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Biomedical subjects

J R Jones

Publications and source records attributed to J R Jones.

At least 19 recordsLinked to original sources

The consequences of the isotope effect on proline dehydrogenation rates estimated by the tritium loss method.

Loss of tritium from a substrate is often used to estimate the rate of dehydrogenation. However, loss of 3H may be much slower than loss of H because of the tritium isotope effect. In order to assess the impact of the tritium isotope effect, loss of 3H from the C-5 position of proline during dehydrogenation by rat liver mitochondria and bacteroids from soybean (Glycine max [L.] Merrill) nodules was compared with appearance of 14C in products of [14C]proline dehydrogenation. Incubations were carried out in the presence of o-aminobenzaldehyde (added to trap the initial product, delta 1-pyroline-5-carboxylate). The fraction of total 14C products trapped by o-aminobenzaldehyde varied from 0.07 to 0.75 depending upon experimental conditions. With rat liver mitochondria, dehydrogenation of [14C]proline was between 3.27 and 9.25 times faster than dehydrogenation of 3H proline, depending upon assay conditions. Soybean nodule bacteriods dehydrogenated [14C]proline about 5 times faster than [3H]proline. We conclude the following: (i) the rate of proline dehydrogenation may be greatly underestimated by the tritium assay because of the tritium isotope effect, and (ii) the 14C assay may underestimate the rate of proline dehydrogenation if it is assumed that o-aminobenzaldehyde quantitatively traps delta 1-pyrroline-5-carboxylate under all conditions. The simplicity of the tritium assay makes it attractive for routine use. However, its use requires determination of the tritium isotope effect, under the specific conditions of the assay, in order to correct the results. The considerations discussed here have broad applicability to any dehydrogenase assay employing tritium loss.

Animals

The effects of amphetamine on body weight and energy expenditure.

Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.

Animals

Effects of amphetamine on food intake and weight: timing of injections and food access.

Although the effects of amphetamine on food consumption and body weight in nondeprived animals are of interest for theoretical and clinical reasons, there are only a few studies on this topic in the literature. In Experiment 1, independent groups of nondeprived rats were given daily injections of 0, 1, 2, 5, or 10 mg/kg d-amphetamine sulfate shortly after light onset for 30 days. While drug treatment did not affect food consumption, all amphetamine-treated groups lost weight over the initial 12 days and then, over the final 18 days of treatment, gained weight at the same rate as controls. Experiment 2 assessed whether the effects of amphetamine on these measures are influenced by the timing of the daily injections relative to the light-dark cycle. As in Experiment 1, injections of amphetamine at light onset again produced weight loss while not affecting food consumption, whereas injections of the drug at light offset did not reliably affect either measure. Experiment 3 showed that the relationships among variables observed in nondeprived animals remain the same in animals restricted to 12 h of access to food each day and replicated the amphetamine-induced hyperphasia observed earlier by Jones and Caul (9).

Animals

Occupational exposures in California wildland fire fighting.

Industrial hygiene measurement of exposures to wildland fire fighters was conducted in northern California during three consecutive fire seasons (1986-1989) in conjunction with three separate health effects studies. Chemicals that were monitored included carbon monoxide, total and respirable particulates, polyaromatic hydrocarbons (PAHs), crystalline silica, aldehydes, and benzene. Measurements were taken at both wildland fires and prescribed (planned) burns. A variety of collection methods were employed--colorimetric detector tubes and a CO monitor were used for direct-reading area measurements; colorimetric diffusion tubes, filter cassettes, sorbent tubes, and passive vapor monitors were used for determining personal time-weighted average exposures. A new screening method (National Institute for Occupational Safety and Health Method 2539) was used to identify the presence of specific aldehydes. Results show that wildland fire fighters may at times be exposed to concentrations of carbon monoxide, total or respirable particulates, or silica at levels near or higher than recommended occupational exposure limits, although group means were generally well below the limits. Time-weighted average formaldehyde levels, measured in a few instances above 0.37 mg/m3 (0.3 ppm), indicate a potential for formaldehyde-induced eye or respiratory irritation under these conditions. Certain characteristics of the work such as high altitude, temperature, and breathing rate; extended work shifts; and additional off-shift exposures suggest that adjustment of 8-hr exposure limits may be necessary to provide adequate protection. In part, because of the rigors of performing industrial hygiene measurements under fire fighting conditions, data are limited and could not be considered representative of the full range of exposures fire fighters may encounter.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational

An epidemiologic study of cancer and other causes of mortality in San Francisco firefighters.

