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Biomedical subjects

V Jain

Publications and source records attributed to V Jain.

At least 73 records · Page 4Linked to original sources
PubMed2000

Retroperitoneal cold abscess with tuberculosis of sacro-iliac joint and pubic bone: a case report of unusual presentation of osteo-articular tuberculosis.

Tuberculosis involving sacro-iliac joint and pubic bone presenting with massive retroperitoneal abscess is a rare entity. A 29-year-old female presented with history of discharging sinus in the sacrococcygeal region of 2 months duration. Plain x-ray revealed osteolytic lesion in right pubic bone and left sacro-iliac joint. Computed tomography scan revealed massive pus collection in the retroperitoneal region. Pus was drained extraperitoneally. Biopsy of the scraping of the abscess wall showed granulation tissue with foreign body type of giant cell. On follow-up the patient was doing well.

Abdominal Abscess↗
PubMed1999

Hematoporphyrin derivatives potentiate the radiosensitizing effects of 2-deoxy-D-glucose in cancer cells.

PURPOSE: Two deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, has been shown to differentially inhibit the repair of radiation damage in cancer cells by reducing the flow of metabolic energy. Since hematoporphyrin derivatives (Hpd) inhibit certain enzymes of the respiratory metabolism, resulting in an increase in the glucose usage and glycolysis, Hpd could possibly enhance the energy-linked radiosensitizing effects of 2-DG in cancer cells. The purpose of the present work was to verify this suggestion. METHODS AND MATERIALS: Two human tumor cell lines (cerebral glioma, BMG-1 and squamous cell carcinoma, 4197) and a murine tumor cell line (Ehrlich ascites tumor [EAT], F-15) in vitro were investigated. A commercially available preparation of Hpd, Photosan-3 (PS-3) was used in the present studies. Cells incubated with 0-10 microg/ml PS-3 for 0-24 h before irradiation were exposed to 2.5 Gy of Co-60 gamma rays and maintained under liquid holding conditions for 1-4 h to facilitate repair. 2-DG (0-5 mM) added at the time of irradiation was present during the liquid holding. Radiation-induced cytogenetic damage (micronuclei formation) and cell death (macrocolony assay) were analyzed as parameters of radiation response. Effects of these radiosensitizers on glucose usage and glycolysis were also studied by measuring the glucose consumption and lactate production using enzymatic assays. RESULTS: The glucose consumption and lactate production of BMG-1 cells (0.83 and 1.43 pmole/cell/h) were twofold higher than in the 4197 cells (0.38 and 0.63 pmole/cell/h). Presence of PS-3 (10 microg/ml) enhanced the rate of glycolysis (glucose consumption and lactate production) in these cells by 35% to 65%, which was reduced by 20% to 40% in the presence of 5 mM 2-DG. In exponentially growing BMG-1 and EAT cells, presence of 2-DG (5 mM; equimolar with glucose) for 4 hours after irradiation increased the radiation-induced micronuclei formation and cell death by nearly 40%, whereas no significant effects could be observed in 4197 cells. In EAT cells, radiation was also observed to induce apoptotic death, which was significantly increased in the presence of the combination (PS-3 + 2-DG). The combination (PS-3 + 2-DG) enhanced the radiation damage in all three cell systems by 60-100%. Furthermore, the radiosensitizing effects of the combination (PS-3 + 2-DG) were higher at pH 6.7 as compared to pH 7. 4. In the plateau phase, presence of 2-DG alone did not significantly influence the radiation response of either BMG-1 or of 4197 cells, whereas in combination with PS-3, 2-DG enhanced the radiation damage in both these cell lines by 40% to 50%. Furthermore, in BMG-1 cells, the effects of 2-DG were observed to be reversible to a very great extent, while that of the combination were mostly irreversible. CONCLUSION: The hematoporphyrin derivative PS-3 enhances the radiosensitizing effects of 2-DG in cancer cells, possibly by further reducing the energy supply leading to an irreversible inhibition of DNA repair, and increased cytogenetic damage and cell death. Since both these compounds have been used in clinical practice, further studies to investigate their use in improving radiotherapy of tumors are warranted.

Animals↗
PubMed1999

Diltiazem enhances tumor blood flow: MRI study in a murine tumor.

PURPOSE: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. METHODS AND MATERIALS: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. RESULTS: The diltiazem+ radiation treated group showed significant tumor regression (in approximately/= 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. CONCLUSION: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor oxygenation status.

Animals↗
PubMed1999

Effect of nitric oxide and carbon monoxide on uterine contractility during human and rat pregnancy.

