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Biomedical subjects

J M Hall

Publications and source records attributed to J M Hall.

At least 109 records · Page 6Linked to original sources

Contrasting properties of bradykinin receptor subtypes mediating contractions of the rabbit and pig isolated iris sphincter pupillae preparation.

Bradykinin contracts both the pig and rabbit iris sphincter preparations. In the pig, the bradykinin antagonists Lys,Lys-[Hyp3, Thi5,8,D-Phe7]-BK and D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE140) inhibited responses with pKB estimates of 6.0 and 8.4, respectively. These affinities are markedly lower than in the rabbit preparation, suggesting that different receptors are present in each of the two species.

Animals↗

Closing in on a breast cancer gene on chromosome 17q.

Linkage of early-onset familial breast and ovarian cancer to 11 markers on chromosome 17q12-q21 defines an 8-cM region which is very likely to include the disease gene BRCA 1. The most closely linked marker is D17S579, a highly informative CA repeat polymorphism. D17S579 has no recombinants with inherited breast or ovarian cancer in 79 informative meioses in the seven families with early-onset disease (lod score 9.12 at zero recombination). There is no evidence for linkage heterogeneity in the families with early-onset disease. The proportion of older-onset breast cancer attributable to BRCA 1 is not yet determinable, because both inherited and sporadic cases occur in older-onset families.

Base Sequence↗

Neurokinin receptors in the rabbit iris sphincter characterised by novel agonist ligands.

We have used novel selective agonist ligands to examine neurokinin receptors mediating the contractile response to tachykinins in the rabbit iris sphincter preparation in vitro. The selective NK-1 receptor agonist delta-amino valeryl-[L-Pro9,N-Me Leu10]SP-(7-11) (GR73632) and the NK-3 receptor-selective agonist succ-[Asp6,N-Me-Phe8] SP-(6-11) (senktide) were both very active (concentration range 0.032 pM-10 nM and 0.1 pM-32 nM respectively), and were 933 and 16.6 times more potent than substance P, respectively, in contracting the iris. In contrast, the NK-2 selective agonist [Lys3,Gly8-R-gamma-lactam,Leu9]NKA-(3-10) (GR64349) was active only at the highest concentrations tested (3.2 nM-32 microM), and had 0.054 the activity of substance P. The presence of several peptidase inhibitors was without effect on the concentration-response relationship to substance P, GR73632, GR64349 or senktide. Tachykinins differed in their offset kinetics. Responses to GR73632, GR64349 and senktide were rapid in offset (times to reach half maximal responses were 1.5, 1.1 and 5.1 min, respectively), whereas responses to substance P were very much more prolonged in duration (time to reach half maximal response was 35.3 min). These results suggest the presence of both NK-1 and NK-3 receptors mediating contraction of the rabbit iris sphincter preparation. In addition, differences in response offset kinetics seem not to be due to differences in peptide metabolism, and suggest a property of substance P not shared by the other tachykinins used in this study.

Animals↗

Bradykinin B2 receptor evoked K+ permeability increase mediates relaxation in the rat duodenum.

We have investigated the receptors and associated coupling mechanisms that mediate the smooth muscle relaxant response to bradykinin (BK) in the rat duodenum in vitro. Relaxation in response to BK seems due to a direct action on the longitudinal smooth muscle since effects were demonstrable in the presence of ibuprofen, mepyramine, atropine, guanethidine (all 1 microM), hexamethonium (10 microM) and TTX (0.3 microM). Receptors involved are of the B2 subtype since agonists and antagonists active at B1 receptors were essentially inactive, and the B2 receptor antagonist Lys,Lys-[Hyp3,Thi5,8,D-Phe7]BK was a potent competitive antagonist of BK-induced relaxation (pKB of 7.2 +/- 0.1). The activity of both BK and the antagonist were unchanged by the presence of peptidase inhibitors including the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (mergetpa, 10 microM), which prevents conversion of BK analogues to des-Arg9-B1-active products. In high-K+ solution, BK (0.1-10 microM) produced concentration-related increases in 86Rb efflux. Both this permeability increase in high-K+ solution, and the relaxant responses in Krebs solution, were inhibited by low concentrations (10-100 nM) of apamin, as well as the B2 receptor antagonist Lys,Lys-[Hyp3,Thi5,8,D-Phe7]BK (1 microM). These results are compatable with the proposal that BK-evoked relaxation of the rat duodenum is mediated via a subset of B2 receptors for which the antagonist Lys,Lys-[Hyp3,Thi5,8,D-Phe7]BK has a high affinity, and results from stabilisation of the smooth muscle membrane through the opening of apamin-sensitive 86Rb-permeable calcium-activated K+ channels.

Animals↗

In vitro study of immunologic changes in long-term cytapheresis donors.

