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Biomedical subjects

S K Mishra

Publications and source records attributed to S K Mishra.

At least 37 records · Page 2Linked to original sources

The influence of hyperbilirubinaemia on malaria-related mortality: an analysis of 1103 patients.

The influence of hyperbilirubinaemia on malaria-related mortality was explored among 1103 cases of acute, Plasmodium falciparum malaria at a referral hospital in Orissa, India. Most (64.3%) of the subjects investigated had > 1.2 mg bilirubin/dl serum and were therefore considered hyperbilirubinaemic. Compared with the other patients, those with hyperbilirubinaemia were much more likely to have cerebral malaria (24.1% v. 9.4%; P < 0.0001) or acute renal failure (9.5% v. 2.3%; P < 0.0001), but not severe anaemia (5.9% v. 4.3%; P < 0.22). Mortality was 7.9% among the patients with hyperbilirubinaemia (all the deaths being attributable to cerebral malaria, acute renal failure and/or severe anaemia) but only 1% among the non-hyperbilirubinaemics. There were no deaths, however, among the 506 hyperbilirubinaemics who did not have cerebral malaria, acute renal failure or severe anaemia, even among those with high serum concentrations of bilirubin. It therefore appears that, in acute, Plasmodium falciparum malaria, hyperbilirubinaemia is not in itself a severe complication, and only appears linked with mortality when associated with at least one other complication.

Acute Disease↗

Pollution monitoring with the help of lichen transplant technique at some residential sites of Lucknow City, Uttar Pradesh.

Samples of foliose lichen, Dirinaria consimillis (Fr.) Awasthi were transplanted at six residential sites of Lucknow city for monitoring the concentration of Cr, Zn, Pb, Cu and Cd metals at two vertical positions. The concentration of chromium and copper were more at the higher vertical position than the lower one. The maximum zinc was at lower vertical position than the upper one. Lead and cadmium were not detected in the present study.

Cities↗

Adsorption of sodium dodecyl benzenesulfonate onto coal.

The adsorption behavior of sodium dodecyl benzenesulfonate (NaDDBS) on a raw (as received) coal sample and its demineralized variety with 11.3% and 1.2% ash contents respectively has been studied. The samples have been characterized by their proximate analysis, particle size distribution, surface area, porosity, density, points of zero charge, etc. Adsorption of NaDDBS on these two samples has been studied as a function of concentration of NaDDBS, temperature, pH, and presence of indifferent electrolyte in the medium. It has been observed that the isotherm exhibits two adsorption plateaus below and above the critical micelle concentration (CMC) of NaDDBS. Low heats of adsorption suggest weak hydrophobic bonding between adsorbent and adsorbate. The present work aims to correlate the adsorption of surfactant onto coal particles with the rheological behavior of coal-water slurry (CWS). The results reveal that addition of a very small amount of NaDDBS (0.3 wt% of coal) to 60% (w/w) CWS results in a marked reduction of the apparent viscosity of the CWS at a shear rate of 100 s(-1). The effect of pH on the apparent viscosity of CWS with and without the presence of the surfactant is also investigated.

Journal Article↗

Assessment of microsatellite instability in bladder and thyroid malignancies.

Microsatellite instability (MSI) is an indicator of a defective DNA mismatch repair system (MMR) that results from somatic mutations. The present work has been planned to investigate MSI and its clinical significance in human urinary bladder and thyroid cancers in Indian patients. Tumor tissues of histologically confirmed cases of urinary bladder and thyroid cancers, respectively, were obtained. Clinical data on tumor stage and histopathological grades were recorded. Corresponding matched peripheral blood was taken as a control. Genomic DNA was isolated from the tumor tissues and blood using a standard phenol-chloroform extraction method. Polymerase chain reaction was done to amplify mononucleotide microsatellite markers, BAT-26, BAT-40, TGFbetaRII, IGFIIR, hMSH3, and Bax by using specific primer sequences. For analysis of allelic patterns, the PCR products were run on 8% denaturing Polyacrylamide gel and sizing was done using a pUC18 sequencing ladder. The instability with BAT-26 and BAT-40 was found to be 20% and 45% in urinary bladder and 33% and 19% in thyroid cancers, respectively. However, no instability was observed with the other four-mononucleotide markers in either of the cancers studied. Eighty-three percent of the unstable urinary bladder cancers were found to have a high grade in a superficial group, whereas only 27% MSI+ve were muscle invasive cancers. Forty percent of unstable thyroid lesions were found to be at high risk of developing metastasis. Association of BAT-26 and BAT-40 instabilities with high grade tumors as well as risk tumors may help in choosing a more definite therapy at the outset.

