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Biomedical subjects

A Basu

Publications and source records attributed to A Basu.

At least 19 recordsLinked to original sources
PubMed2006

Downregulation of Bid is associated with PKCepsilon-mediated TRAIL resistance.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent as it selectively kills tumor cells but spares normal cells. Resistance to TRAIL by tumor cells limits its therapeutic use. We have previously shown that protein kinase C-epsilon (PKCepsilon) acts as an antiapoptotic protein in MCF-7 breast cancer cells. In the present study, we have investigated the mechanism(s) by which PKCepsilon contributes to TRAIL resistance. Overexpression of PKCepsilon inhibited caspase-8 and -9 activation, release of mitochondrial cytochrome c and cell death induced by TRAIL, but did not interfere with the recruitment of caspase-8 to the death-inducing signaling complex. Knockdown/inhibition of PKCepsilon resulted in enhanced sensitivity to TRAIL. The level of Bcl-2 was increased and Bid was decreased by PKCepsilon at both the protein and mRNA level but PKCepsilon had no effect on Bax. Knockdown of Bcl-2 by siRNA reversed TRAIL resistance in PKCepsilon-overexpressing cells, whereas depletion of Bid contributed to TRAIL resistance in MCF-7 cells. A decrease in Bid content was also associated with inhibition of TRAIL-induced caspase-8 activation. Furthermore, PKCepsilon depletion or overexpression of DN-PKCepsilon was associated with a decrease in Bcl-2 protein level. Thus, our results suggest that PKCepsilon acts upstream of mitochondria and mediates TRAIL resistance via both Bcl-2 and Bid in MCF-7 cells.

Apoptosis↗
PubMed2006

Cloning and functional expression of an acyl-ACP thioesterase FatB type from Diploknema (Madhuca) butyracea seeds in Escherichia coli.

A cDNA of fatty acyl-acyl carrier protein (ACP) thioesterase (Fat) from developing seed of Madhuca butyracea has been cloned. The deduced amino acid sequence of the cDNA corresponding to the mature polypeptide showed 30-40% and 60-75% identity to the reported FatA and FatB class of plant thioesterases, respectively. This gene, MbFatB, is present as a single copy in M. butyracea genome and the MbFatB protein was detected clearly in seed tissues of this plant but not in that of Indian mustard (Brassica juncea). Heterologous expression of the MbFatB gene driven by different promoters in E. coli wild type and fatty acid beta-oxidation mutant (fadD88) strains resulted production of the recombinant protein with various fusion tags either as biologically inactive (insoluble) or functionally active forms. Expression of functionally active recombinant MbFatB in E. coli affected bacterial growth and cell morphology as well as changed the fatty acid profiles of the membrane lipid and the culture supernatant. Alteration of the fatty acid composition was directed predominantly towards palmitate and to a lesser extent myristate and oleate due to acyl chain termination activity of plant thioesterase in bacteria. Thus, this new MbFatB gene isolated from a non-traditional oil-seed tree can be used in future for transgenic development of oil-seed Brassica, a widely cultivated crop that expresses predominantly oleoyl-ACP thioesterase (FatA) in its seed tissue and has high amount of unwanted erucic acid in edible oil in order to alter the fatty acid profile in a desirable way.

Amino Acid Sequence↗
PubMed2006

Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials.

OBJECTIVE: To review the effects of tomato product supplementation, containing lycopene, on biomarkers of oxidative stress and carcinogenesis in human clinical trials. RESULTS: Supplementation of tomato products, containing lycopene, has been shown to lower biomarkers of oxidative stress and carcinogenesis in healthy and type II diabetic patients, and prostate cancer patients, respectively. Processed tomato products like tomato juice, tomato paste, tomato puree, tomato ketchup and tomato oleoresin have been shown to provide bioavailable sources of lycopene, with consequent increases in plasma lycopene levels versus baseline. Dietary fats enhance this process and should be consumed together with food sources of lycopene. The mechanisms of action involve protection of plasma lipoproteins, lymphocyte DNA and serum proteins against oxidative damage, and anticarcinogenic effects, including reduction of prostate-specific antigen, upregulation of connexin expression and overall decrease in prostate tumor aggressiveness. There is limited in vivo data on the health benefits of lycopene alone. Most of the clinical trials with tomato products suggest a synergistic action of lycopene with other nutrients, in lowering biomarkers of oxidative stress and carcinogenesis. CONCLUSIONS: Consumption of processed tomato products, containing lycopene, is of significant health benefit and can be attributed to a combination of naturally occurring nutrients in tomatoes. Lycopene, the main tomato carotenoid, contributes to this effect, but its role per se remains to be investigated.

