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Biomedical subjects

A Chakraborty

Publications and source records attributed to A Chakraborty.

At least 37 records · Page 2Linked to original sources

Variation of CAG repeats and two intragenic polymorphisms at SCA3 locus among Machado-Joseph disease/SCA3 patients and diverse normal populations from eastern India.

OBJECTIVES: MJD1/SCA3 is the most common type of spinocerebellar ataxia (SCA) worldwide. To explain the low prevalence of the disease among SCA patients from eastern India, we analysed CAG repeats and two bi-allelic intragenic markers at SCA3 locus among 412 normal individuals and 10 patients. MATERIALS AND METHODS: For CAG repeat analysis, PCR amplified fragments were run on polyacrylamide gel, transferred to a membrane, probed with (CAG)10 and detected on an autoradiograph. Bi-allelic markers were analysed using allele specific PCR amplification. RESULTS: Large normal alleles (>33 CAG repeats) were 0.015 in pooled populations. All the patients had the common haplotype C-A as observed worldwide. Frequency of C-A haplotype among large normal alleles was 0.75. CONCLUSIONS: Observed low prevalence of SCA3 could be because of the low prevalence of large normal alleles that might act as the reservoir for the expanded alleles. SCA3 mutation in Indian populations had the same origin as found worldwide.

Ataxin-3↗

Trigeminal neuralgia presenting as Chiari I malformation.

Chiari I malformation usually presents with headache, numbness, weakness and gait abnormalities. We present a 38-year-old female with trigeminal neuralgia who was found to have a Chiari I malformation. She had a foramen magnum decompression with complete resolution of her symptoms.

Adult↗

Noonan syndrome: a brief overview.

Noonan syndrome is a relatively common dysmorphic syndrome. The typical features include short stature, cardiovascular abnormalities and a characteristic facies. Children with Noonan syndrome have a considerable number of potential health problems, which are highlighted in this article. However, most individuals with this condition live a normal life.

Age Factors↗

Study of alkaloids from Adhatoda vasica Nees on their antiinflammatory activity.

Adhatoda vasica Nees is a shrub widespread throughout the tropical regions of southeast Asia. It possesses a wide spectrum of medicinal properties including positive effects on inflammatory diseases. The antiinflammatory activity of the methanol extract, the non-alkaloid fraction, the saponins and the alkaloids was evaluated by the modified hen's egg chorioallantoic membrane test. The alkaloid fraction showed potent activity at a dose of 50 microg/pellet equivalent to that of hydrocortisone while the MeOH extract and the other fractions showed less activity.

Alkaloids↗

An outbreak of Salmonella enteritidis infection in pygmy hogs (Sus salvanius).

An outbreak of salmonellosis was recorded in captive pygmy hogs (Sus salvanius), a critically endangered species of mammal. Of 42 captive animals maintained for conservation breeding by the Pygmy Hog Conservation Programme, Guwahati, Assam, India, 7 (16.67%) died within 3 days. The organism associated with this outbreak was identified as Salmonella enteritidis. The organisms were highly susceptible to chloramphenicol, gentamicin, norfloxacin and cefotaxim but were resistant to ampicillin, oxytetracycline, mezlocillin and sulfamerazin. The strain belonged to phage type 13a/7 and harboured two plasmids (38 and 44 megadaltons). The organisms were enterotoxigenic in CHO cell assay and were found to carry stn, sef and pef genes.

Animals↗

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Animals↗

Intraocular pressure changes and mountaineering--preliminary observations and possible application.

Measurement of intraocular pressure (IOP) has been suggested as an indirect way of assessing the intra cranial pressure (ICP) because of the anatomical relationship between the brain and the eyeball. Mountain-sickness during high altitude climbing results from acute rise in ICP. In this preliminary study, we have observed gradual increase in IOP with gain in altitude in a group of healthy mountain trekkers. Although the rise in IOP had not been steep in most climbers who did not experience any significant symptoms, the rise had been steep into two subjects who experienced symptoms of acute mountain sickness with raised IOP. While clearly further work is needed in this field with larger number of subjects, measurement of IOP appears to be a useful non-invasive screening test in high altitude climbers to avert the risk of acute mountain sickness.

