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Biomedical subjects

S Srinivasan

Publications and source records attributed to S Srinivasan.

At least 109 records · Page 6Linked to original sources
PubMed2000

Aging-induced osteopenia in avian cortical bone.

Cortical bone loss contributes substantially to the degradation of skeletal integrity associated with aging. However, animal models that closely mimic age-related alterations in cortical bone are limited. The objective of this study was to determine if aged rooster cortical bone demonstrates phenotypic alterations similar to those observed in aged human cortical bone (i.e., expansion of the endocortical and periosteal envelopes and elevated cortical porosity). When compared with young adult roosters, aged roosters demonstrated significant expansion of the endocortical (16%) and periosteal (10%) envelopes, resulting in significantly increased cross-sectional moments of inertia. In addition, aged rooster bone demonstrated significantly elevated cortical porosity (51%) and average area of porosity (83%). We conclude that rooster bone demonstrates age-related adaptations similar to those of humans at both tissue and cellular levels, and may therefore represent a relatively useful, inexpensive animal model for investigating the mechanisms of age-related bone loss.

Age Factors↗
PubMed2000

Comparison of blood-film microscopy, the OptiMAL dipstick, Rhodamine-123 fluorescence staining and PCR, for monitoring antimalarial treatment.

In an attempt to see if the OptiMAL dipstick (Flow Inc., Portland, OR) can be used to monitor antimalarial treatment, a pilot study of 17 patients with Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases in London, U.K., was conducted. Sequential, follow-up, blood specimens were obtained from day 1 to day 3, 4 or 5 post-admission. Thin and thick films prepared from these samples were examined for the presence of malarial parasites, and the intensities of parasitaemia were estimated. In addition, each specimen was tested with the OptiMAL dipstick, Rhodamine-123 fluorescence staining and, on specimens collected on day 1 and the last follow-up before discharge, by a PCR-based test. The results showed that OptiMAL has good sensitivity for the initial diagnosis of P. falciparum malaria and also mirrors the decline in viability of the parasites on treatment, giving the potential to follow the efficacy of drug treatment. The results of the PCR-based tests were still positive when the blood film and OptiMAL result were negative. The OptiMAL dipstick compared well with blood-film microscopy for monitoring antimalarial treatment and could be a useful replacement for microscopy to monitor treatment in places where facilities for microscopy are either lacking or inadequate. In developed countries it could be a useful adjunct to blood-film microscopy, and it might permit a reduction in the duration of hospitalization and give an early warning of treatment failure.

Humans↗
PubMed2000

New insights into neural injury, repair, and adaptation in visceral afferents and the enteric nervous system.

In this brief review, we focus on some of the proposed mechanisms of injury in peripheral visceral afferents (sensory) pathways and the enteric nervous system, including the interstitial cells of Cajal. Injury involving afferent neurons is discussed because of the relevance of these neurons to the pathophysiology of pain syndromes. The effect of various noxious stimuli on sensory and enteric neural function is examined. Finally, we discuss recent data on the role of autoimmune antibodies in neuronal injury in systemic diseases, such as diabetes mellitus and the Lambert-Eaton myasthenic syndrome. Neither central nervous system manifestations of peripheral nerve injury nor functional bowel disorders are addressed in this review. An improved understanding of the pathophysiology of peripheral neuronal dysfunction will probably result in new treatment strategies for a broad range of gastrointestinal disorders, including constipation, pseudo-obstruction, ileus, and inflammatory bowel disorders.

Journal Article↗
PubMed2000

Retinoic acid stimulates immature lung fibroblast growth via a PDGF-mediated autocrine mechanism.

All trans-retinoic acid (RA) enhances alveolarization in neonates and reinitiates alveolarization in emphysematous adult rat lungs, suggesting that RA may stimulate cell proliferation by upregulating growth factor ligand and/or receptor expression either indirectly or directly by acting on RA-responsive genes encoding growth factors. We report that RA and 1,25-dihydroxyvitamin D(3) (Vit D), alone and in combination, significantly increase [(3)H]thymidine incorporation in cultured fetal and postnatal rat lung fibroblasts (P < 0.05). The greatest increase (11-fold) was seen in 4-day cells treated with the two agents in combination (P < 0.0001). [(3)H]thymidine incorporation was age dependent. The greatest response to RA occurred in 4-day fibroblasts (P < 0.01), whereas the response to Vit D was greatest in embryonic day 20 fibroblasts (P < 0.001). Neutralizing antibody to platelet-derived growth factor (PDGF)-AB decreased [(3)H]thymidine incorporation in response to RA alone or in combination with Vit D, indicating a role for PDGF. Expression of mRNAs for PDGF-A and PDGF receptor (PDGFR)-alpha and -beta was upregulated at the transcriptional level in an age- and treatment-dependent manner. Thus exogenous RA may influence alveolarization by stimulating fibroblast proliferation through a PDGF-mediated autocrine mechanism, which is enhanced when RA and Vit D are administered in combination.

