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Biomedical subjects

A Bhattacharya

Publications and source records attributed to A Bhattacharya.

At least 109 records · Page 6Linked to original sources
PubMed1998

Blockade of the delayed rectifier potassium current in Drosophila by quinidine and related compounds.

Quinidine is a potent blocker of the delayed rectifier K+ channels (IK). Although it has been used for understanding the physiology of K+ channels in many organisms and for treating cardiac arrhythmia in humans, mechanisms of its interaction with the channel molecule are not well understood. As a first step in understanding these mechanisms, we used the Shaker mutant of Drosophila in which the delayed rectifier can be resolved in complete isolation from other currents and determined the importance of the major groups of quinidine (methoxy, quinoline, quinuclide and the bridge groups) in the blockade of IK. It appears that the quinoline moiety, while possessing little channel-blocking activity by itself, may provide a template for positioning the groups that may be important for affinity and blockade. These groups, in the order of importance in imparting inhibitory activity to quinoline, seemed to be quinuclide > methylene bridge > 6-methoxy group. In particular, the quinoline ring and the quinuclide group, when linked-together by a hydroxymethylene bridge, might be responsible for a major part of the IK blocking activity of quinidine. Action of quinidine was not affected by either quinuclidine, which did not block IK, or by quinoline.

Animals↗
PubMed1998

The effect of succimer therapy in lead intoxication using postural balance as a measure: a case study in a nine year old child.

Postural balance testing was used as a measure of the effect of therapy on a 9 year old boy with high lead levels. Following therapy with CaEDTA and succimer, the patient's postural sway responses were comparable to a low-lead (< 10 micrograms/dL) comparison group for 3 out of 4 tests which rely relatively less on the higher centers for balance. This improvement in postural balance may be attributable to the combined influence of pharmacologic and age associated maturational effects. This case study provides suggestive evidence that while chelation therapy can reduce PbB levels quickly, it can also modify gross neuromotor function manifested by postural balance characteristics.

Administration, Oral↗
PubMed1997

Thermodynamics of metal ion binding and denaturation of a calcium binding protein from Entamoeba histolytica.

The thermodynamics of the binding of calcium and magnesium ions to a calcium binding protein from Entamoeba histolytica was investigated by isothermal titration calorimetry (ITC) in 20 mM MOPS buffer (pH 7.0) at 20 degrees C. Enthalpy titration curves of calcium show the presence of four Ca2+ binding sites. There exist two low-affinity sites for Ca2+, both of which are exothermic in nature and with positive cooperative interaction between them. Two other high affinity sites for Ca2+ exist of which one is endothermic and the other exothermic, again with positive cooperative interaction. The binding constants for Ca2+ at the four sites have been verified by a competitive binding assay, where CaBP competes with a chromophoric chelator 5,5'-Br2 BAPTA to bind Ca2+ and a Ca2+ titration employing intrinsic tyrosine fluorescence of the protein. The enthalpy of titration of magnesium in the absence of calcium is single site and endothermic in nature. In the case of the titrations performed using protein presaturated with magnesium, the amount of heat produced is altered. Further, the interaction between the high-affinity sites changes to negative cooperativity. No exchange of heat was observed throughout the addition of magnesium in the presence of 1 mM calcium. Titrations performed on a cleaved peptide comprising the N-terminus and the central linker show the existence of two Ca2+ specific sites. These results indicate that this CaBP has one high-affinity Ca-Mg site, one high-affinity Ca-specific site, and two low-affinity Ca-specific sites. The thermodynamic parameters of the binding of these metal ions were used to elucidate the energetics at the individual site(s) and the interactions involved therein at various concentrations of the denaturant, guanidine hydrochloride, ranging from 0.05 to 6.5 M. Unfolding of the protein was also monitored by titration calorimetry as a function of the concentration of the denaturant. These data show that at a GdnHCl concentration of 0.25 M the binding affinity for the Mg2+ ion is lost and there are only two sites which can bind to Ca2+, with substantial loss of cooperativity. At concentrations beyond 2.5 M GdnHCl, at which the unfolding of the tertiary structure of this protein is observed by near UV CD spectroscopy, the binding of Ca2+ ions is lost. We thus show that the domain containing the two low-affinity sites is the first to unfold in the presence of GdnHCl. Control experiments with change in ionic strength by addition of KCl in the range 0.25-1 M show the existence of four sites with altered ion binding parameters.

Amino Acid Sequence↗
PubMed1997

In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA receptor.