Adult↗

Improved pharmacokinetic properties of a polyethylene glycol-modified form of interferon-beta-1a with preserved in vitro bioactivity.

Interferon therapies suffer from a relatively short half-life of the products in circulation. To address this issue we investigated the effects of polyethylene glycol modification (PEGylation) on the pharmacokinetic properties of human interferon (IFN)-beta-1a. PEGylation with a linear 20-kDa PEG targeted at a single site on the N-terminal amine had no deleterious effect on its specific activity in an in vitro antiviral assay. In monkeys, PEG IFN-beta-1a treatment induced neopterin and beta2-microglobulin expression (pharmacodynamic markers of activity). Systemic clearance values in monkeys, rats, and mice decreased, respectively, from 232, 261, and 247 ml/h/kg for the unmodified IFN-beta-1a to 30.5, 19.2, and 18.7 ml/h/kg for the PEGylated form, while volume of distribution values decreased from 427, 280, and 328 ml/kg to 284, 173, and 150 ml/kg. The decreased clearance and volume of distribution resulted in higher serum antiviral activity in the PEG IFN-beta-1a-treated animals. In the rat, a more extensive set of dosing routes was investigated, including intraperitoneal, intratracheal, and oral administration. Bioavailability for the PEG IFN-beta-1a was similar to the unmodified protein for each of the extravascular routes examined. For the intraperitoneal route, bioavailability was almost 100%, whereas for the oral and intratracheal routes absorption was low (<5%). In rats, subcutaneous bioavailability was moderate (28%), whereas in monkeys it was approximately 100%. In all instances an improved pharmacokinetic profile for the PEGylated IFN-beta-1a was observed. These findings demonstrate that PEGylation greatly alters the pharmacokinetic properties of IFN-beta-1a, resulting in an increase in systemic exposure following diverse routes of administration.

Animals↗

Strategy for qualitative and quantitative analysis in proteomics based on signature peptides.

This paper describes a new analytical strategy for identifying proteins in concentration flux based on isotopic labeling peptides in tryptic digests. Primary amino groups in peptides from control and experimental samples were derivatized with acetate and trideuteroacetate, respectively. After mixing samples thus labeled from these two sources, the relative concentration of peptides was determined by isotope ratio analysis with MALDI and ESI mass spectrometry. More than a 100-fold difference in relative concentration could be detected. Simplification of complex tryptic digests prior to mass spectral analysis was achieved by selection of histidine-containing peptides with immobilized metal affinity sorbents or of glycopeptides by lectin columns. Because most of these peptides have sequences that are unique to a single protein, they are a signature of the protein from which they were derived; providing a facile route to protein analysis.

Chromatography, Affinity↗

Delineation and mapping of Stat5 isoforms activated by granulocyte colony-stimulating factor in myeloid cells.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine critical for proliferation and differentiation of granulocytic precursors and neutrophil functions that has previously been demonstrated to activate Stat3 and Stat5, two members of the signal transducer and activator of transcription (STAT) protein family. Stat3 has been identified to be critical for G-CSF receptor (G-CSFR)-mediated signaling for granulocyte differentiation. Stat5 activation has been mapped to the proximal portion of the cytosolic region of the G-CSFR. However, delineation and mapping of the specific Stat5 isoforms activated by G-CSF in myeloid cells have not been reported. In this study, we demonstrated that G-CSF activated a Stat5 complex in human myeloid cells containing three isoforms of Stat5: Stat5A, Stat5B, and Stat5 p80. Activation of Stat5A and Stat5B maps to the proliferation-specific domain of the G-CSFR, whereas Stat5 p80 is recruited by phosphotyrosine-704 within the region of G-CSFR required for differentiation. G-CSF-activated Stat5A/B, but not Stat5 p80, formed a heterodimer with Stat3. The Stat5A/B-Stat3 heterodimer can bind to specific DNA sequences preferred by both Stat3 and Stat5. These findings are consistent with the possibility that Stat5 p80 contributes to G-CSF-induced myeloid differentiation.

Amino Acid Sequence↗

Stimulatory and inhibitory differentiation of human myeloid dendritic cells.

