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S Das

Publications and source records attributed to S Das.

At least 289 records · Page 16Linked to original sources

The circadian pattern of ischaemic heart disease events in Indian population.

A circadian variation of the onset of almost all ischaemic heart disease (IHD) manifestations with an increased incidence between 6:00 a.m. to 12:00 noon has been reported in several publications during the last decade. This study included 605 patients of various IHD subgroups, i.e., acute Q-wave myocardial infarction (n = 174), unstable angina (n = 266), non-Q myocardial infarction (n = 67), acute pulmonary oedema (n = 35) and sudden cardiac death (n = 63) proven to be due to IHD by electrocardiogram and/or autopsy. In overall, 33.55% (p < 0.0001) of patients had the IHD events with an increased frequency between 6:00 a.m. To 12:00 noon (2nd quarter of the day.) The distribution in the remaining, 1st 3rd and 4th quarters was 22.64%, 20.99% and 22.80%, respectively. Similar circadian rhythm (2nd quarter peak) was seen in males (n = 486), females (n = 119), patients ages < 60 years (n = 388), patients without past history of IHD (n = 434) and in those not on any medications (n = 359). However in patients with past history of IHD and diabetics, the circadian distribution did not differ from the random and the cases were distributed almost evenly in all the four quarters of the day. 39.08% of all the acute Q wave myocardial infarction (A-QMI), 33.45% of unstable angina and 36.5% of sudden cardiac deaths also occurred between 6:00 a.m. and 12:00 noon. However 51.42% cases of acute pulmonary oedema were encountered in the 4th quarter of the day and patients with non Q-myocardial infarction (non-QMI) did not show any particular pattern in relation to circadian rhythm. Thus it was inferred that in Indian population too the circadian pattern of IHD manifestations are similar to other population studies and morning appears to be the time, when the triggers (transient precipitating risk factors) that lead to these events are likely to be prominent. Study of these triggers and/or early morning pathophysiological changes may go a long way in understanding ischaemic heart disease and suggesting possible means of prevention.

Angina Pectoris↗

Prevention of carbon tetrachloride-induced hepatic injury in mice by Picrorhiza kurrooa.

OBJECTIVE: Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian indigenous system of medicine. We undertook this study to determine whether Pk extract possesses hepatoprotective function and if so to determine its nature and mechanism. METHODS: Liver injury was induced in 16 mice by thrice-a-week injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection. Control mice (n = 6) were injected with olive oil for the same period. Serum markers of liver injury and histology of liver tissues were studied. Hepatic glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD), catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also determined. RESULTS: CCl4 treatment resulted in significant elevation of serum ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control 358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced. Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole MDA/mg protein] and histologic changes characteristic of liver injury were also seen. Feeding of Pk extract in CCl4-treated mice caused significantly less alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi released/min/mg protein]. Histologic lesions of liver and lipid peroxidation [1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals. CONCLUSION: The extract of Pk appears to offer significant protection against liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor of lipid peroxidation of liver plasma membrane.

Animals↗

Comparative outcome analysis of laparoscopic colposuspension, abdominal colposuspension and vaginal needle suspension for female urinary incontinence.

PURPOSE: The long-term surgical outcome of abdominal colposuspension, laparoscopic colposuspension and vaginal needle suspension for managing anatomical stress urinary incontinence in women was evaluated. MATERIALS AND METHODS: Three nonrandomized contemporaneous groups of 10 women each with anatomical stress urinary incontinence were treated with abdominal colposuspension, laparoscopic colposuspension or vaginal needle suspension. Immediate postoperative and subsequent outcomes were evaluated using a 10-point questionnaire annually up to 36 months. RESULTS: Immediately after surgery the laparoscopic colposuspension group required less analgesia as well as briefer catheterization and hospital stay. Continence rates 10 months postoperatively were 100% for the abdominal colposuspension group, 90% for the laparoscopic colposuspension group and 100% for the vaginal needle suspension group. At 36 months postoperatively these results had declined to 50, 40 and 20%, and satisfaction with surgical outcome was 60, 90 and 60%, respectively. CONCLUSIONS: Despite initially high success rates of these 3 surgical procedures based on the principle of retropubic suspension of the proximal portion of the urethra, responses to questionnaires given at longer postoperative intervals showed a sharp decline in success. We probably should redirect our treatment strategy for women with anatomical stress incontinence to include urethral coaptation and direct suburethral suspension.

