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Biomedical subjects

W Wechsler

Publications and source records attributed to W Wechsler.

At least 73 records · Page 4Linked to original sources

Affinity cytochemistry of vascular endothelia in brain tumors by biotinylated Ulex europaeus type I lectin (UEA I).

The vascularization of 50 tumors of the central nervous system (CNS) including 17 meningiomas, 25 neuroectodermal tumors, i.e., astrocytomas, oligodendrogliomas, mixed gliomas, glioblastomas, medulloblastomas, seven metastatic carcinomas, and one malignant hemangioendothelioma were investigated using biotinylated Ulex europaeus type I lectin (UEA I) in an indirect avidinbiotin-peroxidase procedure. The cytochemical staining pattern of UEA I on paraffin sections was compared with that of biotinylated Dolichos biflorus lectin (DBA), and with the immunocytochemical staining of factor VIII related antigen (F VIII/RAG) by polyclonal antisera using the PAP technique. UEA I visualized the endothelia of blood vessels with equal intensity, sensitivity, and reliability in normal brain and in tumor tissue with neovascularization. While large, medium, and small vessels were equally well demonstrated by UEA I and antibodies against FVIII/RAG, capillaries and endothelial sprouts were stained more consistently and intensely by UEA I. No reliable cytochemical staining could be obtained by DBA regardless of tissue or cell type investigated. It is concluded that UEA I is a highly useful cytochemical marker for the identification of vascular endothelia in paraffin sections of human brain tumors.

Antibodies↗

The mouse blood-brain barrier and blood-nerve barrier for IgG: a tracer study by use of the avidin-biotin system.

To study the permeability of the blood-brain barrier (BBB) and the blood-nerve barrier (BNB) for immunoglobulin G (IgG) we adapted the avidin-biotin system for postembedding demonstration of the tracer IgG in the central and peripheral nervous system (CNS, PNS). Normal mouse and human IgG were biotinylated and injected daily into the intraperitoneal (i.p.) space of adult BDF1 mice. After 24h, IgG was detected in blood vessels and in the interstitium of various organs, but staining was restricted to the dura mater in the CNS, to the spinal ganglia, and to the perineurium of peripheral nerves. After 4 days, IgG was also present in the endoneurial connective tissue of peripheral nerves, while the brain, spinal cord, and spinal roots remained free of IgG. Our results show a partial permeability of the normal mouse BNB for homologous and heterologous IgG.

Animals↗

Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies.

Post-embedding immunocytochemical studies on immunoglobulins (Ig) and other serum proteins were carried out on 38 human sural nerve biopsies using the PAP method. In addition to toxic, hereditary, metabolic, dysproteinemic, and vasculitic-neuritic neuropathies, morphologically normal sural nerves were included as controls. The intensity of the immunocytochemical reactions was strong for proteins, such as IgG, the light chains of Igs, and albumin, but weak or absent for others like complement component C3, IgA, ceruloplasmin, and alpha-1-antitrypsin (AAT) in normal nerve biopsies and in all pathologic groups. IgG, the light chains of immunoglobulins, and albumin could readily be detected in perineurium, endoneurial interstitium, and blood vessel walls. IgM, C3, and beta-lipoprotein (BLP) were largely confined to the walls of blood vessels and perineurium, thus indicating that they do not penetrate the blood nerve barrier. Only in a few cases, in vasculitic-neuritic and dysproteinemic neuropathies, staining of the endoneurial interstitium for IgM and C3 was observed. Increased staining for the corresponding heavy or light chains was not detected in the endoneurium in any of the neuropathies associated with gammopathy. The results stress that PAP immunocytochemistry is suitable for studying the blood-nerve barrier (BNB) and provides new aspects to the concept of the BNB with respect to the steady state of serum proteins between endoneurial and vascular spaces. It is suggested that, in addition to serum concentration and molecular weight of serum proteins, the permeability of the BNB is influenced by other yet undefined factors.

Adolescent↗

Adult-onset mixed myopathy with nemaline rods, minicores, and central cores: a muscle disorder mimicking polymyositis.

A woman, aged 75 years, presented with a 15-year history of progressive, generalized, painful muscle weakness and wasting. Clinical and laboratory investigation revealed a sporadic muscle disorder. Muscle biopsy showed a mixed pattern of nemaline myopathy with minicores and central cores and severe atrophy of type-1 and type-2 fibers. A trial of immunosuppressive treatment did not improve her condition, which clinically mimicked chronic progressive polymyositis. Mixed myofibrillar myopathies of this type have so far only been described among the group of congenital myopathies.

Age Factors↗

Disseminated (metastatic) tumors in nude mice produced by intravenous injection of cells of human and nonhuman neurogenic tumor lines.