Anticarcinogenic Agents↗
PubMed2006

Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy.

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.

Adult↗
PubMed2006

Need for an individualized and aggressive management of multinodular goiters of endemic zones by specially trained surgeons: experience in western Nepal.

BACKGROUND: The goals of the present study were to explore the presentation of multinodular goiter (MNG) and solitary thyroid nodules (STN) in the sub-Himalayan belt, including the risk of malignancy, and to evaluate whether specialized surgeon training in endocrine surgery has an effect on reducing complications. METHODS: This retrospective study (1998-2003) analyzed 624 patients with thyroid disorders seen in the thyroid clinic of a tertiary care hospital in western Nepal. The findings included 67.7% (n = 423: euthyroid, 297, toxic, 126) multinodular goiters (MNG) and 18.5% (n = 116) STN. Rest of patients of other thyroid disorders were excluded from the study. Ultrasonography and fine-needle aspiration cytology (FNAC) were the available diagnostic adjuncts. To evaluate the role of surgeon training, outcomes were compared between patients cared for by surgeons specially trained in endocrine surgery and those who were not. Prognostic markers indicated aggressiveness of cancers. RESULTS: Of the 539 MNG and STN patients in this series, 236 underwent operation. Of these, 25.7% (139/539) were toxic, and 11.31% had associated carcinoma. Aggressive cancers, like poorly differentiated (4.9%) and anaplastic types (18%), were more common than in series of patients from iodine-sufficient regions. Patients 40-55 years of age were more likely to have toxicity, and those > 60 years of age were more likely to have aggressive cancers. Postoperative complication rates were lower in the group treated by surgeons who had special training in endocrine surgery. CONCLUSIONS: There is a higher incidence of toxicity and malignancy in MNG in an endemic goiter zone. The limited diagnostic and therapeutic facilities in the region under study warrant a high degree of clinical suspicion and judgment, sound knowledge of thyroid physiology, thorough interpretation of hormone test results, and meticulous surgical techniques. The treatment must be individualized with consideration of humanitarian and socioeconomic factors, without compromising the quality of care and its long-term consequences. Aggressive management of malignancy and toxicity with total thyroidectomy is needed as primary therapy in many instances. However, subtotal excision is more useful in carefully selected cases with a small remnant. Specialized training in thyroid surgery appears to be valuable in reducing complications.

Adolescent↗
PubMed2006

Multiple synchronous spinal extra-osseous intradural chordomas: is it a distinct entity?

Chordomas are most commonly of extradural origin and are associated with bone destruction. Extra-osseous intradural chordomas are extremely rare and most of the cases described are located near the clivus. We report an extremely rare case of multiple extra-osseous intraspinal chordomas in a 36-year-old male patient with autopsy findings. This case highlights that behaviour of spinal intradural chordomas is not universally low grade, but is variable and aggressive.

Adult↗
PubMed2005

A microcosm study on bioremediation of p-nitrophenol-contaminated soil using Arthrobacter protophormiae RKJ100.

p-Nitrophenol (PNP), a toxic nitroaromatic compound, can build up in soils due to extensive usage of nitrophenolic pesticides and hence needs to be removed. Arthrobacter protophormiae RKJ100, a PNP-degrading organism, was used in this work to study factors affecting its growth, and then evaluated for its capacity to degrade PNP in soil microcosms. Molasses (10%) treated with 0.1% potassium hexacyanoferrate was found to be a suitable and cheap carbon source for inoculum preparation. Induction studies showed that PNP depletion was quicker when cells were induced by pre-exposure to PNP. The efficiency of PNP degradation in soil by strain RKJ100 was seen to be dependent on pH, temperature, initial PNP concentration and inoculum size. Microcosm studies performed with varying concentrations (1.4-210 ppm) of PNP-spiked soils showed that strain RKJ100 could effectively degrade PNP over the range 1.4-140 ppm. A cell density of 2x10(8) colony forming units/g soil was found to be suitable for PNP degradation over a temperature range of 20-40 degrees C and at a slightly alkaline pH (7.5). Our results indicate that strain RKJ100 has potential for use in in situ bioremediation of PNP-contaminated sites. This is a model study that could be used for decontamination of sites contaminated also with other compounds.

