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Biomedical subjects

S Datta

Publications and source records attributed to S Datta.

At least 271 records · Page 15Linked to original sources

Chronically administered progesterone decreases halothane requirements in rabbits.

The MAC for halothane is 25% lower in pregnant than that in nonpregnant ewes. The reason for this is uncertain, but changes in both steroidal and endogenous opiate have been implicated. This study was undertaken to assess the effect of exogenous progesterone on minimal alveolar concentrations (MAC) of halothane in ovariectomized rabbits. Minimal alveolar concentration of halothane was determined in 84 female rabbits, 37 intact (group A), 20 ovariectomized and injected with inert carrier peanut oil (group B), and 27 ovariectomized and injected with progesterone in peanut oil (group C). Minimal alveolar concentration in group A, 1.68 +/- 0.06% (mean +/- SEM), did not differ significantly from that in group B rabbits, 1.77 +/- 0.06%. However, MAC in progesterone-treated rabbits, 1.48 +/- 0.06%, was significantly lower than the MAC of the other two groups (P less than 0.01). Plasma progesterone concentrations in group A, B, and C were 5.28 +/- 0.62 ng/ml, 6.83 +/- 2.00 ng/ml, and 37.33 +/- 4.25 ng/ml, respectively. These results suggest that experimental treatment with progesterone can reduce the amount of halothane required to produce anesthesia and may explain the phenomenon of decreased need of inhalation anesthetic in human parturients.

Animals↗

Epidural butorphanol-bupivacaine for analgesia during labor and delivery.

A double-blind, randomized, dose-response study of a combination of 0.25% bupivacaine combined with 0, 1, 2, or 3 mg of butorphanol was studied in 40 laboring parturients. The optimal dose of butorphanol combined with 8.5 to 10 ml 0.25% bupivacaine was 2 mg; with 2 mg, the duration of analgesia was significantly greater and the time to onset of analgesia significantly shorter than when no butorphanol was added, and the amount of bupivacaine could be reduced 50%. Adverse fetal effects were not observed except that of a low amplitude sinusoidal fetal heart rate pattern with doses of 3 mg butorphanol. All neonatal observations were normal. It is concluded that epidural butorphanol can be a useful and safe adjunct to bupivacaine used for epidural analgesia during labor.

Analgesia, Epidural↗

Human hepatic lipase. Cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization, and evolutionary relationships with lipoprotein lipase and pancreatic lipase.

Human hepatic lipase is an important enzyme in high density lipoprotein (HDL) metabolism, being implicated in the conversion of HDL2 to HDL3. Three human hepatic lipase cDNA clones were identified in two lambda gt11 libraries from human liver. The cDNA-derived amino acid sequence predicts a protein of 476 amino acid residues, preceded by a 23-residue signal peptide. Four potential N-glycosylation sites are identified, two of which are conserved in rat hepatic lipase. On alignment with human, mouse, and bovine lipoprotein lipase, the same two sites were also conserved in lipoprotein lipase in all three species. Stringent conservation of the cysteine residues was also evident. Comparative analysis of amino acid sequences shows that hepatic lipase evolves at a rapid rate, 2.07 x 10(-9) substitutions/site/year, about four times that in lipoprotein lipase and half that in pancreatic lipase. Further, hepatic lipase and pancreatic lipase appear to be evolutionarily closer to each other than either of them is to lipoprotein lipase. Southern blot analysis revealed high frequency restriction fragment length polymorphisms of the hepatic lipase gene for the enzymes HindIII and MspI. these polymorphisms will be useful for haplotype and linkage analysis of the hepatic lipase gene. Using cloned human hepatic lipase cDNA as a hybridization probe, we performed Southern blot analysis of a panel of 13 human-rodent somatic cell hybrids. Concordance analysis of the various hybrid clones indicates that the hepatic lipase gene is located on the long arm of human chromosome 15. Analysis of hybrids containing different translocations of chromosome 15 localized the gene to the region 15q15----q22.

Amino Acids↗

Analysis of cis and trans elements involved in cAMP-inducible gene expression in Dictyostelium discoideum.

