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Biomedical subjects

G A Wilson

Publications and source records attributed to G A Wilson.

At least 19 recordsLinked to original sources
PubMed1992

SJL/J resistance to mouse hepatitis virus-JHM-induced neurologic disease can be partially overcome by viral variants of S and host immunosuppression.

The basis of the resistance of SJL/J mice to various strains of mouse hepatitis virus (MHV) has been the subject of some debate, especially as it relates to the number and nature of the determinants involved. Our previous work demonstrated that resistance by primary SJL/J glial cultures may involve events subsequent to viral gene expression, possibly due to a defect in cell-to-cell spread of the infection. Since S, the virion's major spike glycoprotein, is known to facilitate the spread of infection due to its syncytiogenic properties, we decided to investigate the role of this viral structural protein in resistance by primary SJL/J glial cells. Variants possessing deletions within the S coding region were able to grow in SJL/J glial cells 10-100 times easier and fuse five-times more efficiently than wt virus. Induction of neurologic disease in SJL/J mice following intracranial inoculation with either wt JHMV or the S deletion variant, AT11f cord, was age-dependent, occurring only in animals inoculated under 4 weeks of age. Resistance in older animals to wt and variant viruses could be abrogated by immunosuppression with cyclosporin A. However, both disease incidence and viral brain titers were higher in animals receiving the JHM variant AT11f cord virus, suggesting that SJL/J resistance to neurologic disease may manifest itself through interactions between inefficient cell-to-cell spread of the infection and protective aspects of the immune response.

Animals↗
PubMed1992

The usefulness of the dynamic phase in pertechnetate thyroid imaging for solitary hypofunctioning nodules.

One hundred patients, each with a solitary thyroid nodule detected by clinical palpation, underwent three-phase Tc-99m pertechnetate thyroid imaging. The degree of perfusion of the thyroid nodule was classified as hypo-perfused, euperfused, or hyperperfused compared to the remainder of the gland by a consensus of three nuclear medicine physicians. The nodules were subsequently biopsied, and the degree of perfusion of the nodules was correlated with their histologic diagnosis. Twenty-two nodules were classified as hyperperfused, 64 as euperfused, and 14 as hypoperfused. Malignancy rates of the hyperperfused, euperfused, and hypoperfused nodules were 36%, 31% and 0%, respectively. This seems to indicate that malignant thyroid nodules demonstrate a degree of perfusion at least equal to or greater than the rest of the thyroid gland. Conversely, none of the hypoperfused nodules was found to be malignant. The perfusion phase of thyroid imaging may provide useful clinical information regarding possible malignancy of a thyroid nodule.

Adenocarcinoma↗
PubMed1991

A developmentally regulated gene encodes the dictyostelium homolog of yeast ribosomal protein S4 and mammalian LLRep3 proteins.

We report the sequence and expression of a single-copy gene from Dictyostelium discoideum which encodes the homolog of yeast ribosomal protein S4, a protein located on the small ribosomal subunit and known to play an important role in maintaining translational fidelity. Over a highly conserved central region, the Dictyostelium protein has 78% sequence similarity to the yeast protein and 83% sequence similarity to mammalian S4 protein homologs, the LLRep3 proteins. The Dictyostelium gene encodes a polypeptide 28,717 Da in size and hence this ribosomal protein has been named rp29. The N-terminal sequence of the Dictyostelium rp29 protein is extended by 61 amino acids and 14 amino acids compared to the mammalian and yeast proteins, respectively, and the C-terminus is correspondingly 15 amino acids or 2 amino acids shorter. Although the coding region of the rp29 gene is present on a single exon, a 157bp intron interrupts the 5' untranslated region and unusually contains four direct repeats of the sequence TCAATCT. The gene is expressed maximally during vegetative growth but a second peak of expression also occurs late in development which is restricted to prestalk cells; rp29 is the first Dictyostelium ribosomal protein gene reported which shows prestalk-specific developmental expression. During each round of expression, only a single 0.9kb transcript is produced which is similar in size to the yeast S4 ribosomal protein transcript (0.8kb) but markedly smaller than the mammalian LLRep3 mRNA (1.7kb) due to a much shorter 5' untranslated region.

Amino Acid Sequence↗
PubMed1991

Accumulation of noradrenaline and its oxidation products by cultured rodent astrocytes.