Aging↗
PubMed2000

Acquisition and analysis of brainstem auditory evoked responses of normal and diseased subjects by spectral estimation.

Human brainstem auditory evoked responses (BAERs) are sensory evoked potentials that can be recorded within a few milliseconds following a transient acoustic stimulus (click signal). This paper suggests a novel technique to clearly demarcate normals and patients with complaints of vertigo and deafness by computing hitherto unused power spectral parameters from the BAER signals recorded on them. The BAER spectrum of normal subjects contains three main frequency components, i.e. low-, mid- and high-frequency components around 100, 500 and 1000 Hz, respectively, which is not so in the case of diseased subjects. The spectral parameters, i.e. the mean power frequency, median frequency, the ratios of the integrated power at dominant frequencies to that of the total power in spectrum and change in spectral power (CP) between these dominant frequency components are used to classify the recorded BAER signals into those of normals and the patients, and aid the clinician in quick and better diagnosis. The ranges of CP are estimated for the different groups and appear to be the most dominant parameter in the classification of the BAER signals.

Adolescent↗
PubMed2000

Synthesis and anti-varicella-zoster virus activity of some novel bicyclic nucleoside inhibitors: effect of enhanced aqueous solubility.

We have recently reported the discovery of an entirely new category of potent antivaricella-zoster virus agents based on novel deoxynucleoside analogues bearing unusual fluorescent bicyclic furo base moieties. Initial studies revealed an absolute requirement of a long alkyl side-chain, with an optimal length of C8-C10, for antiviral activity. However, the impact of this requirement on the physical properties of these compounds is high: inherent lipophilicity and extremely poor aqueous solubility, which may limit the use of these nucleosides as drugs. In order to address this issue, we have now prepared a new series of analogues, bearing ether and glycol type side-chains, designed to improve the aqueous solubility of the compounds. Synthesis of target nucleosides involved Pd-catalysed coupling of terminal alkynes with 5-iodo-2'-deoxyuridine. The 5-alkynyl nucleosides thus obtained were then treated with copper (I) iodide to produce the desired bicyclic analogues. As anticipated, the new compounds exhibited a dramatic increase in aqueous solubility, although antiviral activity was significantly reduced. A possible correlation between antiviral activity and overall compound lipophilicity is discussed.

Antiviral Agents↗
PubMed2000

Processing of the Drosophila Sog protein creates a novel BMP inhibitory activity.

Structurally unrelated neural inducers in vertebrate and invertebrate embryos have been proposed to function by binding to BMP4 or Dpp, respectively, and preventing these homologous signals from activating their receptor(s). In this study, we investigate the functions of various forms of the Drosophila Sog protein using the discriminating assay of Drosophila wing development. We find that misexpression of Drosophila Sog, or its vertebrate counterpart Chordin, generates a very limited vein-loss phenotype. This sog misexpression phenotype is very similar to that of viable mutants of glass-bottom boat (gbb), which encodes a BMP family member. Consistent with Sog selectively interfering with Gbb signaling, Sog can block the effect of misexpressing Gbb, but not Dpp in the wing. In contrast to the limited BMP inhibitory activity of Sog, we have identified carboxy-truncated forms of Sog, referred to as Supersog, which when misexpressed cause a broad range of dpp(-) mutant phenotypes. In line with its phenotypic effects, Supersog can block the effects of both misexpressing Dpp and Gbb in the wing. Vertebrate Noggin, on the other hand, acts as a general inhibitor of Dpp signaling, which can interfere with the effect of overexpressing Dpp, but not Gbb. We present evidence that Sog processing occurs in vivo and is biologically relevant. Overexpression of intact Sog in embryos and adult wing primordia leads to the developmentally regulated processing of Sog. This in vivo processing of Sog can be duplicated in vitro by treating Sog with a combination of the metalloprotease Tolloid (Tld) plus Twisted Gastrulation (Tsg), another extracellular factor involved in Dpp signaling. In accord with this result, coexpression of intact Sog and Tsg in developing wings generates a phenotype very similar to that of Supersog. Finally, we provide evidence that tsg functions in the embryo to generate a Supersog-like activity, since Supersog can partially rescue tsg(-) mutants. Consistent with this finding, sog(- )and tsg(-) mutants exhibit similar dorsal patterning defects during early gastrulation. These results indicate that differential processing of Sog generates a novel BMP inhibitory activity during development and, more generally, that BMP antagonists play distinct roles in regulating the quality as well as the magnitude of BMP signaling.