Arthrobacter↗
PubMed2005

Reversal of acute cellular rejection after renal transplantation with Campath-1H.

Between September 2002 and February 2004, 40 kidney transplant (27 from deceased and 13 from living donors) recipients (25 male and 15 female, aged 50.3 +/- 15.1 years) were treated with Campath 1H (C 1H; 30 mg/dose IV) for biopsy-proven steroid-resistant rejection (SRR) or rejections equal to or worse than Banff 1B. All transplantations occurred between August 2001 and May 2003. All patients had received antibody preconditioning (RATG 5 mg/kg, n = 34; C 1H 60 mg, n = 4; C 1H 30 mg, n = 2) preoperatively and were treated with Tacrolimus monotherapy (target level 10 ng/ml) postoperatively and subsequent spaced weaning. Elevated creatinine levels at follow-up were evaluated by renal transplant biopsy. Rejection was treated with steroids, reversal of weaning, addition of sirolimus, and/or antibody treatment, depending on grade of rejection. The mean duration of follow-up was 453 +/- 163 days after C 1H administration. Twenty-nine patients received C 1H for SRR and 11 patients for Banff 1B or worse rejections; 26 patients received more than 1 dose of C 1H. Graft survival was 62.5% (25 patients); 6 of the 15 allografts (40%) that failed had presented with rejections because of noncompliance. Graft survival in compliant patients with SRR or rejections equal to or worse than Banff 1B was 73.5% (25 of 34). Fourteen patients (35%) had infectious complications, of whom 2 patients (5%) died. C 1H is an effective agent for SRR and Banff 1B or worse rejections, with 95% patient survival and 73.5% graft survival (in compliant patients). The number of doses of 30 mg C 1H should be restricted to two, as there is a high incidence of potentially fatal infectious complications.

Acute Disease↗
PubMed2005

Steroid-free tacrolimus monotherapy after pretransplantation thymoglobulin or Campath and laparoscopy in living donor renal transplantation.

Living donor renal transplantation was performed under a regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. From October 9, 2002, to December 31, 2004, 196 consecutive, unselected laparoscopic live donor nephrectomies resulting in 196 living donor renal transplantations were performed. Recipients were pretreated with rabbit antithymocyte globulin (thymoglobulin; 24 patients or [12%]) or Campath 1H (alemtuzumab; 166 patients [85%]), or were not in protocol (6 patients [3%]), and were given postoperative steroid-free low-dose tacrolimus immunosuppressive monotherapy with subsequent weaning. There was no donor mortality. Major and minor donor morbidities were 2.6% and 4.2%, respectively. Laparoscopic live donor nephrectomy recipient outcomes with a mean follow-up of 401 days included (1) recipient and graft survival of 99.0% and 97.4%, respectively; (2) no ureteral stenosis; (3) 0.5% delayed graft function, from recurrent focal segmental glomerulosclinosis; and (4) no vascular thrombosis. The incidence of acute rejection at 30, 90, and 401 days was 1.5%, 3.8%, and 11.2% (all 196 recipients), 0%, 25%, and 29.2% (thymoglobulin recipients), and 1.8%, 3.9%, and 8.4% (Campath 1H recipients), respectively. Sixty-six patients (33.7%) are receiving spaced-dose immunosuppressive monotherapy. The mean creatinine concentration in all recipients was 1.5 +/- 1.1 mg/dL. There were no instances of cytomegalovirus tissue invasive disease or posttransplantation lymphoproliferative disease. The incidence of new-onset posttransplantation insulin-dependent diabetes was 0.5%. At current follow-up, the use of Campath 1H rather than thymoglobulin for pretreatment seems to have significantly improved the efficacy of our regimen.

Adult↗
PubMed2005

Ectopic pregnancy with postcoital contraception--a case report.

