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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 199 records · Page 11Linked to original sources
PubMed1987

First-pass hepatic extraction and metabolic effects of insulin and insulin analogues.

First-pass hepatic extraction of insulin and hepatic and peripheral contributions to hypoglycemia were compared in conscious dogs during portal infusion of insulin A1, B29 diacetyl insulin, or A1-B29 dodecoyl insulin at 7 and 14 pmol X kg-1 X min-1. The liver removed 43 +/- 2% of insulin, 12 +/- 1% of dodecoyl, and 8 +/- 1% of diacetyl insulin, in a single transhepatic circulation. The hypoglycemia induced by insulin and diacetyl insulin and the ensuing glucagon response were greater than that produced by the dodecoyl analogue. Diacetyl insulin primarily increased glucose utilization, dodecoyl insulin solely inhibited hepatic production, and insulin affected both. The lack of hepatic effect of diacetyl insulin during hypoglycemia can be ascribed to greater counterregulation, because under euglycemic clamp conditions, this analogue caused suppression of glucose production. The different patterns of hypoglycemia exhibited can be explained by the combined effects of altered distribution between the liver and peripheral tissues caused by differences in hepatic extraction, the effect of this phenomenon on the counterregulatory response, and the intrinsic biological potency of the analogues.

Animals↗
PubMed1987

Epizootic vesicular stomatitis in Colorado, 1982: epidemiologic and entomologic studies.

An epizootic of vesicular stomatitis (VS) caused by the New Jersey serotype of VS virus affected livestock and humans in 14 western states in 1982-1983. Epidemiological observations were made on at least 10% of the cattle in 4 dairy herds that were located in the vicinity of Grand Junction, Colorado. High rates of neutralizing antibody to the New Jersey serotype were seen in all cattle regardless of whether livestock in the dairy had clinical VS or a decrease in mild production. Antibody titers remained high in these cattle for as long as 2 years after the epizootic. No virus isolations were made from 32 humans with clinical signs compatible with viral disease. Entomological information was obtained during the epizootic from 23 premises in northwestern Colorado. Insect collections yielded 4 isolates from Culicoides spp. midges, 2 from C. variipennis, and 1 each from C. stellifer and C. (Selfia) spp. This is the first report of VS virus isolations from field-collected Culicoides.

Aedes↗
PubMed1987

Recognition of reversible and irreversible myocardial injury by technetium pyrophosphate extraction kinetics.

The need for a more accurate method of detecting episodes of myocardial ischemia during cardiac operations, particularly during the ischemic arrest interval, prompted us to investigate the usefulness of measuring the active extraction of technetium pyrophosphate in identifying and quantitating ischemic injury. Twenty-four adult mongrel dogs were subjected to cardiopulmonary bypass, and normothermic global ischemia was induced by cross-clamping the proximal aorta. Technetium pyrophosphate (1 mCi) was injected through a standard cardioplegia line with normal saline, simulating administration of cardioplegic solution, upon placement of the aortic cross-clamp (time 0), at 15, 30, 45, and 60 minutes of global ischemia, and with the onset and completion of ischemic contracture. Radioactive counts were recorded over the heart at 1 second intervals, and the extraction fraction and half-time of clearance were calculated. The extraction fraction increased from 0.22 at time 0 to 0.58 at 15 minutes, 0.82 at 30 minutes, 0.85 at 45 minutes, and 0.91 at 60 minutes. The halftime increased from a baseline of 114 seconds (time 0) to a maximum of 321 seconds at 60 minutes of ischemia. The onset and completion of ischemic contracture showed a return toward baseline of both the extraction fraction and halftime of clearance, with an extraction fraction of 0.44 and 0.46 and a halftime of 135 and 133 seconds, respectively. These data clearly show that reversible myocardial injury increased the extraction and reduced the clearance of technetium pyrophosphate and that the magnitude of change related to the extent of injury. The progression to irreversible myocardial injury decreased the active extraction of technetium pyrophosphate. This simple procedure for real-time documentation of myocardial injury promises to provide easily obtainable endpoints of injury for use during cardiac operations in humans.

