Biomedical subjects
Publications and source records attributed to S Kumar.
We report a measurement of the branching fraction for the decay B+ --> rho(+) pi(0) based on a 140 fb(-1) data sample collected with the Belle detector at the KEKB asymmetric e(+)e(-) collider. We measure the branching fraction B(B(+) --> rho(+)pi(0)) = (13.2 +/- 2.3(stat)(+1.4)(-1.9)(syst)) x 10(-6), and the CP-violating asymmetry A(CP)(B-/+ -->rho(-/+)pi(0))=0.06 +/- 0.17(stat)(+0.04)(-0.05)(syst).
From May 1999 to April 2002, we treated 14 patients with subtrochanteric femoral fractures and seven patients with ipsilateral fractures of the femoral neck and shaft using a second-generation cephalomedullary interlocked nail. Patients mean age was 36 (20-60) years, and 19 fractures were caused by high-energy trauma. Four patients had associated injuries. The average follow-up was 23 (16-30) months. Per-operatively, we had problems in locating the entry portal in four patients, and one nail was driven through the inter-condylar notch. All fractures except two united. One patient had non-union of the femoral neck and one of both neck and shaft. One patient united with shortening of more than 1.5 cm and varus angulation at the fracture site. Two patients had loosening and backing out of the proximal screw. The second-generation cephalomedullary nail is a suitable treatment option for proximal femoral fractures, but it requires a high degree of accuracy and technical expertise.
Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.
Immediate breast reconstruction is being increasingly offered to patients requiring mastectomy for breast cancer. An audit was carried out to determine whether it affected time to initiation of chemotherapy, delays during chemotherapy, percentage intended dose and need for support with antibiotics or granulocyte-colony stimulating factor. A total of 44 patients undergoing a variety of reconstructive procedures followed by chemotherapy were identified and patient records were reviewed. These were compared with a control group of 49 patients undergoing mastectomy alone and chemotherapy in the same 4-year period and institution. Patients undergoing transverse rectus abdominis myocutaneous flap reconstruction experienced an average of 5 more days delay to chemotherapy initiation than controls with the commonest reason being poor wound healing. Percentage intended dose, delays during chemotherapy and need for support with granulocyte-colony stimulating factor or antibiotics were comparable in all groups.
Digestive enzymes of Catla catla were studied during ontogenic development. Specific amylase activity was 0.12+/-0.01 mg maltose mg protein(-1) h(-1) in fish 4 days after hatching (DAH) and reached a maximum on (0.41+/-0.12 mg maltose mg protein(-1) h(-1)) 34 DAH. Total protease activity was minimum (123.2+/-16.5 mU mg protein(-1) min(-1)) on day-8 and reached its highest level (2713+/-147.2 mU mg protein(-1) min(-1)) on day-32. Trypsin activity showed constant increasing trend from day-16 onwards and was maximum on day-34 (118.1+/-7.09 mU mg protein(-1) min(-1)). Highest chymotrypsin activity was found on day-32 (1789.0+/-111.7 mU mg protein(-1) min(-1)). Lipase activity was detected in 4 DAH catla. Lipase activity increased steadily from day-22 onwards. SDS-PAGE of crude enzyme extracts showed that high molecular mass bands (41.8-127.8 kDa) appeared during the early stages followed by low molecular mass bands (17.8-37.2 kDa). The number of protease activity bands in substrate SDS-PAGE increased with age of fish. During ontogenesis of carp, soybean trypsin inhibitor (SBTI), PMSF and TLCK inhibited 75.5+/-1.19% to 92.8+/-0.85%, 53.3+/-9.47% to 90.5+/-2.6% and 39.8+/-3.8% to 84.7+/-1.54% of total protease activity, respectively. There was only 2.58+/-0.66% to 10.21+/-0.09% inhibition of protease activity with EDTA. SBTI and PMSF inhibited 8 and 4 activity bands, respectively. TLCK, a specific trypsin inhibitor, inhibited four trypsin-like enzymes in carp during ontogenesis.
