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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 289 records · Page 16Linked to original sources

Identification of a subpopulation of human renal microvascular endothelial cells with capacity to form capillary-like cord and tube structures.

Endothelial specialization is a prominent feature within distinct capillary beds of organs such as mammalian kidney, yet immunological markers for functionally distinct subpopulations of cultured endothelial cells from tissue sources such as kidney have not been available. We developed a simple and reproducible isolation and culture procedure to recover human renal microvascular endothelial cells (HRMEC) from the cortex of unused donor kidneys. This procedure yields highly purified preparations of cells that display endothelial markers that include Factor VIII antigen, acetyl-LDL receptors, and determinants that bind Ulex europaeus lectin. HRMEC assemble into capillary-like cord and tube structures when plated on the surface of basement membrane-like matrix (BMM) in media containing phorbol myristate acetate. To further define subpopulations of HRMEC, we generated a panel of monoclonal antibodies and screened for those recognizing cell surface determinants. One monoclonal antibody recovery from this screen recognized a cell surface protein expressed on a subpopulation of HRMEC that we have designated PEC-1 (pioneer endothelial cell antigen-1). Cells expressing PEC-1 extended long, interconnecting filopodial processes in response to phorbol myristate acetate and assembled into capillary-like structures when plated on BMM. Anti-PEC-1 immunoprecipitated proteins of 25 and 27 kDa. Magnetic bead separation of PEC-1 (+) cells selected cells that assemble into capillary-like cord and tube structures. The remaining PEC-1 (-) HRMEC population formed matrix adherent patches. In the kidney, the PEC-1 determinant is expressed on a small subpopulation of microvascular glomerular cells and is prominently expressed on the apical membrane of proximal tubule cells. The PEC-1 determinant discriminates among subpopulations of HRMEC, identifying a subpopulation that contributes to assembly of capillary-like structures.

Adult↗

Word-frequency effects on short-term memory tasks: evidence for a redintegration process in immediate serial recall.

Four experiments investigated the mechanisms responsible for the advantage enjoyed by high-frequency words in short-term memory tasks. Experiment 1 demonstrated effects of word frequency on memory span that were independent of differences in speech rate. Experiments 2 and 3 showed that word frequency has an increasing effect on serial recall across serial positions, but Experiment 4 showed that this effect was abolished for backward recall. A model that includes a redintegration process that operates to "clean up" decayed short-term memory traces is proposed, and the multinomial processing tree model described by R. Schweickert (1993) is used to provide a quantitative fit to data from Experiments 2, 3, and 4.

Adult↗

Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients.

The concentration of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was determined in the serum of 90 untreated and 42 treated metastatic cancer patients, including patients with colorectal, breast, ovarian and renal carcinomas, with an enzyme-linked immunosorbent assay (ELISA). Levels higher than the 95th percentile of the concentrations of a control group, i.e. 7.5 pg ml(-1) for bFGF and 500 pg ml(-1) for VEGF, were identified as 'elevated'. One measurement during follow-up was included into the analysis per patient. For 19 treated patients, consecutive serum samples were analysed. Fifty-seven per cent of all untreated patients had elevated serum levels of one or both angiogenic factors. The fraction of patients with elevated serum levels of bFGF and/or VEGF was similar in the different tumour types. Agreement of bFGF levels and VEGF levels, classified in relation to their respective cut-off values, was present in 67% of all patients. Fifty-eight per cent of the patients with progressive disease during treatment compared with 15% of the patients showing response to treatment (chi-squared test P < 0.05) had elevated bFGF and/or VEGF serum levels. When consecutive serum samples were analysed, two-thirds of the patients showing progressive disease had increasing serum levels of the angiogenic factors compared with less than one-tenth of the patients showing response (chi-squared test P < 0.05). The lack of association between the serum bFGF and VEGF levels and the tumour type may suggest an aspecific host reaction responsible for solid tumour-related angiogenesis. The main determinants of the serum bFGF and VEGF concentration are the progression kinetics of the metastatic carcinomas.

