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Biomedical subjects

W Wechsler

Publications and source records attributed to W Wechsler.

At least 91 records · Page 5Linked to original sources
PubMed1979

Morphologic and biochemical characteristics of transplantable neurogenic tumors induced by N-ethyl-N-nitrosourea in inbred BD IX rats.

Brain and nerve tumors were induced transplacentally in inbred BD IX rats by systemic application of N-ethyl-N-nitrosourea. Because primary gliomas and neurinomas produced in this way are composed of heterogeneous cell populations, changes in tumor morphology were expected to occur during serial transplantation in syngeneic hosts. In this study such changes in morphology were correlated with the expression of two biochemical nervous system markers, S-100 protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Several changes were observed during serial transplantation, including increased growth rate (even after one passage), preferential growth of anaplastic versus differentiated glial and Schwann's cells, varying degrees of fibrosarcomatous changes after prolonged serial transplantation, and reduced levels of S-100 protein. In contrast, tumors derived from biochemically differentiated clonal cell lines retained their morphologic and biochemical characteristics to a much greater extent, even after prolonged periods of sc transplantation.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

Transplacental and neonatal induction of neurogenic tumors in mice: comparison with related species and with human pediatric neoplasms.

The literature on chemical induction and natural occurrence of neurogenic tumors in mice and some unpublished data from our laboratories are reviewed. Neurogenic tumors are a minor component of the total tumorigenic response of mice to alkylating agents such as ENU and MNU. In comparison with rats, a given dose of ENU induces a much lower incidence of neurogenic tumors in mice, and the mean latency is much longer than in rats. Although most neurogenic tumors induced by ENU in mice by either transplacental or direct postnatal exposure are of glial or Schwann cell origin, as in rats, and occur most frequently in the cerebrum or cranial nerves, respectively, medulloblastomas of the cerebellum also occur in treated mice. Transplacental and neonatal exposure to ENU were much more effective in inducing neurogenic tumors than treatment later in life. Ependymomas were not seen in mice, although they are common in ENU-treated rats. Neuroblastoma of the adrenal medulla, a common human pediatric tumor, has not been induced to either species, but it does occur spontaneously in mice. The induction by ENU of medulloblastomas demonstrates that this rodent equivalent of an embryonal tumor of the human nervous system can result from exposure to exogenous chemical agents.

Animals↗
PubMed1978

Glucocorticoid induction of tyrosine hydroxylase in a continous cell line of rat pheochromocytoma.

We have established a continous cell line (G1) in which the tyrosine hydroxylase specific activity is increased as much as 50-100-fold in response to dexamethasone. This response is specific for the glucocorticoid class of steroid hormones; it is elicited by dexamethasone, corticosterone, and triamcinolone, but not by estradiol, testosterone, progesterone, or deoxycorticosterone acetate. The increase in tyrosine hydroxylase specific activity is likely to be due to the increased synthesis of new enzyme protein rather than an activation of existing protein molecules, inasmuch as this increase is completely blocked by cycloheximide.

Adrenal Gland Neoplasms↗
PubMed1978

Immune status in Crohn's disease. I. Leukocyte and lymphocyte subpopulations in peripheral blood.

Proportions and absolute numbers of circulating leukocyte populations and lymphocyte subpopulations (T- and B-cells) were determined in 33 patients with Crohn's disease (group CD), and were compared with those of age- and sex-matched healthy subjects. Group CD comprised 15 patients with newly diagnosed, short-standing, and untreated CD (group CD 1) and 18 patients with long-standing, previously drug treated CD (group CD 2). All CD groups showed a significant absoulte leukocytosis, based on a significant absolute and relative increase of the neutrophils, and, as far as group CD and CD 1 were concerned, also of the absolute number of monocytes. In group CD 1, absolute lymphocyte and relative as well as absolute T-cell numbers were close to normal. In contrast, in group CD 2 absolute as well as relative numbers of lymphocytes and absolute numbers of T-cells were highly significantly reduced, whereas the reduction of the relative T-cell concentration barely reached significance. The proportion of B-cells was significantly above normal in all patient groups, the absolute number in group CD only. Also group CD 1 showed considerably, though statistically insignificantly, higher than normal absolute B-cell numbers. In group CD 1 , there was an inverse correlation between absolute T-cell numbers and disease activity, and between absolute lymphocyte numbers and duration of disease. These data indicate that there is no gross numerical reduction of the carriers of the cell-mediated immunity as a primary predisposing factor for CD, but that a reduction of these cells occurs in the circulation after the disease has started.

Adult↗
PubMed1978

Association between susceptibility to experimental allergic encephalomyelitis and the major histocompatibility system in congenic rat strains.

The genetics of the inducibility of experimental allergic encephalomyelitis (EAE) was studied in ten inbred rat strains by injection of guinea pig spinal cord in complete Freund's adjuvant. LEW rats were highly susceptible and AS2, AVN, BDV and BN rats were poorly susceptible. Congenic strains which carried the major histocompatibility haplotype of the poorly susceptible strains on the genetic background of the susceptible LEW strain were only moderately susceptible. It is concluded that major histocompatibility-linked genes exert a strong influence on the susceptibility to EAE, but that genetic background genes are also involved.

Animals↗
PubMed1977

Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system.

Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas. This could not be attributed solely to zones of regression or necrosis but was a general characteristic of the neoplasms. The activities were predominantly particulate and most likely lysosomal in localization. In schwannomas a similar increase in hydrolases was found in comparison with normal neural tissues but aryl-sulfatase was not increased. Cytochrome oxidase activities were markedly reduced in all tumors studied. The proportionate reduction with respect to normal brain was comparable to that noted in man. No differences were found with respect to fairly well differentiated gliomas.

Animals↗
PubMed1976

14-3-2 protein in rat primary and transplanted gliomas and neurinomas and in clonal cell lines.

Experimental neurogenic tumors were induced transplacentally in rats by single injections of ethylnitrosourea (ENU). The resulting primary tumors as well as isogenic transplantation tumor lines and clonal cell lines derived therefrom were examined for their content of the brain specific protein 14-3-2 by a quantitative microcomplement fixation assay. The content of S-100 protein in the samples studied is given as well. Some of the tumors of glial or Schwann cell origin did contain 14-3-2 protein ranging from 0.6 to 1.5 mug 14-3-2 per mg total soluble protein. Our experiments also showed that the ability of a tumor to produce this specific protein is transplantable over a series of subcutaneous isogenic transplantations while in the transplantation tumors the content of this protein seemed to be reduced. We were not able so far to find a correlation between the morphology of a tumor and its capability to produce a specific protein. The clonal cell line RN2 of Schwann cell origin which has been previously described in detail contained both the brain specific proteins 14-3-2 and S-100 in comparable amounts ranging from 0.3 to 0.6 and from 0.4 to 1.0 mug specific protein per total soluble protein respectively.

Animals↗
PubMed1976

Sequential adsorption analysis of antibodies to neuroectodermal cells by an indirect quantitative method.

An indirect radioimmunoassay was developed for the sequential adsorption analysis of rabbit antibodies raised against rat neuroectodermal cells. The quantitativee relationship between primary adsorbed rabbit antitumor antibodies and secondary adsorbed goat antibodies to rabbit IgG was explored by paired radioiodine analysis. In the final indirect method, the amount of unlabeled rabbit antibody removed by cultured monolayers of cells at each step in a sequence of cells could be determined from an equation relating the unlabeled amount to values of bound 125I-labeled goat antirabbit IgG. To obtain the total quantity of rabbit antibody in a particular antiserum reagent, a sequential adsorption analysis was done with successive steps of homologous cells. To obtain the amount of antibody that was cross-reactive for other cell lines, we included those lines in the first several steps of the sequence. The sequential adsorption profile was considered as a more important indicator of the quality of a particular antiserum reagent than was the total amount of antibody contained in it. Neuroectodermal cell lines used as illustrative examples included subclones of the C6 astrocytoma and of the RN-2 schwannoma.

Animals↗
PubMed1975

Transplacental induction of neurogenic tumors in BD IX rats by intragastric administration of ethylnitrosourea precursors.

The concurrent daily intragastric administration of ethylurea at two dose levels (50 mg/kg and 100 mg/kg bodyweight) together with one dose level of sodium nitrite (50 mg/kg bodyweight) by a stomach tube to pregnant BD IX rats from day 15 to day 22 of gestation resulted in the induction of neurogenic tumors in all offspring. Since both ENU-precursors alone do not produce neurogenic tumors, these results are evidence of ENU formation from its precursors under the influence of gastric juice. Differences in the survival time and the incidence of tumors at both dose levels were not significant. The amount of ethylnitrosourea synthesized in the animals was very close at both dose levels, and was dependent on the amount of sodium nitrite applied. The experimental results are consistent with the conclusion, that the rat fetuses had been exposed to a total amount of about 60 mg/kg ethylnitrosourea. Neurogenic tumors dominated with 98% incidence over the non-neurogenic. The incidence of neurogenic tumors per rat was high (6.0 for Group I and 6.7 for Group II). Neurogenic tumors were equally distributed among the central and peripheral nervous systems. The neurogenic tumors induced with the precursors of ethylnitrosourea were morphologically similar in all aspects to those induced with the carcinogen itself and could be classified as oligodendroglioma, astrocytoma, mixed glioma, anaplastic glioma, glioependymoma, ependymoma, and neurinoma. Three unusual tumors were found: one early anaplastic "septum ependymoma" in the dorsal column of the spinal cord, and two special mixed tumors of the cranial nerves, i.e. a neurinoma with portions of an oligodendroglioma and a neurinoma with parts of an invasive ependymoma.

Animals↗
PubMed1975

Differential oncogenic effects of methylnitrosourea.

We investigated differences in the oncogenic effects of methylnitrosourea (MNU) which were induced by varying dose schedules and changing administration routes. The nervous system represented the target organ when MNU was given intravenously to rats. Carcinogen by other routes resulted in decreased numbers of neurogenic tumors and the appearance of neoplasms at the injection site. Increased oral doses of MNU caused shorter survival times, a decreased incidence of neuroglial tumors, and increased numbers of thymic lymphomas and mesenchymal tumors of the nervous system. The results suggest that many tissues are susceptible to the oncogenic effects of MNU, but the degree of exposure necessary for neoplastic transformation varies.

Administration, Oral↗