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Biomedical subjects

R W Simpson

Publications and source records attributed to R W Simpson.

At least 19 recordsLinked to original sources
PubMed1988

Temporal study of metabolic change when poorly controlled noninsulin-dependent diabetics change from low to high carbohydrate and fiber diet.

Thirteen poorly controlled noninsulin-dependent diabetic subjects ingested in succession over 5.5 wk their usual low-carbohydrate, low-fiber diet (LCF) for 3 d, a high-carbohydrate, high-fiber diet (HCF) for 3 wk, and the LCF diet again for 2 wk. All diets were designed to be individually isoenergetic. Fasting plasma glucose fell significantly during the HCF diet and then rose significantly during the last LCF diet. Dietary change rather than hospitalization had its full effect by 18 d. Urinary glucose excretion rose transiently on the HCF diet before also falling significantly. Similarly, pancreatic immunoreactive glucagon (IRG) fell significantly on the HCF diet and increased significantly on the LCF diet. No significant differences were observed in plasma insulin, serum free fatty acids, or monocyte insulin binding activity between the two diets. Reduction in circulating IRG may in part explain the lower fasting (or basal) plasma glucose observed on HCF diets.

Blood Glucose↗
PubMed1988

Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects.

Seventeen non-insulin-dependent diabetic patients were randomly allocated to their usual diet supplemented daily with either 28 g sucrose or 30 g starch (isoenergetic with sucrose) and saccharin (equivalent sweetness). After 6 weeks, the supplements were reversed. No significant treatment effects were observed on fasting concentrations of blood glucose, plasma insulin or serum triglycerides, or on urinary excretion of glucose, sodium or potassium. Following a standard breakfast with either sucrose or saccharin and starch, no differences between meal responses were observed. This study demonstrates no medium-term metabolic contraindications to including a moderate amount of sucrose in the diets of patients with non-insulin-dependent diabetes mellitus.

Blood Glucose↗
PubMed1987

Transcriptionally defective nucleocapsids of vesicular stomatitis virus from cells treated with indomethacin.

Indomethacin blocks the biosynthesis of vesicular stomatitis virus (VSV) at the level of primary transcription, RNA replication, and protein synthesis (P. K. Mukherjee and R. W. Simpson (1985), Virology 140, 188-191). Nucleocapsids of infecting virus particles recovered from indomethacin-treated cells were analyzed for in vitro transcriptase activity. Incorporation of [3H]UTP in mixtures containing nucleocapsids from HEp-2 cells pretreated with 10(-3) M indomethacin was inhibited approximately 80% compared to control reactions containing nucleocapsids from untreated infected cells. The level of inhibition of in vitro transcriptase activity of viral nucleocapsids from drug-treated cultures varied according to the cell line used for infection. After indomethacin removal, cells regained their ability to produce enzymatically competent viral-transcribing complexes unless they were subsequently exposed to metabolic inhibitors such as actinomycin D or alpha-amanitin. Enzymatically defective nucleocapsids from indomethacin-treated cells showed enhanced in vitro transcriptase activity in the presence of modulators of prostaglandins and cyclic nucleotides. Electrophoretic analysis of product from in vitro transcriptase reactions revealed that these defective nucleocapsids are unable to synthesize VSV messenger RNA or normal size leader RNA species but only smaller transcripts of undetermined identity.

Animals↗
PubMed1987

Resistance to biological and chemical challenge in rodents treated with xerosin II, a natural product of Achromobacter xerosis.

The biological response-modifying activity of acid-precipitable material from Achromobacter xerosis was first described as suppression of viral pneumonia in mice. Later, this acid-precipitable material (xerosin) was found to have antiinflammatory activity and to induce tumor regression in chickens infected with Rous sarcoma virus. Here, we report further purification of xerosin resulting in a product (xerosin II) that retains high biological activity against viral and endotoxin-induced pneumonia in mice. In addition, we describe new activities of xerosin II in two rat tumor systems. Female CD rats received gastric intubations of 7,12-dimethylbenz(a)anthracene; 2 weeks later, half began 4 weeks of treatment with xerosin II, while others received saline only. Xerosin II treatment significantly delayed the appearance of the first palpable mammary tumors per rat. In female F344 rats implanted with the 13762 mammary tumor, 4 weeks of xerosin II treatment prolonged the survival of rats by an average of 5-11 days (12-24%) in two separate trials. Tumor growth and incidence of metastasis appeared unaffected by xerosin II treatment. Thus, this refined bacterial extract proved to be a potent biological response modifier in four different rodent systems.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Pathogenesis of cocaine-induced ischemic heart disease. Autopsy findings in a 21-year-old man.