Adenocarcinoma↗

Ds elements on all five Arabidopsis chromosomes and assessment of their utility for transposon tagging.

The maize transposons Activator (Ac) and Dissociation (Ds) tend to transpose to sites close to their original position and can be efficiently used to transposon-tag genetically linked genes. To facilitate this approach, we describe the locations of seven T-DNAs carrying Ds elements, including at least one on each of the five chromosomes. For five of these T-DNAs, we have confirmed that the Ds element transposes preferentially to genetically linked sites. A large-scale transposon-tagging experiment was performed by activating Ds from eight chromosomal locations that included at least one on each of the five chromosomes. These experiments produced a total of 1132 F3 families that were predicted to carry around 870 independent Ds insertions. In these populations, 33 independently isolated mutants that were visibly different from wild-type were identified. Twenty-nine of these mutants were studied genetically, and 14 were not tagged with Ds because the element could be separated from the mutation by recombination. The remaining 15 mutations were possibly tagged because the transposon and the mutation were not separated by recombination. These experiments provide tools for transposon-tagging on each chromosome, and indicate that approximately 50% of identified mutations are likely to be tagged, thereby enabling cloning of the affected genes.

Arabidopsis↗

Three determinants in ezrin are responsible for cell extension activity.

The ERM proteins--ezrin, radixin, and moesin--are key players in membrane-cytoskeleton interactions. In insect cells infected with recombinant baculoviruses, amino acids 1-115 of ezrin were shown to inhibit an actin- and tubulin-dependent cell-extension activity located in ezrin C-terminal domain (ezrin310-586), whereas full-length ezrin1-586 did not induce any morphological change. To refine the mapping of functional domains of ezrin, 30 additional constructs were overexpressed in Sf9 cells, and the resulting effect of each was qualitatively and semiquantitatively compared. The removal of amino acids 13-30 was sufficient to release a cell-extension phenotype. This effect was abrogated if the 21 distal-most C-terminal amino acids were subsequently deleted (ezrin31-565), confirming the existence of a head-to-tail regulation in the whole molecule. Surprisingly, the deletion in full-length ezrin of the same 21 amino acids provided strong cell-extension competence to ezrin1-565, and this property was recovered in N-terminal constructs as short as ezrin1-310. Within ezrin1-310, amino acid sequences 13-30 and 281-310 were important determinants and acted in cooperation to induce cytoskeleton mobilization. In addition, these same residues are part of a new actin-binding site characterized in vitro in ezrin N-terminal domain.

Animals↗

Adherence to antihypertensive medications across the life span.

Although treatment for hypertension is readily available, poor control of hypertension is a major health problem frequently manifested in late life. Researchers believe that one of the major causes of uncontrolled hypertension is failure to take medication as directed. In this preliminary study, the medication-taking behaviors of 48 adults diagnosed with hypertension, ranging in age from 35 to 87, were recorded for 2 months with credit card-sized bar-code scanners. The social-cognitive model (Park, 1992) for understanding medication adherence, which proposes that medication adherence is governed by both beliefs and cognitive factors, was used as a basis for this research. Therefore, measures of health behaviors, attitudes about health and medication taking, and cognitive function were recorded, as well as blood pressure readings. The main findings were that (a) the oldest-old and groups of middle-aged adults were the most nonadherent, whereas the young-old were more likely to adhere than the other age groups; (b) high blood pressure readings predicted adherence to antihypertensive medications; and (c) medication beliefs influenced adherence in some situations.

Adult↗

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors↗

Handedness dependency in recall from everyday memory.

A number of previous studies have demonstrated systematic misremembering of the direction in which the Queen's head faces on British coins. Two experiments were carried out to investigate whether this phenomenon is affected by a person's handedness. In both experiments, right-handed and left-handed participants were found to differ significantly in their verbal responses, with recall performance significantly worse than chance for right-handed but not for left-handed participants. Experiment 2 also examined degrees of handedness, and found significant variation in recall across the handedness range. Performance in this everyday-memory paradigm appears to be determined by both handedness and schema factors. It is proposed that although in this task the response was verbal one, relevant motor imagery may nevertheless have been activated and led to the highly unusual observation of an effect of handedness upon cognitive performance.