Expression of the Dictyostelium discoideum pst-cath (CP2) gene is transcriptionally regulated during multicellular development, and the gene is inducible in competent single cells following administration of exogenous cAMP. The 5' flanking region of pst-cath (CP2) that extends from -313 to the Cap site (+1) has previously been shown to contain sufficient cis-acting regulatory elements for proper developmental and cAMP-inducible expression of a foreign gene [Datta and Firtel, 1987, Mol Cell Biol 7:149-159]. The -283 to -201 region includes two exceptional "G-boxes" centered at -233 and -217 respectively, and this approximately 80 bp region is essential for basal as well as regulated expression of the pst-cath (CP2) gene. Here we summarize results obtained from a detailed analysis of a series of linker-scanner mutants and mutants that carry small internal deletions within the essential 80-bp region. Insertion of a synthetic oligonucleotide that includes the downstream G-box is demonstrated to rescue a low level of cAMP-inducible expression following insertion into cassette mutants. The effect of introducing a change in the relative spacing between regulatory elements has also been investigated. We have analyzed nuclear extracts for the presence of DNA-binding proteins that interact specifically with the pst-cath (CP2) regulatory region and identified two such putative trans-acting factors: 1) the AT-factor that is observed within a few hours following the onset of starvation and that binds tightly to stretches of alternating adenine-thymine residues (poly(dA-dT]; and 2) the AG-factor that is present in nuclear extracts of aggregated cells. Competition studies have demonstrated significant differences in the affinity that characterizes the binding of the two factors to G-box-containing sequences. The binding specificities of these DNA-binding proteins have been analyzed using gel mobility-shift and DNaseI footprinting assays.

Base Sequence↗

A small nonconjugative plasmid encoded for streptomycin-resistant character in Shigella dysenteriae.

Conjugative transfers of drug-resistant plasmids in Shigella dysenteriae type 1 isolated from the epidemic in West Bengal were unsuccessful. The plasmids were non-transmissible in spite of having the fertility factor F, genetically labelled with kanamycin-resistant transposon Tn903 (pWS 7). A small 2.5 kb nonconjugative plasmid encoded for the streptomycin-resistant character. Cured plasmid-less strains of S. dysenteriae 1 showed resistance to sulfonamides.

Drug Resistance, Microbial↗

Interrelationship of thermal and sleep-wakefulness changes elicited from the medial preoptic area in rats.

The study investigated the possible interrelationship between changes in sleep-wakefulness and body temperature, primarily induced by manipulation of the noradrenergic system in the medial preoptic area. Saline, norepinephrine, and its alpha- and beta-blockers were injected in the medial preoptic area and in some control areas of rats, during their sleeping and active periods. 5-Hydroxytryptamine was injected in the medial preoptic area in another group of animals. Simultaneous changes in sleep-wakefulness and the body temperature were continuously recorded. Norepinephrine produced hypothermia and arousal, whereas alpha-adrenergic blockers induced hyperthermia and sleep. These changes in body temperature and in sleep-wakefulness did not follow an identical time course. 5-Hydroxytryptamine induced hyperthermia without affecting sleep-wakefulness. It is suggested that there are different neuronal mechanisms in the medial preoptic area that bring about the drug-induced changes in temperature and sleep-wakefulness.

Animals↗

Anesthesia for the obstetric patient with multiple sclerosis.

Data on all obstetric patients delivering at the Brigham and Women's Hospital during the years 1982 through 1987 were collected. The anesthetic techniques used, the type and amount of anesthetic agents administered, and the postpartum relapse rate of multiple sclerosis patients were compared. Women who received epidural anesthesia for vaginal delivery did not have a significantly higher incidence of relapse than those who received local infiltration. However, all of the women who experienced postpartum relapses had received concentrations of bupivacaine greater than 0.25%. This finding may suggest that a higher concentration of drug over a longer period of time may adversely influence the relapse rate.

Anesthesia, Epidural↗

Developmental neurophysiology of mammalian peripheral nerves and age-related differential sensitivity to local anaesthetic.

Using an in vitro nerve preparation, we have studied the relative electrophysiological properties of myelinated and unmyelinated nerve fibres in the vagus nerve of 1-, 9- and 36-month-old rabbits and their sensitivity to local anaesthetic. The baseline (values before infusion of local anaesthetic) mean amplitude and conduction velocity (CV) of the compound action potential (APc) were recorded and the nerve was exposed to a range of concentrations (0.5-4.0 mmol litre-1) of lignocaine for periods sufficient to attain equilibrium block. There was an increase in the amplitude of the A fibre elevation from the 1-month to the 9- and 36-month-old rabbits. The CV of the A and B fibres increased significantly with age, while the CV of the C fibres did not change. The ED50 values of lignocaine for reduction of the A fibre elevation in the 1-, 9- and 36-month-old rabbits were 0.66, 0.94 and 0.85 mmol litre-1, respectively. The respective values for the B fibres were 0.74, 1.21 and 0.82 mmol litre-1, while those of the C fibres were 1.50, 2.44 and 2.07 mmol litre-1. In general, nerves from young and old rabbits were more sensitive to local anaesthetic-induced conduction blockade, suggesting that smaller doses of local anaesthetic are required clinically for anaesthesia in paediatric and older age groups.

