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Biomedical subjects

J Shaw

Publications and source records attributed to J Shaw.

At least 199 records · Page 11Linked to original sources

Bone mineral content of Gambian and British children aged 0-36 months.

The influence of age, sex and body size on the bone mineral content of the radius (BMC) measured by single-photon absorptiometry has been studied in 134 British and 243 rural Gambian children aged 0-36 months. Growth rates and childhood nutrition, including calcium intakes, were markedly different in the two communities. In both groups BMC increased with age and was higher in boys (8%, P less than 0.001). Adjustment for body size (height, weight, bone width), using multiple regression analysis, removed the age effect and reduced the sex difference to 4% (P less than 0.01). Gambian children had significantly lower BMCs than British children of the same age (P less than 0.001), averaging 11% close to birth and diverging to a calculated difference of 31% at 36 months. The differential was reduced after adjustment for body size but remained significant (P less than 0.01) with BMC values diverging from birth to a predicted difference of 12% at 15 kg body weight. The extent to which these results reflect the low calcium intakes of Gambian children requires further study.

Aging↗

Absence of abnormalities of the c-erbB-1 and c-erbB-2 proto-oncogenes in human thyroid neoplasia.

The c-erbB-1 and c-erbB-2 proto-oncogenes are frequently activated by gene amplification and overexpression in a variety of human cancers. In an analysis of a large series of benign and malignant thyroid tumours, no abnormalities of structure or expression of either of c-erbB-1 or c-erbB-2 were found. Activation of these oncogenes is not a necessary event in neoplasia of this epithelial system.

DNA, Neoplasm↗

Play therapy with the sexual workhorse: successful treatment with twelve cases of inhibited ejaculation.

This paper explores play as treatment for inhibited ejaculation (IE), based on success with 12 heterosexual and homosexual men. The focus is on men able to ejaculate with their own touch but not with partner touch or penile containment. A definition of IE includes: compulsive need to please partner, response anxiety, nonsexual automatic erections, and the penis's refusal to be commanded interpersonally. Treatment options with individuals and/or couples begin with reframing the symptom as compulsive giving and are not directed at forcing ejaculation. Playing, interfering with erroneous beliefs about sexual arousal, and avoiding helping the workhorse work harder are the trust of this paper.

Creativity↗

Wrongful birth and the politics of reproduction: West German and English law considered.

This article considers the law relating to compensation in tort and contract for failed sterilizations and failed abortions leading to the birth of an unplanned but healthy child in the Federal Republic of Germany and England. It uses a policy-based analysis which takes the social construction of gender as a significant factor in judicial decision making. It criticizes existing literature for failing to take into account gender divisions in society and points to ways in which both the framework within which wrongful birth cases are discussed generally and the limitations which have been placed on recovery specifically reflect gender stereotyped notions of female and male behaviour and sexuality. I conclude that there are three main areas of concern in the wrongful birth cases: a) the inadequate recognition which the law accords to women's work in the home when awarding damages for maintenance of the unplanned child to majority; b) the awarding damages exercised by the politics of abortion, which can lead to undue restrictions on recovery; and c) the difficulties which the law experiences when attempting to conceptualize an interference in a woman's procreative autonomy in the same terms as an interference in a typically 'male' sphere of life, such as professional autonomy. Thus there is an urgent need to reconsider the categories of the law of obligations such as 'damage' and 'compensation', which are central to the principle of individual responsibility for harm caused, in order to reveal their gendered content and differential effects.

Abortion, Induced↗

Effect of non-steroidal anti-inflammatory drugs on neutrophil chemotaxis--an in vitro and in vivo study.

We have studied the effects of the two non-steroidal anti-inflammatory drugs (NSAIDs), nabumetone and indomethacin, on neutrophil chemotaxis in vitro and in vivo. When used in therapeutic concentrations in vitro, neither agent had any effect on the chemotactic response of neutrophils isolated from healthy volunteers. This was true for the three chemotactic agents studied: FMLP, zymosan activated serum and purulent sputum. Nabumetone and indomethacin decreased neutrophil chemotaxis over a period of 2 weeks in 12 normal subjects in vivo. The average chemotactic response to 10(-8) mol/l FMLP for all 12 during the control period was 42.1 +/- 6.1 cells per high power field and this fell to 26.1 +/- 4.9 (P less than 0.025) after 7 days and to 15.6 +/- 2.5 (P less than 0.005) after 14 days. The results were similar for both drugs analysed independently. The results suggest that NSAIDs have no effect on the chemotactic response of mature cells in vitro, but suppress chemotaxis progressively when given in vivo. This may be explained by an effect of NSAIDs on maturing cells prior to release into the circulation.

Adult↗

Breast-milk calcium concentrations during prolonged lactation in British and rural Gambian mothers.

