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Biomedical subjects

K Das

Publications and source records attributed to K Das.

At least 127 records · Page 7Linked to original sources
PubMed1996

Characterization of multiple mRNAs that encode mammalian translation initiation factor 5 (eIF-5).

Eukaryotic translation initiation factor 5 (eIF-5) interacts with the 40 S initiation complex (40S.mRNA.MettRNAf.eIF-2.GTP) to promote the hydrolysis of bound GTP with the concomitant joining of the 60 S ribosomal subunit to the 40 S initiation complex to form a functional 80 S initiation complex. In this paper, the multiple mRNAs that encode mammalian eIF-5 have been characterized. In rat tissues, three major eIF-5 mRNAs of 3.5, 2.8, and 2.2 kilobases in length are detected. All major eIF-5 mRNAs are initiated from a single transcription initiation site, contain identical 5'-untranslated and coding regions, but differ from one another only in the length of their 3'-untranslated regions. The different lengths of the 3'-untranslated region of eIF-5 mRNAs are generated by the use of alternative polyadenylation signals. Additionally, we demonstrate tissue-specific variations in eIF-5 mRNA expression as well as preference for polyadenylation sites. These results should lead to increased understanding of the regulation of eIF-5 gene expression.

Alternative Splicing↗
PubMed1996

Conformation, protein-carbohydrate interactions and a novel subunit association in the refined structure of peanut lectin-lactose complex.

The structure of the complex of the tetrameric peanut lectin with lactose has been refined to an R-value of 16.4% using 2.25 angstroms resolution X-ray diffraction data. The subunit conformation in the structure is similar to that in other legume lectins except in the loops. It has been shown that in the tertiary structure of legume lectins, the short five-stranded sheet plays a major role in connecting the larger flat six-stranded and curved seven-stranded sheets. Furthermore, the loops that connect the strands at the two ends of the seven-stranded sheet curve toward and interact with each other to produce a second hydrophobic core in addition to the one between the two large sheets. The protein-lactose interactions involve the invariant features observed in other legume lectins in addition to those characteristic of peanut lectin. The "open" quaternary association in peanut lectin is stabilised by hydrophobic, hydrogen-bonded and water-mediated interactions. Contrary to the earlier belief, the structure of peanut lectin demonstrates that the variability in quaternary association in legume lectins, despite all of them having nearly the same tertiary structure, is not necessarily caused by covalently bound carbohydrate. An attempt has been made to provide a structural rationale for this variability, on the basis of buried surface areas during dimerisation. A total of 45 water molecules remain invariant when the hydration shells of the four subunits are compared. A majority of them appear to be involved in stabilising loops.

Carbohydrate Metabolism↗
PubMed1996

Development of a genus specific primer set for detection of Leishmania parasites by polymerase chain reaction.

We have compared the sequences of a major class of kinetoplast DNA (kDNA) minicircle (pLURkE3) of Leishmania strain UR6 with other minicircle sequences from different Leishmania species. Alignment of these sequences allowed the selection of a pair of oligonucleotides suitable as primers in polymerase chain reaction (PCR) which is specific for Leishmania parasites. PCR with this genus-specific primer set is capable of detecting 1 femtogram of kDNA. These primers have been tested with kDNAs from both old world and new world Leishmania species. The results indicate that the primers may be suitable for detection of any kind of leishmaniasis.

Animals↗
PubMed1996

Primary sclerosing cholangitis: an experience from India.

Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim of the present study was to investigate the incidence, clinical profile and outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July, 1984-June, 1994) 18 patients of PSC were diagnosed at cholangiography (14 patients by endoscopic retrograde cholangiopancreatography, two patients by percutaneous transhepatic cholangiography and two patients by both methods). The presence of secondary causes, such as choledocholithiasis, biliary tract surgery, congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases, were excluded. These patients were evaluated retrospectively with respect to their clinical presentation, radiological findings, presence of associated idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean (+/- s.d.) age at diagnosis of PSC was 39.0 (+/- 16.1) years with a male:female ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of the IUC preceded that of PSC in all but one case. Fifteen (83.3%) patients had cholestatic jaundice at presentation, while three (16.7%) patients had asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent cholangitis and five (27.8%) patients developed portal hypertension during the course of the disease. At cholangiography, intrahepatic radicles were involved in all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with steroids (n = 7), colchicine (n = 3), ursodeoxycholic acid (UDCA; n = 2) and methotrexate (n = 1), along with symptomatic measures. Mean duration of follow up available in 11 (61%) patients was 20.1 months (range: 1 month-8 years). Four (36.4%) patients died. Steroids and colchicine did not have any effect while the one patient on UDCA and one on methotrexate showed improvement. In conclusion, in India PSC does not seem to be a rare entity. Its clinical profile and outcome are somewhat similar to those seen in Western countries.

Adult↗
PubMed1996

Helicobacter pylori eradication--evaluation of triple therapy containing omeprazole.

