Biomedical subjects
Publications and source records attributed to S Kumar.
We report a search for the flavor-changing neutral current decay B-->K(*)l+l- using a 29.1 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- storage ring. We observe the decay process B-->Kl+l-(l = e, mu), for the first time, with a branching fraction of B(B-->Kl+l-) = (0.75(+0.25)(-0.21)+/-0.09)x10(-6).
PURPOSE: Disability due to work injury, trauma or disease is prevalent in our society. Also, due to slower growth of population and rapid increase in ageing population there may be an increasing pressure on shrinking labour pool. The purpose of this study is to review disability profile with common disabilities, socioeconomic impact of these disabilities, make a case for ergonomics as an enabler, and provide a couple of case studies to illustrate the point. METHOD: Major disability statistical records were reviewed to reveal rates of disability in some countries of the world. Among them the age and gender association of disability has been described. Furthermore the major categories of disabilities associated with systemic disorders and their gradations have been described, e.g. cardiovascular conditions, pulmonary conditions and joint diseases. Finally, using a feed forward mechanism a specific and customized ergonomic intervention was designed for two workers with knee injury. RESULTS: The prevalence of disability has been reported to range between 0.2% -20.9%. A significant association of disability with ageing was reconfirmed. A significant socio-economic impact of disability including differential employment rate for normal and disabled was discovered. A strategy and a means to achieve increased functionality in people with disability using ergonomic intervention has been described. Using a custom designed shin pad for rehabilitation of two workers with injured knee who were also on compensation were successfully returned to work many weeks before they may have been able to resume their work. CONCLUSION: Using a functional classification and developing functional profiles of people with disability may allow ergonomists to develop generic as well as specific solutions to successfully intervene in many cases and improve their functional capacity.
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The Black Mango fault is a structural discontinuity that transforms motion between two segments of the active Himalayan Frontal Thrust (HFT) in northwestern India. The Black Mango fault displays evidence of two large surface rupture earthquakes during the past 650 years, subsequent to 1294 A.D. and 1423 A.D., and possibly another rupture at about 260 A.D. Displacement during the last two earthquakes was at minimum 4.6 meters and 2.4 to 4.0 meters, respectively, and possibly larger for the 260 A.D. event. Abandoned terraces of the adjacent Markanda River record uplift due to slip on the underlying HFT of 4.8 +/- 0.9 millimeters per year or greater since the mid-Holocene. The uplift rate is equivalent to rates of fault slip and crustal shortening of 9.6(-3.5)(+7.0) millimeters per year and 8.4(-3.6)(+7.3) millimeters per year, respectively, when it is assumed that the HFT dips 30 degrees +/- 10 degrees.
Vascular endothelial cell growth factor (VEGF, a potent endothelial cell mitogen in vitro) may be important in tumour development and its spread in vivo. In this preliminary study, we tested the hypotheses that (i) raised serum levels in Wilms' tumour fall after surgery, and (ii) rising levels predict adverse outcome. Serum VEGF was measured (ELISA) in 13 children about to undergo surgery, and serially on the following day, a week later, and finally 3-6 months after surgery. A simple follow-up at 6 months was also performed. The control group was 60 healthy adults. Before surgery, the median (inter-quartile range) VEGF in the children was 20 ng/ml (10.4-70.5) and was 1 ng/ml (0.5-4.0) in the adults. This difference is statistically highly significant (P=0.0001). After surgery, levels in the children fell significantly to 1.3 ng/ml (0.5-7.95) the following day and to 1.9 ng/ml (0.5-5.0) the following week (P<0.001, ANOVA). Six months after surgery, three of the children had died. A level of >10 ng/ml measured 3 months after surgery correctly identified all three deaths: levels were 1.3 ng/ml (0.5-1.9) in the survivors and were 20.0 ng/ml (15-104) in those who died. These data indicate a rapid reduction in raised VEGF following surgery for Wilms' tumour, but that rising levels predict poor prognosis.
Here, we analyze the thermodynamic parameters and their correlations in families containing homologous thermophilic and mesophilic proteins which show reversible two-state folding <--> unfolding transitions between the native and the denatured states. For the proteins in these families, the melting temperatures correlate with the maximal protein stability change (between the native and the denatured states) as well as with the enthalpic and entropic changes at the melting temperature. In contrast, the heat capacity change is uncorrelated with the melting temperature. These and additional results illustrate that higher melting temperatures are largely obtained via an upshift and broadening of the protein stability curves. Both thermophilic and mesophilic proteins are maximally stable around room temperature. However, the maximal stabilities of thermophilic proteins are considerably greater than those of their mesophilic homologues. At the living temperatures of their respective source organisms, homologous thermophilic and mesophilic proteins have similar stabilities. The protein stability at the living temperature of the source organism does not correlate with the living temperature of the protein. We tie thermodynamic observations to microscopics via the hydrophobic effect and a two-state model of the water structure. We conclude that, to achieve higher stability and greater resistance to high and low temperatures, specific interactions, particularly electrostatic, should be engineered into the protein. The effect of these specific interactions is largely reflected in an increased enthalpy change at the melting temperature.
