Biomedical subjects

S Subramanian

Publications and source records attributed to S Subramanian.

At least 91 records · Page 5Linked to original sources

PubMed2000

Setting the target for a better cervical screening test: characteristics of a cost-effective test for cervical neoplasia screening.

OBJECTIVE: To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer. METHODS: Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40-90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from $0 to $15. RESULTS: When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions. CONCLUSION: Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.

Adolescent↗

PubMed2000

Supplemental oxygen improves resolution of injury-induced pneumothorax.

BACKGROUND/PURPOSE: Traditionally, supplemental oxygen is administered to patients with asymptomatic pneumothorax to accelerate spontaneous resolution. However, this practice is based on models that did not include injury to the visceral pleura and ongoing pleural air leak. This study evaluated the effects of increased inspired oxygen concentration on pneumothorax resolution in a visceral pleural injury model. METHODS: A total of 27 New Zealand white rabbits were divided randomly into 3 groups: room air (RA), 40% FIO2 (40%), and 60% FIO2 (60%). A complete unilateral pneumothorax was created in each animal by a thoracoscopically guided visceral pleural puncture. The animals were then housed in designated oxygen chambers, and observers were blinded to the inspired oxygen concentration. Cross table anteroposterior chest x-rays were obtained preoperatively, postoperatively, and twice a day until the pneumothorax resolved. Time to resolution between the 3 groups was analyzed with 1-way analysis of variance (ANOVA). RESULTS: Twenty of 27 (74%) of the animals completed the study successfully. Mean time to resolution in the RA group (n = 7; 111.2 +/- 30.8 hours) was longer than in the 40% group (n = 6; 71.8 +/- 22.3 hours) and the 60% group (n = 7; 39.4 +/- 14.2 hours). The time to resolution also was longer in the 40% group than in the 60% group. Seven rabbits died before completion of the study of tension pneumothorax (3 of 7) or anesthetic complications (4 of 7). CONCLUSIONS: Supplemental oxygen improves resolution of injury-induced pneumothorax. The tradition of administering supplemental oxygen to patients with asymptomatic pneumothorax should be continued even if there is ongoing pleural air leak.

Animals↗

PubMed2000

Immunocontraceptive efficacy of synthetic peptides corresponding to major antigenic determinants of chicken riboflavin carrier protein in the female rats.

PROBLEM: Earlier studies have demonstrated that antibodies directed towards the N-terminal (residues 10-17) and C-terminal (residues 200-207) regions on chicken riboflavin carrier protein (RCP; 219 AA) are effective in pregnancy termination in rodents and sub-human primates. In the present study, the immunocontraceptive potential of three additional immunodominant sequences comprising of residues 33-49, 64 83 and 130-147 (CYA, CED and CGE peptides, respectively) of chicken RCP was investigated. METHOD OF STUDY: The three antigenic peptides were synthesized by using Fmoc chemistry. Oligoclonal antibodies were generated in rabbits. Bioneutralizing capacity of these peptides was assessed by passive and active immunoneutralization studies. RESULTS: All the three peptides-specific antisera recognized their cognate epitopes on native RCP. When the affinity purified peptide IgG were administered on three consecutive days to pregnant rats (on days 10, 11 and 12), it was observed that the rats injected with CED and CGE-IgG failed to deliver any pups whereas the animals which received CYA IgG delivered normal pups. Active immunization of fertile female rats with CED or CGE peptide conferred protection from pregnancy. CONCLUSIONS: These results demonstrate the presence of two additional stretches in chicken RCP which can serve as mini-vaccines.

Amino Acid Sequence↗

PubMed2000

Synergistic effects of nateglinide and meal administration on insulin secretion in patients with type 2 diabetes mellitus.

