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Biomedical subjects

J M Hall

Publications and source records attributed to J M Hall.

At least 73 records · Page 4Linked to original sources
PubMed1995

Interaction of human adrenomedullin 13-52 with calcitonin gene-related peptide receptors in the microvasculature of the rat and hamster.

1. Adrenomedullin (ADM), a recently discovered circulating hypotensive peptide, shares limited sequence homology with the sensory nerve-derived vasodilator, calcitonin gene-related peptide (CGRP). This study compared the vasodilator effect of sequence 13-52 of human adrenomedullin (ADM13-52) with that of human alpha CGRP (CGRP), in the microvasculature of the hamster cheek pouch and rat skin in vivo. 2. Single arterioles (20-40 microns diameter) in the hamster cheek pouch were visualised by intravital microscopy and video recording, and measured by image analysis. Both ADM13-52 (1 pmol-0.4 nmol) and CGRP (0.1 pmol-1 nmol) evoked dose-related increases in the diameter of preconstricted arterioles (n = 6). ADM13-52 (ED50 14 pmol) was 20 fold less active than CGRP (ED50 0.71 pmol). The kinetics of onset and decline of vasodilator responses to both peptides were similar, with vasodilator responses to both peptides reaching a maximum at ca. 2 min, and reversing after 10-15 min (n = 5-7). The submaximal increase in blood flow evoked by ADM13-52 was significantly inhibited (P < 0.05; n = 6) by the CGRP1 receptor antagonist, CGRP8-37, at a dose (300 nmol kg-1, i.v.) that we have previously shown to inhibit significantly equivalent vasodilator responses to CGRP in this preparation. 3. In experiments measuring changes in local blood flow in rat skin by a 133xenon clearance technique, intradermal injection of both ADM13-52 (3-300 pmol) and CGRP (0.1-30 pmol) evoked dose-related increases in local blood flow. ADM13-52 (ED50 27 pmol) was 17 fold less potent than CGRP (ED501.6 pmol) (n = 6). The submaximal increase in blood flow evoked by both peptides was significantly inhibited (P<0.02; n = 5) by CGRP837 (100 nmol kg-1, i.v.).4. We conclude that ADM13-52 is a potent vasodilator in the microvasculature of the hamster and rat invivo. It mediates its vasodilator effect by arteriolar dilatation and this effect is due, at least in part, to the stimulation of CGRPI receptors.

Adrenomedullin↗
PubMed1995

Bradykinin B1 receptors in the rabbit urinary bladder: induction of responses, smooth muscle contraction, and phosphatidylinositol hydrolysis.

