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Biomedical subjects

Atul Kumar

Publications and source records attributed to Atul Kumar.

At least 19 recordsLinked to original sources
PubMed2004

Requirement of c-myb in T cell development and in mature T cell function.

Previous reports have suggested that the protooncogene c-myb participates in T cell development in the thymus and mature T cell proliferation. We have generated two T cell-specific c-myb knockout mouse models, myb/LckCre and myb/CD4Cre. We have demonstrated that c-myb is required for the development of thymocytes at the DN3 stage, for survival and proliferation of double-positive thymocytes, for differentiation of single-positive CD4 and CD8 T cells, and for the proliferative responses of mature T cells. In addition, our data show that c-myb is directly involved in the formation of double-positive CD4+CD8+CD25+, CD4+CD25+, and CD8+CD25+ T cells, developmental processes that may imply a role for c-myb in autoimmune dysfunction.

Animals↗
PubMed2004

Appraisal of four novel approaches to the prevention and treatment of sepsis.

PURPOSE: Four novel approaches to the management of sepsis are discussed. SUMMARY: Drotrecogin alfa (activated) has FDA-approved labeling for use in the treatment of severe sepsis. Risk of bleeding and identification of the most suitable patients have been the major issues related to use of this drug. Tight glycemic control and early goal-directed therapy (EGDT) are promising supportive strategies. Both have challenged existing views regarding safe glucose levels and the usefulness of increased oxygen delivery in sepsis. The routine maintenance of euglycemia is resource intensive, however, and benefits during treatment of sepsis are unclear. Very early initiation of measures to optimize hemodynamic variables and the ability to identify patients with cryptic shock appear to be key reasons for successful EGDT. The use of corticosteroids for septic shock has been extensively researched and has provoked controversy. Selection of patients likely to benefit on the basis of relative adrenal insufficiency and prolonged treatment may account for recently observed positive results. A model for combining the four strategies is proposed. CONCLUSION: Novel strategies for treating sepsis include drotrecogin alfa (activated), tight glycemic control, EGDT, and low-dose corticosteroids.

Adrenal Cortex Hormones↗
PubMed2004

Diaryl naphthyl methanes a novel class of anti-implantation agents.

Diaryl naphthyl methanes and the corresponding 1, 2, 3, 4- and 5, 6, 7, 8-tetrahydro naphthyl methane derivatives have been synthesized as novel estrogen receptor binding ligands. The secondary and tertiary amino alkoxy derivatives of diaryl naphthyl and tetrahydro naphthyl methane interact with the estrogen receptor to elicit promising estrogenic, antiestrogenic and implantation inhibition activities in rats. The most active compounds in this series are 7, 9 and 20, cent percent active in preventing implantation in rats at 2.5 mgkg(-1) dose.

Animals↗
PubMed2004

A simple technique to reduce fluid intravasation during endometrial resection.

The rate of fluid intravasation may abruptly and alarmingly increase during endometrial resection. Left unchecked, this may lead to complications of fluid overload. In 20 patients, temporary cessation of surgery in the form of a 10-minute glycine-free interval reduced the rate of fluid intravasation by 38.75% to 85.81% (mean 67.09%) in the later part of surgery. This was possibly due to hemostatic sealing of open blood vessels which prevented further intravasation of distending medium into systemic circulation.

Absorption↗
PubMed2004

Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization.

PURPOSE: To assess the efficacy of transpupillary thermotherapy (TTT) for the management of idiopathic subfoveal choroidal neovascularization (CNV). METHODS: This was a prospective, non-controlled, clinical case trial involving 21 eyes of 21 patients with a mean age of 36 years. All 21 eyes had idiopathic subfoveal CNV and were subjected to diode laser TTT. Laser beam size ranged from 1.2 mm to 3.0 mm and power settings ranged between 300 mW and 600 mW. The end-point was an area of no visible colour change. Pre- and post-laser evaluations of ETDRS visual acuity, contrast sensitivity, slit-lamp biomicroscopy and fluorescein angiography were carried out. RESULTS: The nine predominantly occult and 12 predominantly classic subfoveal membranes were followed-up for a mean of 5.1 months after TTT. Overall, 17 eyes (81%) showed improvement or stabilization in ETDRS visual acuity. Contrast sensitivity improved in 17 eyes (81%). Reading speed improved in 15 eyes (71%). Retreatment was needed in three eyes (14%). CONCLUSION: Transpupillary thermotherapy treatment is a potential strategy for treating idiopathic subfoveal CNV in both its classic and occult forms.

Adult↗
PubMed2004

A prospective controlled trial to evaluate the adjunctive role of posterior subtenon triamcinolone in the treatment of diffuse diabetic macular edema.

