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Biomedical subjects

S Das

Publications and source records attributed to S Das.

At least 325 records · Page 18Linked to original sources

Acute myelofibrosis.

Acute myelofibrosis is a rare disorder. Five such cases have been diagnosed out of 3,149 Bone Marrow (B.M) Aspirations and Trephine Biopsies studied over a period of eight and a half years. Four out of five patients were males and the other female. Their age ranged from 14-71 years. Neither splenomegaly not red cell poikilocytosis (tear drop cells) were prominant features. B.M. trephine biopsy showed increase of atypical megakaryocytes/megakaryoblasts and marked fibrosis. There was rapid downhill clinical course of the disease in all cases.

Acute Disease↗

Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition. Indian Consensus Group for the Prevention of Diabetes.

BACKGROUND: There has been a rapid increase in the prevalence of diabetes and cardiovascular disease in India, in association with rapid changes in diet and lifestyle. In adults, the prevalence of diabetes, hypertension and coronary artery disease is two- to threefold greater in the urban population than in rural populations; it is associated with modest insulin resistance in urban groups. METHODS: In response to a proposal by the International College of Nutrition that specialist experts should develop consensus recommendations for the prevention of chronic diseases, Indian specialists in diabetes and vascular disease have collaborated to produce guidelines relevant to the population of India. RECOMMENDATIONS: Because Indian urban populations have a modest increase in overweight and low rates of obesity in association with the rapid emergence of diabetes and cardiovascular risk, a body mass index of 21 kg/m2 should be considered safe, with a range of 19-23 kg/m2 acceptable; > 23 kg/m2 should be considered overweight, and > 25 kg/m2 should be taken to indicate obesity. A waist:hip ratio > 0.88 in males and > 0.85 in females should be considered to indicate central obesity, because the prevalence of coronary disease, hypertension and associated disturbances of insulin resistance are more common above these limits. For the prevention of vascular disease, there is general international consensus that the desirable serum concentration of cholesterol should be < 170 mg/dl (> 4.42 mmol/l), which may also be optimal for Indians; values between 170 and 200 mg/dl (4.42-5.2 mmol/l) should be considered borderline. The critical values for low density lipoprotein cholesterol may be < 90 mg/dl (ideal), 90-110 mg/dl (borderline high) and > 110 mg/dl (high) (< 2.32, 2.32-2.84 and > 2.84 mmol/l, respectively). Fasting triglycerides should be < 150 mg/dl (< 1.69 mmol/l) and high-density lipoprotein cholesterol > 35 mg/dl (> 0.9 mmol/l). The limit for the total energy derived from fat intake should be < 21%/day (7% each for saturated, polyunsaturated and mono-unsaturated fatty acids). The carbohydrate intake should provide more than 65% of daily energy, mainly from complex carbohydrates. A daily dietary intake of 400 g fruits, vegetables and legumes, 400 g cereals, in conjunction with 25 g soya bean or mustard or canola oils (rich in n-3 fatty acids) in place of fats rich in saturated fat, may be protective against diabetes and vascular disease. Moderate physical activity with the aim of burning 300 Kcal/day (> 1255 KJ/day), and cessation of tobacco and alcohol consumption, may provide an effective programme for prevention of diabetes and its vascular complications in Indians.

Adult↗

Simple renal cyst: an observation.

In the present study 1500 patients having abdominal ultrasonography were included. Unsuspected renal cysts were detected in 76 patients (5.06%). The age range was between 8 and 86 years with a maximum incidence being at 41-60 years age group. These asymptomatic cysts were observed commonly in the upper pole of right kidney. Incidence as well as size increased with age. Usually these cysts do not require any surgical intervention unless complicated.

Adolescent↗

Characterization of two genes, p11 and p5, on the Borrelia burgdorferi 49-kilo base linear plasmid.

A putative operon encoding two Borrelia burgdorferi N40 genes, p11 and p5 was cloned and localized to the 49 kilobase linear plasmid. p11 encodes an 11 kDa protein and p5 encodes a 5 kDa protein. The first 88 nucleotides of p11 have 81% identity with orf5 on a circular plasmid from Borrelia afzelii strain Ip21, suggesting that homologues of these genes may be present in different regions of the B. burgdorferi genome.