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The concentration of melanin determines the intensity of colors of the skin and hair of animals. Melanin pigments are tyrosine-based polymers formed in melanocytes within specialized organelles called melanosomes. In order to understand the mechanism of melanin polymerization, lactoferrin, a basic protein with a pI value of 9.0, has been used to produce melanin. Lactoferrin is a monomeric iron-binding protein with a molecular weight of 80 kDa. The crystals of lactoferrin were soaked in a solution containing dihydroxyphenylalanine (DOPA) and tyrosinase enzyme. These crystals were used for X-ray intensity data collection. The intensity data were collected to 2.7-A resolution to an overall completeness of 91% with an R(sym) of 0.071. The crystals belong to orthorhombic space group P2(1)2(1)2(1) with cell dimensions: a = 85.0 A, b = 99.8 A, c = 103.4 A. The structure was determined by molecular replacement method, using the model of diferric mare lactoferrin, and refined to an R-factor 0.215 (R(free) = 0.287) for all the data to 2.7-A resolution. The final model comprises 5,281 protein atoms from 689 amino acids, 2Fe(3+), 2CO(2-)(3) ions, 2 indole-5,6-quinone molecules (IQ), and 73 water molecules. Two IQ molecules, one in each lobe, bind to lactoferrin. In the C-lobe, the IQ binds in the iron-binding cleft, whereas in the N-lobe, it is located in the side pocket between two alpha-helices, filled with solvent molecules in the native iron-saturated mare lactoferrin. The IQ molecules interact with protein molecule mainly through glutamic acid in both lobes, without significant perturbation to the protein structure. The orientation of N- and C-lobes in the present structure is similar to that observed in the native iron-saturated protein. However, as a result of the binding of IQ molecules, the orientations of the domains N1, N2 and C1, C2 in the two cases differ slightly.
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OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions.
Human mesenchymal stem/progenitor cells (MSCs) have been identified in adult bone marrow, but little is known about their presence during fetal life. MSCs were isolated and characterized in first-trimester fetal blood, liver, and bone marrow. When 10(6) fetal blood nucleated cells (median gestational age, 10(+2) weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean number (+/- SEM) of adherent fibroblastlike colonies was 8.2 +/- 0.6/10(6) nucleated cells (69.6 +/- 10/microL fetal blood). Frequency declined with advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages with a mean cumulative population doubling of 50.3 +/- 4.5. In their undifferentiated state, fetal blood MSCs were CD29(+), CD44(+), SH2(+), SH3(+), and SH4(+); produced prolyl-4-hydroxylase, alpha-smooth muscle actin, fibronectin, laminin, and vimentin; and were CD45(-), CD34(-), CD14(-), CD68(-), vWF(-), and HLA-DR(-). Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of cord blood CD34(+) cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 +/- 2.0/10(6) nucleated cells) and bone marrow (12.6 +/- 3.6/10(6) nucleated cells). Their morphology, growth kinetics, and immunophenotype were comparable to those of fetal blood-derived MSCs and similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages, even after sorting and expansion of a single mesenchymal cell. MSCs similar to those derived from adult bone marrow, fetal liver, and fetal bone marrow circulate in first-trimester human blood and may provide novel targets for in utero cellular and gene therapy.
Data on replacement mutations in genes of disease patients exist in a variety of online resources. In addition, genome sequencing projects and individual gene sequencing efforts have led to the identification of disease gene homologs in diverse metazoan species. The availability of these two types of information provides unique opportunities to investigate factors that are important in the development of genetically based disease by contrasting long and short-term molecular evolutionary patterns. Therefore, we conducted an analysis of disease-associated human genetic variation for seven disease genes: the cystic fibrosis transmembrane conductance regulator, glucose-6-phosphate dehydrogenase, the neural cell adhesion molecule L1, phenylalanine hydroxylase, paired box 6, the X-linked retinoschisis gene and TSC2/tuberin. Our analyses indicate that disease mutations show definite patterns when examined from an evolutionary perspective. Human replacement mutations resulting in disease are overabundant at amino acid positions most conserved throughout the long-term history of metazoans. In contrast, human polymorphic replacement mutations and silent mutations are randomly distributed across sites with respect to the level of conservation of amino acid sites within genes. Furthermore, disease-causing amino acid changes are of types usually not observed among species. Using Grantham's chemical difference matrix, we find that amino acid changes observed in disease patients are far more radical than the variation found among species and in non-diseased humans. Overall, our results demonstrate the usefulness of evolutionary analyses for understanding patterns of human disease mutations and underscore the biomedical significance of sequence data currently being generated from various model organism genome sequencing projects.