BACKGROUND: There is a need to develop alternative regimen(s) for treating Helicobacter pylori infection because of problems of drug compliance, side-effects and resistance with the conventional regimen consisting of bismuth, metronidazole and an antibiotic. AIMS: To compare prospectively the efficacy of conventional triple therapy (bismuth subcitrate 120 mg QID, amoxycillin 500 mg QID and metronidazole 400 mg TID for 2 weeks with one containing omeprazole (20 mg OD), bismuth subcitrate and amoxycillin (regimen B). METHODS: Sixty two consecutive patients with H pylori infection associated with antral gastritis and/or duodenal ulcer were randomized to two treatment groups and re- evaluated after completion of 2 weeks of therapy and then after a further 4 weeks for eradication of H pylori, ulcer healing and drug side-effects. RESULTS: Regimen B resulted in higher H pylori eradication rate as compared to regimen A (76.7% vs 63.3%, better ulcer healing rate (90.9%, vs 70.6%), lesser side-effects (10.0% vs 36.7%) and better drug compliance (100% vs 93.3%). The difference between the two regimens was significant (p < 0.05) only in respect to side-effects. CONCLUSION: For H pylori eradication, omeprazole, bismuth and amoxycillin combination for 2 weeks is as effective as the conventional therapy and is better tolerated.

Adult↗
PubMed1996

Targeting HIV reverse transcriptase for anti-AIDS drug design: structural and biological considerations for chemotherapeutic strategies.

The reverse transcriptase of HIV is a key target for the antiviral treatment of AIDS. Numerous potent inhibitors of RT have been described including all of the drugs that have been currently licensed for the treatment of AIDS, but their efficacy has been limited by the emergence of drug-resistant HIV variants. Extensive biochemical, genetic, and clinical data about HIV RT enzymatic mechanisms, inhibition, and drug resistance have been reported. This information, taken together with structural data from crystallographic studies of HIV-1 RT, has set the stage for structure-based design of improved inhibitors of this essential viral enzyme. Comparisons of the different crystal structures of HIV-1 RT shows that the enzyme has great conformational flexibility, providing additional possibilities for drug targeting. Recent clinical and virological data suggest that HIV-1 RT enzymes that carry drug-resistance mutations can be substantially impaired and that combinations of RT inhibitors can produce significant clinical benefit in the treatment of AIDS. An immediate goal is to use the available information to design specific inhibitors or combination therapies that will select for relatively less fit HIV variants.

Binding Sites↗
PubMed1996

Population structure and genetic differentiation among 16 tribal populations of central India.

Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.

Ethnicity↗
PubMed1995

Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures.

Microglia activation by lipopolysaccharides (LPS) significantly decreased choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cultures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the media level of the NO metabolite nitrite, and the NOS inhibitor Ng-nitro-L-arginine methylester (NAME) protected the ChAT+ neurons from LPS. The combination of beta-amyloid peptide (1-42) and interferon-gamma (INF-gamma) also increased the media nitrite level and decreased ChAT+ neuron number. Cholinergic neurons are lost early in the course of Alzheimer's disease, and the enhanced sensitivity of these neurons to microglial activation in mixed neuronal/glial culture may be useful for modeling Alzheimer's disease and developing therapeutic strategies to combat this disease.

Amyloid beta-Peptides↗
PubMed1995

Structure of HIV-1 reverse transcriptase in a complex with the non-nucleoside inhibitor alpha-APA R 95845 at 2.8 A resolution.

BACKGROUND: HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that copies the RNA genome of HIV-1 into DNA. It is a heterodimer composed of a 66 kDa (p66) and a 51 kDa (p51) subunit. HIV-1 RT is a crucial target for structure-based drug design, and potent inhibitors have been identified, whose efficacy, however, is limited by drug resistance. RESULTS: The crystal structure of HIV-1 RT in complex with the non-nucleoside inhibitor alpha-anilinophenyl-acetamide (alpha-APA) R95845 has been determined at 2.8 A resolution. The inhibitor binds in a hydrophobic pocket near the polymerase active site. The pocket contains five aromatic amino acid residues and the interactions of the side chains of these residues with the aromatic rings of non-nucleoside inhibitors appear to be important for inhibitor binding. Most of the amino acid residues where mutations have been correlated with high levels of resistance to non-nucleoside inhibitors of HIV-1 RT are located close to alpha-APA. The overall fold of HIV-1 RT in complex with alpha-APA is similar to that found when in complex with nevirapine, another non-nucleoside inhibitor, but there are significant conformational changes relative to an HIV-1 RT/DNA/Fab complex. CONCLUSIONS: The non-nucleoside inhibitor-binding pocket has a flexible structure whose mobility may be required for effective polymerization, and may be part of a hinge that permits relative movements of two subdomains of the p66 subunit denoted the 'palm' and 'thumb'. An understanding of the structure of the inhibitor-binding pocket, of the interactions between HIV-1 RT and alpha-APA, and of the locations of mutations that confer resistance to inhibitors provides a basis for structure-based design of chemotherapeutic agents for the treatment of AIDS.

