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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 127 records · Page 7Linked to original sources
PubMed2001

Oral immunization with recombinant Streptococcus gordonii expressing porphyromonas gingivalis FimA domains.

Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology of adult periodontitis. P. gingivalis fimbriae are one of several critical surface virulence factors involved in both bacterial adherence and inflammation. P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is considered an important antigen for vaccine development against P. gingivalis-associated periodontitis. We have previously shown that biologically active domains of P. gingivalis fimbrillin can be expressed on the surface of the human commensal bacterium Streptococcus gordonii. In this study, we examined the effects of oral coimmunization of germfree rats with two S. gordonii recombinants expressing N (residues 55 to 145)- and C (residues 226 to 337)-terminal epitopes of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness of immunization in protecting against alveolar bone loss following P. gingivalis infection was also evaluated. The results of this study show that the oral delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary (IgA) antibody responses and that the immune responses were protective against subsequent P. gingivalis-induced alveolar bone loss. These results support the potential usefulness of the S. gordonii vectors expressing P. gingivalis fimbrillin as a mucosal vaccine against adult periodontitis.

Administration, Oral↗
PubMed2001

Development of a gene inactivation system for Bacteroides forsythus: construction and characterization of a BspA mutant.

Bacteroides forsythus is a gram-negative anaerobic bacterium associated with periodontitis. The bspA gene encoding a cell surface associated leucine-rich repeat protein (BspA) involved in adhesion to fibronectin and fibrinogen was recently cloned from this bacterium in our laboratory. We now describe the construction of a BspA-defective mutant of B. forsythus. This is the first report describing the generation of a specific gene knockout mutant of B. forsythus, and this procedure should be useful in establishing the identity of virulence-associated factors in these organisms.

Antigens, Bacterial↗
PubMed2001

Identification of Enterococcus, Streptococcus, and Staphylococcus by multivariate analysis of proton magnetic resonance spectroscopic data from plate cultures.

A new fingerprinting technique with the potential for rapid identification of bacteria was developed by combining proton magnetic resonance spectroscopy ((1)H MRS) with multivariate statistical analysis. This resulted in an objective identification strategy for common clinical isolates belonging to the bacterial species Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus milleri group. Duplicate cultures of 104 different isolates were examined one or more times using (1)H MRS. A total of 312 cultures were examined. An optimized classifier was developed using a bootstrapping process and a seven-group linear discriminant analysis to provide objective classification of the spectra. Identification of isolates was based on consistent high-probability classification of spectra from duplicate cultures and achieved 92% agreement with conventional methods of identification. Fewer than 1% of isolates were identified incorrectly. Identification of the remaining 7% of isolates was defined as indeterminate.

Culture Media↗
PubMed2001

Is glucose/amino acid supplementation after exercise an aid to strength training?

BACKGROUND: The precise timing of carbohydrate and amino acid ingestion relative to a bout of resistance exercise may modulate the training effect of the resistance exercise. OBJECTIVE: To assess whether regular glucose/amino acid supplementation immediately after resistance exercise could enhance the gain in muscle strength brought about by resistance training. METHODS: Seven untrained participants with a median age of 23 years and mean (SD) body mass 68.9 (13.5) kg resistance trained on a leg extension machine for five days a week for 10 weeks, using four sets of 10 repetitions. Alternate legs were trained on successive days, one leg each day. Subjects ingested either a supplement including 0.8 g glucose/kg and 0.2 g amino acids/kg, or placebo, on alternate training days immediately after training. Therefore the supplement was always ingested after training the same leg (supplement leg). Isometric, isokinetic, and 1 repetition maximum (RM) strength were measured before, during, and after training. Blood samples were analysed to determine the acute responses of insulin and glucose to resistance exercise and supplementation or placebo. RESULTS: Serum insulin concentration peaked 20 minutes after supplement ingestion at ninefold the placebo level, and remained significantly elevated for at least 80 minutes (p<0.01). Isometric, isokinetic, and 1 RM strength improved on both supplement and placebo legs (p<0.05). There were no significant differences in the gain in strength between the supplement leg and the placebo leg (p>0.05). CONCLUSION: Regular glucose/amino acid supplementation immediately after resistance exercise is unlikely to enhance the gain in muscle strength brought about by resistance training.

Adult↗
PubMed2001

Factors influencing pneumothorax rate at lung biopsy: are dwell time and angle of pleural puncture contributing factors?

