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Biomedical subjects

A Chu

Publications and source records attributed to A Chu.

At least 73 records · Page 4Linked to original sources

Cytoplasmic Ca2+ does not inhibit the cardiac muscle sarcoplasmic reticulum ryanodine receptor Ca2+ channel, although Ca(2+)-induced Ca2+ inactivation of Ca2+ release is observed in native vesicles.

Single channel properties of cardiac and fast-twitch skeletal muscle sarcoplasmic reticulum (SR) release channels were compared in a planar bilayer by fusing SR membranes in a Cs(+)-conducting medium. We found that the pharmacology, Cs+ conductance and selectivity to monovalent and divalent cations of the two channels were similar. The cardiac SR channel exhibited multiple kinetic states. The open and closed lifetimes were not altered from a range of 10(-7) to 10(-3) M Ca2+, but the proportion of closed and open states shifted to shorter closings and openings, respectively. However, while the single channel activity of the skeletal SR channel was activated and inactivated by micromolar and millimolar Ca2+, respectively, the cardiac SR channel remained activated in the presence of high [Ca2+]. In correlation to these studies, [3H]ryanodine binding by the receptors of the two channel receptors was inhibited by high [Ca2+] in skeletal but not in cardiac membranes in the presence of adenine nucleotides. There is, however, a minor inhibition of [3H]ryanodine binding of cardiac SR at millimolar Ca2+ in the absence of adenine nucleotides. When Ca(2+)-induced Ca2+ release was examined from preloaded native SR vesicles, the release rates followed a normal biphasic curve, with Ca(2+)-induced inactivation at high [Ca2+] for both cardiac and skeletal SR. Our data suggest that the molecular basis of regulation of the SR Ca2+ release channel in cardiac and skeletal muscle is different, and that the cardiac SR channel isoform lacks a Ca(2+)-inactivated site.

Animals↗

In situ Ca(2+)-induced Ca2+ release from a ryanodine-sensitive intracellular Ca2+ store in corneal epithelial cells.

1. In a number of tissues, Ca2+ signaling involves Ca(2+)-induced Ca2+ release (CICR) from ryanodine- and caffeine-sensitive intracellular Ca2+ stores. We sought evidence for such a mechanism in bovine corneal epithelial cells (BCE). 2. We have identified a microsomal fraction of BCE which possesses high-affinity [3H]-ryanodine binding sites indicating the presence of the ryanodine receptor Ca2+ channel. 3. Functional evidence for CICR is that in fura-2 loaded BCE the magnitude of Ca2+ transients induced by the addition of either the adenylate cyclase activator, forskolin, or the L-type Ca2+ channel agonist, BAY-K 8644, were both enhanced by preincubation with 5 microM ryanodine. This ryanodine enhancement provides evidence that Ca2+ release from a ryanodine-sensitive intracellular Ca2+ store also contributes to the Ca2+ transients. Therefore, Ca(2+)-induced Ca2+ release is a component of Ca2+ signaling in BCE.

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

Conflicting measurements of depression in a substance abuse population.

Methadone maintenance patients (N = 217) were administered a computerized screening version of the National Institute for Mental Health (NIMH) Diagnostic Interview Schedule (DIS), the Beck Depression Inventory (BDI) and the Addiction Severity Index (ASI) 2-4 weeks after treatment entry. Few differences were found between African-American, Hispanic, and Caucasian subjects. Only 1.7% of the patients met a lifetime diagnosis of major depressive disorder, and 1.4% qualified for a current diagnosis major depressive disorder. In contrast, 35.8% of the patients reported moderate to serious depression on the BDI during the previous week, and 19.3% reported serious depression during the previous month on the ASI (38.7% lifetime depression). Because moderate correlations were found between the DIS, the BDI, and the ASI measures of depression, there is some indication that they were tapping a similar construct. Therefore the lower rates of depression found with the DIS are probably attributable to its more stringent definition of depression. The findings tend to confirm previous literature indicating that the DIS, as contrasted with other structured psychiatric interviews, underestimates depression.

