Synchronous T-cell lymphoblastic lymphoma, chronic myelomonocytic leukemia and myeloma with sequential acute myeloid leukemia transformation.
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Letter↗
Biomedical subjects
Rajeev Gupta
Publications and source records attributed to Rajeev Gupta.
Global genomic population structure of wild and cultivated oat reveals signatures of chromosome rearrangements.
The genus Avena consists of approximately 30 wild and cultivated oat species. Cultivated oat is an important food crop, yet the broader genetic diversity within the Avena gene pool remains underexplored and underexploited. Here, we characterize over 9000 wild and cultivated hexaploid oat accessions of global origin using genotyping-by-sequencing and explore population structure using multidimensional scaling and population-based clustering methods. We also conduct analyses to reveal chromosome regions associated with local adaptation, sometimes resulting from large-scale chromosome rearrangements. We report four distinct genetic populations within the wild species A. sterilis, a distinct population of cultivated A. byzantina, and multiple populations within cultivated A. sativa. Some chromosome regions associated with local adaptation are also associated with confirmed structural rearrangements on chromosomes 1A, 1C, 3C, 4C, and 7D. This work provides evidence suggesting multiple polyploid origins, multiple domestications, and/or reproductive barriers amongst Avena populations caused by differential chromosome structure.
Avena↗
In vivo fluorescein staining of SI-30NB silicone intraocular lens.
We report a case of a 48-year-old pseudophakic woman who presented 3 weeks after Heidelberg retinal angiography using intravenous sodium fluorescein 2%. Bilateral retinal vasculitis with severe retinal ischemia and extensive capillary dropouts had been diagnosed. Anterior segment examination revealed green staining on the silicone optic of the 3-piece SI-30NB intraocular lens (IOL) (AMO), with no cell or flare in the aqueous humor. The anterior and posterior capsules were not stained. The patient did not report dark vision, double vision, or altered color vision. The anterior and posterior IOL surfaces demonstrated an autofluorescence at the time of fundus photography, which persisted to the 6-week examination although there were no symptoms. This is suggestive of deposits of sodium fluorescein on the IOL surface following angiography.
Female↗
Zero prevalence of diabetes in camel milk consuming Raica community of north-west Rajasthan, India.
OBJECTIVES: Preliminary trials reflected the low prevalence of diabetes in Raica community consuming camel milk habitually. Our objective was to describe the prevalence and clinical factors associated with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) among adults (>or=20 years) in large population group. DESIGN: Population based, cross sectional study METHODS: 2099 participants from different villages of north-west Rajasthan were selected using stratified sampling of a representative Raica and non-Raica Community, consuming or not consuming camel milk. Demographic, clinical, anthropometric parameters were obtained and oral glucose tolerance tests were performed in all individuals to diagnose IFG, IGT and DM. Associations were investigated using multivariate logistic regression using SPSS Version 10.0. RESULTS: In the present study, the prevalence of diabetes in Raica community consuming camel milk (RCCM, n=501) was 0%; Raica community not consuming camel milk (RCNCM, n=554) was 0.7%; non-Raica community consuming milk (NRCCM, n=515) was 0.4% and non-Raica community not consuming camel milk (NRCNCM, n=529) was 5.5%. Stepwise logistic regression analysis showed that consumption of camel milk was statistically highly significant as protective factor for diabetes. Multiple logistic regression analysis revealed that camel milk consumption and community factor were associated with decreased prevalence of diabetes. CONCLUSION: Camel milk consumption and lifestyle have definite influence on prevalence of diabetes. Hence, adopting such life pattern may play protective role in preventing diabetes to some extent.
Adult↗
Characterization of the particulate methane monooxygenase metal centers in multiple redox states by X-ray absorption spectroscopy.
