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Biomedical subjects

U Singh

Publications and source records attributed to U Singh.

At least 19 recordsLinked to original sources
PubMed1998

The novel core promoter element GAAC in the hgl5 gene of Entamoeba histolytica is able to direct a transcription start site independent of TATA or initiator regions.

Entamoeba histolytica, an enteric protozoa, is the third leading parasitic cause of death worldwide. Investigation of the transcriptional machinery of this eukaryotic pathogen has revealed an unusual core promoter structure that consists of nonconsensus TATA and initiator regions and a novel third conserved core promoter sequence, the GAAC element. Mutation of this region in the hgl5 promoter decreases reporter gene expression and alters the transcription start site. Using positional analysis of this element, we have now demonstrated that it is able to direct a new transcription start site, 2-7 bases downstream of itself, independent of TATA and Inr regions. The GAAC region was also shown to control the rate of transcription via nuclear run on analysis and an amebic nuclear protein was demonstrated to specifically interact with this sequence. This is the first description in the eukaryotic literature of a third conserved core promoter element, distinct from TATA or initiator regions, that is able to direct a transcription start site. We have formulated two models for the role of the GAAC region: (i) the GAAC-binding protein is a part of the TFIID complex and (ii) the GAAC-binding protein functions to "tether" TATA-binding protein to the TATA box.

Animals↗
PubMed1997

Transcription initiation is controlled by three core promoter elements in the hgl5 gene of the protozoan parasite Entamoeba histolytica.

Entamoeba histolytica is a single cell eukaryote that is the etiologic agent of amoebic colitis. Core promoter elements of E. histolytica protein encoding genes include a TATA-like sequence (GTATTTAAAG/C) at -30, a novel element designated GAAC (GAACT) that has a variable location between TATA and the site of transcription initiation, and a putative initiator (Inr) element (AAAAATTCA) overlying the site of transcription initiation. The presence of three separate conserved sequences in a eukaryotic core promoter is unprecedented and prompted examination of their roles in regulating transcription initiation. Alterations of all three regions in the hgl5 gene decreased reporter gene activity with the greatest effect seen by mutation of the GAAC element. Positional analysis of the TATA box demonstrated that transcription initiated consistently 30-31 bases downstream of the TATA region. Mutation of either the TATA or GAAC elements resulted in the appearance of new transcription start sites upstream of +1 in the promoter of the hgl5 gene. Mutation of the Inr element resulted in no change in the site of transcription initiation; however, in the presence of a mutated TATA and GAAC regions, the Inr element controlled the site of transcription initiation. We conclude that all three elements play a role in determining the site of transcription initiation. The variable position of the GAAC element relative to the site of transcription initiation, and the multiple transcription initiations that resulted from its mutation, indicate that the GAAC element has an important and apparently novel role in transcriptional control in E. histolytica.

Animals↗
PubMed1997

Oxidation of low-density lipoproteins produces levuglandin-protein adducts.

Free-radical oxidation of human low-density lipoprotein (LDL) produces levuglandin (LG)-protein adducts that were detected with an enzyme-linked immunosorbent assay using LGE2-KLH antibodies which recognize LGE2-derived pyrroles. The level of immunoreactivity increases with time of oxidation and reaches a maximum by 8 h. The yield of pyrrole varies nonlinearly with the level of LG adduction to LDL. At low LG:LDL ratios, such as those detected in oxidized LDL, the reaction of primary amino groups with LGE2 produces mostly non-pyrrole adducts that are not immunoreactive. Concomitant phospholipolysis must occur if the generation of immunoreactive epitopes in LDL involves oxidation of arachidonyl phospholipids. Thus, since a protein adduct prepared from synthetic LGE2-2-lysophosphatidylcholine ester showed, at most, only 0.5% cross-reactivity with the LGE2-KLH antibodies, the epitopes detected in oxidized LDL are almost certainly not protein adducts of LG-phospholipid esters. As expected, hydrolysis of the carboxylic ester in the protein adduct of LGE2-2-lysophosphatidylcholine ester by treatment with phospholipase A2 produced a fully immunoreactive LGE2-protein adduct.

Cross Reactions↗
PubMed1996

(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta.