1. The aim of this study was to analyse the pharmacological characteristics, and second-messenger coupling-mechanisms, of bradykinin B1 receptors in an intact tissue, the rabbit urinary bladder; and to investigate the influence of inhibition of endogenous peptidases on kinin activities. 2. In preparations of rabbit mucosa-free urinary bladder, at 90 min after mounting of the preparations, bradykinin (1 nM-10 microM) evoked contractile responses. In contrast, the B1 receptor-selective agonist [des-Arg9]-BK (10 mM-10 microM) was only weakly active at this time. Contractile responses to [des-Arg9]-BK increased with time of tissue incubation in the organ bath, reaching a maximum after 3 h, when the pD2 estimates were 6.4 +/- 0.3 for bradykinin, and 6.9 +/- 0.2 for [des-Arg9]-BK. 3. Once stabilized, responses to [des-Arg9]-BK in the bladder were competitively antagonized by the B1 receptor-selective antagonists [Leu8,des-Arg9]-BK and D-Arg-[Hyp3,Thi5,D-Tic7,Oic8,des-Arg9]-BK ([des-Arg10]-Hoe140) (pKB estimates were 6.1 +/- 0.1 and 7.1 +/- 0.1, respectively; n = 17-21), but responses were unaffected by the B2 receptor-selective antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe140) (100 nM; n = 4). Contractile responses to bradykinin itself were partially, but significantly, inhibited by the B1 receptor-selective antagonist, [Leu8,des-Arg9]-BK (10 microM) (P < 0.05), or by the B2 receptor-selective antagonist Hoe140 (100 nM) (P < 0.005) alone, and were largely blocked by a combination of the two antagonists (P < 0.0001). 4. The combined presence of the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidinoethylthiopropanoicacid (mergetpa; 10 microM), the neutral endopeptidase inhibitor, phosphoramidon (1 microM),and the angiotensin-converting enzyme inhibitor, enalaprilat (1 microM) increased the potency of bradykinin17 fold (P<0.001), but that of [des-Argl-BK was unchanged (P>0.05): pD2 estimates were 7.6 +/- 0.1 and 6.8 +/- 0.1 for bradykinin and [des-Argl-BK, respectively, in treated preparations. In the presence of peptidase inhibitors, the affinities of the antagonists [Leu8,des-Arg9]-BK and [des-Arg'j-Hoel4O were unchanged as compared with those determined in the absence of peptidase inhibitors (P> 0.05).[Leu8,des-Argj-BK inhibited responses to bradykinin under these conditions (n = 4).5. In endothelium-denuded preparations of the rabbit isolated aorta, an archetypal B1 receptor preparation,contractile responses to the B1 receptor-selective agonist [des-Argl-BK (10nM- 1O0 AM) (and to bradykinin) increased progressively with time of tissue incubation; and [des-Argl-BK responses were completely antagonized by the B. receptor antagonist [Leu8,des-Arg9]-BK (pKB 6.3 +/- 0.2; n = 13).6. In experiments measuring stimulation of hydrolysis of phosphatidylinositol in rabbit urinary bladder,[des-Argl-BK (10 microM- 1 mM), and bradykinin (100 microM) significantly increased accumulation of inositol phosphates (P<0.0001). The increase in accumulation of inositol phosphates evoked by [des-Arg9]-BK(10 microM - 1 mM) was significantly inhibited by [des-Arg'j-Hoe 140 (10 microM) (P <0.01).7. We conclude that in the mucosa-free rabbit urinary bladder, [des-Argl-BK evokes contraction largely via activation of B1 receptors which have similar properties, including time-dependent induction,to B1 receptors in the rabbit isolated aorta. Bradykinin evokes contraction via stimulation of both B1 and B2 receptors, but does not require conversion by peptidases in order to activate B1 receptors. We demonstrate, for the first time, B1 receptor-coupling to phosphatidylinositol hydrolysis in an intact tissue preparation.

Amino Acid Sequence↗
PubMed1994

How lesbians recognize and respond to alcohol problems: a theoretical model of problematization.

To determine how one specific at-risk population problematizes alcohol use and responds to alcohol-related difficulties, findings from an ethnographic interview study of lesbians recovering from alcohol problems were used to develop a theoretical model of problematization. Problematization consists of two phases: recognition and response. Recognition involves problem indicators varying by type (cumulative vs immediate) and source (personal vs environmental). Movement from recognition to response is hindered by perceptual and environmental constraints. Response consists of interrelated processes of construction, interaction, action, and validation. On the basis of validation, problems are reconstructed and new problems are recognized as the cycle continues.

Adaptation, Psychological↗
PubMed1994

Marginalization: a guiding concept for valuing diversity in nursing knowledge development.

This article explicates marginalization as a guiding concept for the development of nursing knowledge that values diversity. The seven key properties of marginalization as it applies to the domain of nursing are (1) intermediacy, (2) differentiation, (3) power, (4) secrecy, (5) reflectiveness, (6) voice, and (7) liminality. Through examination of each of these properties, the relationship between marginalization and vulnerability is clarified, and by this means the relevance of marginalization for health is established. The implications for shaping future nursing research, theory, and practice related to the health of diverse populations are discussed.

