Search PubMed⌕ Search

Biomedical subjects

J M Hall

Publications and source records attributed to J M Hall.

At least 91 records · Page 5Linked to original sources

Receptor subtypes or species homologues: relevance to drug discovery.

Cell surface receptors are targets for the pharmacological manipulation of physiological processes and thus represent a key direction for the development of selective therapeutic agents. Traditional pharmacological techniques, together with the development of synthetic ligands, have led to the identification of differences in receptor recognition properties and the proposal of multiple receptor subtypes. Molecular biological studies have confirmed the existence of receptor subtypes within a single species by demonstrating differences in receptor primary sequences. However, equivalent receptors between species also show differences in primary structure, albeit to a much lower degree. This review by Judith Hall and colleagues addresses the question of how differences in receptor primary structure between species relate to changes in pharmacology. The relevance of this to the choice of screens in the testing of potential therapeutic drugs is discussed.

Animals↗

What really worked? A case analysis and discussion of confrontational intervention for substance abuse in marginalized women.

Confrontations, including ultimatums and withdrawal of services, are used by health care providers to break down denial in substance abusers. This case analysis and discussion explores the ramifications of confrontation for marginalized women and raises questions about the ethics and efficacy of this approach for substance abusers in general. Nursing is beginning to incorporate substance abuse as a substantive area of knowledge and practice. It is argued in this article that nurses should not uncritically adopt the current orthodoxy about this problem, but view it anew from our own unique, comprehensive perspective.

Adult↗

Plasma exchange for homozygous familial hypercholesterolaemia: the Cape Town experience.

Homozygous familial hypercholesterolaemia (FH) is a rare disorder having a greater frequency in populations with founder effects for the mutations in low density lipoprotein (LDL) receptors. It is characterized by early signs of cholesterol infiltrates with premature coronary artery disease and does not respond to conventional lipid-lowering therapy. Plasma exchange is an established mode of treatment which improves the biochemical abnormality and may allow reversal of the physical manifestations as well as favourably influencing the clinical course of the disease. The efficacy, safety and tolerability of this procedure is confirmed by our experience over the 15 years following the previous report. In a subset of these patients who have residual LDL receptor activity, further lowering of the plasma cholesterol concentration was achieved by adding simvastatin, an hydroxy-methylglutaryl coenzyme A reductase inhibitor. It is concluded that this combined approach may be of benefit in selected cases of homozygous FH undergoing regular plasmapheresis.

Adolescent↗

Tachykinin receptors mediating responses to sensory nerve stimulation and exogenous tachykinins and analogues in the rabbit isolated iris sphincter.

1. We have used selective tachykinin receptor agonists and antagonists to investigate the nature of the receptors mediating responses to endogenous and exogenous tachykinins in the rabbit iris sphincter preparation in vitro. 2. The NK1-selective agonist, substance P methyl ester, induced contraction with a pD2 of 9.16 indicating the presence of NK1 receptors. In confirmation, the NK1-selective antagonist, GR82334, competitively antagonized responses to substance P methyl ester with high affinity (pKB 7.46). 3. NK3 receptors also mediate contraction since NK3-selective agonists exhibited high potency, e.g. the pD2 of [Me-Phe7]-neurokinin B was 9.67, and their responses were not inhibited by GR82334 (10 microM). 4. NK2 receptor activation does not seem to contribute to contraction since the NK2-selective agonist [beta-Ala8]-neurokinin A(4-10) had relatively low potency (pD2 6.43), and the NK2-selective antagonists MEN10207 (1 microM) and L-659,877 (10 microM) were inactive or had low affinity, respectively. 5. GR82334 (1 microM) significantly inhibited responses to electrical field-stimulation of non-adrenergic non-cholinergic sensory nerves (3, 10 and 30 Hz), and caused a rightward shift of the log concentration-response curve to bradykinin (lateral shift ca. 1000 fold). Higher concentrations of GR82334 (10 microM) significantly attenuated responses to capsaicin (1-60 microM) whilst completely abolishing responses to field-stimulation (3, 10 and 30 Hz) and bradykinin (1 nM- 3 microM). 6. In conclusion, NK1 and NK3 receptor activation results in contraction of the rabbit iris sphincter. The contractile response following sensory nerve stimulation by bradykinin, capsaicin and electrical field stimulation results from NK1 receptor activation.

