker of blood volume. The development of brain tumors was accompanied by severe vasogenic brain edema, which was clearly confined to the ipsilateral white matter. The increase of water was paralleled by an increase of sodium, calcium, and serum proteins. Potassium and magnesium content remained constant. The calculated sodium and calcium content of edema fluid approximated that of blood serum. The content of blood proteins was about 50% lower, but the ratio of albumin/immunoglobulin was the same as in blood. It is concluded that peritumoral edema is a combination of plasma ultrafiltrate and whole plasma extravasation with different modes of formation. Implications for the pathophysiology and therapy of peritumoral edema are discussed.

Animals↗

PubMed1989

Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67.

The proliferative activity of 133 human tumors of the nervous system was investigated by means of immunohistochemistry using the monoclonal antibody Ki-67 in order to evaluate the usefulness of this method for histopathological tumor grading. Ki-67 recognizes a proliferation-associated nuclear antigen present in human cells during all active phases of the cell cycle but absent in the G0 phase [Gerdes J, Schwab U, Lemke H, Stein H (1983) Int J Cancer 31:13-20]. In 28 WHO grade I and II gliomas of all major types Ki-67 indices were generally low with mean values ranging from less than 1% in pilocytic astrocytomas to 4.2% in grade II oligodendrogliomas. Individual cases of grade II astrocytomas and oligodendrogliomas had, however, values up to 8.5%. In 13 primary anaplastic gliomas of WHO grade III consistently higher statistical means were obtained with values ranging from 8.6% for anaplastic astrocytomas to 14.2% for anaplastic mixed gliomas. Interestingly, 18 WHO grade IV glioblastomas demonstrated a mean value of only 7%, which is probably due to the pronounced phenothypic heterogeneity in this tumor group. This heterogeneity results in enormous intra- and intertumor variability in Ki-67 indices (range less than 1%-22.1%). Investigation of 17 recurrent gliomas revealed mean values for Ki-67 ranging from 1.7% for three WHO grade II astrocytomas up to 48.5% obtained in two highly anaplastic recurrent astrocytomas corresponding to WHO grade IV. Other tumors of the nervous system evaluated included 9 medulloblastomas (mean 17.9%, range 5.0%-42.0%), 17 benign meningiomas (mean 1.1%, range 0%-5%), 15 metastatic carcinomas (mean 16.5%, range less than 1%-46.0%), and individual tumors of various types. Our results indicate that Ki-67 immunohistochemistry can add useful additional information for histopathological grading which, by supplementing and refining the traditional WHO grading system, might lead to a better assessment of the biological behaviour of human tumors of the nervous system.

Antibodies, Monoclonal↗

PubMed1989

Expression of vimentin and glial fibrillary acidic protein in ethylnitrosourea-induced rat gliomas and glioma cell lines.

The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immunohistochemically 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 oligodendrogliomatous 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 oligodendroglial or astroglial phenotype.

Animals↗

PubMed1989

Immunohistochemical determination of protein kinase C expression and proliferative activity in human brain tumors.

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 neuro-oncology.

Adult↗

PubMed1989

Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system.

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 factyr 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 plasmacytomas 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 EGFr-expression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.

Cell Division↗

PubMed1989

Experimental transplantation gliomas in the adult cat brain. 1. Experimental model and neuropathology.

Tumours were produced in the adult cat brain by injection of the rapidly growing anaplastic rat glioma clone F98 in order to study their neuropathology, pathophysiology, regional biochemistry and magnetic reasonance imaging. We report here the neuropathological behaviour of cell suspensions in the basal ganglia and the left cerebral hemisphere one, two, three, four and six weeks after stereotactic implantation with respect to tumour growth, immunological tumour regression and alterations of the blood-brain barrier with associated vasogenic brain oedema. Injected cell suspensions produce consistently growing tumours during the first, second and third weeks. Tumour sizes varied according to the survival time and were only slightly dependent on the inoculated cell number, i.e., 3 and 6 x 10(6) tumour cells, respectively. Immunohistochemistry with respect to proteins of the cytoskeleton and other cell markers showed positive tumour cell immunoreactions for vimentin and S 100, but not for GFAP, Leu-7, Leu-M1 and MBP. While leucocyte infiltration is apparent after only one week, major tumour regression phenomena develop after three weeks in conjunction with severe lymphocytic reactions of the host, resulting in complete tumour rejection with scar gliosis after four and six weeks, respectively. This transplantation glioma model is accompanied by vasogenic brain oedema both within the tumour area and in the homolateral hemisphere. Immunohistochemistry of serum proteins, i.e. total serum protein, albumin and IgG reveals impairment of the blood-brain barrier after one week, reaching its maximum after two and three weeks. The oedematous changes decrease dramatically after four and six weeks, when most of the serum proteins are reabsorbed by cellular activities in the tumour scar. The vasogenic brain oedema in this xenogeneic glioma transplantation model may be enhanced by the immunological reactions in the brain.

