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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 73 records · Page 4Linked to original sources
PubMed2001

Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.

The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.

Adrenomedullin↗
PubMed2001

Multisite randomized controlled trials in health services research: scientific challenges and operational issues.

Although well-designed randomized controlled trials (RCT) provide the strongest evidence regarding causation, only relatively recently have they been used by health services researchers to study the organization, delivery, quality, and outcomes of care. More recent yet is the extension of multisite RCTs to health services research. Such studies offer numerous methodological advantages over single-site trials: (1) enhanced external validity; (2) greater statistical power when studying conditions with a low incidence or prevalence, small event rate in the outcome (eg, mortality), and/or large variance in the outcome (eg, health care costs); and (3) rapid recruitment to provide health care organizations and policy makers with timely results. This paper begins by outlining the advantages of multisite RCTs over single-site trials. It then discusses both scientific challenges (ie, standardizing eligibility criteria, defining and standardizing the intervention, defining usual care, standardizing the data collection protocol, blinded outcome assessment, data management and analysis, measuring health care costs) and operational issues (ie, site selection, randomization procedures, patient accrual, maintaining enthusiasm, oversight) posed by multisite RCTs in health services research. Recommendations are offered to health services researchers interested in conducting such studies.

Cost Control↗
PubMed2001

The role of academic discipline and gender in high school teachers' AIDS-related knowledge and attitudes.

Adolescents represent the fastest growing segment of HIV+ individuals in the United States. Therefore, high school teachers should be both knowledgeable of and comfortable with issues related to HIV/AIDS. This study examined high school teachers' AIDS-related knowledge and attitudes. One hundred forty-one high school teachers from nine central Massachusetts high schools participated. Participants completed the "HIV/AIDS Knowledge and Attitudes Scales for Teachers," as well as questions regarding their teaching experience and academic disciplines. Results indicated a direct relationship between teachers' knowledge of HIV/AIDS and positive or supportive attitudes toward HIV/AIDS. Significant differences were found based on academic discipline, with allied health teachers scoring significantly higher on the knowledge scale than teachers in any other discipline. Specific examples are discussed, as is the need for increased teacher training and comprehensive AIDS education.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Adrenomedullin expression and growth inhibitory effects in distinct pulmonary artery smooth muscle cell subpopulations.

The vasodilator peptide adrenomedullin is elevated in patients with pulmonary hypertension and has been implicated in the inhibition of vascular remodeling. We questioned whether adrenomedullin is released by human pulmonary artery smooth muscle cells (PASMCs) and inhibits PASMC growth and release of endothelin, a known smooth muscle cell mitogen. The majority of PASMCs isolated from proximal pulmonary arteries and all PASMCs from distal pulmonary arteries released adrenomedullin, although at differing rates (mean, 177 +/- 28 and 62 +/- 11 fmol/10(5) cells/24 h, respectively). These cells were designated ADM+. However, some proximal PASMC isolates did not release adrenomedullin, designated ADM-. Northern blot analysis confirmed adrenomedullin expression in proximal ADM+ but not ADM- isolates. ADM- and distal ADM+ PASMCs proliferated faster in serum than did proximal ADM+ cells. Adrenomedullin potently and dose-dependently (mean EC(50) = 2.2 +/- 0.5 nM) increased intracellular cyclic adenosine monophosphate (cAMP) in ADM- isolates via specific adrenomedullin receptors. In contrast, both adrenomedullin and calcitonin gene-related peptide modestly elevated cAMP in 50% of ADM+ isolates. Adrenomedullin dose-dependently inhibited platelet-derived growth factor-stimulated [3H]thymidine incorporation and endothelin release in ADM- cells but did not affect [3H]thymidine uptake in ADM+ isolates. We conclude that distinct subpopulations of human PASMCs release and respond to adrenomedullin. The heterogeneity of adrenomedullin release and the inhibition of PASMC DNA synthesis and endothelin release suggest that adrenomedullin may function as a paracrine mediator in the inhibition of pulmonary vascular remodeling.

Adrenomedullin↗
PubMed2001

Differential adrenomedullin release and endothelin receptor expression in distinct subpopulations of human airway smooth-muscle cells.

