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Biomedical subjects

T W Smith

Publications and source records attributed to T W Smith.

At least 73 records · Page 4Linked to original sources
PubMed1998

Basimeningeal/spinal axis primitive neuroectodermal tumor without intraaxial lesion: radiological features.

Over a 12-year period, the authors encountered 2 patients with spinal axis/basimeningeal primitive neuroectodermal tumor (PNET) involving the spinal axis extramedullary, intradural compartment and the basimeninges. In neither patient was an intraaxial focus demonstrated. A 48-year-old woman had computed tomography (CT) findings of hydrocephalus and later abnormal basimeningeal enhancement. Cervical myelography revealed a low cervical intradural block. A 10-year-old boy was evaluated initially with non-contrast-enhanced CT of the brain, which revealed hydrocephalus. Contrast-enhanced CT revealed abnormal basimeningeal enhancement implicating cisternal obstruction. Subsequent magnetic resonance examination of the entire spine with and without gadolinium enhancement revealed diffuse abnormal enhancement of the spinal axis intradural, extramedullary compartment. While intraaxial PNETs are well recognized, the patients described here represent a distinctly unusual pattern of intradural spinal meningeal and basimeningeal infiltration by PNET in the absence of a demonstrable intraaxial lesion.

Brain Neoplasms↗
PubMed1998

Construct validation of health-relevant personality traits: interpersonal circumplex and five-factor model analyses of the Aggression Questionnaire.

The general literature on personality traits as risk factors for physical illness--as well as the specific literature on health consequences of anger, hostility, and aggressive behavior--often suffers from incomplete or inconsistent construct validation of personality measures. This study illustrates the utility of two conceptual tools in this regard--the five-factor model and the interpersonal circumplex. The similarities and differences among anger, hostility, verbal aggressiveness, and physical aggressiveness as measured by the Buss and Perry (1992) Aggression Questionnaire were identified. Results support the interpretation of anger and hostility as primarily reflecting neurotic hostility and antagonistic hostility to a lesser extent. In contrast, verbal and physical aggressiveness can he seen as primarily reflecting antagonistic hostility, and to a lesser extent neurotic hostility. Further, verbal aggressiveness was associated with hostile dominance, whereas hostility was associated with hostile submissiveness. These findings identify potentially important distinctions among these related constructs and illustrate the potential integrative value of standard validation procedures.

Journal Article↗
PubMed1998

The gender gap in reporting household gun ownership.

OBJECTIVES: This study examined errors in estimating household gun ownership that result from interviewing only 1 adult per household. METHODS: Data from 2 recent telephone surveys and a series of in-person surveys were used to compare reports of household gun ownership by husbands and wives. RESULTS: In the telephone surveys, the rate of household gun ownership reported by husbands exceeded wives' reports by an average of 12 percentage points; husbands' reports also implied 43.3 million more guns. The median "gender gap" in recent in-person surveys is 7 percentage points. CONCLUSIONS: Future research should focus on respondents' reports about personally owned guns.

Adult↗
PubMed1998

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

The chemokine receptors CCR5 and CXCR4 are co-receptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Bacterial density and survey of cultivable heterotrophs in the surface water of a freshwater marsh habitat of Anopheles quadrimaculatus larvae (Diptera: Culicidae).

We examined surface water samples collected in September and October 1994 from a freshwater marsh habitat containing larval Anopheles quadrimaculatus mosquitoes. Bacterial densities in direct microscopic counts ranged from 9.7 x 10(5) to 1.3 x 10(7) cells/ml. Densities of cultivable bacteria on trypticase soy agar medium ranged from 1.0 to 1.5 x 10(5) cells/ml. The majority of 888 isolates were gram-positive rods (41%) followed by gram-negative rods (28%). Analysis of the cellular fatty acid profiles of 824 isolates using gas chromatography and Microbial Identification Systems TSBA (Rev. 3.60) library software grouped the bacteria into Bacillus spp. (35%), other gram-positive bacteria (16%), pseudomonads (15%), other gram-negative bacteria including mainly Enterobacteriaceae and Vibrionaceae (21%), and profiles not recognized (13%). Among 33 genera within these groups, the most common were Bacillus, Pseudomonas, Aeromonas, and Arthrobacter.