Adult↗

Effects of RP 55778, a tumor necrosis factor alpha synthesis inhibitor, on antiviral activity of dideoxynucleosides.

Tumor necrosis factor alpha (TNF-alpha) is overexpressed during human immunodeficiency virus (HIV) infection. RP 55778, a TNF-alpha synthesis inhibitor, decreases HIV replication in monocytes/macrophages. Therapeutic use of RP 55778 in vivo, like that of other biological response modifiers, would theoretically require association with dideoxynucleosides. We have evaluated here the combinatory effects of zidovudine (AZT) or dideoxyinosine (ddI) and RP 55778. This TNF-alpha inhibitor antagonizes the antiviral effects of both dideoxynucleosides, especially AZT. The more favorable anti-HIV activity of ddI in resting cells may explain these unequal degrees of antagonism.

Anti-HIV Agents↗

Back pain among echocardiographers.

OBJECTIVE: By having to adopt unnatural postures, echocardiographers place themselves at risk of back injury. The present study sought to document the incidence and severity of back pain among echocardiographers, and to identify personal, lifestyle and occupational characteristics that may predict risk of back pain. DESIGN: A questionnaire concerning occupational, personal, and lifestyle characteristics, as well as the extent and severity of back pain was completed and returned by 183 echocardiographers. RESULTS: The standard echocardiography examination position of "machine on the left, patient on the right, and transducer held in the right hand" (used by 66% of respondents) greatly increased the risk of back pain (odds ratio (OR) = 4.9; 95% confidence interval (95% CI) = 1.49-16.4). Echocardiographers with more than 11 years experience in the field were also at risk of back pain (OR) = 3.4; 95% CI = 0.97-11.6). The intensity of back pain was strongly associated with the amount of time spent on echocardiography examinations (P = 0.035), limitation of lifestyle (P < or = 0.001), and interference with work (P < or = 0.001). There was a significantly higher relative risk of back pain for the respondents whose job involved frequent or occasional lifting compared with nonlifters (P = 0.01; OR = 4.8, 95% CI = 1.25-18.7). At least some limitation of lifestyle from back pain was reported by 56% of the respondents. CONCLUSIONS: There is a high incidence of back pain among echocardiographers, and specific tasks and activities increase the risk of back pain. Further research should focus on preventative measures and optimum work station designs that may serve as a guide to echocardiography departments.

Back Pain↗

Ca2+ permeation through Na+ channels in guinea pig ventricular myocytes.

This study was undertaken to test the hypothesis that, in the absence of extracellular Na+, Ca2+ can permeate tetrodotoxin (TTX)-sensitive Na+ channels in Cs(+)-loaded whole cell voltage-clamped guinea pig ventricular myocytes (22-24 degrees C). With 10 mM extracellular Ca2+, 50-ms step depolarizations (-50 to +25 mV) from holding potentials of -100 or -80 mV elicited fast and slow types of inward current: 1) a small (< 400 pA) dihydropyridine-insensitive inward current that exhibited similar voltage dependence to that of Na+ channels, with an activation threshold and peak near -45 mV and -30 mV, respectively; and 2) a larger and slower L-type Ca2+ current that activated and peaked at more positive potentials. Extracellular replacement of Ca2+ by Mg2+ abolished both currents. The lack of sensitivity of the low-threshold Ca(2+)-current amplitude to 50 or 200 microM Ni2+ suggests that this current is not produced by T-type Ca2+ current. In contrast, TTX dose dependently inhibited the low-threshold Ca2+ current, with a half-maximal inhibition concentration of 2.4 microM. Veratridine (10-50 microM), a plant alkaloid that alters the gating and permeability properties of Na+ current, induced an outward shift of time-dependent current during steps to -25 mV and typical slowly decaying inward tail currents after repolarization to -80 mV. Cell exposure to 10 and 50 microM extracellular Na+ inhibited the inward current by 21.2 +/- 3.9% (n = 23) and 14.0 +/- 3.0% (n = 14), respectively, whereas 1 microM Na+ (n = 14) was without effect. The application of 200 microM Na+ produced a small enhancement of the current (+6.2 +/- 4.1%; n = 14) which was just at the limit of significance. Our data support the notion that Ca2+ can permeate cardiac Na+ channels in the absence of an agonist and external Na+.