Although adrenomedullin (ADM) is implicated in the control of airway tone, regulation of ADM release from airway smooth-muscle cells (ASMCs) has not been explored. Preliminary experiments have indicated that human ASMC populations were heterogeneous in their rate of ADM release and expression of endothelin (ET)(A) and ET(B) receptors. We isolated these phenotypically distinct ASMCs from explants derived from the same airway segment. ASMCs possessing exclusively ET(A) receptors appeared smaller and proliferated faster than ET(A)/ET(B) isolates. Macroautoradiographic analysis confirmed the presence of both receptors in human bronchi. ADM release and messenger RNA expression was greater in ET(A)/ET(B) isolates compared with ET(A) isolates. No measurable ET release was detected from ASMCs. Exogenous ET-1 (1 to 100 nM) more potently stimulated the release of ADM from ET(A)/ET(B) compared with ET(A) isolates. In addition, ET-3 (1 to 100 nM) stimulated ADM release only from ET(A)/ET(B) isolates, implicating the ET(B) receptor in this response. Exogenous ET-1 potentiated platelet- derived growth factor-stimulated [3H]thymidine uptake in ET(A)/ ET(B) but not ET(A) isolates. ET-3 did not affect [3H]thymidine uptake in either cell type. Possession of ET(A)/ET(B) receptors is associated with higher rates of ADM release and slower proliferation, but a capacity for ET-1 stimulated DNA synthesis via ET(A) receptors. These results support a paracrine role for the regulation of ADM release predominantly via the ET(B) receptor in human ASMCs.

Adrenomedullin↗
PubMed2001

Oxyntomodulin inhibits food intake in the rat.

Oxyntomodulin is derived from proglucagon processing in the intestine and the central nervous system. To date, no role in the central nervous system has been demonstrated. We report here that oxyntomodulin inhibits refeeding when injected intracerebroventricularly and into the hypothalamic paraventricular nucleus of 24-h fasted rats [intracerebroventricularly and into the paraventricular nucleus, 1 h, oxyntomodulin (1 nmol), 3.1 +/- 0.5 g; saline, 6.2 +/- 0.4 g; P < 0.005]. In addition, oxyntomodulin inhibits food intake in nonfasted rats injected at the onset of the dark phase (intracerebroventricularly, 1 h: oxyntomodulin, 3 nmol, 1.1 +/- 0.19 g vs. saline, 2.3 +/- 0.2 g; P < 0.05). This effect of oxyntomodulin on feeding is of a similar time course and magnitude as that of an equimolar dose of glucagon-like peptide-1. Other proglucagon-derived products investigated [glucagon, glicentin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol), and spacer peptide-1 (intracerebroventricularly and into the paraventricular nucleus, 3 nmol)] had no effect on feeding at any time point examined. The anorectic effect of oxyntomodulin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol) was blocked when it was coadministered with the glucagon-like peptide-1 receptor antagonist, exendin-(9-39) (intracerebroventricularly, 100 nmol; into the paraventricular nucleus, 10 nmol). However, oxyntomodulin has a lower affinity for the glucagon-like peptide-1 receptor compared with glucagon-like peptide-1 (IC(50): oxyntomodulin, 8.2 nM; glucagon-like peptide-1, 0.16 nM). One explanation for this is that there might be an oxyntomodulin receptor to which exendin-(9-39) can also bind and act as an antagonist.

Animals↗
PubMed2001

Seasonal abundance of aphids (Homoptera: Aphididae) in wheat and their role as barley yellow dwarf virus vectors in the South Carolina coastal plain.

Aphid (Homoptera: Aphididae) seasonal flight activity and abundance in wheat, Triticum aestivum L., and the significance of aphid species as vectors of barley yellow dwarf virus were studied over a nine-year period in the South Carolina coastal plain. Four aphid species colonized wheat in a consistent seasonal pattern. Greenbug, Schizaphis graminum (Rondani), and rice root aphid, Rhopalosiphum rufiabdominalis (Sasaki), colonized seedlingwheat immediately after crop emergence, with apterous colonies usually peaking in December or January and then declining for the remainder of the season. These two aphid species are unlikely to cause economic loss on wheat in South Carolina, thus crop managers should not have to sample for the subterranean R. rufiabdominalis colonies. Bird cherry-oat aphid, Rhopalosiphum padi (L.), was the second most abundant species and the most economically important. Rhopalosiphum padi colonies usually remained below 10/row-meter until peaking in February or March. Barley yellow dwarf incidence and wheat yield loss were significantly correlated with R. padi peak abundance and aphid-day accumulation on the crop. Based on transmission assays, R. padi was primarily responsible for vectoring the predominant virus serotype (PAV) we found in wheat. Pest management efforts should focus on sampling for and suppressing this aphid species. December planting reduced aphid-day accumulation and barley yellow dwarf incidence, but delayed planting is not a practical management option. English grain aphid, Sitobion avenae (F.), was the last species to colonize wheat each season, and the most abundant. Sitobion avenae was responsible for late-season virus transmission and caused direct yield loss by feeding on heads and flag leaves during an outbreak year.

