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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 415 records · Page 23Linked to original sources
PubMed1998

Exploration of the perceptual magnet effect using the mismatch negativity auditory evoked potential.

The goals of this study were (i) to assess the replicability of the "perceptual magnet effect" [Iverson and Kuhl, J. Acoust. Soc. Am. 97(1), 553-561 (1995)] and (ii) to investigate neurophysiologic processes underlying the perceptual magnet effect by using the mismatch negativity (MMN) auditory evoked potential. A stimulus continuum from /i/ to /e/ was synthesized by varying F1 and F2 in equal mel steps. Ten adult subjects identified and rated the goodness of the stimuli. Results revealed that the prototype was the stimulus with the lowest F1 and highest F2 values and the nonprototype stimulus was close to the category boundary. Subjects discriminated stimulus pairs differing in equal mel steps. The results indicated that discrimination accuracy was not significantly different in the prototype and the nonprototype condition. That is, no perceptual magnet effect was observed. The MMN evoked potential (a preattentive, neurophysiologic index of auditory discrimination) revealed that despite equal mel differences between the stimulus pairs the MMN was largest for the prototype pair (i.e., the pair that had the lowest F1 and highest F2 values). Therefore the MMN appears to be sensitive to within category acoustic differences. Taken together, the behavioral and electrophysiologic results indicate that discrimination of stimulus pairs near a prototype is based on the auditory structure of the stimulus pairs.

Adult↗
PubMed1998

Cloning, expression, and sequencing of a cell surface antigen containing a leucine-rich repeat motif from Bacteroides forsythus ATCC 43037.

Bacteroides forsythus is a recently recognized human periodontopathogen associated with advanced, as well as recurrent, periodontitis. However, very little is known about the mechanism of pathogenesis of this organism. The present study was undertaken to identify the surface molecules of this bacterium that may play roles in its adherence to oral tissues or triggering of a host immune response(s). The gene (bspA) encoding a cell surface-associated protein of B. forsythus with an apparent molecular mass of 98 kDa was isolated by immunoscreening of a B. forsythus gene library constructed in a lambda ZAP II vector. The encoded 98-kDa protein (BspA) contains 14 complete repeats of 23 amino acid residues that show partial homology to leucine-rich repeat motifs. A recombinant protein containing the repeat region was expressed in Escherichia coli, purified, and utilized for antibody production, as well as in vitro binding studies. The purified recombinant protein bound strongly to fibronectin and fibrinogen in a dose-dependent manner and further inhibited the binding of B. forsythus cells to these extracellular matrix (ECM) components. In addition, adult patients with B. forsythus-associated periodontitis expressed specific antibodies against the BspA protein. We report here the cloning and expression of an immunogenic cell surface-associated protein (BspA) of B. forsythus and speculate that it mediates the binding of bacteria to ECM components and clotting factors (fibronectin and fibrinogen, respectively), which may be important in the colonization of the oral cavity by this bacterium and is also a target for the host immune response.

Amino Acid Sequence↗
PubMed1998

p300 mediates transcriptional stimulation by the basic helix-loop-helix activators of the insulin gene.

Pancreatic beta-cell-type-specific and glucose-inducible transcription of the insulin gene is mediated by the basic helix-loop-helix factors that bind to and activate expression from an E-box element within its enhancer. The E-box activator is a heteromeric complex composed of a beta-cell-enriched factor, BETA2/NeuroD, and ubiquitously distributed proteins encoded by the E2A and HEB genes. Previously, we demonstrated that the adenovirus type 5 E1A proteins repressed stimulation by the E-box activator in beta cells. In this study, our objective was to determine how E1A repressed activator function. The results indicate that E1A reduces activation by binding to and sequestering the p300 cellular coactivator protein. Thus, we show that expression of p300 in beta cells can relieve inhibition by E1A, as well as potentiate activation by the endogenous insulin E-box transcription factors. p300 stimulated activation from GAL4 (amino acids 1 to 147) fusion constructs of either BETA2/NeuroD or the E2A-encoded E47 protein. The sequences spanning the activation domains of BETA2/NeuroD (amino acids 156 to 355) and E47 (amino acids 1 to 99 and 325 to 432) were required for this response. The same region of BETA2/NeuroD was shown to be important for binding to p300 in vitro. The sequences of p300 involved in E47 and BETA2/NeuroD association resided between amino acids 1 and 1257 and 1945 and 2377, respectively. A mutation in p300 that abolished binding to BETA2/NeuroD also destroyed the ability of p300 to activate insulin E-box-directed transcription in beta cells. Our results indicate that physical and functional interactions between p300 and the E-box activator factors play an important role in insulin gene transcription.