Animals↗
PubMed1997

Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment.

The endothelium is morphologically and functionally adapted to meet the unique demands of the underlying tissue. At the present time, little is known about the molecular basis of endothelial cell diversity. As one approach to this problem, we have chosen to study the mechanisms that govern differential expression of the endothelial cell-restricted von Willebrand factor (vWF) gene. Transgenic mice were generated with a fragment of the vWF gene containing 2,182 bp of 5' flanking sequence, the first exon and first intron coupled to the LacZ reporter gene. In multiple independent lines of mice, beta-galactosidase expression was detected within endothelial cells in the brain, heart, and skeletal muscle. In isogeneic transplantation models, LacZ expression in host-derived auricular blood vessels was specifically induced by the microenvironment of the heart. In in vitro coculture assays, expression of both the transgene and the endogenous vWF gene in cardiac microvascular endothelial cells (CMEC) was upregulated in the presence of cardiac myocytes. In contrast, endothelial cell levels of thrombomodulin protein and mRNA were unchanged by the addition of ventricular myocytes. Moreover, CMEC expression of vWF was not influenced by the addition of 3T3 fibroblasts or mouse hepatocytes. Taken together, the results suggest that the vWF gene is regulated by vascular bed-specific pathways in response to signals derived from the local microenvironment.

Animals↗
PubMed1997

Dynamic targeting of the agonist-stimulated m2 muscarinic acetylcholine receptor to caveolae in cardiac myocytes.

In cardiac myocytes, as well as specialized conduction and pacemaker cells, agonist binding to muscarinic acetylcholine receptors (mAchRs) results in the activation of several signal transduction cascades including the endothelial isoform of nitric-oxide synthase (eNOS) expressed in these cells. Recent evidence indicates that, as in endothelial cells, eNOS in cardiac myocytes is localized to plasmalemma caveolae, specialized lipid microdomains that contain caveolin-3, a muscle-specific isoform of the scaffolding protein caveolin. In this report, using a detergent-free method for isolation of sarcolemmal caveolae from primary cultures of adult rat ventricular myocytes, we demonstrated that the muscarinic cholinergic agonist carbachol promotes the translocation of mAchR into low density gradient fractions containing most myocyte caveolin-3 and eNOS. Following isopycnic centrifugation, the different gradient fractions were exposed to the muscarinic radioligand [3H]quinuclidinyl benzilate (QNB), and binding was determined after membrane filtration or immunoprecipitation. In a direct radioligand binding assay, we found that [3H]QNB binding can be detected in caveolin-enriched fractions only when cardiac myocytes have been previously exposed to carbachol. Furthermore, most of this [3H]QNB binding can be specifically immunoprecipitated by an antibody to the m2 mAchR, indicating that the translocation of this receptor subtype is responsible for the [3H]QNB binding detected in the low density fractions. Moreover, the [3H]QNB binding could be quantitatively immunoprecipitated from the light membrane fractions with a caveolin-3 antibody (but not a control IgG1 antibody), confirming that the m2 mAchR is targeted to caveolae after carbachol treatment. Importantly, atropine, a muscarinic cholinergic antagonist, did not induce translocation of m2 mAchR to caveolae and prevented receptor translocation in response to the agonist carbachol. Thus, dynamic targeting of sarcolemmal m2 mAchR to caveolae following agonist binding may be essential to initiate specific downstream signaling cascades in these cells.

Animals↗
PubMed1997

Alzheimer's disease, Lewy body disease and aging: a comparative study of the perforant pathway.

