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V Jain

Publications and source records attributed to V Jain.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effect of gestational age on in-vitro responses of pregnant rat aorta.

The hypothesis that the changes in vascular reactivity seen during pregnancy are determined by the gestational age was examined. Experiments were designed to investigate changes in vascular responses with progression of pregnancy. The contractile responses to potassium and phenylephrine (in the presence and absence of N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor) and the relaxant responses to acetylcholine and sodium nitroprusside were measured in isolated aortic rings from pregnant rats at various stages of gestation and from non-pregnant female rats. Potassium-evoked contractile response was higher early in pregnancy and was decreased at term (P < 0.05). The contractile response to phenyllephrine was decreased and the relaxant response to acetylcholine was increased in early pregnancy (P < 0.05). Inhibition of nitric oxide synthase caused an increase in the contractile response to phenylephrine in all the groups, but the attenuation of the response in early pregnancy was maintained (P < 0.05). There was a small decrease in the maximal relaxant response to sodium nitroprusside at term (P < 0.05). It was concluded that the effects of pregnancy on the responses of rat aorta in vitro vary at different stages of gestation. Vascular resistance may be lowered by changes in vascular reactivity in early gestation and by a decrease in the contractile potential of the vasculature during the later stages.

Analysis of Variance↗
PubMed1998

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

Adult↗
PubMed1998

Radioprotective effects of DNA ligands Hoechst-33342 and 33258 in whole body irradiated mice.

Radioprotective effects of bisbenzimidole derived DNA ligands Hoechst-33342 (H-342) and Hoechst-33258 (H-258) have been investigated in whole body irradiated stain-A and Balb/c mice (Co-60 Gamma-ray, absorbed doses of 2.5 to 10 Gy delivered at dose rates of 0.01 to 0.50 Gy/min). Biodistribution of Hoechst dyes (2 or 5 mg/kg, body wt., i.v.) and their effects on cell cycle kinetics in bone marrow were studied by flow cytometry. Protection against radiation-induced chromosomal aberrations, micronuclei formation, alterations in DNA content dispersion, inhibition of erythropoiesis and animal lethality were investigated. Significant amount of DNA bound Hoechst could be observed in liver, intestine, kidney and brain for more than 14 days after its administration, while in the bone marrow cells, a reduction in the bound Hoechst was noticed after 7 days. H-342 significantly reduced the radiation-induced chromosome aberrations mainly due to a decrease in the frequency of acentrics (nearly 30%), while a marginal decrease (10%) in the dicentrics was observed at all the dose rates studied. Both H-342 and H-258 reduced the radiation-induced micronuclei formation in a dose dependent manner (2-10 mg/kg body wt.) and this protective effect was observed up to 6 days after the administration. Neither of the two compounds induced any cytogenetic damage in the bone marrow cells of unirradiated animals nor induced tumours at the doses used here (< 5 mg/kg, body wt. i.v.). Reduction in cytogenetic damage of bone marrow cells led to a faster recovery of erythropoesis as observed by increased PCE/NCE ratio in the peripheral blood erythrocytes of the animals which received Hoechst before irradiation. H-258 (5 mg/kg body wt.) given 18 hr before irradiation reduced radiation-induced animal death (5-9 Gy), while no significant effect was observed at higher doses (10 Gy). However, H-342, which has a higher cell permeability, even at a lower dose (2 mg/kg body wt.) showed significant protection at 10 Gy. The protective effects could be enhanced further, by combining these DNA binding agents with the glucose analogue, 2-deoxy-D-glucose (2-DG) which has been shown earlier to protect bone marrow cells against radiation damage.

Animals↗
PubMed1998

Effects of calcium on phthalocyanine sensitized photohemolysis.

Influence of divalent Ca2+ ions in sulphonated chlorophthalocyanine (ClAlPcS2) induced photohemolysis in rabbit red blood cells has been investigated. Loading of excess Ca2+ to ClAlPcS2 sensitized RBC suspension enhanced hemolysis in a concentration dependent manner. Protein kinase C (PKC) inhibitor chlorpromazine and cation chelator EDTA reduced Ca2+ enhanced photohemolysis. Photohemolysis increased with calcium channel blockers diltiazem and nifidipine. Enhancement in photohemolysis by Ca2+ ions can arise either by its ability to liberate Fe2+ bound to phosphatidylserine or by stimulation of PKC. Inability of calcium channel blockers to prevent Ca2+ influx following photodynamic treatment of red blood cells suggest nonspecific leakage rather than involvement of Ca2+ channels in erythrocytes.

