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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 451 records · Page 25Linked to original sources
PubMed1998

Histologic chorioamnionitis & its association with prematurity in a hospital-based study.

This prospective study was undertaken to study the occurrence of histologic chorioamnionitis and determine its association with prematurity; and to assess whether colonization of the genital tract of pregnant women by genital mycoplasmas or Chlamydia trachomatis is a risk factor for histologic chorioamnionitis. A total of 268 women with singleton pregnancies of over 26 weeks gestation were subjected to high vaginal cultures of genital mycoplasmas and endocervical specimens for chlamydia antigen. Placental histopathology was performed on multiple sections. Histologic chorioamnionitis was documented in 22.4 per cent (60/208) placentae. Genital tract colonization with Ureaplasma urealyticum or C. trachomatis was not a risk factor for histologic chorioamnionitis. Neonates born in association with histologic chorioamnionitis had a mean birth weight 111 g lower than those born without this lesion (2626.9 +/- 702 g vs 2737.8 +/- 500 g, NS). The relative risk (95% confidence interval) of prematurity in the presence of histologic chorioamnionitis was 1.49 (0.87-2.53). Analysis of linear trend in proportions for prevalence of histologic chorioamnionitis with decreasing gestation showed a significant association (P = 0.047, 1-tail). These results taken together suggest that histologic chorioamnionitis may be a risk factor of prematurity, but of only a modest magnitude.

Chorioamnionitis↗
PubMed1997

Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease.

Recent evidence supports a role for estrogens in both normal neural development and neuronal maintenance throughout life. Women spend 25-33% of their life in an estrogen-deprived state and retrospective studies have shown an inverse correlation between dose and duration of estrogen replacement therapy (ERT) and incidence of Alzheimer's disease (AD), suggesting a role for estrogen in the prevention and/or treatment of neurodegenerative diseases. To explore these observations further, an animal model was developed using ovariectomy (OVX) and ovariectomy with estradiol replacement (E2) in female Sprague-Dawley rats to mimic postmenopausal changes. Using an active-avoidance paradigm and a spatial memory task, the effects of estrogen deprivation were tested on memory-related behaviors. OVX caused a decline in avoidance behavior, and estrogen replacement normalized the response. In the Morris water task of spatial memory, OVX animals showed normal spatial learning but were deficient in spatial memory, an effect that was prevented by estrogen treatment. Together these data indicate that OVX in rats results in an estrogen-reversible impairment of learning/memory behavior. Because a plethora of information has been generated that links decline in memory-related behavior to dysfunction of cholinergic neurons, the effects of estrogens on cholinergic neurons were tested. We demonstrated that OVX causes a decrease in high affinity choline uptake and choline acetyltransferase activity in the hippocampus and frontal cortex; ERT reverses this effect. Further, we showed that estrogens promote the expression of mRNA for brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), 2 neurotrophic substances that have been shown to ameliorate the effects of age and injury on cholinergic neurons. Tissue culture models were used to evaluate whether estrogen treatment increases the survival of neurons when exposed to a variety of insults. 17-beta-Estradiol (beta-E2) protects cells from the neurotoxic effects of serum deprivation and hypoglycemia in human neuroblastoma cell lines. We have also observed that 17-alpha-estradiol (alpha-E2), a weak estrogen, shows neuroprotective efficacy in the SK-N-SH cell line at concentrations equivalent to beta-E2. Finally, we have observed that tamoxifen, a classic estrogen antagonist, blocks only one-third of the neuroprotective effects of either alpha-E2 or beta-E2. Collectively, these results indicate that estrogen is behaviorally active in tests of learning/ memory; activates basal forebrain cholinergic neurons and neurotrophin expression; and is neuroprotective for human neuronal cultures. We conclude that estrogen may be a useful therapy for AD and other neurodegenerative diseases.

Alzheimer Disease↗
PubMed1997

Functions and specificity of T cells following nucleic acid vaccination of mice against Mycobacterium tuberculosis infection.