Animals↗

Multifactorial etiology of anemia in SIV-infected rhesus macaques: decreased BFU-E formation, serologic evidence of autoimmune hemolysis, and an exuberant erythropoietin response.

We attempted to define the etiology of anemia in SIV-infected rhesus macaques. Bone marrow culture showed significantly decreased (75% reduction) burst forming unit-erythroid (BFU-E) growth in end-stage SIV+ "sick" animals. Direct antiglobulin tests (DAT) were positive in nine of 35 SIV+ "well" and 14 of 14 SIV+ "sick" monkeys (0 of 25 control animals had positive DATs). In animals with a positive DAT, moderate to severe anemia was observed, as was increased LDH and spherocytosis. Erythropoietin was measured in four control, eight SIV+ "well" and five SIV+ "sick" animals with mean levels of 4.0, 15.4, and 1176 mU/mL (r = .94) in the three groups. These data suggest that the cause of anemia in the SIV-infected rhesus macaque is multifactorial, that there may be a defect in erythropoiesis, and that, serologically, an IgG mediated autoimmune hemolytic anemia is also present.

Anemia↗

THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21.

In order to pinpoint the locale of the gene for early-onset familial breast and ovarian cancer (BRCA1), polymorphisms were developed within the locus for thyroid hormone receptor alpha (THRA1) and for several anonymous sequences at chromosome 17q12-q21. The THRA1 polymorphism is a dinucleotide repeat with 10 alleles and heterozygosity.79. Gene mapping in extended families with inherited, early-onset breast and ovarian cancer indicates that BRCA1 is distal to THRA1 and proximal to D17S183 (SCG43), an interval of < 4 cM. This locale excludes HER2, THRA1, WNT3, HOX2, NGFR, PHB, COLIA1, NME1, and NME2 as candidates for BRCA1 but does not exclude RARA or EDH17B. Resolving the remaining recombination events in these families by new polymorphisms in the THRA1-D17S183 interval will facilitate positional cloning of the breast-ovarian cancer gene on chromosome 17q12-q21.

Adult↗

Restriction fragment length polymorphism analysis of ERBB2 oncogene by capillary electrophoresis.

Capillary electrophoresis (CE) with a sieving buffer containing ethidium bromide was applied to the detection of PCR-amplified RFLP samples. With CE, in contrast to agarose gel electrophoresis, run times are short, i.e., typically less than 30 min, the capillary can be re-used, and full automation is feasible. The addition of ethidium bromide to the buffer system in conjunction with a field amplification injection technique led to increased sample detectability and resolution. Migration time precision was better than 0.2% RSD with a approximately 12-bp resolution for the DNA fragment sizes of interest. RFLP samples were analyzed for homo- or heterozygosity based on the presence of 500- and/or 520-bp DNA fragments. Special software was used to correct for run-to-run migration time variations, thus facilitating genotype assignment.

DNA↗

Developing the construct of role integration: a narrative analysis of women clerical workers' daily lives.

There is a gap in nurses' knowledge about how women integrate their multiple roles on a daily basis amidst the economic, social, political, and cultural contingencies of their environments. Quantitative results from a triangulated study of work, maternal, and spousal role experiences of 87 women clerical workers from five ethnic/racial groups indicated that role integration was important in predicting health outcomes. This prior work is extended in this article with an indepth secondary analysis of the qualitative interview data from the same study to develop a theoretical understanding of the construct of role integration. Using techniques of narrative analysis, a theoretical framework was derived to identify and relate aspects, processes, and patterns of role integration as they are experienced in women's everyday lives. Concepts are identified, defined, and visually represented, propositions are elaborated, and implications for further research and practice are suggested.