Base Pair Mismatch↗

Adenosine affects the calcium dynamics of rat portal vein.

1. The present study was carried out to characterize the effect of adenosine on calcium dynamics in the rat portal vein. Isolated portal vein of male albino rats was used as the experimental model as it exhibits autorhythmicity. 2. Adenosine and its analogues 2-CAD, N6-CHA and NECA were used to characterize the type of adenosine receptor involved and 2-CAD was used along with adenosine throughout the other part of study to characterize the effect of adenosine on Ca2+ dynamics. Adenosine and its analogues were found to inhibit the spontaneous contractions of rat portal vein in a concentration-related manner. The order of potency was NECA > 2-CAD > N6-CHA > adenosine. Incubation of the tissue with CGS-15943A, an adenosine receptor antagonist, had a per se enhancing effect on autorhythmicity. Adenosine and 2-CAD failed to reverse the contractile response produced by hypertonic KCl (80 or 30 mM). Whereas adenosine and 2-CAD effectively relaxed the tissues contracted with phenylephrine (10(-5) m). 3. Preincubation of the tissue with 2-CAD (10(-4), 10(-5) or 10(-6) m) for 5 min raised the threshold concentration of CaCl2 to evoke contractile response and also significantly increased the mean EC50 values of CaCl2. Nifedipine was found to be more potent than 2-CAD on Ca2+ channels. 4. The results of the present study suggest that the endogenous adenosine plays a significant role in producing vascular relaxation through the participation of A2 receptor subtype. This effect may be due to its inhibitory effect on release of Ca2+ from the intracellular stores. Further to this effect, 2-CAD had a major inhibitory effect on voltage-operated Ca2+ channels compared with receptor-operated Ca2+ channels. 5. It can be concluded that adenosine through its A2 receptor produces vasorelaxant effect by interfering with the release of Ca2+ from the intracellular stores coupled with influx of Ca2+ from the extracellular sources.

Adenosine↗

Use of telemedicine in evading cholera outbreak in Mahakumbh Mela, Prayag, UP, India: an encouraging experience.

Telemedicine (TM) services a process in which expert medical advice from afar is provided using electronic signals to transfer the medical data from one site to another. As a pilot project to assess the efficacy of TM in developing countries like India, a telemedicine center was set up at the main hospital of Mahakumbh mela--a grand religious fair, at Prayag, a city in north India. The daily reporting of the in-patient and outpatient cases at the fair revealed a surge of diarrhea cases among the pilgrims at the fair. This information was communicated to the referral center at Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), which, with the help of its microbiology department, conducted microbiological examinations of stool samples and rectal swabs of patients along with various water samples. Vibrio cholerae was isolated in 22.6% (7/31) of the samples. This information was immediately relayed to the Main Hospital at the fair online, and then to the health authorities, who took strict and prompt measures to improve hygiene. Subsequently, the number of diarrhea cases decreased considerably in a matter of a few days, and thus an epidemic disaster was averted, which could have created havoc in such a large gathering.

Aged↗

Influence of renal impairment on plasma concentrations of conjugated bilirubin in cases of Plasmodium falciparum malaria.