The cell surface urokinase-type plasminogen activator receptor (uPAR) has been shown to be a key molecule in regulating plasminogen-mediated extracellular proteolysis. To investigate the role of uPAR in invasion of brain tumors, human glioblastoma cell line SNB19 was stably transfected with a vector capable of expressing an antisense transcript complementary to the 300 base pair of the 5' end of the uPAR mRNA. Parental and stably transfected (vector, sense, and antisense) cell lines were analysed for uPAR mRNA transcript by Northern blot analysis, and receptor protein levels were measured by radioreceptor assays and Western blotting. Significant reduction of uPAR sites was observed in the antisense transfected cell lines. The levels of uPAR mRNA were significantly decreased in antisense clones compared to control, vector and sense clones. The invasive potential of the cell lines in vitro was measured by Matrigel invasion assay and migration of cells from spheroids to monolayers. The antisense transfected cells showed a markedly lower level of invasion and migration than the controls. The antisense clones were more adhesive to the ECM components compared to parental, vector and sense clones. All transfected (vector, sense and antisense) clones and parental cells produced similar levels of uPA activity without any significant difference however, MMP-2 activity was decreased in antisense clones compared to controls. These results demonstrate that uPAR expression is critical for the invasiveness of human gliomas and down regulation of uPAR expression may be a feasible approach to decrease invasiveness.

Blotting, Northern↗
PubMed1997

An ergonomic education and evaluation program for apprentice carpenters.

Eighteen new apprentice carpenters received sixteen hours of ergonomics awareness education as a part of their regular apprenticeship training during 1994 and 1995. An equal number of apprentices received no training but served as controls. The training took place in the Southwest Ohio District Council of Carpenter's Joint Apprenticeship and Training School. The curriculum was designed to be "learner-centered." Instruction included short lectures presented by a journeyman carpenter and emphasized participatory activities in the school's carpentry shop. Ongoing program evaluation assessed trainees' reactions to the content and structure of the curriculum and its influence on their behavior. Trainees and controls completed brief quizzes on ergonomic knowledge. Hands-on exercises enabled trainees to apply recently acquired ergonomic knowledge in the school's carpentry shop. Trainees scored significantly higher on one-half of the post-session quizzes and the comprehensive test. Trainees preferred participatory teaching methods, especially those using redesigned tools (93%) and evaluating ergonomic risks (86%); and they supported continued safety and health education during apprentice training. The authors conclude that apprentice-ship programs should provide regular "learner-centered" occupational safety and health education that includes ergonomics, and these programs should be integrated with their shop-based manual arts instruction.

Ergonomics↗
PubMed1997

Characterization of EhCaBP, a calcium-binding protein of Entamoeba histolytica and its binding proteins.

A novel calcium-binding protein (EhCaBP) has been recently identified and characterized from the protozoan parasite Entamoeba histolytica. In order to decipher the function of this protein, a few basic properties were investigated and compared with the ubiquitous Ca(2+)-signal transducing protein calmodulin (CaM). Indirect immunofluorescence and immunoprecipitation analyses using specific antibodies against EhCaBP suggest that it is a soluble cytoplasmic protein with no major post-translational modification. EhCaBP did not stimulate cAMP-phosphodiesterase activity, differentiating it from all known CaMs. Affinity chromatography of [35S]methionine-labelled proteins of E. histolytica trophozoites using EhCaBP-sepharose column showed Ca(2+)-dependent binding of a group of proteins. Radiolabelled proteins from the same extract also bound to CaM-sepharose. However, the proteins bound to the two columns were different as revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. At least one of the EhCaBP-binding proteins became phosphorylated as revealed by in vivo phosphorylation analysis. The binding-proteins could not be detected in E. invadens (a species that is pathogenic in reptiles) and E. moshkovskii (which is found in the human gut but is not pathogenic), two species in which EhCaBP-like protein has not been found. Two distinct Ca(2+)-dependent protein kinases, which get activated by EhCaBP and CaM respectively, were detected in E. histolytica. These kinases require different levels of Ca2+ for their maximal activities. Affinity chromatography also showed the binding of protein kinase(s) to EhCaBP in a Ca(2+)-dependent manner. Our data suggest that there may be novel Ca(2+)-signal transduction pathway in E. histolytica mediated by EhCaBP.

Animals↗
PubMed1997

Prediction of probable genes by Fourier analysis of genomic sequences.

MOTIVATION: The major signal in coding regions of genomic sequences is a three-base periodicity. Our aim is to use Fourier techniques to analyse this periodicity, and thereby to develop a tool to recognize coding regions in genomic DNA. RESULT: The three-base periodicity in the nucleotide arrangement is evidenced as a sharp peak at frequency f = 1/3 in the Fourier (or power) spectrum. From extensive spectral analysis of DNA sequences of total length over 5.5 million base pairs from a wide variety or organisms (including the human genome), and by separately examining coding and non-coding sequences, we find that the relative-height of the peak at f = 1/3 in the Fourier spectrum is a good discriminator of coding potential. This feature is utilized by us to detect probable coding regions in DNA sequences, by examining the local signal-to-noise ratio of the peak within a sliding window. While the overall accuracy is comparable to that of other techniques currently in use, the measure that is presently proposed is independent of training sets or existing database information, and can thus find general application. AVAILABILITY: A computer program GeneScan which locates coding open reading frames and exonic regions in genomic sequences has been developed, and is available on request.