Animals↗

Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas.

PURPOSE: Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells. METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage.

Adult↗

A randomised controlled trial comparing two schedules of antenatal visits: the antenatal care project.

OBJECTIVE: To compare the clinical and psychological effectiveness of the traditional British antenatal visit schedule (traditional care) with a reduced schedule of visits (new style care) for low risk women, together with maternal and professional satisfaction with care. DESIGN: Randomised controlled trial. SETTING: Places in south east London providing antenatal care for women receiving shared care and planning to deliver in one of three hospitals or at home. SUBJECT: 2794 women at low risk fulfilling the trial's inclusion criteria between June 1993 and July 1994. MAIN OUTCOME MEASURES: Measures of fetal and maternal morbidity, health service use, psychosocial outcomes, and maternal and professional satisfaction. RESULTS: Pregnant women allocated to new style care had fewer day admissions (0.8 v 1.0; P=0.002) and ultrasound scans (1.6 v 1.7; P=0.003) and were less often suspected of carrying fetuses that were small for gestational age (odds ratio 0.73; 95% confidence interval 0.54 to 0.99). They also had some poorer psychosocial outcomes; for example, they were more worried about fetal wellbeing antenatally and coping with the baby postnatally, and they had more negative attitudes to their babies, both in pregnancy and postnatally. These women were also more dissatisfied with the number of visits they received (odds ratio 2.50; 2.00 to 3.11). CONCLUSIONS: Patterns of antenatal care involving fewer routine visits for women at low risk may lead to reduced psychosocial effectiveness and dissatisfaction with frequency of visits. The number of antenatal day admissions and ultrasound scans performed may also be reduced. For the variables reported, the visit schedules studied are similar in their clinical effectiveness. Uncertainty remains as to the clinical effectiveness of reduced visit schedules for rare pregnancy problems.

Anxiety↗

IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination.

Studies have implicated defective Ig class switch in the pathogenesis of IgA deficiency. To understand better the molecular events that regulate IgA class switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in murine embryonic stem cells. The I alpha exon-deficient mice derived from these embryonic stem cells had normal IgA levels in serum and secretions and normal numbers of IgA B cells in Peyer's patches and spleen. Further, I alpha exon-deficient B cells efficiently underwent IgA class switch in vitro, despite the absence of I alpha exon-containing germline transcripts. Notably, I alpha exon-deficient B cells did not require TGF-beta for IgA class switch since stimulation with LPS alone led to IgA expression. Nonetheless, whereas I alpha exon-deficient B cells constitutively expressed human hypoxanthine phosphoribosyltransferase transcripts, they did not produce IgA in the absence of LPS stimulation. These results demonstrate that the I alpha exon or transcripts containing the I alpha exon are not required for IgA class switch. Further, the effects of TGF-beta on I alpha locus transcription can be supplanted by expression of a heterologous minigene at that locus, but a second signal is required for the induction of IgA class switch.

Animals↗

Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats.

Microinjections of the cholinergic receptor agonist nicotine and the cholinesterase inhibitor neostigmine were made into the ventral tegmental area (VTA) of urethane-anesthetized rats, and dopamine (DA) efflux in the nucleus accumbens was measured using in vivo chronoamperometry. Dose-dependent increases in the chronoamperometric signals corresponding to increased DA efflux were observed in the nucleus accumbens of normal intact rats after cholinergic stimulation of the VTA. The source of the cholinergic input to the VTA was investigated by making excitotoxic lesions in either the laterodorsal tegmental nucleus (LDTg) or the pedunculopontine tegmental nucleus (PPTg). Compared with sham-operated control animals, which showed the same response as intact, nonlesioned rats, ibotenate lesions of the LDTg attenuated the stimulatory effects of intra-VTA neostigmine on DA efflux in the nucleus accumbens. In contrast, rats with ibotenate lesions of the PPTg showed normal nucleus accumbens DA eflux after intra-VTA injections of neostigmine. Such lesions in the PPTg attenuate DA efflux in the caudate-putamen stimulated by injections of neostigmine into the substantia nigra pars compacta (SNc). The present data show that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of DA-containing neurons in the VTA, which complements previous data showing that cholinergic neurons in the PPTg regulate DA-containing neurons in the SNc.