Abdomen↗

Effect of leaf extract from Clerodendron colebrookianum on CNS function in mice.

Effect of acute multiple (20, 40 and 80 mg/kg body wt, i.p.) doses of C. colebrookianum leaf extract on behaviour, convulsion, analgesia and sedative-hypnosis was studied in mice. A marginal reduction of awareness and motor activity was observed in low (20 mg) and moderate (40 mg) dose level of extract. However, 80 mg dose caused marked inhibition of awareness and motor activity. Grip strength and stereotypy was observed in all the dose levels. The extract alone did not show loss of righting reflex but it prolonged the effect of meprobamate, diazepam, chlorpromazine and pentobarbitone significantly in a dose dependent manner. The extract neither produced analgesia alone nor it altered analgesic effect of morphine and pethidine. Pretreatment of the extract caused significant protection of strychnine and leptazol induced convulsion and mortality. The results suggest a mild (or dose dependent) CNS depressant action of leaf extract of C. colebrookianum in mice.

Animals↗

Humoral immunity status in neonates born to pre-eclamptic toxaemia mothers.

A prospective study on 90 neonates born to age matched normal mothers (set I) and mothers (set II) with pre-eclamptic toxaemia (PET) was undertaken to assess and compare the humoral immunity status of the neonates. All of them had normal vaginal delivery. IgG, IgA and IgM were estimated by radial immunodiffusion technique from cord blood of neonates. It was observed that IgA and IgM levels were insignificant in the cord blood. IgG level was low in normal birth weight (NBW) neonates born to PET mothers, when compared to that of NBW neonates born to normal mothers. Again low birth weight (LBW) babies of both the sets showed lower values of IgG than that of NBW babies. Apgar scoring showed direct relationship with IgG levels e.g., higher the Apgar score higher the level of IgG. Thus the IgG level was directly related to the birth weight of the neonates of the respective sets as well as with the Apgar scoring of the neonates.

Adolescent↗

The effects of maternal intake and gestational age on materno-fetal transport of vitamin C in the guinea-pig.

The effects of maternal intake and gestational age on materno-fetal transport of vitamin C were investigated in female Dunkin-Hartley guinea-pigs. Twenty-four time-mated dams were fed on either a moderate-vitamin C (group A) or a high-vitamin C (group B) diet, throughout pregnancy. At days 49, 63 and 66 of gestation, and at term, three animals from each group were killed and fetuses removed by hysterectomy. Plasma, liver, kidney, lungs, heart, placenta and amniotic fluid were collected from dams and fetuses and subsequently analysed for vitamin C. Fetal plasma and amniotic fluid concentrations showed negative associations with gestational age for both dietary groups, independent of an effect of dam (P < 0.001). A similar, though not significant, effect of gestational age was observed on placental vitamin C and group A fetal tissue concentrations. Fetal plasma, placental and amniotic fluid vitamin C concentrations were significantly higher in group B than group A (P < 0.001), suggesting the influence of maternal diet. Although the level of maternal vitamin C intake can influence the circulating concentration in the fetus, there is a decrease associated with increasing gestational age, independent of the maternal diet. The gestational age-dependent change in the fetal accumulation of vitamin C may reflect changes in the rate of placental transfer.

Amniotic Fluid↗

Enhanced neuronal death from focal ischemia in AMPA-receptor transgenic mice.