Animals↗
PubMed1997

Differential expression of multidrug resistance gene product, P-glycoprotein, in normal, dysplastic and malignant oral mucosa in India.

Multidrug resistance (MDR) in human cancer is often associated with over-expression of the mdr-1 gene, which encodes a 170-kDa transmembrane protein, termed P-glycoprotein (P-gp). We evaluated the immunoreactivity of P-gp in oral tissues at different stages of tumorigenesis in the Indian population by flow cytometry, using the MRK-16 monoclonal antibody, which recognizes an external epitope of P-gp. The expression of P-gp was studied in human oral normal tissues (12 cases), dysplastic lesions (13 cases), primary untreated squamous-cell carcinomas (12 cases) and recurrent tumors (18 cases). Quantitative flow-cytometric analysis of P-gp expression showed a significant increase in P-gp levels in untreated primary oral tumors (p < 0.01) and in dysplastic lesions (p < 0.05) as compared with normal oral tissues. A marked significant increase in P-gp expression was observed in recurrent oral carcinomas as compared with normal oral tissues (p < 0.001) and dysplastic lesions (p < 0.01). Among recurrent tumors, a significant increase in the level of P-gp was observed in T4-stage tumors as compared with T3-stage tumors (p < 0.01). We conclude that P-gp is differentially expressed during oral tumorigenesis, and may be an indicator of the biological behavior of oral malignancies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effect of chronic treatment with 17beta-estradiol and progesterone on endothelium-dependent and endothelium-independent relaxation in isolated aortic rings from ovariectomized rats.

OBJECTIVE: Our purpose was to study the influence of chronic treatment with sex hormones on endothelium-dependent and endothelium-independent relaxation of rat aortic rings. STUDY DESIGN: Rings of aortas, with and without endothelium, from rats treated with sex hormones or vehicle for 10 days were mounted in organ baths for isometric tension recording. Indomethacin (10(-5) mol/L) and N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), alone or in combination, were used to block cyclooxygenase and nitric oxide synthase, respectively. Mean data of contraction induced by potassium chloride (60 mmol/L), the relaxation by acetylcholine (10(-6) mol/L) in potassium chloride-contracted rings, tension induced by phenylephrine, and the negative logarithm of the concentration of acetylcholine or 3-morpholinosydnonimine producing a 50% relaxation, and area under the curve were calculated. RESULTS: Treatment with 17beta-estradiol (10 microg/rat/day) decreased the tension induced by 60 mmol/L potassium chloride and increased the relaxation by acetylcholine in the rings with endothelium precontracted with potassium chloride. Contraction induced by potassium chloride and relaxation induced by acetylcholine were not influenced by the treatment with progesterone (2 mg/rat/day) or estrogen-progesterone combination. Treatment with estradiol, progesterone, or both hormones had no effect on tension developed in intact rings in response to phenylephrine and did not influence endothelium-dependent relaxation to acetylcholine or endothelium-independent relaxation to 3-morpholinosydnonimine in rings contracted with phenylephrine. The inhibition by N(omega)-nitro-L-arginine methyl ester of endothelium-dependent relaxation by acetylcholine was attenuated after the treatment with the sex hormones. CONCLUSIONS: Chronic treatment with sex hormones did not increase production or release of endothelium-derived relaxing factor and did not change the sensitivity of rat aortic smooth muscle to nitric oxide. The treatment slightly counteracted the inhibition of endothelium-dependent relaxation produced by nitric oxide synthase blocker.

Acetylcholine↗
PubMed1997

The relaxation responses to corticotropin-releasing factor in rat aorta are endothelium dependent and gestationally regulated.