This study assessed the synergistic effects of nateglinide (a non-sulfonylurea D-phenylalanine derivative) and meals on insulin secretion in 24 patients with type 2 diabetes. Oral doses of 60 and 180 mg or 120 and 240 mg were administered to two cohorts of subjects 10 min before meals (or fasting) three times daily for 7 days, with washout intervals between treatment periods. Dose-dependent increases in plasma insulin occurred, with the peak effect within 2 h after treatment. Significantly greater insulin secretion was observed when nateglinide was taken before a meal compared to nateglinide given in the fasted state or in response to just the meal. Nateglinide lowered plasma glucose concentrations significantly vs. placebo at all doses, and doses of 120 and 240 mg were more effective than 60 mg (P < 0.05). Adverse event rates were similar for nateglinide and placebo, and no hypoglycemic episodes or serious adverse events were reported during the study. Nateglinide (120 mg) was the maximum effective dose in this study and was shown to be a safe and well tolerated therapy for control of mealtime glucose excursions in patients with type 2 diabetes. Results indicate that a synergistic interaction occurs between nateglinide and elevated mealtime plasma glucose concentrations to stimulate insulin secretion.

Adult↗

PubMed2000

Limiting harm in the ICU.

This year, the US Institute of Medicine has estimated that medical errors kill up to 98,000 Americans each year,1 a problem surpassing automobile fatalities. For patients on the medical ward, drug therapy is the primary intervention they are receiving yet medication errors occur in as many as 4% of inpatients.2 Although greater monitoring intensity and much lower nurse-patient ratios in the ICU may reduce the incidence of medication errors, the shear number if interventions dramatically increases the risk of error.3 Furthermore, the study by the Institute of Medicine only addressed a small part of the problem. The taxonomy of errors includes both "accidents" (skill-based errors) and intentional "mistakes" (knowledge-based and rule-based errors).2 Thus, the Institute of Medicine would not consider the proscribing of human growth hormone for cachexia an error unless the proscribed dose was not administered or it was given to the wrong patient. In the ICU, the risks associated with both kinds of errors are considerable. In this review we will focus on the second kind of errors and examine harms associated with the care of patients with sepsis.

Anesthesia↗

PubMed2000

Strain-dependent variability in immune response to chicken riboflavin carrier protein in mice with different haplotypes.

Active immunization of fertile female mice, rats and sub-human primates with linearized chicken riboflavin carrier protein (RCP) curtailed pregnancy suggesting that sequence-specific RCP antibodies interfere with fertilization/early embryo development. To investigate the genetic basis of variations in immunogenecity, antibody response to reduced and carboxymethylated RCP (RCM-RCP) was studied in different strains of mice of independent H-2 haplotypes. Among these, AKR (H-2k) were low or non-responders. Measurement of antibody titers in hyperimmune sera showed that among responder strains of mice, C57BL/6 (H-2b) and BALB/c (H-2d) generated higher levels of antibody compared to mice of SJLJ (H-2S). The relative affinities of these antibodies also varied depending upon the strain, with BALB/c mice showing highest affinity. Epitope mapping by pepscan ELISA revealed significant variability in determinant-specific antibody populations, with SJLJ strain lacking antibodies to N-terminal half of RCP sequence. However, four immunodominant sequential epitopes (residues 100-107, 134-141, 174-181 and 200-207) common to all the three strains of mice have been identified. Binding to these regions was not haplotype restricted although there were qualitative differences in recognition patterns. Present investigations have shown that site-specific antibodies directed towards any one of the four epitopic regions comprising of residues 3-24, 64-83, 130-147 and 200-219 in chicken RCP sequence effectively interfered with pregnancy establishment in female BALB/c mice. This implies the propensity of RCP antibodies to curtail pregnancy in the other two responder mouse strains also.

Amino Acid Sequence↗

PubMed2000

Dysphagia due to anterior cervical osteophytes--a case report.

Dysphagia due to osteophytes in a young person is uncommon. We present a rare case of Forestier's disease causing dysphagia in a young lady without other bony involvement. The osteophytes were surgically removed and her symptoms resolved completely.

Adult↗

PubMed1999

Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors.

A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu/nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0. 05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RARalpha, RXRalpha, and RXRbeta were similar in the two cell lines, while RARbeta expression was higher in SCC-2 over SCC-38, and RARgamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

Animals↗

PubMed1999

Immunological relatedness of chicken and human riboflavin carrier protein.

