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Biomedical subjects

N Wong

Publications and source records attributed to N Wong.

At least 73 records · Page 4Linked to original sources

Isolation of Arabidopsis thaliana mutants hypersensitive to gamma radiation.

A screening method for mutants of Arabidopsis thaliana hypersensitive to gamma-radiation has been devised. Plants grown from ethyl methanesulfonate (EMS)-treated seeds were irradiated at the seedling stage, which is highly radiosensitive due to extensive cell division. Severe growth inhibition of mutant plants by a gamma-ray dose which only slightly affects wild-type plants was the selective criterion. Twelve true-breeding hypersensitive lines were isolated from a total of 3394 screened plants. Genetic analysis of five of the lines revealed five new genes, designated RAD1-RAD5. These Arabidopsis RAD mutants are phenotypically similar to mutants in the RAD52 epistasis group of Saccharomyces cerevisiae, which are highly sensitive to ionizing radiation but not hypersensitive to UV light. One possibility is that the Arabidopsis mutants are defective in a nonhomologous or illegitimate recombination mechanism used by plants for repair of chromosome breaks.

Arabidopsis↗

Antiinflammatory 4,5-diarylpyrroles: synthesis and QSAR.

A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.

Animals↗

Acute cocaine administration induces ventricular regional wall motion and ultrastructural abnormalities in an anesthetized rabbit model.

Whether acute doses of cocaine can induce left ventricular (LV) regional wall motion abnormalities in animals with otherwise normal coronary arteries is unknown. We studied rabbits receiving constant cocaine infusions (group I: 0.025 to 1.5 mg/kg/min, n = 10), multiple cocaine boluses (group II: 3-5 mg/kg each bolus, n = 10), or saline (group III; n = 8). In group I rabbits, short-axis LV area and diameter increased by 15% to 40% at 60 minutes compared to baseline and to controls (p < 0.01), but percentage of global area fractional shortening was unchanged. Eight rabbits in each of groups I and II, but no controls, developed LV regional wall motion abnormalities as detected by echocardiography: 15 (7 hypokinesis and 8 akinesis or dyskinesis) in the anteroseptal and 2 (hypokinesis) in the posterior LV wall. Among rabbits showing LV wall motion abnormalities, anteroseptal fractional shortening and % area reduction averaged > 20% less (p = 0.03 for area reduction) at 30 minutes versus controls. Only 50% of group I or II rabbits with LV anteroseptal wall motion abnormalities had intraventricular conduction disturbances. Radioactive microsphere flow studies (n = 6) 1 minute after a 4 mg/kg cocaine bolus revealed an equivalent decrease (10% to 20%, average) in septal and LV free wall perfusion (p value not significant). Electron microscopy revealed myocardial cell contraction band necrosis in 3 and sarcoplasmic reticular edema in 7 of 10 cocaine rabbits (unrelated to dose). We conclude that acute cocaine administration in rabbits frequently produces LV anteroseptal wall motion abnormalities even in the absence of differentially decreased perfusion or intraventricular conduction disturbances and produces ultrastructural abnormalities of the myocytes. These findings suggest a direct, nonuniform effect of cocaine on the LV myocardium.

Animals↗

Inhibition of expression of major histocompatibility complex class II molecules in macrophages infected with Leishmania donovani occurs at the level of gene transcription via a cyclic AMP-independent mechanism.

Among the important pleiotropic responses to gamma interferon (IFN-gamma) during the activation of macrophages (M phi) is the increased expression of major histocompatibility complex class II genes. In the present study, infection with Leishmania donovani was shown to inhibit in parallel the induction by IFN-gamma of H-2 A beta gene transcription, class II mRNA accumulation, and H-2 Ad protein expression in cells of the murine macrophage cell line P388D1. Treatment of P388D1 cells with either the adenylate cyclase activator cholera toxin or the protein kinase A activator N6-2'-O-dibutyryl cyclic AMP (dibutyryl cAMP) similarly inhibited the induction by IFN-gamma of class II protein expression, and in parallel with Leishmania infection, cholera toxin inhibited the induction of mRNA for the H-2 A alpha and H-2 A beta proteins. Concentrations of intracellular cAMP were significantly increased in cholera toxin-treated cells but not in leishmania-infected cells. These findings indicate that at least one mechanism by which Leishmania infection attenuates the activation of M phi by IFN-gamma involves selective, transcriptional inhibition of major histocompatibility complex class II genes via a cAMP-independent mechanism.