OBJECTIVE: We sought to study the effects of authentic nitric oxide and carbon monoxide on the contractile activity of pregnant human and rat myometrium. STUDY DESIGN: Strips were prepared from uterine biopsy specimens of 10 pregnant, nonlaboring women at term gestation undergoing cesarean delivery. In addition, rings were prepared from the uteri of pregnant rats at midterm (day 14) and at term (day 22) gestation (n = 10-12). The tissues were mounted in organ chambers filled with Krebs-Henseleit solution continuously aerated with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. The effects of nitric oxide and carbon monoxide gases on spontaneous contractile activity were studied. Responses to hemin (hemoxygenase substrate), which produces endogenous carbon monoxide, were also examined. Responses to nitric oxide and carbon monoxide were also studied in aortic and tail artery rings from pregnant rats after contraction with phenylephrine. RESULTS: Nitric oxide significantly inhibited contractility of human myometrium at term (area under the concentration-response curve, 145.36 +/- 30.02 vs 40.56 +/- 22.81 in controls; P <.05) and rat myometrium at midterm gestation (264.23 +/- 47.86 vs 121.82 +/- 23.50; P <.05) but not at term. No statistically significant inhibition was induced in human or rat myometrium by carbon monoxide, whereas hemin significantly attenuated contractility in human myometrium at term and in rat myometrium at midterm gestation (P <. 05). Nitric oxide, carbon monoxide, and hemin relaxed aortic and tail artery rings. CONCLUSIONS: Authentic nitric oxide inhibits rat uterine contractile activity at midterm gestation but not at term. However, nitric oxide inhibits human myometrium activity at term. Authentic carbon monoxide does not appear to modulate uterine contractility, whereas hemin may have some inhibitory properties.

Adult↗
PubMed1999

Development and validation of a quantitative polymerase chain reaction assay to evaluate minimal residual disease for T-cell acute lymphoblastic leukemia and follicular lymphoma.

The presence of occult disease in cancer patients after therapy is one of the major problems faced by oncologists. For example, although 95% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients have a complete therapeutic response to multiagent chemotherapy, half will relapse, indicating that they must have harbored low levels of residual cancer cells at the end of therapy. Sensitive detection assays promise to help identify those patients that carry this minimal residual disease (MRD) and are at risk of relapse. We have developed and validated a quantitative polymerase chain reaction (PCR) assay targeting tumor-specific chromosomal rearrangements, including del(1) involving the tal-1 locus in pediatric T-ALL and t(14;18) involving the bcl-2 locus in follicular lymphoma. This quantitative PCR assay utilizes a synthetic internal calibration standard (ICS) that contains priming sequences identical to those found flanking the chromosomal rearrangement breakpoints. Using this ICS-PCR method, the limits of detection were 5 tumor cells at ratios of 1 tumor cell in 10(5) normal cells and a linear range up to 100% tumor cells. This ICS-PCR method has also performed well in terms of precision and accuracy as indicated by low coefficients of variation, minimal random, proportional, and constant errors, and good clinical sensitivity and specificity characteristics. This technique will allow for the evaluation of parameters such as the rate of therapeutic response and the levels of MRD as predictors of patient outcome.

Base Sequence↗
PubMed1999

CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma.

BACKGROUND: Oligodeoxynucleotides (ODNs) containing the dinucleotide CpG in a specific sequence context (CpG-ODNs) have the ability to prevent the development of eosinophilic airway inflammation and bronchial hyperreactivity in a murine model of asthma. We have previously demonstrated that CpG-ODNs stimulate expression of the T(H1)-inducing cytokines IFN-gamma and IL-12 in a murine model of asthma and that this stimulation is associated with the protection against asthmatic inflammation. OBJECTIVE: The purpose of this study was to examine whether the protection conferred by CpG-ODNs in a schistosome egg-egg antigen murine model of asthma is dependent on the induction of IFN-gamma, IL-12, or both. METHODS: C57BL/6 mice were sensitized to schistosome eggs in the presence or absence of CpG-ODNs or control ODNs and then stimulated with soluble egg antigen in the airway. The protection offered by CpG-ODNs in these mice was compared with the protection induced by CpG-ODNs in IL-12 and IFN-gamma knockout mice and in mice treated with anticytokine blocking antibodies. Double-knockout mice (IL-12/IFN-gamma) were also generated and used in these studies. Determinations included airway eosinophilic inflammation and bronchial hyperreactivity to inhaled methacholine. RESULTS: We found that CpG-ODNs confer protection against both airway eosinophilia and bronchial hyperreactivity in the absence of IFN-gamma or IL-12 or in the presence of both cytokines together. However, in the absence of either IL-12 or IFN-gamma, mice require 10 times as much CpG-ODNs to be protected against the induction of airway eosinophilia. The T(H2) cytokines IL-4 and IL-5 were reduced in all of the CpG-treated mice, although less in the absence of IL-12 and IFN-gamma. CONCLUSION: These data indicate that CpG-ODNs prevent the generation of T(H2)-like immune responses by multiple mechanisms, which involve, but do not require, IL-12 and IFN-gamma. A direct suppressive effect of CpG-ODNs on T(H2) responses is suggested by their reduction in IFN-gamma and IL-12 knockout mice.

