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Biomedical subjects

S Datta

Publications and source records attributed to S Datta.

At least 19 recordsLinked to original sources

l(1)trol and l(1)devl, loci affecting the development of the adult central nervous system in Drosophila melanogaster.

Adult optic lobes of Drosophila melanogaster are composed of neurons specific to the adult which develop postembryonically. The structure of the optic lobes and aspects of its development have been described, and a number of mutants that affect its development have been identified. The focus of every screen to date has been on disruption of adult structure or function. Although these loci were originally identified on the basis of viable mutants, some have proven capable of giving rise to lethal alleles. It seems reasonable to assume that mutants which strongly affect development of the imaginal-specific central nervous system may evidence abnormalities during the late larval or pupal stages when the adult central nervous system is undergoing final assembly and might show a lethal phase prior to eclosion (as is true for mutations at the previously defined l(1)ogre locus). We have carried out the first screen of autosomal and sex-linked late larval and pupal lethals to identify mutations that affect the development of the optic lobes. Our screen yielded nine mutants that could tentatively be grouped into three classes, depending on the neuroblast population affected and imaginal disc phenotypes. Two of these, including one that is allelic to l(1)zw1, were chosen for further analysis.

Animals

Does epidural administration of butorphanol offer any clinical advantage over the intravenous route? A double-blind, placebo-controlled trial.

The differential effects of intravenous versus epidural administration of short-acting, lipid-soluble opioids is controversial. This study was undertaken to compare these two routes of administration using the mixed agonist-antagonist opioid, butorphanol. Forty-five women undergoing elective cesarean delivery at term under epidural lidocaine anesthesia were randomized to receive a single bolus of either epidural or intravenous butorphanol 2 mg or saline control for postoperative analgesia. At precisely 60 min after the last dose of epidural local anesthetic, all patients received a simultaneous epidural and intravenous injection in a randomized, double-blinded fashion. The intravenous group received butorphanol intravenous and saline epidurally; the epidural group received saline intravenous and butorphanol epidurally; and a control group received saline via both routes. When additional analgesia was requested, all patients received patient-controlled analgesia (PCA) with intravenous morphine (2-mg demand dose, 7-min lockout interval). Analgesia was quantitated using a visual analogue scale and subsequent PCA morphine requirements. The interval from study drug injection until first request for PCA use was equivalent for the intravenous and epidural groups (89 +/- 9 and 83 +/- 8 min, respectively) and significantly longer than in control group (39 +/- 4 min, P less than 0.001, intravenous and epidural vs. control). Analgesia was equivalent in the intravenous and epidural groups at all observation points, and pain scores were significantly lower than control for the first 120 min after study drug injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of progesterone on the cardiac electrophysiologic action of bupivacaine and lidocaine.

Pregnancy is accompanied by an increased cardiac and neural sensitivity to some local anesthetic agents such as bupivacaine. The current study was initiated to investigate the relationship between increased progesterone concentrations and the electrophysiologic effects of bupivacaine, and lidocaine in isolated Purkinje fiber (PF)-ventricular muscle (VM) preparations. Twenty-four oophorectomized female white rabbits were killed after receiving 30 mg.kg-1.day-1 of progesterone intramuscularly or peanut oil alone for 4 days. PF and VM action potentials were recorded using standard electrophysiologic procedures. Plasma progesterone concentrations were 5 +/- 2.9 ng/ml in control animals compared to 59.8 +/- 11.0 ng/ml in progesterone-treated animals (P less than 0.05). Bupivacaine (3.5-17.4 microM) depressed the maximal rate of depolarization (Vmax) of PF to a significantly greater extent in tissues from progesterone-treated animals as compared to control animals. For example, at 3.5 microM bupivacaine decreased PF Vmax 52% in progesterone-treated tissues compared to 32% in controls (P less than 0.05); the Vmax of VM was also depressed to a greater extent in tissues from progesterone-treated animals (P less than 0.001). Lidocaine did not demonstrate an enhanced depressant effect in tissues from progesterone-treated animals. These results indicate that progesterone selectively increases the cardiac membrane depressant effects of bupivacaine but not lidocaine. This may contribute to the enhanced toxicity of bupivacaine in pregnant animals.

Action Potentials

A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia.

