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Biomedical subjects

G Das

Publications and source records attributed to G Das.

At least 55 records · Page 3Linked to original sources
PubMed1995

Macrophage-T cell interaction in experimental visceral leishmaniasis: failure to express costimulatory molecules on Leishmania-infected macrophages and its implication in the suppression of cell-mediated immunity.

The most important immunopathological consequence of infection with Leishmania seen in murine and human hosts is the suppression of T cell-mediated immune responses to both mitogens and leishmanial antigens. It has been suggested that this suppression is mediated by macrophages, either by defective antigen processing and presentation or by the elaboration of suppressive mediators like prostaglandins. Optimum activation of T helper cells requires not only T cell receptor occupancy by the antigen-Ia complex, but also costimulatory signals provided by the antigen-presenting cells. We investigated the status of several costimulatory molecules on infected macrophages from both genetically susceptible BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon parasitization, the macrophages become unable to deliver costimulatory signals to T helper cells, and that this effects is mediated by prostaglandins, as the inhibition of its synthesis by indomethacin recovered the defect. Upon infection with L. donovani, B7-1 expression was decreased, while ICAM-1 was marginally increased in BALB/c macrophages and there was no significant change in the expression of B7-1 and ICAM-1 in Leishmania-infected C57BL/6 macrophages. Expression of VCAM-1 did not change during infection. This selective alteration in the expression of costimulatory molecules on L. donovani-infected BALB/c macrophages was caused by the living parasite, as shown by the fact that killing of the parasites by stibogluconate led to no alteration in the levels of costimulatory molecules. We found that the change in B7-1 expression on the surface of infected macrophages resulted in the inhibition of delayed-type hypersensitivity-mediating functions of T helper cells from BALB/c mice. The results described in this study not only throw light on the possible mechanism of leishmanial pathogenesis, but also open up the possibility of immunotherapy of leishmaniasis by selective manipulation of costimulatory molecules.

Animals↗
PubMed1995

Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled study. Sotalol Multicenter Study Group.

Sotalol is an antiarrhythmic agent with combined beta-blocking and class III antiarrhythmic properties. This study was designed to assess the safety and efficacy of sotalol in terminating supraventricular tachycardia (SVT), atrial fibrillation (AFib), and atrial flutter (AFl). Ninety-three patients with spontaneous or induced SVT (n = 45) or AF (AFib or AFl; n = 48) with a ventricular rate of > or = 120 beats/min were studied. In the first phase, the double-blind phase, patients were randomly assigned to receive placebo or intravenous (i.v.) sotalol, 1.0 or 1.5 mg/kg. If SVT or AF did not convert to sinus rhythm or if the ventricular rate did not slow to < 100 beats/min within 30 minutes, patients then entered the second phase, the open-label phase, which also lasted 30 minutes, and were given 1.5 mg/kg iv sotalol. In the SVT group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 10 (67%) of 15 who received sotalol, 1.0 mg/kg (p < 0.05 vs placebo), and 10 (67%) of 15 who received 1.5 mg/kg sotalol (p < 0.05 vs placebo); during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (41%) of 17 of patients. In the AF group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 2 (11%) of 18 who received 1.0 mg/kg sotalol (p not significant [NS] vs placebo), and 2 (13%) of 16 who received 1.5 mg/kg sotalol (p = NS vs placebo); in these groups, a > 20% reduction of ventricular rate without conversion to sinus rhythm occurred in 0 (0%) of 14, 13 (72%) of 18 (p < 0.05 vs placebo), and 12 (75%) of 16 of patients (p < 0.05 vs placebo), respectively; during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (30%) of 23 of patients. The most common adverse events were hypotension and dyspnea. During the double-blind phase they occurred in 10% of patients who received placebo, 9% of those who received 1.0 mg/kg i.v. sotalol (p = NS vs placebo), and 10% of those who received 1.5 mg/kg i.v. sotalol (p = NS vs placebo). Most of these events were mild to moderate, but all were transient and clinically manageable.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Distribution of taste buds on the epiglottis of the rat and house shrew, with special reference to air and food pathways.