Black or African American↗

Sample design: Third National Health and Nutrition Examination Survey.

This report presents a detailed description of the sample design for the Third National Health and Nutrition Examination Survey, 1988-94, including a brief description of research that led to the choice of the final design. The National Health and Nutrition Examination Survey (NHANES) is one of the major surveys of the National Center for Health Statistics, Centers for Disease Control. Information on the health and nutritional status of the noninstitutionalized population of the United States is collected through the NHANES household interviews and standardized physical examinations.

Adolescent↗

Esthesioneuroblastoma presenting as sudden unilateral blindness. Histopathologic confirmation of optic nerve demyelination.

We report here a case of esthesioneuroblastoma an 11-year-old girl presenting as acute loss of vision with minimal evidence of orbital, nasal, or paranasal sinus disease, a rare presenting symptom for this tumor. The initial diagnosis was postviral optic neuritis, a pattern of presentation not previously reported. When vision failed to improve, magnetic resonance imaging revealed a lesion in the posterior ethmoid and sphenoid sinuses. After a biopsy, the tumor was excised through the cranium and paranasal sinuses. A mass completely surrounding the optic nerve without invasion was found. Histochemical staining suggested demyelination secondary to compression, confirming the clinical impression of optic neuritis. Anti-Leu 7 monoclonal antibody is useful in characterizing of this tumor, since other immunochemical stains can be misleading. Radiation and chemotherapy were given after the tumor was removed. Two years later, the patient has had neither recurrence nor complications.

Antineoplastic Combined Chemotherapy Protocols↗

Phosphatidylinositol 4,5-bisphosphate-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum terminal cisternal membranes. Ca2+ flux and single channel studies.

We report here that the inositol 1,4,5-trisphosphate (IP3) precursor, L-alpha-phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent molecule (1 microM) which activates the ryanodine-sensitive Ca2+ release channel from rabbit skeletal muscle terminal cisternae incorporated into a phospholipid bilayer. It also stimulates Ca2+ release from these membrane vesicles. Therefore, it may play a modulating role in excitation-contraction coupling. In the bilayer, PIP2 added on the cytoplasmic side increased the mean channel opening probability 2-12-fold in the presence and absence of physiological Mg2+ and ATP. From flux studies, PIP2-induced Ca2+ release, occurring through the ryanodine-sensitive Ca2+ release channel, displayed saturation kinetics. The rate of Ca2+ release induced by PIP2 was approximately greater than 50% slower than the rates induced by other agents (e.g. caffeine, Ca2+, ATP). PIP2, and not IP3, effectively elicited Ca2+ release from terminal cisternae. On the contrary, IP3, and not PIP2, specifically mediated Ca2+ release from dog brain cerebellum microsomes, where IP3 receptors are known to be found. The PIP2-induced Ca2+ release from muscle membranes was not dependent on medium [Ca2+] (from less than 10(-9) to approximately 10(-4) M). However, IP3 could activate the terminal cisternae Ca2+ channel in the bilayer when there was low Ca2+ (less than 10(-7) M). The data suggest that the ionic microenvironment around the Ca2+ channel may be different for observing the two phosphoinositide actions.

Animals↗

Brown tumor and secondary hyperparathyroidism.

Brown tumor is a focal, bony lesion of hyperparathyroidism that results from parathyroid hormone on bone increasing osteoclastic activity with bone resorption and trabecular fibrosis. This leads to microfractures and hemorrhage and the appearance of brown tumors, which are seen most commonly in primary hyperparathyroidism and less frequently in secondary hyperparathyroidism. Rarely do these tumors involve the orbit. We report the sixth case, to our knowledge, of orbital involvement, in a patient with chronic renal failure (secondary hyperparathyroidism) and review the literature.

Adult↗

Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs.

The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses greater than or equal to 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular end-diastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest does of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholine-stimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions.