Animals↗

Multiple domain protein diagnostic patterns.

We have implemented an iterative algorithm for the identification of diagnostic patterns from sets of multiple-domain proteins, where domains need not be common to all the proteins in the defining set. Our algorithm was applied to sequences gathered using a variety of methods, including BLAST, common keywords, and common E.C. numbers. In all cases, useful diagnostic patterns were obtained, possessing both high sensitivity and specificity. The patterns were found to correlate in several cases with both functional and structural domains. Patterns generated from a large number of sequence families were analyzed for probable multiple-domain structure.

Algorithms↗

Successful early copper therapy in Menkes disease associated with a mutant transcript containing a small In-frame deletion.

Classical Menkes disease is a fatal X-linked neurodegenerative disorder caused by defects in a gene (MNK) that encodes a copper-transporting ATPase. Treatment with parenteral copper has been proposed for patients identified before symptoms develop. We recently described suboptimal outcomes despite early copper replacement in two classical Menkes patients whose mutation predicts little if any functional copper transporter. Here, we describe successful copper replacement therapy in a patient with Menkes disease with a splice acceptor site mutation (IVS8,AS,dup5) that causes exon-skipping and generates a mutant transcript with a small in-frame deletion in a noncritical region. The patient was diagnosed by analysis of neurochemical levels in cord blood, and parenteral copper replacement was begun at 8 days of life. Throughout infancy, he showed normal head growth, brain myelination, and age-appropriate neurodevelopment, including independent walking at 14 months of age. In contrast, his affected half-brother and first cousin with the same mutation, but who were not diagnosed and treated from an early age, showed arrested head growth, cerebral atrophy, delayed myelination, and abnormal neurodevelopment. We propose that the successful neurological outcome in this patient was related to early repletion of circulating copper levels, in combination with residual copper transport by a partially functional MNK ATPase containing the small deletion. We hypothesize that raising plasma copper concentrations in patients with Menkes disease with some residual functional gene product can increase the ligand: transporter ratio and thus alter favorably the kinetics of copper transport into and within the brain.

Adenosine Triphosphatases↗

Giardia lamblia: increased UDP-N-acetyl-D-glucosamine and N-acetyl-D-galactosamine transferase activities during encystation.

The cyst wall of Giardia lamblia is essential for survival of the parasite outside the host. N-acetyl-D-glucosamine (GalNAc) has been reported as a major terminal sugar of cyst wall glycoproteins and N-acetyl-D-galactosamine (GalNAc) as the major sugar of the fibrous insoluble cyst wall fraction. Therefore, we measured UDP-glycosyltransferase activities as the incorporation of [3H]UDP-sugar into an alcohol-insoluble product. We found that during encystation only UDP-GlcNAc and UDP-GalNAc transferase (UDP-GT) activities increased approximately three- to five-fold compared to nonencysting trophozoites. These activities were distributed approximately equally in the pellet and soluble fractions. The apparent K(m) and V(max) of UDP-GT in these fractions were similar. The activities from both fractions were dependent on Mn2+; however, the pellet enzymes were also partially activated by other metal ions. Both pUDP-GT and sUDP-GT were inhibited by uridine, UDP, and UDP sugars, but not by GlcNAc or GalNAc. Isolation and analysis of the reaction products suggest that pUDP-GT incorporate GlcNAc and GalNAc into glycoproteins, since the products were proteinase sensitive. In contrast, sUDP-GT products were resistant to proteinase treatment. Hydrolysis of the product of UDP-GlcNAc-T incorporation by trifluoroacetic acid released only glucosamine, while both glucosamine and galactosamine were released from UDP-GalNAc-T products, supporting the presence of an epimerase in Giardia which can convert GalNAc to GlcNAc during incorporation. This study suggests that at least two UDP-GT activities are induced during encystation, which are responsible for the transfer of GlcNAc and GalNAc from UDP-GlcNAc or UDP-GalNAc into both proteinase-sensitive and proteinase-resistant components of the Giardia cyst wall.