Cultural Characteristics↗
PubMed1994

Quantitative analysis of CD34+ stem cells using RT-PCR on whole cells.

We have employed RT-PCR of whole cells to develop a quantitative method for estimating the number of rare cells expressing a unique mRNA in a large, mixed population of cells. We have demonstrated that RT-PCR can be done on whole cells without the need for extraction of the RNA. This allows for a great saving of time and effort, as well as allowing quantitative analysis to be based on the total number of cells analyzed in a given aliquot and the presence or absence of the specific RT-PCR product. We have employed a limiting dilution series on whole cells, with multiple aliquots at each cell concentration to achieve more statistical power in the analysis of a rare cell type. We have used a nested amplification of the CD34 mRNA to be able to detect a single cell expressing the CD34 mRNA in a larger population of non-CD34-expressing cells. We demonstrate that by using this technique, cells from blood and bone marrow containing the CD34 mRNA can be followed quantitatively during a multistep purification involving immunoadsorption followed by fluorescence-activated cell sorting. We also demonstrate that many cells that express the CD34 protein on their surface no longer contain detectable levels of CD34 mRNA, a phenomenon that appears to be developmentally regulated.

Antigens, CD↗
PubMed1994

Typical and atypical NK1 tachykinin receptor characteristics in the rabbit isolated iris sphincter.

1. A contraction of the rabbit isolated iris sphincter smooth muscle follows activation of either tachykinin NK1 or NK3 receptors. We have here characterized the pharmacological activity profiles of various tachykinin receptor agonists considered to have NK1-receptor-preferring activity in this preparation. 2. Two groups of NK1-receptor-preferring agonists could be distinguished in terms of a common pharmacological profile. The first group (Group 1) included [Glp6,L-Pro9]-SP(6-11) (septide), [Glp6]-SP (6-11), substance P methyl ester, delta-aminovaleryl-[L-Pro9, N-MeLeu10]-SP(7-11) (GR73632), and [Apa9-10]-SP. The second group (Group 2) included [Pro9]-SP, substance P, physalaemin and ranamargarin. 3. Under control conditions, the responses to Group 1 agonists were relatively fast in offset (time for reversal of maximal responses, 11.2-18.2 min), and were antagonized by NK1-receptor-selective antagonists (range of pKB estimates vs various agonists; GR82334, 7.1-8.2; (+/-)-CP-96,345, 8.9-9.5; RP67580, 7.0-7.4). Following incubation of the tissue with phenoxybenzamine (20 microM, 10 min), the affinity of GR82334, tested against the Group 1 agonists, substance P methyl ester and septide, was not significantly different (P < 0.05; n = 7-18) to that determined in untreated tissues (substance P methyl ester pKB 7.5 +/- 0.1 and 7.2 +/- 0.2, respectively; septide 7.7 +/- 0.2 and 7.9 +/- 0.2, respectively). Further, response offset times (5.0-8.5 min) were little reduced as compared to those observed in untreated tissues. 4. Under control conditions, the response to Group 2 agonists was markedly slow in offset (times for reversal of maximal responses, 51.4-70.4min), and was not attenuated significantly by the NK1-receptor-selective antagonists GR82334 (I MicroM), (+/-)-CP-96,345 (0.1 MicroM) or RP67580 (1 MicroM). In contrast,after phenoxybenzamine pretreatment, responses to Group 2 agonists reversed rapidly (times for reversal of maximal responses, 13.1-24.2 min), and were now antagonized by GR82334 (pKB estimates, 6.4-7.1).5. The responses to the NK3-receptor-selective agonist Succ-[Asp6,Me-Phe8]-SP(6-l1) (senktide) were relatively fast in offset (time for reversal of maximal response was 18.6 +/- 1.7 min) and were not inhibited by GR82334 (10 MicroM; n = 5). The contractile response resulting from co-application of the Group 1 agonist, septide together with senktide, did not exhibit prolonged response offset kinetics.6. Assuming simple competition at equilibrium, these data from the rabbit iris smooth muscle could be explained either by interaction of the various ligands with two separately-existing NK1 receptor-subtypes or -isoforms; or alternatively by a preferential interaction of the two agonist groups with different binding domains on a common NK1 receptor.

