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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 415 records · Page 23Linked to original sources
PubMed1990

Early HIV infection.

Explore the source record for details and available documents.

CD4-Positive T-Lymphocytes↗
PubMed1990

Consultation rates among middle aged men in general practice over three years.

OBJECTIVE: To provide data on consultation rates in general practice for middle aged men over three years according to their age and social class. DESIGN: Prospective study of men over eight years. Data on consultation rates during years 6-8 were collected retrospectively from practice records. SETTING: Over 1000 general practices in Great Britain by year 8. Initially (in 1978-80) the men had been selected at random from one practice in each of 24 towns. SUBJECTS: 7013 Men aged 46-65 in the sixth year of follow up. MAIN OUTCOME MEASURE: Number of consultations a year over three years. RESULTS: The mean annual consultation rate over the three years rose steadily with age (7.0 at age 46-50 to 9.7 at age 61-65) and with social class (6.4 in class I to 10.0 in class V) but was potentially misleading as the distribution was skew: 10.5% of men (736) did not consult over the three years and 17.2% (1209) consulted only once or twice, whereas 11.4% (798) of men were seen more than 18 times. The percentage of men who did not consult over three years fell only slightly with age and was unrelated to social class, with roughly a tenth of all age and social class groups not consulting. Two thirds of non-consulters in year 6 (1598/2334) consulted in year 7 or 8. CONCLUSIONS: The mean is not an appropriate summary measure of consultation rates and may conceal important differences among practices or other groups. The new general practitioner contract stipulates that all patients aged 16-74 must be provided with information to promote health and prevent illness at least once every three years. Most practices will have to approach a tenth of their men aged 46-65 specially to provide this service even if one consultation in three years is regarded as sufficient to allow a service to be provided.

Age Factors↗
PubMed1990

Association within a family of a balanced autosomal translocation with major mental illness.

282 pedigrees in the MRC Cytogenetics Registry, Edinburgh, with familial autosomal anomalies were examined for the presence of associated mental illness. In one large pedigree there were 23 cases of mental and/or behavioural disorders meeting Research Diagnostic Criteria. 34 of the 77 family members available for cytogenetic analysis carried a balanced translocation t(1:11) (q43,q21). Psychiatric diagnoses had been recorded for 16 of the 34 members with the translocation compared with only 5 of the 43 without it. The lod scores (against chance linkage of the translocation with mental illness) were greatest when the mental disorders in the phenotype were restricted to schizophrenia, schizoaffective disorder, recurrent major depression, and adolescent conduct and emotional disorders. Although the mental illness in this family may not be typical of that in the general population, the findings suggest that the q21-22 region of chromosome 11 may be a promising area to examine for genes predisposing to major mental illness.

Adolescent↗
PubMed1990

Physiological levels of plasma non-esterified fatty acids impair forearm glucose uptake in normal man.

1. The purpose of the present study was to maintain physiological plasma non-esterified fatty acid levels and to (i) examine their effect on skeletal muscle insulin-stimulated glucose uptake and metabolite exchange using the forearm technique, and (ii) evaluate their effect on whole-body glucose uptake and fuel oxidation. 2. Intralipid (10%) and heparin (Lipid) or saline (Control) was administered to eight healthy male subjects on separate occasions for 210 min. Insulin, glucagon and somatostatin were administered from 60 to 210 min in each study and euglycaemia was maintained. 3. Plasma non-esterified fatty acid levels plateaued at 420 +/- 50 mumol/l with the Lipid infusion but were completely suppressed during the Control clamp. Forearm non-esterified fatty acid uptake increased with the Lipid infusion (+50 +/- 10 nmol min-1 100 ml-1 of forearm) and was accompanied by a significant decrease in forearm glucose uptake (+3.23 +/- 0.25 versus +3.65 +/- 0.35 mumol min-1 100 ml-1 of forearm, Lipid and Control, respectively; P less than 0.05) and alanine release (-84 +/- 12 versus -113 +/- 15 nmol min-1 100 ml-1 of forearm, Lipid and Control, respectively; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The lipophilic muramyl peptide MTP-PE is a potent inhibitor of HIV replication in macrophages.

Cultured monocyte-derived macrophages were productively infected with human immunodeficiency virus in vitro. Treatment of these cells shortly after infection and several times thereafter with the free form of MTP-PE had an inhibitory effect on virus production. When the liposomal formulation of MTP-PE was used, higher levels of protection were achieved. The drug was not only effective when added to cells immediately after infection, but it also reduced virus production by cells with an established infection. When the liposomal formulation of MTP-PE was used only one treatment was required to achieve maximal effects. During these studies it was noted that the placebo liposomes had some effect in reducing the reverse transcriptase levels found in the supernatants of infected cells. This reduction could not be explained by direct cytotoxic effect. Both free and liposomal MTP-PE lipid significantly prevented formation of giant cells during the course of infection as well as reduced the cell associated viral antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Synergy between the NF-E1 erythroid-specific transcription factor and the CACCC factor in the erythroid-specific promoter of the human porphobilinogen deaminase gene.

A 114-base-pair promoter fragment of the human porphobilinogen deaminase gene functioned in an erythroid-specific manner in transient transfection experiments. Site-directed mutagenesis of the binding site for the erythroid-specific transcription factor (NF-E1) or an adjacent CACCC motif abolished the promoter activity. Increasing the spacing between these sites progressively reduced promoter activity, but there was no evidence that a critical alignment of the two factors on the DNA helix was required.

