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Biomedical subjects

S Das

Publications and source records attributed to S Das.

At least 145 records · Page 8Linked to original sources

PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma.

Loss of heterozygosity and mutations in the PTEN (MMAC1) tumor suppressor gene are frequent in endometrial carcinoma. Promoter hypermethylation has recently been identified as an alternative mechanism of tumor suppressor gene inactivation in cancer, but its importance in the PTEN gene in endometrial carcinoma is unknown. The purpose of our study was to assess the frequency of promoter methylation of the PTEN gene and to determine its correlation with clinicopathologic variables in a prospective and population-based series of endometrial carcinomas with complete follow-up. Presence of PTEN promoter methylation was seen in 26 of 138 patients (19%). Methylation was significantly associated with metastatic disease (p = 0.01) and a microsatellite unstable phenotype (p = 0.006). In conclusion, we find that PTEN promoter methylation is relatively frequent in endometrial carcinoma. Its association with metastatic disease and microsatellite instability implicates its importance in the development of this tumor type.

Alleles↗

Target cell induced activation of NK cells in vitro: cytokine production and enhancement of cytotoxic function.

This study examines the effect of fixed AK-5 tumour cells on rat NK cells. Co-culture of NK cells with fixed tumour cells augmented the cytotoxicity of NK cells against NK-sensitive targets, YAC-1 and AK-5, and induced the secretion of IFN-gamma by NK cells. Antibody against IFN-gamma suppressed the anti-tumour activity of NK cells, whereas the addition of T cells during co-culture enhanced this activity. However, macrophages and B cells had no significant effect when present during co-culture with NK cells. All the inducible cytotoxicity was contained within the NK (CD161+) and NKT (CD3+, CD161+) subsets of lymphocytes. However, in the presence of T cells, the cytolytic potential of NKT cells was higher than that of NK cells alone. The augmentation of cytotoxic activity of NK cells by AK-5 cells in presence of T cells was dependent on IL-2 and IFN-gamma secretion. NK cell activation was blocked by specific antibodies to IL-2 and IFN-gamma in the presence of T cells. Interaction between fixed AK-5 cells with NK and T cell populations induced the expression of Fas-L and perforin in NK cells. These data demonstrate that fixed AK-5 cells initiated cytokine synthesis by NK cells, and the enhanced cytotoxic activity in the presence of T cells was induced as a consequence of the products secreted by activated T lymphocytes. The present observations reflect the possible interactions taking place in vivo after the transplantation of AK-5 tumour in animals. They also suggest direct activation of NK cells after their interaction with the tumour cells.

Animals↗

Clinical appraisal of Ascaris lumbricoides, with special reference to surgical complications.

Over a period of 4 years (January 1993-December 1997), 509 patients were treated for abdominal colic with or without intestinal obstruction and a history of passage of adult roundworms either in the stool or in vomitus. All patients were below the age of 10 years, the youngest 6 months old, and were treated successfully with antispasmodics and normal saline enemas. When the pain subsided, an anthelminthic drug was given. Of 209 patients admitted to the hospital, 105 responded to conservative management and 104 (50%) required surgical intervention. The procedures included squeezing out of worms, resection and anastomosis, and treatment of other pathologies like acute appendicitis, tubercular stricture of the small intenstine, etc. Five patients died in the postoperative period due to various complications. There were no deaths among those treated by conservative management. Early recognition of the condition can prevent serious surgical complications and morbidity.

Animals↗

Rectourinary fistula with a narrow urethra.

A rectourinary fistula is a common accompaniment of anorectal malformations (ARM) in boys. Most boys pass urine normally after reconstruction and closure of the fistula, but a few have serious problems because of a narrow urethra. In our series, a narrow urethra was encountered in three types of male ARM: 3 rectourethral fistulae, 4 rectovesical fistulae, and 6 H-fistulae. We have studied the diagnostic and therapeutic problems that a narrow urethra produces in patients afflicted with each of these malformations.

