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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 181 records · Page 10Linked to original sources
PubMed1992

Morphometric analysis of Mycobacterium tuberculosis infection in mice suggests a genetic influence on the generation of the granulomatous inflammatory response.

There is evidence in natural human disease and experimental infection in mice that host genetic factors influence susceptibility to infection with Mycobacterium tuberculosis and the progress of the disease. In mouse models, both H-2 and non-H-2 genes have been implicated. In this study, four inbred strains of mice (Balb/b, Balb/k, B10, B10.BR), selected for combinations of two different H-2 haplotypes on two different non-H-2 backgrounds, were inoculated with M. tuberculosis, strain H37Rv, by intraperitoneal injection. The histological features of the granulomatous inflammatory response in the liver and lungs were investigated during the first 18 weeks of the infection. Granuloma fraction, mean granuloma area, bacillary load, and the density of acid-fast bacilli within granulomata were measured. Animals of all four strains showed the same general pattern of infection with an early, and later self-limiting, infection of the liver and delayed onset, but progressive, infection of the lung. The non-H-2 related genetic background appears to influence the morphology of the granulomatous inflammatory response. In comparison, H-2 differences appeared to be small and inconsistent.

Animals↗
PubMed1992

Mitotic indices, anti-PCNA immunostaining, and AgNORs in thick cutaneous melanomas displaying paradoxical behaviour.

Those melanomas which fail to behave as expected from their Breslow thickness provide interesting material for study. In an attempt to explain differences in behaviour, we have evaluated three distinct proliferative markers in 23 thick melanomas which failed to metastasize and in 20 well-matched control tumours with documented metastasis. The test group demonstrated significantly greater numbers of mitoses when expressed as an index (mitoses per 1000 cells), whilst no difference was found when the results were expressed in terms of mitoses per unit area. Tumours showing epidermal ulceration possessed higher mitotic indices than those of non-ulcerated lesions. High fractions of PCNA immunolabelling combined with low mitotic indices were observed frequently in the non-metastasizing group. This result and its possible relation to survival advantage are discussed in detail. Both AgNOR numbers and patterns failed to act as prognostic variables--indeed, AgNORs failed to correlate with the other proliferative indices, suggesting that their value as a marker of tumour growth is severely limited.

Cell Division↗
PubMed1992

Prevalence of dust mites in the homes of people with asthma living in eight different geographic areas of the United States.

The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.

Adolescent↗
PubMed1992

The effect of intravesical Marcain instillation on hyperreflexic detrusor contractions.

Thirty-six patients with suprasacral spinal injury were treated with intravesical local anaesthetic instillation. Eighteen of 32 patients (56%) were converted from an 'ice water positive' hyperreflexic state to an 'ice water negative' state by bupivacaine hydrochloride. Four patients treated with lignocaine hydrochloride showed no benefit. Intravesical local anaesthetic instillation is suggested as a possible treatment for selected cases of detrusor hyperreflexia in patients on intermittent catheterisation.

Administration, Intravesical↗
PubMed1992

A randomized controlled trial to compare three types of fetal scalp electrode.

OBJECTIVES: To compare three scalp electrodes in respect of need for reapplication, trace quality and scalp trauma. DESIGN: Randomized controlled trial. SETTING: Maternity Unit, Royal Berkshire Hospital, Reading. PARTICIPANTS: 780 women in labour at term, with cephalic fetal presentation, deemed to require electronic fetal heart rate monitoring using a scalp electrode. INTERVENTIONS: Three types of fetal scalp electrode: Rocket-Rolon (double-helix spiral); Hewlett-Packard (double-helix spiral); and Surgicraft-Copeland (clip). MAIN OUTCOME MEASURES: Need for more than one electrode; reason for replacement; trace quality; scalp trauma; direct financial costs. RESULTS: Reapplication was significantly least likely in the Surgicraft-Copeland group (odds ratio vs Hewlett-Packard = 0.61, 95% CI 0.41-0.90; odds ratio vs Rocket-Rolon = 0.43, 95% CI = 0.29-0.62). This reflected a much lower rate of replacement because of detachment. The Hewlett-Packard was, however, least likely to be replaced because of poor trace quality. Interpretable traces were equally common, but trace quality tended to be superior in the Hewlett-Packard group. There was no serious scalp trauma. Difficulty removing the electrode was least often reported in the Hewlett-Packard group, and a mark on the scalp persisted least often in the Rocket-Rolon group. CONCLUSIONS: The Surgicraft-Copeland performed the best overall, and particularly in respect of attachment to the scalp. It appears to be the electrode of choice of the three tested.

Adult↗
PubMed1992

Epidermal growth factor receptors in the oesophagus.

