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Biomedical subjects

A Das

Publications and source records attributed to A Das.

At least 37 records · Page 2Linked to original sources

Recurrent Guillain Barre' syndrome.

BACKGROUND: Recurrent Guillain Barre' syndrome (RGBS) is a rare condition and there is a paucity of clinical and neurophysiological studies. AIM: This study was undertaken to evaluate the clinical and neurophysiological changes in patients with recurrent GB syndrome and their outcome. METHODS: We report 11 patients with RGBS out of 200 patients with GB syndrome seen over last 10 years. These patients had 2 or more attacks of acute inflammatory demyelinating neuropathy with an onset to peak time of 4 weeks or less having complete or near complete recovery. All the patients underwent complete neurological evaluation. The disability was graded on a 0-10 clinical grading scale. Antinuclear antibody, rheumatoid factor C3, C4, urine test for porphyria, serum test for HIV and CSF examination were carried out in all the patients. Motor nerve conduction of median, ulnar, peroneal, F response and concentric needle electromyography were carried out in all. Sensory conduction of ulnar, median and sural, central motor conduction to abductor digiti minimi and tibialis anterior were also carried out. RESULTS: Patients' age ranged between 5 and 40 years and 6 were children. Eight patients had 2 attacks, 2 had 3 attacks and 1 had 4 attacks. The interval between attacks ranged between 4 months to 10 year (mean 39.5 month). The triggering events were noted in 7 patients and were identical to the previous event in 4 patients. Six patients had pure motor weakness, 4 had associated sensory symptoms and 1 had both sensory symptoms and signs. The severity of different attacks was not related to number of recurrences. Nerve conduction studies were consistent with demyelinating neuropathy. Central motor conduction was abnormal in 5 out of 7 episodes studied Eight patients recovered completely after initial attack and 3 had persistent foot drop at 6 month follow up. Following the second attack 4 patients recoveredfully and the remaining 7 had foot drop and in 2 there was mild proximal weakness as well. After the third attack 1 patient recoveredfully and the other 2 had residual deficit in the form of handgrip weakness and foot drop. There seems to be a tendency to accumulate neurological deficits with increasing frequency of attacks of GB syndrome.

Adolescent↗

A study of HIV/STD infections amongst commercial sex workers in Kolkata. (India) Part-IV laboratory investigation of STD and HIV infections.

Out of 867 sex workers examined during 1998-2000 from the five important red light areas of Kolkata, 26.18%(227) were suffering from active syphilitic infection having positive VDRL test with titre 1/8 and above. Vaginal smear for gram staining was collected from all sex workers, and found positive for active gonorrhoeal infection in 41.8% (362). Culture positivity for gonorrheal infection was 34.14% (296). Sex workers were also having other STD infection, 23.64% (205) Trichomonas infection, 13.26% (115) Candidiasis, 8.77% (76), Gardenella and 3.0% (26) Chanchroid for which vaginal samples were found positive. HIV sero-positivity was found to be 13.2% (115) out of 867 blood samples examined from all sex workers under study. There were 0.34% (3) sex workers who were also positive for HIV II infection along with HIV-I infection. A case of HIV II alone was not detected in any of the sex workers. Around 49.6% (430) knew that STD/HIV can be prevented by use of condom. However, condom was used by only 6.57% (57) sex workers.

Chancroid↗

Cross-cultural adaptation and validation of the English version of the International Index of Erectile Function (IIEF) for use in Malaysia.

We adapted the English International Index of Erectile Function (IIEF) into Malay. This was difficult as many sex-related terms do not exist in colloquial Malay. In the pretest, there was no difficulty with comprehension and all subjects judged the Malay IIEF equivalent to the English IIEF. After slight modification, a final instrument was evaluated in two studies. Study A included 136 subjects. It showed that the instrument had good reliability and discriminant validity. The factor structure of the English IIEF was not reproducible. Study B included 26 ED subjects who underwent oral sildenafil therapy. The Malay IIEF was sensitive to treatment response. The area under the ROC curve of the Malay IIEF-5 was 0.86; the optimal cutoff score has a sensitivity of 85% and specificity of 75%. The results suggest that the Malay IIEF requires more work, but the Malay IIEF-5 has acceptable measurement properties to recommend its use in clinical practice and research.