OBJECTIVE: Our purpose was to examine the hypothesis that the relaxant response to corticotropin-releasing factor is endothelium dependent and changes during pregnancy. STUDY DESIGN: Relaxant responses to cumulative concentrations of corticotropin-releasing hormone were measured in rings of thoracic aorta, precontracted with phenylephrine, from pregnant and nonpregnant female rats. Each group consisted of 5 to 10 rats. RESULTS: The relaxation induced by corticotropin-releasing factor in aortic rings from nonpregnant rats decreased after deendothelization and treatment with N omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor), LY-83,583 (a guanylate cyclase inhibitor), or alpha-helical corticotropin-releasing factor 9-41 (a corticotropin-releasing factor antagonist). The percent decrease in relaxation at 1 nmol/L of corticotropin-releasing factor was about 88% with deendothelization, 100% with N omega-nitro-L-arginine methyl ester, 76% with LY-83,583, and 100% with alpha-helical corticotropin-releasing factor 9-41. The responses to corticotropin-releasing factor in intact rings from rats in early pregnancy were not significantly different from those in the nonpregnant female rats, but the responses were decreased during the later stages of gestation (percent decrease in relaxation at 1 nmol/L of corticotropin-releasing factor about 71% at day 20 and 98% at term). The relaxation induced by corticotropin-releasing factor during pregnancy was also inhibited by deendothelization, N omega-nitro-L-arginine methyl ester, or LY-83,583. CONCLUSIONS: The relaxant response to corticotropin-releasing factor in the rat aorta is endothelium dependent and is mediated by the nitric oxide-cyclic guanosine monophosphate pathway. The receptor involved in this effect is alpha-helical corticotropin-releasing factor 9-41 sensitive. This inhibitory response is unchanged during early pregnancy but reduced toward the end of gestation.

Animals↗
PubMed1997

Cellular accumulation and biological activity of hematoporphyrin derivative(L) in comparison with photofrin II.

Hematoporphyrin derivative, a drug used in the photodynamic therapy of solid tumours was synthesized in the laboratory and was called Hpd(L). Physico-chemical and biological properties of this drug have been compared with Photofrin II, the commercially available drug. Both Hpd(L) and Photofrin II possess similar properties qualitatively. Quantitatively, Hpd(L) was half as active as Photofrin II in its efficacy in causing photodynamic cytotoxicity or in the optical densities at the absorption peaks. These differences could be due to the differences in the compositions. Hpd(L) is a non-purified complex mixture of a number of porphyrin derivatives whereas Photofrin II is a relatively purer compound consisting of di- and tri-hematoporphyrins linked through ether or ester bonds. In vitro cellular uptake and retention of these drugs has been found to be a passive process not involving energy expenditure. pH and temperature of the incubation media have been found to profoundly influence these processes, while a complex relation seems to exist between physiological state of a cell and accumulation of these photosensitizers.

Animals↗
PubMed1997

Effects of photofrin II and light on cellular adenine nucleotides and their modulation.

Effects of photofrin II (PII) and light on the intra cellular nucleotide levels have been investigated using BHK-21 cell line. Results indicate that lower concentrations of photofrin II in dark increases ATP levels in a non linear manner, however, there has been no change in energy charge and levels of other nucleotides. Photoirradiation of PII-treated cells leads to a significant reduction in ATP levels and energy charge along with an increase in ATP breakdown products like ADP and AMP. The phosphorylation potential [ATP]/[ADP][Pi] also reduces upon photoirradiation of PII treated cells. Incubation conditions like pH of the medium and temperature modulate the cellular responses to a great extent.

Adenine Nucleotides↗
PubMed1997

Prevention of radiation induced taste aversion in rats.

Diltiazem, a calcium channel blocker, and a cardiovascular therapeutic agent offers significant protection to mice against lethal dose of ionizing radiation. Considering the potential efficacy of diltiazem as a radioprotector for human use, it was deemed necessary to investigate its influence on radiation-induced behavioural changes like nausea, vomiting, learning, memory and performance. In the present studies, conditioned taste aversion (CTA) test based on consumption of saccharin solution, was used as a marker of behavioural changes. Significant CTA (97 +/- 2%) was observed in rats irradiated with Co-60 gamma rays (absorbed dose 1 Gy). Administration of diltiazem at doses greater than 10 mg/kg, body wt, evoked CTA in a dose-dependent manner and that was found to be further aggravated on irradiation. At a lower dose of 5 mg/kg, body wt, diltiazem did not evoke CTA and protected against radiation induced aversion significantly (62 +/- 3%). The results suggest that diltiazem at concentrations lower than 10 mg/kg, body wt, in rats may be useful in preventing radiation induced behavioural changes. This observation could be of particular significance in clinical radiotherapy where radiation induced nausea and vomiting are of great concern.