Animals↗
PubMed1987

Left ventricular dysfunction and dilatation resulting from chronic supraventricular tachycardia.

It has been suggested that patients with chronic supraventricular tachycardia may have impaired ventricular function, which returns to normal after surgical procedures that eliminate the tachycardia. The purpose of this study was to determine the functional consequences of prolonged supraventricular tachycardia in 12 awake dogs in which permanent asynchronous atrial pacemakers were implanted and programmed to a rate of 190 +/- 5 beats/min. Serial radionuclide angiograms were obtained immediately after pacemaker activation and at regular intervals over a 3 month period. Chronic tachycardia resulted in a significantly depressed ejection fraction (49% +/- 1% to 29% +/- 3%; p less than 0.0005) compensated for by a dramatic increase in left ventricular end-diastolic volume (69 +/- 4 to 105 +/- 9 ml, p less than 0.005). Stroke volume and cardiac output were not significantly changed. Five dogs were allowed to recover, and serial radionuclide angiograms were obtained for 12 weeks. Although ejection fraction returned to control values (50% versus 47%, p = no significant difference), end-diastolic volume remained persistently elevated after a 12 week recovery period in all animals (67 +/- 5 versus 91 +/- 6 ml, p less than 0.05). Thus prolonged tachycardia resulted in significant functional changes associated with cardiac enlargement, which were not immediately reversible.

Animals↗
PubMed1986

Computerized detection of the lactate threshold in coronary artery disease.

A computer program for identifying oxygen consumption at the lactate threshold was evaluated by expired gas analysis during treadmill exercise testing in 15 patients with prior myocardial infarction. There was a strong correlation (r = 0.85, p less than 0.001) between computer-identified oxygen consumption (14.1 +/- 4.6 ml/kg/min) and the oxygen consumption (14.6 +/- 4.8 ml/kg/min) corresponding to an increase of arterial lactate level to above the normal value at rest (1.3 mM). The computer program was superior to previously described visual methods for identifying the ventilatory threshold.

Adult↗
PubMed1986

Evidence for an early degradative event to the insulin molecule following binding to hepatocyte receptors.

We have used photoreactive insulin analogues to investigate as related processes, early structural modification of the receptor-bound insulin molecule and internalisation of the insulin-receptor complex. In isolated rat hepatocytes an initial modification of bound insulin leads to the generation of a molecular species unchanged in molecular weight but with reduced receptor and antibody binding affinities and altered electrophoretic mobility. Using photoreactive insulin analogues and density gradient cell fractionation the insulin receptor complex has been shown to undergo internalisation from the plasma membrane to a low density vesicular fraction, the endosome. No labelled material was found in lysosomal fractions after up to 10 min incubation at 37 degrees C. The degree of labelling of the endosome fraction depended on the position of the photoreactive group within the insulin molecule. The data suggest that before or during endocytosis, a small peptide is proteolytically cleaved from the C terminus of the insulin B chain.

Animals↗
PubMed1986

Demonstration that the insulin receptor undergoes an early structural modification following insulin binding.

Processing of the insulin receptor by hepatocytes was studied using a 125I-labelled photoreactive insulin derivative which could be covalently attached to the receptor and facilitate the analysis of receptor structure in isolated subcellular fractions by SDS-polyacrylamide gel electrophoresis. Following binding at the cell surface, the label was rapidly internalised and located in a low-density subcellular fraction ('endosomes'). The intact receptor (350 000 molecular weight) and binding (alpha) subunit (135 000), produced by in vitro disulphide reduction of the samples, were found in the plasma membrane fraction but not in endosomes. In endosomes, the label was concentrated in a band at 140 000 (non-reduced) which on reduction generated species of 100 000 and 68 000 predominantly. The insulin receptor therefore undergoes an early structural change during endocytosis. This modification does not involve complete disulphide reduction and may be due to a proteolytic event.

