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Biomedical subjects

T W Smith

Publications and source records attributed to T W Smith.

At least 109 records · Page 6Linked to original sources
PubMed1996

Interpersonal control and cardiovascular reactivity: goals, behavioral expression, and the moderating effects of sex.

Cardiovascular responses to stressful stimuli have been implicated in the development of cardiovascular disease. However, the effects of social stressors on short-term changes in blood pressure and heart rate (i.e., cardiovascular reactivity [CVR]) are not well understood. The independent effects of an incentive to exert interpersonal influence and the expression of socially controlling behavior on CVR were examined in 96 undergraduates. For men, both the incentive to exert influence and the enactment of a controlling interpersonal style produced larger increases in systolic blood pressure. By contrast, although the incentive to be influential increased women's CVR, the enactment of a cooperative role produced the largest increases in blood pressure among women. The effects of social dominance on CVR, sex differences in CVR, and interpersonal approaches to the study of these psychophysiological mechanisms are discussed.

Blood Pressure↗
PubMed1996

A meta-analytic review of research on hostility and physical health.

A new meta-analysis of research on hostility and physical health was conducted that includes 15 studies used in previous meta-analytic reviews and 30 new independent studies. Overall, the results suggest that hostility is an independent risk factor for coronary heart disease (CHD). For structured interview indicators of potential for hostility, the weighted mean r was .18. After controlling for other risk factors for CHD, the widely used Cook-Medley Hostility Scale and other cognitive-experiential measures were most predictive of all-cause mortality (weighted mean r = .16) and, to a lesser extent, CHD (weighted mean r = .08). Similar to other areas of research, the increased use of high-risk studies in recent years produced an increase in null findings.

Anger↗
PubMed1996

Borrelia burgdorferi-infected Ixodes scapularis (Acari: Ixodidae) and Peromyscus leucopus in northeastern Wisconsin.

Populations of the blacklegged tick, Ixodes scapularis Say, are established in western and central Wisconsin in the upper midwestern United States, but appear to be expanding geographically there. Here, we report a previously unknown population in northeastern Wisconsin. Questing I. scapularis nymphs and adults were collected by flagging vegetation from a riverine site in Marinette County, Wisconsin, in spring of 1993 and 1994. Dissection and culture of tick guts in modified Barbour-Stoenner-Kelley II medium showed that some of the ticks were infected with Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwald & Brenner, causative agent of Lyme disease. Fifteen of 30 white-footed mice, Peromyscus leucopus (Rafinesque), live-trapped at the site on 23-24 August 1994 were infested with immature I. scapularis, and ear-punch biopsies yielded B. burgdorferi cultures from 2 of the mice. However, none of 50 white-tailed deer, Odocoileus virginianus (Zimmermann), shot by hunters in Marinette County in November 1994 had I. scapularis on them, probably because no deer were shot at the same site where the tick population is located. These findings document existence of an established population of I. scapularis and a focus of Lyme disease in northeastern Wisconsin.

Animals↗
PubMed1996

Regulation of melanoma cell adhesion stabilization to fibronectin.

Tumour cell arrest and the formation of stable adhesive interactions between tumour cells and endothelial cells or underlying matrix in the microvasculature are crucial steps in the metastatic process. We have developed a sensitive hydrodynamic adhesion assay to investigate the regulation of melanoma cell adhesion stabilization to the extracellular matrix protein fibronectin. Modulators of human MeWo melanoma Ca2+ concentration and stores, including ionomycin, thapsigargin, dantrolene and caffeine, inhibited cell adhesion stabilization to fibronectin; however, removal of Ca2+ from the extracellular medium did not affect stabilization. The calmodulin inhibitor W-7 and the protein kinase C inhibitor chelerythrine also blocked MeWo adhesion stabilization to fibronectin, as did the tyrosine kinase inhibitor genistein and the cytoskeletal inhibitor cytochalasin D. Manipulation of MeWo cell intracellular CAMP levels had no effect of adhesion stabilization to fibronectin, nor did treatment of cells with phorbol ester, pertussis toxin or cholera toxin. Drug treatments that inhibited adhesion stabilization also had significant effects on the actin cytoskeleton organization of the melanoma cells. This study suggests a role for calcium, calmodulin, protein kinase C and tyrosine kinases in the intracellular regulation of MeWo adhesive stabilization.

Actin Cytoskeleton↗
PubMed1996

Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation.

Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to beta-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min) were performed before and after the intracoronary administration of the specific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose-dependent increase in peak first derivative of pressure (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%, respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/- 17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo.

Adrenergic beta-Agonists↗
PubMed1996

Frequency-dependent activation of a constitutive nitric oxide synthase and regulation of contractile function in adult rat ventricular myocytes.