We report the first observation of the exclusive decay process B-->J/psi K(1)(1270) using a sample of 11.2M BB macro meson pairs collected in the Belle detector at the KEKB asymmetric energy e(+)e(-) collider. We measure branching fractions of B[B(0)-->J/psi K(0)(1)(1270)] = (1.30+/-0.34+/-0.32) x 10(-3) and B[B(+)-->J/psi K(+)(1)(1270)] = (1.80+/-0.34+/-0.39) x 10(-3), where the first error is statistical and the second is systematic. These modes constitute approximately 15% of the total number of B-->J/psi X decays. No evidence is seen for B-->J/psi K(1)(1400) and we set an upper limit for this branching fraction.
Dynactin has been proposed to link the microtubule-associated motor cytoplasmic dynein with membranous cargo; however, the mechanism by which dynactin-membrane interaction is regulated is unknown. Here we show that dynein and dynactin exist in discrete cytosolic and membrane-bound states in the filamentous fungus Neurospora crassa. Results from in vitro membrane-binding studies show that dynein and dynactin-membrane interaction is co-dependent. p150(Glued) of dynactin has been shown to interact with dynein intermediate chain and dynactin Arp1 filament; however, it is not known to play a direct role in membrane binding. In this report we describe our analysis of 43 p150(Glued) mutants, and we show that C-terminal deletions which remove the terminal coiled-coil (CC2) and basic domain (BD) result in constitutive dynactin-membrane binding. In vitro addition of recombinant p150(Glued) CC2+BD protein blocks dynactin-membrane binding. We propose that the C-terminal domains of p150(Glued) regulate dynactin-membrane binding through a steric mechanism that controls accessibility of the Arp1 filament of dynactin to membranous cargo.
Staphylococcus aureus is a common cause of bacterial infections in patients infected with human immunodeficiency virus (HIV). We studied 53 male patients who had 57 episodes of S. aureus bacteremia (SAB). The incidence of SAB per 1000 hospitalized patients was 13.2 among HIV-positive male patients and 0.8 among HIV-negative male patients, yielding a 16.5-fold increase in the odds ratio for SAB among HIV-positive male patients. Almost all episodes of SAB were community acquired. Long-term indwelling catheters were the most common predisposing factor. Prior antibiotic use was more frequently associated with SAB in HIV-positive patients than in HIV-negative patients. A trend was seen among HIV-positive patients toward more numerous infections with beta-lactam antibiotic-resistant (i.e., methicillin-resistant) S. aureus, but such patients had similar outcomes, even though they often did not receive vancomycin during the initial 48 hours of treatment. A better understanding of the epidemiology and clinical manifestations of SAB in HIV-positive patients will offer important opportunities for prevention of this frequent complication.
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Remote sensing was employed for the first time to measure NH3 levels in the exhaust of on-road light duty motor vehicles. The sensor also measured the concentration of CO2, CO, hydrocarbons, and NO, among other pollutants, in the emitted exhaust. Field measurements were conducted at a Los Angeles freeway on-ramp; vehicles traveled at cruise speeds between 20 and 25 m s(-1) (45-55 mi h(-1)). Mean fleet NH3 levels of 44.7 +/- 4.1 ppm were observed. These emissions exhibited a highly skewed distribution: 50.1% of the emitted NH3 was contributed by 10% of the sampled fleet. The pollutant distribution among high NH3 emitters is analyzed to identify the conditions that lead to three-way catalyst malfunction and, hence, NH3 formation. In contradiction with previous reports, we found that high NH3 emissions could not be attributed to vehicles running under rich air-fuel conditions. We estimate a mean fleet NH3 mass emission rate of 667 +/- 57 mg L(-1) (Er = 94 +/- 8 mg km(-1)). These findings could have significant implications on air quality in the South Coast Air Basin (SoCAB) of California, since they support the hypothesis that emissions from motor vehicles constitute a dominant regional source of NH3, between 20 and 27% of total daily emissions. As NH3 is the predominant atmospheric base, tropospheric levels play a key role in the buffering capacity of the atmosphere and, hence, the formation of fine aerosol. Our results could explain the ubiquitous distribution of ammonium fine particles observed during fall stagnation conditions in the SoCAB.