Animals↗
PubMed1986

Computerized estimation of lactate threshold.

Traditional approaches to estimating a lactate threshold during a progressive exercise test have utilized visual inspection of the data. We describe a computerized approach which utilizes a log-log transformation to yield two approximately linear segments. Linear regression lines are fit to these segments and the intersection of the two lines yields an estimate of the lactate threshold. An approximate 95% confidence interval is also generated.

Algorithms↗
PubMed1986

Should the intent of testing influence its interpretation?

A test is often interpreted as "normal" or "abnormal" by a single criterion, regardless of the intent of testing. The discriminate accuracy of this convention was critically analyzed using information content (I), likelihood ratio and the area under the receiver-operating characteristic curve. Three ejection fraction variables were assessed--ejection fraction at rest, exercise ejection fraction and the change in ejection fraction from rest to exercise--each relative to three intentional goals: diagnosis of coronary artery disease in 929 patients without previous myocardial infarction, prediction of multivessel disease in these same 929 patients and prediction of multivessel disease in 507 patients with previous myocardial infarction. The information content of exercise ejection fraction (IEX) was higher than for ejection fraction at rest (IR) or for the change from rest to exercise (IEX-R), and was relatively constant regardless of the goal of testing. In contrast, neither IR nor IEX-R was constant. IR was lowest for diagnosis of coronary artery disease, whereas IEX-R was highest for this same goal. These empiric observations are consistent with the quantitative relation predicted by information theory: IEX = IR + IEX-R. Thus, ejection fraction at rest has little discriminate value relative to the diagnosis of coronary artery disease, but does have value in evaluating the extent of disease in patients after myocardial infarction. Exercise ejection fraction and change in ejection fraction are nearly equally useful for purposes of diagnosis, whereas the former is most useful for functional evaluation in postinfarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effect of dexamethasone on hepatic glucose and insulin metabolism after oral glucose in conscious dogs.

To examine whether hyperinsulinemia associated with glucocorticoid treatment results solely from hypersecretion of insulin or also involves altered fractional hepatic extraction, oral glucose (1 g/kg body wt) was administered to dogs with or without dexamethasone treatment (2 mg/d for 2 d). Dexamethasone significantly increased basal glucose and insulin concentrations in the portal vein, hepatic vein, and femoral artery, reduced basal fractional hepatic extraction of insulin from 43 +/- 4% to 22 +/- 4%, and, after oral glucose, increased retention by the liver of net glucose released into the portal system from 27 +/- 4% to 53 +/- 13%. Intraportal insulin infusion (1 and 2 mU/kg per min) after 7 d of dexamethasone treatment (2 mg/d) caused less suppression of endogenous glucose production, and less exogenous glucose was required to maintain an euglycemic clamp than in control animals. Dexamethasone treatment is associated with: decreased basal fractional hepatic insulin extraction contributing to hyperinsulinemia; and less suppression of endogenous glucose production and increase in peripheral uptake in response to insulin, but no reduction in net hepatic glucose uptake after oral glucose.

Administration, Oral↗
PubMed1985

Repeated measures, interventions, and time series analysis.

Classical repeated measures designs assume treatments are given in a randomized order. When randomization is not performed and an experiment involves a sequence of observations on each subject collected over time, serial correlations may become important. An example of these types of data is an intervention experiment wherein subjects are observed before and after a treatment or other manipulation. This situation falls within the realm of time series analysis. The correlations between observations often depend on the time intervals between the observations; observations that are closely spaced in time usually are more highly correlated than those with a larger time separation. This report demonstrates a test for such serial correlation and discusses a method of adjusting for it in repeated measures experiments.

Random Allocation↗
PubMed1985

The biological properties of insulins with tyrosine replaced by phenylalanine at positions 14 and 19 of the A chain.