Cells of two human glioma lines (UC-35AG, UC-58EG), a human medulloblastoma line (UC-51MB), two rat glioma lines C6, RG2), and a rat schwannoma line (Lew-MS) were injected i.v. into male nude mice (BALB/c nu/nu). Each animal was injected with 10(6) viable cells of a particular line; for each line there was a group of eight to nine animals. The mice developed disseminated (metastatic) tumors from all lines. The incidence of mice developing metastatic tumors was different for the various lines: 2/8 for the UC-34AG, 7/9 for the UC-58EG, 1/8 for the UC-51MB, 7/8 for the C6 line, 8/8 for the RG2 and 1/9 for the Lew-MS line. The shortest survival of the mice with tumors was observed with C6 (all died on days 10-14 post injection), and with RG2 (all died from day 32 to day 39 following injection). With the remaining lines, all mice survived until they were killed on day 40 after injection. Most frequently the tumors developed in the lung. Other organs, e.g., kidney or liver, were sometimes also involved, but usually to a considerably lesser degree than the lung. Metastases never developed in the CNS. It was observed that tumors of certain glioma lines tended to grow in the lung in characteristic patterns and involved or spared other organs.

Animals↗

Congenital Leigh's disease: panencephalomyelopathy and peripheral neuropathy.

A dystrophic newborn girl (38th week of gestation) presented as a floppy infant with relapsing episodes of lactic acidosis and progressive cerebral deterioration. She died after serious apnoea at the age of 8 weeks. Neuropathological examination demonstrated widespread changes of Leigh's subacute polioencephalomyelopathy affecting the cerebral cortex, basal ganglia, mesencephalon and spinal cord. In addition, there was severe leukoencephalopathy of the cerebral hemispheres with sudanophilic tissue degregation, advanced axonal loss and reactive astrocytic gliosis. There was marked demyelination of the sciatic nerves. Electron-microscopical examination of the hypertrophic heart revealed pathological mitochondria with tubular inclusions suggestive of primary mitochondrial cardiomyopathy. Similar mitochondrial changes were not detected in the CNS and PNS. The complex of neuropathological alterations in this case is nevertheless consistent with a congenital variant of Leigh's disease.

Brain↗

Brain tumor growth and response to chemotherapy in the subrenal capsule assay.

Pieces from eight freshly biopsied human gliomas and tumors grown from a human glioma (U118MG) established by transplantation and a rat glioma (RG2) were transplanted under the renal capsule of normal, immunocompetent rats. The effects of chemotherapy administered intraperitoneally to host rats were evaluated by measuring the growth of implanted tumor specimens. Results could be obtained within 7 days of transplantation and suggest that the subrenal capsule assay might be useful in the future for the rapid evaluation of the sensitivity of human brain tumors to therapeutic manipulation. The limitations of the assay are discussed.

Animals↗

Radiation and drug response of the rat glioma RG2.

A clonogenic cell assay was developed for the chemically induced rat glioma RG2 that allows in vivo, in vitro, and in vivo to in vitro studies of cell survival after experimental therapy. RG2 monolayer cells were resistant to BCNU up to high concentrations. The radiation survival curves were characterized by a Do of 2.4 gray and n = 2.2 for monolayer cells, a Do of 3.5 gray and n = 1.3 for cells irradiated as brain tumors in air-breathing rats, and a Do of 5.9 gray and n = 1.2 for cells irradiated as brain tumors in nitrogen-asphyxiated rats. There was no evidence of a radiobiologically hypoxic fraction of cells in the brain tumors, but their radiosensitivity was definitely smaller than that of monolayer cells.

Animals↗

Characterization of cell cycle and biological parameters of transplantable glioma cell lines and clones.

Aberrant biological characteristics of established cell lines and clones, derived from nitrosourea-induced gliomas in CDF rats were compared with normal rat glial cells. Despite their tumorigenicity and unrestrained proliferation due to inherent cytogenetic anomalies, these neoplastic cells retained certain normal glial attributes to a variable degree. Differentiated glioma cells resembled normal glial cells to a greater extent than they resembled anaplastic glioma cells. They were also less malignant upon implantation. Cell cycle analyses revealed that considerable variations not only for the G1 phase but also for the S period were demonstrated among different tumor cell types. Shortening of the G1 phase may dictate a shorter generation time (shorter doubling time) since a larger potential proliferative pool may overcome the effect of a prolonged generation period may constitute a faster proliferation rate. Although the cell generation period of neoplastic cells is not necessarily shorter than that of normal glial cells, the lower proportion of nonproliferative cells results in a much faster growth rate when compared wo non-neoplastic glial cells in culture.

Animals↗

Adenovirus type 12-induced rat tumor cells of neuroepithelial origin: persistence and expression of the viral genome.

Four cell lines derived from adenovirus type 12-induced rat brain tumors were studied. The polyploid cells displayed neuroepithelial characteristics and were transplantable into syngeneic rats and nude mice. In tissue culture the cells grew in monolayers and multilayers. A very high saturation density was reached, and the cells plated in agar and were easily agglutinated with low concentrations of concanavalin A. Between 2 and 11 copies of the viral genome per diploid cellular genome were detected by reassociation kinetics analysis in the different lines. The patterns of distribution of viral DNA sequences in these lines, as revealed by blot analysis, suggest colinear integration of the intact viral genome into the cellular DNA. The patterns of integration were stable after more than 15 months of prolonged tissue culture and after animal reimplantation. Integration patterns were identical in three of the tumor lines and different in another line. Viral sequences were transcribed. The extent of homology found toward adenovirus type 12 DNA in polyadenylated polysome-associated mRNA isolated from the tumor lines suggests that the early and some of the late genes of adenovirus type 12 DNA are transcribed in these tumor cells. Infectious virus was not rescuable from these lines.

Adenoviruses, Human↗