Detailed investigation of breast-milk calcium concentrations during 2 years of lactation have been conducted in Cambridge, UK, and rural Gambia. Mature milk concentrations remained steady for 3 months but declined during months 4-12 by over 25% (p less than 0.001). The pattern was identical in both communities despite differences in breast-feeding practices. Calcium concentrations were not related to feed frequency or breast-milk sodium concentrations, suggesting that breast involution is not responsible for the decrease after 3 months. Breast-milk calcium concentrations were characteristic of the individual, varied twofold between mothers and were independent of maternal age, parity and milk output. Gambian breast-milk contained 19% less calcium than Cambridge milk, throughout lactation (p less than 0.001). The extent to which this reflected the lower calcium intakes of Gambian mothers is unknown. Further studies are required to determine factors regulating breast-milk calcium secretion.

Breast Feeding↗

Studies of intestinal lymphoid tissue. XIV--HLA status, mucosal morphology, permeability and epithelial lymphocyte populations in first degree relatives of patients with coeliac disease.

Fifty two first degree relatives of patients with coeliac disease were investigated for HLA status, small intestinal permeability, and mucosal morphology together with the size of the intraepithelial lymphocyte pool and indices of lymphocyte activation, in an attempt to identify genetically determined markers of the disease. Thirty eight per cent of these subjects had increased intraepithelial lymphocyte populations and a highly significant association with HLA-DR3 compared with controls. Their intestinal permeability to 51chromium-labelled ethylenediamine tetraacetate was invariably normal and there was no evidence of abnormal mucosal architecture, increased crypt cell mitotic activity or lymphocyte 'activation'. Although increased intraepithelial lymphocyte counts clearly do not cause alterations in intestinal structure or function, it is likely that this parameter together with the HLA-DR3 status identifies a genetically determined predisposition to the disease which may only become clinically evident with larger doses of ingested gluten.

Adolescent↗

Regional localisation of the Friedreich ataxia locus to human chromosome 9q13----q21.1.

We have previously assigned the Friedreich ataxia locus (FRDA) to chromosome 9; the current maximal lod score between FRDA and MCT112 (D9S15) is greater than 50 at a recombination fraction of theta = 0. The physical assignment of the locus defined by MCT112, and hence FRDA, has not been determined, although linkage analysis of MCT112 with other chromosome 9 markers inferred a location close to the centromere. We have used in situ hybridisation with MCT112, a corresponding cosmid MJ1, and DR47 (D9S5), coupled with mapping studies on hybrid cell panels, to define more precisely the location of the disease locus. The in situ location of all three probes is 9q13----q21.1, distal to the variable heterochromatin region. Physical assignment of FRDA will allow us to identify hybrid cell lines containing the mutated gene.

Chromosome Mapping↗

Effect of alpha-1-proteinase inhibitor on neutrophil chemotaxis.

Factors that modulate neutrophil migration into the lung are poorly understood. However, there is evidence that neutrophil activation by formylmethionylleucylphenylalanine (FMLP) depends upon a surface proteinase with chymotrypsin-like activity. This suggests that chymotrypsin inhibitors such as alpha-1-proteinase inhibitor (alpha 1PI) could modify neutrophil migration in response to FMLP. We have studied neutrophil chemotaxis using the multiple blind well assay system. This article presents evidence that alpha 1PI is an inhibitor of neutrophil migration in response to FMLP. The effect is related to the inhibitory function of the protein. Alpha-1-antichymotrypsin is more potent than alpha 1PI as an inhibitor of this movement, whereas antileukoprotease is less potent. The results suggest that a cell membrane-bound serine proteinase (perhaps cathepsin G) is necessary for the enhancement of cell movement after receptor binding of FMLP. Oxidized alpha 1PI or a 4,000-D peptide cleaved from alpha 1PI by porcine pancreatic elastase or human neutrophil elastase are capable of enhancing cell motility. The results suggest that alpha 1PI may play a role in cell migration into the lung during acute inflammatory process.

Animals↗

Suicide in United States Army personnel, 1985-1986.

A sixth biennium of epidemiological data on suicide in the U.S. Army was compiled. The annual crude suicide rate per 100,000 soldiers-at-risk for 1985-1986 was found to be 13.8, an increase of 3.8 points from 1983-1984. Sex-specific, race-specific, age-specific, grade-specific, and marital-status-specific rates were studied, and can be compared with the same indices in the previous six biennia. The standardized mortality ratio was calculated for 1986 and was found to be 69, significantly lower than the 100 expected from a civilian population of the same size and age-sex-race composition as the U.S. Army. Demographic data and information on circumstances surrounding the suicidal act were also made available for comparison with previous data. Analysis of the suicidal person's psychosocial situation (as reflected in the kinds of personal problems recorded in the reports and investigations of the incident and as reflected in assessment made of the victims presuicidal "motivational state") showed remarkable constancy in the five time periods studied, and indicates a powerful, consistent association between a dyadic love-object relationship in total collapse and the completed suicide.

Adolescent↗

Intercellular adhesion molecule 1 on liver allografts during rejection.