Animals↗
PubMed1998

Possible mechanism of alprazolam-induced amnesia in mice.

Alprazolam produced anterograde as well as retrograde amnesia in mice assessed using elevated plus-maze. Flumazenil (10 mg/kg i.p.) attenuated anterograde and retrograde amnesia produced by alprazolam. It is proposed that anterograde amnesia produced by alprazolam may be mediated through the activation of benzodiazepine receptors. Retrograde amnesia of alprazolam may be mediated through the blockade of PAF receptors. Moreover, flumazenil facilitates learning and memory perhaps by modulating the release of PAF and consequently attenuated alprazolam and BN-50730-(PAF receptor antagonist)-induced retrograde amnesia.

Alprazolam↗
PubMed1998

Potential of limited day 21 post-chemotherapy CT scan in predicting need for post-chemotherapy surgery in nonseminomatous testicular germ cell cancer.

UNLABELLED: Nonseminomatous germ cell cancers (NSGCC) have a varied response to chemotherapy, some melting away with resultant cure, some have tumour stem cell necrosis and residual benign disease whilst others are resistant to treatment. The latter two require surgical excision in order to identify those needing high intensity chemotherapy. OBJECTIVE: The aim of this study was to investigate whether it was possible to give an earlier prediction of need for surgery after chemotherapy on the basis of a limited CT scan performed after the first course. MATERIALS AND METHODS: Twenty-three patients with metastatic NSGCC undergoing induction chemotherapy were studied. The site of the maximum disease was noted before treatment and only this area was rescanned at day 21. The change in disease bulk, measured as maximum transverse diameter (MTD), was compared with appearances on a CT scan immediately after chemotherapy and post-treatment response. RESULTS: Of those patients showing a poor response on the day 21 scan (i.e. no change, or less than 50% reduction in MTD), 70% required early surgical excision of residual disease, while none of the good responders (i.e. greater than 50% reduction in MTD), required immediate surgery (p < 0.001). CONCLUSION: It is concluded that a limited day 21 CT scan may represent an independent predictor of good and poor response to chemotherapy, thus enabling reduction in chemotherapy and its toxicity in good responders and early identification of those who may need surgical excision, thereby permitting easier scheduling of these often difficult surgical procedures.

Adult↗
PubMed1998

Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity.

Plasma leptin shows a nocturnal rise and a pulsatile pattern. This work was undertaken to determine the effects of gender and obesity on this pattern. Twenty-four-hour leptin profiles were evaluated in 31 subjects [17 male, 14 female; age: 36 +/- 2 yr (mean +/- SEM); body mass index: 27.5 +/- 1.0 kg/m2]. Plasma leptin profiles were higher in obese (body mass index > 27 kg/m2) than in lean subjects and higher in women than in men, regardless of fat mass. Leptin showed diurnal rhythmicity with peaks between 2200-0300 (median: 0120) and nadirs between 0800 and 1740 (median: 1033). Spectral analysis revealed 2 components (periodicities: 24 and 12 h) with higher relative amplitudes in lean than in obese subjects. The relative diurnal amplitude also was higher in men than in women, controlling for adiposity. Insulinemia, female sex, and age were negative determinants of diurnal rhythm relative amplitude. Pulse analysis revealed 3.6 +/- 0.3 pulses/24 h, occurring mostly 2-3 h after meals. Pulse frequency correlated negatively with fat mass and insulinemia (Spearman's r = -0.54 and -0.37, respectively; P < 0.05 for each). Thus, obesity is associated not only with higher leptin levels but also with blunted diurnal excursions and dampened pulsatility. This abnormal rhythmicity may contribute to leptin resistance in obesity. The significance of the sexual dimorphism in the diurnal amplitude is unclear, but it may be related to leptin's putative role as a metabolic signal to the reproductive axis.