Algorithms↗
PubMed1997

Preemptive epidural morphine for postoperative pain relief after lumbar laminectomy.

This study was designed to evaluate the efficacy of preemptive epidural morphine for postoperative analgesia after lumbar laminectomy. Thirty ASA physical status I adults undergoing elective lumbar laminectomy under general anesthesia were randomly allocated to one of two groups. Group 1 (study group) received 3 mg epidural morphine preemptively 60 min before surgery, followed by epidural placebo at the end of surgery. Group 2 (control group) received epidural placebo at the same time preoperatively as the study group, followed by 3 mg epidural morphine at the conclusion of surgery. Pain was assessed using visual analog scales (VAS), and sedation was graded on a 4-point rank drowsiness score. Time to first postoperative analgesic (TFA), the supplementary analgesia, and the amount of morphine used over the 24-h period were noted for the groups. VAS pain scores were significantly less in Group 1 (preemptive group) than in Group 2 8 h after surgery (P < 0.05). TFA in the study group (19.9 +/- 2.3 h) was significantly prolonged compared with the control group (8.5 +/- 1.0 h, P < 0.05). The demand for supplementary analgesia and postoperative morphine consumption in the preemptive group was significantly lower than that in control group (P < 0.05). Patients in the control group were significantly sedated after 12 h and had a high incidence of nausea and vomiting (P < 0.05). The study shows that preemptive epidural morphine is superior to epidural morphine given postoperatively for pain relief after lumbar laminectomy.

Adult↗
PubMed1997

Effect of chronic low-level exposure to jet fuel on postural balance of US Air Force personnel.

This study used the postural stability technique to investigate the neurological effects of cumulative low-level exposure to raw JP-8 jet fuel vapor on aircraft maintenance personnel. All subjects performed two sets of four 30-second postural sway tests. The results of mean cumulative exposure levels (in parts per million +/- standard error of mean) were the following: naphthas, 1308 +/- 292; benzene, 21.2 +/- 5.7; toluene, 23.8 +/- 6.1; and m-,o-, p-xylene, 22.7 +/- 5.4. Covariate adjusted regression analysis of the exposed group data showed a statistically significant association (P < 0.05) between the solvents (benzene, toluene, and xylene) and increased postural sway response. For all solvent exposures, the "eyes closed, on foam" test provided the strongest association between sway length and JP-8 benzene (r2 range, 0.45 to 0.52), implying subtle influence on vestibular/proprioception functionalities.

Adult↗
PubMed1997

Short report: Leishmania DNA in Phlebotomus and Sergentomyia species during a kala-azar epidemic.

The presence of Leishmania donovani DNA in sand flies caught in Indian kala-azar patients' dwellings during the epidemic of 1990-1992 was studied using the polymerase chain reaction (PCR). Amplification of miniexon-derived RNA genes and gpG3 mRNA was achieved in single Phlebotomus argentipes, P. papatasi, and Sergentomyia babu flies. The data suggest the possible involvement of multiple sandfly species in kala-azar transmission.

Animals↗
PubMed1996

Identification of novel genes from Entamoeba histolytica by expressed sequence tag analysis.

Shotgun sequencing of cDNA clones is now an established approach to gain insight into the expressed nucleotide (nt) sequences in a given cell. We analysed 100 randomly picked cDNA clones of the protozoan parasite, Entamoeba histolytica, by nt sequencing, with a view to obtain novel gene sequences not detected so far by biochemical and genetic analyses. About 56% of the analysed clones showed significant homology with other genes in the database, including a number of genes whose presence may not be suspected in E. histolytica owing to its unusual subcellular organization. The results suggest that this approach can provide important clues to understand unique biochemical mechanisms in this parasite.

Animals↗
PubMed1996

Functional interaction between a RARE and an AP-2 binding site in the regulation of the human HOX A4 gene promoter.

