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Biomedical subjects

G L Wilson

Publications and source records attributed to G L Wilson.

At least 109 records · Page 6Linked to original sources

Use of pancreatic beta cells in culture to identify diabetogenic N-nitroso compounds.

Epidemiological observations suggest that environmental factors play a role in the pathogenesis of insulin dependent diabetes mellitus (1). Several chemicals have been identified as specific beta cell toxins (2-4). We report here studies to determine the feasibility of using monolayer cultures of pancreatic beta cells from neonatal rat to screen potential diabetogenic chemicals. Cytotoxicity was monitored both by phase microscopy and the release of insulin into the culture medium. In comparative studies, cellular protein and release of 51chromium (51Cr) were measured after addition of test compounds to cultures of fibroblasts derived from pancreatic tissue. The nitrosoamides 1 methyl-l-nitrosourea (MNU), 1,3 bis (2-choroethyl) nitrosourea (BCNU), chlorozotocin (CLZ), and the beta cell toxin, streptozotocin (SZ), were examined. CLZ and SZ were more toxic to pancreatic beta cells than to fibroblasts. In contrast, MNU and BCNU damaged both beta cells and fibroblasts at identical concentrations. These results suggest that in vitro techniques can be used to identify chemicals that selectively injure beta cells. Although SZ-induced toxicity was ameliorated with addition of nicotinamide to cultures of beta cells, nicotinamide did not prevent damage caused by CLZ. This observation indicates different mechanisms of drug-induced cytotoxicity.

Animals↗

The "bathroom game": a systematic program for the elimination of encopretic behavior.

The present investigation utilized a unique, variable ratio schedule of reinforcement (the "bathroom game") to treat a 10-year-old encopretic male. Dependent measures included confirmed incidents of (a) soiling and (b) appropriate bowel movements monitored across an ABAB design (Baseline 1, "Bathroom Game 1", Baseline 2, "Bathroom Game 2") with one-year follow-up. During "bathroom game" conditions, contingent monetary rewards were provided for non-instances of soiling and appropriate bowel movements. Such rewards were progressively and systematically leaned-out over the course of treatment on a pre-determined variable ratio schedule. Results indicated a clear demonstration of functional control and clinically significant treatment effects during both experimental periods. These findings are discussed with regard to the positive features of the "bathroom game" procedure and recommendations are made for future investigations in the area.

Behavior Therapy↗

Effects of the rodenticide Vacor on cultured rat pancreatic beta cells.

Human ingestion of the rodenticide Vacor has been implicated in the onset of diabetes mellitus. We report here studies of the effects of Vacor on cultured rat pancreatic beta cells and fibroblasts to determine if this agent preferentially intoxicates insulin-producing beta cells. Cytotoxicity in beta cells was monitored both by phase contrast microscopy and the release of insulin into the culture medium. Changes in cellular protein were correlated with morphologic observations to determine fibroblast viability. Beta cells were 10-fold more sensitive to the toxic effects of Vacor than were fibroblasts. Vacor toxicity was reduced by treatment with nicotinamide but was unchanged by 3-O-methyl glucose. Both of these agents reduced the toxic effects of the known beta cell poison streptozotocin. The present studies indicate that Vacor possesses a toxic affinity for pancreatic beta cells and that its mechanism of toxicity may be similar but not identical to that of streptozotocin.

Animals↗

Transformation in the presence of dimethyl sulfoxide facilitates recovery of Epstein-Barr virus.

Human umbilical cord blood lymphocytes were immortalized by infection with Epstein-Barr virus (EBV) in the presence of various concentrations of dimethyl sulfoxide (DMSO). 13 continuous lymphoblastoid cell lines were established. DMSO did not affect the efficiency of transformation and establishment of these lines. After a period of 2 months in culture, the lines were tested for EBV production by lethal irradiation (6,000 rad) from a 60Co source and subsequent cocultivation with primary umbilical cord lymphocytes. Cell lines transformed in the presence of 2% DMSO yielded transforming activity in 46.6% of test cultures, compared with 9.5% for lines established without DMSO in the medium. These findings imply that a permanent change in the host/virus relationship resulted from a brief exposure (48 h) to DMSO at the time of transformation.

