Biomedical subjects
J Bell
Publications and source records attributed to J Bell.
Meningitis caused by a penicillin- and chloramphenicol-resistant Streptococcus pneumoniae.
We report here a case of a five-month-old infant with pneumococcal meningitis, which was both penicillin- and chloramphenicol-resistant, and the difficulties that arose, both in the laboratory diagnosis of the resistance and in the therapy of this infection.
The detection of at-risk drinking in a teaching hospital.
We studied a sample of 302 inpatients from all medical and surgical wards of Westmead Hospital. Twenty-six per cent of patients (47% of men and 4% of women) were identified as past or current "at-risk" drinkers. Current drinkers preponderantly were male and were more likely to be admitted to hospital with trauma. Apart from trauma, alcohol-related disease was not diagnosed commonly, and most drinkers were admitted to hospital with diagnoses that were not related clearly to alcohol abuse. Hospital medical staff members appeared reluctant to address alcohol abuse; a low rate of alcohol problems was identified, and alcohol-related diseases appeared to be underdiagnosed.
Organization of two genes encoding cytotoxic T lymphocyte-specific serine proteases CCPI and CCPII.
The genes encoding two recently described cytotoxic T cell proteases, CCPI and CCPII, have been isolated and sequenced. The organizations of the coding and noncoding portions of the two genes are very similar to each other and also to the gene encoding rat mast cell protease type II. Similarly to other serine protease genes, each of the active-site residues is contained on a separate exon; however, two introns were found in particularly interesting positions. One occurs within the postulated activation dipeptide and the other in a position close to the active-site Asp residue. This latter intron interrupts the amino acid sequence in the invariant core region of the protein. We believe that these genes represent a new subfamily of serine protease genes.
The human glutathione S-transferases. Immunohistochemical studies of the developmental expression of Alpha- and Pi-class isoenzymes in liver.
Immunohistochemical studies of the developmental expression of the Alpha- and Pi-class glutathione S-transferases in human liver have shown that the Pi enzyme is expressed in bile-duct epithelium and some hepatocytes but not in haematopoietic cells. This locus is down-regulated during gestation in hepatocytes but not in epithelium. The enzymes of the Alpha set were also found in only some hepatocytes, and it appears that many cells express neither these nor the Pi forms.
Protein kinase C increases the activity of the polyoma virus middle T antigen-associated phosphatidylinositol kinase.
Exposure of polyoma virus-transformed fibroblasts to the protein kinase C-stimulating phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) is known to increase the transforming potential of the virus's middle T antigen. Here it is shown that this TPA treatment also stimulates an 85 kDa phosphatidylinositol kinase associated with the middle T antigen. Since activation of this kinase is known to be necessary, although not by itself sufficient for the transformation of cells by polyoma virus, bursts of protein kinase C activity, triggered by TPA or various cellular receptors, might enhance the oncogenicity of polyoma virus by stimulating this middle T antigen-associated phosphatidylinositol kinase.
Cervical spine injury. Stabilization and management.
The results of a spinal cord injury may be irreversible, or many months of rehabilitation may be required to restore a meaningful, functional lifestyle to the patient. Complications of the injury are numerous, and the financial burden of treatment can be overwhelming. The incidence of debilitating injury has decreased, however, since the advent of intensive education on emergency treatment and preventive methods. With continuing research, aggressive medical care, and innovative surgical methods, the prognosis for these patients, once dismal and devastating, may be greatly improved.
Surgical aspects of drug smuggling.
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Studies on the expression of Cu,Zn superoxide dismutase in human tissues during development.
The developmental expression of Cu,Zn superoxide dismutase in human lung and erythrocytes has been studied using activity measurements, immunoblotting and immunohistochemistry. Enzyme activity in erythrocytes increased significantly during gestation but no developmental trend was seen in lung. Immunoblotting identified a single enzyme form that was present in a variety of tissues and immunohistochemistry showed the enzyme to have widespread distribution in lung tissue. These data indicate that Cu,Zn superoxide dismutase is consistently expressed during human development and that, unlike in other species, no late-fetal surge in expression occurs.
Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination.
The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a serologically undefined DQ allelic product. DNA restriction fragment analysis with the use of several unrelated individuals and an informative family has allowed us to identify unique DQ alpha- and beta-fragments associated with the DR3, DQw- haplotype. Based on fragment size, the DQ alpha genes of the DR3, DQw- and DRw8, DQw- haplotypes are similar as are the DQ beta genes of DR3, DQw-; DRw8, DQw-; and DR4, DQw- haplotypes. In addition, a DX beta gene polymorphism has been identified which is associated with some DR3 haplotypes including the American black DR3, DQw- haplotype. cDNA sequence analysis has revealed a DQw2-like alpha gene and a DQ beta gene which is similar to that previously described for a DR4, DQw- haplotype. It is postulated that recombination between DQ alpha and DQ beta genes and between the DQ and DX subregions has generated the various DR3 haplotypes and has played an important role in creating diversity in the HLA-D region.
Tuberculosis patient compliance in the western Cape, 1984.
Patient non-compliance is regarded as a major cause of treatment failure in tuberculosis. In view of the rising tuberculosis incidence rate in the western Cape it was decided to determine which factors were related to treatment compliance. Information about patients on treatment for tuberculosis was obtained from 75% of the 68 local authorities surveyed (representing 90% of the surveyed population). Patients who had received greater than or equal to 75% of their expected doses by the survey date were considered compliant. Overall compliance was 82.5%. The lowest rates were reported in teenagers, children under 5 years, blacks and unemployed patients. The results have implications for tuberculosis control strategies.
Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast.
Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.
Synthesis and turnover of late H2B histone mRNA in developing embryos of the sea urchin, Strongylocentrotus purpuratus.
In sea urchins, "early" histone proteins are synthesized during cleavage and blastula formation, "late" histone proteins in subsequent stages of development. To understand the molecular mechanisms responsible for this ontogenic switch in histone subtype synthesis, we determined the absolute amounts, rates of synthesis, and rates of turnover of late H2b histone mRNAs during development. We showed previously that late H2b mRNA comprises several mRNA isotypes. In this study, we used both a class-specific DNA probe to measure the amounts of the late H2b mRNA isotypes collectively, and a gene-specific probe to measure amounts of a particular late H2b mRNA encoded by a gene known as L1. We found that the amount of late H2b mRNA increased dramatically from 85,000 molecules per embryo in the 16-hr blastula to a peak of 670,000 molecules per embryo in the 24-hr mesenchyme blastula, and fell to 380,000 molecules per embryo in the 72-hr pluteus larva. The L1 late H2b mRNA achieved its maximum abundance earlier than the late H2b mRNA class as a whole, reaching a peak of 34% of total late H2b in the 14-hr blastula and declining to 7% in the pluteus larva. Measurements of the rate of incorporation of [3H]uridine into late class H2b mRNA, performed by a novel in vivo isotope incorporation method, enabled us to calculate both synthesis rates and half-lives of late H2b mRNA during development. These calculations showed (1) that the increase in late H2b mRNA level between 16 and 24 hr postfertilization is regulated primarily if not entirely at the level of mRNA synthesis; and (2) that the half-life of late H2b mRNA is comparatively short, around 20 min, at all stages examined.
Increased central noradrenergic activity during benzodiazepine withdrawal: an electrophysiological study.
Spontaneous discharge rates of cerebellar Purkinje neurons were decreased in rats withdrawn from chronic treatment with alprazolam, diazepam, and lorazepam relative to discharge rates recorded from control rats. Prior treatment with 6-hydroxydopamine to deplete cerebellar levels of norepinephrine significantly reduced this effect of diazepam upon Purkinje cell firing rates. The data suggest that increased noradrenergic activity may be occurring during withdrawal from benzodiazepines.
Comparison of peripheral and central administration of naloxone in precipitating abstinence in morphine-dependent rats.
Although it has been known that a morphine abstinence syndrome can be induced by naloxone administered centrally or peripherally, data on a detailed qualitative and quantitative comparison are not available. In the present study morphine pellets were implanted into rats and naloxone was administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) 72 h later. A full array of abstinence signs with similar latency, duration, and intensity was seen in morphine-dependent rats following naloxone by either route. There were no major differences in the spectrum of withdrawal signs or in the proportion of rats showing the individual signs. In terms of body weight and temperature, the highest doses tested by each route produced similar quantitative effects. Our results demonstrate that naloxone given i.c.v. can precipitate the full morphine abstinence syndrome in rats at about 1/3 the dose needed for comparable effects when the antagonist is administered s.c.
Diagnostic imaging of post-irradiation changes in the chest.
Thirty-nine patients were studied with regard to post-irradiation changes in the chest. Twenty of these were reviewed retrospectively and 19 studied prospectively. All patients had chest radiographs and computed tomography (CT) of the chest following radiotherapy. Nineteen also had ventilation and perfusion studies of the lung, including single photon emission computed tomography (SPECT) and these were correlated with the chest radiographs and computed tomography. The majority showed abnormalities on computed tomography, the commonest being areas of lung opacification and evidence of volume loss. Several patients also showed a reduction in the size of pulmonary vessels. In most but not all, the changes were also seen on the chest radiographs. Abnormalities were not confined to the radiation fields, the vascular changes being present in large areas of lung which had not been directly irradiated. The structural and functional abnormalities correlated well as shown by ventilation and perfusion scintigraphy. However, single photon emission computed tomography was more sensitive than planar scintigraphy in showing perfusion defects, and it also showed some defects in areas of lung which appeared normal on computed tomography and the chest film. Computed and photon emission tomography were considerably more sensitive than chest radiography in showing the changes due to irradiation. The chest radiograph is clearly an insensitive indicator of post-irradiation change in the lung. Functional abnormalities are more profound and extensive than the chest film suggests, even when it is positive. There are clear implications for the planning of radiotherapy fields affecting the chest in patients who have good prospects of long-term survival. The maximum damage is related to irradiation of the hilum or mediastinum and this should be avoided wherever possible.
The use of serum methadone levels in patients receiving methadone maintenance.
Trough serum methadone concentration was measured in 43 patients under treatment for heroin addiction and complaining of withdrawal symptoms. Low serum levels were noted only in patients taking very low doses and in 10 patients who were concomitantly using enzyme-inducing drugs. The 27 patients in the maintenance program who had trough levels greater than 100 ng/ml were given no dose increase and were followed up prospectively. Alternate explanations for the patient's symptoms were well accepted in almost all cases, and subsequent performance in the treatment program appeared to be independent of serum level. We conclude that a trough serum level of 100 ng/ml is adequate for effective methadone maintenance. Measurement of serum levels can be a valuable intervention in patients with difficulties.
Sodium fluoride stimulates osteocalcin in normal subjects.
To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.