Several in vitro measurements of immune function were examined retrospectively in a population of active long-term cytapheresis donors (group I; n = 50) and the results were compared to age- and sex-matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T-cells (P = .0026) and T-helper cells (P less than .0001), and helper-to-suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B-cell count, T-suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T-helper cell numbers and accounted for the imbalance in the helper-to-suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.

Adult↗

Subtypes and excitation-contraction coupling mechanisms for neurokinin receptors in smooth muscle of the guinea-pig Taenia caeci.

This study investigated the subtype and coupling mechanisms mediating the direct contractile response to tachykinins in the guinea-pig Taenia caeci preparation in vitro. Coupling of neurokinin receptors was compared throughout with coupling of muscarinic receptors. The smooth muscle neurokinin receptors seem to be predominantly of the NK-1 subtype. Thus, the relative activities of the common naturally-occurring tachykinins fell within one order of magnitude, and the selective NK-1 receptor agonist substance P methyl ester was high in activity (0.38 relative to substance P). Some contribution from NK-3 receptors is, however, possible in view of the appreciable activity of the selective NK-3 agonist succ-[Asp6, N-MePhe8]-SP(6-11) (senktide; activity 0.004 relative to substance P), and NK-2 or NK-3 receptors in view of the higher activity of the D-isomer of [Glp6, *Pro9]-SP(6-11) as compared to its NK-1 selective L-isomer (D/L-activity ratio 1.53). Contractile actions of tachykinins were compared with carbachol for reliance on membrane-potential dependent (electromechanical) and membrane-potential independent (pharmacomechanical) coupling mechanisms. Log concentration-response curves to carbachol and substance P in normal Krebs' medium were compared with curves obtained in a high-K+ solution where processes dependent on changes in membrane potential could play no part in excitation. In the high-K+ depolarizing solution, a concentration-related relationship was maintained, though with some diminution in the maximal additional tension generated: the maximum tension with carbachol was under both conditions greater than that with substance P. The relative effects of several tachykinins and carbachol in producing receptor-mediated changes in membrane permeability through presumed receptor-operated ion channel opening, was estimated in terms of the ability to increase 86Rb-efflux, as a marker for K+, in a high-K+ depolarizing solution. Carbachol (10 microM) consistently increased 86Rb-efflux. In contrast, no permeability increase could be detected with any tachykinin tested (substance P, eledoisin, substance P methyl ester, neurokinin A, neurokinin B, 1 or 10 microM). Tachykinins and carbachol were compared in terms of ability to increase phosphatidylinositol hydrolysis. Both substance P and carbachol showed a concentration-related increase in accumulation of total inositol phosphates; though the maximal response to carbachol was considerably greater than that to any tachykinin (substance P, eledoisin, substance P methyl ester, senktide, neurokinin A, neurokinin B), or combination of two tachykinins (substance P and eledoisin, senktide and substance P methyl ester).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Osteomyelitis of the mandible in a patient with dysosteosclerosis. Report of a case.

Dysosteosclerosis is a rare bone dysplasia that has radiographic, histopathologic, and clinical similarities to osteopetrosis. This article reviews the dental findings reported in patients with dysosteosclerosis and presents the first reported case of osteomyelitis of the mandible in a patient with this disease. This is also the first report that demonstrates ankylosis of impacted teeth in dysosteosclerosis.

Adult↗

Rigor in feminist research.

Verifying the scientific adequacy of feminist studies is necessary to assure that research processes and outcomes are well grounded, cogent, justifiable, and relevant. The authors analyze what scientific adequacy means in feminist inquiry and propose standards of rigor by which nurse investigators can plan and evaluate their studies. In the process, conventional empiricist criteria of reliability and validity are critiqued, and more appropriate concepts representing dimensions of adequacy in feminist research are presented.

Female↗

Immunohistochemical staining for ferritin in neuroblastomas.

Immunohistochemical staining for ferritin was examined in 35 neuroblastomas from 27 children and compared with serum ferritin levels. All but two of the patients presented with advanced (stages III and IV) disease, and the adrenal was the most common primary site (20/27, 74%). Immunostaining was positive in only one of 14 tumour biopsies taken at the time of diagnosis (7%), but eight of 21 neuroblastomas (38%) marked for ferritin after chemotherapy. No consistent association was established between tumour- and serum-associated ferritins in the untreated or treated groups. Ferritin staining in treated neuroblastomas was usually more marked in partly differentiated tumour cells. The increased frequency of ferritin positive neuroblastomas after chemotherapy appeared to be associated with large local accumulations of ferritin and haemosiderin within the treated tumours, and (probably) with the blood transfusions which these children received.

Antineoplastic Agents↗

Novel selective agonists and antagonists confirm neurokinin NK1 receptors in guinea-pig vas deferens.