Adult↗

Identification of novel genes for secreted and membrane-anchored proteins in human keratinocytes.

BACKGROUND: Both intercellular and intracellular signals are transduced primarily by interactions of secreted and/or membrane-anchored polypeptides, and they play a pivotal role in regulating proliferation, differentiation and apoptosis of keratinocytes within the epidermis. Despite recent identification of these polypeptides, it is likely that several important molecules remain undisclosed. OBJECTIVES: To identify novel genes encoding secreted or membrane-anchored polypeptides expressed by human keratinocytes. METHODS: We employed a signal sequence (SS) trap of a 5'-end-enriched cDNA library prepared from primary cultured human keratinocytes. Gene expression analysis was performed using Northern blotting. R Screening of 4018 cDNA clones yielded 82 positive clones (57 independent genes), most of which encoded SSs in their N-termini. Most of the positive clones were known genes registered in the GenBank database. Seven genes were identified in the EST database, four of which encoded novel membrane-anchored polypeptides with features of type I transmembrane proteins; the other three genes encoded novel non-type I transmembrane polypeptides. These EST genes were expressed differentially by keratinocytes subjected to low vs. high calcium concentrations and by basal vs. squamous cell carcinomas. CONCLUSIONS: Using the SS trap, we isolated many genes known to be involved in constituting epidermal structures and others that had not previously been associated with keratinocytes. In addition, we identified novel genes (EST genes) that differ in kinetics of gene expression in keratinocyte differentiation. Our results validate the effective use of this SS trap method for identifying secreted and membrane-anchored polypeptides expressed by human keratinocytes. The identification will better illuminate the molecular mechanisms responsible for co-ordinated regulation of epidermal homeostasis.

Amino Acid Sequence↗

Expression of NF-kappaB in epidermis and the relationship between NF-kappaB activation and inhibition of keratinocyte growth.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a transcription factor involved in a number of signalling pathways in many cell types. NF-kappaB in mice has been implicated as an important regulator of keratinocyte proliferation and differentiation. OBJECTIVES: To evaluate the role of NF-kappaB in keratinocyte growth in human beings, we examined its expression in keratinocytes both in culture and in situ, and studied the relationship between NF-kappaB activation and the inhibition of keratinocyte proliferation induced by known modulators of keratinocyte growth. METHODS: The expression of subunits of the NF-kappaB family was examined in human skin, primary cultured keratinocytes and an immortalized keratinocyte line by immunohistochemistry and reverse transcriptase-polymerase chain reaction analysis. NF-kB activation was examined in keratinocytes treated with various modulating agents by electrophoretic mobility shift assay (for DNA-binding activity) and by immunocytochemistry (nuclear translocation). The proliferative capacity of treated keratinocytes was also examined by 3H-thymidine incorporation, cell cycle analysis, and expression of Ki-67, a nuclear marker for cell proliferation. The involvement of NF-kappaB was assessed using sodium salicylate, which inhibits NF-kappaB activation. RESULTS: The NF-kappaB subunits, p50, p65, RelB, and c-Rel (but not p52), were detected in keratinocytes and in normal epidermis at mRNA and protein levels. The four subunits were expressed in a cytoplasmic (rather than a nuclear) pattern in both basal and suprabasal keratinocytes. Phorbol myristate acetate (PMA), tumour necrosis factor alpha, and interferon gamma each activated NF-kappaB and inhibited keratinocyte proliferation. Lipopolysaccharide and dexamethasone did not activate NF-kappaB and had the least effect on proliferation. Finally, a high concentration of calcium (Ca2+) and retinoic acid each failed to activate NF-kappaB, but were potent inhibitors of keratinocyte proliferation, respectively. PMA-induced cell cycle arrest of keratinocytes was blocked by pretreatment with sodium salicylate. CONCLUSIONS: NF-kappaB is constitutively expressed in a resting state in both human cultured keratinocytes and the epidermis. Activation of NF-kappaB is required for PMA-induced keratinocyte growth arrest.

Cell Cycle↗

Nosocomial outbreak of diarrhoea by enterotoxigenic Escherichia coli among preterm neonates in a tertiary care hospital in India: pitfalls in healthcare.