Protein kinase C (PKC) is a family of closely related serine and threonine kinases. Overactivation of some PKC isozymes has been postulated to occur in several diseases states, including diabetic complications. Selective inhibition of overactivated PKC isozymes may offer a unique therapeutic approach to disease states such as diabetic retinopathy. A novel series of 14-membered macrocycles containing a N-N'-bridged bisindolylmaleimide moiety is described. A panel of eight cloned human PKC isozymes (alpha, beta I, beta II, gamma, delta, epsilon, sigma, eta) was used to identify the series and optimize the structure and associated activity relationship. The dimethylamine analogue LY333531 (1), (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene++ +-1,3(2H)-dione, inhibits the PKC beta I (IC50 = 4.7 nM) and PKC beta II (IC50 = 5.9 nM) isozymes and was 76- and 61-fold selective for inhibition of PKC beta I and PKC beta II in comparison to PKC alpha, respectively. The additional analogues described in the series are also selective inhibitors of PKC beta. LY333531 (1) exhibits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to other ATP dependent kinases (protein kinase A, calcium calmodulin, caesin kinase, src tyrosine kinase). The cellular activity of the series was assessed using bovine retinal capillary endothelial cells. Retinal endothelial cell dysfunction has been implicated in the development of diabetic retinopathy. Plasminogen activator activity stimulated by a phorbol ester (4 beta-phorbol 12,13-dibutyrate) in endothelial cells was inhibited by the compounds in the series with ED50 values ranging from 7.5 to 0.21 microM. A comparison of the PKC isozyme and related ATP dependent kinase inhibition profiles is provided for the series and compared to the profile for staurosporine, a nonselective PKC inhibitor. The cellular activity of the series is compared with that of the kinase inhibitor staurosporine.

Amino Acid Sequence↗
PubMed1996

Phytic acid, in vitro protein digestibility, dietary fiber, and minerals of pulses as influenced by processing methods.

The objective of this project was to determine the effect of various types of processing on selected nutrition related parameters of commonly consumed Indian pulses and soybean. Germination reduced the phytic acid content of chickpea and pigeonpea seeds by over 60%, and that of mung bean, urd bean, and soybean by about 40%. Fermentation reduced phytic acid contents by 26-39% in all these legumes with the exception of pigeonpea in which it was reduced by more than 50%. Autoclaving and roasting were more effective in reducing phytic acid in chickpea and pigeonpea than in urd bean, mung bean, and soybean. Germination and fermentation greatly increased the in vitro protein digestibility (IVPD). IVPD was only slightly increased by roasting and autoclaving of all legumes. Germination and fermentation also remarkably decreased the total dietary fiber (TDF) in all legumes. Autoclaving and roasting resulted in slight increases in TDF values. All the processing treatments had little effect on calcium, magnesium and iron contents.

Dietary Fiber↗
PubMed1996

Infectious etiologies of rhabdomyolysis: three case reports and review.

Rhabdomyolysis can be precipitated by trauma, ischemia, metabolic defects, electrolyte abnormalities, drugs, and a wide variety of infectious diseases. At our institution, recent cases of rhabdomyolysis induced by influenza prompted us to review the infectious etiologies of this entity. In addition, a thorough literature search revealed numerous case reports but no general review on this subject. This study describes representative recent cases from our institution and details the wide variety of infections that can cause muscle damage. The pathophysiological mechanisms, muscle histology, and correlation with renal dysfunction are also discussed.

Adolescent↗
PubMed1995

Variability in phytic acid content and protein digestibility of grain legumes.

Several genotypes, number given within parenthesis, of chickpea, pigeonpea, urd bean, mung bean and soybean, differing in seed characteristics were analyzed for phytic acid, in vitro protein digestibility (IVPD), protein, total phosphorus, and seed size. Phytic acid contents and IVPD values differed significantly among and within these species. Phytic acid content (mg/g) was the highest in soybean (36.4) followed by urd bean (13.7), pigeonpea (12.7), mung bean (12.0) and chickpea (9.6). On an average, phytic acid constituted 78.2 percent of the total phosphorus content and this percentage figure was the highest in soybean and the lowest in mung bean. In vitro protein digestibility (IVPD) of pigeonpea and chickpea genotypes varied from 60.4 to 74.4 percent and 65.3 to 79.4 percent, respectively. The IVPD values of genotypes of mung bean, urd bean and soybean ranged from 67.2 to 72.2 percent, 55.7 to 63.3 percent and 62.7 to 71.6 percent, respectively. There was a significant negative correlation between phytic acid and IVPD of these genotypes. Phytic acid was significantly and positively correlated with protein but the magnitude of correlation was very low in chickpea and pigeonpea. Results indicate that the genotypes of pulses with low phytic acid content could be identified and used in breeding program to improve their nutritive value and utilization.

Dietary Proteins↗
PubMed1995

Haematological profile in typhoid fever.

