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Biomedical subjects

T W Smith

Publications and source records attributed to T W Smith.

At least 19 recordsLinked to original sources
PubMed1992

Transcriptional regulation in cardiac muscle. Coordinate expression of Id with a neonatal phenotype during development and following a hypertrophic stimulus in adult rat ventricular myocytes in vitro.

The transcriptional regulatory mechanisms in heart muscle that direct cardiac development and allow for a flexible, adaptive response to physiologic stress are not well understood. We demonstrate that a negative regulator of gene transcription termed Id that has been described predominantly in proliferating cell lines and in undifferentiated tissue during growth, is expressed in freshly isolated terminally differentiated adult rat ventricular myocytes, in contrast to most other tissues in the adult rat. Id mRNA expression is regulated in ventricular myocytes during post-natal development, peaking at the transition from hyperplastic to hypertrophic growth at day 17 in the rat, declining subsequently to lower, stable levels in adult myocytes. Although Id mRNA becomes undetectable in adult ventricular myocytes 48 h following isolation in the absence of serum, it can be rapidly reinduced by an alpha-adrenergic agonist, accompanied by increased protein synthesis and the reexpression, in defined media, of the neonatal genes prepro-ANP and skeletal muscle alpha-actin. Thus, the differential regulation of Id during cardiac development, the presence of Id mRNA in normal cardiac myocytes, and its increased expression following a hypertrophic stimulus all suggest a role for this transcriptional regulator in the control of cardiac muscle cell phenotype.

Aging↗
PubMed1992

Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids.

The highly unsaturated n-3 fatty acids from fish oils, eicosapentaenoic acid [EPA; C20:5 (n-3)] and docosahexanoic acid [DHA; C22:6 (n-3)], prevent the toxicity of high concentrations of the cardiac glycoside ouabain to isolated neonatal rat cardiac myocytes. Arachidonic acid [C20:4 (n-6)] lacks such protective action. The protective effect of the n-3 fatty acids is associated with their ability to prevent high levels of cytosolic free calcium from occurring in response to the ouabain. This in turn results, at least in part, from a 30% reduction in calcium influx rate induced by the n-3 fatty acids. This protective effect is simulated by nitrendipine, a dihydropyridine inhibitor of the L-type calcium channels in cardiac myocytes. Nitrendipine (0.1 mM) alone, however, inhibits myocyte contractility, as do verapamil (10 microM) and diltiazem (1.0 microM). EPA or DHA (5 microM) blocks the inhibitory effects of nitrendipine but not those of verapamil or diltiazem. Bay K8644, a known dihydropyridine agonist of L-type calcium channels, produces a ouabain-like effect that is also prevented by EPA or DHA. Specific binding of [3H]nitrendipine to intact myocytes is noncompetitively inhibited by EPA or DHA in a manner that reduces the number of high- and low-affinity binding sites (Bmax) and increases their affinities. The fish oil fatty acids prevent calcium overload from ouabain and Bay K8644. They also prevent a calcium-depleted state in the myocytes caused by the L-type calcium channel blocker nitrendipine. The protective effects of the n-3 fatty acids appear to result from their modulatory effects on nitrendipine-sensitive L-type calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Family support, physical impairment, and adherence in hemodialysis: an investigation of main and buffering effects.

Patient noncompliance is a pervasive problem among end-stage renal disease (ESRD) patients. Previous studies have implicated social support as an important correlate of adherence behavior in other chronic illness groups, but little research has examined this relationship in a hemodialysis population. The present study examined the main and interactive effects of social support in the family and illness-related physical impairment with regard to patient compliance in a sample of 78 hemodialysis patients. Results indicated that patients holding perceptions of a more supportive family environment exhibited significantly more favorable adherence to fluid-intake restrictions than did patients reporting less family support. Family support was not associated with adherence to dietary restrictions. The effect of family support on fluid-intake adherence was not moderated by level of physical impairment. This pattern suggests that the influence of support on adherence is more attributable to a main or direct effect, as opposed to a buffering process in the face of increased physical impairment.

Activities of Daily Living↗
PubMed1992

The indusium griseum in Alzheimer's disease: an immunocytochemical study.