A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously. We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously. Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally (n = 9), epidurally (n = 8), or intravenously (n = 7), using a combined spinal-epidural technique. The sufentanil was administered alone, without concomitant local anesthetics. Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient's request for additional analgesia via the epidural catheter (bupivacaine 0.25%). The median duration of analgesia (median, interquartile range) was 84 (70-92) min in the intrathecal group, 30 (23-32) min in the epidural group, and 34 (17-30) min in the intravenous group (P < 0.001). The intrathecal group showed rapid and significant decrease in visual analogue scale scores, whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points. Side effects were limited to pruritus in 3 patients (2 moderate and 1 severe) in the intrathecal group. No patient developed post-dural puncture headache. We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1-2-h duration during labor. Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Thyroid hormone receptor mediates transcriptional activation and repression of different promoters in vitro.

The thyroid hormone receptor (TR) has the dual ability to activate or repress transcription of specific genes. A cell-free transcription system was used to study the effects of TR on transcription by positively (TREpMLP) and negatively (TSH alpha) regulated promoters. Receptor-deficient HeLa cell extracts were complemented with baculovirus-produced TR. TR stimulated transcription from the TREpMLP promoter by 3-fold, and trans-activation did not require hormone. Transcriptional stimulation by TR required the presence of the TRE sequence and was diminished by the addition of competitor TRE binding sites. Baculovirus-produced TR repressed transcription in vitro from the TSH alpha promoter by 30-50%, also in a hormone-independent manner. Transcription from a control adenovirus 2 major late promoter was unaffected by added TR. Receptor-specific antisera and competition with TRE binding sites impaired TR-mediated repression of the TSH alpha promoter. Unlike transcriptional stimulation, which was optimal when TR and HeLa extracts were added concomitantly, transcriptional repression by the TR was most effective when the receptor was preincubated with the alpha-promoter, suggesting that receptor binding to the promoter may block access of other proteins to cause transcriptional repression. These results indicate that baculovirus-expressed TR mediates transcriptional activation and repression in a promoter-specific manner in vitro. This system provides a valuable model for examining transcriptional control by the TR.

Baculoviridae

Demographic survey of opinions towards smoking: a pilot study.

A survey was conducted by means of a questionnaire, on 865 smokers to analyse their opinions towards some general aspects of smoking. The subjects were mostly males (97.11%) and belonged to the age group of 21 to 50 years (80%). Heavy smoking is injurious to health is the opinion of most of the smokers (90.41%) particularly when maintained with other addictions (80%); tobacco is harmful not only when smoked but also when used in other forms (63%) and moderate smoking may not be much harmful (43%). However, smoking is not necessary to make or maintain relations with others (70%). Statutory warning has no marked effect on the habit (69.83%), the role of legal restrictions is dubious but advertisements encourage the habit definitely (62.54%). Three out of 4 persons know the problems of smoking and almost the same proportion of the people think that smoking can be stopped or at least checked. But there is difference of opinion about the person to be consulted, if any such problems arises from the habit of smoking. Family physicians may play an important role in controlling the habit.

Adolescent

The natural history of smoking.

This study is a small collection of the natural history of smoking of 865 persons - all smokers and majority (97.11%) of them were males, more than 80% were between 21-50 years, most (90%) were Hindus and 75% were service holders. It revealed that most of the subjects started smoking between 10 and 25 years of age, frequently being requested by their friends but felt nothing mentionable at their first experience. Most of them (64%) were smoking for more than 10 years, 48.56% were smoking more than 10 cigarettes in a day, filter-tipped more often (by 64% subjects) and without any history of break by 56% subjects. Majority (80%) used to inhale the smoke and 40% had no specific time of choice. Most of the subjects (80%) like to smoke in deep thoughts, 66% during excitement, 60% when depressed, 82% when relaxed and 62.5% when alone. But most of them (64%) did not smoke when busy. Majority (70.87%) felt relaxed when smoking. Most of the people (45%) stood reasonable having no cigarette in their stock. Majority (84%) used to smoke even when not offered. Tobacco was consumed largely as smoke by 75% subjects; 78% subjects smoked only cigarettes and about half of the smokers smoked even when they did not enjoy it.

Adult

Cholinergic microstimulation of the peribrachial nucleus in the cat. I. Immediate and prolonged increases in ponto-geniculo-occipital waves.

The cholinergic agonist carbachol was injected into the pontine Pb area where PGO bursting cells have been recorded. When microinjections were localized to the ventrolateral aspect of the caudal Pb nucleus near aggregates of ChAT immunolabeled cholinergic neurons, carbachol produced an immediate onset of state-independent PGO waves in the ipsilateral LGB. These state-independent PGO waves persisted for 3-4 days. After the first 24 hrs PGO wave activity increasingly became associated with REM sleep and with REM transitional SP sleep as both of these PGO-related states increased in amount to 3-4 times baseline levels. The increase in amount of PGO-related states peaked on days 2-4 following one carbachol injection and persisted for 10-12 days. These results suggest a two stage process: stage one, PGO enhancement, is the direct consequence of the membrane activation of cholinoceptive PGO burst neurons by carbachol; stage two, REM enhancement, is the consequence of metabolic activation of endogenous cholinergic neurons. This experimental preparation is a useful model for the study of the electrophysiology and functional significance of PGO wave and REM sleep generation.