Cardiac myocytes have recently been shown to express a constitutive Ca(2+)-sensitive isoform of NO synthase (NOS3), although the mechanism(s) responsible for activation of NOS3 and its physiological function remain to be determined. Since the activity of NOS3 is known to be regulated in part by the intracellular Ca2+ activity ([Ca2+]i) in endothelial cells, we determined whether increasing myocyte [Ca2+]i by uniform electric field pacing was accompanied by an increase in NOS3 activity, detected as nitrite accumulation in the medium. A higher [Ca2+]i with increasing pacing frequencies was shown to be accompanied by a time-dependent accumulation of nitrite in medium that bathed adult rat ventricular myocytes stimulated at 3 Hz. Nitrite release by paced cells was significantly attenuated by treatment with either the NO synthase inhibitor nitro-L-arginine (L-NA, 1 mmol/L) or the intracellular Ca2+ chelator BAPTA-AM (20 mumol/L). Paced myocytes also exhibited a frequency- and time-dependent increase in intracellular cGMP content that could be inhibited significantly by either L-NA or the soluble guanylate cyclase inhibitor LY83583 (5 mumol/L). To determine whether the increase in NOS3 activity with pacing affected contractile function, myocytes were sequentially paced at frequencies from 0.5 to 3 Hz. Methylene blue, L-NA, and LY83583 all increased the amplitude of shortening of myocytes paced at 3 Hz. Furthermore, a significantly greater positive inotropic response to high extracellular Ca2+ (3 mmol/L) was demonstrated by myocytes pretreated with L-NA compared with control cells. These data indicate that myocyte NOS3 activity is regulated in part by [Ca2+]i, whether induced by changes in pacing frequency or [Ca2+]o, and depresses myocyte contractile responsiveness to higher stimulation frequencies.

Animals↗
PubMed1996

Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells.

We examined the role of endogenous NO in the autonomic regulation of atrioventricular (AV) nodal function by studying spontaneous action potentials (SAPs) and L-type Ca2+ current (ICa-L) in isolated single AV nodal cells from adult rabbit hearts. Both the perforated and the membrane-ruptured patch-clamp techniques in the whole-cell configuration were used under conditions known to alter NO production. Three NO donors, 3-morpholinosydnonimine (SIN-1, 0.1 mmol/L), S-nitroso-acetylcysteine (0.1 mmol/L), and sodium nitroprusside (0.1 mmol/L), suppressed the beta-adrenergic agonist isoproterenol (ISO, 1 mumol/L)-stimulated increase in ICa-L. SIN-1 also decreased the frequency and amplitude of SAPs. In cells in which ICa-L had been previously attenuated by the muscarinic agonist carbamylcholine (CCh, 1 mumol/L), SIN-1 had no additive effect. CCh activated an acetylcholine-sensitive outward K+ current (IK(ACh)) in AV nodal cells, in addition to the ICa-L inhibition. Intracellular dialysis with the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA, 0.5 mmol/L) blocked CCh-induced, but not SIN-1-induced, ICa.L attenuation. However, intracellular dialysis with methylene blue (20 mumol/L), which inhibits NO-mediated activation of guanylyl cyclase and cGMP production, blocked the effects of both CCh and SIN-1 on ICa-L. In these cells, neither L-NMMA nor methylene blue affected the CCh-activated IK(ACh). Direct application of cGMP (10 mumol/L) via internal dialysis significantly inhibited ISO-stimulated ICa-L. In AV nodal cells internally perfused with either a nonhydrolyzable cAMP analogue, 8-Br-cAMP (0.5 mmol/L), or a high concentration of cAMP (0.5 mmol/L), CCh did not inhibit, ICa-L but still activated IK(ACh). CCh-induced ICa-L attenuation could be abolished or quickly reversed by the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (20 mumol/L). However, CCh still significantly suppressed ISO-stimulated ICa-L after the cGMP-inhibited PDE isozyme (PDE3) had been selectively inhibited by milrinone (5 mumol/L). Immunohistochemical staining identified the presence of the endothelial constitutive NO synthase (ecNOS or NOS3) in both single AV nodal cells in vitro and in cryostat sections of AV nodal tissue in situ. These results demonstrate that endogenous NO is involved in the muscarinic cholinergic attenuation of ICa-L in AV nodal cell; the mechanism likely involves the cGMP-stimulated PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Familial and sporadic Alzheimer's disease: neuropathology cannot exclude a final common pathway.

Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue. We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid percursor protein gene), and 11 sporadic AD (SAD) patients. There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group. However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology. These differences may reflect differences in age at onset rather than different etiopathologic mechanisms. The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD.

Age of Onset↗
PubMed1996

Cognitive dysfunction as the major presenting feature of Becker's muscular dystrophy.