An outbreak of watery diarrhoea accompanied by low-grade fever and weight loss in 16 preterm neonates (age range 2-20 days) admitted to a neonatal intensive care unit (NICU) over four days in August 2000 is reported. Escherichia coli having similar antibiograms were identified on routine bacterial stool cultures in 14 (87.5%) neonates and none of the other known enteropathogens were detected. An investigation was undertaken to trace the source of infection. Surveillance cultures of swabs from the utensils used to prepare milk feed, culture of the formula feed and all items handled by one particular cook yielded growth of E. coli as did culture of his hand swabs and faecal sample. The causative agent was identified as enterotoxigenic E. coli (ETEC) as toxin production could be demonstrated by reverse passive latex agglutination in all the strains of E. coli isolated both from the infected neonates and the source of infection. The outbreak was effectively controlled by appropriate therapy and institution of proper measures of hygiene after identification of the source of infection.

Animals↗

Vertebral cryptococcosis simulating tuberculosis.

Infection with the fungus Cryptococcus neoformans is seen predominantly in two forms: (a) pulmonary and (b) cerebromeningeal. Skeletal cryptococcosis is uncommon. There have been only occasional case reports of thoracic vertebral cryptococcosis presenting as cord compression. A young female had cervical lymphadenopathy diagnosed as tuberculosis by fine needle aspiration cytology (FNAC) and was on antitubercular therapy (ATT) for 5 months. She developed rapidly progressive paraparesis and imaging demonstrated a destructive vertebral body lesion involving T2-3 with a paraspinal abscess producing cord compression. A costotransversectomy with excision of the diseased bone and bone grafting was done. Histopathological examination revealed cryptococcosis. The patient was put on antifungal medication, but expired 2 weeks after surgery. Radiological, magnetic resonance imaging and surgical finding of vertebral cryptococcosis can mimic tuberculosis. The definite diagnosis of cryptococcosis depends upon microscopic identification of the organism. A high index of suspicion leading to early surgical confirmation and institution of anti fungal therapy is necessary to reduce the mortality and morbidity.

Adult↗

Apophysomyces elegans: an emerging zygomycete in India.

Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)(5) and (GAC)(5)] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.

Adult↗

A study of HIV/STD infections amongst commercial sex workers in Kolkata (India). Part-I: some socio-demographic features of commercial sex workers.

A community-based survey of Human Immunodeficiency Virus (HIV) and sexually transmitted diseases (STD) was carried out among commercial sex worker's (CSW) in different red light areas of Kolkata. By multistage random sampling technique 867 female sex workers (FSW) studied who were belonging to Sonagachi 77.28%, Metiabruz 14.07%, Rampurgali and Khidderpore 8.65% red light areas. Among sex workers surveyed 58.94% were Hindu and 33.33% Muslims. There were 22.07% CSW of foreign origin, out of which 17.99% from Bangladesh and 4.04% from Nepal. Majority of CSW 74.28% were under thirty years of age. The lowest age was 13 years and mean age was 26.55 years. There were 22.26% sex workers under twenty years and 6.92% above forty years of age. About 79.0% of sex workers were illiterate. The average number of clients visiting each sex workers was 2.67, with a range between 1 to 8 clients per day. The average duration for which sex workers remain in the trade was 6 to 7 years. Around 60.09% sex workers were in the trade for five years, while 2.64% were for more than twenty years. Average monthly income of sex workers was around Rs. 500-1000. History of pregnancy was present in 84.66% with one child in 24.91 % to maximum eight in 0.23% sex workers. The mean number of pregnancies was 1.9 per female sex workers. About 36.2% had history of abortion and 65.51 % had living children.

Adolescent↗

A study of Hiv/STD infections amongst commercial sex workers in Kolkata (India). Part-II: sexual behaviour, knowledge and attitude towards STD/HIV infections.