The integral membrane enzyme particulate methane monooxygenase (pMMO) converts methane, the most inert hydrocarbon, to methanol under ambient conditions. The 2.8-A resolution pMMO crystal structure revealed three metal sites: a mononuclear copper center, a dinuclear copper center, and a nonphysiological mononuclear zinc center. Although not found in the crystal structure, solution samples of pMMO also contain iron. We have used X-ray absorption spectroscopy to analyze the oxidation states and coordination environments of the pMMO metal centers in as-isolated (pMMO(iso)), chemically reduced (pMMO(red)), and chemically oxidized (pMMO(ox)) samples. X-ray absorption near-edge spectra (XANES) indicate that pMMO(iso) contains both Cu(I) and Cu(II) and that the pMMO Cu centers can undergo redox chemistry. Extended X-ray absorption fine structure (EXAFS) analysis reveals a Cu-Cu interaction in all redox forms of the enzyme. The Cu-Cu distance increases from 2.51 to 2.65 A upon reduction, concomitant with an increase in the average Cu-O/N bond lengths. Appropriate Cu2 model complexes were used to refine and validate the EXAFS fitting protocols for pMMO(iso). Analysis of Fe EXAFS data combined with electron paramagnetic resonance (EPR) spectra indicates that Fe, present as Fe(III), is consistent with heme impurities. These findings are complementary to the crystallographic data and provide new insight into the oxidation states and possible electronic structures of the pMMO Cu ions.
Copper↗
Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms.
BACKGROUND: Renal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects. METHODS: Twelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of > or =2 years duration and moderate CRI diagnosed by serum creatinine > or =3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes. RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01-3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88-4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97-3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16-2.14 and O.R. 1.81, 95%CI: 1.21-2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34-3.17) were also observed. CONCLUSION: SNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising.
Asian People↗
Field- and pressure-induced phases in Sr4Ru3O10: a spectroscopic investigation.
We have investigated the magnetic-field- and pressure-induced structural and magnetic phases of the triple-layer ruthenate Sr4Ru3O10. Magnetic-field-induced changes in the phonon spectra reveal dramatic spin-reorientation transitions and strong magnetoelastic coupling in this material. Further, we are able to deduce key magnetoelastic coupling parameters, and evidence that the magnetic moments are localized on the Ru sites. Additionally, pressure-dependent Raman measurements at different temperatures reveal an anomalous negative Gruneisen parameter associated with the B(1g) mode (approximately 380 cm(-1)) at low temperatures (T < 75 K), which can be explained consistently with the field-dependent Raman data.
Journal Article↗
Role of scheimpflug imaging in traumatic intralenticular foreign body.
PURPOSE: The role of Pentacam Scheimpflug imaging in evaluation of penetrating eye injury and intralenticular foreign body (ILFB). DESIGN: Interventional case report. METHODS: A 35-year-old male presented to our clinical practice with penetrating eye injury and endophthalmitis. Scheimpflug imaging helped localize the intralenticular foreign body (ILFB). It confirmed the posterior capsule to be intact. He underwent phacoemulsification, foreign body removal, and intraocular lens (IOL) implant. Postoperatively, IOL was imaged with Pentacam Scheimpflug imaging. RESULTS: Scheimpflug imaging allowed us to confirm the presence and exact location of ILFB and its relation to the intact posterior capsule as well as the postoperative IOL positioning. This helped in better planning of management of traumatic cataract with ILFB. CONCLUSIONS: Pentacam is a potential tool for accurate localization of foreign bodies lodged in the lens and provides an objective basis for better patient counseling and surgical planning.
Adult↗
Scheimpflug imaging in late Capsular Bag Distention syndrome after phacoemulsification.
PURPOSE: To describe two cases of late Capsular Bag Distention syndrome (CBDS) and posterior capsular opacification (PCO) as documented on Pentacam. DESIGN: Case series. METHODS: A 55-year-old male and a 72-year-old female presented three years after phacoemulsification and intraocular lens (IOL) implantation with a complaint of decreased vision. Scheimpflug imaging was done using Pentacam. Patients underwent Nd:YAG capsulotomy for PCO, and postcapsulotomy capsular bag dynamics were imaged on Pentacam. RESULTS: Three years after phacoemulsification, patients presented with blurred vision and posterior bowing of opacified posterior capsule. Anterior capsular opening was apparently sealed by lens optic, and space between IOL and opacified posterior capsule was filled with turbid fluid. Nd:YAG laser capsulotomy was done. All findings, including collapse of distended bag, were precisely documented on Scheimpflug images. CONCLUSIONS: Pentacam Scheimpflug imaging is a useful technique to diagnose and document the presence and progress of CBDS and PCO.