Dendritic cells (DCs) play a critical obligate role in presenting antigens to T cells for activation. In the process, upon antigen capture, DCs undergo maturation and become more stimulatory. Human myeloid DCs can be generated from various sources, including blood, bone marrow, and CD34(+) stem cells. As such, plastic-adherent monocytes from circulation have served as a ready source for generating myeloid DCs in culture in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for translational research in active specific immunotherapy, especially in cancer, with the belief that they are essentially stimulatory or "immunogenic." Here we show that in vitro cultures of plastic-adherent circulating monocytes in GM-CSF and IL-4 followed by further maturation in interferon-gamma plus bacterial superantigens (DC maturing agents) can give rise to two diametrically opposite types of DCs-one stimulatory and another inhibitory. The stimulatory DCs express higher amounts of costimulatory molecules, synthesize IL-12, and efficiently stimulate naive allogeneic T cells in mixed lymphocyte reaction (MLR). The inhibitory DCs, in contrast, express lower concentrations of the critical costimulatory molecules, synthesize large amounts of IL-10, and are nonstimulatory in allogeneic primary MLR. Moreover, while the stimulatory DCs further amplify proliferation of T cells in lectin-driven proliferation assays, the inhibitory DCs totally block T cell proliferation in similar assays, in vitro. Most interestingly, neutralization of the endogenously derived IL-10 with anti-IL-10 antibody in DC cultures repolarizes the inhibitory DCs toward stimulatory phenotype. Accordingly, these observations have important implications in translational research involving myeloid DCs.

Cell Differentiation↗

Dynamic balancing in NMR double rotor system.

An exact solution to the problem of dynamic balancing in a NMR double rotor system is presented. This will enable one to perform high speed spinning about two intersecting axes. Double rotation is used in solid state NMR to average away second-order broadening, thus enhancing the resolution of spectra from quadrupolar nuclei in solid state NMR. An exact expression for imbalance due to asymmetric distribution of weights about the rotation axes is provided.

Magnetic Resonance Spectroscopy↗

Enterogenous cyst of the posterior fossa.

We report the case of a 13-year-old boy who presented with deafness due to a posterior fossa cystic lesion which was surgically excised. Histological examination showed it to be an enterogenous cyst. These extremely rare lesions seldom occur within the neural axis.

Adolescent↗

Algorithm for application of Fourier analysis for biorhythmic baselines of pharmacodynamic indirect response models.

The change of an indirect pharmacological response R(t) can be described by a periodic time-dependent production rate kin(t) and a first-order loss constant kout. If kin(t) follows some biological rhythm (e.g., circadian), then the response R(t) also displays a periodic behavior. A new approach for describing the input function in indirect response models with biorhythmic baselines of physiologic substances is introduced. The present approach uses the baseline (placebo) response Rb(t) to recover the equation for kin(t). Fourier analysis provides an approximate equation for Rb(t) that consists of terms (usually two or three) of the Fourier series (harmonics) that contribute most to the overall sum. The model differential equation is solved backward for kin(t), yielding the equation involving Rb(t). A computer program was developed to perform the square L2-norm approximation technique. Fourier analysis was also performed based on nonlinear regression. Cortisol suppression after inhalation of fluticasone propionate (FP) was modeled based on the inhibition of the secretion rate kin(t) using ADAPT II. The pharmacodynamic parameters kout and IC50 were estimated from the model equation with kin(t) derived by the new approach. The proposed method of describing the input function needs no assumption about the behavior of kin(t), is as efficient as methods used previously, and is more flexible in describing the baseline data than the nonlinear regression method.

Administration, Inhalation↗

Differentiation of typhoid fever from fulminant hepatic failure in patients presenting with jaundice and encephalopathy.