AIMS: The role of postoperative radiotherapy (PORT) after non-curative resections for cancer oesophagus is not well defined. A policy of offering PORT after non-curative resections for cancer oesophagus has been followed at our institution, and we report an audit of our experience. MATERIAL AND METHODS: Between March 1990 and September 2002, 139 patients underwent resections for cancer oesophagus. Of these, 86 patients received PORT to a dose of 45-50.4 Gy/25-28 fractions. Eleven of these patients also received concurrent and adjuvant 5-fluorouracil (5-FU). Disease-free survival and overall survival were computed from the day of surgery using the Kaplan-Meier method. RESULTS: Seventy-six per cent (65/86) of patients had squamous cell carcinoma and 69% (59/86) of patients had tumours in the lower-third of the oesophagus. The median interval between surgery and PORT was 41 days, and 93% of patients received doses as planned. Strictures at the anastomotic site and ulcerations in the stomach mucosa were seen in 17% and 5% of patients, respectively. The median and 5-year disease-free survival was 12 months (95% CI 9.9-14.1) and 14%; whereas the median and 5-year overall survival was 17 months (95% CI 12.4-21.6) and 17%, respectively. Local and distant failures were seen in 29% and 45% of patients, respectively. CONCLUSIONS: PORT, after a non-curative resection of cancer oesophagus, is well tolerated with acceptable morbidity and survival.
AIMS: Vascular endothelial growth factor (VEGF)-C and VEGF-D are angiogenic and lymphangiogenic members of the VEGF family of growth factors. Increased VEGF-C or VEGF-D expression in human tumours may be associated with lymph-node metastasis and lymphatic invasion. Circulating plasma levels of VEGF-A, VEGF-C and VEGF-D were measured in patients with colorectal cancer, and assessed for their usefulness as a diagnostic tool for determining lymph-node metastasis. MATERIALS AND METHODS: One hundred and twenty patients with colorectal cancer and 50 healthy control patients were included in the study. Plasma growth-factor levels were assessed by enzyme-linked immunosorbent assays. RESULTS: No significant differences in plasma VEGF-C or VEGF-D levels were seen between patients subgrouped by clinicopathological variables. In particular, there were no differences in median plasma VEGF-C or VEGF-D level in patients with and without lymph-node involvement (VEGF-C: 11.2 U/ml [range, 4.9-51.9] vs 9.9 U/ml [4.4-93.4 U/ml]; P = 0.90; VEGF-D: 335 pg/ml [113-1102] vs 316.5 pg/ml [0-1343]; P = 0.68). CONCLUSIONS: Circulating plasma levels of VEGF-C and VEGF-D do not allow pre-operative identification of lymph-node status in patients with colorectal cancer.
AIM: To compare T1-weighted magnetization transfer (MT) with fluid attenuated inversion recovery (FLAIR) imaging for evaluating conspicuity and number of lesions in individuals with brain tuberculoma. MATERIALS AND METHODS: In all 28 patients with brain tuberculoma underwent MR examination using fast spin-echo (FSE) T2, spin-echo (SE) T1, T1-weighted MT and FLAIR imaging. Post-contrast T1-weighted MT imaging was taken as the gold standard for assessing the number of lesions. Tuberculomas detected both on T1-weighted MT and FLAIR imaging were examined for the wall to be defined, and were divided into two groups on the basis of presence (group 1) or absence (group 2) of perilesional oedema visible on FLAIR imaging. The mean signal intensity of the wall of the lesions and adjacent oedema or brain parenchyma was analyzed qualitatively and quantitatively. RESULTS: The number of lesions detected on T1-weighted MT was higher than on FLAIR imaging (209 versus 163). Conspicuity in both groups was better on T1-weighted MT images qualitatively as well as quantitatively. The difference in the signal intensity of the wall of the lesion and perilesional oedema was statistically significant only on T1-weighted MT images in group 1 (p=0.0003 versus 0.3), whereas in group 2 it was statistically significant both on T1-weighted MT and FLAIR imaging (p=0.009 versus 0.05). CONCLUSION: FLAIR imaging is not helpful in the examination of brain tuberculomas compared with T1-weighted MT imaging, as it neither contributes to the characterization of lesion nor assesses the true disease load.