Animals↗

Expression of the gastric H/K-ATPase alpha-subunit in the thymus may explain the dominant role of the beta-subunit in the pathogenesis of autoimmune gastritis.

The two subunits of the gastric H/K ATPase, namely the catalytic alpha-subunit and the glycoprotein beta-subunit, are the major targets of parietal cell autoantibodies associated with human and murine autoimmune gastritis. The murine disease induced by neonatal thymectomy is T cell-mediated. We have previously shown that transgenic expression of the H/K ATPase beta-subunit gene in the thymus prevented the development of autoimmune gastritis induced by thymectomy. However, little is known of the contribution of the H/K ATPase alpha-subunit in disease development. Here, we show that (1) in contrast to the gastric H/K ATPase beta-subunit, the alpha-subunit gene is expressed in normal BALB/c thymus. (2) transgenic expression of the gastric H/K ATPase alpha-subunit gene in the thymus failed to prevent the development of autoimmune gastritis and (3) normal BALB/c and transgenic mice expressing the alpha-subunit in the thymus develop autoimmune gastritis following immunisation with purified murine gastric H/K ATPase, whereas transgenic mice expressing the beta-subunit in the thymus do not. We propose that the expression of the H/K ATPase alpha-subunit in the normal thymus may account for the predominant role of the beta-subunit in the development of autoimmune gastritis induced either by thymectomy or by immunisation with the ATPase.

Animals↗

The 21st-century college student: implications for athletic training education programs.

OBJECTIVE: With the onset of the 21 st century and increasing student diversity, institutions of higher education must become more attuned to the challenges, concerns, and needs of students entering the professions of athletic training and sports medicine. This review discusses the characteristics of the 21st-century college student. DATA SOURCES: The sources for this information were courses of study in the authors' doctoral programs from 1980 to 1994. DATA SYNTHESIS: In the 21 st century, students of increasingly diverse ages, races, cultures, ethnicities, and classes will enter the professions of athletic training and sports medicine. Institutions of higher education that recognize the needs of their nontraditional students will be better able to serve these students. CONCLUSIONS/RECOMMENDATIONS: To effectively serve the 21st-century student, institutions of higher education must provide multicultural training, flexible schedules, accelerated programs, and learning experiences that are both practical and tangible.

Journal Article↗

Enhanced expression of the Kin17 protein immediately after low doses of ionizing radiation.

Kin17 is a mammalian nuclear protein sharing a slight sequence homology with the bacterial RecA protein. Kin17 has a zinc-finger motif and binds efficiently to curved DNA, a genomic topology associated with illegitimate recombination junctions. We investigated the relationship between the level of Kin17 protein and genomic alteration due to either impaired wild-type p53 functions or exposure to gamma rays. We used BP cells, a rodent epithelial cell system. The cell lines used were syngeneic and harbored wild-type or mutant p53 alleles and exhibited different sensitivities to gamma irradiation. In radioresistant cells (wild-type p53 genotype), the level of Kin17 protein peaked 30 min after a low dose of radiation (2 Gy), whereas maximum accumulation of p53 protein was observed 3 h postirradiation. Radiosensitive cells carrying the same mutation in both alleles of the p53 gene showed elevated basal levels of both Kin17 and p53 proteins and failed to accumulate Kin17 and p53 proteins after exposure to ionizing radiation. These cells exhibited enhanced cell death by apoptosis after gamma irradiation. Our results indicate that Kin17 protein accumulated immediately after DNA damage in cells carrying a wild-type p53 genotype, and that levels of constitutive Kin17 protein increased in highly proliferating tumorigenic cells when wild-type p53 functions were abrogated.

Animals↗