Animals↗

PubMed1989

Primary intracerebral malignant lymphoma presenting with ophthalmological symptoms: bioptical and autoptical case study.

A case of primary malignant lymphoma of the brain with preceding first unilateral, then bilateral uveitis and retinochorioiditis is presented. The diagnosis was established on brain biopsy material using immuno-histochemical methods. The autopsy disclosed a polymorphous immunocytoma with bilateral brain involvement including structures of the posterior optic pathways. Clinical and pathogenetic implications regarding this "oculo-cerebral type" of malignant lymphoma, which has been only seldom reported in the literature are discussed.

Brain Neoplasms↗

PubMed1989

Nerve growth factor receptor in tumours of the human nervous system. Immunohistochemical analysis of receptor expression and tumour growth fraction.

The expression of nerve growth factor receptor (NGFr) was investigated by means of immunohistochemistry in 135 tumours of the human central and peripheral nervous system. The results were compared to the proliferative activity of the tumours as determined by immunostaining for the proliferation-associated antigen Ki-67. Immunoreactivity for NGFr was most consistently observed in tumours derived from the neural crest such as neurinomas, neurofibromas and ganglioneuromas. In tumours of the central nervous system, NGFr-immunostaining was particularly strong in pilocytic astrocytomas while the majority of other gliomas were either NGFr-negative or contained only a minor fraction of NGFr-positive tumour cells. Among all other investigated tumours including medulloblastomas, pituitary adenomas and meningiomas only exceptional cases demonstrated a significant number of positive tumour cells. Choroid plexus papillomas and metastatic carcinomas were always NGFr-negative. Our results indicate that NGFr-expression in tumours of the human nervous system is heterogenous with respect to tumour type and appears to be unrelated to proliferative activity.

Humans↗

PubMed1988

Significance of lymphocytes and blood vessel changes for edema formation in polyradiculoneuritis.

Human sural nerve biopsies of eight cases with acute, subacute and chronic polyradiculoneuritis were studied by means of immunohistochemistry to characterize the inflammatory infiltrates. In addition, the structural changes of the endoneurial blood vessels were examined by electron microscopy, since both factors are likely to contribute to disturbances of the blood-nerve barrier. By use of six monoclonal antibodies, it was shown that the inflammatory infiltrates in cases with more acute polyradiculoneuritis are predominantly recruited by Leu 3a- and Leu 4-positive T lymphocytes. In more chronic polyradiculoneuritis beside of few Leu 3a-positive and Leu 4-positive T lymphocytes also B cells occurred. Leu M3-positive macrophages were detected in all cases with fluoride myelin degeneration. Since immunoreactivity for antigens of the HLA-D-locus (Leu-HLA-DR and Leu 10) were present on the infiltrating mononuclear cells, it can be postulated that they represent active and immunocompetent cells. Ultrastructurally, the amount of pinocytotic vesicles in the endothelial cells of the endoneurial blood vessels was increased. Moreover, a prominent folding of the luminal and abluminal surface of vascular endothelial cells and diminution of the intercellular tight junctions were observed. These findings appear suitable to explain the increased leakage of serum proteins across the blood-nerve barrier in polyradiculoneuritis sharing general features of cell-mediated immunity.

Adolescent↗

PubMed1988

Vascularization of syngenic intracerebral RG2 and F98 rat transplantation tumors. A histochemical and morphometric study by use of ricinus communis agglutinin I.

The vascularization of intracerebral transplantation tumors of the two rat glioma clones RG2 and F98 was studied in various stages of progressive tumor growth by use of biotinylated Ricinus communis agglutinin I (B-RCA I) in avidin-biotin-peroxidase complex (ABC)-histochemistry. The tumors were induced by stereotactic implantation of 1000 glioma cells into the right caudate nucleus of 26 adult CDF-rats and examined after 10, 14, 18, and 21 days following controlled intracardial perfusion of the host animals. Our histochemical results on paraffin sections demonstrate that B-RCA I selectively stains vascular endothelial cells of arteries, veins, and capillaries not only in the normal rat brain but also in the transplantation tumors. Subsequently morphometric measurements of the B-RCA I-stained sections were performed to define the tumor vascularization in quantitative terms. There was an increase in the mean tumor vessel diameters during tumor growth in both transplantation tumor types leading to values about two times above those of the normal rat striatum. On the contrary, the mean vessel density and the mean vessel surface per tumor area were markedly reduced in the late stages of both tumor types when compared to the normal striatum. The RG2 and F98 transplantation tumors differed with regard to the intercapillary distance, which was two times higher in the F98 transplantation tumors than in the RG2 tumors on day 21. In conclusion, B-RCA I is a very sensitive histochemical marker for rat vascular endothelia on paraffin sections. Moreover, this method appears to provide the possibility for qualitative and quantitative study of the development of vasculature in intracerebral transplantation systems including tumors.

Animals↗