Biomedical subjects

S Srivastava

Publications and source records attributed to S Srivastava.

At least 127 records · Page 7Linked to original sources

PubMed2000

Systemic lipopolysaccharide and interleukin-1beta activate the interleukin 6: STAT intracellular signaling pathway in neurons of mouse trigeminal ganglion.

We have studied the activation of signal transducers and activators of transcription (STATs) in trigeminal ganglion after intraperitoneal injection of lipopolysaccharide (LPS) and Interleukin-1beta (IL-1beta). Using electrophoretic mobility shift assays we have shown that STAT1 and STAT3 are activated within 1 to 2 h. of injection of either LPS or IL-1beta. Eight hours after LPS injection the DNA binding activity of these complexes is still elevated while induction by IL-1beta returns to baseline levels within 4 h. By immunohistochemistry, using an antibody specific for the tyrosine phosphorylated, activated form of STAT-1, we show that this induction occurs in sensory neurons. IL-6 may be important in this cascade since induction of STATs by IL-1beta is blocked in Interleukin-6 knock out mice.

Animals↗

PubMed2000

p53 regulates the expression of the tumor suppressor gene maspin.

Maspin has been shown to inhibit tumor cell invasion and metastasis in breast tumor cells. Maspin expression was detected in normal breast and prostate epithelial cells, whereas tumor cells exhibited reduced or no expression. However, the regulatory mechanism of maspin expression remains unknown. We report here a rapid and robust induction of maspin expression in prostate cancer cells (LNCaP, DU145, and PC3) and breast tumor cells (MCF7) following wild type p53 expression from an adenovirus p53 expression vector (AdWTp53). p53 activates the maspin promoter by binding directly to the p53 consensus-binding site present in the maspin promoter. DNA-damaging agents and cytotoxic drugs induced endogenous maspin expression in cells containing the wild type p53. Maspin expression was refractory to the DNA-damaging agents in cells containing mutant p53. These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), define a new category of molecular targets of p53 that have the potential to negatively regulate tumor invasion and/or metastasis.

Adenoviridae↗

PubMed2000

Percutaneous transluminal angioplasty of the aorta in children with nonspecific aortoarteritis: acute and follow-up results with special emphasis on left ventricular function.

Nonspecific aortoarteritis (NSAA) is a chronic disease of unknown etiology and may result in stenosing and obstructive lesions of the aorta. Transluminal balloon angioplasty was carried out in 17 children, 4-12 years of age (mean 8.9 +/- 2.7 years) with symptomatic stenosis of thoracic or abdominal aorta due to NSAA. Hypertension was present in 15 children, and 11 had significant left ventricular dysfunction. All children had a clinically inactive disease. The stenosis was in descending thoracic aorta in 10, thoracoabdominal in 3 and only abdominal in 4. Symptomatic improvement with relief of stenosis was seen in 16 of 17 children, although in 3, the results were suboptimal. The peak systolic gradient fell from 70.9 +/- 19.3 mmHg to 32.0 +/- 19.2 mmHg immediately after dilation (P < 0.0001). Angiographically measured luminal diameter stenosis also fell from 82.5 +/- 7.7% to 19.4 +/- 11.8% (P < 0.0001). Dissection flap was seen in 13 cases. It was large in cases with long, diffuse and eccentric stenosis of the thoracic or thoracoabdominal aorta. On follow-up (available for 14 of 16 cases for a period of 2-87 months mean 20.7 +/- 21.5 months, median 15.5 months) two patients developed restenosis. Left ventricular function improved in all 8 children that had sustained benefit of angioplasty. Blood pressure normalized in 9 of 13 children and the drug requirements fell in 4 others. Further remodeling of the lesion with decrease in gradients and luminal stenosis was observed in 11 children that have been restudied. Balloon angioplasty of aorta in children with NSAA is a feasible and safe procedure. Small intimal flap is seen in the majority, extensive dissection is more likely in the long diffuse lesions in descending thoracic aorta. Hypertension and left ventricular dysfunction improve after relief of obstruction.

Angioplasty, Balloon↗

PubMed2000

A simple microbiological assay for the stereospecific differentiation of alpha and beta isomers of arteether.