Polyclonal antibodies (pAbs) to riboflavin carrier protein (RCP) purified from human amniotic fluid were raised in two rabbits. These pAbs apart from recognizing the parent antigen, reacted significantly with chicken RCP as well. When all the 212 octapeptides overlapping by one amino acid residue and covering the entire primary amino acid sequence of chicken RCP immobilized on polyethylene rods were probed with rabbit anti-human RCP antibodies, it was found that these antibodies recognize five epitopic sequences (residues 37-42, 73-76, 133-140, 174-176 and 200-207) in chicken RCP primary structure common to both the rabbits. In addition, the antisera from the two individual animals also recognized additional epitopes characteristic to that particular animal. The reactivities of these antigenic determinants have been confirmed with polyclonal anti-human RCP sera by using synthetic peptides harbouring these chicken RCP sequences in inhibition ELISA. This high level of immunological similarities among linear epitopes observed may reflect the degree of conservation of local conformations among linear antigenic determinants shared by the two evolutionarily distant homologous proteins.

Amino Acid Sequence↗

PubMed1999

Surface Chemical Studies on the Competitive Adsorption of Poly(acrylic acid) and Poly(vinyl alcohol) onto Alumina.

The adsorption of poly(acrylic acid) (PAA) and poly(vinyl alcohol) (PVA) onto alumina has been studied as a function of pH, both individually and in the presence of each other. The adsorption density of PAA is found to decrease with an increase of pH while that of PVA shows the opposite trend. In a binary system containing PAA and PVA, the presence of PVA does not affect the adsorption of PAA onto alumina, but the addition of PAA diminishes the adsorption of PVA in the pH range investigated. The adsorption isotherm of PAA at acidic pH exhibits high-affinity Langmuirian behavior. The isotherms for PVA appear rounded and are of the low-affinity type. Once again the adsorption isotherms of PAA remain unaltered in the presence of PVA whereas those of PVA are significantly affected resulting in a lowering of the adsorption density consequent to PAA addition. A variation in the sequence of addition of PAA and PVA does not affect the adsorption behavior of either of the polymers. The electrokinetic behavior of alumina with PAA is hardly influenced by the addition of PVA. On the other hand, the electrophoretic mobility of alumina in the presence of PVA is significantly altered in the presence of PAA and closely resembles the trend observed with PAA alone. Desorption studies reveal that over 80% of PVA could be desorbed in the pH range 3-9 whereas in the case of PAA, the percent desorption increases from 20 to about 70% as the pH is increased from about 3 to 8. Solution conductivity tests confirm interaction of aluminum species and PAA in the bulk solution. FTIR spectroscopic data provide evidence in support of hydrogen bonding and chemical interaction in the case of the PAA-alumina system and hydrogen bonding with respect to the PVA-alumina interaction. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes.

1. We used confocal Ca2+ imaging and fluo-3 to investigate the transition of localized Ca2+ releases induced by focal caffeine stimulation into propagating Ca2+ waves in isolated rat ventricular myocytes. 2. Self-sustaining Ca2+ waves could be initiated when the cellular Ca2+ load was increased by elevating the extracellular [Ca2+] ([Ca2+]o) and they could also be initiated at normal Ca2+ loads when the sensitivity of the release sites to cytosolic Ca2+ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca2+ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining Ca2+ waves on elevation of [Ca2+]o. Inhibition of SR Ca2+ uptake by thapsigargin in cells already preloaded with Ca2+ above normal levels did not prevent local Ca2+ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 %. Tetracaine (0.75 mM) caused transient complete inhibition of both local and propagating Ca2+ signals, followed by full recovery of the responses due to increased SR Ca2+ accumulation. 3. Computer simulations using a numerical model with spatially distinct Ca2+ release sites suggested that increased amounts of releasable Ca2+ might not be sufficient to generate self-sustaining Ca2+ waves under conditions of Ca2+ overload unless the threshold of release site Ca2+ activation was set at relatively low levels (< 1.5 microM). 4. We conclude that the potentiation of SR Ca2+ release channels by luminal Ca2+ is an important factor in Ca2+ wave generation. Wave propagation does not require the translocation of Ca2+ from the spreading wave front into the SR. Instead, it relies on luminal Ca2+ sensitizing Ca2+ release channels to cytosolic Ca2+.

Algorithms↗

PubMed1999

High-speed data acquisition system and receiver configurations for time-domain radiofrequency electron paramagnetic resonance spectroscopy and imaging.