Acetamides↗
PubMed1995

Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors.

We report the structure of HIV-1 reverse transcriptase (RT) complexed with the nonnucleoside inhibitor TIBO R 86183 at 3.0 A resolution. Comparing this structure with those of complexes of HIV-1 RT/alpha-APA R 95845 and HIV-1 RT/nevirapine provides a basis for understanding the nature of nonnucleoside inhibitor binding, the structure of the binding site and the interactions between the bound inhibitors and surrounding amino acid residues as well as for understanding mechanisms of inhibition by and resistance to nonnucleoside inhibitors. All three inhibitors considered assume a similar butterfly-like shape and bind to HIV-1 RT in a very similar way. Important differences occur in the conformation of amino acid residues that form the binding pocket.

Acetamides↗
PubMed1995

Ultrastructure of cellular components of human trophoblasts during early pregnancy.

Two cell types, the cyto- and syncytio-trophoblasts, were identified in human chorionic villi of 6-10 weeks' gestation. The intracellular organization of these cells was examined. Ultrathin sections of small pieces of chorionic villi revealed the presence of a multinucleate syncytiotrophoblastic layer, whose surface was covered with microvilli. The cytotrophoblasts, however, had a single large nucleus with a prominent nucleolus. An interesting feature of the basement membrane of these cells was the presence of aggregates of dark granules in samples of the earlier gestational age (6-8 weeks) and granular bodies having a dense outer ring and a translucent inner ring with a lucid central area in samples of 8-10 weeks' gestation. Both types of granules are mineralized and are assumed to perform a buffering role for maintaining the neutrality of the layer.

Cell Nucleus↗
PubMed1995

Hysteroscopic cannulation for proximal tubal obstruction: a change for the better?

OBJECTIVE: To compare overall the results of hysteroscopic tubal cannulations and resection anastomosis for proximal tubal occlusion. DESIGN: Nonrandomized retrospective analysis of patients operated on by two surgeons. SETTING: University and large tertiary referral private practice. PATIENTS: Seventy-four patients over a 10-year period, with bilateral or unilateral proximal occlusion of a single tube. INTERVENTIONS: Hysteroscopic cannulation, resection anastomosis, or both. MAIN OUTCOME MEASURES: Intrauterine and ectopic pregnancy rates, long-term tubal patency, and pathology of tubal segments. RESULTS: In patients with normal distal tubes, intrauterine pregnancy rates were similar (12/21, 57% versus 12/24, 50%) and ectopic pregnancy rates were lower (0/21, 0% versus 7/24, 29.1%) in the cannulation group. One-year patency rates in nonpregnant patients was higher in the anastomosis group (12/15, 80% versus 3/8, 33%). CONCLUSIONS: Hysteroscopic cannulation should be first choice in the management of proximal tubal obstructions in selected patients. It may be a treatment option for delayed occlusion after successful cannulation or resection anastomosis.

Anastomosis, Surgical↗
PubMed1995

Linkage disequilibrium and haplotype analysis among Polish families with spinal muscular atrophy.

Spinal Muscular Atrophy (SMA) is an inherited degenerative disorder of anterior horn cells that results in progressive muscle weakness and atrophy. The autosomal recessive forms of childhood-onset SMA have been mapped to chromosome 5q11.2-13.3, in a number of studies examining different populations. A total of 9 simple sequence repeat markers were genotyped against 32 Polish families with SMA. The markers span an approximately 0.7 cM region defined by the SMA flanking markers D5S435 and MAP1B. Significant linkage disequilibrium (corrected P < .05) was detected at four of these markers, with D/Dmax values of < or = .89. Extended haplotype analysis revealed a predominant haplotype associated with SMA. The apparently high mutation rate of some of the markers has resulted in a number of haplotypes that vary slightly from this predominant haplotype. The predominant haplotype and these closely related patterns represent 25% of the disease chromosomes and none of the nontransmitted parental chromosomes. This predominant haplotype is present both in patients with acute (type I) and in chronic (types II and III) forms of SMA and occurs twice in a homozygous state, both times in children with chronic SMA.

Adolescent↗
PubMed1995

Immunoglobulin levels in populations with low hemoglobin levels: study of five tribes of central India.

Average hemoglobin levels for 424 individuals belonging to 5 tribes of central India vary between 10.64 g/dl and 11.30 g/dl among males and between 9.62 g/dl and 9.97 g/dl among females. These ranges indicate the poor state of health and nutrition in these tribes. Three immunoglobulin levels (IgG, IgA, and IgM) measured in a subset of the 424 individuals reveal that immunoglobulin and hemoglobin levels are inversely related to some extent. Levels of all three classes of immunoglobulins were found to be significantly correlated. This suggests that humoral immunity is not impaired even under acute nutritional stress.

Adolescent↗