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Biomedical subjects

M Sarkar

Publications and source records attributed to M Sarkar.

At least 37 records · Page 2Linked to original sources

Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study.

OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors' goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%-3%.

Abnormalities, Drug-Induced↗

Cloning and expression of Drosophila melanogaster UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.

A TBLASTN search of the Drosophila melanogaster expressed sequence tag (EST) database with the amino acid sequence of human UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I, EC 2.4.1.101) as probe yielded a clone (GM01211) with 56% identity over 36 carboxy-terminal amino acids. A 550 base pair (bp) probe derived from the EST clone was used to screen a Drosophila cDNA library in lambda-ZAP II and two cDNAs lacking a start ATG codon were obtained. 5'-Rapid amplification of cDNA ends (5'-RACE) yielded a 2828 bp cDNA containing a full-length 1368 bp open reading frame encoding a 456 amino acid protein with putative N-terminal cytoplasmic (5 residues) and hydrophobic transmembrane (20 residues) domains. The protein showed 52% amino acid sequence identity to human GnT I. This cDNA, truncated to remove the N-terminal hydrophobic domain, was expressed in the baculovirus/Sf9 system as a secreted protein containing an N-terminal (His)6 tag. Protein purified by adsorption to and elution from nickel beads converted Man alpha1-6(Man alpha1-3)Man beta-octyl (M3-octyl) to Man alpha1-6(GlcNAc beta1-2Man alpha1-3)Man beta-octyl. The Km values (0.7 and 0.03 mM for M3-octyl and UDP-GlcNAc respectively), temperature optimum (37 degrees C), pH optimum (pH 5 to 6) and divalent cation requirements (Mn > Fe, Mg, Ni > Ba, Ca, Cd, Cu) were similar to mammalian GnT I. TBLASTN searches of the Berkeley Drosophila Genome Project database with the Drosophila GnT I cDNA sequence as probe allowed localization of the gene to chromosomal region 2R; 57A9. Comparison of the cDNA and genomic DNA sequences allowed the assignment of seven exons and six introns; all introns showed GT-AG splice site consensus sequences. This is the first insect GnT I gene to be cloned and expressed.

Amino Acid Sequence↗

Prevention of adrenocortical hyperactivity by dietary casein in rats exposed to forced swimming stress.

Adrenal weight, adrenal hydroxysteroid dehydrogenase activity and serum corticosterone level were significantly higher in rats fed with 5% casein diet after 7 days of swimming stress (45 min/day) as compared to their controls. All the parameters were similar to their control levels in rats receiving 20% casein diet and exposed to swimming stress. The results suggest that casein can play an important role in preventing adrenocortical hyperactivity in swimming stressed rats.

3-Hydroxysteroid Dehydrogenases↗

Nonparametric techniques to extract fuzzy rules for breast cancer diagnosis problem.

This paper addresses breast cancer diagnosis problem as a pattern classification problem. Specifically, the problem is studied using Wisconsin-Madison breast cancer data set. Fuzzy rules are generated from the input-output relationship so that the diagnosis becomes easier and transparent for both patients and physicians. For each class, at least one training pattern is chosen as the prototype, provided (a) the maximum membership of the training pattern is in the given class, and (b) among all the training patterns, the neighborhood of this training pattern has the least fuzzy-rough uncertainty in the given class. Using the fuzzy-rough uncertainty, a cluster is constructed around each prototype. Finally, these clusters are interpreted as the fuzzy rules that relate the prognostic factors and the diagnosis results. The advantages of the proposed algorithm are, (a) there is no need to know the structure of the training data, (b) the number of fuzzy rules does not increase with the increase of the number of input dimensions, and (c) small number of fuzzy rules is generated. With the three generated fuzzy rules, 96.20% classification efficiency is achieved, which is comparable to other rule generation techniques.

Algorithms↗

Fuzzy K-means clustering with missing values.

Fuzzy K-means clustering algorithm is a popular approach for exploring the structure of a set of patterns, especially when the clusters are overlapping or fuzzy. However, the fuzzy K-means clustering algorithm cannot be applied when the real-life data contain missing values. In many cases, the number of patterns with missing values is so large that if these patterns are removed, then sufficient number of patterns is not available to characterize the data set. This paper proposes a technique to exploit the information provided by the patterns with the missing values so that the clustering results are enhanced. There are various preprocessing methods to substitute the missing values before clustering the data. However, instead of repairing the data set at the beginning, the repairing can be carried out incrementally in each iteration based on the context. In that case, it is more likely that less uncertainty is added while incorporating the repair work. This scheme is further consolidated in this paper by fine-tuning the missing values using the information from other attributes. The applications of the proposed method in medical domain have produced good performance.