We report four patients, currently aged 15, 17, 19, and 42 years, with X-linked dystrophinopathy who presented with mental retardation (IQ range, 60-68) and psychiatric disturbance in the absence of muscle weakness. All patients had elevated serum creatine kinase and dystrophic changes on muscle biopsy. There were alterations in the size and abundance of dystrophin on immunohistochemistry and immunoblotting in all cases, consistent with a molecular diagnosis of Becker's muscular dystrophy. Two patients had deletions of the dystrophin gene on DNA analysis. These findings suggest that Becker's muscular dystrophy may be associated with a predominantly neuropsychiatric presentation and that dystrophinopathy should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males. Serum creatine kinase may provide an adequate screening test in this clinical situation.

Adolescent↗
PubMed1996

Meningeal gliomatosis presenting as multiple cerebral infarcts: a case report.

A 70-year-old man presented to the hospital with a history of progressive cognitive decline, and shortly after admission he developed sudden neurologic deterioration leading to coma. CT revealed multiple contrast-enhancing lesions within the cerebral hemispheres and midbrain tectum. Autopsy revealed a left occipital glioblastoma associated with widespread meningeal dissemination of tumor, occlusive vasculopathy, and multifocal infarcts.

Aged↗
PubMed1996

Cellular interactions among marrow stromal and normal/neoplastic pre-B- and B-lymphoblastic cells.

The direct interaction between B-cells, both normal and neoplastic, and marrow stromal cells (MSC) or MSC-secreted extracellular matrix proteins is believed to play a decisive role in lymphopoiesis as well as in the sustained proliferation and homing of lymphoid malignancies. Although information has been accruing on possible obligatory cell-cell and cell-extracellular matrix adhesion molecules, our current state of knowledge regarding B-cell interaction with the marrow microenvironment is rather limited. We discuss in this review what is currently known regarding adhesion molecules involved in the apposition between B-cells and MSC. In addition, we describe how the cellular interactions are modulated by cytokines present in the marrow microenvironment. Further, we present possible signal transduction pathways activated by B-cell/MSC apposition and attempt to integrate in vitro data with in vivo observations. We close this review by providing implications for novel clinical and therapeutic applications based on the current knowledge of B-cell/MSC adhesion mechanisms and signaling pathways.

B-Lymphocytes↗
PubMed1996

Changes in gonadal weights, serum lipids, and glucose during maturation in the juvenile northern bobwhite quail (Colinus virginianus).

Changes in serum lipids, serum glucose, and gonadal development during maturation of Colinus virginianus were determined in two trials. In Trial 1, sex, BW, and serum concentrations of total cholesterol, high, low, and very low density lipoprotein cholesterol, triglycerides, and glucose were determined every 2 d from 2 to 14 d and weekly from 21 to 49 d. Relative ovary or testis weights between 14 and 49 d were determined weekly. Body weight increased and all measured serum constituents changed in males and females between 2 and 49 d; however, relative testis weight decreased between 14 and 49 d. In Trial 2, sex, BW, cholesterol, and relative ovary and testis weights were determined in birds at 56 and 63 d of age. The distinctness of external sexual phenotype and its relationship to BW, cholesterol, and relative gonadal weight were also determined at 56 and 63 d. Body weight increased and serum cholesterol decreased in both sexes between 56 and 63 d, but had no association with the distinctness of external sexual phenotype. It was concluded that the development of external sexual identity in male and female Northern Bobwhite quail prior to sexual maturity was not related to changes in BW, gonad weight, serum lipids, or serum glucose before 63 d of age.

Aging↗
PubMed1996

Cytokines and cardiac hypertrophy: roles of angiotensin II and basic fibroblast growth factor.

1. While the haemodynamic influences that cause cardiac hypertrophy are well known, the cellular and molecular mechanisms by which a mechanical stimulus is translated into a growth response by cardiac muscle have remained uncertain. 2. Current evidence suggests that a number of trophic factors may be released by cellular constituents of the heart, acting in an autocrine or paracrine manner to influence the growth response and phenotype of neighbouring cells. 3. Angiotensin II, acting via the AT1 receptor subtype, and both basic fibroblast growth factor and heparin-binding epidermal growth factor have been shown to exert hypertrophic actions in vivo and in vitro. Studies also indicate that cardiac myocytes themselves are capable of releasing all of these cytokines in response to increased mechanical load.

Angiotensin II↗
PubMed1995

Glucocorticoids increase osteopontin expression in cardiac myocytes and microvascular endothelial cells. Role in regulation of inducible nitric oxide synthase.