Ammonia-Lyases↗
PubMed1990

Parents' awareness of children's suicide attempts.

In independent psychiatric interviews with 175 children and their mothers, either the mother or the child reported that 13 (7%) of the children had made a suicide attempt. Eight of the 13 children reported attempts that were not reported by their mothers.

Adolescent↗
PubMed1990

No excess of DR*3/4 in Ashkenazi Jewish or Hispanic IDDM patients.

The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility.

Diabetes Mellitus, Type 1↗
PubMed1990

Regulation of erythroid-specific gene expression.

The aim of our group's work has been to elucidate how the alpha- and beta-globin genes come to be co-expressed together with a set of characteristic non-globin genes during erythroid cell differentiation. Our most significant progress concerns the identification and analysis of a species-conserved transcription factor, EF1, that appears to play a general role in the regulation of erythroid-specific gene transcription. We have shown that the 4 kb of 5' flanking region of the mouse alpha-globin gene contains two erythroid-specific cis-control elements, both of which involve EF1 binding sites. We have also identified functionally active EF1 binding sites in the mouse beta-globin promoter, as well as in the erythroid-specific promoter of the gene encoding the haem biosynthetic enzyme, porphobilinogen deaminase (PBG-D). The function of the PBG-D promoter depends in part on the cooperation between an EF1 binding site and an adjacent CACCC motif, this being abolished if their spacing is increased beyond 40 nt. We have also investigated the mechanisms involved in the up-regulation in erythroid cells of two non-globin genes we have cloned, encoding the RBC-specific lipoxygenase (LOX) and glutathione peroxidase (GSHPX). As judged by the presence of tissue-specific DNAse I hypersensitive sites, the tissue-specific regulation of the GSHPX gene seems to be due to regulatory regions 3' to the gene. The level of GSHPX is also regulated by selenium and this occurs at two levels: during mRNA formation, and during translation of the mRNA due to the regulation of selenocysteine incorporation specified by a unusual use of the UGA codon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Re-endothelialization of isolated segments of the canine carotid artery with reference to the possible role of the adventitial vasa vasorum.

This study was designed to determine if the adventitial vasa vasorum contribute to re-endothelialization of the canine carotid artery after removal of the endothelial flow surface. Casting studies demonstrated that vasa vasorum are present only in the adventitia of the canine carotid artery. Ninety autograft segments of the carotid artery from which the endothelium had been removed were implanted in both carotid arteries of 45 dogs. Glutaraldehyde-processed canine carotid allografts were positioned at each end to prevent pannus ingrowth and a Gore-Tex wrap to prevent periarterial tissue growth was placed into the outer wall. Three methods were used, with observations at 4 and 8 weeks. In method 1 the test segment was treated with superficial endarterectomy. In method 2 a balloon catheter was used to remove the endothelium. In method 3 balloon catheter denudation of the flow surface was also employed and, in addition, the adventitia was removed surgically as completely as possible, although a few vasa vasorum were shown to remain in some grafts. In method 1 all the patent endarterectomized arteries were partially re-endothelialized at both the 4- and 8-week intervals. In method 2, 72% of the balloon-denuded patent arteries with intact adventitial vasa vasorum were partially re-endothelialized at 4 weeks and 84% at 8 weeks. However, in method 3 the flow surfaces had no endothelium at 4 weeks and 83% still had none at 8 weeks. These findings suggest that, in the absence of pannus ingrowth, re-endothelialization of the canine carotid artery depends on not only the presence but also the number of adventitial vasa vasorum.

Animals↗
PubMed1990

Ketotifen prevents skin fibrosis in the tight skin mouse.

Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma.

Animals↗
PubMed1990

Development of brachytherapy technique for nasal tumors in dogs.

Two groups of 4 dogs underwent nasal and ethmoidal turbinectomies followed by irradiation (mean minimal) doses of 5,390 and 6,550 cGy of radiation, respectively) from implanted intracavitary sources of iridium 192. Two dogs from each group were euthanatized for histologic evaluation at 3 months after irradiation. The remaining 2 dogs from each group were euthanatized for similar evaluation at 6 months after irradiation. During the course of the study, few clinical complications were encountered. Histologic evaluation of the tissues forming the nasal passages revealed loss of epithelial lining and fibrous tissue replacement of surrounding bone. A direct correlation of pathologic changes could not be associated with the amount of radiation received, but there seemed to be a tendency for greater change in those dogs given higher doses and those kept alive for 6 months.

Animals↗
PubMed1989

Electron microscopy of negatively stained scallop myosin molecules. Effect of regulatory light chain removal on head structure.

The heads of myosin molecules from the striated adductor muscle of scallop have been studied by electron microscopy after negative staining. In common with vertebrate skeletal muscle myosin visualized by this method, the scallop myosin heads were pear-shaped and often showed pronounced curvature. Staining suggestive of two or, more frequently, three domains could often be observed. Removal of regulatory light chains (R-LCs) resulted in a reduction in the length of the heads of about 2.6 nm, with no significant change in maximum width. In desensitized preparations a majority of heads displayed anticlockwise curvature, whereas intact heads were usually seen curved clockwise. Analysis of the head curvature in both intact and desensitized molecules was consistent with an ability of each head to rotate about its long axis. Desensitization resulted in an increased incidence of heads showing two domains. It seems likely that the reduction in length upon removal of the R-LC is due to the two small domains located in the neck region of the head collapsing into one.

Animals↗