Acetylcholine

Cholinergic microstimulation of the peribrachial nucleus in the cat. II. Delayed and prolonged increases in REM sleep.

The hypothesis that REM sleep is cholinergically mediated is supported by the identification of a cholinoceptive trigger zone in the FTG. Since this trigger zone is devoid of cholinergic neurons, the aim of the present study was to test the hypothesis that a cholinergic drive for REM sleep may come from the cholinergic cells of the PBL region. Chronically implanted freely moving cats with electrodes for sleep and PGO wave recordings were used. Guide tubes were implanted for carbachol microinjections (4 micrograms/250 nl) in the PBL and FTG. All microinjections were delivered in close vicinity of ChAT+ cholinergic cells in the PBL region. Results showed that a single unilateral carbachol microinjection into the PBL induced sustained (24 hr) state-independent ipsilateral PGO wave activity. This PGO wave activity was followed by a prolonged enhancement of REM sleep lasting for more than six days. We also observed that REM enhancement was followed by a delayed but marked enhancement of S sleep episodes with PGO waves (SP), which are normally brief transitions from S to REM sleep. Our findings strongly support the hypothesis that cholinergic drive for REM sleep comes from the lateral pontine tegmentum and we suggest that the PBL region plays a major role in both PGO wave generation and long-term regulation of REM sleep induction.

Acetylcholine

Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves.

We have previously hypothesized that the spike bursts of brainstem peribrachial (PB) neurons, leading to ponto-geniculo-occipital (PGO) waves in thalamocortical systems, are triggered by phasic hyperpolarizations of sufficient magnitude or by excitatory inputs reaching a steadily hyperpolarized membrane. We have proposed that the source of these hyperpolarizing actions are substantia nigra pars reticulata (SNr) cells that project to, and exert inhibitory effects upon, PB neurons. Here we tested this hypothesis by recording antidromically identified SNr-PB cells in chronically implanted, naturally sleeping cats. A subpopulation of SNr-PB cells exhibited tonically increased firing preceding by 70-200 ms the thalamic PGO wave. These data support the hypothesis that an enhancement in SNr-cells' discharges may lead to hyperpolarization of PB neurons, with the consequence of spike bursts in one class of PGO-related PB-thalamic neurons.

Animals

Effect of recombinant fibroblast interferon and recombinant immune interferon on growth and the antigenic phenotype of multidrug-resistant human glioblastoma multiforme cells.

To study the effect of drug resistance on the response of stage IV astrocytomas to interferon, a human glioblastoma multiforme cell line, GBM-18, was transfected with an expression-vector plasmid containing a human multidrug resistance (MDR) gene (pHaMDR1/A), and clones surviving in colchicine were isolated. GBM-18 multidrug-resistant subclones displayed cross-resistance to other chemotherapeutic agents, including vincristine, doxorubicin, and dactinomycin. The multidrug-resistant phenotype was reversible when GBM-18 multidrug-resistant cells were cultured in colchicine and the calcium-channel blocker verapamil. The level of the MDR1 gene (also known as PGY1) message was increased in GBM-18 multidrug-resistant cells selected for increased resistance to colchicine, and this effect was not correlated with an amplification of the MDR1 gene. In both parental GBM-18 and GBM-18 multidrug-resistant cells, growth was suppressed to a greater degree when cultures were treated with the combination of fibroblast interferon (IFN-beta) and immune interferon (IFN-gamma). Parental cells and multidrug-resistant subclones varied in their de novo and/or interferon-modulated expression of HLA class I and class II antigens, a high-molecular-weight melanoma-associated antigen, and intercellular adhesion molecule 1 (ICAM-1). Of the antigens tested, ICAM-1 and HLA class I antigens were the most sensitive to enhanced expression induced by IFN-beta and IFN-gamma when used alone or in combination. The results of the present study indicate that multidrug-resistant human glioblastoma multiforme cells retain their increased sensitivity to the antiproliferative activity of the combination of IFN-beta plus IFN-gamma, and differences in antigenic phenotype are apparent in independent multidrug-resistant glioblastoma multiforme clones.

Antibodies, Monoclonal

Human thyroid hormone beta 1 receptor produced by recombinant baculovirus-infected insect cells.