Animals↗
PubMed2000

Toward improved health: disaggregating Asian American and Native Hawaiian/Pacific Islander data.

The 2000 census, with its option for respondents to mark 1 or more race categories, is the first US census to recognize the multiethnic nature of all US populations but especially Asian Americans and Native Hawaiians/Pacific Islanders. If Asian Americans and Native Hawaiians/Pacific Islanders have for the most part been "invisible" in policy debates regarding such matters as health care and immigration, it has been largely because of a paucity of data stemming from the lack of disaggregated data on this heterogeneous group of peoples. Studies at all levels should adhere to these disaggregated classifications. Also, in addition to oversampling procedures, there should be greater regional/local funding for studies in regions where Asian American and Native Hawaiian/Pacific Islander populations are substantial.

Asian↗
PubMed2000

Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction.

We hypothesized that diabetic sensory neuropathy is associated with activation of apoptosis and concomitant mitochondrial dysfunction. Studies were performed in excised intact and acutely dissociated dorsal root ganglion (DRG) neurons from control and streptozotocin-induced diabetic rats with decreased peripheral nerve conduction velocities (NCV). Apoptosis was increased in acutely dissociated DRG neurons from 3- to 6-week-old diabetic rats. Basal mitochondrial membrane potential (deltapsi) was significantly more positive in DRG neurons from diabetic rats. Depolarization with glutamate resulted in significantly more positive deltapsi and delayed recovery of deltapsi in neurons from diabetic rats. Restoration of euglycemia for 2 weeks with insulin implants normalized NCV, deltapsi, and apoptosis. Intact and acutely dissociated neurons from diabetic rats demonstrated decreased Bcl-2 levels and translocation of cytochrome C from the mitochondria to the cytoplasm. Neither levels of Bax nor levels of Bcl-XL were altered in diabetic neuropathy. Apoptosis associated with mitochondrial dysfunction may contribute to the pathogenesis of diabetic sensory neuropathy.

Animals↗
PubMed2000

Discovering missed synonymy in a large concept-oriented Metathesaurus.

The Unified Medical Language System (UMLS) [1, 2] Metathesuarus is concept-oriented; its goal is to unite all names with identical meaning in a single Concept. The names come from its constituent vocabularies or "sources"--a wide variety of biomedical terminologies including many controlled vocabularies and classifications used in patient records, administrative health data, bibliographic, research, full-text, and expert systems. Many offer little definitional information, and many are not themselves concept-oriented, so identifying synonymy is a challenging semantic task [3]. The rapidly increasing size of the Metathesaurus makes the task daunting, demanding effective computational support; there are more than 1.5 million names for 730,000 concepts in the January 2000 release. Vocabularies are added and updated using sophisticated lexical matching, selective algorithms, and expert review [4, 5, 6]. Yet the result is imperfect; we have discovered and corrected missed synonymy in approximately 1% of previously released concepts each year. This paper reviews general methods for finding missed synonymy and describes several specific novel approaches which we have found effective.

Algorithms↗
PubMed2000

Fetal echocardiography.

Since the first report of fetal echocardiography in 1972 by Winsberg, several advances in ultrasound technology have occurred allowing detailed evaluation of cardiac anatomy in the second trimester fetus. Fetal echo is indicated in high risk pregnancies where the chances of fetus having a congenital heart disease (CHD) are likely to be high e.g., in fetus with extracardiac anomalies picked up on obstetric ultrasound, those with a history of CHD in family, maternal diabetes (especially insulin dependent), maternal connective tissue disorder etc. The reported sensitivity of fetal echo has ranged from 4-96% in various series depending upon the equipment, level of training, study design and examination technique. Although many CHD can be detected in four chamber view, an important group malformations that would need early intervention are likely to be missed. Hence a detailed echocardiographic examination including the outflow views must be done. Defects like atrial septal defect and patent ductus arteriosus cannot be diagnosed in fetal echo, as these are part of normal fetal physiology. Other CHD like coarctation of aorta, small ventricular septal defects, mild valvular stenosis, partial anomalous pulmonary venous drainage are also difficult to diagnose. Ultrasound assessment of fetus, however, has a clear role in the diagnosis, monitoring and management of fetuses with sustained arrhythmias. Prenatal diagnosis of CHD helps in planning the optimal management of the baby e.g. a fetus with a ductus dependent lesion can be planned to be delivered in a tertiary care centre for stabilization and early initiation of prostaglandin therapy to avoid acidosis and organ damage. Future of fetal medicine lies in fetal cardiac surgery for which echocardiography will play a very important role.