Acetylcholine↗

Hematological indices in a cohort of HTLV-I/II and HIV-1 infected intravenous drug users in New York City.

The prevalence and clinical consequences of human T-cell lymphotropic viruses types I and II (HTLV-I/II) infection in human immunodeficiency virus-1 (HIV-1) infected persons are areas of continuing interest. This article reports the preliminary findings of the hematological indices in 454 patients infected with HIV-1 and HTLV-I/HTLV-II. Based on serology, 46.2% of the patients had evidence of HIV-1 infection only, 4.6% had evidence of HTLV-I/II only, 14.3% had evidence of both HIV-1 and HTLV-I/II, and 34.8% had evidence of neither HIV-1 or HTLV-I/II. The patient group with both HTLV-I/II and HIV-1 infection had lower total white blood cell, platelet, and serum hematocrits than patients with either HIV-1 or HTLV-I/II infection. While these differences were insignificant, they do not suggest any HTLV-I/II-induced protective effect against HIV-1 related hematological consequences.

Acquired Immunodeficiency Syndrome↗

Surgical treatment of thyroid-related lid retraction: a new variation.

We describe a cutaneous approach for retraction of the upper eyelid which incorporates a levator aponeurotic/Mueller's muscle recession with maintenance of the normal orbital septum levator aponeurosis anatomy. With success defined as asymmetry between the two eyelids of 1 mm or less, with a marginal reflex distance as close to 4 mm as possible, this technique was successful in 87% of 15 consecutive patients. All patients reported improved comfort. This approach is quick and easy, bleeding is minimal, height and contour are predictable, the upper eyelid crease is preserved, and spacers are avoided, with less postoperative eyelid thickening and reaction.

Eyelid Diseases↗

Seroepidemiology and clinical aspects of human T-cell lymphotropic virus type I/II infection in a cohort of intravenous drug users in New York City.

To define further the magnitude, epidemiology, and clinical features of human T-cell lymphotropic/leukemia virus type I/II (HTLV-I/II) infection in 454 intravenous drug users in New York City, we evaluated previously frozen aliquots of sera for HTLV-I/II antibodies using enzyme-linked immunoassay, Western blot, and radioimmunoprecipitation techniques. We found HTLV-I/II infection in 18.9% of the subjects. Age (p = 0.001), race (p = 0.001), having a same gender sexual relationship (p = 0.01), and HIV-1 infection (p = 0.041) were clear correlates of HTLV-I/II infection. HTLV-I/II seropositive subjects, in contrast to seronegative subjects, had lower leukocyte counts (p = 0.05) and higher globulin (p = 0.005) and gamma globulin (p = 0.009) levels even when HIV-1 serostatus was controlled. The considerable prevalence of HTLV-I/II infection and the morbidity of HTLV-I/II-associated disorders strongly suggest a continued need to define the dimensions of HTLV-I/II infection.

Adult↗

Specific association of calmodulin-dependent protein kinase and related substrates with the junctional sarcoplasmic reticulum of skeletal muscle.

A systematic study of protein kinase activity and phosphorylation of membrane proteins by ATP was carried out with vesicular fragments of longitudinal tubules (light SR) and junctional terminal cisternae (JTC) derived from skeletal muscle sarcoplasmic reticulum (SR). Following incubation of JTC with ATP, a 170,000-Da glycoprotein, a 97,500-Da protein (glycogen phosphorylase), and a 55,000-60,000-Da doublet (containing calmodulin-dependent protein kinase subunit) underwent phosphorylation. Addition of calmodulin in the presence of Ca2+ (with no added protein kinase) produced a 10-fold increase of phosphorylation involving numerous JTC proteins, including the large (approximately 450,000 Da) ryanodine receptor protein. Calmodulin-dependent phosphorylation of the ryanodine receptor protein was unambiguously demonstrated by Western blot analysis. The specificity of these findings was demonstrated by much lower levels of calmodulin-dependent phosphorylation in light SR as compared to JTC, and by much lower cyclic AMP dependent kinase activity in both JTC and light SR. These observations indicate that the purified JTC contain membrane-bound calmodulin-dependent protein kinase that undergoes autophosphorylation and catalyzes phosphorylation of various membrane proteins. Protein dephosphorylation was very slow in the absence of added phosphatases, but was accelerated by the addition of phosphatase 1 and 2A (catalytic subunit) in the absence of Ca2+, and calcineurin in the presence of Ca2+. Therefore, in the muscle fiber, dephosphorylation of SR proteins relies on cytoplasmic phosphatases. No significant effect of protein phosphorylation was detected on the Ca2(+)-induced Ca2+ release exhibited by isolated JTC vesicles. However, the selective and prominent association of calmodulin-dependent protein kinase and related substrates with junctional membranes, its Ca2+ sensitivity, and its close proximity to the ryanodine and dihydropyridine receptor Ca2+ channels suggest that this phosphorylation system is involved in regulation of functions linked to these structures.