Action Potentials↗

An 80-bp cis-acting regulatory region controls cAMP and development regulation of a prestalk gene in Dictyostelium.

We have analyzed an 80-bp region containing the cis-acting sequences necessary for regulation of the Dictyostelium discoideum prestalk gene pst-cathepsin at the appropriate stage during multicellular development and in response to cAMP in single-cell culture. The region lies between approximately -280 and -200 bp upstream from the Cap site and contains two intertwined G/C-rich sequences, including a palindromic sequence and a direct repeat of the 3' portion of the palindrome. In a previous set of experiments, we showed that the direct repeat, or G-box, is important in the regulation of pst-cath expression. In this paper, we use a series of nested internal deletions to define other regions within the promoter required for cAMP and developmental expression, to further examine the importance of the two G-boxes, and to examine the functional relationship of the G-boxes with respect to the other regulatory sequences. Analysis of the expression of these constructs in transformed cells showed that both the 5' portion of the palindrome and the two G-boxes are required for promoter function and are capable of developmentally regulating pst-cath expression. An A/T-rich sequence located 5' to the G/C-rich sequence is also essential for maximal expression, whereas insertion of a linker 5' to this region suggests the presence of a negative element functional during multicellular development. The spacing between the G-box sequences proved to be important for the full induction of gene expression. Constructs containing the G-boxes at wild-type spacing or closer show wild-type or near wild-type levels of expression, whereas expansion of the region between the G-boxes leads to a substantial drop in the level of gene expression in response to cAMP. Insertion of an oligonucleotide containing one of the G-boxes and surrounding sequences can partially complement deletions in which this region has been removed. Analysis of the expression of the cassette constructs, in some cases, revealed significant differences in the quantitative level of expression under the two developmental conditions. This suggests that there are either qualitative or quantitative differences in the factors controlling the expression of this gene under these two conditions.

Base Sequence↗

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound. Improved cardiac performance after hypothermic cardioplegic arrest.

The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.

Adenosine Triphosphate↗

Decreased incidence of tourniquet pain during spinal anesthesia with bupivacaine. A possible explanation.

In a previous report, the incidence of tourniquet pain was found to be 25% with bupivacaine and 60% with tetracaine (P less than 0.05) spinal anesthesia. On the other hand, tetracaine is more potent than bupivacaine in abolishing the single-compound action potential in vitro in isolated nerves. These conflicting observations may be reconciled if bupivacaine produced greater frequency-dependent conduction blockade of nerve action potentials. This hypothesis was tested in C fibers of isolated, desheathed rabbit vagus nerves. The nerves were supramaximally stimulated at frequencies of 9 or 15 Hz. After a control period, the nerves were exposed to bupivacaine (0.2 mM) or tetracaine (0.02 mM) for 30 minutes. The local anesthetics were then washed out by continuous constant-rate perfusion. The decline and recovery of the first and last action potential amplitudes of the train were measured. Bupivacaine and tetracaine produced similar depression of the first action potential of the 9-Hz and 15-Hz trains. However, bupivacaine caused a delayed recovery of the last action potential of the 15-Hz train but not of the 9-Hz train. These results show that bupivacaine produces greater frequency-dependent conduction blockade of C fibers than does tetracaine. These findings offer a possible explanation as to why spinal anesthesia with bupivacaine results in a lower incidence of tourniquet pain than tetracaine.

Action Potentials↗

Autoantibodies of various specificities encoded by genes from the VH J558 family bind to foreign antigens and share idiotopes of antibodies specific for self and foreign antigens.

We examined the binding to foreign antigens and the expression of crossreactive idiotypes by a panel of 20 murine monoclonal autoantibodies encoded by V genes from the VH J558 family. 9 of 20 antibodies bound to foreign antigens such as bacterial polysaccharides, poly(Glu50, Tyr50), poly(Glu54,Lys37,Phe9), arsonate, and lysozyme, known to interact with antibodies encoded by genes from the VH J558 family. A high proportion of our panel of autoantibodies expressed crossreactive idiotypes originally borne by monoclonal rheumatoid factors, anti-Sm, and anti-DNA antibodies, all encoded by V genes from the VH J558 family. Some of these VH J558+ autoantibodies shared crossreactive idiotypes with VH J558+ antibodies directed against foreign antigens such as influenza virus hemagglutinin, poly(Glu60,Ala30,Tyr10), arsonate, and dextran. The implications of these findings are discussed with respect to the process of activation of self-reactive clones.

Animals↗