OBJECTIVE: To determine the clinical and laboratory features that allow the early diagnosis of typhoid fever in patients who present with jaundice and encephalopathy. PATIENTS AND METHODS: This 12-month prospective study, conducted in Bangalore, India, between 1990 and 1991, evaluated the clinical and laboratory features of all patients (N=47) who presented with encephalopathy within 8 weeks of onset of jaundice. Ciprofloxacin and dexamethasone were used to treat 11 patients diagnosed on blood culture as having typhoid fever. The other 36 patients were presumed to have fulminant hepatic failure with a viral cause and were treated with supportive measures (bioartificial liver support and transplantation were not available). RESULTS: In patients with jaundice and encephalopathy, a liver span of greater than 9 cm on physical examination, thrombocytopenia, elevated alkaline phosphatase level, aspartate aminotransferase level greater than alanine aminotransferase level, and only mild prolongation of the prothrombin time suggested a diagnosis of typhoid fever. All 11 patients diagnosed as having typhoid fever had an excellent response to treatment with ciprofloxacin and dexamethasone with no mortality and with normalization of the liver test results in 2 weeks. On the other hand, 30 of the 36 patients with nontyphoid fulminant hepatic failure died. CONCLUSIONS: In patients presenting with jaundice and encephalopathy, physical examination and simple laboratory tests can help make an early diagnosis of typhoid fever. We believe that patients with a presumptive diagnosis of typhoid fever should be treated with ciprofloxacin and dexamethasone, even before the results of blood cultures are available.

Adult↗

Differential modulation of xenobiotic metabolizing enzymes by vanadium during diethylnitrosamine-induced hepatocarcinogenesis in Sprague-Dawley rats.

Effect of vanadium on hepatic xenobiotic biotransformation in rats exposed to diethylnitrosamine (DENA, 200 mg/kg body weight, intraperitoneally) was investigated to elucidate a possible mechanism of vanadium mediated prevention of chemical carcinogenesis. Vanadium supplementation (0.5 ppm ad libitum with drinking water), at different phases before and after DENA treatment, significantly modulated the decrease in contents of total cytochrome P-450, cytochrome b5, activity of nicotinamide adenine dinucleotide phosphate (NADPH), (reduced form) cytochrome reductase, and uridine diphospho-glucuronyl transferase (UDPGT) in microsomal fractions of whole liver, hyperplastic nodules (HNs) and non nodular surrounding parenchyma (NNSP) as induced by DENA, 20 weeks following its administration. Supplementary vanadium had also substantial influence on the activities of cytosolic enzymes, like, uridine diphospho (UDP)-glucose dehydrogenase and NAD(P)H: quinone oxidoreductase (DT-diaphorase) in the concerned tissue which were observed to be remarkably decreased as a result of DENA treatment in comparison to that of the control counterparts. However, vanadium was found to have little or no effect on the lowering ofaryl hydrocarbon hydroxylase (AHH) activity by DENA administration. On the basis of significant modulation of DENA induced alterations in cytosolic and microsomal enzyme activity it can be presumed that the chemoprotective effect of vanadium might be mediated through elevation of phase II conjugating enzymes which in turn, lead to a move and shift of metabolic profile that reduces the intracellular concentration of carcinogen derived reactive intermediates.

Animals↗

Tuberculosis and HIV illness.

The HIV infection leading to AIDS is considered to be one of the greatest biomedical challenges in the present century. Like all other communicable diseases AIDS is gradually penetrating the underprivileged sections of society in all countries. Nearly 5 million people in India are living with AIDS at present that makes India a single country with highest number of HIV infected people in the world. The hallmark of HIV disease is the reduction of CD4+ T-lymphocytes, the key cells of immunity. The initial phase of the disease may be termed as HIV seroconversion illness. The next phase is termed asymptomatic HIV infection. When the CD4 count falls below 400/microliter, the patient develops early opportunistic infections which may be termed as early symptomatic HIV infection or AIDS related complex (ARC). Mycobacterial infections are also common in these patients and have led to an alarming resurgence of tuberculosis (TB) in many countries. The available information suggests that TB may be the commonest HIV related disease in the world. The clinical presentation of TB in HIV infected individual is influenced by the degree of HIV related immunosuppression. The atypical features like extrapulmonary TB and absence of positive Mantoux test are generally noticed at a fairly advanced stage. The x-ray chest is also an important adjunct to diagnosis of TB in HIV infected individual. The studies on TB and AIDS in the early part of HIV epidemic in developed countries suggest that extrapulmonary TB is more common in co-infected people but when TB infection is considered in all HIV infected persons, extrapulmonary TB is less common than pulmonary TB. The result of treatment in co-infected pulmonary TB cases is almost similar with the cases suffering from TB alone. Treatment failure, however, has been noticed rarely at extrapulmonary sites.

AIDS-Related Opportunistic Infections↗