PURPOSE: To study factors that may influence pneumothorax and chest tube placement rate, especially needle dwell time and pleural puncture angle. MATERIALS AND METHODS: In 159 patients, 160 coaxial computed tomography (CT)-guided lung biopsies were performed. Dwell time, the time between pleural puncture and needle removal, was calculated. The smallest angle of the needle with the pleura ("needle-pleural angle") was measured. These and other variables were correlated with pneumothorax and chest tube rates. RESULTS: One hundred fifty biopsies were included. There were 58 (39%) pneumothoraces (14 noted only at CT), with eight (5%) biopsies resulting in chest tube placement. Longer dwell times (mean, 29 minutes; range, 12-66 minutes) did not correlate with pneumothoraces (P =.81). Smaller needle-pleural angles (< 80 degrees) [corrected], decreased forced expiratory volume in 1 second to vital capacity ratio (<50%), lateral pleural puncture, and lesions along fissures were associated with higher [corrected] pneumothorax rates (P <.05). Emphysema along the needle path, pulmonary function tests showing ventilatory obstruction, and lesions along fissures predisposed patients to chest tube placement (P <.05). Pleural thickening and prior surgery were associated with lower pneumothorax rates (P <.05). CONCLUSION: Longer dwell times do not correlate with pneumothorax and should not influence the decision to obtain more biopsy samples. A shallow pleural puncture angle may increase the pneumothorax rate.

Aged↗
PubMed2001

Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression.

Although type 2 diabetes mellitus is associated with insulin resistance, many individuals compensate by increasing insulin secretion. Putative mechanisms underlying this compensation were assessed in the present study by use of 4-day glucose (GLC; 35% Glc, 2 ml/h) and lipid (LIH; 10% Intralipid + 20 U/ml heparin; 2 ml/h) infusions to rats. Within 2 days of beginning the infusion of either lipid or glucose, plasma glucose profiles were normalized (relative to saline-infused control rats; SAL; 0.45% 2 ml/h). During glucose infusion, plasma glucose was maintained in the normal range by an approximately twofold increase in plasma insulin and an approximately 80% increase in beta-cell mass. During LIH infusion, glucose profiles were also maintained in the normal range. Plasma insulin responses during feeding were doubled, and beta-cell mass increased 54%. For both groups, the increase in beta-cell mass was associated with increased beta-cell proliferation (98% increase during GLC and 125% increase during LIH). At the end of the 4-day infusions, no significant changes were observed in islet-specific gene transcription (i.e., the expression of islet hormone genes, glucose metabolism genes, and insulin transcription factors were unaffected). Two days after termination of the infusions, the glucose-stimulated plasma insulin response was increased approximately 67% in glucose-infused animals. No sustained effect on insulin secretory capacity was observed in the LIH animals. The increase in plasma insulin response after glucose infusion was achieved in the absence of any change in insulin clearance. We conclude that, in rats, an increase in insulin demand after an increase in glucose appearance or free fatty acid leads to an increase in beta-cell mass, mediated in part by an increase in beta-cell proliferation, and that these compensatory changes lead to increased insulin secretion, normal plasma glucose levels, and the maintenance of normal islet gene expression.

Adaptation, Physiological↗
PubMed2001

Clinical benefit and approach of ultrafiltration in acute heart failure.

Because of the increasing incidence of acute heart failure admissions to critical care units, nephrologists have been asked to become more involved in the management of these patients. Renal dysfunction is a major element in impeding clinical recovery. In acute heart failure, renal function is often abnormal. The judicious application of ultrafiltration techniques may represent an efficacious adjunct to present conventional practice. In patients with refractory congestive heart failure, the ability to provide continuous, daily, large volume removal not only improves volume status but also the clinical symptoms of the decompensated patient. A thorough literature review supports the premise that starting hemofiltration is an appropriate alternative for difficult and unstable cardiac patients. An optimal strategy utilizing continuous renal replacement therapy can dramatically improve the patient's clinical condition, mitigate the neurohumoral stimulation, increase urinary output and promote absorption of excessive extravascular fluid.

Aged↗
PubMed2001

Tolerability of the low-affinity, use-dependent NMDA antagonist AR-R15896AR in stroke patients: a dose-ranging study.