For optimal expression of delta-endotoxins from Bacillus thuringiensis in plants, preferential changes in the codon sequences, and reduction in overall AT content in the nucleotide sequence of the genes is important. Reports suggest that sequences with such modifications cannot be overexpressed in bacteria. We report here that the modified genes can be overexpressed in a strain of Escherichia coli carrying extra tRNA genes for some of the codons occurring at high frequency in plant genes and less preferred in E. coli. We also demonstrate that proteins when expressed as fusion products with NusA protein, are obtained as soluble fraction rather than in inclusion bodies. This allows easy and accurate LC50 analysis on insect pests.
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Babesia parasites generally require a defined percentage of serum in the culture medium for their in vitro growth. In this study, we attempted to culture Babesia bovis in a serum-free condition. The growth pattern and morphology of B. bovis in serum-free (plain) GIT medium were unaltered as compared to those of the standard growth condition containing 40% bovine serum in M199. When exposed to the test drugs, the parasite in plain GIT medium showed clearly lower IC50 values than those in 40% serum-containing G IT medium, indicating that several serum components may interfere with the drug bio-availability. Therefore, the serum-free culture system is useful for standardizing drug test protocols and understanding the roles of serum factors in the drug test.
OBJECTIVE: To improve the management of obese adults (18-75 y) in primary care. DESIGN: Cohort study. SETTINGS: UK primary care. SUBJECTS: Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. INTERVENTION: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. MAIN OUTCOME MEASURES: Proportion of practices trained and recruiting patients, and weight change at 12 months. RESULTS: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. CONCLUSION: The Counterweight programme provides a promising model to improve the management of obesity in primary care.
Thalidomide alone or in combination with steroids has significant activity in multiple myeloma (MM). However, given its teratogenic potential, analogs have been synthesized, retaining the anti-MM activity without these side effects. We examined the anti-MM activity of two thalidomide analogs, CPS11 and CPS49. Direct cytotoxicity of the drugs on myeloma cell lines and patient myeloma cells was examined using thymidine uptake. Tumor cell apoptosis was evaluated by flow cytometry as well as Western blotting for caspase and PARP cleavage. Cellular signaling events were examined by immunoblotting for phosphorylated proteins. Both drugs inhibit proliferation of several MM cell lines sensitive and resistant to conventional therapies. They decrease secretion of IL-6, IGF, and VEGF by marrow stromal cells. Importantly, they inhibit proliferation of MM cells adherent to stromal cells. These drugs induce caspase-mediated apoptosis in MM cell lines, as well as patient MM cells. They inhibit the PI3K/Akt and JAK/STAT (signal transducers and activators of transcription) pathways in MM cells and are antiangiogenic in matrigel-based assays. CPS11 and CPS49 have potent antimyeloma activity and can overcome protective effects of the tumor microenvironment. They have potent antiangiogenic activity and direct effect on bone marrow stroma. These encouraging preclinical data provide the basis for further evaluation in the clinic.
Multiple myeloma (MM) is characterized by accumulation of clonal plasma cells (PCs). CD45, a key regulator of antigen-mediated signaling and activation in lymphocytes, is present in early stages of PCs development. We studied CD45 expression on MM PCs by flow cytometry, correlating it to important biological disease characteristics. Additionally, we examined the expression of various adhesion molecules on PCs. A total of 75 patients with untreated MM (29), relapsed MM (17), smoldering MM (12), and monoclonal gammopathy of undetermined significance (MGUS) (17) were studied. The proportion of PCs expressing CD45 was higher among those with early disease (MGUS or smoldering MM) compared to those with advanced disease (new or relapsed MM) (43 vs 22%; P=0.005). Among those with advanced disease, patients with bone lesions had a lower percentage of CD45-positive (CD45+) PCs; 14 vs 34% (P=0.02). Patients with high-grade angiogenesis had a lower percentage of CD45+ PCs; 13 vs 31% (P=0.03). The median overall survival for the CD45+ group (>20% PCs positive) was 39 vs 18 months for the CD45-negative (CD45-) group (P=0.07). The expression of CD138, CD56 and CD54 were higher among the CD45- PCs. This study demonstrates important biological correlates of CD45 expression on myeloma cells.
