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Biomedical subjects

R M Williams

Publications and source records attributed to R M Williams.

At least 199 records · Page 11Linked to original sources
PubMed1978

Sex differences in the multiple-dose streptozotocin model of diabetes.

The hyperglycemic response to multiple low-dose SZ injections was measured in castrated and non-castrated male and female mice with or without testosterone treatment. On the 10th day of the experiment, control males had plasma glucose concentrations that were significantly higher than those of control females. Castration of males decreased the hyperglycemic response, while testosterone treatment restored it. The glucose concentrations in castrated females were significantly greater than control females, but not different from castrated males. Testosterone administration to castrated or non-castrated females increased the hyperglycemic response to that seen in control males and in testosterone-treated castrated males. Thus, castration negates the sex difference in the hyperglycemic response to the multiple low-dose SZ injections. Testosterone enhances the hyperglycemic response in castrated or non-castrated females, and in castrated males.

Animals↗
PubMed1978

Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies.

Pancreatic insulitis and diabetes mellitus were induced in Charles River CD-1 mice with five subdiabetogenic injections of streptozotocin. Plasma glucose and immunoreactive insulin levels were measured and animals were sacrificed at intervals for morphologic studies of pancreatic islets and measurements of extractable pancreatic immunoreactive insulin. Light microscopy revealed striking insulitis, 5 to 6 days after streptozotocin injections, with cell necrosis and eventual islet atrophy due to beta-cell necrosis, and numerous type C viruses within many of the surviving beta-cells. Light microscopic immunoperoxidase stains of islet cell hormones and electron microscopy identified relatively increased numbers of alpha- and delta-cells within the atrophic islets 6 and 12 months after streptozotocin injections. Plasma glucose, plasma immunoreactive insulin, and extractable pancreatic immunoreactive insulin measurements documented the persistence of profound hyperglycemia, as well as the reduction of plasma and pancreatic immunoreactive insulin levels. Immunofluorescence studies demonstrated the absence of circulating islet cell antibodies during both the acute and chronic stages of the syndrome. The pathogenesis of this model of insulin-deficient diabetes is believed to be a cell-mediated autoimmune reaction directed against pancreatic beta-cells altered by subdiabetogenic injections of streptozotocin. The importance of the increased number of type C viruses within surviving beta-cells remains obscure.

Animals↗
PubMed1978

Procedure for processing of central nervous system tissue for immunofluorescence, light, and electron microscopic evaluation.

A rapid and simple procedure has been developed for the simultaneous localization of viral antigen in central nervous system tissues by immunofluorescnece and concomitant correlation with viral induced lesions in the contralateral brain hemisphere. In this study, one-half of the brain was excised from the dog under deep general anesthesia and samples were collected for immunofluorescence by snap freezing in liquid nitrogen. The other half of the brain was perfused under pressure with a buffered glutaraldehyde-paraformaldehyde mixture for subsequent light microscopic and ultrastructural evaluation. The technique was useful in studying central nervous system diseases in large outbred experimental subjects in which economic and other considerations developed for tissue processing in rodents was not feasible.

Animals↗
PubMed1977

Genetic influence of the streptozotocin-induced insulitis and hyperglycemia.

Multiple injections of subdiabetogenic doses of streptozotocin (SZ) to CD-1 male mice produce a diabetic syndrome that includes a cell-mediated immune reaction against the pancreatic islet. The importance of the host genetic background in the pathogenesis of this model of diabetes was studied by comparing various inbred strains of mice. Of eight strains of mice studied, only C57BL/KsJ developed insulitis and hyperglycemia comparable to that observed in CD-1 mice. In two mouse strains (DBA/J and BALB/cJ) having an H-2d haplotype similar to the C57BL/KsJ, only mild insulitis and glucose intolerance were observed. These data suggest that major histocompatibility complex genes, as presently defined, cannot be the only determinant of the severity of hyperglycemia and insulitis in this model.

Animals↗
PubMed1977

Rapid murine mixed lymphocyte cultures assessed by emergence of T cell insulin receptors.

Murine T lymphocytes incubated in the mixed lymphocyte culture with allogeneic lymphocytes incompatible for the H-2 region or subregions thereof rapidly develop insulin receptors. In contrast, T cells cultured with syngeneic or H-2 and M-locus compatible cells do not develop insulin binding sites. The emergence of insulin receptors may allow rapid HLA-D typing in man.

