PubMed Health⌕ Search

Biomedical subjects

J H Jones

Publications and source records attributed to J H Jones.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one.

A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methy lpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.

Aminopyridines↗
PubMed1992

Estimating transit time for capillary blood in selected muscles of exercising animals.

The mean minimal capillary transit time was estimated in muscles of various animals using a combination of physiological and morphometric methods. Radioactive microspheres were injected intravascularly in various animals running on a treadmill at maximum oxygen consumption rate (VO2,max) to label blood flow to individual muscles. The muscles were then removed and preserved by standard methods for electron microscopy. The volume density of mitochondria was measured to assess muscle oxidative capacity. Capillary densities in muscle cross-sections, capillary diameters and tortuosities were incorporated into an estimate of capillary volume per unit muscle mass. Mean capillary transit time (tc) in the exercising muscles was estimated by dividing mass-specific capillary volume by mass-specific blood flow. Estimates of tc ranged from values near 1 s in horse heart and thigh muscles to 0.2 s in duck gastrocnemius. The relationship between muscle blood flow and tc was hyperbolic. The experimental data indicate a limiting value of 0.2 s for transit times at very high blood flows. There was no correlation between tc and body-mass-specific VO2,max.

Animals↗
PubMed1992

O2 delivery at VO2max and oxidative capacity in muscles of standardbred horses.

The purpose of this study was to describe the relationships between 16 physiological, biochemical, and morphological variables presumed to relate to the oxidative capacity in quadriceps muscles or muscle parts in Standardbred horses. The variables included O2 delivery (blood flow) and mean capillary transit time (MTT) during treadmill locomotion at whole animal maximal O2 consumption (VO2max, 134 +/- 2 ml.min-1 x kg-1), capillary density and capillary-to-fiber ratio, myoglobin concentration, oxidative enzyme activities, glycolytic enzyme activities, fiber type populations, and fiber size. These components of muscle metabolic capacity were found to be interrelated to varying degrees using correlation matrix analysis, with lactate dehydrogenase activity showing the most significant correlations (n = 14) with other variables. Most of the "oxidative" variables occurred in the highest quantities in the deepest muscle of the group (vastus intermedius) and in the deepest parts of the other quadriceps muscles where the highest proportions of type I fibers were localized. The highest blood flow measured with microspheres in the muscle group during exercise was in vastus intermedius muscle (145 ml.min-1 x 100 g-1), and the lowest was in the superficial part of rectus femoris muscle (32 ml.min-1 x 100 g-1). Average muscle blood flow during exercise at whole animal VO2max was 116 ml.min-1 x 100 g-1. Because skeletal muscle comprised 43% of total body mass (453 +/- 34 kg), total muscle blood flow was estimated at 226 l/min, which was approximately 78% of total cardiac output (288 l/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Determination of sensitivity to metocurine in exercised horses.

On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the hoof twitch (eg, digital extensor) occurred with simultaneous quantification of blood values of metocurine. Pharmacokinetic and pharmacodynamic analyses of the data were done by a nonlinear regression program, using the Hill equation. There were no differences in findings between exercised and nonexercised horses. The mean blood concentration for the 50% paralyzing dose of metocurine was 0.44 +/- 0.11 (SD) microgram/ml in exercised horses, and 0.58 +/- 0.22 microgram/ml in nonexercised horses. Despite evidence for a response to conditioning, a significant change in the sensitivity of the neuromuscular junction to metocurine was not found.

Animals↗
PubMed1992

The incidence of post minor traumatic brain injury syndrome: a retrospective survey of treating physicians.

There is a relative lack of information in the literature regarding the epidemiology, functional significance, and clinical resolution of the consequences of minor traumatic brain injury (MTBI). Most retrospective studies to date have been elicited by direct patient interview. Because it was supposed that a minor, but significant, traumatic brain injury would require continuing medical intervention beyond the emergency room contact, a survey was conducted of primary care physicians who were believed to be providing continuing medical care. Had their patients required reevaluations for symptoms of the post-MTBI syndrome? Two hundred fifty-six patients with traumatic brain injury initially seen in the emergency room of two community hospitals were reviewed. One hundred ninety-two (75%) had MTBIs (Glasgow coma scale more than 12 and a negative head CAT scan). One hundred twenty-two physicians were surveyed by mail; 67 (55%) responded. Twenty-one percent of their patients were experiencing symptoms of the post-MTBI syndrome from two to six months after their injuries. Studies relying on patient interviews have also estimated the post-MTBI syndrome at 20%. This correlation implies that "suggestion" does not bias patient interview style research in evaluating the post-MTBI syndrome.

Adult↗
PubMed1991

Portable data acquisition cart for equine transportation stress study.