HOX A genes are induced in a temporal fashion after retinoic acid (RA) treatment in non-N-ras-transformed PA-1 human teratcarcinoma cells. However, In N-ras-transformed PA-1 cells, RA-Induced expression of HOX A genes is delayed. The mRNA for the transcriptional activator AP-2 is overexpressed in these ras-transformed cells, but AP-2 transcriptional activity is inhibited relative to non ras-transformed PA-1 cells. Constitutive expression of AP-2 mimics the effect of ras by transforming cells and inhibiting differentiation in culture. We analyzed 4 kb of the human HOX A4 gene promoter and identified seven putative AP-2-binding sites in the DNA sequence. Transcription assays with variably sized HOX A4 promoter reporter constructs revealed that a 365 bp region of the promoter, -2950 to -3315 relative to the mRNA start, controls RA responsiveness and ras-mediated inhibition of HOX A4 activity. This region contains an AP-2 binding site and a RARE. Elimination of the AP-2 site by site-directed mutagenesis demonstrated that the AP-2 site is involved in RA-mediated transcriptional activation of the human HOX A4 promoter in combination with the RA receptor response element (RARE). In N-ras-transformed cells, low HOX A4 promoter activity results from ras inhibition of AP-2 transactivation.

Base Sequence↗
PubMed1996

Fluorescence energy transfer measurement of distances between ligand binding sites of tubulin and its implication for protein-protein interaction.

9-(Dicyanovinyl) julolidine (DCVJ) is a fluorescent probe, which binds to a unique site on the tubulin dimer and exhibits different properties that are dependent upon its oligomeric state (Kung & Reed, 1989). DCVJ binds to tubulin, the tubulin-colchicine complex, and the tubulin-ruthenium red complex equally well, but binds tighter to the ANS-tubulin complex than to tubulin alone. The energy transfer studies indicate a small amount of energy transfer with colchicine, but a significant energy transfer with ANS. It was shown previously that ruthenium red binds near the C-terminal tail region of the alpha-subunit. Ruthenium red causes major quenching of fluorescence of the tubulin-DCVJ complex, suggesting proximity of binding sites. The derived distances are consistent with DCVJ binding near the alpha beta interface, but on the opposite face of the colchicine binding site. Location of the binding site correlates with the observed effect of a different polymerized state of tubulin on the DCVJ spectroscopic properties. The effect of dimer-dimer association on DCVJ binding, at high protein concentrations (Kung & Reed, 1989), suggests that such an association may occur through lateral contacts of the elongated tubulin dimer, at least in a significant fraction of the cases. Transmission of ANS-induced conformational change to the DCVJ binding site, which is near important dimer-dimer contact sites, makes it possible that such conformational changes may be responsible for polymerization inhibition by anilino-naphthalene sulfonates.

Anilino Naphthalenesulfonates↗
PubMed1996

The disposition kinetics and residues of fenvalerate in tissues following a single dermal application to black Bengal goats.

The disposition kinetics of fenvalerate were studied in goats after dermal application of 100 ml of 0.25% (w/v) solution. The insecticide persisted in the blood for 72 h. The mean (+/- SEM) Vd(area) and apparent t 1/2 (beta) were 9.92 +/- 1.44 L/kg and 17.51 +/- 2.65 h, while the AUC and ClB values were respectively 82.15 +/- 7.40 micrograms h/ml and 0.56 +/- 0.05 L/(kg h). Four days after the dermal application, the highest concentration of fenvalerate residues was found in the adrenal gland, followed by the biceps muscle, omental fat, liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia but had no effect on serum protein and cholesterol levels. Serum acetylcholinesterase activities were increased after 24 h but were below the initial values from 48 to 120 h.

Acetylcholinesterase↗
PubMed1996

Effect of workers' shoe wear on objective and subjective assessment of slipperiness.

Subjective rating of slipperiness tests were conducted for 12 male industrial workers on three slippery surfaces, with poor or good lighting conditions, and with new or workers' own old shoes. A strain gauge force platform was used to evaluate dynamic coefficient of friction (COF) of shoes for the same surface conditions representing objective measurements. The shoe wear, available tread pattern, and hardness of old shoes were determined by instruments including a digital caliper, a digitizer, and a durometer, respectively. The surface effect was found to be highly significant on subjective ratings as well as dynamic COF (p < 0.0001). The correlation between dynamic COF values and subjective ratings was significant only for old shoes under medium oily conditions (r = 0.55, p < 0.04). For a slightly oily surface, decreasing the percent of tread available significantly increased dynamic COF values (p < 0.016). In addition, the effect of increased shoe hardness significantly increased the available tread pattern when only the data from the most deteriorated old shoes were included in the analyses (p < 0.004). These results emphasize the need to consider subjective assessment of slipperiness as a valid way to evaluate floor slipperiness. Further study is needed to (1) evaluate the effects of physical fatigue due to workload on subjective assessment of slipperiness and workers' ability to assess slipperiness during task performance; (2) consider the effect of available shoe tread on COF values and slip potential; and (3) determine if guidelines should be developed regarding when work shoes should be replaced to reduce slip and fall injuries.

Accidental Falls↗