Adaptation, Psychological↗

Putative novel bradykinin B3 receptors in the smooth muscle of the guinea-pig taenia caeci and trachea.

The bradykinin receptors mediating contraction in smooth muscle of the guinea-pig taenia caeci were compared with the proposed novel B3 receptors of the guinea-pig trachea. The activities of several antagonists in functional and binding studies were found to be very similar between these two guinea-pig preparations, but pKBs were markedly lower than in a number of typical B2 preparations from other species, suggesting that the characteristics of the proposed B3 receptor may be in part species-related.

Animals↗

Carcinoma arising in a dentinogenic ghost cell tumor.

A 13-year-old black girl was referred for evaluation of a nonhealing extraction site of 2 years' duration. Radiographs revealed a large, irregularly shaped, mixed radiolucent/radiopaque lesion that occupied almost the entire left area of the maxilla and crossed the midline. Microscopic examination revealed irregular dentinoid material with odontogenic epithelium that exhibited ghost cell keratinization and anaplastic changes. The patient underwent a hemimaxillectomy, and 7 years after surgery she appears to be free of disease.

Adolescent↗

Bradykinin receptors: pharmacological properties and biological roles.

Kinins contribute to the acute inflammatory response and are implicated in the pathophysiology of inflammatory disease. The development of therapeutically viable agents that counteract the effects of kinins is, therefore, potentially very rewarding. Since kinin actions are generally mediated via an interaction with cell-surface receptors, one approach is the development of site-specific receptor antagonists. The emphasis in this review is to outline our current understanding of the properties of bradykinin receptors and the potential therapeutic applications for drugs acting at these sites. As a result of the recent introduction of potent bradykinin receptor antagonists and the cloning of bradykinin receptor genes, considerable advances in kinin research can now be confidently anticipated.

Amino Acid Sequence↗

Experiences of women clerical workers in patient care areas.

Nurse managers at all levels have a stake in the well-being and job satisfaction of clerical workers in patient care areas. The authors discuss the results of a qualitative interview study of 46 women employed as unit clerks and clinic clerks. As these women described their work experiences, they identified interactional dynamics in the workplace, issues of relative powerlessness, stresses involved in dealing with ill clients, organizational problems, and occupational hazards.

Adult↗

Bradykinin receptors in the guinea-pig taenia caeci are similar to proposed BK3 receptors in the guinea-pig trachea, and are blocked by HOE 140.

1. Bradykinin (BK) receptors of the guinea-pig taenia caeci were compared with those of the guinea-pig trachea, a preparation proposed to possess novel BK3 receptors. 2. Bradykinin-evoked contractile responses were unaffected in both preparations by the selective BK1 receptor antagonist [des-Arg9,Leu8]-BK (1 microM-10 microM). The BK2 receptor antagonists, D-Arg-[Hyp3,D-Phe7]-BK and D-Arg-[Hyp3,Thi5,8,D-Phe7]-BK, both had low affinities (apparent pKB estimates less than 6) which did not differ significantly between the two preparations (P greater than 0.05). In contrast, the novel bradykinin receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE 140) potently antagonized responses to bradykinin with relatively high affinity (apparent pKB = 8.42 +/- 0.15 and 8.94 +/- 0.16 in the taenia caeci, and trachea, respectively). 3. We conclude that the bradykinin receptors in the guinea-pig taenia caeci have similar recognition properties to those present in the guinea-pig trachea, and in this respect the taenia caeci represents a useful preparation for the further study of proposed novel BK3 receptors.

Amino Acid Sequence↗

A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder.

1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum.

Animals↗

Applying critical theories to nursing in communities.

Public health realities in the United States indicate that unsafe physical surroundings, oppressive social arrangements, economic impoverishment, and political disenfranchisement threaten the safety and well-being of countless aggregates. To affect change in health-damaging conditions, nurses are urged to join with vulnerable groups, working together to expose oppressive situations and take action. As a guide for such emancipatory practice, the use of critical theories as the conceptual basis for community health nursing is advocated.

Community Health Nursing↗