A remote data sampling cart has been designed and built for studying environmental factors that produce stress in horses during transportation. This dedicated sampling cart uses an XT-compatible mother board powered by a 12 V battery, with customized BIOS and ROM program. Sampling is performed using two digital and eight A/D (bipolar, differential) channels in burst mode at a frequency of 1 kHz. Digitized data are stored on magnetic tape for retrieval after the experiment. Configuration of sampling parameters is accomplished via a serial communications link to a host computer, and is stored in battery backed-up RAM, so that the cart can be self initializing. The digitized data consist of samples from transducers that measure 3-axis accelerations, air flow, sound intensity, environmental temperatures, and heart rates of two horses. Twenty four digital output lines control external sampling devices to collect gas samples for quantification and identification of airborne particles, noxious gas concentrations, and airborne microbes. The sampling cart has been used in an initial study of the effects of tethering position (head forward vs. head backward) on heart rates in horses being trailered, and in continuing studies designed to modify the transport environment to minimize stress imposed on animals during transit.

Animals↗
PubMed1989

Total muscle mitochondrial volume in relation to aerobic capacity of horses and steers.

The relationship between maximal oxygen consumption rate (VO2max) and mitochondrial content of skeletal muscles was examined in horses and steers (n = 3 each). Samples of the heart left ventricle, diaphragm, m. vastus medialis, m. semitendinosus, m. cutaneous thoracicus and m. masseter, as well as samples of muscles collected in a whole-body sampling procedure, were analyzed by electron microscopy. VO2max per kilogram body mass was 2.7 x greater in horses than steers. This higher VO2max was in proportion to the higher total volume of mitochondria in horse versus steer muscle when analyzed from the whole-body samples and from the locomotor muscle samples. In non-locomotor muscles, total mitochondrial volume was greater in horses than steers, but not in proportion to their differences in VO2max. The VO2max of the mitochondria was estimated to be close to 4.5 ml O2.ml-1 mitochondria in both species. It is concluded that in a comparison of a highly aerobic to a less aerobic mammalian species of similar body size, a higher oxidative potential may be found in all muscles of the more aerobic species. This greater oxidative potential is achieved by a greater total volume of skeletal muscle mitochondria.

Animals↗
PubMed1989

High rate of O2 consumption in exercising foxes: large PO2 difference drives diffusion across the lung.

The fox has one of the highest mass specific rates of maximal oxygen consumption (VO2max/Mb) that has been measured, yet its specific pulmonary diffusing capacity (DLO2/Mb, measured morphometrically) is similar to that of most mammalian species. It achieves a high O2 flux per unit DLO2 with a large partial pressure difference driving O2 diffusion from alveolar gas to capillary blood (PAO2-PbO2). This paper explores the mechanisms that the fox utilizes to achieve this large pressure difference and the extent to which it exploits its structural diffusing capacity. Foxes were exercised on a treadmill at maximal rates of O2 uptake. The following parameters were measured or calculated: arterial and mixed venous PO2, PCO2, pH and O2 concentration of the blood, cardiac output, hemoglobin concentration and O2 equilibrium curve of the blood, and morphometric estimates of pulmonary capillary volume and pulmonary diffusing capacity for O2. These data were used to calculate pulmonary capillary transit time and the time course of the change in O2 concentration and PO2 of the blood as it transits the lung. The fox has a morphometric pulmonary diffusing capacity of 0.098 ml O2.sec-1.mm Hg-1.kg-1. At VO2 max (3.6 ml O2.sec-1.kg-1) the fox hyperventilates, resulting in a high PAO2 (124 mm Hg); it also maintains a low PbO2 (88 mm Hg) by having a short transit time (0.13 sec) due to a high specific cardiac output (25 ml.sec-1.kg-1). Our calculations indicate that at VO2max the fox uses almost all of the pulmonary capillary transit time for O2 equilibration, in contrast to other species.

Animals↗
PubMed1989

Oxygen transport during exercise in large mammals. I. Adaptive variation in oxygen demand.

This study investigated mechanisms used by horses and steers to increase O2 uptake and delivery (VO2) from resting to maximal rates and identified the mechanisms that enable horses to achieve higher maximal rates of O2 consumption (VO2max) than steers. VO2 and circulatory variables were measured while Standardbred trotting horses and steers (450-kg body mass) stood quietly and ran on a treadmill at speeds up to those eliciting VO2max. As VO2 increased in both species, heart rate and circulating hemoglobin (Hb) concentration increased, thereby increasing O2 delivery by the circulation, while cardiac stroke volume remained unchanged. At VO2max arterial PCO2 increased from its resting value in horses but was unchanged in steers, and arterial PO2 decreased in both species. Although the horses hypoventilated and were hypoxemic at VO2max, no significant decrease in arterial Hb saturation occurred. VO2max of the horses was 2.6 times higher than that of the steers and was associated with a 100% larger cardiac output, 100% larger stroke volume, and 40% higher Hb concentration, whereas heart rates at VO2max were identical in the two species. The higher cardiac output of the horses at VO2max resulted from a 1.2-fold higher mean arterial pressure and 1.6-fold lower peripheral tissue resistance (associated with a larger skeletal muscle capillary bed). Both the magnitude of the difference in VO2max between horses and steers and the mechanisms used to achieve it are the same as observed in smaller pairs of mammalian species with large variation in aerobic capacity.