The immunocytochemical features of the indusium griseum (IG) were compared with the corresponding hippocampus in 5 patients with Alzheimer's disease (AD) and 5 age-matched nondemented individuals using antibodies against beta-amyloid, the A68 protein (Alz-50 antibody), tau, ubiquitin and synapsin I. beta-Amyloid-positive plaques were prominent in the AD hippocampus but were not present in the IG. Numerous Alz-50, tau and ubiquitin-positive neurofibrillary tangles and dystrophic neurites were observed in the AD hippocampus but were infrequent in the IG. Synapsin I immunoreactivity was significantly reduced in both the AD hippocampus and the AD IG when compared to age-matched patients. These findings suggest that the IG may be resistant to factors that trigger production of abnormal AD-associated proteins. Loss of synaptic input alone may not account for the AD-associated changes in the hippocampus since synaptic depletion was seen in both the hippocampus and the unaffected AD IG.

Aged↗
PubMed1992

Neuropathology of the spinal cord in the acquired immunodeficiency syndrome.

The neuropathologic findings in the spinal cord were reviewed in 138 consecutive autopsies of patients with the acquired immunodeficiency syndrome. In all cases both the brain and spinal cord were examined by conventional histologic techniques, and in 63 cases immunohistochemistry was used to detect human immunodeficiency virus (HIV), Toxoplasma gondii, cytomegalovirus, and JC papovavirus antigens. The most common observation was a normal spinal cord (60%). Vacuolar myelopathy (VM) was observed in 23 (17%) cases. Human immunodeficiency virus myelitis was evident in 8% of cases. Human immunodeficiency virus myelitis was associated with HIV encephalitis in 65% of the cases. Opportunistic infections of the spinal cord were uncommon, consisting of cryptococcosis (five cases), cytomegalovirus (four cases), toxoplasmosis (one case), and progressive multifocal leukoencephalopathy (one case), and almost always were seen with cerebral and/or systemic infection by these agents. Malignant lymphoma rarely involved the spinal cord (four cases); all were B-cell lymphomas and were associated with cerebral and/or systemic lymphoma. Other abnormalities rarely observed were Wallerian degeneration of the corticospinal tracts or posterior columns (6%) and focal microinfarcts. Most cases of VM (78%) were not associated with HIV myelitis, and in the five patients with both VM and HIV myelitis, HIV-infected cells were not found in the regions affected by VM. In contrast, 65% of cases with VM were associated with HIV encephalitis. The pathogenesis of VM remains unknown; it is probably not due to direct infection by HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Angiotropic lymphoma (intravascular large cell lymphoma) presenting with cauda equina syndrome.

A 50-year-old man developed cauda equina syndrome of unknown etiology that was stable for 20 months. Two months prior to sudden death, he experienced new back pain, confusion, seizures, and multiple cranial nerve palsies. Neuropathologic examination revealed angiotropic lymphoma without parenchymal involvement or infarcts in the brain, spinal cord, and muscle. In addition, nerve roots in the cauda equina contained angiotropic lymphoma and infarcts of various ages. Angiotropic lymphoma should be considered as a cause of cauda equina syndrome and of disorders that affect the central and peripheral nervous systems concurrently.

Brain Neoplasms↗
PubMed1992

Differential antinociceptive effects of morphine and methylmorphine in the formalin test.

The antinociceptive activities of morphine, and its quaternary analogue methylmorphine, have been compared after intraperitoneal and intracerebroventricular administrations in the mouse paw formalin test. Systemic morphine inhibited both the early and late phases of the formalin-induced licking response and this activity was naloxone sensitive. In contrast, systemic methylmorphine inhibited only the late phase, and this activity was blocked by pre-treatment with methylnaloxone. Central administration of either morphine or methylmorphine inhibited the early phase of the licking response partially and the late phase completely. Systemic naloxone inhibited the central action of both opioids, whilst systemic methylnaloxone did not affect the central action of methylmorphine. The results indicate that the early phase of the response to formalin in the mouse may be inhibited by stimulation of central opioid receptors whilst inhibition of the late phase may involve both peripheral and central opioid receptors.

Analgesics↗
PubMed1992

Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1 beta 193-195.