BACKGROUND AND PURPOSE: AR-R15896AR is a use-dependent, low-affinity blocker of the NMDA ion channel with neuroprotective effects in animal models of focal cerebral ischemia. This study aimed to establish the highest safe and tolerated loading and maintenance dosing regimen of AR-R15896AR in acute ischemic stroke patients and to determine the associated plasma concentrations of AR-R15896AR. METHODS: This was a 4-part, multicenter, randomized, double-blind, placebo-controlled study in 175 patients (mean age, 69 years) within 24 hours of acute stroke symptom recognition. Ascending 60-minute intravenous infusion loading doses of AR-R15896AR were initially examined (100, 150, 200, 250, or 300 mg or placebo in 3:1 randomization, n=36 treated); in part 2, 250, 275, or 300 mg was compared with placebo (n=33). In part 3, a 250-mg loading dose was followed by 9 maintenance doses of 60, 75, 90, 105, or 120 mg every 8 hours versus placebo in 3:1 randomization (n=59); subsequently, in part 4, maintenance doses of 90, 105, and 120 mg after the 250-mg loading dose were directly randomized against placebo (n=42). Safety, tolerability, and pharmacokinetics were the primary end points; NIHSS at 1 week and Barthel and modified Rankin scores at 1 month were also recorded, but the study was neither designed nor powered to assess efficacy. RESULTS: Rates for mortality and serious adverse events (SAE) were similar in active and placebo groups (9% mortality and 23% SAE for all active combined versus 11% mortality and 33% SAE for placebo). Adverse events associated with AR-R15896AR were dizziness, vomiting, nausea, stupor, and some agitation/hallucination. Withdrawal from treatment occurred only in response to loading doses with AR-R15896AR: placebo, 3 of 46 (7%); 250 mg, 11 of 89 (12%); 275 mg, 1 of 8 (12.5%); and 300 mg, 3 of 15 (20%). No significant difference in outcome was observed between groups. Plasma concentrations of AR-R15896AR were 1524+/-536 ng/mL at the end of the 250-mg loading infusion and were 1847+/-478 ng/mL at steady state after the 9 maintenance doses of 120 mg. CONCLUSIONS: The maximum tolerated loading infusion of AR-R15896AR in this study was 250 mg over a period of 1 hour. Subsequent maintenance infusions of 120 mg every 8 hours were well tolerated. With these doses, putative neuroprotective concentrations of 1240 ng/mL are attained by the loading dose and are satisfactorily maintained thereafter. The loading dose may be improved further by adjustment on an individual patient basis, but tolerability issues remain.

Aged↗
PubMed2001

The Community Readiness Survey. Development and initial validation.

This article reports on the development and evaluation of a mail survey measuring population attitudes toward substance use of potential receptivity of communities to different prevention efforts. The Community Readiness Survey was designed through a series of prevention practitioner and consultant meetings and focus groups. Psychometric evaluation revealed five distinct domains: perception of alcohol, tobacco, or other drug problem; support for prevention; permissive attitudes toward teen substance use; perception of adolescent access; and perception of community commitment. Evidence of construct validity was demonstrated by the small but significant relationships between selected scale scores and community readiness as evaluated by prevention planners.

Attitude to Health↗
PubMed2001

Role of intracellular calcium in the spermicidal action of 2',4'-dichlorobenzamil, a novel contact spermicide.

The Na+-Ca2+ exchanger and Ca2+-ATPase pumps reported to be present on the sperm membrane are responsible for maintaining the intracellular Ca2+ concentration that is involved in regulation of sperm function. We have investigated the role of intracellular Ca2+ in the presence of 2',4'-dichlorobenzamil hydrochloride (benzamil), a Na+-Ca2+ exchange inhibitor, on human sperm motility. The mechanism of the complementary spermicidal action produced by a combination of benzamil and propranolol on human spermatozoa has been investigated also. When administered alone benzamil and propranolol produced a dose- and time-dependent decrease in motility of sperm in ejaculated semen and spermatozoa separated from semen. A combination of benzamil and propranolol exhibited a complementary spermicidal action, thereby resulting in dose reduction of both drugs for obtaining total immotility within 1 min of administration. An increase in the intracellular Ca2+ level was found to contribute to the spermicidal activity. Inhibition of the Na+-Ca2+ exchange system on sperm membrane by benzamil and membrane stabilization by propranolol resulted in accumulation of Ca2+ inside the sperm cells. When the two drugs were used in combination the time required for the total loss of motility of spermatozoa was significantly reduced due to a similar mechanism of action of both drugs.