We investigated the positioning of the epiglottis in the pharyngo-laryngeal region and the distribution of taste buds on the epiglottis in the rat and house shrew, animals which have different feeding habits. In the fixed samples of both species, when the mouth was closed or slightly opened, the epiglottis was found to protrude into the nasopharyngeal hiatus above the soft palate. But it retracted from its position when the mouth was widely opened. In omnivorous rats (n = 6), the mean number (mean density +/- s.d.) of taste buds was 52 (12.6 +/- 2.2/mm2) on the laryngeal surface but only 4 (1.3 +/- 1.0/mm2) on the oral surface. The three-dimensional view was reconstructed from serial sections. The taste buds were distributed most densely close to the caudal base and became fewer toward the more rostral tip. In insectivorous house shrews (n = 2), 4 taste buds on average were found only on the laryngeal surface of the epiglottis. Epiglottal taste buds may work as chemosensory detectors to initiate the reflex reaction to protect the airway from oral substances during swallowing and drinking.

Animals↗
PubMed1994

Characterization and partial purification of the human receptor for the heat-stable enterotoxin.

The receptor for the Escherichia coli heat-stable enterotoxin has been characterized and partially purified from the T84 human colonic cell line. Using a novel mutant heat-stable enterotoxin peptide as a radioligand (the C-terminal tyrosine residue is replaced by phenylalanine in the mutant), a single class of high-affinity receptor sites was detected in T84 cells, with a Kd of 0.1 nM, similar in affinity to the receptor described in human intestinal tissue. The receptor was solubilised from T84 cell membranes and affinity cross-linking of the solubilised preparation indicated that a single species of M(r) 160,000 served as the receptor. Freshly solubilised preparations of the receptor retained heat-stable enterotoxin-activable guanylyl cyclase activity. Purification of the receptor was achieved through sequential affinity chromatography on GTP--epoxy-Sepharose and wheat-germ-agglutinin columns resulting in purification of the receptor by 3000 fold. The heat-stable enterotoxin-binding characteristics of the receptor were unchanged during the purification and silver staining of the purified receptor preparation indicated a band of M(r) 160,000, which was specifically cross-linked to the 125I-labeled mutant peptide. The purified receptor retained guanylyl cyclase activity, but the activity was not stimulated on addition of human heat-stable enterotoxin, suggesting that accessory structural factors may be involved in the activation of the guanylyl cyclase/receptor.

Bacterial Toxins↗
PubMed1994

Macrophage-T cell interaction in experimental mycobacterial infection. Selective regulation of co-stimulatory molecules on Mycobacterium-infected macrophages and its implication in the suppression of cell-mediated immune response.

The most important immunopathological consequence of experimental mycobacterial infection is the suppression of T cell-mediated immune response to both mitogens and mycobacterial antigens. We registered that there was decreased concanavalin A-induced spleen cell proliferation in infected susceptible BALB/c mice as compared to normal mice. In resistant (C3H/HeJ) mice, infection with the bacteria did not induce any suppression in the mitogen-induced lymphoproliferation. Likewise, delayed-type hypersensitivity (DTH) responses, to keyhole limpet hemocyanin and mycobacterial crude soluble antigen were suppressed in infected BALB/c mice but not in C3H/HeJ mice. This depressed T helper cell function may either be due to defective T cell-receptor occupancy by antigen-Ia complex or altered co-stimulatory signals provided by antigen-presenting cells. In the present study, we have investigated the status of certain co-stimulatory molecules on the infected macrophages from both susceptible and resistant mice. Our results demonstrate that upon mycobacterial infection, the macrophages are rendered incapable of delivering the co-stimulatory signals to T helper cells, possibly due to the involvement of prostaglandin, as inhibition of its biosynthesis by indomethacin reversed the defect. Furthermore, the selective regulation was bacteria-induced as killing of the bacteria by rifampicin abrogated the derangements in the expression of co-stimulatory molecules on the Mycobacterium-infected macrophages. Our observations revealed that upon infection with Mycobacterium tuberculosis, B7 was down-regulated while ICAM-1 was increased only in BALB/c but not in C3H/HeJ mice. Expression of VCAM-1 did not change during the infection in either strain of mice. We found that these changes in ICAM-1 and B7 expression on the surface of infected macrophages resulted in inhibition of DTH-mediating functions of T helper cells from BALB/c mice. The results obtained in this study describe not only a novel immune evasion strategy adopted by Mycobacterium, but also open up the possibility of immunotherapy of mycobacterial infection by selective manipulation of co-stimulatory molecules.