In heart muscle, the cytokine-inducible isoform of nitric oxide synthase (NOS2) is expressed in both cardiac myocytes and microvascular endothelial cells (CMEC). mRNA levels for both NOS2 and for osteopontin, a multifunctional extracellular matrix phosphoprotein containing and RGD integrin binding domain, are increased in cardiac muscle following intraperitoneal injection of adult rats with lipopolysaccharide. In vitro, interleukin-1 beta and interferon-gamma increased osteopontin mRNA levels in CMEC as well as NOS2 expression in both CMEC and cardiac myocytes. However, osteopontin mRNA levels in heart muscle in vivo, and in cardiac myocytes and CMEC in vitro, also are increased 10-30-fold by the synthetic glucocorticoid dexamethasone, an agent that suppresses cytokine induction of NOS2 in both cell types. The hexapeptide GRGDSP, which interrupts binding of RGD-containing proteins to cell surface integrins, increased NOS2 mRNA, while a synthetic osteopontin peptide analogue decreased NOS2 mRNA and protein levels in both cytokine-pretreated cardiac myocytes and CMEC cultures. Also, transfection with a full-length antisense-osteopontin cDNA in cytokine-pretreated CMEC decreased endogenous osteopontin mRNA and increased NOS2 mRNA levels. These results suggest that osteopontin could regulate the location and extent of NOS2 induction in the heart. Increased expression of osteopontin also may be one mechanism by which glucocorticoids suppress NOS2 activity in cardiac myocytes and microvascular endothelial cells.

Animals↗
PubMed1995

Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes.

Nitric oxide synthase (NOS) isoforms are discovered in an increasing variety of cell types with different roles in signaling. The inducible NOS (i.e. iNOS or NOS II) is expressed in cardiac myocytes in response to specific cytokines. Independent of iNOS induction, however, receptor-dependent signaling is modulated by a constitutive nitric oxide (NO) synthase isoform in these cells (Balligand, J. L., Kelly, R.A., Marsden, P.A., Smith, T. W., and Michel, T. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 347-351). We now show that cardiac myocytes constitutively express the endothelial isoform of NO synthase (ecNOS or NOS III). Transcripts for NOS III were detected by Northern blot in myocyte extracts using as a probe a polymerase chain reaction-generated cDNA amplified with isoform and species-specific primers. In subcellular fractionation experiments, a calcium-sensitive NO synthase activity was present primarily in the particulate fraction, coinciding with the distribution of NOS III analyzed by protein immunoblotting. The localization of NOS III within cardiac myocytes was further demonstrated by immunohistochemistry. The functional role of NOS III was explored by analyzing the effects of NOS inhibitors on single myocyte L-type calcium current and contractility. Inhibition of NOS blocked the attenuation by carbamylcholine of the increases in both parameters induced by beta-adrenergic stimulation. We conclude that NO-dependent parasympathetic signaling is mediated by NOS III in cardiac myocytes.

Amino Acid Oxidoreductases↗
PubMed1995

Transforming growth factor-beta: neuronal and glial expression in CNS degenerative diseases.

We have previously shown that the brains of patients with Alzheimer's disease (AD) express transforming growth factor (TGF)-beta 2 in neurofibrillary tangle (NFT)-bearing neurons and reactive astrocytes. The present study was undertaken to determine whether other neurodegenerative diseases were also associated with an alteration of the TGF-beta's. The immunohistochemical expression of TGF-beta 1, -2 and -3 was assessed in the brains of patients with progressive supranuclear palsy (n = 2), amyotrophic lateral sclerosis (n = 3), Lewy body disease (n = 5), Parkinson's disease (n = 1), Shy-Drager syndrome (n = 1), Pick's disease (n = 3), lobar atrophy (n = 1), and corticobasal degeneration (n = 2). Our results were compared to norms for controls (n = 8). We found expression of TGF-beta 2 in both NFT bearing neurons and tangle-bearing glial cells in progressive supranuclear palsy and in neurons with age-related NFT formation. Widespread staining of reactive astrocytes for TGF-beta 2 was observed in all degenerative diseases. TGF-beta 1 and -3 staining was not selectively altered in these diseases. We conclude that induction of TGF-beta 2 may be an intrinsic part of the processes that underlie NFT formation and reactive gliosis in a variety of neurodegenerative diseases.

Adult↗
PubMed1995

Personality and patient adherence: correlates of the five-factor model in renal dialysis.

The five-factor taxonomy of personality traits has received increasing attention in the literature regarding personality correlates of health outcomes and behaviors. We examined the association of the five NEO Five-Factor Inventory dimensions to medical regimen adherence in a sample of 72 renal dialysis patients. Results indicated that Conscientiousness (Dimension III) is a five-factor trait significantly associated with adherence to the medication regimen. No other NEO-FFI dimension was significantly associated with patient adherence.

Adult↗