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Biomedical subjects

M Agarwal

Publications and source records attributed to M Agarwal.

At least 55 records · Page 3Linked to original sources
PubMed2000

Human chorionic gonadotrophin is an endothelium-independent inhibitor of rat aortic smooth muscle contractility.

The study tested the hypothesis that human chorionic gonadotrophin (hCG) attenuates isolated vascular smooth muscle contractility and investigated the role of the vascular endothelium in hCG-induced altered responses of vascular smooth muscle. The contractile responses of isolated aortic rings from normal, hCG-treated, and estrogen-treated female virgin Wistar rats to phenylephrine, angiotensin II, KCl, and CaCl2 were compared. The effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), methylene blue, indomethacin, calcium-free medium, and de-endothelialization on responses to phenylephrine of aortic rings from control and hCG-treated rats were also examined. Intraperitoneal administration of hCG caused attenuation of contractile responses of isolated aortic rings to all agents. The attenuated responses to phenylephrine were not reversed by de-endothelialization, or pretreatment of the rings with L-NMMA, methylene blue, or indomethacin. It was concluded that hCG attenuates vascular smooth muscle contractility. The effect is independent of the vascular endothelium, not agonist-specific, and appears to involve alterations of calcium availability.

Angiotensin II↗
PubMed2000

An ultrasonographic evaluation of gallbladder emptying in patients with cholelithiasis.

Impaired gallbladder emptying producing biliary stasis may provide potent carcinogen, which comes in contact with gallbladder mucosa for a prolonged period, inducing carcinogenesis. The aim was to study gallbladder emptying pattern in cholelithiasis. Postprandial gallbladder emptying was measured ultrasonographically in terms of fasting volume (FV), postprandial residual volume at 30 minutes (PP30), 60 minutes (PP60), and 90 minutes (PP90), residual fraction, and ejection volume (EV) in 58 patients with gallstones. Patients were divided into two groups of poor and good contractors on the basis of 50% maximal postprandial gallbladder emptying. Malonaldehyde level was estimated in 15 patients with cholelithiasis. Twenty-nine patients (50%) were poor contractors. The FV in patients with cholelithiasis (mean, 30.08 mL) was larger than the controls (mean, 17.55 mL) and the difference was statistically significant (p < 0.02). The FV in the cholelithiasis group correlated significantly with the PP30 (r = 0.85, p < 0.001), PP60 (r = 0.85, p < 0.001), PP90 (r = 0.78, p < 0.001), and EV (r = 0.65, p < 0.001). Ejection volume was significantly less in poor contractors (p <0.001). Residual fraction was significantly higher in poor contractors (p < 0.001). The biliary malonaldehyde in poor contractors (2.27 micromol/mL) was higher than in good contractors (1.78 micromol/mL), but the difference was statistically not significant. Significantly larger volumes of PP30, PP60, PP90, and residual fraction and a low EV indicate poor contraction leading to biliary stasis.

Cholelithiasis↗
PubMed2000

Effects of a 6-month vitamin intervention on DNA damage in heavy smokers.

Because their formation is associated with tumor development in specific tissues, DNA adducts have potential usefulness as intermediate end points in chemoprevention studies. To determine the efficacy of a combination of antioxidant vitamins (vitamins C and E and beta-carotene), a randomized clinical trial was conducted among heavy smokers using DNA damage as the end point. Immunological methods were used to measure polycyclic aromatic hydrocarbon-DNA adducts and oxidative DNA damage (8-oxo or hydroxydeoxyguanosine) in mononuclear and oral cells. A total of 121 subjects were randomized to the 6-month intervention and received either vitamins or placebo. Dropout rates were higher in the placebo than in the vitamin group; 65% of subjects in the vitamin group, but only 47% in the placebo group, provided specimens at 6 months. Plasma levels of all three antioxidants rose significantly in the vitamin group but not in the placebo group. All four measures of DNA damage decreased in both groups; the between-group differences were not statistically significant. These data do not provide clear evidence that antioxidant vitamin intake prevents DNA damage. However, the study demonstrates that DNA damage is a useful end point in chemoprevention trials.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Effect of scaffold attachment region on transgene expression in retrovirus vector-transduced primary T cells and macrophages.

