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Biomedical subjects

J E Harrison

Publications and source records attributed to J E Harrison.

At least 19 recordsLinked to original sources

Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.

In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.

Animals

The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs.

Biochemical examination of the Rev-dependent expression of gag mRNAs produced from gag-Rev-responsive element (RRE) expression plasmids showed a large discrepancy between the level of cytoplasmic gag mRNA and the produced Gag protein. Significant levels of the mRNA produced in the absence of Rev were localized in the cytoplasm, while very low levels of Gag protein were produced. In the presence of Rev, the levels of mRNA increased by 4- to 16-fold, while the Gag protein production increased by 800-fold. These findings indicated that in addition to promoting nucleus-to-cytoplasm transport, Rev increased the utilization of cytoplasmic viral mRNA. Poly(A) selection and in vitro translation of cytoplasmic gag mRNA verified that the mRNA produced in the absence of Rev was functional. To analyze the translational defect in the absence of Rev, we examined the association of the cytoplasmic gag mRNA with ribosomes. gag mRNA produced in the absence of Rev was excluded from polysomes, while gag mRNA produced in the presence of Rev was associated with polysomes and produced Gag protein. These observations showed that the presence of Rev was required for efficient loading of gag mRNA onto polysomes. This effect required the presence of the RRE on the mRNA. Analysis of mRNAs produced from a rev-minus proviral clone confirmed that the presence of Rev promoted polysomal loading of both gag/pol and vpu/env mRNAs. The localization of gag mRNA was also examined by in situ hybridization. This analysis showed that in the presence of Rev, most of the gag mRNA was found in the cytoplasm, while in the absence of Rev, most of the gag mRNA was found in the nucleus and in the region surrounding the nucleus. These results suggest that a substantial fraction of the gag mRNA is retained in distinct cytoplasmic compartments in the absence and presence of Rev. These findings indicate that the presence of Rev is required along the entire mRNA transport and utilization pathway for the stabilization, correct localization, and efficient translation of RRE-containing mRNAs.

Blotting, Northern

The orthodontic/restorative interface. Restorative procedures to aid orthodontic treatment.

Restorative procedures which complement orthodontic treatment and which may be carried out by the orthodontist are summarized. The importance of planning, with the restorative requirements in mind and the maintenance of prepared space (individual tooth or abutment positions) in all three planes of space during the period of retention, is described. The importance of liaison regarding the timing of the placement of the definitive restoration, if it is to be carried out by another dental surgeon, is stressed.

Dental Restoration, Permanent

Work-related electrical fatalities in Australia, 1982-1984.

Work-related electrical fatalities were studied as part of a larger investigation into all work-related fatalities in Australia in the period 1982-1984. The 95 electrical fatalities (all men) represented an incidence of 0.49 per 100,000 persons (0.79/100,000 men) in the employed civilian labor force during the study period. Electricity was the fifth highest cause of work-related fatalities in Australia and resulted in 10% of all workplace deaths. Ninety-four percent of the workers were performing their usual tasks at the time of their death, and 38% of them were doing work of an electrical nature at the time. The greatest number of deaths occurred on farms and nonconstruction industrial sites, with overhead powerlines as the main source of current. Better placement of overhead powerlines, improved worker awareness of electrical hazards, and the use of residual current devices would probably have prevented most of the deaths.

Accidents, Occupational

The effects of fluoride on ectopic bone formation.