To test the hypothesis that firefighter exposures may increase cancer risk, mortality rates were calculated for 3,066 San Francisco Fire Department firefighters employed between 1940 and 1970. Vital status was ascertained through 1982, and observed and expected rates, rate ratios (RR), and 95% confidence intervals (CI) were computed using United States death rates for comparison. The total number deceased (1,186) was less than expected and there were fewer cancer deaths than expected. However, there were significant excess numbers of deaths from esophageal cancer (12 observed, 6 expected), cirrhosis and other liver diseases (59 observed, 26 expected), and accidental falls (21 observed, 11 expected). There were 24 line-of-duty deaths, which were primarily due to vehicular injury, falls, and asphyxiation. Heart disease and respiratory disease deaths occurred significantly less often than expected. It was concluded that the increased risks of death from esophageal cancer and cirrhosis and other liver diseases may have been due to firefighter exposures, alcohol consumption, or interaction between alcohol and exposures. Because this was an older cohort and firefighter exposures have changed due to the increasing use of synthetic materials, it is recommended that the effects of modern-day exposures be further studied.

Accidental Falls

Regiospecific deuteriation and tritiation of various drugs using a homogeneous rhodium trichloride catalyst.

The deuteriation and tritiation of a number of drugs containing carboxyl, amide, aralkylamine, and anilide functional groups have been investigated using homogeneous rhodium trichloride as a catalyst. Good incorporation of deuterium was observed and the regiospecificity for ortho exchange was very high for most of the drugs studied. Similarly, with tritium, good incorporation (specific activities) and regiospecificities were achieved in many cases. Satisfactory results were also obtained from the small number of heterocyclic-containing drugs that were included in the present study.

Catalysis

Rebound cue state following a single dose of haloperidol.

It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within-subjects design have both theoretical and methodological importance.

Amphetamine

Ultrasonography in slipped capital femoral epiphysis. Diagnosis and assessment of severity.

We used ultrasonography to study 26 hips with slipped capital femoral epiphyses. In recently slipped epiphyses the ultrasound image revealed a step at the anterior physeal outline (mean 6.4 mm), diminished distance between the anterior acetabular rim and the femoral metaphysis (mean 4.3 mm) and an effusion. As metaphyseal remodelling progressed the physeal step decreased. The femoral neck appeared straighter in hips which had been symptomatic for longer than three weeks. It was possible to measure posterior epiphyseal displacement without projectional errors and the method was accurate in diagnosing minimal slip and in staging displacement. The suggested criteria are, less than 7 mm for a mild slip, 7 to 11 mm for a moderate slip and more than 11 mm for a severe slip. We recommend ultrasonography for the diagnosis, staging and follow-up management of slipped upper femoral epiphysis.

Adolescent

Purification and properties of parathyroid hormone-related peptide isolated from milk.