The sexual behaviour, knowledge, attitude and practice for prevention and control measures against STD/HIV are discussed in this paper. In all 867 sex workers, belonging to different red light areas of Kolkata viz. Sonagachi 77.28% (670), Metiabruz 14.07% (122) and 8.65% (75) from Rampurgali, Khidderpore and Bow Bazar were studied. Majority of sex workers 74.28% (644) were under thirty years of age. Around 22.26% (193) were within 20 years and 5.85%(51) were above 40 years of age. Sex workers had more than one habit but commonest were betel nut chewing in 67.59%(586) and alcohol consumption either alone or with the clients in 61.1% (529). Drug abuse (IVD) was not agreed to by any of the sex workers. Around 78.09% (677) were in the trade for last ten years, and 21.91%(190) for more than ten years. The mean duration for which sex workers remain in the trade is 6.71 years. The average number of clients visiting them were 2.67 per sex workers per day. The commonest sexual practice was normal peno-vaginal in 94.1 % (823). Peno-oral sex is practiced by 32.5%(282) sex workers, of which 2.65 % (23) always, 2.31%(20) often and 27.0%(59) sometimes practiced it. Peno-rectal sex was practiced by 5.42% (47), with 2.31% (20) often and 3.11% (27) sometimes. Around 13.96% (121) sex workers participate in the group sex. The knowledge of STD/HIV infection was quite low, 49.48% (429) of CSWs had heard about STD/HIV/AIDS and around 49.6% (430) knew that STD/HIV could be prevented by condom use.

Adolescent↗

A study of HIV/STD infections amongst commercial sex workers in Kolkata (India). Part-III, clinical features of sexually transmitted diseases.

The clinical features of sexually transmitted disease (STD) infection in female sex workers found in a community based study in different red light areas of Kolkata are discussed in this paper. Out of 867 sex workers clinically examined in the clinics in their respective areas, 80.16% were having different signs and symptoms of sexually transmitted diseases. The vaginal discharge was the commonest feature present in 49.6% sex workers. The chronic vaginal discharge of more than a month was found in 47.44%, while 37.90% sex workers had vaginal discharge of less than one month. The genital ulcer was present in 25.03% (217) sex workers. The other sexually transmitted infection that was found includes genital warts 13.73%, scabies 12.11 and Inguinal bubo in 1.73% sex workers. The sex workers were also having other symptoms e.g. chronic weight loss, prolonged fever and chronic diarrhoea in 13.73% (119), 10.03% (87) and in 1.96% (17) sex workers respectively.

Female↗

Laser-generated ultrashort multimegagauss magnetic pulses in plasmas.

We demonstrate ultrashort (6 ps), multimegagauss (27 MG) magnetic pulses generated upon interaction of an intense laser pulse (10(16) W cm(-2), 100 fs) with a solid target. The temporal evolution of these giant fields generated near the critical layer is obtained with the highest resolution reported thus far. Particle-in-cell simulations and phenomenological modeling is used to explain the results. The first direct observations of anomalously rapid damping of plasma shielding currents produced in response to the hot electron currents penetrating the bulk plasma are presented.

Journal Article↗

Free-energy component analysis of 40 protein-DNA complexes: a consensus view on the thermodynamics of binding at the molecular level.

Noncovalent association of proteins to specific target sites on DNA--a process central to gene expression and regulation--has thus far proven to be idiosyncratic and elusive to generalizations on the nature of the driving forces. The spate of structural information on protein--DNA complexes sets the stage for theoretical investigations on the molecular thermodynamics of binding aimed at identifying forces responsible for specific macromolecular recognition. Computation of absolute binding free energies for systems of this complexity transiting from structural information is a stupendous task. Adopting some recent progresses in treating atomic level interactions in proteins and nucleic acids including solvent and salt effects, we have put together an energy component methodology cast in a phenomenological mode and amenable to systematic improvements and developed a computational first atlas of the free energy contributors to binding in approximately 40 protein-DNA complexes representing a variety of structural motifs and functions. Illustrating vividly the compensatory nature of the free energy components contributing to the energetics of recognition for attaining optimal binding, our results highlight unambiguously the roles played by packing, electrostatics including hydrogen bonds, ion and water release (cavitation) in protein-DNA binding. Cavitation and van der Waals contributions without exception favor complexation. The electrostatics is marginally unfavorable in a consensus view. Basic residues on the protein contribute favorably to binding despite the desolvation expense. The electrostatics arising from the acidic and neutral residues proves unfavorable to binding. An enveloping mode of binding to short stretches of DNA makes for a strong unfavorable net electrostatics but a highly favorable van der Waals and cavitation contribution. Thus, noncovalent protein-DNA association is a system-specific fine balancing act of these diverse competing forces. With the advances in computational methods as applied to macromolecular recognition, the challenge now seems to be to correlate the differential (initial vs. final) energetics to substituent effects in drug design and to move from affinity to specificity.