Adrenergic beta-Antagonists↗
PubMed2001

A case of sensorineural deafness following ingestion of Ecstasy.

Ecstasy is a substance of abuse commonly associated with the dance scene and taken by many young people. A brief history of Ecstasy and its side-effects is given. A case of ototoxicity is presented, as an additional side-effect to the long list of complications caused by Ecstasy.

Adult↗
PubMed2001

Mulberry moracins: scavengers of UV stress-generated free radicals.

Mulberry leaves treated with UV-C were found to accumulate three different phytoalexins, moracin C, moracin N, and chalcomoracin. The increased level of malondialdehyde in UV-treated leaves along with moracins suggested their role as a free-radical scavenger in stressed plants. All the three moracins induced under UV stress were capable of scavenging the superoxide anion generated by the xanthine-xanthine oxidase system. Also, moracins were capable of inhibiting lipid peroxidation, which strongly indicates their role as a scavenger.

Free Radical Scavengers↗
PubMed2001

Analysis of integrated optical waveguides: variational method and effective-index method with built-in perturbation correction.

We show analytically that for the modal analysis of rectangular waveguides, the recently developed effective-index method with built-in perturbation correction is identical to the first-iteration cycle of the variational method that we had developed earlier [Opt. Quantum Electron. 12, 517 (1989)]. We also show that in a number of cases the accuracy improves considerably through iteration beyond the first cycle.

Journal Article↗
PubMed2001

A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells.

The effects of a vasoactive intestinal peptide (VIP) receptor antagonist (VIPhyb) on human glioblastoma cells were characterized. Pituitary adenylate cyclase activating polypeptide (125I-PACAP-27) bound with high affinity to U87, U118, and U373 cells. Specific 125I-PACAP-27 binding to U87 cells was inhibited, with high affinity, by PACAP but not VIP or VIPhyb (IC50 = 10, 1500, and 500 nM, respectively). By reverse transcriptase-polymerase chain reaction (RT-PCR), a major 305 bp band was observed indicative of PAC1 receptors. PACAP-27 caused cAMP elevation and the increase in cAMP caused by PACAP-27, was inhibited by the VIPhyb. Also, PACAP-27 caused cytosolic Ca2+ elevation in Fura-2AM loaded U87 cells and the VIPhyb inhibited this increase. Using the MTT growth assay, the VIPhyb was shown to inhibit glioblastoma growth in a concentration-dependent manner. Using a clonogenic assay in vitro, 10 microM VIPhyb significantly inhibited proliferation of U87, U118, and U373 cells. In vivo, 0.4 microg/kg VIPhyb inhibited U87 xenograft proliferation in nude mice. These results suggest that the VIPhyb antagonizes PAC1 receptors on glioblastoma cells and inhibits their proliferation.

Animals↗
PubMed2001

A rare non-syndrome case of concomitant multiple supernumerary teeth and partial anodontia.

Concomitant hypo-hyperdontia is an uncommon condition of coexistence of partial anodontia and supernumerary teeth. Its etiology is still unknown. Very few cases have been reported in the literature of this condition. Presented here is a rare and first such case of simultaneous presence of multiple supernumerary teeth and a missing tooth (canine) without any associated systemic conditions or syndromes involving both jaws.

Anodontia↗
PubMed2001

Beta-cell adaptation and decompensation during the progression of diabetes.

Inadequate beta-cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta-cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS). This review discusses the ways in which beta-cells successfully adapt to increased demand and then decompensate as diabetes develops. Successful adaptation is achieved through increased beta-cell mass and increased insulin secretion. The hypothesis is explored that beta-cells exposed to the diabetic milieu lose their differentiation, which leads to loss of specialized functions such as GIIS. This concept has been strengthened by the finding of dedifferentiation of beta-cells in a rat model of partial pancreatectomy that includes a reduction of insulin gene expression, which may further contribute to decreased insulin production. Another finding was increased expression of c-Myc, which probably contributes to an increase in the expression of lactate dehydrogenase and the development of beta-cell hypertrophy. Arguments are developed that the beta-cell changes found in diabetes are better correlated with increased glucose levels than with non-esterified fatty acid levels, thus supporting the importance of glucose toxicity.

Adaptation, Physiological↗