Abnormalities, Multiple↗

A role of the Drosophila homeless gene in repression of Stellate in male meiosis.

The homeless gene of Drosophila melanogaster encodes a member of the DE-H family of ATPase and RNA helicase proteins. Loss-of-function homeless mutations were previously found to cause female sterility with numerous defects in oogenesis, including improper formation of both the anterior-posterior and dorsal-ventral axes and failure to transport and localize key RNAs required for axis formation. One homeless mutation was also found to affect male meiosis, causing elevated X-Y nondisjunction. Here we further analyze the role of homeless in male meiosis. We show that homeless mutations cause a variety of defects in male meiosis including nondisjunction of the X-Y and 2-2 pair, Y chromosome marker loss, meiotic drive, chromosome fragmentation, chromatin bridges at anaphase, and tripolar meiosis. In addition, homeless mutations interact with an X chromosomal factor to cause complete male sterility. These phenotypes are similar to those caused by deletion of the Suppressor of Stellate [Su(Ste)] locus. Like Su(Ste) deficiencies, homeless mutants also exhibit crystals in primary spermatocytes and derepression of the X-linked Stellate locus. To determine whether the regulatory role of hls is specific for Stellate or includes other repeated sequences as well, we compared testis RNA levels for nine transposable elements and found that all but one, copia, were expressed at the same levels in hls mutants and wild type. Copia, however, was strongly derepressed in hls mutant males. We conclude that hls functions along with Su(Ste) and other recently described genes to repress the Stellate locus in spermatocytes, and that it may also play a role in repressing certain other repeated sequences.

Adenosine Triphosphatases↗

Functional significance and mechanism of eIF5-promoted GTP hydrolysis in eukaryotic translation initiation.

Eukaryotic translation initiation factor 5 (eIF5), a monomeric protein of about 49 kDa in mammals and 46 kDa in the yeast Saccharomyces cerevisiae, in conjunction with GTP and other initiation factors plays an essential role in initiation of protein synthesis in eukaryotic cells. Following formation of the 40S initiation complex (40S . eIF3 . mRNA . Met-tRNAf . eIF2 . GTP) at the AUG codon of an mRNA, eIF5 interacts with the 40S initiation complex to promote the hydrolysis of bound GTP. Hydrolysis of GTP causes the release of bound initiation factors from the 40S subunit, an event that is essential for the subsequent joining of the 60S ribosomal subunit to the 40S complex to form the functional 80S initiation complex. Detailed characterization of the eIF5-promoted GTP hydrolysis reaction shows that eIF5 functions as a GTPase-activating protein (GAP) in translation initiation. First, eIF5 promotes hydrolysis of GTP only when the nucleotide is bound to eIF2 in the 40S initiation complex. eIF5, by itself, does not hydrolyze either free GTP or GTP bound to the Met-tRNAf . eIF2 . GTP ternary complex in the absence of 40S ribosomal subunits. Second, as with typical GAPs, eIF5 forms a complex with eIF2, the GTP-binding protein. This interaction, which occurs between the lysine-rich N-terminal region of the beta subunit of eIF2 and the glutamic acid-rich C-terminal region of eIF5, is essential for eIF5 function both in vitro and in vivo in yeast cells. Finally, like typical GAPs, eIF5 also contains an arginine-finger motif consisting of an invariant arginine residue at its N-terminus that is also essential for its function. This invariant arginine residue is presumably involved in the stabilization of the transition state of the GTP hydrolysis reaction catalyzed by initiation factor eIF2.

Amino Acid Sequence↗

Urologic laparoscopy: the future is now.

Recent interest in urologic laparoscopy is a welcome renaissance of minimally invasive procedures that provide superior benefit to patients. It behooves the urologist to avoid complacency and embrace the resurgence of laparoscopy. Dedicated pursuit and perseverance will facilitate the evolution and future of urologic laparoscopy.

Forecasting↗

Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments.