The quantity and distribution of epidermal growth factor receptors (EGF-R) in oesophageal mucosa was studied in the oesophagus in order to determine its role in oesophageal disease. Fifty five biopsies were taken from different levels of the oesophagus in 25 consecutive patients undergoing endoscopy. Another group of eight patients with histologically proven Barrett's oesophagitis had a biopsy taken from the area of columnar lined oesophagus. A peripheral, membranous pattern was seen predominantly confined to the basal and immediately suprabasal cells in all of the first group of patients. In the superficial cells a few granular cytoplasmic structures were positive. All patients with Barrett's oesophagitis showed EGF-R staining of the surface epithelium. A computerised planimeter was used to determine the proportion of stained areas of squamous cells which were expressed as a percentage of the total area of squamous cells. The difference in the area of cells stained for EGF-R between normal and inflamed oesophageal mucosa (29.5% and 43.1% respectively) was significant (p less than 0.001).

Adult↗
PubMed1992

Measurement of the immunoperoxidase staining of macrophages within liver granulomata of mice infected with Mycobacterium tuberculosis.

A quantitative image analysis technique developed for the measurement of the extent of macrophage activation and epithelioid cell differentiation was performed on mice infected experimentally with Mycobacterium tuberculosis. The granulomatous inflammatory response within the liver reached a peak at day 23 and declined by day 33. Animals of strain B10.BR (H-2k) showed an increased granuloma fraction as compared to Balb/k (H-2k) mice, thus confirming the influence of non-H2 genes in the control of granuloma formation in mice. Using a monoclonal antibody against CD11b/CD18 (Mac1;CR3), we observed two subpopulations of macrophages within the granulomata. The small, darkly staining cells at the periphery of granulomata appear to be newly recruited macrophages. Larger, paler staining cells toward the center of granulomata represent activated and mature epithelioid macrophages. Using a semiautomated image analyzer (Quantimet 970), we measured the relative numbers of these macrophage subpopulations. There were more activated macrophages (epithelioid cells) associated with the increased granuloma fraction in the B10.BR mice than in the Balb/k. However, similar numbers of newly recruited peripheral macrophages were found in both Balb/k and B10.BR strains. This technique has shown qualitative as well as quantitative differences in the granulomatous inflammatory response in this murine model of tuberculosis in strains of mice with quite different antibody repertoires to mycobacterial antigens.

Animals↗
PubMed1992

The TEAM evaluation approach to Project FAMUS, a pan-Canadian risk register for primary care.

The application of the TEAM--Total Evaluation and Acceptance Methodology--to the development of Project FAMUS--Family Medicine, University of Sherbrooke--is described. Project FAMUS is concerned with the establishment of a pan-Canadian risk register, the data being provided from a network of 800 family physicians distributed across Canada. Emphasis is on the first phase of the project and the overall evaluation strategy.

Computer User Training↗
PubMed1991

Characterization of glucose-6-phosphatase in hepatocytes. Effects of amiloride and pentamidine.

The hepatic microsomal glucose-6-phosphatase enzyme is situated inside the lumen of the endoplasmic reticulum and, for normal enzyme activity in vivo, three transport systems are needed for the substrate glucose-6-phosphate and the products phosphate and glucose. Previous studies using isolated microsomes showed that the drugs amiloride and pentamidine do not affect the glucose-6-phosphatase enzyme but can activate the glucose-6-phosphate transport system. Here we demonstrate that, very surprisingly, the addition of pentamidine (and to a lesser extent amiloride) to isolated hepatocytes results in an inhibition of the catalytic subunit of glucose-6-phosphatase.

Amiloride↗
PubMed1991

Identification and characterization of a hepatic microsomal glucose transport protein. T3 of the glucose-6-phosphatase system?

A 52 kDa polypeptide in rat liver microsomes was identified as a glucose-binding protein by its ability to weakly bind cytochalasin B and by its cross-reactivity to an antibody raised against the human erythrocyte glucose transport protein. The microsomal glucose binding polypeptide was purified by affinity chromatography and an antibody was raised against it. The inhibitory effect of this antibody on rat microsomal glucose-6-phosphatase activity and on glucose transport out of microsomal vesicles indicates that this protein is a microsomal glucose transport protein.

Animals↗
PubMed1991

Differential expression of the GLUT1 and GLUT4 glucose transporters during differentiation of L6 muscle cells.

Skeletal muscle is the main tissue responsible for glucose utilization in the fed state, and it expresses the ubiquitous GLUT1 glucose transporter and the muscle/fat specific GLUT4 glucose transporter. Here we investigated the expression of these transporters during muscle cell differentiation in vitro. Rat L6 muscle cells were grown to the stages of myoblasts, alignment and fused myotubes. Glucose (2-deoxy-D-glucose) transport was higher in myoblasts, decreasing with the progression of alignment and cell fusion. Conversely, insulin-stimulated glucose uptake was negligible in myoblasts, and increased with cell alignment and fusion. The cellular content of GLUT1 transporters decreased and that of GLUT4 transporters increased with cell fusion. Insulin rapidly stimulated glucose uptake in fused myotubes maintained in 2% serum but not in 10% serum. In 10% serum, basal glucose uptake increased as did the cellular content of GLUT1 transporters, while GLUT4 transporter content did not change. These results indicate that both transporters are regulated oppositely during muscle cell differentiation, and that high serum concentrations override the capacity of insulin to regulate transport by inducing overexpression of the GLUT1 transporter.

Animals↗