1. The hyperalgesic effects of interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) were measured in rats. 2. Hyperalgesic responses to IL-1 beta were inhibited in a dose-dependent manner by alpha-melanocyte stimulating hormone (alpha-MSH)-related peptides with the following order of potency: [N1(4),D-Phe7]alpha-MSH greater than alpha-MSH greater than Lys-D-Pro-Val greater than Lys-Pro-Val greater than Lys-D-Pro-Thr greater than D-Lys-Pro-Thr. 3. Hyperalgesic responses to PGE2 were not inhibited by Lys-D-Pro-Thr and D-Lys-Pro-Thr but were inhibited in a dose-dependent manner by the other peptides with the same order of potency as against IL-1 beta. 4. The potencies of [N1(4), D-Phe7]alpha-MSH and alpha-MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys11-Pro-Val13. 5. Nor-binaltorphimine (Nor-BNI) largely reversed the analgesic effects of alpha-MSH, [N1(4), D-Phe7]alpha-MSH, Lys-Pro-Val and Lys-D-Pro-Val indicating that kappa-opioid receptors mediated the analgesic activity of these peptides. 6. Nor-BNI did not antagonize the inhibition by Lys-D-Pro-Thr and D-Lys-Pro-Thr of IL-1 beta evoked hyperalgesia indicating that these peptides were not acting via kappa-opioid receptors.

Amino Acid Sequence↗
PubMed1992

Neuropathology of immunosuppression.

Traditionally, the brain has been considered an "immunologically privileged" organ. Under normal conditions, the blood-brain barrier (BBB) is highly effective in preventing both cellular and humoral constituents of the blood from entering the brain parenchyma. In certain pathological conditions, such as viral infections and demyelinating disorders, the BBB may become altered, activated T cells and monocytes may gain access to the brain parenchyma, and microglia may assume the functions of antigen-presenting cells and macrophages. Naturally-occurring or clinically-induced immunosuppression may dramatically alter various cellular and/or humoral aspects of the immune system. Consequently, the brain may become susceptible to disorders that would otherwise be excluded or may develop more severe manifestations of diseases, such as certain infections. This review considers the neuropathologic aspects of various conditions that may be encountered in the setting of both acquired and inherited immunosuppression. The major categories include infectious, neoplastic, vascular, and metabolic disorders. The review also briefly addresses the neuropathology of complications of chemotherapeutic agents, radiotherapy, and organ transplantation inasmuch as they often occur in the clinical setting of acquired immunosuppression.

Animals↗
PubMed1992

Na+ efflux mechanisms in ventricular myocytes: measurement of [Na+]i with Na(+)-binding benzofuran isophthalate.

We characterized the Na(+)-sensitive dye benzofuran isophthalate (SBFI) with fluorescence microscopy in isolated, adult rat ventricular myocytes. When cells were loaded with SBFI by incubation with 10 microM of the acetoxymethyl ester, fluorescence excitation spectra were markedly attenuated below 340 nm and the isoemissive point was blue shifted by approximately 25 nm when compared with spectra from SBFI acid in buffered solutions. Fluorescence intensity (49 +/- 3%) was partially released by permeabilization of the sarcolemma with digitonin, suggesting that one-half of the dye molecules are sequestered subcellularly in a compartment shown most likely to be mitochondrial. Intracellular Na+ concentration ([Na+]i) was determined by in situ calibration using cation-selective ionophores and was found to be 14 +/- 2 mM in cells studied at 37 degrees C. The relative importance of Na+ efflux mechanisms in myocytes was investigated. Substitution of Ca2+ and Mg2+ with EGTA in the superfusing medium resulted in a reversible rise of [Na+]i from 13 +/- 2 to 31 +/- 5 mM, which was blocked by 1 microM verapamil. Cellular efflux of Na+ after loading in this manner was found to be insensitive to blockade of Na(+)-Ca2+ exchange but was abolished when Na(+)-K(+)-ATPase was inhibited with zero extracellular K+ concentration. We conclude that SBFI can be used to measure [Na+]i in ventricular cells nondestructively and without impalement. Na+ efflux after loading by Ca2+ and Mg2+ withdrawal is mediated by the Na+ pump with no measurable contribution from Na(+)-Ca2+ exchange.