In a study of the influence of malaria-associated renal impairment on plasma concentrations of bilirubin, 111 Indian cases of Plasmodium falciparum malaria who had >34.2 microM total bilirubin/litre plasma were investigated. As the aim was to exclude those cases who had concomitant hepatic or (non-malarial) renal dysfunction, 19 cases who had serum concentrations of alanine aminotransferase (ALT) or alkaline phosphatase (AP) that were at least double the normal mean values were withdrawn. Of the remaining 92 patients, 47 showed evidence of renal impairment, the other 45 having plasma concentrations of creatinine that were <177 microM/litre. Plasma concentrations of the liver enzymes ALT and AP were similar for those with and without renal impairment. The plasma concentration of conjugated bilirubin (P<0.02), that of total bilirubin (P<0.05) and the ratio between the two (P<0.01) were, however, all significantly higher in the 47 patients with renal impairment than in the 45 with apparently normal renal function. The plasma concentration of creatinine was found to be not only positively correlated with the plasma concentrations of total (r=0.34; P<0.01) and conjugated (r=0.41; P<0.001) bilirubin but also negatively correlated with the urinary excretion rate for conjugated bilirubin (r=-0.34; P<0.001). The malaria-associated mortality was significantly higher among the patients with renal impairment than among those with apparently normal renal function, with 12 and three deaths, respectively (P<0.001). With increasing renal impairment there therefore appears to be a fall in the renal excretion of conjugated bilirubin. This leads to a disproportionate rise in the plasma concentration of conjugated bilirubin and this, since bilirubin can be toxic to renal tissue, may further worsen the renal impairment.

Bilirubin↗

Muscle sarcopenia: an overview.

Sarcopenia is the physiological age related decline in muscle mass and strength. The aetiology is multifactorial involving changes in muscle metabolism, endocrine changes, nutritional factors and mitochondrial & genetic factors. Various treatment modalities have been utilized including hormone replacement therapies but only high resistance training (HIRT) exercise has been of significant benefit. Despite recent advances the exact pathogenesis and therapies are not well understood and need further investigation. This paper reviews the current knowledge of aetiopathogenesis and treatments of sarcopenia and suggests future strategies to enhance the understanding of muscle aging and potential therapies.

Aged↗

An ab initio theoretical study of electronic structure and properties of 2'-deoxyguanosine in gas phase and aqueous media.

Molecular geometries of two structural forms of 2'-deoxyguanosine (keto-N9R and keto-N7R, R = the sugar moiety) considering both the C2'-endo and C3'-endo conformations of the sugar ring and those of the complexes of these species with two water molecules each were optimized employing the ab initio RHF procedure. A mixed basis set consisting of the 6-311+G* basis set for the nitrogen atom of the amino group and the 4-31G basis set for all the other atoms was used. The RHF calculations were followed by correlation correction of the total energy at the MP2 level. Both the structural forms of 2'-deoxyguanosine were solvated using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory and the corresponding RHF optimized geometries at the RHF and MP2 levels. Geometry optimization was also performed in aqueous media using the Onsager model at the RHF level using the above-mentioned mixed basis set, and subsequently, using the reoptimized geometries, single-point MP2 calculations were performed. It is found that both the keto-N9R and keto-N7R forms of 2'-deoxyguanosine as well as their complexes with two water molecules each would occur, particularly at the water-air interface. Though the normal Watson-Crick-type base pairing would not be possible with the keto-N7R form of 2'-deoxyguanosine(G*), two other (G*-C and G*-T) base pairing schemes may occur with this form of the nucleoside, which may cause mutation. The present calculated geometry of the keto-N9R form of the anti-conformation of 2'-deoxyguanosine including the dihedral angle chi(CN) agree satisfactorily with the available crystallographic results. The present results also agree satisfactorily with those obtained by other authors earlier for the keto-N9R form of 2'-deoxyguanosine using B3LYP and MP2 methods employing the 6-31G* basis set. Using transition state calculations, it is shown that tautomerism of guanine and other similar molecules where the tautomers would coexist would be facilitated by the occurrence of the H(+) and OH(-) fragments of water molecules. Further, this coexistence of the two tautomers appears to make the C8 carbon atom located between the N7 and N9 nitrogen atoms susceptible to attack by the OH(-) group. Thus, an explanation is obtained for the efficient formation of the reaction product 8-hydroxy-2'-deoxyguanosine, which serves as a biomarker for oxidative damage to DNA in biological systems.