The aim of the present prospective controlled trial was to evaluate the adjuvant role of posterior subtenon triamcinolone in the treatment of diffuse diabetic macular edema (DDME). Thirty one (31) eyes with DDME were divided into an interventional group subjected to grid laser photocoagulation and 0.5 mL of 40 mg/mL posterior subtenon triamcinolone, and a noninterventional group subjected to grid laser photocoagulation only. Best-corrected visual acuity, contrast sensitivity, and intraocular pressures were assessed at presentation, and at 6, 12, and 24 weeks after intervention. The interventional group showed a statistically significant (p < 0.05) change in both mean best corrected visual acuity, from 20/160 to 20/100 (two-line increase on Early Treatment Diabetic Retinopathy Study (ETDRS)) (p = 0.024), and mean contrast sensitivity, from 0.9 to 1.09 (p = 0.01), at the end of 24 weeks. A significant rise in intraocular pressure was not described in any of the patients in either group. Posterior subtenon triamcinolone injection is a useful and safe adjunct to the conventional management of diabetic macular edema.

Adult↗
PubMed2003

c-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic differentiation.

The c-myb proto-oncogene plays a central role in hematopoiesis and encodes a major translational product of 75 kDa. c-Myb is highly expressed in immature hematopoietic cells, and its expression is down-regulated during terminal differentiation. Deregulated expression of c-Myb has been shown to block terminal differentiation of hematopoietic cells. Here we have studied the mechanism of action and the nature of target genes through which c-Myb mediates the block in differentiation of 32Dcl3 murine myeloid cells. We show that the ectopic overexpression of c-Myb in 32Dcl3 cells results in the overexpression of c-Myc. However, enforced expression of c-Myc in 32Dcl3 cells did not alter the normal pattern of differentiation. In addition, expression of dominant-negative mutants of c-Myc relieved c-Myb-mediated block in differentiation. These results led us to conclude that c-myc is a target gene of c-Myb and activation of the c-myc gene is a necessary event in Myb-mediated transformation. However, c-Myc expression alone is inadequate to elicit the phenotypic effects seen with Myb-mediated block in differentiation of myeloid cells, suggesting that activation of additional transcriptional targets by c-Myb plays a critical role in this process.

Animals↗
PubMed2003

Metabolism of the polynuclear sulfur heterocycle benzo[b]phenanthro[2,3-d]thiophene by rodent liver microsomes: evidence for multiple pathways in the bioactivation of benzo[b]phenanthro[2,3-d]thiophene.

Benzo[b]phenanthro[2,3-d]thiophene (BPT), a thia analogue of dibenz[a,h]anthracene (DBA), is a carcinogenic environmental pollutant. We have examined the metabolism of BPT by rodent liver microsomes to investigate the mechanism by which BPT produces mutagenic and carcinogenic effects. Both rat and mouse liver microsomes biotransformed [G-(3)H]BPT to various metabolites including BPT 3,4-diol and BPT sulfoxide, which are significantly more mutagenic than the parent compound. Liver microsomes from both control mice and rats metabolize BPT at similar rates. Treatment of mice with P450 inducers DBA, 3-methylcholanthrene (3-MC), Aroclor 1254, and phenobarbital enhanced the rate of metabolism of BPT by 74-, 28-, 77-, and 6-fold, respectively. In comparison, the treatment of rats with DBA and 3-MC increased the rate of metabolism of BPT by 22- and 34-fold, respectively, suggesting that P450 enzymes responsible for the metabolism of BPT are enhanced to different extents in rats and mice by a similar class of compounds. In general, the liver microsomes from mice treated with DBA or 3-MC were more active than those from similarly treated rats in metabolizing BPT to its 3,4-diol, a precursor to the bay-region diol epoxide of BPT. BPT sulfone was a minor metabolite (if formed) in all cases. The liver microsomes from rats treated with DBA or 3-MC or from mice treated with PB produced a significant proportion of BPT sulfoxide (12-41%). In contrast, the liver microsomes from DBA- or 3-MC-treated mice formed BPT sulfoxide as a minor metabolite (<2%). These studies indicate that cytochrome P450 enzymes induced by PAHs (e.g., P450 1A1 and P450 1B1) and by PB (e.g., P450 2B1, 3A1, and/or 3A2) are involved in the metabolism of BPT to mutagenic BPT 3,4-diol and BPT sulfoxide, providing evidence for the first time that BPT and possibly other thia-PAHs are metabolically activated via the formation of both the dihydrodiol (and subsequently diol epoxide) and the sulfoxide.

Animals↗
PubMed2003

Comparison of scleral buckling with combined scleral buckling and pars plana vitrectomy in the management of rhegmatogenous retinal detachment with unseen retinal breaks.