A 21-year-old man with a five-year history of recreational intravenous cocaine abuse developed chest pain within one minute and cardiopulmonary arrest within one hour following an injection. He died and, on autopsy, was found to have severe coronary obstructive lesions, as a result of chronic intimal proliferation, and acute platelet thrombosis. Secondary chronic and acute myocardial ischemic lesions also were observed. Cocaine-induced coronary artery spasm may have occurred and produced focal endothelial injury and platelet aggregation; this pathogenetic mechanism may have accounted for both the chronic and the acute coronary obstructive lesions. In addition, lymphocytic myocarditis was present and may have been related to the long-term cocaine abuse.

Adult↗
PubMed1985

Indomethacin inhibits viral RNA and protein synthesis in cells infected with vesicular stomatitis virus.

Treatment of HEp-2 cells with 10(-3) M indomethacin prior to infection with vesicular stomatitis virus (VSV) blocked synthesis of viral RNA species and proteins. Host cell macromolecular synthesis was also inhibited by this antagonist of prostaglandin metabolism. The reversibility of this drug-mediated inhibition was a time-dependent process that could be prevented after removal of indomethacin if cells were exposed to low concentrations of cycloheximide which do not normally interfere with VSV replication. That indomethacin exerts its inhibitory effect at an early stage of infection is suggested by the finding that this drug can compromise viral transcription either in vitro or in vivo.

Carcinoma, Squamous Cell↗
PubMed1985

A hybrid model for predicting the distribution of pollutants dispersed from line sources.

This paper applies a hybrid modeling methodology to the problem of the dispersion of pollutants from line sources. The model combines a deterministic component, the GM model (Chock, 1978), with a statistical component, the two-parameter Weibull distribution, to produce estimates of the entire distribution of pollutant concentration. The approach is demonstrated using hourly average carbon monoxide data recorded in Melbourne, Australia. Using a second data set a model validation exercise is performed. The hybrid model has worked well, producing estimates of pollutant concentration with an accuracy better than a factor of two over all percentiles of the distribution of pollutant concentration.

Air Pollutants↗
PubMed1985

Inhibitory effect of papaverine on RNA and protein synthesis of vesicular stomatitis virus.

Papaverine, an inhibitor of cAMP phosphodiesterase, reduced yields of infectious vesicular stomatitis virus in HEp-2 cells approximately 100-fold if added to cultures at a concentration of 30 microM before and after virus infection. The extent of papaverine-induced suppression of viral growth was dependent on drug dose and treatment regimen. Cells progressively recovered their viral permissive state after removal of drug. The cyclic nucleotide, cGMP, nullified the inhibitory effect of papaverine if added to cells during drug treatment. Pulse labeling experiments with [35S]methionine showed that papaverine compromises production of all virus-specific proteins in infected cells without adversely affecting host cell protein synthesis. Treatment of cells with papaverine strongly inhibited the production of viral RNA and both cellular RNA and DNA. It was found that VSV causes an immediate but transient stimulation of DNA synthesis in HEp-2 cells which is prevented by papaverine treatment. This drug also selectively blocked primary transcription of VSV in vivo and to a lesser extent in vitro RNA polymerase activity of the virion-bound transcriptase. The finding that papaverine has a strong inhibitory effect on viral biosynthesis including early transcription suggests that VSV replication may depend on host factors that regulate intracellular levels of cyclic nucleotides such as cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Macronutrients have different metabolic effects in nondiabetics and diabetics.

The glycemic and hormonal responses to protein, fat and carbohydrate alone and together were studied in normal, noninsulin-dependent (NIDD) and insulin-dependent (IDD) diabetic subjects. Fat and protein markedly reduced the glycemic response to oral carbohydrate in nondiabetics. In NIDD, the presence of protein and fat had no significant effect on the glycemic response. In IDD, while fat had no effect, protein enhanced the glycemic response. The insulin and GIP responses to the macronutrients together and individually were remarkably similar in all subject groups. Protein behaved as an insulin secretagogue in normal and NIDD while fat acted as a GIP secretagogue in normal and both diabetic groups. Protein appeared to function as a GIP secretagogue when combined with both fat and carbohydrate. It is concluded that caution is required when the glycemic responses to foods observed in nondiabetics are extended to diabetics.