Animals↗
PubMed1994

Inhibition by SR 140333 of NK1 tachykinin receptor-evoked, nitric oxide-dependent vasodilatation in the hamster cheek pouch microvasculature in vivo.

1. This study investigated tachykinin-evoked vasodilatation in the microvasculature of the hamster cheek pouch in vivo. Arterioles and venules were observed by intravital microscopy with video recording, and vasodilatation and constriction, defined as changes in blood vessel diameter, measured by image analysis. All agents were applied topically by superfusion. None of the agents tested had a significant effect on venule diameter. 2. When arterioles were preconstricted (by ca. 50%) with endothelin-1 present in the superfusing medium, substance P (0.3-30 nM) was a potent vasodilator, being 10 fold more active than both neurokinin A and the NK1 receptor-selective agonist, substance P methyl ester. The NK2 receptor-selective agonist, [beta-Ala8]-NKA(4-10)(0.1-10 microM) was active only at high concentrations, and the NK3 receptor-selective agonist senktide (0.1-10 microM) was virtually inactive (n = 8 hamsters). Dilatation evoked by tachykinins and analogues was rapid in onset (< 0.5 min) and readily reversible. 3. At low concentrations (1-10 nM), the non-peptide tachykinin NK1 receptor antagonist SR140333 ((S)1-(2-[3(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)pi peridin-3- yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octone, chloride) had no effect on the diameter of preconstricted arterioles per se, but potently inhibited dilator responses to substance P methyl ester (apparent pKB 9.9 +/- 0.2; n = 5 hamsters, n = 10 estimates). SR140333 (10 nM) did not inhibit submaximal dilator responses evoked by human alpha calcitonin gene-related peptide (alpha CGRPh; 1.0 nM; P > 0.05; n = 5). 4 The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 microM) caused a51.3 +/- 5.4% arteriolar constriction. In the presence of L-NAME, submaximal vasodilator responses to substance P (10-I00 nM) and carbachol (0.1-1.0 microM) were significantly attenuated (n = 5 hamsters;P<0.05) as compared to responses obtained in preparations that were preconstricted to a similar extent by endothelin-l (48.0 +/- 5.6%). L-NAME (10 M) was without effect on submaximal vasodilator responses to alpha CGRPh (0.1 nM) or sodium nitroprusside (1O nM) (n = 5 hamsters; P> 0.05).5 We conclude that tachykinin-evoked arteriolar vasodilatation in the hamster cheek pouch is mediated via NK, receptor activation and depends, at least in part, on the release of nitric oxide. The NKI receptors mediating vasodilatation can be blocked by topical application of SR140333; which may therefore be useful in the investigation of the role of NK1 receptors in neurogenic inflammation in the microvasculature.

Animals↗
PubMed1994

Bradykinin B2 receptors and coupling mechanisms in the smooth muscle of the guinea-pig taenia caeci.