The scaffold attachment region of the human interferon beta gene (IFN-SAR) inserted into a retroviral vector improved transgene expression in human primary CD4+ and CD8+ T cells, and in primary monocytemacrophages. In T cells, expression of the Maloney murine leukemia virus (Mo-MuLV)-based retroviral vectors was high in activated cells but low in resting cells. Addition of the IFN-SAR sequence enhanced vector expression 2- to 10-fold, and the effect was particularly pronounced in resting T cells. In CD33+CD14+CD4+ monocyte-macrophages derived from transduced hematopoietic stem/progenitor cells (HSPCs) in vitro, the IFN-SAR enhanced vector expression three- to sixfold. We have used the IFN-SAR-containing vectors to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) rev gene. Compared with a standard retroviral vector, the IFN-SAR-containing vector was significantly (p < 0.01) more potent at inhibiting HIV-1 replication in infected CD4+ peripheral blood lymphocytes. In monocytes, however, addition of the IFN-SAR did not significantly improve antiviral efficacy. To understand better the reason for the strong effect of the SAR on antiviral efficacy in T cells we have studied the expression of HIV, Mo-MuLV, and Mo-MuLV + SAR vectors in resting and activated cells. While the expression of all three vectors was lower in resting compared with activated cells, the kinetics of the decrease in expression were fastest for the Mo-MuLV vector, followed by the HIV vector and then the Mo-MuLV + SAR vector. Thus, higher level expression of the Mo-MuLV + SAR vector relative to wild-type HIV at all stages of T cell activation is the most likely explanation for the strong antiviral efficacy. Overall, this study demonstrates the utility of the IFN-SAR sequence for achieving high-level retroviral vector expression in lymphoid and myeloid hematopoietic cells.

Animals↗
PubMed1999

Appendicectomy under local anaesthesia.

OBJECTIVE: To analyse our results of appendicetomy under local anaesthesia. DESIGN: Prospective study. SETTING: University hospital, India. SUBJECTS: 165 patients who presented with appendicitis between January 1996 and December 1997. INTERVENTION AND MAIN OUTCOME MEASURES: Appendicectomy after infiltration of local anaesthetic. No patient required general or spinal anaesthesia. RESULT: Five patients (3%) developed postoperative wound infections. Mean operating time was 20 minutes (range 15-30) and median hospital stay 2 days (range 1-3). CONCLUSION: Appendicectomy under local anaesthesia is quick, cost-effective and carries little morbidity. It can be safely used for all age groups.

Adolescent↗
PubMed1999

Multiple familial keratoacanthoma of Witten and Zak - A report of three siblings.

Three out of 11 siblings of a nonconsanguineous marriage suffering from biopsy-proven multiple small eruptive keratoacanthoma (KA) of Grzybowski as well as large nodular KA of Ferguson-Smith are reported. The response to oral methotrexate was not encouraging. Intravenous 5-fluorouracil (5-FU) at a dose of 12 mg/kg/day in isotonic saline given in weekly 5-day cycles resulted in almost complete resolution of small eruptive lesions and signs of involution in older large agglomerate noduloulcerative KA after 6 cycles. Thus, intravenous 5-FU was found to be an effective therapeutic modality for the Witten and Zak type of KA.

Adult↗
PubMed1999

Hyponatremic-hypertensive syndrome with renal ischemia: an underrecognized disorder.

Renal artery stenosis or occlusion causing the hyponatremic-hypertensive syndrome has been rarely reported. Our impression, however, was that the disorder is not uncommon. Case records from patients in one city (population 350 000) presenting between 1980 and 1997 with hypertension, hyponatremia, and evidence of renal ischemia were scrutinized. Thirty-two patients fulfilling inclusion criteria were identified. Admission supine arterial pressures were high (mean 228/124 mm Hg), but there was a vigorous fall in pressure on standing (26/12.7 mm Hg recorded in 27 patients). Mean plasma concentrations of sodium (129.7 mmol/L) and potassium (2.7 mmol/L) were low, and 24-hour urine protein excretion was elevated in 19 of 26 patients. Twenty-two of the 32 patients were female, the majority were asthenic, and all but 5 were smokers. Symptoms precipitating hospitalization were headache, clouding of consciousness, confusion, weakness, weight loss, thirst, and polyuria. Plasma renin levels, measured in 20 patients, were elevated in most cases and correlated inversely (r=-0.63, P<0.01) with the plasma sodium concentration. The hyponatremic-hypertensive syndrome in patients with renal ischemia is not rare: Rather, it is underreported. It tends to affect elderly asthenic women who smoke heavily. Stimulation of renin release from the ischemic kidney is probably central to the pathophysiology. The syndrome deserves better recognition to ensure appropriate investigations and management.

Adult↗
PubMed1999

Renal handling of endogenous human chorionic gonadotrophin in preeclampsia.