Adipose Tissue↗
PubMed1998

Changes in plasma leptin during the menstrual cycle.

OBJECTIVE: To measure the plasma concentration of leptin, which is expressed in ovarian follicles and may have a reproductive function, in healthy women during the menstrual cycle. DESIGN: This study included nine women with regular menstrual cycles (mean+/-S.E.M. age 28+/-2 years: body mass index 23.9+/-1.8 kg/m2). From the onset of menses, fasting blood samples were collected every 1-2 days throughout the menstrual cycle. As a control, plasma leptin was measured in six postmenopausal women and six men every other day for 28 days. RESULTS: In menstruating women, plasma leptin increased from 14.9+/-2.9 ng/ml in the early follicular phase to 20.4+/-4.2 ng/ml (P<0.01) at the midluteal phase and returned to the baseline by the subsequent menses. In contrast, leptin concentrations did not change significantly in postmenopausal women or men. The changes in plasma leptin during the menstrual cycle were not related to changes in sex hormones. CONCLUSIONS: The cause of the increase in plasma leptin during the late follicular and luteal phases of the menstrual cycle is not clear. It may be attributed to augmented adipocyte production of leptin in response to increased caloric intake or hypothalamic release of neuropeptide Y. or to release of leptin from mature ovarian follicles. Leptin may have a role in regulating the menstrual cycle and preparing the body for the metabolic demands of pregnancy.

Adipose Tissue↗
PubMed1998

Effects of chemotherapy on osseointegration of implants: a case report.

A patient underwent mandibular resection for high-grade osteosarcoma with immediate reconstruction with a microvascular fibula free bone graft and simultaneous placement of osseointegrated implants. Following initial healing, she underwent six cycles of chemotherapy and had further revision surgery prior to implant exposure and construction of a prosthesis. The chemotherapy appears to have had no deleterious effects on implant osseointegration or survival.

Adult↗
PubMed1998

Physiological insulinemia acutely modulates plasma leptin.

Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/-2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0 kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by 37+/-2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.

Adult↗
PubMed1998

Cancer metastasis: a search for therapeutic inhibition.

Failure of cancer treatment is often due to the growth of secondary, metastatic lesions in distant organs. Because initiation of metastasis is an early event in malignancy, patients often present not only with a primary tumor but also with occult metastases. Treatment of these metastases requires aggressive, systemic chemotherapy, since surgical removal of all metastatic foci is normally not feasible. However, drug toxicity caused by many of the currently used anticancer agents often limits chemotherapeutic approaches to malignant disease. In contrast, the development and use of novel cytostatic, antimetastatic agents could be less toxic and more applicable for long-term treatment in combating latent and/or residual disease. Practical intervention with such nontoxic agents has been envisioned as maintenance therapy after cytoreduction of a tumor or as a prophylactic treatment after the removal of a precancerous tumor exhibiting a genetic predisposition to a carcinomatous state. In this review, we discuss targets of the metastatic cell that may be potentially exploitable with chemotherapy, and present the current status of several novel, antimetastatic agents. Clinical evaluation of such agents will require new and appropriate clinical models for evaluating their antimetastatic efficacy. The recent successes achieved with certain proteinase inhibitors for the treatment of cancer are paving the way for the development of other therapeutic agents of this type, aimed at unique biochemical pathways associated with oncogenic behavior.

Animals↗
PubMed1998

Evaluation of various diagnostic signs on percutaneous transhepatic cholangiography in obstructive jaundice.

Twenty patients of obstructive jaundice were subjected to percutaneous transhepatic cholangiography (PTC) of which 17 were operated on. Patients were divided in 4 groups according to the site of obstruction. The diagnostic signs observed were: Complete block with interface having convexity downwards (4), convexity upwards (3), biconcave caudal cut off (6), smooth edged cut off (one), irregular edged cut off (one) and non-specific appearance (one); incomplete block with interface having convexity upwards (one); biconcave caudal cut off (2) and multiple smooth central filling defects (2). In one case there was incomplete obstruction at two sites giving rise to two different signs. PTC was 100% correct in accurately telling the site of lesion. As regards the nature of the lesion the diagnosis on PTC was found correct in 15 out of 17 cases (88.5%).

Cholangiography↗
PubMed1998

Mesangial proliferative glomerulonephritis in chronic obstructive pulmonary disease.