Animals↗
PubMed1977

Passive enhancement of rat renal allografts by antibodies to a non-SD (Ag-B) locus analogous to Ia and demonstration of linkage to the MHC.

The rat MHC contains a distinct locus for Ia-like antigens. The alleles of this locus are not always associated with like alleles of the MLR and Ag-B (SD) loci in inbred strains. This is demonstrated by the Fischer strain, which is MLR and tag-B (SD) 1 (H-11) but shares an Ia specificity with BN (Ag-B3, H-1n). The biologic significance of anti-Ia is distinctive, having in vivo graft-enhancing capability, even when it is cross-reacting (i.e., Lew anti-Fi enhances BN). In contrast, anti-AG-B (SD) does not enhance in the rat model.

Animals↗
PubMed1976

The evolution of the cooperative group.

A simple model, illustrating the transition from a population of free swimming, solitary cells (Chlamydomonas-type) to one consisting of small colonies (Gonium-type) serves as a basis to discuss the evolution of the cooperative group. The transition is the result of a mutation of the dynamics of cell division, delayed cell separation leads to colonies of four cells. With this mutation cooperative features appear, such as synchronised cell divisions within colonies and coordinated flagellar function which enables the colony to swim in definite directions. The selective advantages under given, environmental conditions are defined and the periods necessary for complete allelic replacement in small populations are calculated for asexual and sexual reproduction. The assumption of a steady-state population during allelic substitution is critically considered, particularly under conditions of competition. It is shown that density-dependent population control must operate in the process of selection, Sexual reproduction slows down the rate of selection even though all cells are haploid. This phenomenon can be explained in general terms of "organizational dominance', where individual units coordinate the function of their neighbours which may be of a different allelotype. Cooperativity is pointed out as an a priori systemic feature which resides in the sub-units of systems, group formation and coordination appears thus as an almost inevitable event. A particular type of system described as 'closed cycle of positive fitness interaction' is discussed in more detail. It has the remarkable feature that its members cannot compete with each other; selection takes place between whole cycles (in analogy to Eigen's 1971 model). Gonium has a wide spectrum of 'somatic plasticity' which enables it to assume various colonial configurations depending on physiological and environmental conditions. This feature can be explained as the result of dynamic flexibilities on the macro-molecular level. The particular relationship between the vast, molecular complexity and the relative simple dynamics of the cell cycle must lead eventually to the genetic fixation of an environmentally induced phenotype.

Animals↗
PubMed1976

Language behaviour in acute and chronic schizophrenia.

A predicition made by Broen (1968) regarding the performance of acute and chronic non-paranoid schizophrenics on measures of dominant verbal response bias was tested in a group of 40 hospitalized schizophrenic patients. A subgroup of 10 chronic patients were found to show an abnormal dominant response bias on two different language tasks and on one task showed a bias significantly greater than that shown by a group of 10 acute patients matched on verbal IQ and rated symptomatology. A correlational analysis of the bias scores of the total sample in relation to three indices of chronicity also showed a trend in the predicted direction of a greater dominant response bias with increasing chronicity. The data are consistent with Broen's (1968) theory of dominant response bias as a learned defence against aversive response interference in acute schizophrenia.

Acute Disease↗
PubMed1976

Specific and nonspecific antitumor immunity. III. Specific T lymphocyte-mediated cytolysis of P815 mastocytoma and SL2 lymphoma by draining lymph node cells from syngeneic tumor-bearing DBA/2J mice.

Tumor-specific cytolytic activity, as measured by the 51Cr release assay, has been demonstrated in the draining lymph node cells from DBA/2 mice bearing the syngeneic P815 mastocytoma or SL2 lymphoma. This lytic activity is mediated by cytolytic T lymphocytes (CTL), since cytotoxicity is eliminated by treatment of the effector cells with anti-Thy 1.2 (theta) serum plus complement but is enhanced or unaffected by anti-Thy 1.2 serum alone, antimouse immunoglobulin plus complement, normal or aggregated mouse immunoglobulin, or removal of adherent cells. The time course of the CTL response has been analyzed and is similar for both P815 and SL2, with a peak around Days 10 to 12 after tumor grafting. Detectable CTL activity then wanes despite continued antigenic stimulation from the growing tumor. The ability of the immunotherapeutic agent Corynebacterium parvum to augment such specific CTL responses is documented as one antitumor pathway by which this agent may act.

Animals↗