A new rapid bioassay has been developed which can precisely differentiate between stereospecific alpha and beta isomers of the antimalarial drug arteether. This method was developed through the disc diffusion bioactivity tests wherein semisynthetically produced alpha arteether was able to inhibit the growth of E. coli strains which are defective in DNA gyrase enzyme. The wild type E. coli with intact DNA gyrase did not show this sensitivity to alpha arteether. The beta isomer of arteether was, however, ineffective against both the mutant and wild type strains. Direct experimental proof of gyrase involvement was obtained through mobilization of gyr genes by transformation of E. coli gyr- mutant strains with wild type gyrA clone pMK90 (carried on the thermo-inducible lambda Col E1 vector). This resulted in alpha arteether resistant and nalidixic acid sensitive phenotype clearly demonstrating the use of gyrA mutant strains in differentiating alpha and beta isomers of arteether by this simple bioassay.

Antimalarials↗

PubMed2000

The hamster heart: a paradox in itself.

Perfusion of all mammalian heart muscle except hamster with Ca(2+)-free Tyrode and thereafter reperfusion with normal Tyrode causes irreversible damage, the calcium paradox. Our study aims at deciphering the role of creatine kinase, high energy phosphates and Ca(2+)influx in the genesis of myocardial injury in the rat and comparing it with the hamster. Isolated hearts from hamster and rats were perfused in the Langendorff mode at 37 degrees C for 30 min with normal Tyrode, for 15 min with Ca(2+)-free Tyrode and thereafter for 30 min of reperfusion with normal Tyrode. The 'high energy phosphate compound' levels were monitored by(31)P-NMR, creatine kinase (CK) release was measured in the perfusate.(45)Ca influx was estimated in the papillary muscle. We observed that in the rat heart: (a) high energy phosphate levels declined significantly within 1 min of Ca(2+)reperfusion; (b) a massive release of CK occurred upon Ca(2+)reperfusion; (c) there was a significant increase of Ca(2+)influx. In the hamster heart, there was preservation of high energy phosphates, CK release was prevented completely and no rise in(45)Ca influx was observed upon Ca(2+)reperfusion. These results suggest that the hamster heart has a remarkable capacity for Ca(2+)homeostasis which protects the heart from Ca(2+)overload.

Adenosine Diphosphate↗

PubMed2000

The hamster heart is resistant to calcium paradox.

Reintroduction of Ca(2+)or modification of internal Ca(2+)stores by caffeine results in widespread irreversible injury. The adult golden hamster, however, is immune to such insult and the present report investigates the phenomenon. Isolated Langendorff perfused hamster and rat heart were subjected to 15 min Ca(2+)-free perfusion followed by 30 min of Ca(2+)perfusion at 37 degrees C. Caffeine was introduced during Ca(2+)-free perfusion in a number of experiments. Papillary muscles were processed for the ultra-structural study. The hamster heart did not exhibit the calcium paradox state whereas rat heart did. Hamster heart treated with caffeine either throughout or 5 min after starting Ca(2+)-free perfusion showed 70%+/-8 or 65%+/-8. 42 recovery, respectively, when Ca(2+)reperfusion was performed. Ultrastructure of muscle from both groups showed relaxed myocytes with slight disorientation of the sarcomere register. This disorientation was not seen in hamster hearts undergoing the conventional calcium paradox protocol. The hamster cardiac muscle is remarkably tolerant to [Ca(2+)]()i loading either induced by Ca(2+)reperfusion or caffeine-induced sarcoplasmic reticulum Ca(2+)release. Structural and functional characterization of Ca(2+)depletion and repletion in the hamster heart have been discussed.

Animals↗

PubMed2000

Prognostic factors for hematologic cancers.

This article reviews the molecular biology of hematologic cancers and the current understanding of prognostic factors for these cancers. Specific molecular biomarkers that have potential as prognostic factors for various hematologic cancers are discussed. Quantitative and statistical methods of evaluating the usefulness of prognostic factors are presented.

Biomarkers, Tumor↗

PubMed2000

Endovascular grafting in patients with short proximal necks: an analysis of short-term results.