Design strategies, system configuration, and operation of a dual-channel data acquisition system for a radiofrequency (RF) time-domain electron paramagnetic resonance (EPR) spectrometer/imager operating at 300 MHz are described. This system wasconfigured to incorporate high-speed analog-to-digital conversion (ADC) and summation capabilities with both internal and external triggering via GPIB interface. The sampling rate of the ADC is programmable up to a maximum of 1 GS/s when operating in a dual-channel mode or 2 GS/s when the EPR data are collected in a single-channel mode. By using high-speed flash ADCs, a pipelined 8-bit adder, and a 24-bit accumulator, a repetition rate of 230 kHz is realized to sum FIDs of 4096 points. The record length is programmable up to a maximum of 8K points and a large number of FIDs (2(24)) can be summed without overflow before the data can be transferred to a host computer via GPIB interface for further processing. The data acquisition system can operate in a two-channel (quadrature) receiver mode for the conventional mixing to baseband. For detection using the single-channel mode, the resonance signals around the center frequency of 300 MHz were mixed with a synchronized local oscillator of appropriate frequency leading to an intermediate frequency (IF) which is sampled at a rate of 2 GS/s. Comparison of quadrature-mode and an IF-mode operation for EPR detection is presented by studying the FID signal intensity across a bandwidth of 10 MHz and as a function of transmit RF power. Imaging of large-sized phantoms accommodated in appropriately sized resonators indicates that IF-mode operation can be used to obtain distortion-free images in resonators of size 50 mm diameter and 50 mm length.

Data Collection↗

PubMed1999

Attenuation of renal ischemia-reperfusion injury with selectin inhibition in a rabbit model.

BACKGROUND: The selectin glycoproteins are involved in the pathogenesis of renal ischemia-reperfusion injury. We investigated the ability of glycyrrhizin, a known selectin inhibitor, to attenuate renal ischemia-reperfusion injury. METHODS: Eighteen New Zealand white rabbits underwent midline laparotomy with renal artery cross-clamping. After 30 minutes of reperfusion, group 1 (control, n = 10) animals received a saline infusion, while group 2 (GLY, n = 8) animals received a glycyrrhizin infusion. Renal function was compared between the two groups after 72 hours of reperfusion. A t test was utilized, with alpha set at P<0.05. RESULTS: Group 1 and group 2 animals had similar baseline renal function. However, after 72 hours of reperfusion, group 1 animals had a significantly higher mean blood urea nitrogen creatinine ratio than group 2 animals (P<0.01), indicating preserved renal function in rabbits treated with glycyrrhizin. CONCLUSIONS: Selectin blockade using glycyrrhizin attenuates renal ischemia-reperfusion injury when given 30 minutes after the onset of reperfusion in a rabbit model.

Animals↗

PubMed1999

Characterization and hormonal modulation of immunoreactive thiamin carrier protein in immature rat Sertoli cells in culture.

Immature rat Sertoli cells synthesize and secrete a protein species which has immunological similarity with chicken egg thiamin carrier protein (TCP) as assessed by immunocytochemical localization, liquid phase radioimmunoassay (RIA), immunoprecipitation of [35S]-methionine incorporated newly synthesized proteins by polyclonal antibodies (pAbs) to chicken TCP and tryptic peptide mapping of iodinated immunoprecipitated proteins. FSH and testosterone together bring about 4-fold induction of Sertoli cell TCP over the control levels which is inhibitable upto 75% by an aromatase inhibitor. Addition of optimal concentrations of exogenous estradiol-17beta to the cultures causes 2-fold enhancement of secretion of TCP which can significantly be inhibited by tamoxifen, when added along with estradiol-17beta. These results show that Sertoli cells produce estrogen-inducible TCP, presumably to transport the vitamin to the developing germ cells.

Animals↗

PubMed1999

The S7 ribosomal protein gene is truncated and overlaps a cytochrome c biogenesis gene in pea mitochondria.