The tyrosine residues at positions 14 and 19 of the insulin A chain are of both theoretical and practical interest. In order to clarify their roles in insulin function we have studied the biological properties of the two chemically modified insulins in which phenylalanine replaces tyrosine at these sites. In comparison to native bovine insulin the lipogenesis potency (in rat adipocytes) of pheA19-insulin was 33% and of pheA14-insulin was 84%. Metabolic clearance rates (MCR) over a range of plasma concentrations were also reduced compared to native insulin both with pheA19-insulin and pheA14-insulin. Plasma half-disappearance times were 4.6 min for insulin, 5.1 min for pheA14-insulin and 7.3 min for pheA19-insulin. However, as a result of these differences in metabolism, the in vivo hypoglycaemic activity of the modified insulins was not reduced. Both modified insulins conform to the general relationship between lipogenesis potency and MCR. These results confirm the importance of the A19 tyrosine to the activity of insulin and show that manipulation at the A14 position can also influence activity even though this residue is not thought to be directly involved in receptor binding.

Animals↗
PubMed1985

Salivary gland homogenates from the vector Culicoides variipennis may aid in detection of bluetongue virus in chronically infected cattle.

Studies were conducted on 2 cows chronically infected with bluetongue virus (BTV) acquired in utero from their dam. In previous research, BTV had been isolated 4 times from 1 cow and 8 times from the other. BTV was undetectable between spontaneous febrile and leukopenic episodes and antibodies to BTV were not detectable in the serum. Previous work had shown that bites by uninfected females of the vector Culicoides variipennis (Coquillett) caused virus to recrudesce in the blood to detectable levels in a bull with a similar BTV infection. After 1 of the 2 cows became hypersensitive to the bites of the vector, the cows were inoculated with homogenized salivary glands from the vector in an effort to increase the viral concentration to detectable levels. Bites by uninfected vectors were used 9.5-48 hr after inoculation of salivary glands in attempts to recover BTV biologically. In 2 of 6 experiments, after inoculations of the glands, BTV was isolated and confirmed from some of the blood samples and from some pools of C. variipennis females that had blood fed on both animals.

Animals↗
PubMed1985

Methodology in preserving field-collected flies for bluetongue virus assay.

Preliminary tests were conducted to evaluate the use of phosphate buffered saline (PBS) as a collecting medium for the preservation of flies for virus assay from our bluetongue (BT) study areas in Colorado, USA. These tests were made possible by the use of a colony of Culicoides variipennis (Coquillett) that is highly susceptible to infection with BT virus (BTV).

Animals↗
PubMed1985

Laboratory infections of Culicoides debilipalpis and C. stellifer (Diptera: Ceratopogonidae) with bluetongue virus.

Six species of field-collected Culicoides females were used in preliminary laboratory tests: C. biguttatus, C. debilipalpis, C. obsoletus, C. stellifer, C. variipennis and C. venustus. Tests were conducted to determine if females would take a blood meal through a membrane, if blood fed females could be maintained in the laboratory for up to 14 days and if they could support replication of bluetongue virus (BTV) serotype 11. One pool of C. stellifer (23 specimens) assayed positive for BTV 7 days following intrathoracic inoculation, which datum suggests that this species might be capable of harboring the virus. One of 52 individually assayed C. debilipalpis females in 2 trials was positive for BTV at 14 days after membrane feeding on a mixture of BTV and sheep blood (infection rate 1.9%), and 1 of 2 pools of C. debilipalpis (26 specimens) was positive 14 days after blood feeding. These data for C. debilipalpis showed that the species can pick up and harbor BTV through replication of the virus.

Animals↗
PubMed1985

The virogenesis of bluetongue virus in Culicoides variipennis.

A direct immunofluorescence (IF) technique was developed to detect bluetongue virus (BTV) antigen in Culicoides variipennis. After approximately 10 days extrinsic incubation (EI), the IF test was as sensitive as virus isolation for detection of infected flies. The IF technique was used to determine the virogenesis of BTV in the fly. After 6 days EI, virus antigen was detected in most midguts; by 10 days, most head squash preparations contained antigen. Other secondary target organs, such as ovaries, abdominal ganglia and thoracic muscle, only infrequently contained detectable BTV antigen.

Animals↗