1. In the smooth muscle of the guinea-pig taenia caeci, bradykinin produces a relaxation followed by a contraction. In the presence of hexamethonium and guanethidine, both these phases of the response were insensitive to tetrodotoxin (100 nM), omega-conotoxin GVIA (100 nM) and ibuprofen (1 microM), suggesting that they are due to a direct action on the smooth muscle. 2. The B1 receptor-selective agonist, [des-Arg9]-BK (1-100 microM), was inactive in the taenia caeci, and the B1 receptor-selective antagonist, [Leu8,des-Arg9]-BK (1-10 microM), did not inhibit either phase of the bradykinin-induced response. The B2 receptor-selective antagonist, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe 140) (30-300 nM), inhibited both the bradykinin-induced relaxation and contraction with a similar affinity (apparent pKB estimates of 8.5 +/- 0.1 and 8.4 +/- 0.1 respectively). 3. In a depolarizing high-K(+)-solution, bradykinin produced concentration-related contractions, though of diminished magnitude; but no relaxation was observed in such media. In Krebs solution, the Ca(2+)-activated K(+)-channel blocker, apamin (10 nM), abolished relaxant responses. These observations suggest that contraction results both from membrane potential-dependent, and membrane potential-independent, mechanisms; whereas relaxant responses result entirely from membrane potential-dependent mechanisms. Contractile responses obtained in the high K(+)-solution were inhibited by D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK with an apparent pKB value of 8.4 +/- 0.1. 4. In a Ca(2+)-free, EGTA-containing medium, relatively high concentrations of bradykinin (> 100 nM) produced transient contractions, suggesting that a component of the contractile response results from release of Ca2+ from an intracellular store. This intracellular Ca2+ store could be refilled in the presence of extracellular Ca2+. The B, receptor antagonist, [Leu8,des-Argj-BK (10 micro M), did not inhibit this bradykinin-induced contraction, whereas the B2 receptor antagonist, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK(100 nM) markedly attenuated it (P<0.001; n = 6).5. Bradykinin (10 nM- 100 micro M) significantly elevated tissue levels of total [3H]-inositol phosphates in the presence of Li?, after incubation with myo-[3H]-inositol. The B, receptor-selective agonist, [des-Argl-BK(100IM) did not stimulate [3H]-inositol phosphate formation, and the B, receptor-selective antagonist,[Leu8,des-Argl-BK, did not inhibit the formation of [3H]-inositol phosphates in response to a submaximal concentration of bradykinin (1I0 1M; P> 0.05). Two B2 receptor antagonists, D-Arg-[Hyp3,DPhe7]-BK and D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK, inhibited bradykinin-induced accumulation of total[3H]-inositol phosphates with apparent pKB estimates of 5.4 +/0 0.3 and 8.4 +/- 0.1, respectively.6. These data suggest that in the guinea-pig taenia caeci, the five aspects of the action of bradykinin studied (the relaxant and the contractile elements of the biphasic mechanical response, the contractile response in a depolarizing high-K' solution medium and zero-Ca2+ media, and stimulation of phosphatidylinositol turnover), all result from activation of B2 receptors. A possible causal relationship is suggested between these B2 receptor-mediated membrane potential-dependent, and -independent events,and their roles in excitation contraction coupling.

Amino Acid Sequence↗
PubMed1994

Scholarly caring in doctoral nursing education: promoting diversity and collaborative mentorship.

One of the most significant, yet not fully developed goals of doctoral education is the graduation of scholars who can make a major contribution to the discipline of nursing. There have been many discourses and debates about the essential criteria for quality in doctoral programs that create and promote scholarliness. Scholarliness in nursing includes critical thinking, a connection to practice, a commitment to the discipline's mission, substantive mastery areas, philosophical analyses, rigorous investigations, and a social awareness of the relationship between knowledge development and impact on society. Promoting scholarship necessitates the development of a culture of scholarly caring. Scholarly caring can be developed through promotion of diversity and through collaborative mentorship. Features of collaborative mentorship are negotiated relations, mutual interactions, facilitative strategies, and empowerment. To develop these properties of a scholarly doctoral program, attention must be paid to actions that compromise scholarly quality of programs such as the lack of resources and lowered expectations of students.

Cooperative Behavior↗
PubMed1994

The experiences of lesbians in Alcoholics Anonymous.