Animals↗
PubMed1999

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma.

BACKGROUND: Rituximab is a chimeric monoclonal antibody directed against the B-cell CD20 antigen which has been utilized for therapy of B-cell non-Hodgkin's lymphoma (NHL). A previous clinical trial demonstrated that treatment with four weekly doses of 375 mg/m2 of Rituximab in patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma was well tolerated and had significant clinical activity. PATIENTS AND METHODS: To assess the safety and efficacy of Rituximab treatment, an open-label, single-arm, multi-center, phase II study of eight consecutive weekly infusions of 375 mg/m2 Rituximab in patients with low-grade or follicular B-cell NHL who had relapsed or had failed primary therapy was conducted. Thirty-seven patients with a median age of 55 years were treated. RESULTS: Grade 1 or 2 adverse events were the majority of reported toxicities and occurred most frequently with the first infusion, decreasing with subsequent infusions. No patients developed a host antibody response (HACA) to Rituximab. The mean serum immunoglobulin levels for IgG, IgA, and IgM stayed within the normal range throughout the study. The majority of patients who were bcl-2 positive at baseline in peripheral blood became bcl-2 negative during treatment and remained negative at the time of B-cell recovery. In the 37 intent-to-treat patients, 5 (14%) had a complete response and 16 (43%) had a partial response for an overall response rate of 57%. Of 35 evaluable patients, 21 (60%) responded to treatment (14% CR and 46% PR). In responders, the median time to progression (TTP) and the median response duration have not been reached after 19.4+ months and 13.4+ months, respectively. CONCLUSIONS: The safety profile and efficacy achieved in this pilot study of extended treatment with Rituximab compares favorably with those seen with four weekly doses. Further studies are warranted to investigate whether this or other extended Rituximab schedules will result in increased efficacy in all or in certain subgroups of patients with low-grade or follicular NHL.

Adult↗
PubMed1999

Follicular carcinoma in a functioning struma ovarii.

We describe a case of follicular carcinoma in a functioning struma ovarii, which presented as an ovarian mass in a patient who had undergone a near-total thyroidectomy for a benign lesion. She underwent bilateral salpingo-oophorectomy and received radiotherapy and L-thyroxine treatment with no evidence of metastases in 4 years follow-up.

Carcinoma, Papillary, Follicular↗
PubMed1999

Role of intrapartum antibiotics in prevention of vertical transmission of neonatal sepsis.

The present study evaluates the role of prophylactic intrapartum antibiotics in the prevention of neonatal sepsis. Labour and delivery characteristics of 1478 women delivering at the Nehru Hospital, PGIMER, Chandigarh were recorded. Intrapartum antibiotics (ampicillin, with or without gentamycin) were given to 69 per cent women. The neonatal sepsis rate was 1.56 per cent. This was not significantly lower in the women who received intrapartum antibiotics (1.47 vs 1.75%). Though there was a lowering of neonatal sepsis rate with intrapartum antibiotic administration when the duration of labour was more than 12 h (1.67 vs 3.09%), duration of ruptured membranes was more than 6 h (1.93 vs 3.81%) and number of pelvic examination was 3 or more (1.63 vs 4.54%), it was not statistically significant. It was concluded that intrapartum antibiotics as per the existing protocol did not prevent neonatal sepsis.

Adult↗
PubMed1999

Optimization of tumour radiotherapy: Part V--Radiosensitization by 2-deoxy-D-glucose and DNA ligand Hoechst-33342 in a murine tumour.