Algorithms↗

Central and autonomic system signs with in utero drug exposure.

AIMS: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure. METHODS: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure. RESULTS: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more. CONCLUSION: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.

Adult↗

Do water molecules mediate protein-DNA recognition?

A comprehensive analysis of interfacial water molecules in the structures of 109 unique protein-DNA complexes is presented together with a new view on their role in protein-DNA recognition. Location of interfacial water molecules as reported in the crystal structures and as emerging from a series of molecular dynamics studies on protein-DNA complexes with explicit solvent and counterions, was analyzed based on their acceptor, donor hydrogen bond relationships with the atoms and residues of the macromolecules, electrostatic field calculations and packing density considerations. Water molecules for the purpose of this study have been categorized into four classes: viz. (I) those that contact both the protein and the DNA simultaneously and thus mediate recognition directly; (II) those that contact either the protein or the DNA exclusively via hydrogen bonds solvating each solute separately; (III) those that contact the hydrophobic groups in either the protein or the DNA; and, lastly (IV) those that contact another water molecule. Of the 17,963 crystallographic water molecules under examination, about 6% belong to class I and 76% belong to class II. About three-fourths of class I and class II water molecules are exclusively associated with hydrogen bond acceptor atoms of both protein and DNA. Noting that DNA is polyanionic, it is significant that a majority of the crystallographically observed water molecules as well as those from molecular dynamics simulations should be involved in facilitating binding by screening unfavorable electrostatics. Less than 2% of the reported water molecules occur between hydrogen bond donor atoms of protein and acceptor atoms of DNA. These represent cases where protein atoms cannot reach out to DNA to make favorable hydrogen bond interactions due to packing/structural restrictions and interfacial water molecules provide an extension to side-chains to accomplish hydrogen bonding.

Base Sequence↗

Solution structure of a guanine-N7-linked complex of the mitomycin C metabolite 2,7-diaminomitosene and DNA. Basis of sequence selectivity.

2,7-Diaminomitosene (2,7-DAM), the major metabolite of the antitumor antibiotic mitomycin C, forms DNA adducts in tumor cells. 2,7-DAM was reacted with the deoxyoligonucleotide d(GTGGTATACCAC) under reductive alkylation conditions. The resulting DNA adduct was characterized as d(G-T-G-[M]G-T-A-T-A-C-C-A-C) (5), where [M]G stands for a covalently modified guanine, linked at its N7-position to C10 of the mitosene. The adducted oligonucleotide complements with itself, retaining 2-fold symmetry in the 2:1 drug-duplex complex, and provides well-resolved NMR spectra, amenable for structure determination. Adduction at the N7-position of G4 ([M]G, 4) is characterized by a downfield shift of the G4(H8) proton and separate resonances for G4(NH(2)) protons. We assigned the exchangeable and nonexchangeable proton resonances of the mitosene and the deoxyoligonucleotide in adduct duplex 5 and identified intermolecular proton-proton NOEs necessary for structural characterization. Molecular dynamics computations guided by 126 intramolecular and 48 intermolecular distance restraints were performed to define the solution structure of the 2,7-DAM-DNA complex 5. A total of 12 structures were computed which exhibited pairwise rmsd values in the 0.54-1.42 A range. The 2,7-DAM molecule is anchored in the major groove of DNA by its C10 covalently linked to G4(N7) and is oriented 3' to the adducted guanine. The presence of 2,7-DAM in the major groove does not alter the overall B-DNA helical structure. Alignment in the major groove is a novel feature of the complexation of 2,7-DAM with DNA; other known major groove alkylators such as aflatoxin, possessing aromatic structural elements, form intercalated complexes. Thermal stability properties of the 2,7-DAM-DNA complex 5 were characteristic of nonintercalating guanine-N7 alkylating agents. Marked sequence selectivity of the alkylation by 2,7-DAM was observed, using a series of oligonucleotides incorporating variations of the 5'-TGGN sequence as substrates. The selectivity correlated with the sequence specificity of the negative molecular electrostatic potential of the major groove, suggesting that the alkylation selectivity of 2,7-DAM is determined by sequence-specific variation of the reactivity of the DNA. The unusual, major groove-aligned structure of the adduct 5 may account for the low cytotoxicity of 2,7-DAM.

Alkylating Agents↗