Excitatory amino acid (EAA) receptors play an important role in neuronal cell death in acute cerebral ischemia. Blocking the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of EAA receptor has been shown to reduce cell death in global cerebral ischemia. However their role in focal stroke, although suggestive, has remained more contentious. To clarify this issue, we generated transgenic mice overexpressing the AMPA receptor (AMPAR) subunit GluR2-flip which would increase AMPAR-mediated currents. Excitatory neurons in these transgenic mice are thus predicted to be more susceptible than wild-type neurons to EAA (glutamate)-induced excitotoxic damage. Consistent with this prediction, cultured neurons from transgenic mice had a lower LD50 for exposure to glutamate (10(-3)-10(-5) M for 5 min) compared to wild-type neurons. Moreover, transgenic mice subjected to permanent focal ischemia of the middle cerebral artery (MCA) using the intralumenal filament model sustained larger infarctions compared to wild-type controls. Hence we have developed a genetic mouse model that demonstrates the crucial role of AMPAR containing GluR2-flip in the pathogenesis of focal hypoxic-ischemic neuronal cell death. This model will be a valuable tool in elucidating molecular mechanisms of glutamate excitotoxicity and evaluating the efficacy of glutamate receptor antagonists in attenuating post-ischemic neuronal cell death.

Alternative Splicing↗

Specific interaction of eukaryotic translation initiation factor 5 (eIF5) with the beta-subunit of eIF2.

Eukaryotic translation initiation factor 5 (eIF5) interacts with the 40 S initiation complex (40 S.mRNA. eIF3.Met-tRNAf.eIF2.GTP) and mediates hydrolysis of the bound GTP. To characterize the molecular interactions involved in eIF5 function, we have used 32P-labeled recombinant rat eIF5 as a probe in filter overlay assay to identify eIF5-interacting proteins in crude initiation factor preparations. We observed that eIF5 specifically interacted with the beta subunit of initiation factor eIF2. No other initiation factors including the gamma subunit of eIF2 tested positive in this assay. Furthermore, both yeast and mammalian eIF5 bind to the beta subunit of either mammalian or yeast eIF2. Binding analysis with human eIF2beta deletion mutants expressed in Escherichia coli identified a 22-amino acid domain, between amino acids 68 and 89, as the primary eIF5-binding region of eIF2beta. These results along with our earlier observations that (a) eIF5 neither binds nor hydrolyzes free GTP or GTP bound as Met-tRNAf.eIF2.GTP ternary complex, and (b) eIF5 forms a specific complex with eIF2 suggests that the specific interaction between eIF5 and the beta subunit of eIF2 may be critical for the hydrolysis of GTP during translation initiation.

Amino Acid Sequence↗

Proof for a nonproteinaceous calcium-selective channel in Escherichia coli by total synthesis from (R)-3-hydroxybutanoic acid and inorganic polyphosphate.

Traditionally, the structure and properties of natural products have been determined by total synthesis and comparison with authentic samples. We have now applied this procedure to the first nonproteinaceous ion channel, isolated from bacterial plasma membranes, and consisting of a complex of poly(3-hydroxybutyrate) and calcium polyphosphate. To this end, we have now synthesized the 128-mer of hydroxybutanoic acid and prepared a complex with inorganic calcium polyphosphate (average 65-mer), which was incorporated into a planar lipid bilayer of synthetic phospholipids. We herewith present data that demonstrate unambiguously that the completely synthetic complex forms channels that are indistinguishable in their voltage-dependent conductance, in their selectivity for divalent cations, and in their blocking behavior (by La3+) from channels isolated from Escherichia coli. The implications of our finding for prebiotic chemistry, biochemistry, and biology are discussed.

Calcium Channels↗

Multifunctional activities of human fibroblast 34-kDa hyaluronic acid-binding protein.