Animals↗
PubMed1994

Regeneration of pacemaker battery after explantation.

In an effort to evaluate changes in voltage output of a pulse generator after explantation, the output of 33 pulse generators was measured at the time of explant and following 3 days of rest (not pacing). Twenty generators were removed secondary to elective replacement indicators (ERI) and 13 for other causes. The output of ERI generators significantly increased, from 2.62 volts at explant, to 3.17 volts, 3 days later. The non-ERI generators on the other hand, showed no significant change in their output. These observations are important when dealing with battery depletion.

Electric Power Supplies↗
PubMed1994

Severe generalized hyperkinesia to nicardipine SR therapy.

A patient who was taking nicardipine SR for angina management suffered two episodes of severe involuntary tonic and clonic muscular contractions, involving both upper extremities and torso without loss of consciousness. This tardive dyskinesia occurred in the absence of hypotension and cardiac rhythm disorder. Intravenous diazepam promptly controlled these symptoms. The precise etiology of the dyskinesia is not clear and its relation to nicardipine remains speculative as the patient refused rechallenge with the drug. Possible hypothesis for tardive dyskinesia and nicardipine are presented.

Aged↗
PubMed1994

Total bladder replacement by detubularised sigmoid colon segment.

A preliminary report of 3 cases of carcinoma bladder is presented in whom, after radical cystoprostatectomy, a low pressure neobladder is created from detubularised pelvic colon, with subsequent colo-urethral anastomosis. In selected cases, this is a feasible procedure with good patient acceptance as the normal body image is maintained. Also the low pressure neobladder ensures protection to the upper urinary tract from backpressure damage.

Adult↗
PubMed1994

Cocaine abuse and reproduction.

Cocaine abuse today is widespread and is on the increase in North America. It is estimated that one in every four Americans has used cocaine for its euphorigenic properties. With increasing participation of younger age subjects in the cocaine abuse, the effects of cocaine on the reproductive system have attracted considerable attention. The impact of cocaine abuse on the health and society has been repeatedly documented in the past, but its effects on human reproduction have only recently been appreciated. The initial reports, on the harmful effects of cocaine on pregnancy and neonatal outcome, documented high incidence of abortions, placental abruption and neonatal neurobehavioral abnormalities. Subsequent studies have confirmed these findings and have documented a high incidence of congenital malformations, intrauterine growth retardation, sudden infant death syndrome and premature labor and delivery following cocaine use. Additionally, since cocaine is freely excreted in the milk, its effects on nursing have raised serious concerns. In this review, the effects of cocaine on various elements of reproduction, namely endocrines, fertility, libido, intercourse, pregnancy, fetal development, childbirth, neonates and infants have been analyzed systematically. It is believed that a clearer understanding of the cocaine's effects on various aspects of reproduction is essential to counsel and treat the pregnant women and to protect the newborn.

Abnormalities, Drug-Induced↗
PubMed1994

Gastrointestinal manifestations of cocaine addiction.