The effects of fluoride (F) on ectopic bone formation induced in rats by implants of demineralized cortical bone tissue were studied. Test rats received sodium fluoride (NaF), 6 mmol/liter in drinking water, and controls received fluoride-free water. Implant accumulations of tracer hydroxyproline ([3H](OH)P), 45Ca, and stable Ca were determined 24 h after injections of tritiated proline ([3H]P) and 45Ca, to estimate rates of collagen synthesis, mineralization, and net mineral mass, respectively. Conventional histology on undemineralized implant sections was done. Mineralized bone was first observed by implant histology, 2 weeks after implantation and continued to increase up to 8 weeks. A few chondrocytes were observed. Prior to bone formation, dense fibrous tissue was observed within the marrow space of the original implant. The rate of collagen synthesis peaked at 1 week, again at 3 weeks, and then continued at a slower rate up to 8 weeks. The rates of mineralization paralleled the rates of collagen synthesis between 2 and 8 weeks, indicating bone mineralization over this period. During the first 2 weeks after implantation no mineral deposition was observed. The initial peak of collagen synthesis without mineralization (0-2 weeks) indicates fibrous tissue formation and is in agreement with the histological analysis. Fluoride treatment increased rates of collagen synthesis during both the initial period of fibrous tissue formation and later bone formation. The ratio of mineralization rate to collagen synthesis rate (45Ca/[3H](OH)P) was decreased by fluoride throughout the 2-8 week period, but net mineral mass was comparable to control rats by 8 weeks, indicating that fluoride delays, but does not prevent, bone mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Fluoride-induced fractures: relation to osteogenic effect.

The possible effects of fluoride in inducing fractures were studied in 61 patients treated with sodium fluoride (NaF), 40-60 mg daily in combination with calcium and vitamin D. Nine patients developed the fluoride-(F) related lower extremity pain syndrome. Four other patients had stress fractures associated with trauma. Seven of the 61 patients had 10 upper femur fractures of which 5 were stress fractures. The bone mineral mass of the central skeleton including the hips was measured by neutron activation and the results expressed as a calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). At the time of hip fracture, 4 patients with a minimal increase in bone mass (mean delta CaBI 0.01) had 4 femur fractures and 3 patients with a marked increase (mean delta CaBI 0.24) had 6. The 7 patients with upper femur fractures at 4 years had a significantly higher bone fluoride retention, 30 mg/g Ca compared with 23.9 mg/g Ca for the other 54 (p less than 0.02) and were older, 73.1 versus 64.2 years (p less than 0.01). Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05). By partial correlation, only the correlation between hip fractures/patient and bone fluoride remained significant after controlling for the effect of age (p less than 0.05). These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass. The lower extremity pain syndrome is not frequently associated with stress fractures in this study.

Aged

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

In vivo measurement of accumulated bone fluorides by nuclear magnetic resonance.

We have developed a localized noninvasive nuclear magnetic resonance (NMR) method for determining the accumulated bone fluoride content in human index fingers. Using a 27 MHz "split-ring" resonator probe, we measure the total fluoride (F) content within a 6.5 cm length of the distal end of the index finger from a calibrated determination of the intensity of the observed 19F free induction decay (FID) signal. Since fluoride impurities accumulate almost exclusively in bone mineral, the 19F resonance signal is broadened by rigid lattice magnetic dipole-dipole interactions, causing the FID signal to have a relatively short lifetime of approximately 75 microseconds. This short signal lifetime, plus the weakness of the signal strength prevents conventional magnetic resonance imaging equipment from observing the 19F in bone mineral. Nevertheless, we have achieved an in vivo sensitivity of +/- 0.5 mg fluoride in an observation period of 30 min. Assuming an index finger has between 0.25 and 0.5 g of bone calcium, this sensitivity is just sufficient to detect fluorides in the index finger of most adults whose bone fluoride concentration is greater than 2.0 mg fluoride/g calcium (0.8 mg/g ash weight). We are particularly interested in using this new NMR technique to monitor the rate of bone fluoride accumulation in osteoporotic patients receiving therapeutic levels of fluoride in their diets.

Bone and Bones

In vivo 19F spin relaxation in index finger bones.

19F free induction decay (FID) signals have been observed from the index fingers of four male and two female adult volunteers using a 27-MHz pulsed nuclear magnetic resonance spectrometer equipped with a split ring resonator probe. The value of the in vivo spin-lattice relaxation time T1 of the fluoride ions naturally accumulated in bone mineral has been determined to be 2.0 +/- 0.3 s. The shape of the observed FID signals in the inhomogeneous external magnetic field indicates that the F distribution is not uniform along the length of the finger. The fluoride ion content of the index finger (within a 65-mm length from its distal end) was measured with a sensitivity of +/- 0.5 mg F within a 30-min observation time.

Adult

Bone mineral mass associated with postmenopausal vertebral deformities.