The haematological profile in 20 culture proven patients with typhoid fever of varying age and of both sexes was studied. Significant changes observed were anaemia, leucopenia, eosinopenia, thrombocytopenia and sub-clinical disseminated intravascular coagulation. The bone marrow of typhoid patients showed myeloid maturation arrest, decrease in the number of erythroblasts and megakaryocytes with increased phagocytic activity of histiocytes.

Adolescent↗
PubMed1995

Effect of low energy diet and weight loss on major risk factors, central obesity and associated disturbances in patients with essential hypertension.

Obesity, especially central, increases the risk of hypertension, hypertriglyceridaemia and diabetes to a significant extent. To determine whether dietary weight reduction can reduce blood pressure (BP) and other cardiovascular risk factors, 217 hypertensives were randomised to receive either 1600 Kcal/day diet (group A, n = 108) or the usual 2100 Kcal/day diet (group B, n = 109). Sodium intake and physical activity were kept similar in both groups. After 16 weeks of follow-up, patients in group A received significantly less energy leading to a 2.8 kg net reduction in mean weight in association with a significant net decrease in mean SBP and DBP (7.5/6.5 mm Hg) compared with nonsignificant changes in group B. There was a significant net decrease in mean total cholesterol (7.0%), low-density lipoprotein (LDL)-cholesterol (7.9%) and triglycerides (8.0%), with a significant net increase in high-density lipoprotein (HDL)-cholesterol (4.0%) in group A compared with group B. New risk factors such as glucose intolerance (8.0%) and central obesity (waist-hip girth ratio, 0.021) showed a significant net reduction compared with group B. Patients with central obesity and other associated disturbances showed maximal reduction in BP and other cardiovascular risk factors with a significantly greater increase in HDL-cholesterol. Mean doses of drugs were similar at entry to the study as well as after 16 weeks in both groups. It is possible that weight reduction due to a low caloric diet can moderate central obesity and associated disturbances in hypertensive subjects.

Antihypertensive Agents↗
PubMed1995

Proximate determinants of fertility in eastern Uttar Pradesh.

Our main objective here is to examine and discuss the effects of some sociocultural and economic factors on the proximate determinants of fertility in rural areas of eastern Uttar Pradesh (population more than 40 million persons). The region is known for its present demographic trends because the crude birth, death, and infant mortality rates are among the highest for India. The determinants considered are age at marriage of female, postpartum amenorrhea (PPA), fecundability and sterility, and menopause. The sociocultural and economic factors studied are caste, education, breast-feeding status, and social status of the currently married females in the reproductive age group. The study population is predominantly Hindu, among whom caste is a strong indicator of socioeconomic conditions. The average age of the female at return marriage (RM) is below 18 years in each religion or caste group but has been increasing over time. Median durations of breast feeding and PPA differ significantly among various socioeconomic and demographic subgroups. These are longest in scheduled castes and shortest in upper-caste Hindus. As the social status of the household increases, the median durations of breast feeding and PPA decrease. The estimates of fecundability consistently decrease with age, whereas those of sterility increase with age after 35 years. The smallest estimate of sterility is 4%, corresponding to the 25-30-year age group in each religion or caste group. Occurrence of menopause is rare before age 35, and it increases with the age of the female irrespective of religion or caste. However, the risk is minimum for females in upper castes and maximum for those in scheduled castes.

Adolescent↗
PubMed1994

Physiochemical characteristics of flours of faba bean as influenced by processing methods.

Wet- and dry-processing with and without heating treatments were used to dehull faba beans for preparation of flours from the cotyledons. Flour qualities were assessed by levels of tannin and trypsin inhibitor and other measures of proximate composition. High roasting temperature and shorter process time that improved the recovered cotyledon yields were verified significant by path analysis methodologies. In turn, the higher cotyledon recoveries correlated with higher protein levels and inversely with the measured tannin levels. Ash reductions were correlated to the wet processing options in hull removal while reductions in the insoluble dietary fiber were notably influenced by level of heating temperatures applied. Trypsin inhibitor levels ranged from 42 to 56% of the original with reductions tied to applications of wet and/or heat processing in each case improved by increased durations and temperatures of treatments.

Chemical Phenomena↗
PubMed1994

Hypotensive infarction of the spinal cord.

Four patients developed infarction of the lumbar cord as a result of induced hypotension. All patients showed a lesion in the territory of the artery of Adamkiewicz. The pathophysiology of the blood supply of the spinal cord is discussed, and in particular the anatomy of the artery of Adamkiewicz. The reason why this artery is so vulnerable to hypotension is discussed.

Aged↗