The accumulation of [3H]noradrenaline ([3H]NA) and its oxidation products was studied in primary cultures of cerebral astrocytes. Astroglial accumulation of radiolabeled catecholamine ([3H] NA and oxidation products) was enhanced by manganese or iron, but it was inhibited by unlabeled NA, dopamine or ascorbate. Tissue: medium ratios of radioactivity increased as extracellular [3H]NA was oxidized. When extracellular oxidation was prevented by ascorbate, as confirmed by high performance liquid chromatography with electrochemical detection, either ouabain pretreatment or nominally Na(+)-free incubation medium inhibited approximately one-half of specific [3H]NA accumulation by rat (but not mouse) astrocytes. These observations suggest that neurological responses to trace metals and ascorbate may arise from the effects of these agents on the clearance of extracellular catecholamines. Astrocytes can accumulate oxidation products of NA more rapidly than they take up NA itself, but ascorbate at physiological concentrations prevents the oxidation process in extracellular fluid. Furthermore, in the presence of ascorbate, Na(+)-dependent transport mediates a significant component of NA accumulation in rat astrocytes.

Animals↗
PubMed1991

Association of high density lipoprotein cholesterol with plasma lipolytic activity and C-peptide concentration in type 2 diabetes.

In order to assess whether insulin concentration or plasma lipolytic activity has any role in the regulation of HDL cholesterol concentrations in type 2 diabetes, fasting plasma C-peptide and HDL2-cholesterol concentrations and the post-heparin plasma activities of lipoprotein lipase and hepatic endothelial lipase were measured in 148 patients with type 2 diabetes (76 male, 72 female). HDL2-cholesterol was related negatively to hepatic lipase activity in men (r = -0.49, p less than 0.001) and women (r = -0.43, p less than 0.001) and positively to lipoprotein lipase activity in men (r = -0.33, p less than 0.01) and women (r = 0.36, p less than 0.01). A significant inverse relationship was confirmed between C-peptide and the HDL2-cholesterol subfraction in both sexes (men, r = -0.40, p less than 0.001, women r = -0.51, p less than 0.001). This persisted after adjustment for the effects of alcohol intake, mode of hypoglycaemic treatment, plasma glucose and body mass index. The relationship was lost in men and greatly diminished in women when hepatic lipase activity was included in multiple linear regression analysis, whereas the inclusion of lipoprotein lipase activity in the analysis had little effect on the relationship between C-peptide and HDL2-cholesterol. We suggest that hepatic lipase may be partly responsible for the commonly observed inverse relationship between measures of insulin secretion and HDL-cholesterol concentrations. We speculate that this may occur through a direct stimulatory effect of insulin on the enzyme's activity.

C-Peptide↗
PubMed1990

In vivo and in vitro models of demyelinating disease. Possible relationship between induction of regulatory subunit from cAMP dependent protein kinases and inhibition of JHMV replication in cultured oligodendrocytes.

The results in this study suggest a unique possible association between inhibition of JHMV replication and the induction of R1 proteins in differentiating oligodendrocytes, involving inhibition of a PPPase found in the endosome fractions of cells. Free R1 protein appears to prevent the dephosphorylation of purified JHMV-NC substrate thereby possibly blocking the normal sequence of events necessary for NC release of viral genomes. Inhibition of host-cell endosome PPPase's may have relevance to controlling JHMV infection since CV particles adsorbing to cell surface receptors are believed to penetrate via clathrin coated pits into endosomes. Thus, the early stages of CV infection, including dephosphorylation of NC protein within endosomes, provide a possible site for controlling the initial stages of viral infection.

Animals↗
PubMed1990

Fractionated doses of radioiodine for ablation of postsurgical thyroid tissue remnants.

Patients who have differentiated thyroid carcinoma and have undergone total thyroidectomy are treated with radioiodine for ablation of functional thyroid remnants. Administration of a single therapeutic dose in excess of 30 mCi of l-131 requires hospitalization. In an attempt to obviate the necessity for hospitalization, the prospective ablative dose was divided into two or three fractions given at weekly intervals on an ambulatory basis. To assess the effectiveness of this approach, this group of patients was compared to a cohort of hospitalized patients treated with a single dose. Ablation was achieved in 9 out of 12 patients treated in a fractionated manner (a 75% success rate), whereas in 16 out of 20 patients given a single dose the thyroid remnants were completely eradicated (an 80% success rate). That the use of split, smaller doses administered at weekly intervals on an ambulatory basis presents a reasonable alternative for ablation of postsurgical, residual-functioning thyroid tissue.

Adult↗
PubMed1989

The reduction of low density lipoprotein cholesterol by metformin is maintained with long-term therapy.

Changes in serum lipoproteins were studied in 14 non-insulin dependent diabetics on long-term metformin therapy, after 6 weeks' placebo, and again 6 weeks after restarting active drug therapy. Withdrawal of metformin resulted in a rise of fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol. Restarting the drug reversed these changes. Multivariate analysis showed that serum total and LDL cholesterol varied with treatment but not with glycaemic control. Metformin can lower serum total and LDL cholesterol in non-insulin dependent diabetics and this effect is maintained long term.