Adaptation, Physiological↗
PubMed1989

Oxygen transport during exercise in large mammals. II. Oxygen uptake by the pulmonary gas exchanger.

Because the maximal rate of O2 consumption (VO2max) of the horse is 2.6 times larger than that of steers of equal size, we wondered whether their pulmonary gas exchanger is proportionately larger. Three Standardbred racehorses [body mass (Mb) = 447 kg] and three domestic steers (Mb = 474 kg) whose cardiovascular function at VO2max had been thoroughly studied (Jones et al. J. Appl. Physiol. 67: 862-870, 1989) were used to study their lungs by morphometry. The basic morphometric parameters were similar in both species. The nearly 2 times larger lung volumes of the horses caused the gas exchange surfaces and capillary blood volume to be 1.6 to 1.8 times larger. Morphometric pulmonary diffusing capacity was 2 times larger in the horse than in the steer; the 2.6-fold greater rate of O2 uptake thus required the alveolar-capillary PO2 difference to be 1.3 times larger in the horse than in the steer. Combining physiological and morphometric data, we calculated capillary transit time at VO2max to be 0.4-0.5 s. Bohr integration showed capillary blood to be equilibrated with alveolar air after 75 and 58% of transit time in horses and steers, respectively; horses maintain a smaller degree of redundancy in their pulmonary gas exchanger.

Animals↗
PubMed1989

Blood gas measurements during exercise: errors due to temperature correction.

This study assessed the degree to which correcting blood gas measurements to rectal temperature (Tre) rather than to the temperatures at which gas exchange occurs [pulmonary arterial (Tpa) or intramuscular (Tm)] introduces errors into blood gas analysis of exercising mammals. Horses and steers weighing 450 kg were run on a treadmill at speeds up to those eliciting maximal rates of O2 consumption (VO2max), and temperatures were measured in various body compartments. In both species Tpa rose faster than Tre during the run, the degree of dissociation being a function of exercise intensity and duration. Tm was measured only in horses, and it rose faster than Tpa during the run and decreased more slowly postrun. Correcting blood gas values measured at an analyzer temperature of 37 degrees C to Tre without accounting for transient increases during the run of Tpa and Tm that were never reflected in Tre significantly biased estimates of blood gases. The biased estimates erroneously indicated that both species experienced more severe hypoxemia than they actually did at VO2max and masked the hypercapnia experienced by the horses at VO2max.

Animals↗
PubMed1988

Limitations to aerobic performance in mammals: interaction of structure and demand.

In this paper we have explored the linked series of structures that collectively comprise the respiratory system. In examining each of these structural resistors, some seem to be primarily fixed, for example, the trachea, while others must be primarily variable or adaptable, for example, the cardiovascular system. Those structures that are truly variable will not be maintained with structural capacity in excess of their functional demand. As a consequence, these structures are the ones that may most often appear to be limiting O2 uptake. However, we question under which in vivo circumstances the most plastic steps in the cascade of resistances will impart the single-step limitation to O2 uptake. When reviewed in this context, available experimental evidence suggests that among the most athletic animals (those with the greatest weight-specific VO2), the respiratory resistors are likely tuned rather than dominated by a single-step limitation. Skeletal muscle must set the demand for O2 in exercising animals; hence, the relationship between total skeletal muscle mitochondria and maximum O2 consumption is quantitatively consistent, spanning broad differences in body size and aerobic capacity. Those respiratory structures that are primarily nonadaptable must be built with enough "excess structure" to accommodate potential adaptation in an animal's aerobic capacity during its lifetime. Consequently, the least aerobic animals will always appear to experience a limitation to VO2max in one of the most plastic or adaptable structures. We suggest that the adaptable structures upstream to the muscle mitochondria are built and maintained at a cost-benefit maximum ("structural efficiency") in all species. This differs from the concept of optimal structural design or symmorphosis.

Animals↗
PubMed1988

Genetic polymorphism of natural Epstein-Barr virus isolates from infectious mononucleosis patients and healthy carriers.

We analyzed Epstein-Barr virus (EBV) genomes from lymphoblastoid cell lines isolated from patients with infectious mononucleosis and from healthy subjects from California, Hawaii, and Hong Kong between 1970 and 1987. Using genetic polymorphism as epidemiological markers, we found that several genotypes of EBV cocirculate in a community and that although most EBV strains isolated from California and Southern China may be differentiated genotypically, there was no specific association between genotype and disease or time of isolation.

B-Lymphocytes↗