Algorithms↗

Effect of casein diet on gonadotropin releasing hormone antagonist induced changes in adrenal gonadal functions in male rats.

Adult male rats received daily injections (sc) of gonadotropin releasing hormone antagonist (0.2 mg/kg(-1) x day(-1)) for 21 days when they were sacrificed on day 22, adrenal weight, adrenal A5-3beta (delta 5-3beta) hydroxysteroid dehydrogenase (Delta5-3beta-HSD) activity and serum level of corticosterone were increased significantly while testicular 17beta (17beta) hydroxysteroid dehydrogenase (17beta-HSD) activity and serum level of testosterone and spermatogenesis were decreased in the rats fed on 5% casein diet. GnRH antagonist treated rats fed on 20% casein diet, resulted significant decrease in adrenal weight, serum corticosterone and adrenal A5-3beta-HSD activity while testicular 17beta-HSD activity serum testosterone levels and the weights of sex organs were increased with respect to anti GnRH treated rats fed on 5% casein diet. But the GnRH antagonist treated rats fed on 20% casein diet showed decreased spermatogenesis quantitatively and sperm count appeared similar to anti GnRH treated rats fed on 5% casein diet. These results indicate that high casein diet protects adrenocortical activity and stimulates testosterone synthesis without effecting spermatogenic arrest in GnRH antagonist treated rats. It may be concluded that GnRH antagonist in presence of high milk protein diet may be considered to be a suitable antihormone in the development of an ideal male contraceptive.

Adrenal Glands↗

Pregnancy outcome following gestational exposure to echinacea: a prospective controlled study.

BACKGROUND: Echinacea products are among the most popular phytomedicines on the North American market. Since at least half of all pregnancies are unplanned, many women inadvertently use echinacea in their first trimester. Presently, there is a paucity of information regarding the gestational safety of this herb. The primary objective of this study was to evaluate the safety of echinacea in pregnancy when used for upper respiratory tract ailments. PATIENTS AND METHODS: The study group consisted of women who were prospectively followed up after contacting the Motherisk Program regarding the gestational use of echinacea. This cohort was disease-matched to women exposed to nonteratogenic agents by maternal age, alcohol, and cigarette use. Rates of major and minor malformations between the groups were compared. RESULTS: A total of 206 women were enrolled in the study group after using echinacea products during pregnancy; 112 women used the herb in the first trimester. There were a total of 195 live births, including 3 sets of twins, 13 spontaneous abortions, and 1 therapeutic abortion. Six major malformations were reported, including 1 chromosomal abnormality, and 4 of these malformations occurred with echinacea exposure in the first trimester. In the control group, there were 206 women with 198 live births, 7 spontaneous abortions, and 1 therapeutic abortion. Seven major malformations were reported. There were no statistical differences between the study and control groups for any of the end points analyzed. CONCLUSIONS: This first prospective study suggests that gestational use of echinacea during organogenesis is not associated with an increased risk for major malformations.

Congenital Abnormalities↗

X-ray crystal structure of rabbit N-acetylglucosaminyltransferase I: catalytic mechanism and a new protein superfamily.

N:-acetylglucosaminyltransferase I (GnT I) serves as the gateway from oligomannose to hybrid and complex N:-glycans and plays a critical role in mammalian development and possibly all metazoans. We have determined the X-ray crystal structure of the catalytic fragment of GnT I in the absence and presence of bound UDP-GlcNAc/Mn(2+) at 1.5 and 1.8 A resolution, respectively. The structures identify residues critical for substrate binding and catalysis and provide evidence for similarity, at the mechanistic level, to the deglycosylation step of retaining beta-glycosidases. The structuring of a 13 residue loop, resulting from UDP-GlcNAc/Mn(2+) binding, provides an explanation for the ordered sequential 'Bi Bi' kinetics shown by GnT I. Analysis reveals a domain shared with Bacillus subtilis glycosyltransferase SpsA, bovine beta-1,4-galactosyl transferase 1 and Escherichia coli N:-acetylglucosamine-1-phosphate uridyltransferase. The low sequence identity, conserved fold and related functional features shown by this domain define a superfamily whose members probably share a common ancestor. Sequence analysis and protein threading show that the domain is represented in proteins from several glycosyltransferase families.

Amino Acid Sequence↗

Optical spectroscopic study of the effects of a single deoxyribose substitution in a ribose backbone: implications in RNA-RNA interaction.