Cell Line↗

Frequency of transforming Epstein-Barr virus in oropharyngeal secretions of rheumatoid arthritis patients.

To determine if rheumatoid arthritis (RA) patients have an increased frequency of Epstein-Barr virus (EBV) shedding into saliva, throat washings were collected from 59 patients with RA and 64 healthy adult controls. EBV in filtered samples was detected by transformation of human umbilical cord lymphocytes. EBV was detected in 27% (16/59) of throat washings of RA patients compared to 11% (7/64) of control samples. This difference is significant (p less than 0.05). RA patients on steroids had a frequency of positivity of 43% (10/23) compared to 17% (6/36) in patients not on steroids. No correlation was demonstrated between steroid dose received by the patient and detection of EBV in throat washings. Parotid fluid samples were collected from 18 RA patients and 11 healthy controls and were tested for EBV by the transformation bioassay. EBV was detected in 18% (2/11) of samples from normal controls, but samples from RA patients were uniformly negative.

Adrenal Cortex Hormones↗

Effect of genetic obesity in mice on the induction of diabetes by encephalomyocarditis virus.

The "M" variant of the encephalomyocarditis (EMC) virus causes a diabetes-like disease in some, but not all, strains of mice. The genetic basis for either resistance or susceptibility to the diabetogenic effect of the virus is not known. After infection with EMC, C57BL/6 mice seldom develop hyperglycemia and the insular lesions are subtle. To explore the possible effects of metabolic influences on the viral susceptibility of the islets, we studied C57BL/6 mice that were carriers of the ob gene. After virus inoculation, obese homozygous C57BL/6-ob/ob mice consistently developed hyperglycemia during the acute stages of infection, whereas nonobese littermates did not. Infection induced more severe lesions in the pancreatic islets of obese mice than in islets of the lean littermates. These studies suggest that the functional activity of the beta-cells influences the severity of the viral injury to the beta-cell, and the consequent occurrence of diabetes.

Animals↗

Isolation and characterization of a multiplication-stimulating activity (MSA)-like polypeptide produced by a human fibrosarcoma cell line.

A human fibrosarcoma cell line, 8387, produces and secretes multiplication-stimulating activity (MSA)-like polypeptide growth factors, which are associated with a high molecular weight binding protein. The purification of 8387-MSA involved concentration of serum-free media conditioned by 8387 cells, dialysis, and chromatography of the acid-soluble growth-promoting activity on Bio-Gel P-100 in 1 M acetic acid and subsequently on carboxymethylcellulose. The purification was followed by a radioreceptor assay specific for MSA and an assay for growth-stimulating activity. Both activities chromatographed through the purification steps of 8387-MSA. 8387-MSA competes with 125I-labeled rat MSA for binding on rat cells with a specific activity 5 times lower than that of rat MSA and stimulates [3H]-thymidine incorporation into DNA of normal rat fibroblasts at comparable concentrations. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the MSA-competing activity co-migrated with a single band of protein that behaved heterogeneously on discpolyacrylamide gels in the presence of 6 M urea, yielding two bands associated with biological activity. 8387-MSA is a single chain polypeptide with an apparent molecular weight of 14,500.

Animals↗

Uterine torsion.

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Animals↗

Ectopic liver tissue mass in the thoracic cavity.

A case is reported in which a liver tissue mass, not connected to the liver, was discovered growing in the right thoracic cavity. This mass appeared following trauma sustained to the liver several years earlier, and was noted to increase slightly in size after its initial detection. After removal of the mass, which proved to be benign hyperplastic liver tissue, the patient did well and remained free of symptoms. It is suggested that during the episode of trauma or during the ensuing surgical repair, a fragment of liver tissue was introduced into the thoracic cavity, and that this fragment eventually developed into a hyperplastic nodular liver mass.

Choristoma↗