Thyroid hormone receptors are nuclear proteins which regulate transcription in a hormone dependent manner. The baculovirus expression system was used for the overexpression of the beta 1 isoform of the human thyroid hormone receptor. The baculovirus produced receptor binds tri-iodothyronine with high affinity, is specifically immunoprecipitated with a beta 1 specific antibody, and binds to DNA that contains a known thyroid hormone receptor recognition site. Large scale production and purification of baculovirus produced receptor will be useful for structure-function analyses and studies of transcriptional regulation.

Animals

Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons.

Administration of interferon as a single therapeutic regimen in cancer patients with various neoplasias has had only limited efficacy in ameliorating the negative clinical course of their disease. In the present study, we have evaluated the effect of recombinant human fibroblast (IFN beta) and immune (IFN gamma) interferon, alone and in combination, on growth, differentiation and the expression of class I and II histocompatibility locus antigens (HLA) and melanoma-associated antigens on the human melanoma cell line H0-1. The effect of combinations of interferons on the antigenic profile of human melanoma cells displaying different organ colonization and spontaneous metastatic potential in athymic nude mice was also determined. H0-1 cells were more sensitive to the antiproliferative activity of IFN beta than to IFN gamma and the combination of interferons resulted in a potentiation of growth suppression. The antiproliferative effect of both interferons was greater in later-passage than in earlier-passage H0-1 cells, possibly reflecting alterations in the evolving tumor cell population as a result of long-term in vitro propagation and/or the selective outgrowth of cells with an increased growth rate. The enhanced growth suppression observed in H0-1 cells treated with the combination of IFN beta plus IFN gamma was not associated with a significant increase in the level of melanin, a marker of melanoma differentiation, above that observed with either interferon used alone. IFN beta and IFN gamma differentially modulated the expression of class I and II HLA and melanoma-associated antigens in H0-1 cells and a series of melanoma cells with different organ colonization and metastatic potential, including MeWo, MeM 50-10, MeM 50-17, 3S5 and 70W. No consistent potentiation or antagonism in the expression of any specific antigen was observed in any of the melanoma cell lines exposed to the combination of interferons. The present study demonstrates that the combination of IFN beta plus IFN gamma can potentiate growth suppression in H0-1 human melanoma cells and that this effect is not associated with an increase in differentiation or a potentiation in antigenic modulation. In addition, no direct correlation between the expression of any specific antigen or its modulation by IFN beta or IFN gamma, alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines.

Animals

Expression of virulence and antibiotic resistance in an Escherichia coli transconjugant carrying a large plasmid pCAT120 of Shigella dysenteriae type I and its spontaneous fragmentations.

The role of a 120-kb plasmid in relation to virulence and drug resistance factor in Shigella dysenteriae was studied. For characterization of plasmids, the mating system is a useful and efficient means of transferring both large and small plasmids to a new host. The conjugative transfer of a 120-kb (pCAT120) ampicillin-resistant plasmid of S. dysenteriae to E. coli K-12 was not successful. Introduction of an E. coli fertility factor plasmid F, did not help to mobilize the plasmid. Low transfer frequencies of antibiotic markers to E. coli were achieved by treatment of the donor S. dysenteriae with N-methyl-N'-nitro-N-nitrosoguanidine. The transconjugants showed resistance to ampicillin, chloramphenicol, tetracycline and cadmium. A transconjugant carrying the 120-kb plasmid of S. dysenteriae produced keratoconjunctivitis in guinea pigs. Repeated subculture of Clmr transconjugant (pCAT120) on tryptic soya agar plates became Clms and showed four distinct DNA bands ranging from 3 to 10 kb in size on agarose gel electrophoresis. Utilization of organic acids, metal resistance (Cd), dye-binding properties (Crb+, Ebr+) and drug resistance (Amp, Tet) were identified on 10, 7, 4 and 3-kb plasmid DNA fragment of pCAT120 respectively. Crb+ 4-kb DNA fragment of pCAT120 was isolated, purified and transferred to an avirulent E. coli K12 by transformation. However, transformant (pET4) showed poor growth on solid media and its growth in liquid culture was only possible after supplementation of the unknown low-molar-mass thermolabile factor(s) secreted by the recipient strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Outer Membrane Proteins

Epidural nalbuphine for analgesia following caesarean delivery: dose-response and effect of local anaesthetic choice.