The 38-kDa glycolipoprotein of Mycobacterium tuberculosis has been known to evoke prominent T cell and Ab responses in patients with active tuberculosis. In this study, we investigated its protective capacity using plasmid DNA immunization in a mouse experimental model. Prior knowledge of several antigenic determinants has been beneficial for analyzing the phenotype and specificity of T cells, which determine the efficacy of this vaccination procedure. C57BL/6 mice responded to the 38-kDa gene-pcDNA3 plasmid with strong CD4+ Th1 and CD8+ cytotoxic T cell responses of the IFN-gamma-producing Tc1 phenotype. After challenge with virulent tubercle bacilli, the bacterial load in the spleens and lungs of vaccinated mice was reduced to a level similar to that imparted by Mycobacterium bovis Bacille Calmette-Guérin vaccination. Notably, the specificity of CD4+ and CD8+ T cells from DNA-vaccinated and tubercle-infected mice was found to be strikingly different in respect of several peptide epitopes. The identified peptides recognized by T cells from protected mice are of further interest for the development of subunit-based vaccines against tuberculosis.

Animals↗
PubMed1997

Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).

The transcription of the murine Ig heavy chain locus is regulated not only by the intronic enhancer, E mu, but also by a 3' regulatory region located downstream of the C alpha membrane exon. Several DNase I-hypersensitive sites (hs1-4) and enhancer elements (e.g., C alpha3'E) have been identified in this 3' regulatory region, and some of these were suggested to comprise a locus control region. However, little is known about the coordinate regulation or function of these individual elements. Here we provide evidence that C alpha3'E and hs3 are virtually mirror images of each other and demarcate the edges of an approximately 25-kb region of quasi-dyad symmetry with 3'alphaE(hs1,2) at its center. Flanking 3'alphaE(hs1,2) are inverted repeats and families of repetitive sequences uniquely located in this region. We have observed that, like 3'alphaE(hs1,2) and hs3, C alpha3'E is DNase I hypersensitive in plasma cell lines, but not in a pre-B cell line. Additionally, we found that C alpha3'E and hs3 show significant transcriptional synergy in transfection assays only in a plasma cell line. The DNA topology of the 3' regulatory region coupled with new and existing data on the activity of its individual enhancers during B cell differentiation lead us to propose a biphasic model for the activity of this region. According to our model, one unit, consisting of the 3'-most enhancer, hs4, is active early and throughout B cell development. The second unit, which comprises C alpha3'E, 3'alphaE(hs1,2), and hs3, becomes active later in development, when it contributes to such processes as class switching and increased levels of Ig heavy chain gene transcription in plasma cells.

Animals↗
PubMed1997

A global scale to measure the quality of the family environment.

BACKGROUND: Simple, reliable measures of the quality of the environment in which a child was reared that can be used in clinical research and practice are lacking. METHOD: The reliability and validity of a global scale to retrospectively appraise the quality of that environment were examined. Fifty-three clinicians from 4 centers in Australia and 1 in Hong Kong, People's Republic of China, used the scale to rate 7 case vignettes; 4 clinicians rated 20 medical records, and 49 rated 211 subjects after clinical interviews. RESULTS: Interrater reliability (intraclass correlation coefficient) was 0.82 (time 1) and 0.84 (time 2) for case vignettes, 0.90 for medical records, and 0.89 for clinical interviews. Consistency in time was high (r = 0.91). Lower ratings, indicative of a less adequate environment, were associated with a clinical diagnosis of oppositional defiant or conduct disorder. CONCLUSIONS: Our simple-to-use scale appears to measure reliably a relevant clinical construct and fills a gap among the instruments available. Ratings may be useful as a cost-effective index to consider in outcome studies, when examining response to treatment, or in other clinical research.