Animals↗

Alternatives for a risk assessment on chronic noncancer effects from oral exposure to trichloroethylene.

Changes in methodologies are presently occurring for dose-response assessment in noncancer and cancer risk assessments. The benchmark dose (BMD) method is an alternative to the no-observed-adverse-effect level (NOAEL)/uncertainty factor (UF) approach for development of toxicity values. A comparison of these two methods was undertaken using trichloroethylene, an important industrial chemical and environmental contaminant. This analysis considered liver effects, kidney toxicity, and developmental defects. A range of toxicity values was obtained using the two methods from which acceptable drinking water concentrations were estimated: 1000-10,000 ppb for liver effects, 1750 ppb from kidney toxicity, and 1000-10,000 ppb from developmental defects of the eye. These values are all higher than those based upon cancer as the critical endpoint. This analysis highlighted the strengths of the BMD approach in the presence of adequate dose-response data, but it also suggested that guidance is required for addressing inadequate dose-response data. The selection of UF and critical studies were identified as areas that have a large impact upon the final dose-response values, sometimes greater than the variations arising from using the BMD rather than the NOAEL.

Administration, Oral↗

Similarity of clozapine's and olanzapine's acute effects on rats' lapping behavior.

As a way of further comparing the behavioral effects of clozapine and olanzapine, dose ranges of these drugs were studied in a task emphasizing fine motor detail of rats' tongue movements during lapping behavior. Rats lapped drops of tap water from a force-sensing disk. From this behavior four variables were derived: peak-force of tongue strikes, duration of tongue contact, number of separate tongue contacts in 2 min, and the rhythm of the lapping behavior as quantified by Fourier analysis. Both clozapine (0.5-4.0 mg/kg, IP, 45 min) and olanzapine (0.25-2.0 mg/kg, IP, 45 min) dose dependently reduced all four measures of behavior. With respect to lick rhythm, a behavioral marker which clearly distinguishes haloperidol from clozapine in this behavioral paradigm, olanzapine was about twice as potent as clozapine, with the two drugs having parallel dose-effect functions. Within-session decrements in behavior previously reported for haloperidol in the lick task were not produced by clozapine nor by olanzapine. Taken together, these data strengthen the idea that the behavioral effects of clozapine and olanzapine are strikingly similar, and thereby emphasize the potential of olanzapine as an atypical anti-psychotic agent.

Animals↗

An update of Fowler and Das: anticholinergic reversal of haloperidol-induced, within-session decrements in rats' lapping behavior.

Dopamine receptor-blocking neuroleptics produce progressive decrements in response output during behavioral test sessions. If these response decrements reflect Parkinson-like motor effects of neuroleptic treatment, then within-session decrements should be ameliorated by concurrent anticholinergic treatment. To investigate this question, new within-session data analyses were performed on previously published data that addressed haloperidol-scopolamine influences across the entire session (Fowler and Das, 1994). The peak force and duration of individual licks were recorded for 36 rats along with the number of licks emitted in each daily 2-min session. The effects on this behavior of vehicle and three doses of haloperidol (0.06, 0.12, and 0.24 mg/kg, IP, 45 min before sessions) were evaluated alone and in combination with vehicle and two doses of scopolamine HCl (0.1 and 0.2 mg/kg, SC, 60 min before sessions). Despite the brief sessions, haloperidol produced pronounced within-session decrements, and pretreatment with scopolamine reversed the haloperidol-induced within-session decrements in lick emission. Scopolamine by itself produced within-session increments in all three measures of lapping behavior. The results support the idea that within-session decrements in licking behavior are Parkinson-like and diminish confidence in hedonic interpretations of neuroleptic-induced within-session decrements.

Animals↗