The analgesic profile of epidural nalbuphine for postoperative pain relief and the impact of local anaesthetic choice upon this profile was investigated in 58 patients undergoing elective Caesarean delivery under epidural anaesthesia. Patients were randomized to receive either lidocaine 2% with 1:200,000 epinephrine or 2-chloroprocaine 3% for perioperative anaesthesia, followed by either 10, 20, or 30 mg of epidural nalbuphine administered at the first complaint of postoperative discomfort. Postoperative analgesia was quantitated on a visual analogue (VAS) scale, and by the time from the epidural opioid injection until the first request for supplemental pain medication. The duration of analgesia after lidocaine anaesthesia followed by 10, 20 or 30 mg nalbuphine was 77 (53-127) min, 205 (110-269) min, and 185 (116-241), respectively (median, 95% confidence interval, P less than 0.01, 20 and 30 mg vs 10 mg). Following 2-chloroprocaine anaesthesia, VAS remained consistently elevated: the median duration of analgesia was only 30-40 min and did not differ among the three doses of nalbuphine. Side-effects consisted only of somnolence, and were noted only following lidocaine anaesthesia. Somnolence was observed in 0, 20% and 50% of those receiving 10 mg, 20 mg and 30 mg of nalbuphine respectively (NS). No evidence of respiratory depression was noted in any patient. It is concluded that 20 or 30 mg of epidural nalbuphine provides analgesia for only two to four hours following Caesarean delivery with lidocaine anaesthesia, but anaesthesia with 2-chloroprocaine resulted in minimal or no analgesia from this opioid. Nalbuphine appears to be a disappointing agent for epidural use after Caesarean delivery.

Adult

Red cell use during cesarean delivery.

The transfusion of red cells (RBCs) was analyzed over a 4-year period (1984-1987), during which 9596 cesarean deliveries were performed. A total of 336 patients were identified as receiving RBC transfusions during or after cesarean delivery; 747 units of RBCs were administered. The overall incidence of transfusion in this patient population declined from 6.2 to 3.2 percent during the study period (p less than 0.001). Slightly more than one-half (54.4%) of all transfusions were given in the operating room or recovery room. The majority of patients (68.4%) received 2 units of RBCs, 11.6 percent received a 1-unit transfusion, and 8.3 percent received 5 units or more. The most common obstetric diagnoses associated with RBC transfusion were disorders of placental implantation, preeclampsia, premature labor with tocolytic therapy, fetal distress, and augmentation of dysfunctional labor. In patients without risk factors for bleeding, there was no trend indicating increased transfusion requirements when general anesthesia was employed. In conclusion, this study documents a decline in the transfusion rate during cesarean delivery.

Anesthesia, Epidural

Maternal temperature regulation during extradural analgesia for labour.

We have studied the effect of analgesia on maternal temperature (oral and tympanic membrane) progression in 53 women during normal spontaneous labour. Three groups were studied: two received extradural analgesia with a continuous infusion of 0.25% bupivacaine with or without the addition of fentanyl; the third group received only parenteral opioid analgesia. All patients were afebrile and without clinical evidence of infection at the beginning of the study. Both groups of patients receiving extradural analgesia had a consistent and significant increase in temperature after approximately 5 h of analgesia; no such trend was observed in the parenteral opioid group. Alterations in mechanisms of heat dissipation may explain these findings.

Adolescent

A preferential inhibition of impulses in C-fibers of the rabbit vagus nerve by veratridine, an activator of sodium channels.

In seeking a means to reverse local anesthetic block of peripheral nerve, we examined the actions of veratridine (VTD), an agent known to antagonize competitively the binding of local anesthetics to Na channels. The actions of VTD, a steroidal alkaloid "activator" of voltage-gated Na channels, were studied in the rabbit vagus nerve by two methods. In one, the effects of VTD on compound action potentials (APc) propagating through a "veratrinized" segment (11-mm) of nerve were measured by extracellular recording. Single volleys of impulses were unaffected by VTD, but trains of impulses, triggered by repetitive stimulation, were selectively diminished. This "use-dependent" reduction was greatest for the C-fiber component of the APc, less for B-fibers, and inconsequential for A-fibers. Use-dependent inhibition was enhanced by higher stimulation frequency and by increased VTD concentration, and reversed rapidly when stimulation ceased. If the nerve sheath remained intact, the rate of VTD action was far less than in desheathed nerves, but the effects were the same. In the other experimental system, membrane potentials were measured in the veratrinized region of the nerve by a sucrose-gap method. Repetitive stimulation, particularly of C-fibers, produced a cumulative VTD-induced depolarization (VID) that was sustained over several seconds and during which the C-fiber APc was selectively reduced. We propose that this local, use-dependent VID provides the means to inhibit impulses propagating through the veratrinized region. The preferential effect of VTD on C-fibers suggests its possibilities as a relatively selective agent for block of impulse trains in nociceptive afferents.

Action Potentials