Cholesterol↗
PubMed1988

The effect of glibenclamide and metformin on serum lipoproteins in type 2 diabetes.

In a cross-over study, the effects of 3 months treatment with metformin or glibenclamide on body weight, blood glucose control, and serum lipoproteins were compared in 35 Type 2 diabetic patients, inadequately controlled by dietary therapy alone. Glibenclamide alone increased body weight (mean change +2.75 kg; 95% confidence intervals +1.95 to +3.55 kg; p less than 0.0001). Glibenclamide and metformin achieved equivalent blood glucose control, independent of initial body mass index. Neither drug affected serum triglyceride concentration. Metformin alone significantly reduced low density lipoprotein cholesterol (mean change -0.34 mmol l-1; 95% confidence intervals -0.12 to -0.57 mmol l-1; p less than 0.01). Neither drug altered high density lipoprotein or subfraction cholesterol.

Blood Glucose↗
PubMed1988

In vivo and in vitro models of demyelinating disease: efficiency of virus spread and formation of infectious centers among glial cells is genetically determined by the murine host.

Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associated with SJL mice was maintained in explanted glial cultures which, by contrast, fully supported a productive infection by the serorelated mouse hepatitis virus type 3. A comparative analysis of the infectious process in glial cell explants from SJL and CD.1 mice helped to define the stage at which restriction is manifested. Cultures of oligodendrocytes and astrocytes from these strains of mice were challenged with JHMV or mouse hepatitis virus type 3, and cell-virus interactions were monitored, including adsorption, uptake of inoculum, transcription, and cell-to-cell dissemination. The sequence of early events from adsorption to genome activation occurred with about equal efficiency with both viruses and genetically different cells, indicating that SJL resistance is not due to any deficiency in specific receptors or penetration of the inoculum or general expression of viral functions. However, intercellular spread of the infection was restricted in SJL glial cells owing to an as yet undefined component. Since cells from (SJL x CD.1)F1 mice were fully susceptible to JHMV, resistance to virus spread must be due to a deficiency in some factor, perhaps a proteolytic activity necessary for dissemination.

Animals↗
PubMed1988

The interleukin-2 receptor and its expression in the acute leukaemias and lymphoproliferative disorders.

The expression of the interleukin-2 receptor (IL-2R) was investigated in a total of 117 cases of acute leukaemia and lymphoproliferative disorder. The results confirm reports that the interleukin-2 receptor can be expressed on cells of myeloid lineage and in cases of Hairy Cell Leukaemia. They extend knowledge of the expression of the IL-2R in cases of lymphoproliferative disorders.

Acute Disease↗
PubMed1987

In vivo and in vitro models of demyelinating diseases, XX: Replication of coronaviruses in primary neural cultures from genetically resistant and susceptible mice.

Resistance of SJL mice to JHMV could be associated with explanted oligodendrocytes and astrocytes in primary neural cultures from newborn mice. The restriction demonstrated is not at the stage of adsorption, uptake by the host or RNA synthesis and does not occur with the serorelated MHV3 strain. Experiments with neural cells from F1 hybrid mice bred from resistant and sensitive parents show that resistance is a recessive trait. It is hypothesized that the defect may involve proteolysis at the cell surface, but to date no clear cut experimental data have been obtained to substantiate this idea. In more general terms our in-vitro observations demonstrate that resistance of SJL mice pertains to both embryonic and newborn animals and involves neural and non neural cell types. Thus, the SJL restriction of JHMV, evident at the cellular level, does not involve an age-related maturation process associated with rat and mouse oligodendrocytes studied previously (1, 14).

Animals↗
PubMed1987

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease.

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of 99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of 99mTc-plasmin, gallium citrate Ga 67, 125I-fibrinogen, and 99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor 99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of 67Ga, 125I-fibrinogen, or 99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed 99mTc-plasmin and 125I-fibrinogen to have the best localization characteristics.

Abscess↗
PubMed1987

Transferrin receptor expression in the leukaemias and lymphoproliferative disorders.

The expression of the transferrin receptor (TfR) was studied in the acute leukaemias and lymphoproliferative disorders by means of indirect immunofluorescence and/or the enhanced alkaline phosphatase anti-alkaline phosphatase (APAAP) techniques using monoclonal antibodies to the receptor. A total of 174 cases of acute leukaemia and lymphoproliferative disorder were studied. The results indicate that the receptor is expressed with increased density in the majority of positive cases of acute leukaemia. The lymphoproliferative disorders, however, only expressed the receptor in a minority of cases and did so with weak density. It is proposed that this weak expression in the lymphoproliferative disorders may be of use as an indicator of an increase in cell activity.

Acute Disease↗