Adolescent↗
PubMed1997

Construction and characterization of genetically-marked bivalent anti-Shigella dysenteriae 1 and anti-Shigella flexneri Y live vaccine candidates.

Bivalent vaccine candidates were developed against Shigella dysenteriae 1 and Shigella flexneri, which are among the most frequent causative agents of shigellosis in developing countries. The rfp and rfb gene clusters, which code for S. dysenteriae serotype 1 O-antigen biosynthesis, were inserted into an arsenite resistance minitransposon and randomly integrated into the attenuated S. flexneri aroD serotype Y strain SFL124. Nine recombinant clones that efficiently expressed both homologous and heterologous O-antigens were obtained. Southern blot analysis showed that in one clone the S. dysenteriae 1 genes had integrated into the chromosome, whereas in all the others they had integrated into the virulence plasmid. All recombinant clones exhibited normal growth characteristics, were able to invade and survive within eukaryotic cells to the same extent as the parental strain, and expressed efficiently the recombinant lipopolysaccharide within invaded cells. Immunization of mice with two of the recombinant clones resulted in the production of antibodies specific for both homologous and heterologous O-antigens. The recombinant clones constitute promising vaccine candidates which can readily be distinguished from endemic shigellae by their non-antibiotic resistance marker.

Animals↗
PubMed1997

Effect of amiloride A Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning: possible involvement of resident cardiac mast cells.

The present study was designed to investigate the effect of amiloride, a Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning in isolated rat heart. Four episodes of ischaemic preconditioning and amiloride (174 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and infarct size in hearts subjected to 30 min of global ischaemia followed by 120 min of reperfusion. Amiloride (174 microM) administered during ischaemic preconditioning (Amiloride in Ischaemic Preconditioning), produced no marked effect on LDH and CK release and infarct size. Ischaemic preconditioning and amiloride treatment significantly reduced ischaemia/reperfusion induced release of mast cell peroxidase (MPO). Four episodes of pH (20 mm of ammonium chloride) preconditioning also produced cardioprotection and decreased ischaemia/reperfusion induced release of MPO. It is interesting to note that a significant increase in release of MPO was observed immediately after ischaemic preconditioning and the release was inhibited by amiloride. Moreover, similar increase in MPO release was noted immediately after pH preconditioning. These findings tentatively suggest that ischaemic preconditioning and pH preconditioning produced cardioprotective effect by activating Na+/H+ exchange and consequent degranulation of resident cardiac mast cells. Amiloride administered during ischaemic preconditioning attenuated the cardioprotective effect of ischaemic preconditioning.

Amiloride↗
PubMed1997

cDNA cloning, expression, and rapid purification of a Kunitz-type winged bean chymotrypsin inhibitor.

A 183-residue Kunitz-type winged bean chymotrypsin inhibitor (WbCI), inhibits its cognate protease at a molar ratio of 1:2, instead of the usual ratio of 1:1 common to other members of the family. From the cDNA pool obtained by reverse transcription of the poly(A)+ RNA of the developing winged bean seeds, the structural gene of WbCI has been amplified by PCR using primers designed to delete the 24-residue signal peptide and introduce EcoRI and SalI sites at the ends of the amplified DNA. The latter is cloned in pBluescript and the insert has been sequenced to confirm its authenticity. Subcloning it in pTrc99A, a high-expression vector for Escherichia coli has generated a chimeric plasmid, pTrc-WbCI, which has a reading frame for a recombinant protein (rWbCI), having an additional tripeptide (M-E-F) fused to the N-terminus of WbCI. The expression of rWbCI has been ascertained by immunoblot analysis using rabbit anti-WbCI immune sera and quantitated by ELISA. The optimal conditions for the induction of the protein by IPTG, avoiding complications of protein-body formation, have also been standardized. rWbCI has been purified by a simple and rapid procedure of immunoaffinity chromatography, with an overall yield of 1.3 mg/g wet cell. SDS-PAGE analysis shows the presence of a single protein band, attesting to the homogeneity of the preparation; functionally, it is indistinguishable from WbCI since they inhibit alpha-chymotrypsin in an identical manner.