The pea mitochondrial genome contains a truncated rps7 gene lacking ca. 40 codons at its 5' terminus. This single-copy sequence is immediately downstream of and slightly overlapping an actively transcribed and edited reading frame of 744 bp (designated ccb248) homologous to the bacterial helC gene which encodes a subunit of the ABC-type heme transporter involved in cytochrome c biogenesis. This region of mitochondrial DNA appears recombinogenic, and the carboxy-termini of helC-type proteins are predicted to vary in sequence and length among plants. Sequences corresponding to the 5' coding region of rps7 were not detected elsewhere in the pea mitochondrial genome using wheat rps7 probes, and only a very short internal rps7 segment was observed in soybean mitochondrial DNA. The presence of rps7-homologous sequences in the nuclear genomes of pea and soybean is consistent with the recent transfer of a functional mitochondrial rps7 gene to the nucleus in certain plant lineages.

ATP-Binding Cassette Transporters↗

PubMed1999

Characterization and hormonal modulation of immunoreactive thiamin carrier protein secreted by adult rat Leydig cells in vitro.

Leydig cells isolated from adult rats and maintained under defined conditions in culture secrete a protein of molecular weight (Mr) 70 000 which is immunologically similar to chicken thiamin carrier protein (TCP). Synthesis of immunoreactive TCP by these cells is demonstrated by immunoprecipitation of [35S]methionine incorporated, newly synthesized proteins with monoclonal and polyclonal antibodies to chicken TCP. The amount of immunoreactive TCP secreted into the culture supernatant is quantitated by using a specific radioimmunoassay. Under the influence of LH, secretion of immunoreactive TCP is enhanced 3-fold and can be inhibited by up to 70% with aromatase inhibitor (1,4,6-androstatrien-3,17-dione). Cyclic AMP acts as a second messenger in the sequence of events involved in LH-induced elevation of immunoreactive TCP in Leydig cells. The effects of exogenous estradiol-17beta and diethylstilbestrol are comparable in terms of stimulation of secretion of immunoreactive TCP by these cells. Tamoxifen brought about a 70% decrease in the elevated levels of immunoreactive TCP. These results suggest that estrogen mediates immunoreactive TCP induction in hormonally stimulated adult rat Leydig cells.

Animals↗

PubMed1999

Modulation of the impaired drug metabolism in sarcoma-180-bearing mice by echitamine chloride.

Echitamine chloride (EC), an indole alkaloid, extracted from the bark of Alstonia scholaris has got highly promising anticancer effect. The effect of this drug on the microsomal drug detoxifying system was studied in sarcoma-180 induced mice. When given sub-cutaneously at a dosage of 5 mg/kg body weight, it was able to alter the impaired drug detoxifying system which was observed in the Sarcoma-180 bearing mice. The levels of microsomal protein, Cyt-P450, Cyt-b5, NADH-Cyt-C-reductase, NADPH-Cyt-C-reductase, and glu-6 phosphatase were determined. The levels of these drug metabolizing enzymes were decreased in S-180 bearing mice. EC treatment corrected to near normal levels of these enzymes and microsomal hemeproteins. In order to understand the mechanism responsible for the decreased protein level and its normalization after treatment with EC, 3H-Phenylalanine incorporation study was carried out. From the results, it is observed that the synthesis of apoproteins is also altered in tumor-bearing animals. All these changes which were observed in tumor-bearing animals were corrected to near normal levels after treatment with EC.

Alkaloids↗

PubMed1998

Identification and mapping of linear antigenic determinants of chicken riboflavin carrier protein.

All of the possible 212 overlapping octapeptides covering the amino acid sequence of chicken egg white riboflavin carrier protein (RCP) was synthesized on polyethylene rods. To identify the peptides constituting the sequential antigenic epitopes on chicken RCP, a PEPSCAN ELISA was employed where antibodies raised against SDS-treated, reduced and carboxymethylated RCP (RCM-RCP) in mice, rats (n = 4), rabbits and monkeys (n = 3) were used. By this approach, we could identify five sequences on chicken RCP commonly recognized by all the antisera from these species which were spanning the residues 10-17, 42-49, 134-141, 172-179 and 200-207. Analysis of the data for each individual antiserum indicated inter- and intra-species variations with N- and C-terminal shifts in peak reactivity. The present study offers clues for development of potential immunocontraceptive vaccines.

Amino Acid Sequence↗