Cocaine is one of the illicit hallucinogenic drugs which can be conveniently taken without resorting to parenteral administration. Almost all organs systems in the body are affected by its abuse. Complications involving the nervous, cardiovascular and reproduction systems have recently been published. In this report, complications relating to gastrointestinal system are reviewed. Acute ischemic syndromes are the most prominent gastrointestinal complication of cocaine use. Severe ischemia results from intense activation of alpha-adrenergic receptors in the mesentery. This ischemia results in gastropyloric ulcerations, gangrene and perforation of small as well as large intestine and colitis. Sudden collapse and deaths have been reported in "body packers" who swallow cocaine filled condoms in an effort to smuggle the drug through the customs. Several cases of acute hepatotoxicity and hepatocellular necrosis from cocaine use have also been reported.

Cocaine↗
PubMed1993

Enhanced activation of the human histone H2B promoter by an Oct-1 variant generated by alternative splicing.

POU homeodomain proteins are important regulators of ubiquitous as well as tissue-specific transcription. These factors include the broadly expressed octamer motif-binding protein Oct-1 and the related cell-specifically expressed protein Oct-2. These two proteins differ in the types of octamer motif-containing promoters they preferentially activate; Oct-1 can activate RNA polymerase II transcription from a small nuclear RNA promoter better than Oct-2, which can better activate an mRNA-type promoter. We describe a variant Oct-1-encoding cDNA resulting from two separate alternate splices of the human oct-1 primary transcript; these alternate splices were present in all cell lines tested. This cDNA encodes an amino-terminally and carboxyl-terminally truncated form of Oct-1, called Oct-1B, which retains the DNA-binding POU domain and acquires a unique 12-amino acid carboxyl-terminal extension. In a transient expression assay, Oct-1B displayed an enhanced ability compared to the larger form of Oct-1 (called Oct-1A in this report) to activate the human histone H2B promoter, an mRNA-type promoter where a natural octamer motif is involved in cell cycle dependent transcription. Thus, the ability of Oct-1 related proteins to activate a natural regulatory target can be influenced by alternative splicing.

Alternative Splicing↗
PubMed1993

Determinants of immediate and follow-up results of pulmonary balloon valvuloplasty.

The data of 93 patients (age 11.4 +/- 9.4 years, range 8 months-56 years) who underwent pulmonary balloon valvuloplasty (PBV) for valvular pulmonic stenosis (PS) in our institution are reviewed. The patients were classified into three groups: Group I (34 patients) had a right ventricular (RV) to aortic systolic pressure ratio of < 1, Group II (39 patients) had suprasystemic RV systolic pressures, and Group III (20 patients) included patients with elevated mean right atrial (RA) pressures irrespective of the RV systolic pressures. The percentage drop in immediate postdilatation peak systolic gradients (PSG) and the follow-up PSG were similar in the three groups and were not influenced by any predilatation patient characteristics. A balloon-annulus ratio < 1 predicted a poorer follow-up outcome. Nine patients, eight of Group III and one of Group II, experienced difficult procedures requiring sequential use of progressively larger balloon catheters. Eleven patients, six of Group II and five of Group III, experienced procedure-related events (hypotension, bradycardia/asystole, hypoxia, apnea, tachyarrhythmias, and seizures) and one patient (Group II) died. Although changes in immediate and follow-up gradients after PBV are not influenced by the severity of PS, difficult procedures and procedure-related events are particularly common in patients with severe PS and elevated RA pressures. A cautious and planned approach is therefore indicated in these patients.

Adolescent↗
PubMed1993

Cocaine abuse in North America: a milestone in history.