Animals↗

Effect of hand-arm exercise on venous blood constituents during leg exercise.

To test the hypothesis that ancillary arm and hand exercise would change the values of antecubital blood constituents during leg exercise, seven healthy men (19-27 yrs) performed static (10% of a maximal voluntary contraction) or dynamic (60 finger flexions/min) hand-arm exercise with one hand during submaximal leg exercise (50% V2 max) in the supine position. Venous blood was analyzed for serum Na+, K+, osmolality, albumin, total Ca2+, and glucose; blood hemoglobin, hematocrit, and lactic acid; and change in plasma volume. During leg exercise there were no significant differences in these blood constituents between right and left arms at rest. Only glucose and lactate were affected by additional arm exercise. Compared with resting arm values during leg exercise, glucose decreased from 4.7 to 4.5 mmol/l (delta = 4%, P less than 0.05) and lactate increased from 2.0 to 2.4 mmol/l (delta = 20%, P less than 0.05) during static arm exercise. With dynamic arm exercise, glucose decreased from a resting level of 4.8 to 4.7 mmol/l (delta = 2%, P less than 0.05). We conclude that additional static or dynamic hand-forearm exercise accompanying leg exercise could introduce significant errors in glucose (2%-4%) and lactic acid (6%-20%) concentrations measured in venous blood.

Adult↗

Exercise thermoregulation in men after 6 hours of immersion.

Rectal (Tre) and mean skin (Tsk) temperature, skin heat conductance (Ksk), heart rate, and total body sweat rate were measured in 6 men (20-35 years) during 70 min of supine leg exercise (Ta = 23.5 degrees C, rh = 40%) at 50% of their peak O2 uptake (VO2 peak); these data were taken after a 6-h control (C) period in air and after immersion to the neck (NI) in water (34.5 degrees C) for 6 h after overnight food and fluid restriction. After NI mean (+/- S.E.) water balance was -1,285 +/- 104 ml for the 6 h and plasma volume (delta Hb and Hct) decreased by 5.2%. End exercise heart rates after C (141 +/- 3 b X min-1) increased to 148 +/- 3 b X min-1 (p less than 0.05) after NI while Vo2 were both 2.2 L X min-1 Tre increased by 0.5 C degrees (p less than 0.05) between the end of NI and the start of exercise. During exercise following C and NI, delta Tre were +1.0 degrees C and +0.9 degrees C (NS), Ksk were 44 +/- 2 and 43 +/- 1 kcal X m-2 X hr-1 X degrees C-1 (NS), while sweat rates increased from 248 +/- 19 to 366 +/- 52 g X h-1 (p less than 0.05), respectively. Both the total integrated Tre and Tsk curves after NI were higher (p less than 0.05) than for C. These results suggest that, compared with control responses, the equilibrium level of core temperature during submaximal exercise is regulated at a higher level after immersion.

Adult↗

Immersion diuresis without expected suppression of vasopressin.

To investigate fluid, electrolyte, and plasma vasopressin (PVP) and renin activity (PRA) responses, six men (20-35 yr) were immersed to the neck (NI) in water at 34.5 degrees C for six h after overnight food and fluid restriction. Diuresis was 1,061 +/- 160 (SE) ml/6 h during immersion and water balance was -1,285 +/- 104 ml/6 h. Preimmersion PVP was 0.7 +/- 0.2 pg/ml and increased to 3.0 +/- 0.6 pg/ml (P less than 0.05) at 6 h. PVP was unchanged at 1.2 +/- 0.1 pg/ml in the 6-h seated nonimmersion experiment at 25 degrees C. Plasma volume increased by 7.8 +/- 1.6% (P less than 0.05) at 60 min of NI and decreased thereafter. Serum osmolality was constant (292 +/- 1 mosmol/kg) throughout NI, whereas PRA decreased progressively from 1.9 to 0.5 ng angiotensin I X ml-1 X h-1 (P less than 0.05) at the end of immersion. In spite of moderate thirst just before NI, thirst sensations were attenuated and no water was consumed ad libitum during immersion. These data indicate that PVP is not suppressed when there is no fluid intake during immersion and suggest that the action of factors other than PVP suppression are necessary to explain the mechanism of immersion diuresis.

Adult↗