Aged↗
Building patient confidence through effective communication.
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Clinical Competence↗
Smoking, educational status and health inequity in India.
Health related behaviours, especially smoking and tobacco use, are major determinants of health and lead to health inequities. Smoking leads to acute respiratory diseases, tuberculosis and asthma in younger age groups and non communicable diseases such as chronic lung disease, cardiovascular diseases and cancer in middle and older age. We observed an inverse association of educational status with tobacco use (smoking and other forms) in western Indian State of Rajasthan. In successive cross-sectional epidemiological studies- the Jaipur Heart Watch (JHW)- in rural (JHWR; n=3148, men=1982), and urban subjects: JHW-1 (n=2212, men=1415), JHW-2 (n=1124, men=550) and JHW-3 (n=458, men=226), we evaluated various cardiovascular risk factors. The greatest tobacco consumption was observed among the illiterate and low educational status subjects (nil, 1-5, 6-10, >10 yr of formal education) as compared to more literate in men (JHW-R 60, 51, 46 and 36% respectively; JHW-1 44, 52, 30 and 18% JHW-2 54, 43, 29 and 24%; and JHW-3 50, 27, 25 and 25%) as well as women (Mantel Haenzel test, P for trend <0.05). In the illiterate subjects the odds ratios (OR) and 95 per cent confidence intervals (CI) for smoking or tobacco use as compared to the highest educational groups in rural (men OR 2.68, CI 2.02, 3.57; women OR 3.13, CI 1.22, 8.08) as well as larger urban studies- JHW-1 (men OR 2.47, CI 1.70, 3.60; women OR 13.78, CI 3.35, 56.75) and JHW-2 (men OR 3.81; CI 1.90, 7.66; women OR 13.73, CI 1.84, 102.45) were significantly greater (P<0.01). Smoking significantly correlated with prevalence of coronary heart disease and hypertension. Other recent Indian studies and national surveys report similar associations. Health ethicists argue that good education and health lead to true development in an underprivileged society. We propose that improving educational status, a major social determinant of health, can lead to appropriate health related behaviours and prevent the epidemics of non communicable diseases in developing countries.
Educational Status↗
Correlation of regional cardiovascular disease mortality in India with lifestyle and nutritional factors.
OBJECTIVE: There is a wide disparity in prevalence and cardiovascular disease mortality in different Indian states. To determine significance of various nutritional factors and other lifestyle variables in explaining this difference in cardiovascular disease mortality we performed an analysis. METHODS AND RESULTS: Mortality data were obtained from the Registrar General of India. In 1998 the annual death rate for India was 840/100,000 population. Cardiovascular diseases contribute to 27% of these deaths and its crude mortality rate was 227/100,000. Major differences in cardiovascular disease mortality rates in different Indian states were reported varying from 75-100 in sub-Himalayan states of Nagaland, Meghalaya, Himachal Pradesh and Sikkim to a high of 360-430 in Andhra Pradesh, Tamil Nadu, Punjab and Goa. Lifestyle data were obtained from national surveys conducted by the government of India. The second National Family Health Survey (26 states, 92,447 households, 301,984 adults) conducted in 1998-1999 reported on various demographic and lifestyle variables and India Nutrition Profile Study reported dietary intake of 177,841 adults (18 states, 75,229 men, 102,612 women). Cardiovascular disease mortality rates were correlated with smoking, literacy levels, prevalence of stunted growth at 3-years (as marker of fetal undernutrition), adult mean body mass index, prevalence of overweight and obesity, dietary consumption of calories, cereals and pulses, green leafy vegetables, roots, tubers and other vegetables, milk and milk products, fats and oils, and sugar and jaggery. As a major confounder in different states is poverty, all the partial correlation coefficients were adjusted for illiteracy, fertility rate and infant mortality rate. There was a significant positive correlation of cardiovascular disease mortality with prevalence of obesity (R=0.37) and dietary consumption of fats (R=0.67), milk and its products (R=0.27) and sugars (R=0.51) and negative correlation with green leafy vegetable intake (R=-0.42) (p<0.05). CONCLUSIONS: There are large disparities in cardiovascular disease mortality in different Indian states. This can be epidemiologically explained by difference in dietary consumption of fats, milk, sugar and green-leafy vegetables and prevalence of obesity.