Radiosensitizing effects of combination of a minor groove DNA ligand, Hoechst-33342, with the glucose analogue and inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG) have been investigated in Ehrlich ascites tumour (EAT) bearing mice following focal irradiation of the tumour with 60Co gamma-rays. Treatment-induced tumour growth delay and tumour free animal survival were evaluated as parameters of radiation response. Focal irradiation of the tumour with a single fraction of 10 Gy induced a moderate delay in tumour growth but did not lead to complete regression in any of the tumours. Intravenous administration of H-342 1 hr before irradiation enhanced radiation-induced growth delay in a dose dependent manner. Complete regression of the tumour was observed only at a dose of 10 mg/kg body wt, leading to a cure (tumour free survival for more than 100 days) rate of 55%. Administration of 2-DG (2 g/kg body wt; i.v.), immediately before irradiation significantly enhanced radiation-induced growth delay and resulted in a cure rate of 45%. In combination with this dose of 2-DG (2 g/kg body wt), H-342 at a lower dose (5 mg/kg body wt) significantly enhanced the cure rate to 66%. H-342 or 2-DG given alone or in combination at the doses investigated here did not show any significant effects on the unirradiated tumour.

Animals↗
PubMed1999

Endothelium-dependent and -independent mechanisms of vasorelaxation by corticotropin-releasing factor in pregnant rat uterine artery.

Corticotropin-releasing factor (CRF), a potent vasorelaxant, is increased tremendously during human pregnancy. Placenta is the main source for this increase. CRF is thought to be important in modulating vascular resistance and uteroplacental blood flow during pregnancy. Here we investigated pathways mediating a vasorelaxant effect of CRF in the uterine artery. Two-millimeter segments of uterine artery (o.d. 300-400 microm) from day 18 pregnant rats were mounted in a small vessel myograph and precontracted with norepinephrine, and relaxation responses to CRF were studied. CRF relaxed the uterine artery in a concentration-dependent manner. Relaxation of uterine artery by CRF was abolished completely by alpha-helical CRF 9-41 (CRF antagonist, 1 micromol) and partially by removal of endothelium, Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor, 0.1 mmol), 6-anilino-5,8-quinolinedione (guanylate cyclase inhibitor, 10 micromol), or thiopental/miconazole (cytochrome P-450 inhibitors, 0.3 mmol/30 micromol), but remained unaffected by indomethacin (cyclo-oxygenase inhibitor, 10 micromol). Relaxation was also inhibited when depolarizing solution (K+, 120 mmol) was used for precontraction. In deendothelized preparations, relaxation was not inhibited by 9-tetrahydro-2-furanyl-9H-purin-6-amine (adenylate cyclase inhibitor, 0.2 mmol), glibenclamide (adenosine triphosphate-dependent K+ channel blocker, 10 micromol), tetrabutyl ammonium (nonspecific K+ channel blocker, 1 mmol), nitrendipine (voltage-gated Ca++ channel blocker, 1 micromol), or when vessels were precontracted with depolarizing solution. CRF causes vasorelaxation by receptor-operated, endothelium-dependent and -independent pathways. The endothelium-dependent relaxation is mediated by nitric oxide-cyclic guanosine monophosphate pathway and endothelium-derived hyperpolarizing factor but not prostacyclin. However, cyclic adenosine monophosphate, K+ channels, or Ca++ channels are not involved in endothelium-independent vasorelaxation by CRF.

Animals↗
PubMed1998

In vivo effects of corticotropin-releasing factor in pregnant rats.

OBJECTIVES: Our purpose was to study the effects of corticotropin-releasing factor on (1) maternal blood pressure, (2) uterine vasculature, and (3) parturition in pregnant rats. STUDY DESIGN: Infusion minipumps containing vehicle, corticotropin-releasing factor, or alpha-helical corticotropin-releasing factor 9-41 (corticotropin-releasing factor receptor antagonist) were inserted subcutaneously in timed pregnant rats on day 16 of gestation. Systolic blood pressure was measured daily by the tail-cuff method. The time of onset of labor was determined and the newborn pups were weighed. Circulating levels of corticotropin-releasing factor were measured in untreated controls by radioimmunoassay. Relaxant responses to corticotropin-releasing factor were studied in isolated segments of uterine artery from late (day 18) and term (day 22) pregnant rats mounted in a wire myograph. RESULTS: The blood pressure was decreased by corticotropin-releasing factor and increased by alpha-helical corticotropin-releasing factor 9-41 (p < 0.05). The time of onset of labor was not affected by either treatment. Pup weight was decreased by corticotropin-releasing factor (p < 0.05). Circulating levels of corticotropin-releasing factor (immunoreactive) were not changed in pregnancy. In vitro, corticotropin-releasing factor caused relaxation of the uterine artery in a concentration-dependent manner and the relaxation was decreased at term compared with late pregnancy (p < 0.05). CONCLUSIONS: Endogenously produced corticotropin-releasing factor lowers blood pressure during pregnancy in rats. It is a relaxant of uterine vasculature and this effect is decreased at term. It does not play an essential role in the initiation of labor in rats.

Animals↗