OBJECTIVE: To test the hypothesis that the elevated maternal serum concentration of human chorionic gonadotrophin (hCG) in preeclampsia is due to altered renal handling of the hormone. SETTING: Department of Obstetrics and Gynecology, Al Ain Hospital, United Arab Emirates, a tertiary center affiliated with the Faculty of Medicine and Health Sciences, UAE University. METHODS: The renal clearances and handling of endogenous creatinine and human chorionic gonadotrophin were compared in 14 normotensive volunteer and 14 preeclamptic mothers who received oral hydration at 34-37 weeks' gestation. The hCG content in the placentas was estimated immunohistochemically after delivery. RESULTS: Maternal serum concentration of hCG (p = 0.0057), the placental hCG immunopositive cell (p < 0.0001), and syncytial knot counts (p < 0.0001) were significantly higher in preeclamptic mothers. The renal clearances of endogenous creatinine and hCG and fractional hCG clearance were not significantly different in both groups. Significantly increased amounts of hCG were filtered (p = 0.007) and excreted (p = 0.007) by preeclamptic mothers. Only a small but fixed proportion of the filtered load of hCG is excreted in both groups and there was a positive correlation (r = 0.5, p = 0.005) between filtered and excreted loads of hCG. CONCLUSION: The results indicate increased placental content of hCG in preeclampsia. The resultant increased maternal serum concentration is probably sustained by the mechanism of renal handling of the hormone.

Analysis of Variance↗
PubMed1998

p21Waf1 inhibits the activity of cyclin dependent kinase 2 by preventing its activating phosphorylation.

Prostaglandin A2 (PGA2), a potent inhibitor of the growth of many cell types, inhibits G1 phase cyclin dependent kinases (cdk). Although PGA2 suppresses cyclin D1 and elevates p21Waf1 levels, it was the failure of cdk2 to become activated by phosphorylation which correlated best with growth inhibition. In kinetic studies, cdk2 activation was inhibited efficiently only if p21Waf1 levels increased prior to the activating phosphorylation; suggesting that p21Waf1 had blocked this phosphorylation. This model was confirmed in cells from p21Waf1 knockout mice where PGA2 was completely unable to block the activating phosphorylation of cdk2, or inhibit cdk2 activity. As expected, growth inhibition of p21Waf1(-/-) cells was not observed at PGA2 concentrations which inhibited cdk2 activity and growth of p21Waf1(+/+) cells.

3T3 Cells↗
PubMed1998

Biosocial factors affecting vitamin D status of women of childbearing age in the United Arab Emirates.

Low serum 25-OHD in female Arab subjects, which may predispose their infants to hypocalcaemia, has been suggested to be due to inadequate sunshine exposure, but may include other sociobiological factors. The effects of duration of sunshine exposure--weighted against the magnitude of clothing (UV exposure) and other sociobiological variables such as age, education and living accommodation--on serum 25-OHD and mineral status of 33 UAE national women of childbearing age were compared with those of 25 non-Gulf Arabs and seventeen Europeans. Serum concentrations of calcium, phosphorus, alkaline phosphatase and intact parathyroid hormone among the groups were not significantly different. The serum concentration of 25-OHD in UAE nationals was 8.6 ng/ml (4.5-17.4), mean +/- 1 SD, and in non-Gulf Arabs 12.6 ng/ml (6.0-26.4); both these values were significantly lower (p = < 0.0001) than the 64.3 ng/ml (49-84.3) found in Europeans. Compared with Europeans, the UAE and non-Gulf Arabs in this study were younger, had fewer years of education and had significantly lower clothing and UV scores (p < 0.0001). Furthermore, there was a positive correlation (r = 0.59425) between serum 25-OHD and UV score, but not with length of exposure. After adjusting for other confounding variables, nationality, clothing and UV scores remained major determinants of serum 25-OHD (p < 0.0001). Therefore, limited skin exposure to sunlight appears to be an important determinant of vitamin D status in our subjects. Strategies to increase vitamin D stores should include vitamin D supplementation or advice on effective sunlight exposure.

Adult↗
PubMed1998

The importance of the renin-angiotensin system in cardiovascular disease.

The renin-angiotensin system is central to the pathophysiology of a number of cardiovascular disorders. Most obviously this is so with renin secreting tumours, but the system is of central importance in other disorders such as scleroderma renal crisis and most cases of malignant hypertension. Activation of the renin-angiotensin system in unilateral renal artery stenosis is pivotal to the development of hypertension and the disturbances in electrolyte and volume balance -- most particularly in the hyponatraemic-hypertensive syndrome. Likewise, stimulation of the renin-angiotensin system is an important contributor, amongst many other systems, to the pathophysiology of cardiac failure. In diabetic nephropathy, the renin-angiotensin system is often suppressed as gauged by circulating levels of renin, yet it appears to make an important contribution to the progressive decline in renal function. Much less clear is the role of the renin-angiotensin system in essential hypertension insofar as it contributes to the level of blood pressure, to the development of left ventricular hypertrophy, and in the evolution of complications such as stroke and myocardial infarction. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors has contributed to our understanding of the role of this system in cardiovascular disease. The advent of selective angiotensin II type-1 receptor blockers will further increase knowledge in this area.