The expression of intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor lymphocyte-function-associated antigen 1 (LFA-1), was studied on liver tissue after transplantation. There was greater ICAM-1 expression on bile ducts, endothelium, and perivenular hepatocytes (structures affected by the rejection process) in patients with acute rejection than in donor livers, patients with stable transplants, or patients with non-rejection complications. The expression on bile ducts and hepatocytes was greater in patients in whom there was progression to chronic, irreversible rejection. In patients with resolving rejection ICAM-1 expression was greatly reduced after high-dose corticosteroid treatment. The expression in patients with non-rejection complications and in those with long-term stable grafts was similar to that seen in the donor controls. The induction of ICAM-1 on tissues may be an important step in the development of the inflammatory response of rejection and in determining which cells are the targets of immune damage. The reduction of ICAM-1 expression seen after successful treatment with high-dose corticosteroids suggests that this might be an important mode of action of these drugs.

Acute Disease↗

CD45R as a primary signal transducer stimulating IL-2 and IL-2R mRNA synthesis by CD3-4-8- thymocytes.

CD45R is a high molecular weight (p205/220) form of a series of transmembrane glycoproteins, collectively known as CD45 and present in some form on all lymphoid cells. We have proposed that CD45R+ thymocytes, a minority (15 to 30%) of total thymocytes, represent the generative thymic lineage whereas CD45 p180+ thymocytes are destined for intrathymic death. To test this hypothesis, we prepared human thymus fractions enriched for the expression of CD45R by exhaustive depletion of CD45 p180+ cells, as well as progenitor CD3-4-8- "multinegative" thymocytes which are predominantly CD45R+. Northern analysis of RNA extracted from CD45 p180- and multinegative thymus fractions demonstrated that these populations are enriched for cells able to synthesize mRNA encoding IL-2 and IL-2R after mitogenic stimulation, as compared to unfractionated thymus, consistent with the properties expected for generative thymocytes. Postulating that the CD45R glycoprotein might represent an important signal delivery molecule, we analyzed the ability of mAb specific for CD45 epitopes to synergize with suboptimal amounts of PHA and PMA in the stimulation of IL-2 mRNA production by multinegative thymocytes. We found that CD45R-specific mAb synergizes strongly with PHA/PMA to stimulate IL-2 and IL-2R mRNA expression. In contrast, mAb to CD45 common determinants were unable to synergize. Multinegative thymocytes depleted of all CD45 p180+ cells were compared to total multinegative cells and found to synthesize fourfold greater levels of IL-2 mRNA after stimulation with anti-CD45R mAb. This CD45 p180- multinegative subset is enriched for cells expressing a high density of CD45R, and for CD45- thymus cells, suggesting a possible enrichment for nonlymphoid cells which may play a role in the stimulation process. Our results suggest that the extended amino acid insert of CD45R plays a fundamental role in transmembrane signalling, and that CD45R may be a primary signal transducer for developing thymic progenitor cells.

Adjuvants, Immunologic↗

Transcriptional regulation of two cytotoxic T lymphocyte-specific serine protease genes.

The expression of two serine proteases is induced by antigenic stimulation in cytotoxic T lymphocytes. Using nuclear run-on analysis the increase in steady state mRNA level has been shown to correspond to transcriptional activation. However, the two genes appear to be sequentially rather than coordinately induced. Both genes were shown to be more sensitive to DNase I digestion than a beta-globin gene in cytotoxic T cells. In addition, for the cytotoxic cell protease 1 gene the 5' region of the gene was more sensitive than the 3' end. Two DNaseI hypersensitive sites were seen in the 5' flanking sequences of both genes. The DNA sequences of the upstream regions of both genes were determined and compared. Although the two flanking sequences are overall quite dissimilar, there are short regions which are shared between the two CTL-protease genes. A number of these have been implicated in regulating the expression of other T cell genes.

Animals↗

"Acadian" and "classical" forms of Friedreich ataxia are most probably caused by mutations at the same locus.

"Acadian ataxia" is a form of Friedreich ataxia found in individuals of Acadian ancestry. It was described by Barbeau (in Sobue I (ed): Spinocerebellar Degeneration; Tokyo: Univ. Tokyo Press, pp 121-142, 1980) as having a slower course of degeneration and less severe secondary symptoms than "classical" Friedreich ataxia. He suggested that these 2 forms of the disease may be distinct. The mutation causing "classical" Friedreich ataxia has recently been mapped to chromosome 9 through genetic linkage studies, and here we show that the locus causing Friedreich ataxia in Acadian families from southwestern Louisiana is tightly linked to the same DNA marker, D9S15. Thus, these 2 disorders, which may be differentiated clinically, are most probably due to mutation(s) at the same locus on chromosome 9.

Chromosome Mapping↗

Prenatal diagnosis of Friedreich ataxia.

Friedreich ataxia is a progressive neurodegenerative disorder affecting the peripheral and central nervous systems. One in 50,000 of the population are affected by this recessively inherited disorder, with onset usually before puberty. The recent localization of the disease locus to chromosome 9 has made it possible to provide genetic counselling to families with at least one affected child. Tight linkage of the disease mutation to an anonymous DNA marker MCT112 (D9S15) has been shown with a pairwise lod score of 36.1 at 0 = 0. We report here the first prenatal diagnosis in Friedreich ataxia. Using MCT112 and the confidence interval approach, we have calculated risks for a fully informative family with one affected sib.

Amniocentesis↗