The relationship between Alzheimer's disease (AD) and Lewy body disease (LBD) is poorly understood. In AD there is severe loss of neurons comprising the perforant pathway. To assess perforant pathway integrity in pure LBD we compared neuronal counts in layer II of the entorhinal cortex (ERC) in 11 cases of pure LBD that did not meet CERAD pathologic criteria for AD with ERC neuronal counts from seven AD cases with a similar disease duration and six cognitively normal individuals. We counted cell bodies/island in layer II of the ERC using formalin-fixed, paraffin-embedded, tau/cresyl violet-stained sections at the level of the rostral-most body of the hippocampus. There was marked variability in neuronal counts among cases in the LBD group; LBD data overlapped with data from both normal and AD groups. Overall, perforant pathway perikaryal counts in LBD differed significantly from those in AD, but not from those in aged normals (mean perikarya/island = 30.09 +/- 8.95, 7.57 +/- 6.08, and 38.83 +/- 8.98, respectively; F = 26.131, P < 0.001). The percent of remaining neurons bearing neurofibrillary tangles in LBD also overlapped with AD and control groups (16.17 = 13.85%, 87.86 +/- 11.81%, and 24.36 +/- 13.30% of remaining neurons, respectively, F = 65.62, P < 0.001). We conclude that although perforant pathway neuronal loss may occur in LBD, it is more often milder and more variable than that seen in AD.

Adult↗
PubMed1997

Fulminating encephalopathy with perivenular demyelination and vacuolar myelopathy as the initial presentation of human immunodeficiency virus infection.

OBJECTIVE: To study the neuropathologic features in a case involving a 22-year-old woman in whom a fulminating encephalopathy developed as the initial manifestation of human immunodeficiency virus (HIV) infection. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: The patient presented with rapidly progressive mental status, changes, cranial nerve abnormalities, and quadriplegia, which led to her death 5 months later. Serologic tests for HIV were initially indeterminate on Western blot analysis but were positive 1 week later. METHODS: A complete autopsy, including examination of the brain and spinal cord, was performed. Paraffin-embedded sections of the brain and spinal cord were examined using standard histologic staining procedures and immunohistochemical techniques. RESULTS: Neuropathologic examination revealed discrete foci of perivenular demyelination disseminated throughout the brain and spinal cord, as well as severe vacuolar myelopathy. Lesions typical of HIV encephalitis were not present. Human immunodeficiency virus-infected monocytes and microglia were observed in the vicinity of, but not restricted to, the perivenular demyelinating lesions. No other infectious agents were identified. CONCLUSIONS: The patient's acute encephalopathy was most likely the direct result of a widespread demyelinating process resembling acute disseminated encephalomyelitis. We suggest that the perivenular demyelination may represent an autoimmune reaction, possibly due to a nonspecific viral infection, occurring in the setting of chronic immunosuppression secondary to HIV. Although less likely, we cannot exclude the possibility that HIV could have directly triggered an autoimmune response that caused the acute disseminated encephalomyelitis-like lesions.

Adult↗
PubMed1997

Nitric oxide attenuates reoxygenation-induced ICAM-1 expression in coronary microvascular endothelium: role of NFkappaB.

Enhanced leukocyte adhesion has been shown to occur in post-ischemic reperfused hearts due to the upregulation of specific cell-surface adhesion molecules. Therefore, we investigated the influence of 4 h of reoxygenation after 20 h of hypoxia on ICAM-1 induction in primary cultures of rat coronary microvascular endothelial cells (CMEC). ICAM-1 surface expression as well as oxygen free radical formation were measured by flow cytometry. Changes in ICAM-1 mRNA levels were assessed by Northern blot and activation of NFkappaB and AP-1 signalling were analysed by electrophoretic mobility shift assays (EMSA) in CMEC lysates. Although hypoxia alone did not affect cell-surface ICAM-1 expression, 4 h of reoxygenation induced a significant upregulation of ICAM-1. ICAM-1 mRNA could not be found after hypoxia alone, but could be detected as early as 1 h following reoxygenation. Unlike AP-1, the activation of which could be detected in CMEC lysates following hypoxia alone, NFkappaB binding activity was induced only following reoxygenation, concurrent with an increase in the formation of reactive oxygen species (ROS). A proteasome inhibitor, nor-Leu (25 microM) inhibited NFkappaB activation by reoxygenation and ICAM-1 expression. Blockade of endogenous nitric oxide (NO) synthesis in CMEC with L-nitroarginine (10 microM) accentuated post-reoxygenation ICAM-1 expression. Finally, an exogenous NO donor, S-nitrosoacetyl-penicillamine (SNAP, 100 microM), suppressed the generation of ROS upon reoxygenation, and blocked the activation of NFkappaB and the upregulation of ICAM-1. Thus, ICAM-1 upregulation in CMEC primary cultures is not induced by hypoxia alone, but appears shortly after reoxygenation in the absence of exogenous cytokines or inflammatory cells. Because upregulation of AP-1 through hypoxia alone did not affect ICAM-1 expression, we conclude that redox-sensitive NFkappaB activation triggers ICAM-1 upregulation. NO inhibits reoxygenation-specific ICAM-1 upregulation, most likely by diminishing oxidative stress that leads to NFkappaB activation.