Animals↗
PubMed1997

Studies on the modulation of DNA damage. 1: A simple kinetic model for radioprotection of DNA in aqueous solution.

A simple kinetic model, based on the assumption that direct and indirect interactions of ionising radiations with DNA lead to formation of DNA-radicals which are precursors of single strand break (ssb) and double strand break (dsb) is presented. Considering accessibility of OH attack on DNA and assuming homogenous kinetics, the model has been validated by using experimental data on radiation-induced strand break formation in presence of methanol (MeOH) and glutathione (GSH). Fitting the D37 values for ssb in aqueous solution of pBR322 DNA in the presence of the predominantly A-T minor groove-ligand Hoechst 33258, the value of the rate constant of OH scavenging by DNA-bound Hoechst was estimated by Martin and his group as 2.7 x 10(11) dm3 mol-1 s-1 (Martin, R.F. and Denison, L. (1992), Int. J. Radiat. Oncol. Biol. Phys., 23, 578-584). Using aqueous solution of calf thymus DNA in the presence of Hoechst this rate constant has been determined by pulse radiolysis as 1.1 x 10(9) dm3 mol-1 s-1. The yield of strand breaks has also been measured by low angle laser light scattering. Using the experimentally measured value of the rate constant of OH scavenging by DNA-bound Hoechst in the model, calculations show that OH scavenging alone could not explain the overall protection provided by Hoechst; there should be quenching of DNA-radicals by Hoechst. Fitting the yield of radiation-induced ssb (G(ssb)) obtained for CT DNA and pBR322 DNA, the rate constant of this DNA-radical quenching has been calculated as 10(6) dm3 mol-1 s-1, which agrees with pulse radiolytic data. Using these rate constant values, calculations show that the protection against radiation-induced dsb formation provided by the combination of Hoechst with GSH is more than that by the combination of MeOH with GSH.

DNA Damage↗
PubMed1997

2-Deoxy-D-glucose induced modulation of DNA damage repair, survival, mutagenesis and recombinogenesis in 8-MOP+UVA treated yeast.

Cellular and genomic effects of post-treatment repair modulation by 2-deoxy-D-glucose (2-DG) and yeast extract were studied in 8-MOP + UVA treated cells of Saccharomyces cerevisiae. The type of lesions and their repair in phosphate buffer glucose (PBG) differed with UVA dose. At low UVA dose (1.4 kJ/m2), lesions were sublethal and mutagenic and did not repair by recombinogensis. The fraction of potentially lethal lesions and lesions repaired by recombinogenesis increased with UVA dose. Cellular repair in PBG was largely error-free and was inhibited by 2-DG. Yeast extract enhanced cellular repair and also recombinogensis; 2-DG in presence of yeast extract promoted error-prone repair. Pulsed-field gel electrophoresed chromosomal DNA bands did not show observable alterations immediately after 8-MOP + UVA treatment. On post-treatment incubation in PBG, the intensity ratio (rho n), of each band altered in a biphasic manner showing decrease first, followed by either increase or no change upto 24 hr depending upon UVA exposure dose. Presence of 2-DG in PBG inhibited decrease in rho n in a concentration dependent manner. Yeast extract reduced the time of first phase of DNA repair. 2-DG and yeast extract together reduced the time of first phase of repair and also inhibited the subsequent increase in rho n, which was observed in the case of yeast extract in PBG. It is proposed that (i) 2-DG in PBG inhibits excision of DNA damage and error-free repair; (ii) yeast extract stimulates the error-prone repair associated with cell cycle and recombinogenesis; (iii) 2-DG in presence of yeast extract allows excision of damage but inhibits build up through recombinogenesis inducing instead, cell cycle associated error-prone repair. A simple schematic model has been proposed to explain these events.

DNA Damage↗
PubMed1996

A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma.

IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)-containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48-hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bolus regimen, the maximum tolerated dose (MTD) was 16 mg/m2/8 d and the dose-limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m2/8 d. Using the CI regimen, the MTD was defined by VLS at 19.2 mg/m2/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (CR; > 40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (Cmax) of 1,209 +/- 430 ng/mL, with a median T1/2 beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the CI regimen at MTD, the mean Cmax was 963 +/- 473 ng/mL, with a median T1/2 beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs.

Adult↗
PubMed1996

Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas.

PURPOSE: Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells. METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage.

Adult↗