The 2'-OH group in the ribose sugars of an RNA molecule plays an important role in guiding tertiary interactions that stabilize different RNA structural motifs. Deoxyribose, or 2'-OH by 2'-H, substitution in both the single-stranded and the duplex part of an RNA backbone has been routinely used to evaluate what role the 2'-OH plays in different tertiary interactions that guide an RNA-RNA contact. A deoxyribose substitution not only has the effect of removing a hydrogen bond donating group, but also introduces a sugar moiety with a preference for C2'-endo pucker in a backbone of predominantly C3'-endo sugars. This study evaluates the effects of a single deoxyribose substitution in both single-stranded and double-helical forms of RNA oligomers. A single-stranded, nonrepetitive 7-mer oligoribonucleotide (7-mer RNA) and four different variants having the same base sequence but with a single deoxyribose sugar at different positions in the strands have been studied by ultraviolet (UV) absorption, circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopy. Duplexes were formed by association with the complementary strand of the 7-mer RNA. The results show that both RNA and DNA single strands have preorganized conformations with spectral properties resembling those of A- and B-form helices, respectively, with RNA being more heterogeneous than its DNA counterpart. A single deoxyribose substitution perturbs the structure of the RNA backbone, with the effect being more pronounced in the single-stranded than in the duplex structure. The perturbation depends on the position of the 2'-H substitution in the strand.

Base Composition↗

Influence of adrenal cortex on testicular activity in the toad during the breeding season.

The aim of the present study was to determine the role of adrenals in gonadal activity in the male toad during the breeding season. Exogenous administration of corticosterone or metapyrone for 6 days inhibited adrenal delta5-3beta(delta 5-3 beta) hydroxysteroid (delta5-3beta-HSD) and testicular 17beta (17 beta) hydroxysteroid dehydrogenase (17beta-HSD) activities, decreased the serum levels of testosterone and inhibited spermatogenesis. When toads were treated with corticosterone a significant rise of serum corticosterone was noted while metapyrone treatment appeared to decrease serum corticosterone levels. It is concluded that adrenocortical hormone plays an indirect role in testicular activity in toads during the breeding season.

3-Hydroxysteroid Dehydrogenases↗

Viral IL-10 gene transfer decreases inflammation and cell adhesion molecule expression in a rat model of venous thrombosis.

Post-thrombotic inflammation probably contributes to chronic venous insufficiency, and little effective treatment exists. IL-10 is an anti-inflammatory cytokine that previously has been shown to decrease perithrombotic inflammation and thrombosis. We investigated in a rat model whether local expression of viral IL-10 (vIL-10) in a segment of vein that undergoes thrombosis would confer an anti-inflammatory effect and how this effect might be mediated. Rats underwent inferior vena cava isolation, cannulation, and instillation of saline or adenovirus encoding either beta-galactosidase or vIL-10. Two days after transfection, thrombosis was induced, 2 days after this the rats underwent gadolinium (Gd)-enhanced magnetic resonance venography exam, and the vein segments were harvested. Tissue transfection was confirmed by either RT-PCR of vIL-10 or positive 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside (X-Gal) staining. vIL-10 significantly decreased both leukocyte vein wall extravasation and area of Gd enhancement compared with those in controls, suggesting decreased inflammation. Immunohistochemistry demonstrated decreased endothelial border staining of P- and E-selectin, while ELISA of vein tissue homogenates revealed significantly decreased P- and E-selectin and ICAM-1 levels in the vIL-10 group compared with those in controls. Importantly, native cellular IL-10 was not significantly different between the groups. However, neither clot weight nor coagulation indexes, including tissue factor activity, tissue factor Ag, or von Willebrand factor levels, were significantly affected by local vIL-10 expression. These data suggest that local transfection of vIL-10 decreases venous thrombosis-associated inflammation and cell adhesion molecule expression, but does not directly affect local procoagulant activity.

Animals↗

Studies on the Interaction of Surfactants with Cationic Dye by Absorption Spectroscopy.

The interaction of methyl violet, a cationic dye, with various surfactants, viz. anionic (SDS), nonionic (Triton X-100), and cationic (CTAB), has been investigated spectrophotometrically in submicellar and micellar concentration range. While in the submicellar concentration region of SDS the higher aggregates of the dye are found, in the micellar concentration region the monomer of the dye predominates. With nonionic surfactant the dye is solubilized primarily as the monomer. CTAB produces no perturbation to the visible spectra of the dye. In the presence of strong electrolytes such as NaNO(3) and NaCl the dye aggregates are formed at a much lower SDS concentrations. Copyright 2000 Academic Press.

Journal Article↗

The reversible antifertility effect of Piper betle Linn. on Swiss albino male mice.