Echocardiography↗
PubMed1999

The prespore vesicles of Dictyostelium discoideum. Purification, characterization, and developmental regulation.

The coordinate fusion of the prespore vesicles (PSVs) with the plasma membrane at the terminal stage of spore differentiation in Dictyostelium discoideum is an important example of developmentally regulated protein secretion. However, little is known about the composition of the vesicles, the molecular signals regulating secretion, or the mechanics of the membrane fusion. Taking a biochemical approach, we purified PSVs from different developmental stages. These preparations are highly enriched for their specific cargo of spore coat proteins while devoid of markers for other cellular compartments. Electron microscopic observations show that the PSV preparations are homogenous, with the soluble spore coat protein PsB/SP85 distributed throughout the lumen and the acid mucopolysaccharide localized in the central core. During development the PSVs increase in size and density concomitant with an increase in their protein cargo. The PSVs contain approximately 80 proteins, and we have identified a PSV-specific GTP-binding protein that may be involved in regulating vesicle fusion. The PSVs are not clathrin-coated and do not contain the SpiA spore coat protein. The PSV preparations are ideal for a global proteome analysis to identify proteins involved in signal reception, vesicle movement, docking, and fusion in this developmentally regulated organelle.

Animals↗
PubMed1999

Two invariant tryptophans on the alpha1 subunit define domains necessary for GABA(A) receptor assembly.

Two invariant tryptophan residues on the N-terminal extracellular region of the rat alpha1 subunit, Trp-69 and Trp-94, are critical for the assembly of the GABA(A) (gamma-aminobutyric acid, type A) receptor into a pentamer. These tryptophans are common not only to all GABA(A) receptor subunits, but also to all ligand-gated ion channel subunits. Converting each Trp residue to Phe and Gly by site-directed mutagenesis allowed us to study the role of these invariant tryptophan residues. Mutant alpha1 subunits, coexpressed with beta2 subunits in baculovirus-infected Sf9 cells, displayed high affinity binding to [(3)H]muscimol, a GABA site ligand, but no binding to [(35)S]t-butyl bicyclophosphorothionate, a ligand for the receptor-associated ion channel. Neither [(3)H]muscimol binding to intact cells nor immunostaining of nonpermeabilized cells gave evidence of surface expression of the receptor. When expressed with beta2 and gamma2 polypeptides, the mutant alpha1 polypeptides did not form [(3)H]flunitrazepam binding sites though wild-type alpha1 polypeptides did. The distribution of the mutant receptors on sucrose gradients suggests that the effects on ligand binding result from the inability of the mutant alpha1 subunits to form pentamers. We conclude that Trp-69 and Trp-94 participate in the formation of the interface between alpha and beta subunits, but not of the GABA binding site.

Amino Acid Sequence↗
PubMed1999

Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity.

This study was undertaken to determine the modulation of uterine function by chorionic gonadotrophin (CG) in a nonhuman primate. Infusion of recombinant human CG (hCG) between days 6 and 10 post ovulation initiated the endoreplication of the uterine surface epithelium to form distinct epithelial plaques. These plaque cells stained intensely for cytokeratin and the proliferating cell nuclear antigen. The stromal fibroblasts below the epithelial plaques stained positively for alpha-smooth muscle actin (alphaSMA). Expression of alphaSMA is associated with the initiation of decidualization in the baboon endometrium. Synthesis of the glandular secretory protein glycodelin, as assessed by Western blot analysis, was markedly up-regulated by hCG, and this increase was confirmed by immunocytochemistry, Northern blot analysis, and reverse transcriptase-PCR. To determine whether hCG directly modulated these uterine responses, we treated ovariectomized baboons sequentially with estradiol and progesterone to mimic the hormonal profile of the normal menstrual cycle. Infusion of hCG into the oviduct of steroid-hormone-treated ovariectomized baboons induced the expression of alphaSMA in the stromal cells and glycodelin in the glandular epithelium. The epithelial plaque reaction, however, was not readily evident. These studies demonstrate a physiological effect of CG on the uterine endometrium in vivo and suggest that the primate blastocyst signal, like the blastocyst signals of other species, modulates the uterine environment prior to implantation.