Animals↗
PubMed2001

Green tea polyphenol epigallocatechin inhibits DNA replication and consequently induces leukemia cell apoptosis.

Consistent with the putative role of green tea in cancer prevention, tea polyphenols have previously been shown to inhibit tumor cell proliferation by inducing G1 or G2/M cell cycle arrests, also documented is their ability to induce apoptosis (programmed cell death). However, it is unclear whether or not the cell cycle effects of polyphenols are related to their cell death-inducing ability. Here we report that the tea polyphenol (-)-epigallocatechin (EGC) inhibits DNA replication in three leukemia cancer cell lines, Jurkat T, HL-60 and K562. Among all the tested tea polyphenols, EGC was found to be the most potent in accumulation of S phase cells and inhibition of the S-G2 progression. In addition, EGC-mediated inhibition of S phase progression results in induction of apoptosis, as determined by sub-G1 cell population, breakage of endonuclear DNA, cleavage of poly(ADP-ribose) polymerase and loss of cell viability. When used in cells containing low S and high G1 and G2/M populations, EGC did not induce apoptosis. Furthermore, EGC did not inhibit M-G1 transition. Our finding that EGC inhibits S phase progression that results in leukemia cell death provides a novel and plausible molecular mechanism for how green tea may inhibit the growth of rapidly proliferating neoplastic cells.

Apoptosis↗
PubMed2001

Sucrose, sodium dodecyl sulfate, urea, and 2-mercaptoethanol affect the thermal inactivation of R-phycoerythrin.

Thermal inactivation kinetics (D- and z-values) of the algal protein, R-phycoerythrin (R-PE), were studied under different buffer conditions (pH 4.0, 7.0, and 10.0) and concentrations of sucrose, sodium dodecyl sulfate (SDS), urea, and 2-mercaptoethanol (ME). R-PE solutions were heated in capillary tubes at temperatures between 40 and 90 degrees C depending on buffer conditions. Thermal inactivation parameters for R-PE, calculated on the basis of fluorescence loss, were modified by addition of chemicals. Overall, sucrose and ME had a thermostabilizing effect, while SDS and urea decreased thermal stability of R-PE. The z-values ranged from 5.9 degrees C in 50 mM NaCl, 20 mM glycine buffer, pH 10.0, to 37.8 degrees C in 60% sucrose, 50 mM NaCl, 20 mM phosphate buffer, pH 7.0. The z-values obtained for R-PE closely matched the z-values of some target microorganisms in food processes, suggesting R-PE might be used as a time-temperature integrator to verify thermal processing adequacy.

Fluorescence↗
PubMed2001

Trichothecene and moniliformin production by Fusarium species from western Canadian wheat.

Fusarium graminearum, Fusarium culmorum, and Fusarium avenaceum, isolated from Fusarium-damaged wheat harvested in western Canada, were cultured and evaluated for mycotoxin production. Extracts of the culture media were assayed for trichothecenes by gas chromatography-mass spectrometry and for moniliformin by liquid chromatography. Deoxynivalenol (DON) was found in 28 of 42 isolates of F. graminearum and 42 of 42 isolates of F. culmorum at levels ranging from 0.5 to 25.0 microg/g. 15-AcetylDON was found in 28 of 42 isolates of F. graminearum at levels ranging from 1.0 to 7.1 microg/g. 3-AcetylDON was found in 41 of 42 isolates of F. culmorum at levels ranging from 0.8 to 13.0 microg/g. Several other trichothecenes were assayed but not detected in the culture medium. Moniliformin was present in 40 of 42 isolates of F. avenaceum at levels ranging from 1.3 to 138.1 microg/g, but was not present in any of the isolates of F. graminearum or F. culmorum.

Chromatography, Liquid↗
PubMed2001

Tannic acid potently inhibits tumor cell proteasome activity, increases p27 and Bax expression, and induces G1 arrest and apoptosis.

Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers, although the involved molecular target remains unknown. In addition, proteasome inhibitors have been shown to suppress human tumor growth in nude mice. Most recently, we have reported that ester-bond-containing tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We have hypothesized that TA, which contains multiple similar gallate moieties linked by ester bonds, should inhibit the proteasome activity. Here, we report that indeed TA potently and specifically inhibits the chymotrypsin-like activity of purified 20S proteasome (IC(50) = 0.06 microg/ml), 26S proteasome of Jurkat T-cell extracts, and 26S proteasome of living Jurkat cells. Inhibition of the proteasome by TA in Jurkat cells results in accumulation of two natural proteasome substrates, the cyclin-dependent kinase inhibitor p27(Kip1) and the proapoptotic protein Bax, followed by growth arrest in G1 and induction of apoptotic cell death. Our present study suggests that TA targets and inhibits the proteasome in tumor cells, which may contribute to the previously observed anticarcinogenic activity of TA.

Apoptosis↗
PubMed2001

Reliability of the Severin classification in the assessment of developmental dysplasia of the hip.

This study was undertaken to investigate the reliability of Severin's classification at various ages, and to determine whether the reliability is improved by careful measurement rather than subjective assessment. The radiographs taken at ages 6, 10 and 16 years of 20 randomly selected patients treated for developmental dysplasia of the hip were graded by six observers on two separate occasions using parameters measured according to Severin's criteria. In addition, four of these observers regraded the same radiographs using subjective assessment without measurements being made on two other separate occasions. Agreements between and within observers were evaluated using the weighted Cohen's kappa statistic for each age group. Intraobserver reliability was good, there being a close association between the measured and the subjectively observed ratings. This accords with the subjective nature of this classification. The interobserver reliability was found to be poor although it improved when direct measurements were made. Overall agreement between observers improves as patient age increases. It is concluded that comparisons between different observers using the Severin classification system are not reliable. However, a single investigator comparing treatment modalities in the same study allowing for individual bias in assessing deformity and subluxation would produce reliable results.

Acetabulum↗
PubMed2000

Clonally related cells are restricted to organ boundaries early in the development of the chicken gut to form compartment boundaries.

The gut organs are all derived from a simple, undifferentiated, linear gut tube. We analyzed the lineage relationships of cells derived from this gut tube in chicken embryos, determining where the progeny of a single cell are located within the gut. We find that daughter cells derived from a single progenitor can populate both the gizzard (chicken stomach) and the small intestine early in development, but that clonally related cells are restricted to a single organ by stage 12. We also find that clonally related cells can populate different mesodermal layers within the radial axis of the gut throughout all of the stages tested in these experiments. Many genes that have organ-specific expression patterns within the gut have been isolated. The onset of these restricted expression patterns correlates with the time that clonal boundaries appear to form, suggesting that these genes might be involved in the establishment of compartment boundaries, which prevent cells on one side of the boundary from intermingling with cells on the other side of the boundary.

Animals↗
PubMed2000

Investigation of the melanocyte stimulating hormones on food intake. Lack Of evidence to support a role for the melanocortin-3-receptor.

The melanocortin receptors, melanocortin-3-receptor (MC3-R) and melanocortin-4-receptor (MC4-R), are expressed in many discrete medial hypothalamic nuclei implicated in feeding regulation. The pro-opiomelanocortin product alpha-melanocyte stimulating hormone (alpha-MSH), an MC3/4-R agonist, decreases food intake following intracerebroventricular (ICV) injection in rats. MC4-R's involvement in feeding has been established although a function for the MC3-R is unclear. We investigated endogenous melanocortin ligand binding and activation at the MC3-R and MC4-R and their effects on feeding. We have shown that alpha-MSH, desacetyl-alpha-MSH and beta-MSH bound to the MC3-R and MC4-R with similar affinity and stimulated cAMP with similar potency in HEK 293 cells transfected with MC3-R and MC4-R. In contrast gamma(2)-MSH showed selectivity for the MC3-R over the MC4-R both in binding affinity and cAMP stimulation. alpha-MSH and beta-MSH injected ICV into fasted rats at doses of 1, 3 and 6 nmol resulted in a decrease in food intake, (2 h food intake: alpha-MSH 6 nmol, 1.7+/-0.3 g; beta-MSH 6 nmol, 1.5+/-0.3 g vs. saline 6.0+/-0.5 g, P<0.001). Desacetyl alpha-MSH did not reduce food intake at low doses but was significant at 25 nmol (2 h food intake: desacetyl-alpha-MSH 6.1+/-1.0 g vs. saline 9.5+/-1.4 g, P<0.05). In contrast, gamma(2)-MSH had no effect on food intake when administered ICV to fasted rats. We were unable to establish a role for the MC3-R in feeding regulation. Our evidence, however, strengthens the hypothesis that the melanocortin's effects on food intake are mediated via the MC4-R.