To study the antifertility effect of an extract (alcoholic) of the leaf-stalk of Piper betle Linn., one set of experiments with two different doses in Swiss male albino mice were evaluated. Initially, 500 mg of the leaf-stalk extractive for 30 days and then 1000 mg for next 30 days/animal/day/kg body weight were administered orally. The extract reduced fertility to 0% within 60 days. Suppression of cauda epididymal sperm count and motility (p <0.05) was observed. Biochemical parameters did not show any marked alterations in testosterone content in serum nor 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in testes although fructose content in seminal vesicles was reduced as are the weights of reproductive organs. The cholesterol content in testes increased, although not appreciably. After cessation of drug (plant extract) treatment, the altered parameters recovered. Results suggest that the contraceptive effect of the extract of leaf-stalk of Piper betle Linn. is mainly on the maturation process of spermatozoa in epididymides without influencing hystemic hormonal profiles. Withdrawal of the extract restored all altered parameters including organ weights and fertility after 60 days.

17-Hydroxysteroid Dehydrogenases↗

Molecular cloning and expression analysis of a mouse UDP-GlcNAc:Gal(beta1-4)Glc(NAc)-R beta1,3-N-acetylglucosaminyltransferase homologous to Drosophila melanogaster Brainiac and the beta1,3-galactosyltransferase family.

We have isolated a murine cDNA coding for a beta1,3-N-acetylglucosaminyltransferase enzyme ( beta3GnT). This enzyme is similar in sequence to Drosophila melanogaster Brainiac and to the murine and human beta1,3-galactosyltransferase family of proteins. The mouse beta 3GnT protein is 397 amino acids in length and contains 7 cysteine residues that are conserved in the human orthologue. beta 3GnT is a type II membrane protein localized to the Golgi apparatus. Enzyme assays with recombinant mouse beta 3GnT reveal that it has a preference for acceptors with Gal(beta1-4)Glc(NAc) at the non-reducing termini. Proton NMR analysis of product showed incorporation of GlcNAc in beta1,3 linkage to the terminal Gal of Gal(beta1-4)Glc(beta1-O-benzyl). Northern blot analysis revealed the presence of a single 3.0[emsp4 ]kb transcript in all adult mouse and human organs tested, with highest levels in the kidney, liver, heart and placenta. The beta 3GnT gene is also expressed in a number of tumor cell lines. The human orthologue of beta 3GnT is located on chromosome 2pl5.

Amino Acid Sequence↗

Life-cycle differentiation in Trypanosoma brucei: molecules and mutants.

Differentiation between bloodstream and tsetse midgut procyclic forms during the life cycle of the African trypanosome is an attractive model for the analysis of stage-regulated events. In particular, this transformation occurs synchronously, there are well-defined markers for stage-regulated processes and cell lines with specific defects in differentiation have been identified. This combination of tools, combined with the developing Trypanosoma brucei genome database is allowing its underlying controls to be investigated at the molecular and cytological levels. This paper examines some recent discoveries that illuminate some of the key events during trypanosome life-cycle progression.

Animals↗

A novel selection regime for differentiation defects demonstrates an essential role for the stumpy form in the life cycle of the African trypanosome.

A novel selection scheme has been developed to isolate bloodstream forms of Trypanosoma brucei, which are defective in their ability to differentiate to the procyclic stage. Detailed characterization of one selected cell line (defective in differentiation clone 1 [DiD-1]) has demonstrated that these cells are indistinguishable from the wild-type population in terms of their morphology, cell cycle progression, and biochemical characteristics but are defective in their ability to initiate differentiation to the procyclic form. Although a small proportion of DiD-1 cells remain able to transform, deletion of the genes for glycophosphatidyl inositol-phospholipase C demonstrated that this enzyme was not responsible for this inefficient differentiation. However, the attenuated growth of the Delta-glycophosphatidyl inositol-phospholipase C DiD-1 cells in mice permitted the expression of stumpy characteristics in this previously monomorphic cell line, and concomitantly their ability to differentiate efficiently was restored. Our results indicate that monomorphic cells retain expression of a characteristic of the stumpy form essential for differentiation, and that this is reduced in the defective cells. This approach provides a new route to dissection of the cytological and molecular basis of life cycle progression in the African trypanosome.

Aconitic Acid↗

Application of K-nearest neighbors algorithm on breast cancer diagnosis problem.

This paper addresses the Breast Cancer diagnosis problem as a pattern classification problem. Specifically, this problem is studied using the Wisconsin-Madison Breast Cancer data set. The K-nearest neighbors algorithm is employed as the classifier. Conceptually and implementation-wise, the K-nearest neighbors algorithm is simpler than the other techniques that have been applied to this problem. In addition, the Knearest neighbors algorithm produces the overall classification result 1.17% better than the best result known for this problem.

Algorithms↗