Ten patients of chronic obstructive pulmonary disease were studied for changes in ultrastructure of the glomeruli, serum immunoglobulin and complement levels. The glomeruli showed proliferation in the mesangium in 90% patients and electron dense deposits in the mesangium in 30% patients. IgA and IgG were usually elevated whereas complements were usually depressed in most of these patients. It is suggested that repeated respiratory infections in these subjects may be responsible for mesangioproliferative type of glomerulonephritis, high IgA and IgG levels. The complements are activated and they take part in immune complex formation getting deposited in mesangium.

Adult↗
PubMed1998

Comparative study of rice-based oral rehydration salt solution versus glucose-based oral rehydration salt solution (WHO) in children with acute dehydrating diarrhoea.

One hundred children with acute dehydrating diarrhoea were studied. They were divided into two groups: Group A (n = 50) were given rice-based oral rehydration salt (ORS) solution and group B (n = 50) were given glucose-based ORS solution (WHO). There was no significant decrease in mean stool output and percentage weight gain with rice-based ORS. Both the groups were comparable for volume of ORS solution consumed, time taken for initial rehydration, mean stool output and for correcting biochemical abnormalities.

Acute Disease↗
PubMed1998

Crouzon disease--a case report.

The present case of a ten year old boy with craniofacial dysostosis with the features of midfacial hypoplasia is a disease known as Crouzon disease. This disease is characterised by cranial deformities, facial malformation, eye changes and occasional other associated abnormalities. The aim of this case is to discuss the clinical, radiographic features and management of the problems.

Abnormalities, Multiple↗
PubMed1998

Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer.

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.

Adult↗
PubMed1998

Clinical pharmacokinetics and pharmacodynamics of a new squalene synthase inhibitor, BMS-188494, in healthy volunteers.

A double-blind, placebo-controlled, parallel-group, ascending, multiple-dose study was completed in 45 healthy male volunteers to assess the maximum tolerated dose, pharmacokinetics, and pharmacodynamics of BMS-187745, a squalene synthase inhibitor, administered as multiple oral doses of its prodrug BMS-188494. Participants received a daily oral dose of 10 mg for 2 weeks, or a daily oral dose of 25, 50, 100, or 200 mg for 4 weeks. The absorption rate constant (ka) and bioavailability (F) values were estimated by fitting the plasma BMS-187745 concentration-time data to a biexponential function with a first-order ka. Values for F were similar for all five dose levels, and thus were independent of dose. The ka values also were similar for all dose groups except the 50-mg group, for which ka values were somewhat higher. The change in urinary excretion rate of farnesyl pyrophosphate metabolite (dioic acid) was determined to be a pharmacodynamic measure. There was no significant change in dioic acid excretion at doses of less than 100 mg given for 4 weeks. An indirect pharmacodynamic response model with threshold concentration (CT) and based on inhibition of squalene synthase was proposed to describe the effect versus time data. The pharmacodynamic data from all dose levels were fitted simultaneously to the proposed model and the fitted parameters estimated as CT = 3.9 micrograms/mL, kout = 0.47 hr-1, IC50 = 4.1 micrograms/mL, and Imax = 1.0. The proposed indirect response model requiring a threshold concentration provides a useful means of quantitating responses for a new type of therapeutic agent.

Adult↗
PubMed1998

Management of teeth with open apices and necrotic pulps with single visit apexification: 3 representative cases.

Apexification is the most widely accepted procedure for the treatment of nonvital immature teeth. Single visit apexification is less time consuming, more economical and an easily acceptable technique with the aim of inducing the formation of a hard tissue barrier, thus allowing proper condensation of gutta percha in the root canal. Factors considered during this procedure are: i. Debridement of root canal minimizing the infection and filling the root canal space with resorbable calcification inducing material i.e. Ca(OH)2. ii. Minimal mechanical intervention to maintain the integrity and vascularity of apical region. Once filled, Ca(OH)2 was not changed again and the treated tooth was examined only radiographically till the desired apical closure was achieved. Three representative cases treated with this single visit apexification technique are discussed here. In all the cases successful apical closure of different types was achieved. Treatment was then concluded with gutta percha obturation in all the cases with successful follow up.

Adolescent↗