The euphoric effects of coca leaves have been known to mankind for thousands of years. Yet the first epidemic of cocaine use in America occurred during the late 19th century. Initially, there were no laws restricting the consumption or sale of cocaine. In fact, cocaine was freely available in drug stores, saloons, from mail-order vendors, and even in grocery stores. It is reported that one drug manufacturer, in 1885, was selling cocaine in 15 different forms, including cigarettes, cheroots, inhalants, cordials, crystals, and solutions. Many famous imported wines, such as "Vin Mariani," contained a mixture of wine and coca. For consumers on budgets, the wonder drug was available as Coca-Cola and dozens of other soda pops and pick-me-up drinks. One of them even had a simple and direct name, Dope. Soon enough, the ill effects of cocaine became apparent, and by the 1920s cocaine was the most feared of all illicit drugs. Most states began enacting laws against cocaine use. President William Taft proclaimed cocaine as Public Enemy No. 1, and in 1914 the Congress passed the Harrison act, which tightly regulated the distribution and sale of cocaine. By the late 1950s, cocaine use in the United States was simply considered a problem in the past. Unfortunately, the people who were aware of the nation's first cocaine epidemic gradually passed away, and America once again was ready for its fling with cocaine in the 1960s. Today, it is estimated that upwards of 50 million Americans, that is one in four, have used cocaine. In addition, another fifty thousand people use this substance for the first time each day. More than 6 million Americans use cocaine on a regular basis. Little wonder, then, that America as well as the other countries have declared a "War on Drugs." In this review, pharmacology of cocaine, major complications arising from its use, and efforts to curb its abuse are discussed.

Cardiovascular System↗
PubMed1993

Chromosomal structure and expression of the human OTF1 locus encoding the Oct-1 protein.

The genomic structure of the POU domain containing oct-1 gene (OTF1 locus) coding region has been determined using human DNA recombinant bacteriophage and a yeast artificial chromosome clone. The gene is encoded by 16 exons spanning over 150 kb, and the Oct-1 protein reading frame has been extended to 766 amino acids. The exonic structure has been compared to the mouse Oct-2 protein and reveals a conservation of exon-intron boundaries as well as protein sequence similarity. To provide insight into Oct-1 control of transcriptional regulation during the cell-cycle the expression of the oct-1 gene was examined during cellular DNA replication and shows that the steady-state level of the oct-1 mRNA is not S-phase regulated.

Amino Acid Sequence↗
PubMed1993

Percutaneous balloon mitral valvuloplasty: analysis of echocardiographic and other variables related to outcome.

To determine whether mitral valve (MV) morphology influences the result of balloon mitral valvuloplasty (BMV) for mitral stenosis, two-dimensional echocardiography was performed before BMV in 53 patients and in 25 normal controls. The two-dimensional echocardiographic features of MV leaflets: thickness, length and motion, diastolic MV excursion, chordal length, MV annular diameter (MVAnD), subvalvular distance ratio (SDR), and effective balloon dilating area (EBDA) and diameter (EBDD) were then correlated to the immediate post-BMV mitral valve area (MVA). For the total patient population, post-BMV MVA increased from 0.76 +/- 0.24 to 1.91 +/- 0.59 cm2 (p < 0.0001) and mean diastolic transmitral gradient decreased from 20.1 +/- 6.15 to 5.8 +/- 3.29 mm (p < 0.0001). The patients were divided into two groups on the basis of post-BMV MVA. Group I had post-BMV MVA < 2.0 cm2 and group II had post-BMV MVA > or = 2.0 cm2. A statistically significant difference was noted in SDR (0.33 +/- 0.057 vs 0.45 +/- 0.042, p < 0.0001); mid-MV anulus to tip of papillary muscle (PM) distance (20.0 +/- 3.8 vs 27.9 +/- 4.54 mm, p < 0.0001); chordal length (4.3 +/- 3.6 vs 9.8 +/- 3.9 mm, p < 0.0001); diastolic MV excursion (15.5 +/- 2.6 vs 18.2 +/- 4.2 mm, p < 0.01); leaflet mobility (p < 0.05); and EBDA (4.4 +/- 0.6 vs 4.9 +/- 0.5 cm2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