Asthma↗
The NLRR gene family and mouse development: Modified differential display PCR identifies NLRR-1 as a gene expressed in early somitic myoblasts.
During vertebrate embryogenesis, the somites form by segmentation of the trunk mesoderm, lateral to the neural tube, in an anterior to posterior direction. Analysis of differential gene expression during somitogenesis has been problematic due to the limited amount of tissue available from early mouse embryos. To circumvent these problems, we developed a modified differential display PCR technique that is highly sensitive and yields products that can be used directly as in situ hybridisation probes. Using this technique, we isolated NLRR-1 as a gene expressed in the myotome of developing somites but not in the presomitic mesoderm. Detailed expression analysis showed that this gene was expressed in the skeletal muscle precursors of the myotome, branchial arches and limbs as well as in the developing nervous system. Somitic expression occurs in the earliest myoblasts that originate from the dorsal lip in a pattern reminiscent of the muscle determination gene Myf5, but not at the ventral lip, indicating that NLRR-1 is expressed in a subset of myotome cells. The NLRR genes comprise a three-gene family encoding glycosylated transmembrane proteins with external leucine-rich repeats, a fibronectin domain, an immunoglobulin domain and short intracellular tails capable of mediating protein-protein interaction. Analysis of NLRR-3 expression revealed regulated expression in the neural system in developing ganglia and motor neurons. NLRR-2 expression appears to be predominately confined to the adult. The regulated embryonic expression and cellular location of these proteins suggest important roles during mouse development in the control of cell adhesion, movement or signalling.
Amino Acid Sequence↗
Stability of photodiodes under irradiation with a 157-nm pulsed excimer laser.
We have measured the stability of a variety of photodiodes exposed to 157-nm light from a pulsed excimer laser by using a radiometry beamline at the Synchrotron Ultraviolet Radiation Facility at the National Institute of Standards and Technology. The intense, pulsed laser light exposed the photodiodes, whereas the low-intensity, continuously tunable light from the synchrotron source measured changes in the characteristics of the photodiodes, such as in the responsivity and the reflectance from the surface of a photodiode. Photodiodes studied include both silicon pn-junction and Schottky-barrier types. Among these photodiodes, we found that the damage mechanism for photodiodes with SiO2-based passivating layers is mainly the buildup of SiO2-Si interface trap states. The interface trap state buildup is well known for other semiconductor devices and is generally recognized as a product induced by radiation with an energy more than the 9-eV SiO2 bandgap energy rather than the 7.9-eV energy of the 157-nm radiation. Based on the generation of interface trap states, a model is proposed to describe the dependence of detector responsivity on exposure to 157-nm radiation. We also observed slow recovery in some of the damaged photodiodes, confirming that some of the interface trap states are only semipermanent. Radiation damage induced by low-power continuous 157-nm synchrotron light was also studied. As for the other photodiodes with no SiO2 layers, measurement results support the assumption that the changes in responsivity are due mainly to the deposition of thin layers on the tops of the detectors during laser irradiation.
Journal Article↗
Developmental impact of leukemic fusion genes on stem cell fate.
Stem and progenitor cells present attractive targets for transformation by leukemia-associated fusion genes generated by chromosomal translocation. The mechanism by which these fusion genes corrupt the transcriptional programs of these cellular compartments remains largely unknown. We have sought to gain insight into these issues through expressing TEL-AML1 and TEL-TRKC fusion genes in murine stem cells and recording effects on cell behavior in a transplant setting.
Animals↗
Treatment of stable angina pectoris with trimetazidine modified release in Indian primary-care practice.