Animals↗
PubMed2000

The role of emergency physicians in the care of the child in school.

Emergency physicians may contribute significantly to the health of children in the school setting. Because children spend the majority of their waking hours in school, they and their adult caretakers experience medical and surgical emergencies on a regular basis. These emergencies include a wide range of problems, such as asthma, seizures, firearms violence, and mass disasters. Additionally, many children in school have limited access to primary care, which increases their risk for medical emergencies. Recent reports from the National Academy of Sciences Institute of Medicine and the Maternal and Child Health Bureau's Emergency Medical Services for Children Program have described the challenges in improving the medical care of children in both the emergency and school settings. The prevalence of school health emergencies provides an opportunity for use of the expertise of emergency physicians. Emergency physicians have an important role in ensuring the proper treatment of emergency medical problems that occur in school. They need to be integrally involved in the development and organization of systems for prevention, initial stabilization, definitive management, and responsible follow-up of medical problems and injuries.

Adolescent↗
PubMed2000

Alcohol modulates cytokine secretion and synthesis in human fetus: an in vivo and in vitro study.

It is well recognized that alcohol passes through the placenta and affects the fetal immune system. The underlying mechanism accounting for immune suppression is not clear. Cytokines are recognized as the principal mediators of a variety of immunologic and pathophysiologic events. The study was designed to examine whether alcohol use during pregnancy affects cytokine synthesis and secretion in the human fetus. Fetal (cord blood) and mother's blood were used for the study. Studies were conducted in vivo and in vitro. For the in vivo study, cytokine levels were measured in cord blood in mothers who drank moderate to heavy (chronic) amounts of alcohol during pregnancy. For the in vitro study, cord blood was obtained from mothers who were drug-free throughout pregnancy. Lymphocytes were isolated and stimulated with lipopolysaccharide (LPS; Escherichia coli, 26:B6). The capacity of lymphocytes to synthesize cytokines was examined in the presence of 20, 50, and 100 mM alcohol. Among the cytokines examined were the tumor necrosis factor (TNF alpha) and interleukins (IL-1 alpha and beta and IL-6). The selection of cytokines was based on their presumptive role in the pathophysiology of alcoholism. Cytokines were measured by using a specific immunoassay. When data obtained from moderate alcohol users were compared with those obtained from nonusers, no significant differences were observed in any of the cytokines examined (p>0.05). In chronic alcohol users, levels for all cytokines increased significantly (p<0.001) in both the fetus and the mother. Among the cytokines, IL-1beta, IL-6, and TNFalpha were the predominant cytokines affected by chronic use of alcohol during pregnancy. The order of stimulation was IL-6, IL-1 beta, TNFalpha, and IL-1 alpha in descending order. In the in vitro study, alcohol blunted LPS stimulation of cytokines, and the alcohol-induced decrease in cytokine synthesis was proportional to the level of alcohol in the media, suggesting a direct effect of alcohol on cytokine synthesis. In general, the blunting effect of alcohol on LPS stimulation was more prominent in the fetus compared with that in mother. We conclude that chronic alcohol use during pregnancy stimulated the fetal cytokine synthesis and secretion, and IL-1beta, IL-6, and TNF alpha were the predominant cytokines affected by alcohol. The in vitro data suggest a direct effect of alcohol on cytokine synthesis.

Adult↗
PubMed2000

Predicting non-elective hospital readmissions: a multi-site study. Department of Veterans Affairs Cooperative Study Group on Primary Care and Readmissions.

OBJECTIVE: To determine clinical and patient-centered factors predicting non-elective hospital readmissions. DESIGN: Secondary analysis from a randomized clinical trial. CLINICAL SETTING: Nine VA medical centers. PARTICIPANTS: Patients discharged from the medical service with diabetes mellitus, congestive heart failure, and/or chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASUREMENT: Non-elective readmission within 90 days. RESULTS: Of 1378 patients discharged, 23.3% were readmitted. After controlling for hospital and intervention status, risk of readmission was increased if the patient had more hospitalizations and emergency room visits in the prior 6 months, higher blood urea nitrogen, lower mental health function, a diagnosis of COPD, and increased satisfaction with access to emergency care assessed on the index hospitalization. CONCLUSIONS: Both clinical and patient-centered factors identifiable at discharge are related to non-elective readmission. These factors identify high-risk patients and provide guidance for future interventions. The relationship of patient satisfaction measures to readmission deserves further study.

Diabetes Mellitus↗