Animals↗
PubMed1997

Laser reflectance imaging of human organs and comparison with perfusion images.

Based on the principle of backscattering of laser radiation from tissues, a non-invasive PC-AT based reflectance imaging technique is developed. The laser beam from a semiconductor laser operating at 670 nm is guided to the tissue site by an optical fibre. The backscattered radiation is collected by another fibre placed in the same probe, and is detected by a photodiode-amplifier assembly. This probe is moved manually over the organs under observation, and the data after the ADC, interpolation and median filtering are displayed in the form of reflectance image of the organ along with grey scale. By this technique images of the human hands and forearms are obtained, which depend on the variations in their colour, composition and blood flow. A comparison is made with perfusion images, obtained by a Periflux laser Doppler flowmeter. These show that the reflectance images provide greater details of the tissue structure than the perfusion images.

Adult↗
PubMed1997

Computerised multiparametric analysis from images of blood flow through frog mesenteric arterial bifurcation.

A computerised multiparametric procedure is developed to analyse the images of blood flow through various locations of the mesenteric arterial bifurcation of frog. The data are recorded by a video microscopic system and, after digitisation and pre-processing, are analysed by an IBM PC/AT based image processing system to obtain erythrocyte and velocity distribution profiles by axial tomographic and image velocimetry techniques, respectively. The vessel radius, haematocrit, blood flow through main and branch arteries and flow separation zones are determined from the data by various analytical procedures. In contrast to the earlier techniques the data are obtained from the same location of the vessel and thus the variability in flow parameters is minimised.

Algorithms↗
PubMed1997

Description of a Blastocystis species from Rattus norvegicus.

Two isolates (WR1 and WR2) of Blastocystis from laboratory-bred Wistar rats were axenized by a method of colony growth in soft agar combined with antibiotic treatment. The colonies were cultured in Iscove's modified Dulbecco's medium (IMDM) and Bacto agar mixture supplemented with 10% horse serum in the presence of thioglycollate. The cells from the colonies had an ameboid outline with a central body. Large inclusions were seen in the central body of some cells. Some granular forms were also found. In the axenic culture of isolate WR2, about one-third of the organisms were granular forms. Cysts were found in the axenic culture of both isolates. This is the first report of such cyst formation in in vitro culture. The karyotypic patterns of both isolates of the rat Blastocystis were analyzed by pulsed-field gel electrophoresis (PFGE). A total of 13 chromosomal bands were separated, ranging from 1.86 Mb to 295 kb. The karyotypic patterns of the rat Blastocystis were different from those of B. hominis and reptilian Blastocystis. On the basis of the above-mentioned differences, the rat Blastocystis is assigned as B. ratti sp. nov.

Animals↗
PubMed1997

Experimental Blastocystis hominis infection in laboratory mice.

Young (less than 8 weeks old) immunocompetent BALB/c mice became infected with Blastocystis hominis after inoculation of fecal cysts orally and of in vitro axenic-culture forms intracecally. This study confirmed that the fecal cyst was the form responsible for external transmission and that the mode of transmission was by the fecal-oral route. The infection was self-limiting and the infected BALB/c mice appeared normal except that some of them showed weight loss and lethargy. Both vacuolar and granular forms were found in the cecum, but only cyst forms were observed in the colon. Histological examination of the cecum and colon showed intense inflammatory-cell infiltration, edematous lamina propria, and mucosal sloughing. It is apparent that although B. hominis is not invasive, it is capable of causing pathogenesis in BALB/c mice.

Animals↗
PubMed1997

Salience of visual parts.