We have already reported that human fibroblast 34-kDa hyaluronic acid-binding protein (HABP) is identical with P32, the protein co-purified with splicing factor SF-2 [Deb and Datta (1996) J. Biol. Chem. 271, 2206-2212]. Data search further revealed that it has 92% sequence homology with a murine protein YL2 which interacts with HIV1 Rev. In this paper we have successfully demonstrated that HIV1 Rev binds with labeled 34-kDa HABP which can be competed with excess unlabeled HABP, suggesting this protein can be a cellular factor promoting HIV1 Rev to function. Interestingly, the multifunctional nature of HABP has been elucidated as it has 100% homology with another protein gC1q, the complement protein. The distinct non-overlapping binding motifs for HA and gC1q have been identified in the same protein, suggesting that either the protein can function independently or its activity is regulated by ligand binding, wherein its binding to one of the ligands may modulate the receptor activity of the other ligand.

Amino Acid Sequence↗

Transgenic elite indica rice plants expressing CryIAc delta-endotoxin of Bacillus thuringiensis are resistant against yellow stem borer (Scirpophaga incertulas).

Generation of insect-resistant, transgenic crop plants by expression of the insecticidal crystal protein (ICP) gene of Bacillus thuringiensis (Bt) is a standard crop improvement approach. In such cases, adequate expression of the most appropriate ICP against the target insect pest of the crop species is desirable. It is also considered advantageous to generate Bt-transgenics with multiple toxin systems to control rapid development of pest resistance to the ICP. Larvae of yellow stem borer (YSB), Scirpophaga incertulas, a major lepidopteran insect pest of rice, cause massive losses of rice yield. Studies on insect feeding and on the binding properties of ICP to brush border membrane receptors in the midgut of YSB larvae revealed that cryIAb and cryIAc are two individually suitable candidate genes for developing YSB-resistant rice. Programs were undertaken to develop Bt-transgenic rice with these ICP genes independently in a single cultivar. A cryIAc gene was reconstructed and placed under control of the maize ubiquitin 1 promoter, along with the first intron of the maize ubiquitin 1 gene, and the nos terminator. The gene construct was delivered to embryogenic calli of IR64, an elite indica rice cultivar, using the particle bombardment method. Six highly expressive independent transgenic ICP lines were identified. Molecular analyses and insect-feeding assays of two such lines revealed that the transferred synthetic cryIAc gene was expressed stably in the T2 generation of these lines and that the transgenic rice plants were highly toxic to YSB larvae and lessened the damage caused by their feeding.

Animals↗

Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host.

The temporal synthesis of the P21 protein of Borrelia burgdorferi and the development of the humoral response to this antigen was assessed in infected mice. p21 is a member of the ospE-F gene family and its protein, P21, has been shown to be expressed by B. burgdorferi within infected mice but not by spirochetes cultured in vitro. P21 was not detected on B. burgdorferi in unfed or engorged Ixodes dammini (also known as I. scapularis) ticks, further supporting the postulate that P21 synthesis is specific for the mammalian host. In B. burgdorferi-infected mice, ospE mRNA and OspE antibodies were observed at 7 d, whereas p21 mRNA and P21-specific antibodies were detected at 21-28 d, suggesting that p21 is expressed later than ospE. Moreover, ospA mRNA was not discernible until day 14, indicating that ospA, like p21, is not expressed in the early stages of tick-transmitted murine Lyme borreliosis. Because p21 is expressed during infection in mice, we assessed the human humoral response to P21. 28% (34 of 122) of the patients with either early- or late-stage Lyme disease, and 33% (11 of 33) of the individuals with Lyme arthritis had P21 antibodies, suggesting that a P21 response may serve, at least partially, as a marker of infection. Active immunization with recombinant P21 did not protect C3H mice from tick-borne B. burgdorferi infection, and passive transfer of P21 antiserum to infected mice did not alter the course of disease. These data suggest that the antigenic structure of B. burgdorferi changes during the early stages of murine infection.

Animals↗

NMDA and D1 receptors regulate the phosphorylation of CREB and the induction of c-fos in striatal neurons in primary culture.