8-Hydroxy-2'-Deoxyguanosine↗

Dynamic chromatin remodeling on the HER2 promoter in human breast cancer cells.

Deregulation of the HER2 oncogene occurs in 30% of human breast cancers and correlates with poor prognosis and increased propensity for metastasis. Since the molecular basis of HER2 overexpression in human cancers is not known, we sought to determine whether chromatin remodeling pathways are involved in the regulation of HER2 expression. We report that compared with breast cancer cells expressing a low level of HER2, HER2-overexpressing breast cancer cells contained significantly higher levels of acetylated and phosphorylated histone H3, and acetylated histone H4 associated with the HER2 promoter. Decreased recruitment of histone deacetylases in the promoter is also noted in the HER2-overexpressing cell. The association of acetylated histone H4 with HER2 gene chromatin and HER2 expression in breast cancer cells was upregulated by an inhibitor of histone deacetylases. Treatment with histone deacetylase inhibitor also reduced the association of histone deacetylase-1 and -2 with the HER2 promoter. In addition, the tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid stimulated the association of phosphorylated histone H3 on serine 10 with the HER2 promoter and also stimulated HER2 expression. These findings identify histone acetylation and histone phosphorylation as novel regulatory modifications that target HER2 gene chromatin, and suggest that elevated levels of these chromatin-relaxing components in the vicinity of the HER2 gene promoter may constitute an important non-genomic mechanism of HER2 overexpression in human breast cancer.

Acetylation↗

Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins.

Clathrin-mediated endocytosis is a major pathway for the internalization of macromolecules into the cytoplasm of eukaryotic cells. The principle coat components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice at plasma membrane bud sites with the aid of several endocytic accessory proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding partner of huntingtin, copurifies with brain clathrin-coated vesicles and associates directly with both AP-2 and clathrin. The discrete interaction sequences within HIP1 that facilitate binding are analogous to motifs present in other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer. Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis.

Amino Acid Sequence↗

Influence of hypothyroid state on 45Ca(2+) influx and sensitivity of rat uterus to nifedipine and diltiazem.

The influence of methimazole-induced hypothyroidism on spontaneous rhythmic contractions and Ca2+ channel function of rat uterus was examined. Hypothyroidism significantly reduced the amplitude and frequency of spontaneous rhythmic contractions. Nifedipine (10(-12)-10(-6) M) and diltiazem (10(-9)-10(-4) M) caused concentration-related inhibition of the myogenic responses of the oestrogenised rat uterus obtained from both eu- and hypothyroid rats. However, nifedipine was less potent (IC(50); 5.4 x 10(-9) M; n=6) in hypothyroid rat uterus as compared to euthyroid controls (IC(50): 8.13 x 10(-12) M; n=9) to inhibit the rhythmic contractions. Similarly, diltiazem was less potent (IC(50): 4.57 x 10(-6) M; n=9) to inhibit the uterine spontaneous contractions in hypothyroid than in euthyroid rat uterus (IC(50): 6.4 x 10(-8) M; n=6). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100 mM)-induced tonic contraction was observed in uterus obtained from hypothyroid rats compared to the controls. Both nifedipine and diltiazem were less potent for causing concentration-related inhibition of K+-stimulated 45Ca2+ influx in uterine strips taken from the hypothyroid rats. Thus, the IC(50) values of nifedipine (1.83 x 10(-8) M; n=12) and diltiazem (1.8 x 10(-6) M; n=9) were significantly greater in tissues obtained from hypothyroid rats compared to the controls (IC(50) of nifedipine, 1.15 x 10(-11) M; n=12, diltiazem, 8.1 x 10(-8) M; n=8). Nifedipine-sensitive influx of 45Ca2+ - stimulated either by K+ (100 mM) or Bay k8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-8) M) was significantly less in uterine strips from hypothyroid rats compared to the controls. The results of the present study suggest that the inhibition of uterine rhythmic contractions may be attributable to a reduction in rat myometrial Ca2+ channel function in the hypothyroid state.

Animals↗