The occurrence and properties of PTH-related peptide (PTH-RP) in milk was investigated. PTH-RP was purified to homogeneity from human and bovine milk using heat and acid to precipitate milk proteins followed by ion exchange chromatography and reverse-phase HPLC. The peak of PTH-RP from HPLC was detected using a sensitive bone cell bioassay. A single band of peptide was detected on silver-stained polyacrylamide gels, which migrated as a 20-21-kDa macromolecule. PTH-RP isolated from either human or bovine milk had similar electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partially purified bovine PTH-RP stimulated cAMP production in UMR106-01 and OK cell lines and elicited a concentration-dependent inhibition of sodium-dependent phosphate transport in OK cells. Incubation of milk extracts with an anti-PTH antiserum did not affect their bioactivity, whereas an antihuman PTH-RP 1-34 antiserum markedly reduced the cAMP response of UMR106-01 cells to the immunoabsorbed milk extracts. A PTH antagonist, norleu PTH 3-34, blocked the stimulation of cAMP production in UMR106-01 cells treated with milk extracts. PTH-RP immunoreactivity and bioactivity occurred in milk extracts of diverse animals from both eutherian and metatherian (marsupial) species. Porcine colostrum also had immunoreactive PTH-RP, although the levels were lower than the immunoreactive PTH-RP concentrations observed in milk samples collected at 7 and 14 days of lactation. Thus, a 20-21-KDa PTH-RP is secreted into milk where it could play a role in the development of suckling, newborn animals.

Adenylyl Cyclases

Remodelling after pinning for slipped capital femoral epiphysis.

We assessed 70 hips at an average of 7.1 years after pinning for slipped upper femoral epiphysis to determine the frequency of remodelling, what factors influence it and its effect on the clinical outcome. Remodelling was defined by a new classification of the anterior femoral head-neck profile as seen on the lateral radiograph. Remodelling occurred in 50% of hips with a head-shaft angle of 30 degrees or more; the probability of remodelling was significantly less the greater the degree of slip, but was significantly increased if the triradiate cartilage was open at the time of presentation. We found no significant effect for age, sex, weight or length of symptoms. The range of internal rotation was significantly greater in those hips that remodelled. We support the treatment of moderate slips in skeletally immature patients by pinning in situ, since the probability of satisfactory remodelling was 75% for slips of 40 degrees or less.

Adolescent

Elevated blood lead in California adults, 1987: results of a statewide surveillance program based on laboratory reports.

California medical laboratories that test for blood lead are required to report results exceeding 1.21 mumols/L (25 micrograms/dl). Between April and December 1987, the California Department of Health Services received 3,077 blood lead reports from 34 laboratories for 1,293 civilian, non-institutionalized adults. Approximately 1 percent of all reports exceeded 3.87 mumols/L (80 micrograms/dl), 7 percent exceeded 2.42 mumols/L (50 micrograms/dl), and 21 percent exceeded 1.93 mumols/L (40 micrograms/dl). Individuals tested were overwhelmingly male (94 percent), disproportionately Hispanic surnamed (44 percent), and most often residents of Los Angeles County (81 percent). Workers in lead smelting, battery manufacturing, and brass foundries accounted for nearly 80 percent of reports. Construction, radiator repair, pottery and ceramics manufacturing, and gun firing ranges accounted for the remainder. All adults with reports of greater than or equal to 2.90 mumols/L who were contacted reported on occupational exposure. Approximately half were not in routine medical monitoring programs. Despite OSHA standards, elevated blood lead with the potential for serious acute and chronic lead poisoning in California adults remains a significant public health and major occupational health concern.

Adolescent

Time course of the effect of amphetamine on eating is biphasic.

The time course of the effect of 1, 2, and 5 mg/kg d-amphetamine sulfate on eating was recorded in independent groups of rats for 12 days with a measure that was sensitive to both increases and decreases in food consumption. The data from the initial drug treatment day suggest that the time course of the drug's effect was biphasic. Furthermore, during the test period, a clear biphasic temporal response developed to the 2- and 5-mg/kg doses. In both cases, on the last drug treatment day, the drug initially suppressed eating but later produced hyperphagia. The hyperphagic response that developed probably resulted from Pavlovian conditioning of compensatory adaptive responses.

Animals

The 57 mm thermal clearance probe: a non-invasive tool for measuring subcutaneous blood flow.