The incidence of ectopic pregnancies is increasing. Common risk factors are tubal pathology, previous tubal surgery, previous ectopic pregnancy, intrauterine device use and embryo transfer. Levonelle-2, a progesterone-only postcoital contraceptive works by a combination of mechanisms including ovulation inhibition, prevention of fertilization, and inhibition of implantation. It is 85% effective and there have been 12 reported cases of ectopic pregnancy in the UK with its use. It is believed that progesterone slows the intratubal migration of the fertilized ovum. In the case reported here, a woman presented with an ectopic pregnancy after use of Levonelle-2 as postcoital contraception; there were no clinical predisposing risk factors. In the absence of any histological evidence of tubal damage, we suspect that the levonorgestrel from Levonelle-2 could have been responsible for delayed embryo transfer which resulted in the ectopic pregnancy.

Adult↗
PubMed2004

Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney and pancreas-kidney transplantation under antibody preconditioning.

We investigated retrospectively the risk factors for cytomegalovirus (CMV) infection under ganciclovir or valganciclovir prophylaxis (oral ganciclovir 1 g tid, valganciclovir 450 mg/d) in our kidney and simultaneous pancreas-kidney (SPK) transplant patients undergoing transplantation between July 1, 2001 and February 28, 2003. Two hundred eleven patients receiving prophylactic oral ganciclovir or valganciclovir were included in the study. All patients were given antibody preconditioning (thymoglobulin 178, alemtuzumab 33). Duration of prophylactic treatment was between 3 and 8 months. Fifteen (7.1%) patients developed a positive CMV antigenemia in the first 6 months after transplantation, and 18 of 176 (10.2%) patients developed a positive CMV antigenemia during the first year. No patient developed tissue invasive CMV disease. At 6 months after transplantation, valganciclovir was slightly more effective than ganciclovir prophylaxis (P=.052). Positive donor CMV serology significantly increased the risk of CMV infection compared to CMV-negative donors (P=.014 and P=.003 at 6 and 12 months, respectively). Duration of CMV prophylaxis for more than 3 months decreased the risk of CMV infection (P=.04 and P=.009 at 6 and 12 months, respectively). Either valganciclovir prophylaxis (450 mg/d) or high-dose oral ganciclovir (1 g tid) is effective in preventing tissue-invasive CMV disease, and results in a low incidence of CMV antigenemia in patients undergoing kidney and SPK transplantation.

Antiviral Agents↗
PubMed2004

Effects of colonoscopy on intracranial pressure: observation in a large animal model.

BACKGROUND AND STUDY AIMS: Increased intra-abdominal pressure has been associated with increased intracranial pressure. Bowel insufflation during colonoscopy may increase the intra-abdominal pressure. It was hypothesized that colonoscopy may be associated with intracranial pressure elevation subsequent to an elevation in intra-abdominal pressure. MATERIALS AND METHODS: Colonoscopy was carried out in seven anesthetized pigs, and the colonoscope was advanced up to 60 cm from the anal verge. Insufflation was used to allow safe advancement of the colonoscope and to allow visualization of the colon, in the same way as in the procedure performed in humans. Intra-abdominal pressure was measured by determining the hydrostatic pressure in the urinary bladder. A subarachnoid screw was used to monitor intracranial pressure. The mean arterial blood pressure and intra-abdominal venous pressure were directly monitored via the femoral vessel access; all parameters were recorded before and during colonoscopy. RESULTS: A statistically significant elevation in intracranial pressure was demonstrated during colonoscopy. The average increase in intracranial pressure was 3.1 mm Hg. The intra-abdominal pressure and intra-abdominal venous pressure were also significantly elevated during the procedure. CONCLUSIONS: Colonoscopy may increase intracranial pressure due to an increase in intra-abdominal pressure. This may have clinical implications when colonoscopy is conducted in patients with brain pathology associated with high intracranial pressure.

Anesthesia, General↗
PubMed2004

Clostridium difficile colitis in patients after kidney and pancreas-kidney transplantation.

Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas-kidney allograft recipients were transplanted. Thirty-nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas-kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P>0.05). All but one patient presented with diarrhea. Twenty-four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%) and M+oral vancomycin (M+V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15-314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated.

Adult↗