Actins↗
PubMed1999

Identification and characterization of golgin-84, a novel Golgi integral membrane protein with a cytoplasmic coiled-coil domain.

The cytoplasmic face of the Golgi contains a variety of proteins with coiled-coil domains. We identified one such protein in a yeast two-hybrid screen, using as bait the peripheral Golgi phosphatidylinositol(4,5)P2 5-phosphatase OCRL1 that is implicated in a human disease, the oculocerebrorenal syndrome. The approximately 2.8-kilobase mRNA is ubiquitously expressed and abundant in testis; it encodes a 731-amino acid protein with a predicted mass of 83 kDa. Antibodies against the sequence detect a novel approximately 84-kDa Golgi protein we termed golgin-84. Golgin-84 is an integral membrane protein with a single transmembrane domain close to its C terminus. In vitro, the protein inserts post-translationally into microsomal membranes with an N-cytoplasmic and C-lumen orientation. Cross-linking indicates that golgin-84 forms dimers, consistent with the prediction of an approximately 400-residue dimerizing coiled-coil domain in its N terminus. The dimerization potential is supported by a data base search that showed that the N-terminal 497 residues of golgin-84 contain a coiled-coil domain that when fused to the RET tyrosine kinase domain had the ability to activate it, forming the RET-II oncogene. Data base searching also indicates golgin-84 is similar in structure and sequence to giantin, a membrane protein that tethers coatamer complex I vesicles to the Golgi.

Adult↗
PubMed1999

Evaluation of microbicidal activity of a new disinfectant: Sterilox 2500 against Clostridium difficile spores, Helicobacter pylori, vancomycin resistant Enterococcus species, Candida albicans and several Mycobacterium species.

The microbicidal activity of a new disinfectant Sterilox, a super-oxidized water, containing a mixture of oxidizing substances, was tested against Clostridium difficile spores, Helicobacter pylori, vancomycin resistant Enterococcus species, Candida albicans and several Mycobacterium species using membrane filters. All tests were performed in duplicate with and without added horse serum at 1% and 5% v/v. Distilled water, 0.35% peracetic acid (Nu-Cidex) and 2% glutaraldehyde were included as controls. Sterilox: spore suspension (9:1 v/v) achieved log10 kill of > 5 with 5% horse serum in 2 min against H. pylori, vancomycin resistant Enterococcus species, C. albicans and four atypical Mycobacterium species: M. avium, M. chelonei, M. xenopi and M. smegmatis. Sporicidal activity of Sterilox against Clostridium difficile was markedly diminished in the presence of 5% horse serum. Sterilox may be an effective alternative in endoscopy units, as it is a potent microbicidal agent and the manufacturer claims it is not corrosive to metal and is nontoxic to biological tissues.

Anti-Bacterial Agents↗
PubMed1999

HIV risk among homosexual, bisexual, and heterosexual male and female youths.

Variations in sexual risk acts and the social-cognitive mediators of sexual acts were examined among young homosexual, bisexual, and heterosexual males and females (N = 478; 13-21 years of age) from four community-based agencies in New York City, San Francisco, and Los Angeles (29% African American, 36% Latino, 36% White/other). The prevalence and frequency of sexual risk acts varied be gender but were similar across youth of different sexual orientations, ethnicities, and ages. Condom use and the social-cognitive mediators of risk varied by sexual orientation and gender. Homosexual youths reported a gap between their positive attitudes toward HIV prevention and their skills to implement safer sex acts, particularly under social pressure. Bisexual youths appeared at greatest risk; their reports of sexual risk were the highest, yet their perceived risk for HIV was relatively low and skills and knowledge were moderate (relative to their peers). Heterosexual youths appear at high risk for HIV based on reports of low rates of condom use and HIV-related beliefs and attitudes. However, heterosexual youths demonstrated the highest level of condom skills. The number of sexual partners was not associated with any HIV-related social cognitive mediator, suggesting that alternative theoretical models must be proposed for partner selection. Longitudinal research with similar subgroups of youths is needed.

Acquired Immunodeficiency Syndrome↗