OBJECTIVES: To evaluate the safety of endovascular graft placement in patients with short proximal aneurysm necks, and assess factors contributing to endoleak formation. METHODS: 55 patients were enrolled over a two year period from five centers following the placement of a Talent endograft with a suprarenal stent. Preoperative and 30-day post-implant CT scans were retrospectively analyzed in a blinded fashion by two physicians. Aortic measurements were obtained, the amount of thrombus was subjectively graded, and any extravasation of contrast into the aneurysm sac defined an endoleak. The data were analyzed using a t-test. Analyses compared patients with proximal necks<10mm (SN), n=13) to those with longer necks (LN, n=42), and then contrasted patients with endoleaks (n=12), to those without (n=43). RESULTS: Endoleak rates were identical in the SN and LN groups (21 and 23%). Maximal aneurysm size was larger in the SN group (63 vs 56 mm, P<0.05). Endoleaks were more frequently noted in larger aneurysms (P<0.05), but not related to SN (P=0.6). There was no correlation between endoleaks and the amount of thrombus, aneurysm length, proximal neck diameter or other morphologic characteristics. One of 12 endoleaks resulted from a problem with proximal fixation, nine were due to perfusing vessels, and two were undefined. The proximal neck diameter increased (0.9 mm) over the 30 days (P<0.005). CONCLUSIONS: Short-term proximal fixation can be achieved in proximal necks measuring less than 10mm. The narrow margin of acceptable seal mandates careful follow-up. Larger aneurysms were associated with an increased incidence of endoleaks. SNs were associated with larger aneurysms, but not with an increased incidence of endoleaks. Proximal neck dilation was noted, but likely relates to the placement of an oversized endograft during this brief period of observation.

Aortic Aneurysm, Abdominal↗

PubMed2000

Syntheses and biological evaluation of 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones as antioxidant and hypolipidemic agents.

A new series of compounds belonging to 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones (4-12a-e) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds, namely 5b, 5d, 6e, 8a, 8b, 10b and 11a, exhibit better antioxidant activity than probucol. Two compounds, 5d and 10b, have been evaluated in detail for antioxidant and hypolipidemic activities and show comparable activity profile to that of probucol and guggulipid. From the present study it may be postulated that the mechanism of action of these compounds could be through activation of lecithin cholesterol acyltransferase (LCAT), liver lipolytic activity, increased faecal bile acid secretion and inhibition of hepatic cholesterol biosynthesis.

Alkenes↗

PubMed2000

Mechanical versus chemical thrombolysis: an in vitro differentiation of thrombolytic mechanisms.

PURPOSE: To assess differing mechanisms of thrombolysis determining time to reperfusion, completeness of thrombus dissolution, and embolic potential. MATERIALS AND METHODS: An in vitro perfusion model designed to mimic arterial flow conditions was created. Bifurcated limbs allowed continuous flow through one channel and the placement of radiolabeled (iodine-125) thrombus housed in a 5-cm segment of polytetrafluoroethylene graft in the other. The three experimental groups consisted of a standard continuous urokinase infusion, a pulsed pressurized injection of saline, and a similar injection with urokinase. A continuous infusion of 5% dextrose served as a control group. Time to reflow (as assessed with ultrasonic flow monitoring), completeness of thrombus dissolution (I-125 liberated into solution), and the number and size of embolic particles produced (detected by a series of graduated filter sizes) were analyzed. RESULTS: Time to reflow was significantly faster for both groups when pressurized injections were used (P < .001). There was no reflow in the control arm at 90 minutes. Completeness of thrombus dissolution was higher when a continuous infusion of urokinase was used in comparison to either of the power injection groups or the control (P < .05). The amount of embolic debris produced was significantly lower with a continuous infusion of urokinase compared with either of the power lysis groups (P < .05), but significantly greater than the control arm (P < .001). The size of the embolic particles in the power pulsed lysis groups was significantly decreased by the addition of urokinase (P < .05). CONCLUSIONS: Reflow is more rapidly established by the use of mechanical means. However, a less complete dissolution of thrombus in conjunction with a greater amount of embolic debris is achieved with this approach. The size of the embolic particles produced is reduced by the addition of a thrombolytic agent.

Blood Vessel Prosthesis↗

PubMed2000