PURPOSE: To study the epidemiology of chronic dacryocystitis and the success rate of external dacryocystorhinostomy (DCR) in Nepal. PATIENTS AND METHODS: This is a retrospective descriptive and interventional case series. A total of 662 records of patients with chronic dacryocystitis due to nasolacrimal duct obstruction, who were treated by means of external DCR without bicanalicular silastic tube intubation, were studied. STATISTICS: Mean for age with standard deviation and confidence intervals were calculated. The significance of the difference in means was calculated using the unpaired t-test. RESULTS: Of 662 patients, 67.6% were female. The mean age of the patients was 27.4 +/- 13.7 years (SE = 0.53, 95% CI = 26.34-28.46). Chronic dacryocystitis due to nasolacrimal duct obstruction was found in 86 patients (13.0%) from the high hills (mean age = 35.3 +/- 11.4 years, 95% CI = 32.85-37.75), but most patients (576, 87.0%) were from the subtropical lowlands with a monsoon climate (mean age = 26.9 +/- 13.3 years, 95% CI = 25.8-28.0; p = < 0.01). An overall success rate of 88.6% (89.8% for high-hill patients and 87.4% for those from the lowlands) was obtained after DCR. CONCLUSION: Chronic dacryocystitis is more common in the subtropical plains of Nepal with a monsoon climate than in the high hills. It is predominantly found in pre-menopausal females. External DCR without bicanalicular silastic tube intubation is an effective method for treating chronic dacryocystitis due to NLDO in these patients.
PURPOSE: To evaluate the effect of low-dose (<50 cGy) whole body ?-irradiation on the antioxidant defense system in the liver and the lungs of mice at various post-irradiation intervals. MATERIALS AND METHODS: Male Balb/c mice, 5 - 6 weeks of age, were divided into irradiated and non-irradiated groups. Whole body irradiation was done with gamma-rays from a (60)Co source at doses of 10, 25 and 50 cGy (48.78 cGy/min). Lipid peroxidation and antioxidant status were measured in the liver and the lungs at 4, 12 and 24 h after irradiation. RESULTS: Lipid peroxidation increased by 1.38 and 2.0 fold in lung and liver respectively at 12 h after exposure to 25 cGy. Whole body exposure to 25 and 50 cGy significantly (p < 0.05) increased the hepatic reduced glutathione at 4 h. Reduced glutathione continued to rise until 12 h and returned to the basal level at 24 h, whereas in the lungs it remained elevated until 24 h at 10 and 25 cGy. Antioxidant enzymes activities for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase increased by 1.22, 1.13, 1.22 and 1.11 fold respectively (p < 0.05) in the liver at 4 h after exposure to 50 cGy and remained elevated at almost the same level up to 12 h after exposure. Surprisingly these antioxidant defense enzymes remained unaltered in the lung at the above radiation doses. CONCLUSIONS: Low-dose whole body gamma-irradiation differentially modulates the antioxidant defense system in the liver and lungs of mice. The induction of endogenous glutathione, immediately after exposure to low-dose -irradiation, may be beneficial in protecting the cells from reactive oxygen species (ROS) induced oxidative stress.
Wastewaters discharged from the defence serviceable industries pose a serious environmental hazard due to their heavy metal load. The present study focused on optimizing the operational variables viz, hydraulic loading rate, bed height and feed concentration through bench scale study and using that for assessing the efficiency of pilot scale system with sulphur loaded carbon (AC-S) as the adsorbent in the removal of Pb (II). Static mode adsorption studies were also carried out for Pb (II) removal using treated (AC-S) and untreated carbon (AC). AC-S shows about 35 percent increase in maximum adsorption capacity over that on AC. The maximum adsorption capacity in the column mode for Pb (II) at the optimized conditions: bed height of 0.4 m, hydraulic loading rate of 7.5 m3h(-1)m(-2) and the feed concentration of 6 mg l(-1) for achieving 50% breakthrough concentration was found to be 2.89 mg g(-1). Adsorption mechanism involved during Pb (1) in the column has also been explored. Bohart-Adams model was used for modeling the bench scale data and predicting the adsorption behavior at pilot scale level.
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