The effects of hypothyroidism on parameters of oxidative stress and on intraneuronal distribution of neurofilaments have been investigated in the developing rat brain. Progressive hypothyroidism during the first 4 weeks of postnatal development led to an increase in superoxide dismutase and catalase activity, decline in the level of glutathione and mitochondrial cytochrome c oxidase activity and increase in the level of .OH radical along with enhanced protein carbonylation and lipid peroxidation. Immunocytochemical staining of cryostat sections of normal and hypothyroid cerebella from 25 day postnatal rats with anti neurofilament (NF) light chain (L) antibody showed aberrant accumulation of neurofilaments in the perikaryon of the hypothyroid Purkinje neurons in contrast to relatively uniform distribution in the controls. The morphological and biochemical alterations in the neurons of the developing hypothyroid brain are comparable to those seen in several neurodegenerative diseases.

Animals↗

Phospholipid remodeling/generation in Giardia: the role of the Lands cycle.

Recent results suggest that Giardia is able to carry out deacylation/reacylation reactions (the Lands cycle) to generate new phospholipids, effectively bypassing the de novo synthesis of the entire phospholipid molecule. The successful operation of this deacylation/reacylation cycle is important for Giardia because this protozoan parasite possesses limited lipid synthesis ability. This article discusses how Giardia might use the Lands cycle to alter phospholipids acquired from the host during its colonization in the human small intestine.

Acylation↗

Food shopping practices are associated with dietary quality in low-income households.

ABSTRACT Nutrition education for low-income audiences often focuses on building skills in food shopping and food resource management to help families receive the best nutrition from the resources they have available. However, empirical evidence for the effect of food shopping practice on dietary quality has been limited. This article presents new analyses from two studies that found an association between food shopping practices and diet quality. Logistic regression of data from 957 respondents from the 1996 National Food Stamp Program Survey found that food shopping practices were significantly (p </= .05) associated with the availability of nutrients in the food the households used during a week. Similarly, analysis of baseline data from 5159 women from selected counties of states who participated in the Expanded Food and Nutrition Education Program found that food shopping practices were significantly (p </= .05) associated with increased consumption of nutrients as measured through a single 24-hour recall. These findings suggest that food shopping practices are an important area for nutrition education with low-income audiences.

Diet↗

Generation of ceramide in murine macrophages infected with Leishmania donovani alters macrophage signaling events and aids intracellular parasitic survival.

In the present study, we examined the involvement of intracellular ceramide in host pathogen interaction of BALB/c mouse peritoneal macrophages infected with the obligate intracellular protozoan, Leishmania donovani. Our findings indicate that the level of intracellular ceramide was enhanced as a result of the in vitro infection. While the elevated ceramide was largely due to de novo synthesis, activation of the sphingomyelinases was also observed. The enhanced ceramide was responsible for the downregulation of classical PKC activity, upregulation of calcium independent atypical PKC-zeta expression and activity of calcium independent PKC. Ceramide also impaired the phosphorylation of MAPK. Evidently, ceramide suppressed the generation of nitric oxide during leishmanial infection and also facilitated the survival of leishmanial parasites in the intramacrophageal milieu. These data present newer insight to the signaling events in leishmania-infected murine macrophages, which might offer ceramide as a new therapeutic target in the future.

Animals↗

Eyeblink conditioning in the rabbit (Oryctolagus cuniculus) with stimulation of the mystacial vibrissae as a conditioned stimulus.

Eyeblink conditioning is a well-understood paradigm for the study of learning and memory and has been successfully employed with the use of auditory and visual conditioned stimuli (CSs). In this study, vibrotactile stimulation of the mystacial vibrissae was examined as an alternative CS in the rabbit (Oryctolagus cuniculus). The technique is described and acquisition of eyeblink conditioning (EBC) with stimulation of a single row of vibrissae in a delay paradigm is reported. Extinction of EBC with presentation of the CS alone is demonstrated, as well as reacquisition with stimulation of a single whisker. Finally, control experiments ensure that the CS has no auditory components. Ipsilateral presentation of the CS and airpuff is a more effective combination for training than contralateral presentations. Vibrotactile stimulation of the vibrissae as a CS will enable further examination of the neural correlates of learning in a well-characterized sensory system.