Adenosine Triphosphate↗

Patterns of HIV-1 and HTLV-I/II in intravenous drug abusers from the middle atlantic and central regions of the USA.

Seroprevalence of human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus types I and II (HTLV-I/II) was determined among 1160 intravenous (iv) drug abusers from five drug treatment or medical centers (Manhattan, Brooklyn, New Jersey, Detroit, and New Orleans). HIV-1 infection ranged from 5% in New Orleans to 48% in New York City. Hispanics and blacks had a significantly higher rate of HIV-1 infection than whites (P less than .01), but within each group rates were similar between males and females and by age stratum. HTLV-I/II seroprevalence increased with age from 3% in the 20-29 year age group to 37% in the group greater than 50 years. New Orleans and Manhattan (24%) had the highest rate, and blacks (19%) had a higher rate than either Hispanics (6.3%) or whites (7.3%). No association between HIV-1 and HTLV-I/II infection was observed except in Manhattan. When compared with iv drug abusers infected only with HIV-1, dually infected subjects had more clinical symptoms related to immune deficiency but a lower prevalence of HIV antigenemia. These data document the frequent occurrence of retroviral infections in iv drug abusers. The contrast between the two classes of virus suggests that HIV-1 is more efficiently transmitted, while the age-dependent rise in HTLV-I/II seroprevalence suggests cumulative exposure of a less-transmissible agent.

Adult↗

Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs.

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.

Animals↗

Preferential proximal coronary dilation by activators of guanylate cyclase in awake dogs.

The vasodilation effects of activators of guanylate cyclase, atrial natriuretic peptide (ANP), nitroglycerin (NTG), and acetylcholine (ACh), on the epicardial conductance arteries and the distal resistance coronary vessels were examined in chronically instrumented awake dogs and related serially to plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels. Left atrial bolus injections of ANP (3 micrograms/kg; n = 7), NTG (13 micrograms/kg; n = 7), or ACh (0.13 micrograms/kg; n = 3) induced sustained increases in epicardial coronary dimension (ultrasonic crystals), 3.3, 5.7, and 6.7%, respectively, lasting greater than 40 min for ANP and NTG and greater than 3 min for ACh, and relatively brief increases in blood flow (resistance artery vasomotion) for each agent. Plasma samples withdrawn serially after injections of each agent demonstrated that only ANP increased cGMP level; the time course of ANP-induced epicardial vasodilation followed more closely the increase in cGMP than that of plasma ANP. These data demonstrated that these three activators of guanylate cyclase induced preferential sustained epicardial vasodilation and only brief distal coronary vasodilation with minor or no change in systemic hemodynamics. The prolonged increase in plasma cGMP after ANP injection suggested continuous cGMP production during ANP-induced proximal vasodilation. These data demonstrate a striking heterogeneity of vasomotor responses in the coronary arterial vasculature and suggest that cGMP-mediated vasodilation mechanisms are more predominant in proximal conductance arteries compared with distal resistance vessels.

Acetylcholine↗

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia.

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