BACKGROUND: The purpose of the present paper was to compare the techniques of conventional scleral buckling and combined pars plana vitrectomy and scleral buckling procedures in rhegmatogenous retinal detachments with unseen retinal breaks. METHODS: Forty-four consecutive eyes with uncomplicated, primary rhegmatogenous retinal detachments with a clear media and unseen retinal breaks were randomized to two groups. The scleral buckling group underwent 360 degrees scleral buckling, cryopexy and external subretinal fluid drainage. In the combined surgery group, 360 degrees scleral buckling, pars plana vitrectomy, air-fluid exchange, endolaser and injection of 14% perfluoropropane gas was done. RESULTS: At 3 months follow up the primary reattachment rate was 80% (16/20 cases) in the combined surgery group, and 70% (14/20 cases) in the scleral buckling group (P = 0.716). The visual acuity improved significantly from a preoperative median of hand movement (HM; range: HM to 6/60; similar in both the groups), to a median of 6/60 (range: perception of light to 6/18) in the combined surgery group and a median of 6/36 (range: HM to 6/18) in the scleral buckling group, the difference between the two groups not being statistically significant (P = 0.4). The number of intraoperative and postoperative complications was more in the combined surgery group. (four cases were lost to follow up and were doing well when last examined.) CONCLUSION: Conventional scleral buckling was found to be a safe and effective technique in the primary management of uncomplicated, rhegmatogenous retinal detachments with unseen retinal breaks when the media is clear.

Adolescent↗
PubMed2003

Laser conjunctivoplasty: a new technique for correction of mild medial ectropion.

Thirty patients with mild medial ectropion of the lower lid were treated by Argon green laser. A diamond-shaped area (6 x 4 mm in size) on the medial part of the tarsal conjunctiva of the lower lid was burnt with overlapping spots until white blanching and visible contraction of tissue were seen. The apex of the diamond was kept 4 mm below the punctal opening. After an average follow-up of 6 months, functional success was achieved in 22/30 eyes. Anatomical success in terms of repositioning of the punctum was attained in 24/30 eyes. The only side effect noted was a mild burning sensation of the eyes lasting for two hours after the procedure. This is the authors' initial experience with a somewhat new and easy procedure to treat mild medial ectropion of the lower lid that can be performed on an outpatient basis.

Conjunctiva↗
PubMed2003

Molecular mechanisms associated with the regulation of apoptosis by the two alternatively spliced products of c-Myb.

The c-myb proto-oncogene encodes two alternatively spliced mRNAs, which in turn code for proteins of 75 kDa and 89 kDa. It is at present unclear whether the two isoforms of c-Myb perform identical functions or whether they mediate different biological effects. To assess their role in apoptotic death of hematopoietic cells, we expressed the two isoforms of c-Myb in the murine myeloid cell lines 32Dcl3 and FDCP1. Our results show that while ectopic overexpression of p75 c-Myb results in the acceleration of cell death, similar overexpression of p89 c-Myb results in the protection of cells from apoptotic death. An analysis of gene expression changes with mouse cDNA expression arrays revealed that while p75 c-Myb blocked the expression of glutathione S-transferase micro mRNA, p89 c-Myb greatly enhanced the expression of this gene. These results were further confirmed by Northern blot analysis. Ectopic overexpression of the glutathione S-transferase micro gene in 32Dcl3 cells resulted in protection of cells from interleukin-3 withdrawal-induced cell death similar to that seen with the ectopic overexpression of p89 c-Myb. These results suggest that the two isoforms of c-Myb differentially regulate apoptotic death of myeloid cells through differential regulation of glutathione S-transferase micro gene expression.

Alternative Splicing↗
PubMed2003

The role of lipids in the development of diabetic microvascular complications: implications for therapy.

Dyslipidemia is a major factor responsible for coronary heart disease and its reduction decreases coronary risk in patients with diabetes mellitus. However, the association of dyslipidemia with microvascular complications and the effect of intervention with lipid-lowering therapy in diabetes have been less investigated. We present the systematic review of association and intervention studies pertaining to dyslipidemia and microvascular disease in diabetes and also review possible mechanisms. Dyslipidemia may cause or exacerbate diabetic retinopathy and nephropathy by alterations in the coagulation-fibrinolytic system, changes in membrane permeability, damage to endothelial cells and increased atherosclerosis. Hyperlipidemia is associated with faster decline in glomerular filtration rate and progression of albuminuria and nephropathy. Recent evidence also suggests a role of lipoprotein(a) in progression of retinopathy and nephropathy in patients with diabetes mellitus. Lipid-lowering therapy, using single agents or a combination of drugs may significantly benefit diabetic retinopathy and diabetic nephropathy. In particular, hydroxymethyl glutaryl coenzyme A reductase inhibitors may be effective in preventing or retarding the progression of microvascular complications because of their powerful lipid-lowering effects and other additional mechanisms. However, most of the data are based on short-term studies, and need to be ascertained in long-term studies. Until more specific guidelines are available, aggressive management of diabetic dyslipidemia, according to currently accepted guidelines, should be continued for the prevention of macrovascular disease which would also benefit microvascular complications.

Diabetic Angiopathies↗
PubMed2003

Intravitreal low molecular weight heparin in PVR surgery.

PURPOSE: To evaluate the efficacy of low molecular weight heparin (LMWH) in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each). Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. RESULTS: At each follow-up visit, the study group showed a better media clarity, which was statistically significant (P = 0.0042). The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33%) compared to 3 patients in the control group (20%). CONCLUSION: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

Adult↗