Animals↗

Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.

Subcortical band heterotopia (SBH) comprises part of a spectrum of phenotypes associated with classical lissencephaly (LIS). LIS and SBH are caused by alterations in at least two genes: LIS1 (PAFAH1B1) at 17p13.3 and DCX (doublecortin) at Xq22.3-q23. DCX mutations predominantly cause LIS in hemizygous males and SBH in heterozygous females, and we have evaluated several families with LIS male and SBH female siblings. In this study, we performed detailed DCX mutation analysis and genotype-phenotype correlation in a large cohort with typical SBH. We screened 26 sporadic SBH females and 11 LIS/SBH families for DCX mutations by direct sequencing. We found 29 mutations in 22 sporadic patients and 11 pedigrees, including five deletions, four nonsense mutations, 19 missense mutations and one splice donor site mutation. The DCX mutation prevalence was 84.6% (22 of 26) in sporadic SBH patients and 100% (11 of 11) in SBH pedigrees. Maternal germline mosaicism was found in one family. Significant differences in genotype were found in relation to band thickness and familial vs sporadic status.

Brain↗

Similar dose-response and persistence of erythema with broad-band and narrow-band ultraviolet B lamps.

Psoriasis may be treated with ultraviolet B from lamps that have a broad emission spectrum or, more effectively, with lamps that have a narrow emission spectrum at 311 +/- 2 nm. There are conflicting reports of either greater or lesser burning episodes with narrow-band compared to broad-band ultraviolet B, even when treatments are based on predetermined minimal erythema dose measurements. This suggests that either the characteristics of the dose-response curve for erythema or the time course for erythema may be different for the two lamps. We examined the erythemal response to narrow-band and broad-band ultraviolet B in 12 patients with psoriasis. A geometric series of 10 doses from each lamp type were used on nonlesional skin on the back. Dose-response curves were constructed from reflectance measurements of erythema at 24 h and 72 h after irradiation. No significant difference was found in steepness of the erythema dose-response curve for the two lamps at 24 or 72 h. Persistence of erythema was assessed as the percentage of erythema remaining at 72 h. The mean persistence was 63% for narrow-band and 64% for broad-band lamps (p = 0.94). Therefore, in terms of erythemal response, no evidence has been found for a difference in burning potential for the two lamps.

Adult↗

Ten years' experience in zygomycosis at a tertiary care centre in India.

OBJECTIVE: To define the spectrum of zygomycosis due to mucorales in an Indian scenario. METHODS: One-hundred and twenty-nine patients with zygomycosis due to mucorales diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, India during 1990-99, were retrospectively analysed regarding the sites of involvement, underlying disease, species of fungi isolated and outcome of therapy. RESULTS: Higher prevalence rate (19.4%) was observed in 1999. Rhino-orbito-cerebral type (44.2%) was the commonest presentation followed by cutaneous (15.5%) and renal (14.0%) involvement. Disseminated zygomycosis was seen in 11.6% patients. Pulmonary and gastrointestinal zygomycosis were diagnosed in 10.1% and 4.7% patients, respectively. Uncontrolled diabetes mellitus (in 50% of cases) was the significant risk factor in rhino-orbito-cerebral type [odds ratio (OR), 9.3; P<or=0.001) and breach of skin (in 40% cases) in cutaneous zygomycosis (OR, 6.9; P<or=0.01). However, a considerable number of 22 (22.9%) patients were apparently healthy hosts in this series. Forty-five patients (34.9%) of this series were diagnosed only at post-mortem. Among 47 patients where culture was attempted, mucorales were isolated from 25 patients with Rhizopus arrhizus (11 patients) and Apophysomyces elegans (eight patients) as the predominant isolates. Adequate therapy could be provided in 33 patients. A combination of aggressive surgical debridement of necrotic tissue and amphotericin-B was found to be the best treatment protocol as 81.3% patients treated with surgical debridement and amphotericin-B were cured, compared with 46.7% patients treated with amphotericin-B alone. CONCLUSION: The study highlights the importance of increased awareness for early diagnosis of zygomycosis and aggressive management. The large number of cases in apparently healthy hosts and increased isolation of A. elegans in the present series are important characteristics of this disease in India and requires further evaluation.