Animals↗
PubMed1997

Differential adhesion of metastatic RAW117 large-cell lymphoma cells under static or hydrodynamic conditions: role of integrin alpha(v) beta3.

RGD-containing substrates were used to study static and hydrodynamic adhesion of murine RAW117 large-cell lymphoma sublines with differential liver-metastatic potentials. Highly liver-metastatic RAW117-H10 cells had higher rates of static adhesion to vitronectin, fibronectin and (GRGDS)4 than poorly metastatic RAW117-P and moderately liver-metastatic RAW117-L17 cells. Under hydrodynamic conditions, adhesion stabilization was more rapid for H10 cells compared to P or L17 cells. Among the RGD peptides, only the polymeric RGD peptide (GRGDS)4 mediated strong static adhesion of H10 cells. Interestingly, all the RGD peptides mediated adhesion stabilization for H10 cells but still not for L17 or P cells under hydrodynamic conditions. Integrin alpha(v) beta3 was involved in stabilizing hydrodynamic adhesion to (GRGDS)4, monomeric RGD peptide R1, but was less important in static adhesion to monomeric RGD peptides. Differential adhesion to liver sinusoidal endothelial cell-derived extracellular matrix (H10 >> L17 > P) was observed under hydrodynamic but not static conditions. Integrin alpha(v) beta3 was also important in hydrodynamic adhesion to liver sinusoidal endothelial cell-derived extracellular matrix. We believe that strong static and hydrodynamic adhesion of H10 cells and their capability of altering adhesive behavior in response to fluid shear may contribute to liver metastasis.

Amino Acid Sequence↗
PubMed1997

Meningioangiomatosis is associated with neurofibromatosis 2 but not with somatic alterations of the NF2 gene.

Meningioangiomatosis occurs sporadically and in patients with neurofibromatosis. The literature, however, is unclear concerning the type of neurofibromatosis associated with meningioangiomatosis. Because determining which form of neurofibromatosis predisposes to meningioangiomatosis would clarify the genetic alterations of this lesion, we reviewed all reported cases of meningioangiomatosis associated with neurofibromatosis in light of current diagnostic criteria for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2). All well-documented cases of meningioangiomatosis occurred in the setting of NF2, implying that germline alterations of the NF2 gene predispose to meningioangiomatosis. To determine whether sporadic (non-NF) cases of meningioangiomatosis arise from somatic alterations of the same gene, we screened the NF2 gene for mutations in 12 sporadic cases of meningioangiomatosis and in constitutional DNA from 6 of these 12 patients. No mutations were found in either the lesional or constitutional DNA, which suggests that sporadic meningioangiomatosis is not a forme fruste of NF2 and that somatic alterations of the NF2 gene do not play a major role in sporadic meningioangiomatosis. For some tumor suppressor genes, germline mutations may predispose to specific tumors, while similar sporadic lesions only rarely suffer somatic mutations in these genes. The present findings suggest a similar dichotomy for the NF2 gene in meningioangiomatosis.

Angiomatosis↗
PubMed1997

Social determinants of cardiovascular reactivity: effects of incentive to exert influence and evaluative threat.

The effects on cardiovascular reactivity of incentive to influence the judgements of the experimenter and the threat of social evaluation were examined in a sample of 60 male and 60 female undergraduates. Participants either were guaranteed $5.00 to prepare and deliver a brief speech or were told that the money was contingent on an evaluation by the experimenter. Participants believed that their speech would be rated for either simple clarity or verbal intelligence. The contingent incentive increased systolic blood pressure reactivity by 6.5 mmHg (32%). Evaluative threat increased systolic reactivity by 7.1 mmHg (36%). These interpersonal processes could increase the risk of cardiovascular disease and are likely to affect the degree of cardiovascular reactivity in laboratory studies.