Adult↗
PubMed1985

Food physical factors have different metabolic effects in nondiabetics and diabetics.

Physical properties of food may account for differences in glycemic and other metabolic responses to food with similar amounts of carbohydrate, fat and protein. Blending of cooked beans made no difference to plasma glucose, insulin, or GIP (gastric inhibitory polypeptide) responses in nondiabetics, NIDD (noninsulin-dependent diabetics), and IDD (insulin-dependent diabetics). The cooked blended beans gave a greater plasma glucose response and a lesser hormonal response than a cooked flummery (containing cornstarch, protein and fat) in nondiabetics. In NIDD and IDD, however, the reverse applied for plasma glucose. In nondiabetics, cooked flummery gave a lesser glycemic response at some time points than uncooked flummery. In NIDD the opposite occurred. Cooking led to no significant change in insulin response in nondiabetics, but to a lesser insulin response in NIDD. The effect of some physical properties of food on diabetic control cannot be inferred from findings in nondiabetics.

Adult↗
PubMed1984

Association of parvoviruses with rheumatoid arthritis of humans.

A small virus resembling parvoviruses in its morphological and physicochemical properties was derived from synovial tissue of a patient with severe rheumatoid arthritis. This virus, designated RA-1, elicits a syndrome in neonatal mice that includes neurological disturbances, permanent crippling of limbs, dwarfism, alopecia, blepharitis, "masking," and a rigid curvature of the thoracic spine. Polyclonal antibodies against RA-1 display high virus neutralizing activity and in immunoassays detect reactive antigen in synovial cells from different rheumatoid arthritis patients but not persons with osteoarthritis. Putative parvoviruses isolated from several other rheumatoid arthritis patients are only weakly pathogenic for newborn mice but can generate RA-1 virus-specific antigens in tissues of these animals. It has not been established that RA-1 and existing parvoviruses of mammalian species are related.

Animals↗
PubMed1984

Reversible restriction of vesicular stomatitis virus in permissive cells treated with inhibitors of prostaglandin biosynthesis.

Indomethacin, a potent nonsteroidal inhibitor of prostaglandin synthetase (cyclooxygenase) reduced yields of infectious vesicular stomatitis virus in HEp-2 cells more than 99% if added to cultures at levels of 10(-3)M either before or after infection. Other permissive cell lines differed according to the treatment period and drug level required for restricting productive infections. The inhibitory effect of indomethacin was progressively reduced if infection of cells was delayed for increasing times after drug removal. Strong inhibition of viral replication also occurred in cells treated with the cyclooxygenase antagonists naproxen, phenylbutazone, and oxyphenylbutazone whereas phenacetin, which does not block cyclooxygenase function, was inactive. Enhanced viral replication occurred in indomethacin-treated HEp-2 cultures when these cells were subsequently exposed to such substances as prostaglandin E1, cyclic AMP, or insulin. Conversely, indomethacin-treated cells remained restrictive for VSV if they were subsequently exposed to metabolic inhibitors of functional DNA (actinomycin D or mitomycin C), messenger RNA synthesis (alpha-amanitin), or protein synthesis (cycloheximide) at concentrations that normally do not compromise viral replication. Pretreatment of HEp-2 cells with mitomycin C markedly shifted the dose response for indomethacin-mediated inhibition of VSV from a 90% inhibitory dose of about 10(-4)M to one of 10(-9)M or lower. These findings suggest that preexisting host factors essential for replication of VSV, although rendered nonfunctional by the drug indomethacin, can be replenished unless their synthesis is blocked by various classes of metabolic inhibitors.

Animals↗
PubMed1983

Hypercalcaemia in association with renal failure: the role of immobilisation.

Hypercalcaemia occurring after ten weeks of immobilisation was observed in four adult patients all of whom had had prior renal failure sufficient to require renal dialysis. In all patients parathyroid hormone levels were normal or low and in three plasma 1,25(OH)2D3 levels were low. These findings are consistent with immobilisation induced increases in bone calcium resorption. Renal excretion of calcium may have been impaired by renal dysfunction resulting in hypercalcaemia and suppression of plasma PTH and 1,25(OH)2D3 levels. Resolution of the hypercalcaemia was associated with remobilisation. Parathyroidectomy is inappropriate treatment.