Adolescent↗

Implications of increased left ventricular mass index on in-hospital outcomes in patients undergoing aortic valve surgery.

BACKGROUND: Increased left ventricular mass index has been shown to be associated with higher mortality in epidemiologic studies. However, the effect of increased left ventricular mass index on outcomes in patients undergoing aortic valve replacement is unknown. METHODS: We studied 473 consecutive patients undergoing elective aortic valve replacement to assess the influence of left ventricular mass index on outcomes in patients having this procedure. Echocardiographic left ventricular dimensions were used to calculate left ventricular mass index (considered increased if >134 g/m(2) in male patients and >110 g/m(2) in female patients). RESULTS: Left ventricular mass index was increased in 24% of patients undergoing aortic valve replacement. Postprocedural complications (respiratory failure, renal insufficiency, congestive heart failure, and atrial and ventricular arrhythmias), length of stay in the intensive care unit, and in-hospital mortality were increased in patients with increased left ventricular mass index. Multivariable analysis identified prior valve surgery (odds ratio, 4.3; 95% confidence interval, 1.2-15.7; P =.030), left ventricular ejection fraction (odds ratio, 1.07; 95% confidence interval, 1.01-1.14; P =.020), history of hypertension (odds ratio, 8.2; 95% confidence interval, 2.2-30.4; P =.002), history of liver disease (odds ratio, 50.4; 95% confidence interval, 4.2-609.0; P =.002), and increased left ventricular mass index (odds ratio, 38; 95% confidence interval, 9.3-154.1; P <.001) as independent predictors of in-hospital mortality. Furthermore, low output syndrome was identified as the most common mode of death (36%) after aortic valve replacement in patients with increased left ventricular mass index. CONCLUSIONS: Increased left ventricular mass index is associated with increased adverse in-hospital clinical outcomes in patients undergoing aortic valve replacement. Although this finding warrants special modification in perioperative management, further studies are needed to address whether outcomes in asymptomatic patients with aortic valve disease could be improved by earlier aortic valve replacement before a significant increase in left ventricular mass index.

Aortic Valve↗

Prospects of inspection and maintenance of two-wheelers in India.

Two-wheeler vehicles in Delhi, India--roughly 70% of the total vehicle fleet--are responsible for a significant portion of the city's vehicle emissions and petroleum consumption. An inspection and maintenance (I/M) program that ensures vehicle emission control systems are well maintained can complement other emission reduction strategies. This paper presents the initial findings of extensive data collected on vehicle characteristics and emissions for two-wheeler vehicles operating in Delhi in a series of I/M camps conducted by the Society of Indian Automobile Manufacturers and various partners in late 1999. The analysis shows idle HC and CO emissions [measured in terms of parts per million (ppm) and volume % (vol %), respectively] in a slow declining trend with subsequent model years, reflecting tighter emission standards and more advanced emission technologies. The I/M benefits--3 vol % and 39% reduction in idle and mass CO, respectively; 40 vol % and 22% reduction in idle and mass HC, respectively; and a 10-20% increase in fuel efficiency--were higher than those reported in the literature. Although these benefits are substantial, any implementation strategy needs to consider cost-effectiveness. In the present study, only 10% of vehicles--contributing 22% of the total vehicle emissions--failed the idle CO standard. Fleet emissions data variability necessitates a large sample size to develop a baseline for the vehicle fleet, but a smaller, scientifically designed sample and better data collection quality could periodically track the benefits at future camps.

Air Pollution↗

Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water.

BACKGROUND: Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. METHODS: Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/-14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. RESULTS: Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases. CONCLUSION: 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.

Adult↗