A feminist ethnographic study of lesbians' experiences in recovery from alcohol problems was done to understand from their perspectives how they identified alcohol use as problematic, sought help, experienced health care interactions and participation in Alcoholics Anonymous (AA), and maintained recovery. Through community-based purposive sampling in San Francisco, 35 lesbians recovering from alcohol problems participated in semistructured ethnographic interviews of 2 hours duration, which were subsequently interpreted using ethnographic coding, narrative analysis, and matrix analysis. A major finding was that participation in AA was fraught with tension in three areas. Each tension was defined by two poles of experience that appear to be in conflict. They were assimilation versus differentiation, authority versus autonomy, and false consciousness versus politicization. These tensions are elaborated and supported by examples from the women's interviews. Nursing implications regarding the role of AA in recovery for marginalized women are discussed.

Adult↗
PubMed1994

An electrochemical method for detection of nucleic acid hybridisation.

Preliminary investigations on the detection of nucleic acid hybridisation by direct electrochemical techniques are described. Initial experiments were performed with calf thymus DNA, while as a model system, plasmid DNA (pEMBL) which can be prepared in single stranded forms from each of two original double stranded plasmids (+19 and -19) was used. Electrochemical analyses have been performed using mercury pool, glassy carbon and screen printed carbon working electrodes.

Animals↗
PubMed1994

Vasodilator responses to calcitonin gene-related peptide (CGRP) and amylin in the rat isolated perfused kidney are mediated via CGRP1 receptors.

This study was designed to characterize the calcitonin gene-related peptide (CGRP) receptors mediating vasodilation in the rat isolated perfused kidney and to address the question as to whether amylin, a 37 amino acid peptide having about 50% overall sequence homology with CGRP, interacts with common CGRP receptors or acts via distinct amylin receptors. Human alpha-CGRP (h alpha CGRP) and human beta-CGRP, rat alpha-CGRP and rat amylin amide produced dose-related vasodilation of the perfused renal vascular bed with pD2 estimates of rat alpha-CGRP (10.8 +/- 0.2), h alpha CGRP (10.5 +/- 0.2), human beta-CGRP (10.5 +/- 0.2) and rat amylin amide (9.4 +/- 0.3). In contrast, the CGRP2 receptor-selective agonist [acetamidomethyl-cysteine2.7]h alpha CGRP (0.1 mumol) was inactive. The CGRP1-receptor antagonist, h alpha CGRP8-37 reversibly antagonized the vasodilator response induced by h alpha CGRP with an apparent pK1 of 8.03 +/- 0.21. The analog h alpha CGRP8-37 (1 microM) also reversibly inhibited submaximal responses to rat amylin amide. In contrast, rat amylin8-37 (1 microM) had no significant inhibitory effect either on rat amylin amide- or on h alpha CGRP-induced vasodilation (P > .05), showing that rat amylin8-37 does not have affinity for the CGRP1 receptor in this preparation. These data suggest that the predominant CGRP receptors in the rat renal vascular bed are of the CGRP1 type, and that the vasodilation induced by rat amylin amide is due to CGRP1 receptor activation.

Amyloid↗
PubMed1993

Differentiation of periapical granulomas and radicular cysts by digital radiometric analysis.

It is generally accepted that two of the most commonly seen radiolucencies, the periapical granuloma and the radicular cyst, cannot be differentiated radiographically. The purpose of this investigation was to determine the feasibility of identifying radiometric differences in these two pathologic conditions by analyzing the patterns of the gray-level distributions of digitized radiographic images. Radiographs used in the study had been sent by practitioners to the School of Dentistry with tissue specimens. Radiographs of lesions identified as periapical granulomas and radicular cysts in the mandibular posterior quadrant were included in the study. The radiographs were digitized and regions of interest were drawn to include the lesions. Frequency distributions (histogram) with 256 gray-scale intervals and a cumulative percent histogram were computed. The typical histograms of the dental granulomas had narrower ranges and lower gray-scale values than did cysts. The results of this study indicate that it is feasible to radiometrically differentiate between lesions that are visually indistinguishable on radiographs.

Diagnosis, Differential↗