Acute Kidney Injury↗
PubMed1982

Insulin receptor binding increased by high carbohydrate low fat diet in non-insulin-dependent diabetics.

In comparison to a traditional low carbohydrate diet (LC), the effect of an isocaloric high carbohydrate, high fibre diet (HC) upon the insulin binding to mononuclear blood cells of seven non-insulin-dependent diabetics was examined. Each subject, in random order, took both diets for 6 weeks each. There was no significant difference in weight during either dietary period, but a significant (P less than 0.05) increase in the monocyte insulin binding activity on the HD diet (tracer specific binding: 4.2% HC; 3.5% LC). This was accompanied by a significantly (P less than 0.02) lower fasting plasma glucose concentration (LC = 7.1 mmol/l; HC = 6.1) without a significant change in the fasting plasma insulin level. In contrast to the usual low carbohydrate diet, a high carbohydrate diet tends to correct the lowered insulin receptor status observed in maturity-onset diabetics.

Body Weight↗
PubMed1982

Diode array digital radiography: initial clinical experience.

Initial clinical results are described for a new method of digital radiography based on high-detail self-scanning linear diode arrays which overcome many of the limitations of present film or other digital methods. The technique uses a fan-shaped x-ray beam to produce a nearly scatter-free image on a phosphor strip that is fiber-optically coupled to six self-scanning arrays of light-sensitive diodes spaced 0.025 mm, thus providing 6,144 discrete sensors across the field of view. Because these diodes have a greatly expanded dynamic range and operate at very low noise, it becomes possible to visualize small density differences or contrast below 1% both in the light and dark areas of the image. Because of the efficiency of detection and display, radiation doses can be reduced for a given information content. Our preliminary clinical studies have shown to broad application of our method in examining the chest and abdomen and in performing intravenous digital arteriography.

Angiography↗
PubMed1981

A high carbohydrate leguminous fibre diet improves all aspects of diabetic control.

In a randomised cross-over study 18 nondependent (NIDDM) and 9 insulin-dependent (IDDM) diabetics were put on to a high carbohydrate diet containing leguminous fibre (HL) for 6 weeks, and also a standard low carbohydrate diet (LC) for 6 weeks. During two identical 24 h metabolic profiles mean preprandial and mean 2 hour postprandial blood glucoses were significantly lower on HL in both groups, as were also several overall measures of diabetic control, including the degree of glycosuria. Total cholesterol was reduced significantly on HL in both groups, and the HDL/LDL cholesterol ratio increased significantly on HL in the NIDDM group. A diet high in complex carbohydrate and leguminous fibre improves all aspects of diabetic control, and continued use of a low carbohydrate diet no longer appears justified.

Adult↗
PubMed1981

Comparison of two twice-daily insulin regimens: ultralente/soluble and soluble/isophane.

The relative efficacy of two twice-daily insulin regimens using highly purified insulins, once daily Ultratard with twice daily Actrapid (ultralente/soluble) and twice daily Actrapid with twice daily Retard (soluble/isophane), has been studied in 12 diabetics in a cross-over study. Control was optimised as an out-patient, and assessed by in-patient 24 hour profiles. Similar day-time glucose control was achieved, but the mean overnight plasma glucose concentrations were more steady on ultralente/soluble (0100, 0300, 0500, 0700, 0800 h values 5.6, 5.3, 5.8, 7.8, 10.4 mmol/l) than on soluble/isophane (4.3, 3.4, 5.2, 7.5, 12.2 mmol/l). The minimum overnight plasma glucose concentrations were lower (p less than 0.05) on soluble/isophane (mean 2.8 mmol/l) than on ultralente/soluble (mean 4.8 mmol/l), associated with higher (p less than 0.05) nocturnal free plasma insulin levels after the evening soluble/isophane injection. The plasma glucose rise between 0700 and 0800 h was greater (p less than 0.05) on soluble/isophane than on ultralente/soluble. The morning insulin injection should probably be taken immediately on rising, to prevent the pre-breakfast plasma glucose rise. The ultralente/soluble combination gave similar day-time plasma glucose control to soluble/isophane with less nocturnal hypoglycaemia.

Adult↗