Numerous in vivo studies have demonstrated that psychostimulant drugs such as amphetamine and cocaine can induce the expression of the immediate early gene c-fos in striatal neurons via the activation of D1 dopamine receptors. NMDA receptor activation is also known to induce c-fos in the striatum. In the present study we have used a primary striatal neuronal culture preparation to examine the mechanisms whereby these stimuli lead to changes in gene expression. Direct application of NMDA to striatal cells in culture caused a rapid increase in the expression of c-fos as well as an increase in the phosphorylation of the transcription factor CRE binding protein (CREB). This was prevented by NMDA receptor antagonists, and required extracellular calcium, but did not involve L-type calcium channels. The induction of c-fos and CREB phosphorylation following NMDA were unaffected by inhibition of protein kinase C; tyrosine kinases or nitric oxide synthase. However, the response to NMDA was blocked by KN62, a selective inhibitor of calcium/calmodulin-dependent protein kinase. Application of the D1 agonist SKF 38393, or direct stimulation of adenylyl cyclase with forskolin, also resulted in the phosphorylation of CREB and the induction of c-fos in striatal neurons. These effects were blocked by the protein kinase A inhibitor H89. These observations are consistent with the hypothesis that calcium/calmodulin-dependent phosphorylation of CREB induced by NMDA, or cAMP-dependent phosphorylation of CREB induced by D1 agonists, underlie the induction of c-fos seen following activation of these receptors in striatal neurons.

Animals↗

Uptake and cellular localization of exogenous lipids by Giardia lamblia, a primitive eukaryote.

Giardia lamblia trophozoites are unable to carry out de novo lipid synthesis. It is therefore likely that lipids are acquired from the small intestine of the host, in which the trophozoites are exposed to free and conjugated fatty acids, various sterols, phospholipids, bile acids, and bile-lipid mixed micelles. Here we show that G. lamblia is capable of taking up exogenous phosphatidylcholine (PC), phosphatidylinositol (PI), sphingomyelin (SM), cholesterol, ceramide (Cer), and fatty acids. Results from epifluorescence and high-resolution confocal microscopy suggest that fluorescent analogs of SM and PC were accumulated in the plasma membranes, whereas palmitic acid and Cer were localized intracellularly. Interestingly, many of these analogs were also concentrated in perinuclear regions. Similar labeling patterns were observed when the fluorescent analogs were delivered to the parasite via liposomes. To test whether G. lamblia was capable of esterifying exogenous fatty acids into membrane or cellular phospholipids, trophozoites were pulse-labeled with 3H-labeled palmitic or myristic acids and the phospholipids analyzed by thin-layer chromatography. Results document that G. lamblia was able to incorporate exogenous fatty acids into various phospholipids, i.e., PI, PC, PE, and PG. Interestingly, a major portion of radiolabeled fatty acids was incorporated into PG, a phospholipid characteristic of prokaryotic membranes.

Animals↗

Giardia lamblia: evidence for carrier-mediated uptake and release of conjugated bile acids.

Giardia lamblia trophozoites colonize the human small intestine, where they are exposed to high concentrations of conjugated bile acids. Previous work has shown that bile acids enhance trophozoite survival, multiplication, and differentiation into the cyst stage. Therefore, experiments were performed to test whether carrier-mediated uptake of conjugated bile acids is present in this primitive parasite. Uptake of both cholyltaurine (C-tau) and cholylglycine (C-gly) was increased manyfold after culturing trophozoites in medium lacking bile acids. Absence of uptake at 4 degrees C and inhibition by other conjugated bile acids provided additional evidence for carrier-mediated uptake. Uptake of C-tau was greater than that of C-gly under all experimental conditions and appeared to be mediated by a different carrier. The major evidence for different carriers is that C-tau uptake was Na(+)-dependent, while C-gly uptake was not. In addition, C-tau uptake was more strongly inhibited by DTNB and several organic anions than C-gly uptake. Radiolabeled C-tau and C-gly were each released rapidly from trophozoites at 37 degrees C but not at 4 degrees C, suggesting that release of conjugated bile acids was also carrier-mediated. These findings are consistent with the notion that multiple transporters for conjugated bile acids are present in a lower eukaryote. We speculate that intracellular bile acids may facilitate lipid trafficking and membrane biosynthesis.

Animals↗