1. This study investigated the recognition characteristics of neurokinin receptors mediating potentiation of the contractile response to field stimulation in the guinea-pig vas deferens. 2. A predominant NK1 receptor population is strongly suggested by the relative activities of the common naturally-occurring tachykinin agonists, which fall within less than one order of magnitude. This conclusion is supported by the relative activities of the synthetic NK1 selective agonists substance P methyl ester, [Glp6,L-Pro9]-SP(6-11) and delta-aminovaleryl-[L-Pro9,N-MeLeu10]- SP(7-11) (GR73632) which were 0.78, 9.3 and 120 as active as substance P, respectively. Furthermore, the NK2 selective agonist [Lys3, Gly8,-R-gamma-lactam-Leu9]-NKA(3-10) (GR64349) was active only at the highest concentrations tested (greater than 10 microM), and the NK3 selective agonist, succ-[Asp6,N-MePhe8]-SP(6-11) (senktide) was essentially inactive (10 nM-32 microM). 3. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP(1-11) antagonized responses to neurokinin A, neurokinin B, physalaemin, eledoisin, [Glp6,D-Pro9]-SP(6-11), GR73632 and GR64349 (apparent pKB s 5.6-6.2), but was less potent in antagonizing responses to substance P, substance P methyl ester and [Glp6,L-Pro9]-SP(6-11) (apparent pKB s less than or equal to 5.0-5.0). 4. In contrast, the recently developed NK1-selective receptor antagonist [D-Pro9[Spiro-gamma-lactam]Leu10,Trp11]-SP(1-11) (GR71251) did not produce agonist-dependent pKB estimates. Schild plot analysis indicated a competitive interaction with a single receptor population where the antagonist had an estimated overall pKB of 7.58 +/- 0.13 for the four agonists of differing subtype selectivity tested (GR73632, GR64349, substance P methyl ester and neurokinin B). This estimate is similar to that we obtained for NK1-mediated (substance P methyl ester) contraction in the guinea-pig ileum preparation (pKB= 7.86+ 0.05). 5. Tachykinin action appears not to depend on release of a number of intermediary mediators including acetylcholine, histamine or cyclo-oxygenase products, nor to involve interaction with neuronal mechanisms including alpha 2-adrenoceptor feedback, noradrenergic Uptake-I or opioid-release, since antagonism or inhibition of these mechanisms did not modify responses to tachykinins. 6. We conclude that tachykinin action in the field-stimulated guinea-pig vas deferens preparation is mediated through interaction with a predominant neurokinin NK, receptor population and this preparation can therefore be used to study NK, modulation of sympathetic neurotransmission.

Animals↗

A critical historical analysis of the medical construction of lesbianism.

Lesbians are frequently treated with insensitivity, antagonism, and discrimination in health care encounters. The authors argue that contemporary health care experiences of lesbian clients cannot be understood apart from a critical examination of the historical construction of medical ideologies that pathologized lesbianism. An excavation of historical data about medical conceptualizations of lesbian women is undertaken to demonstrate how cultural and medical ideologies throughout the century have reinforced each other to shape lesbians' health care experiences and influence public policies. By illuminating both the prejudical content of medical theories as well as the emancipatory actions of lesbian and gay communities to change stigmatizing diagnostic and treatment situations, the authors attempt to demystify ideologies about lesbians that motivate clinicians, administrators, educators, researchers, and theorists in the delivery of health services.

Female↗

Case report and review: alloimmunization, delayed hemolytic transfusion reaction, and clinically significant anti-Yt(a) in a patient with Beta-thalassemia/sickle cell anemia.

A 26-year-old female with Beta-thalassemia/sickle cell anemia was admitted to the hospital with symptoms of a painful crisis. During the next 4 days her hematocrit decreased to 13 percent, and there was reticulocytopenia. She was transfused with four units of red blood cells that were microscopically incompatible, and the hematocrit increased to 29 percent. Eight days later the patient was readmitted with back pain, hemoglobinuria, and a hematocrit of 27 percent. Anti-E, -c, -Jka, and -Yta were identified. The direct antiglobulin test was positive, and the eluate contained anti-c and -Jka. The patient's hematocrit continued to decrease to 14 percent. Transfusions were withheld and the patient recovered uneventfully. Separate 51Cr red blood cell survival studies showed significantly shortened survival of both autologous and R(1)R(1), Jk(a-), Yt(a+) erythrocytes. This case illustrates the complexity of transfusion management in hemoglobinopathy patients.

Journal Article↗

Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease.

The estrogen-receptor locus is a candidate gene for inherited susceptibility to human breast cancer, particularly among families with later onset, primarily estrogen-receptor-positive tumors. For one extended family with eight patients with late-onset disease, one estrogen-receptor haplotype was consistently coinherited with breast cancer, yielding a +1.85 lod score for linkage at zero recombination. Simulation of this pedigree assuming independent inheritance of breast cancer and estrogen-receptor genotypes led to a lod score greater than or equal to 1.85 only once in 2,000 replicates. We suggest testing linkage of this gene to breast cancer in other families with late-onset disease.

Adult↗

Linkage of early-onset familial breast cancer to chromosome 17q21.

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

Breast Neoplasms↗