1. The segmented thermal clearance probe is a non-invasive instrument which measures heat thermal clearance, a variable directly proportional to superficial blood flow, with a depth sensitivity theoretically proportional to the sensor diameter. We compared an 18 mm sensor and a recently developed 57 mm sensor with the reference technique of xenon washout. 2. The theoretical depth sensitivity of the sensors was assessed using Perspex spacers. Ninety-five per cent of sensitivity had been lost at the respective depths of 3.5 mm and 7.1 mm for the 18 mm and 57 mm sensors. 3. A comparison was made between heat thermal clearance reading and 133Xe decay curves using the two probes for 15 min after injection of 133Xe at 2 mm and 6 mm depths in the anterior thigh in 41 subjects. The 57 mm sensor showed similar correlation with xenon washout at 2 mm injection depth (r = 0.89) and 6 mm injection depth (r = 0.86), whereas the 18 mm sensor showed greater correlation at 2 mm (r = 0.92) than at 6 mm (r = 0.62). 4. The 57 mm sensor was compared with xenon washout at 6 mm in eight insulin-treated diabetic subjects. The relationship was similar to that in non-diabetic subjects (r = 0.79), with no significant difference in slope or intercept. 5. It is concluded that the 57 mm thermal clearance probe may be used to study blood flow at the depth of insulin injection (6 mm) in diabetic and non-diabetic subjects.

Adult

Acute traumatic haemarthrosis of the knee: expectant treatment or arthroscopy?

We have prospectively studied 50 patients with an acute traumatic haemarthrosis of the knee to investigate the place of examination under anaesthesia and arthroscopy in a district general hospital. There was a wide spectrum of injury to the knee, and 30% of patients required operative procedures. These important injuries could not be diagnosed reliably on initial clinical examination. We conclude that in the active patient under 35 years of age this policy allows prompt and appropriate treatment.

Acute Disease

Amphetamine's effects on food consumption and body weight: the role of adaptive processes.

Three experiments were conducted to characterize the time course of amphetamine's effects on food consumption using procedures that would allow both decreases and increases in eating to be evident relative to control levels. In Experiment 1 we measured eating over 12 postinjection hr in rats. Orderly changes in within-day temporal patterns of eating over the 12 days of amphetamine administration suggest the role of conditioned adaptive processes. In Experiment 2, animals were not presented food until 2 hr after drug administration. Initial anorexia and subsequent hyperphagia were produced by repeated administration of amphetamine. Experiment 3 assessed both within-day and over-day changes in body weight and food consumption and showed that in addition to the drug's anorectic effect, amphetamine also reduces body weight via other mechanisms. In interpreting tolerance to anorectic drugs, it is necessary to evaluate such changes in body weight that indicate shifts in hunger that occur over days as well as shifts in within-day temporal patterns of eating that indicate the presence of conditioned adaptive changes. It is proposed that these two adaptive mechanisms account for pharmacodynamic tolerance.

Animals

Primary total hip replacement for displaced subcapital fracture of the femur.

The results of primary total hip arthroplasty for sub-capital femoral neck fracture in previously normal hips are reported. Thirty-seven patients aged 70 or less at the time of surgery were reviewed at an average follow-up of 56 months. Eighteen (49%) had undergone or were awaiting revision surgery. A further four (11%) had definite radiological signs of loosening. Harris hip scores were calculated and correlated well with the results of gait analysis; these suggested that it was the more vigorous patients that were more liable to early failure. Consequently, primary total hip replacement is not recommended for subcapital fractures in the younger patient without pre-existing hip pathology.

Aged

Evidence of neurologic dysfunction related to long-term ethylene oxide exposure.

Eight hospital workers with chronic ethylene oxide exposure were age-sex matched with eight nonexposed controls with no significant differences in educational backgrounds and vocabulary scores. The exposed group performed more poorly on all eight measures of cognition, memory, attention, and coordination, with 71.3% less accuracy on the Hand-Eye Coordination Test. There was a dose-response relationship between exposure and the following: Continuous Performance Test and sural velocity. These findings suggest that neurologic dysfunction may result from long-term low-dose exposure to ethylene oxide, and that these effects may occur at exposure levels common in hospital sterilizer operations.

Adult