Adult↗
PubMed1997

S-nitrosothiols inhibit neuronal norepinephrine transport.

Although it has been recently shown that nitric oxide (NO) and its congeners (NO(x)), including nitrosothiols, may modify catecholamine turnover in the brain, it is not known whether NO(x) affect norepinephrine (NE) uptake by sympathetic neurons. The nitrosothiol NO donor S-nitroso-acetylpenicillamine (SNAP, 100 microM for 1 h) elicited a concentration-dependent reduction in desipramine-sensitive [3H]NE uptake into PC-12 cells (66 +/- 3%; P < 0.01) or cultured rat superior cervical ganglia (74 +/- 5%; P < 0.001), whereas desipramine-insensitive [3H]NE uptake was unaffected, indicating a selective effect on uptake-1-mediated transport. Short-term coculture of PC-12 cells with microvascular endothelial cells expressing the cytokine-inducible NO synthase (NOS2) also exhibited a reduction in [3H]NE uptake (33 +/- 3%, P < 0.001) that could be prevented by the addition of the NOS inhibitor N-monomethyl-L-arginine (L-NMMA, 1 mM). Endogenous production of NO(x) by nerve growth factor-pretreated PC-12 cells also exhibited an L-NMMA-inhibitable reduction in [3H]NE uptake. Whereas SNAP resulted in a 10-fold elevation of PC-12 guanosine 3',5'-cyclic monophosphate (cGMP) content (P < 0.01), its effect on [3H]NE uptake was not mimicked by exposure to 8-bromo-cGMP. However, the inhibitory effect of SNAP on uptake-1-mediated [3H]NE transport could be attenuated by 1 mM cysteine, a sulfhydryl compound that could act as a sink for NO(x)-mediated nitrosation reactions, although cysteine did not affect the increase in intracellular cGMP with SNAP. These data suggest that an endogenous NO(x) source(s) modifies the activity of the uptake-1 catecholamine transporter in postganglionic sympathetic neurons, which, as we demonstrate, express both NOS1 and NOS3 isoforms, possibly by S-nitrosothiol-mediated nitrosation of regulatory sites on the transporter.

Animals↗
PubMed1997

Regulation of bFGF expression and ANG II secretion in cardiac myocytes and microvascular endothelial cells.

Basic fibroblast growth factor (bFGF; fibroblast growth factor-2) and angiotensin II (ANG II), among other peptide signaling autacoids (cytokines), are known to regulate the phenotypic adaptation of cardiac muscle to physiological stress. The cell type(s) in cardiac muscle responsible for ANG II synthesis and secretion and the role of endogenous cytokines in the regulation of bFGF induction remain unclear. With the use of confluent, serum-starved, low-passage cultures of cardiac microvascular endothelial cells (CMEC), ANG II could be detected in cellular lysates and in medium conditioned by these cells with the use of high-performance liquid chromatography followed by radioimmunoassay. The secretion of angiotensins by individual CMEC could be detected with a cell-blot assay technique. ANG II secretion was decreased by brefeldin A, an agent that interrupts constitutive and regulated secretory pathways for peptide autacoid/ hormone synthesis, suggesting de novo synthesis, activation, and secretion of angiotensins by CMEC. In primary isolates of adult rat ventricular myocytes (ARVM) and CMEC, ANG II, acting at ANG II type 1 receptors in both cell types, was found to increase bFGF mRNA levels measured by ribonuclease protection assay. Endothelin-1 (ET-1), which is known to be synthesized by CMEC, and bFGF itself, which has been detected in both ARVM and CMEC, increased bFGF transcript levels in both cell types. Interleukin-1beta (IL-1beta), which like ANG II and ET-1 is known to activate mitogen-activated protein kinases in both ARVM and CMEC, increased bFGF mRNA levels only in cardiac myocytes. Thus cytokines such as ANG II, ET-1, bFGF, and IL-1beta locally generated by cellular constituents of cardiac muscle, including CMEC, regulate bFGF mRNA levels in a cell type-specific manner.

Angiotensin II↗