Angiotensin II↗
PubMed1998

Scaffold attachment region-mediated enhancement of retroviral vector expression in primary T cells.

We have studied retroviral transgene expression in primary human lymphocytes. Our data demonstrate that transgene expression is high in activated primary CD4+ T cells but significantly decreased in mitotically quiescent cells. Incorporation of a DNA fragment from the scaffold attachment region (SAR) of the human beta interferon gene into the vector improved transgene expression, particularly in quiescent cells. The SAR element functioned in an orientation-dependent manner and enhanced expression of Moloney murine leukemia virus- and murine embryonic stem cell-based vectors. Clonal analysis of transduced T cells showed that the SAR sequence did not confer position-independent expression on a transgene but rather prevented the decrease of expression when cells became quiescent. The SAR sequence also enhanced transgene expression in T cells generated from retrovirally transduced CD34-enriched hematopoietic progenitor-stem cells in a SCID-hu thymus-liver mouse model. We have used the SAR-containing retroviral vector to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) Rev gene. Compared to a standard retroviral vector, the SAR-containing vector was up to 2 orders of magnitude more efficient in inhibiting replication of the HIV-1 virus in infected CD4+ peripheral blood lymphocyte populations in vitro. This is the first demonstration that SAR elements can be used to improve retroviral vector expression in human primary T cells.

3T3 Cells↗
PubMed1997

Effects of PEEP on respiratory mechanics are tidal volume and frequency dependent.

How the effects of frequency, tidal volume (VT) and PEEP interact to determine the mechanical properties of the respiratory system is unclear. Airway flow and airway and esophageal pressures were measured in ten intubated, anesthetized/paralyzed patients during mechanical ventilation at 10-30 breaths/min and VT of 250-800 ml. From these measurements, Fourier transformation was used to calculate elastance (E) and resistance (R) of the total respiratory system (subscript rs), lungs (subscript L) and chest wall (subscript cw) at 5, 10 and 0 cm PEEP. As PEEP increased from 0-5 cmH2O, all elastances and resistances decreased (P < 0.05). Increasing PEEP to 10 cmH2O decreased EL, Rrs, and RL further (P < 0.05). The changes in Ers, EL, Rrs and RL caused by PEEP were less (P < 0.05) as VT increased, while changes in Rrs, RL and Ers were less (P < 0.05) as frequency increased. VT dependences in Ers and Rrs were enhanced (P < 0.05) at 0 cmH2O PEEP. The ratio of EL to chest wall elastance was not affected by PEEP (P > 0.05), but increased (P < 0.05) with increasing VT at 5 and 10 cmH2O PEEP. We conclude that it is critical to standardize ventilatory parameters when comparing groups of patients or testing clinical intervention efficacy and that the differential effects on the lungs and chest wall must be considered in optimizing the application of PEEP.

Adult↗
PubMed1997

High transdominant RevM10 protein levels are required to inhibit HIV-1 replication in cell lines and primary T cells: implication for gene therapy of AIDS.

Expression of antiviral genes in CD4+ T cells has been proposed as a strategy for gene therapy of AIDS. Over the past years, we and others have developed retroviral vectors encoding the RevM10 protein, a dominant-negative mutant of the HIV-1 Rev trans-activator protein. We could demonstrate gene transfer and inhibition of HIV-1 replication in cultured T cell lines and primary T cells. However, little is known about the levels of the antiviral protein required to achieve a therapeutic effect, particularly in primary cells. In this report, we compare different vector designs with regard to expression of the antiviral gene to develop an optimal vector for clinical applications. Our results demonstrate that intracellular steady-state RevM10 protein levels expressed from the Moloney murine leukemia virus (MoMLV), myeloproliferative sarcoma virus (MPSV) or mouse embryonic stem cell virus (MESV) promoters located in the long terminal repeat (LTR) were uniformly higher than from internal promoters (eg CMV, PGK). Analysis of selected vectors in acutely and chronically HIV-infected cell lines suggested that threshold levels of RevM10 expression are required to achieve inhibition of HIV replication. LTR-driven RevM10 expression also yielded high steady-state protein levels in activated primary T cells resulting in inhibition of HIV replication, and there was no apparent difference between the MoMLV, MPSV and MESV-LTR vectors. However, RevM10 expression was down-regulated in resting primary cells and consequently anti-HIV efficacy was significantly reduced. Taken together, the data suggest that relatively high steady-state levels of RevM10 protein are required to achieve inhibition of HIV replication and that the MPSV- and MESV-derived retroviral vectors show no advantage over the MoMLV-based vectors for expression of anti-HIV genes in human T cells.

CD4-Positive T-Lymphocytes↗