Vertebral morphometry on thoracic and lumbar spine radiographs and bone mass measurements were carried out on 215 patients investigated for postmenopausal osteoporosis. Bone mineral mass was measured on the central third of the skeleton by neutron activation analysis and the result, normalized for body size, expressed as a calcium bone index (CaBI). The normal CaBI value for females (20-40 years) is 0.97 (0.11) with a lower limit for these young, normal women, of 0.75. Vertebral compression deformity was defined as a mean height more than 15% lower than adjacent normal vertebrae. Thoracic and lumbar anterior wedge deformities and central compression were defined as anterior/posterior (A/P) or mid/posterior (M/P) height ratios of less than 0.75. For the 129 patients without vertebral deformities, the mean CaBI was 0.80 (0.12) (1 SD) and 32% of these patients had CaBI values below the normal young adult range (CaBI less than 0.75). In 20 patients, vertebral deformities were limited to 1 or 2 mid-thoracic vertebrae, and the mean CaBI values for these 20 patients was 0.81 (0.15), equal to that for patients without any vertebral deformity. For the remaining 67 patients, (i.e., patients with one or more vertebral deformities involving at least one distal thoracic or one lumbar vertebra) the mean CaBI value was 0.66 (0.10), 17% below the value for patients without vertebral deformities. Low CaBI values (CaBI less than 0.75) were observed in 87% of these patients, consistent with the diagnosis of osteoporotic fractures. Based on our CaBI results, however, mid-thoracic deformity was not associated with significant osteopenia and is not, therefore, diagnostic of osteoporotic fracture.

Adult

Improved clinical facility for in vivo nitrogen measurement.

The design and construction of a hospital clinical facility for in vivo prompt gamma neutron activation analysis for total body nitrogen (TBN) measurement is described. The use of 252Cf neutron sources gives a better signal-to-background ratio compared with 238Pu-Be sources of equal strength, thus yielding better reproducibility of measurements. By measuring the hydrogen and nitrogen signals separately using appropriate gating circuits, signal-to-background ratio is further improved. Measurements using a urea phantom (5.63 kg nitrogen as urea in 34.53 kg of water) show that 2 x 6 micrograms 252Cf sources gives a nitrogen signal-to-background ratio of 5.6 (compared with 3.4 in the case of a 2 x 10 Ci 238Pu-Be source) and a reproducibility for nitrogen signal of +/- 1.1% (CV) and for hydrogen signal (internal standard) of +/- 2.33% (CV). Approximately 30 minutes of patient's time is required for each TBN measurement with an estimated reproducibility of +/- 3.8% (CV). The radiation dose to the patient is about 0.2 mSv (effective dose equivalent; QF = 10) per 20 min measurement. A report for the clinician is produced within a few minutes after the measurement by a dedicated IBM-PC computer. The entire facility is clean, comfortable and the electronics and computer processing are simple and economical.

Body Composition

Deaths as a result of work-related injury in Australia, 1982-1984.

A comprehensive study of deaths of work-related injuries which occurred throughout Australia in the years 1982-1984 was undertaken by means of coroners' records. Of 16,246 coroner-certified deaths that were attributed to trauma or to acute poisoning (excluding deaths of suicide or medical misadventure), the coroners' files were located for 15,462 (95.2%) deaths. From the files, a total of 1738 fatalities was judged to be work-related during the three-year period; of these, 1544 fatalities occurred in persons who were employed in the civilian labour force, which gave an average annual fatality incidence of 8.06 fatalities per 100,000 persons in the labour force. The death rate was much higher in men (12.05 fatalities per 100,000 men) than it was in women (1.34 fatalities per 100,000 women), increased with age, and was highest for the traditionally-dangerous occupations (such as mining, transport and rural occupations). The distribution of work fatalities by the main cause of death, and the nature of the injury event is described.

Accidents, Occupational

Investigation of factors which lead to the background in the measurement of nitrogen by IVNAA.

A major problem in the measurement of nitrogen in the body by in vivo neutron activation analysis is the size of the background. Investigations show that random summing of gamma rays in the range 4-7 MeV is a major contributor. By direct comparison, 252Cf is shown to be a better neutron source than Pu-Be in this regard. Data are presented on the contribution to the background of water and chloride in the body.

Beryllium