INTRODUCTION: In primary-care practice, trimetazidine is frequently used in combination with other antianginal drugs to enhance antianginal efficacy because of its metabolic mode of action. This study investigates whether a new twice-daily trimetazidine modified release formulation with improved pharmacokinetic properties is more effective and acceptable than the older thrice-daily immediate-release formulation. METHODS: In a multicenter prospective study, patients with uncontrolled stable angina pectoris receiving combination antianginal treatment that included the thrice-daily trimetazidine were identified. The immediate-release trimetazidine formulation was substituted with twice-daily trimetazidine modified release (Flavedon) MR), with no other changes in the treatment regimen. Follow-up was for 3 months. The primary outcomes were entirely clinical: frequency of anginal attacks and nitroglycerin (glyceryl trinitrate) consumption. RESULTS: In 279 patients, substitution of thrice-daily trimetazidine with twice-daily trimetazidine modified release reduced mean frequency of angina by four attacks per week (95% CI 3.1, 4.9; p < 0.01) and nitroglycerin consumption by 3.6 tablets per week (95% CI 2.9, 4.3; p < 0.01). The magnitude of these benefits was directly proportional to the number of antianginal drugs used in combination with trimetazidine. There were no withdrawals due to adverse effects, and daily compliance was 98%. CONCLUSION: The twice-daily trimetazidine modified release is more effective and acceptable than the thrice-daily formulation for the combination treatment of stable angina in primary-care practice.
Aged↗
Structural analysis uncovers a role for redox in regulating FKBP13, an immunophilin of the chloroplast thylakoid lumen.
Change in redox status has long been known to link light to the posttranslational regulation of chloroplast enzymes. So far, studies have been conducted primarily with thioredoxin-linked members of the stroma that function in a broad array of biosynthetic and degradatory processes. Consequently, little is known about the role of redox in regulating the growing number of enzymes found to occur in the lumen, the site of oxygen evolution in thylakoid membranes. To help fill this gap, we have studied AtFKBP13, an FKBP-type immunophilin earlier shown to interact with a redox-active protein of the lumen, and found the enzyme to contain a pair of disulfide bonds in x-ray structural studies. These disulfides, which in protein mutagenesis experiments were shown to be essential for the associated peptidyl-prolyl isomerase activity, are unique to chloroplast FKBPs and are absent in animal and yeast counterparts. Both disulfide bonds were redox-active and were reduced by thioredoxin from either chloroplast or bacterial sources in a reaction that led to loss of enzyme activity. The results suggest a previously unrecognized paradigm for redox regulation in chloroplasts in which activation by light is achieved in concert with oxygen evolution by the oxidation of sulfhydryl groups (conversion of SH to S-S). Such a mechanism, occurring in the thylakoid lumen, is in direct contrast to regulation of enzymes in the stroma, where reduction of disulfides targeted by thioredoxin (S-S converted to SH) leads to an increase in activity in the light.
Amino Acid Sequence↗
Chalcogens as terminal ligands to iron: synthesis and structure of complexes with Fe(III)-S and Fe(III)-Se motifs.
Metal complexes with terminal chalcogenido ligands are known for the early transition-metal complexes, yet for the heavier congeners (e.g., sulfido and selenido), there are no analogous examples for the late 3d metal ions. Reported herein is the isolation and characterization of monomeric iron(III) complexes containing sulfido and selenido ligands; isolation was accomplished using the tripodal ligand tris[(N'-tert-butylureaylato)-N-ethylene]aminato ([H3buea]3-). The FeIII-E (E = S2-, Se2-) complexes were prepared from the iron(II) precursor, [FeII(H3buea)]2-, and the elemental forms of the chalogen. The formulation of [FeIIIH3buea(S)]2- and [FeIIIH3buea(Se)]2- as monomeric complexes with Fe-E units is supported by spectroscopic, analytical, and X-ray diffraction studies. For instance, X-band EPR spectra contain well-resolved axial signals, which are consistent with each complex having S = 5/2 ground states. The solid-state molecular structures reveal FeIII-E bond lengths of 2.211(1) and 2.355(1) A for [FeIIIH3buea(S)]2- and [FeIIIH3buea(Se)]2-, respectively. The primary coordination sphere for each complex also contains three deprotonated urea nitrogen atoms from [H3buea]3-; the apical amine nitrogen atom weakly interacts with the iron centers at distances of greater than 2.6 A. The terminal chalcogenido ligands appear to weakly hydrogen-bond with the urea NH groups of the [H3buea]3-; however, open H-bond cavities are observed for [FeIIIH3buea(S)]2- and [FeIIIH3buea(Se)]2-, which may contribute to their observed long-term instability.
Ferric Compounds↗