Many objects have component parts, and these parts often differ in their visual salience. In this paper we present a theory of part salience. The theory builds on the minima rule for defining part boundaries. According to this rule, human vision defines part boundaries at negative minima of curvature on silhouettes, and along negative minima of the principal curvatures on surfaces. We propose that the salience of a part depends on (at least) three factors: its size relative to the whole object, the degree to which it protrudes, and the strength of its boundaries. We present evidence that these factors influence visual processes which determine the choice of figure and ground. We give quantitative definitions for the factors, visual demonstrations of their effects, and results of psychophysical experiments.

Analysis of Variance↗
PubMed1997

Biodegradable norethindrone (NET:cholesterol) contraceptive implants: phase II-A: a clinical study in women.

Safety, contraceptive efficacy and biodegradability of subdermal norethindrone (NET)-cholesterol implants (Anuelle) were investigated in 19 healthy, sexually active women. Mean serum NET levels in women with four and five pellets, containing 174 mg and 266.5 mg NET, showed a "burst-effect" of 3.17 and 3.71 ng/ml, respectively, within 24 h post implantation. Subsequently, for the four- and five-pellet groups, respectively, the levels declined from 0.75 to 0.40 ng/ml and 1.05 to 0.61 ng/ml during the months 12-15, from 0.40 to 0.11 ng/ml and 0.61 to 0.25 ng/ml up to month 36. The serum NET levels were undetectable at 36 months and beyond, indicating complete biodegradability of NET pellets. Serum E2 levels remained within normal limits (> 50 pg/ml), whereas serum P indicated anovulatory cycles in 78% of the four-pellet group and 99% of the five-pellet group. FSH and LH levels were subnormal and acyclic. Plasma lipids showed reduced total and LDL cholesterol and triglycerides. HDL cholesterol remained unchanged. Drug-related adverse effects were essentially limited to irregular bleeding. There were no pregnancies in either group.

Adolescent↗
PubMed1997

Survival of Blastocystis hominis clones after exposure to a cytotoxic monoclonal antibody.

Our previous studies have shown that monoclonal antibodies (MAbs) to Blastocystis hominis react mainly with carbohydrate epitopes, while 1 MAb (1D5) reacts specifically with a protein of 30.5 kDa. In the present study, 3 monoclonal antibodies (1D5, 1E7 and 4F7) were used in immunogold localization. 1E7 and 4F7 were found to react primarily with the surface coat, while 1D5 was plasma membrane-specific. In the presence of complement, only 1D5 exhibited a cytotoxic effect on B. hominis whereas 1E7 and 4F7 did not, suggesting that the surface coat of B. hominis could serve as an immunological barrier against host antibodies. Using a recently described agar plating method, only 1D5 exhibited significant (P < 0.01) complement-independent cytotoxicity to B. hominis, inhibiting colony growth at low concentrations. Parasites that had been exposed to 1D5 were morphologically smaller than those that were not exposed to this MAb. Colonies that grew in the presence of 1D5 were isolated and grown in liquid medium containing increasing amounts of the cytotoxic MAb. Two clones that grew well in liquid medium containing 1D5 were also able to develop into colonies in soft agar. This study has shown that the 30.5 kDa protein found on the plasma membrane of B. hominis is a functionally important protein and that not all cells within a certain population would be susceptible to the cytotoxic effects of 1D5. These findings suggest that a heterogenous population exists in continuously maintained cultures of B. hominis.

Animals↗
PubMed1997

Endogenous protein phosphorylation and protein kinase activity in winged bean.

In winged bean (Psophocarpus tetragonolobus) protein kinases (E.C. 2.7.1.37) were found in all tissues studied. There was a significant increase in kinase activity during seed development, with a concomitant enhancement in the phosphorylation of a number of polypeptides; this was reversed in germinating seed cotyledons. Protein phosphorylation was apparently correlated with the increase in the protein content of the developing seed and the growing axis. At least three distinct autophosphorylating proteins could be distinguished in the developing seeds after SDS-PAGE, indicating the presence of different types of protein kinases in winged bean.

Fabaceae↗