Animals↗
PubMed1992

Cholesterol increases the L-type voltage-sensitive calcium channel current in arterial smooth muscle cells.

To determine whether membrane free cholesterol affects calcium currents in vascular smooth muscle cells, whole-cell patch clamp recordings were made before and after cholesterol enrichment of cells by exposure to cholesterol-rich liposomes. Exposure to cholesterol-rich liposomes resulted in a gradual increase in the L-type current over 20 hours and a plateau (73 +/- 7% increase over basal) between 20 and 32 hours. This effect was associated with a rightward shift in the inactivation potential and a decrease in the sensitivity to (-)-PN-202-791, a dihydropyridine antagonist. There was no change in the maximum L-type current stimulated by (+)-PN-202-791, a dihydropyridine agonist. Liposome exposure caused a small, transient increase in the T-type current (peak effect, 20 minutes). We conclude that membrane cholesterol has important effects on the L-type calcium current in vascular smooth muscle cells, which is most likely due to an alteration in channel functional state rather than an increase in channel expression.

Animals↗
PubMed1992

Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels.

To test the hypothesis that direct contact between sympathetic neurons and myocytes regulates expression and function of cardiac Ca channels, we prepared cultures of neonatal rat ventricular myocytes with and without sympathetic ganglia. Contractile properties of myocytes were assessed by an optical-video system. Contractility-pCa curves showed a 60% greater increase in contractility for innervated myocytes compared with control cells at 6.3 mM [Ca]0 (n = 8, P less than 0.05). Cells grown in medium conditioned by growth of ganglia and myocytes were indistinguishable physiologically from control cells. [Bay K 8644]-contractility curves revealed a 60 +/- 10% enhancement of the contractility response at 10(-6) M for innervated cells compared with control cells. The increased response to Bay K 8644 was not blocked by alpha- or beta-adrenergic antagonists. Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture. Dihydropyridine binding sites were assessed with the L channel-specific radioligand 3[H]PN200-110. PN200-110 binding sites were increased by innervation (51 +/- 5 to 108 +/- 20 fmol/mg protein, P less than 0.01), with no change in KD. Peak current-voltage curves were determined by whole-cell voltage clamp techniques for myocytes contacted by a neuron, control myocytes, and myocytes grown in conditioned medium. Current density of L-type Ca channels was significantly higher in innervated myocytes (10.5 +/- 0.4 pA/pF, n = 5) than in control myocytes (5.9 +/- 0.3 pA/pF, n = 8, P less than 0.01) or myocytes grown in conditioned medium (6.2 +/- 0.2 pA/pF, n = 10, P less than 0.01). Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties.

Animals↗
PubMed1979

Localization of the neurally mediated arrhythmogenic properties of digitalis.

Available evidence suggests that the propensity of digitalis glycosides to produce cardiac arrhythmias is due in part to their neuroexictatory effects. We have performed experiments in cats which support the existence of a neurogenic component in the etiology of digitalis-induced ventricular arrhythmias. Our data further indicate that the locus of this neural effect lies within an area of the medulla 2 millimeters above to 2 millimeters below the obex. These findings, when considered with the effects of polar cardiac glycosides that do not cross the blood-brain barrier, suggest that the area postrema may be the site of neural activation.

Animals↗
PubMed1979

A new test of visual acuity using a holographic phase grating and a laser.

A new visual acuity testing device is able to determine a specific visual acuity of the retina even in the presence of opacities of the ocular media, such as a cataract. This is achieved by forming two spatially coherent, quasimonochromatic point sources near the nodal point of the eye. The two spherical waves that emanate from the point sources interact to produce a pattern of stripes on the retina. The intensity of the pattern is easily varied. More importantly, the pattern can be projected over different-sized retinal areas corresponding to visual fields of 0.5 to 15 degrees in diameter. The device may be useful for vision research and preoperative assessments of visual potential.

Holography↗
PubMed1979

The hydrodynamics of pyelorenal reflux.

Our study was done to determine the hydrodynamics of pyelorenal reflux. It is considered important in the pathophysiology of chronic pyelonephritis. An animal model of pyelorenal reflux was studied. The model seems to approximate closely the findings in man, both in the pressure required and the types of pyelorenal reflux observed.

Animals↗