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Biomedical subjects

A Grover

Publications and source records attributed to A Grover.

At least 19 recordsLinked to original sources
PubMed2003

Estrogen potentiates the combined effects of transforming growth factor-beta and tumor necrosis factor-alpha on adult human osteoblast-like cell prostaglandin E2 biosynthesis.

Reports that estrogen treatment modulates arachidonic acid metabolism by bone and bone cells are found in the literature. However, conflicting indications of the relationship that exists between estrogen and arachidonic acid metabolism emerge from the analysis of those reports. The present studies were undertaken to determine if estrogen effected the production of prostaglandins (PG) in human osteoblast-like (hOB) cell cultures derived from adults, under basal or cytokine-stimulated conditions. A 48-hour estrogen pretreatment did not modify hOB cell PG biosynthesis on a qualitative basis, and PGE2 formation predominated under all tested conditions. Estrogen pretreatment did lead to increased PGE2 production in specimens stimulated conjointly with transforming growth factor-beta1 and tumor necrosis factor-alpha ( p < 0.001). No changes in PGE2 production were observed in estrogen pretreated specimens stimulated singly with either tested cytokine, nor in samples in which either TGFbeta or TNF was replaced by interleukin-1beta. Anti-estrogen (ICI 164,384) inclusion prevented the estrogen-dependent increase in PGE2 production in the TGFbeta plus TNF-stimulated samples. These results suggest that an estrogen effect on bone cell prostaglandin biosynthesis may be most evident and significant under conditions in which the cells are exposed to multiple osteotropic cytokines, a condition that applies during the bone remodeling process.

Adult↗
PubMed2003

Maternal and perinatal outcome in rheumatic heart disease.

OBJECTIVES: To study the maternal and perinatal outcome of pregnancies complicated by rheumatic heart disease. METHODS: A retrospective study was carried out in the cardio-obstetric clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh (India) over a period of 13 years (1987-1999) involving 486 pregnant patients with rheumatic heart disease. Maternal and perinatal outcome was reviewed. RESULTS: Three hundred and four patients (63.3%) had single valve involvement and mitral stenosis was the most predominant lesion (89.2%). One hundred and seventy one (38.6%) patients had undergone surgical correction prior to the onset of pregnancy. One hundred and thirteen patients (22.6%) were identified as NYHA class III-IV. Mitral valvotomy was performed during pregnancy in 48 patients. The incidence of preterm birth and small for gestational age newborns was 12% and 18.2%, respectively. There were 10 maternal deaths, of which eight patients were NYHA III and IV. CONCLUSIONS: Rheumatic heart disease in pregnancy is associated with significant maternal and perinatal morbidity in NYHA class III-IV patients.

Adult↗
PubMed2003

Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease.

BACKGROUND: Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardiovascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation. AIMS: In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control. RESULTS: ADP- and epinephrine-induced platelet aggregation was 78.2 +/- 12.8% and 76.7 +/- 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 +/- 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 +/- 11.4% and 50.3 +/- 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 +/- 11.7% and 38.5 +/- 19.8% platelet aggregation with ADP, respectively). CONCLUSION: Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg.

Adenosine Diphosphate↗
PubMed2002

Isolation and expression analysis of salt stress-associated ESTs from contrasting rice cultivars using a PCR-based subtraction method.

Salt stress adversely affects the growth of rice plants. To understand the molecular basis of salt-stress response, four subtracted cDNA libraries were constructed employing specific NaCl-stressed tissues from salt-tolerant (CSR 27 and Pokkali) and salt-sensitive (Pusa basmati 1) rice cultivars. An efficient PCR-based cDNA subtraction method was employed for the isolation of the salt-stress responsive cDNA clones. In all, 1,266 cDNA clones were isolated in the course of this study, out of which 85 clones were end-sequenced. Database search of the sequenced clones showed that 22 clones were homologous to genes that have earlier been implicated in stress response, 34 clones were novel with respect to their function and six clones showed no homology to sequences in any of the public database. Northern analysis showed that the transcript expression pattern of selected clones was variable amongst the cultivars tested with respect to stress-regulation.

Blotting, Northern↗
PubMed2001

Distribution of cells bearing B-cell alloantigen(s) in North Indian rheumatic fever/rheumatic heart disease patients.

Numerous investigators have developed monoclonal antibodies against B-cell alloantigen(s) of rheumatic fever. However, the developed monoclonals do not have the same significance in all the populations. We have developed a battery of monoclonals against B-cell alloantigens of North Indian rheumatic fever patients. In the present study, we have used these monoclonals to examine the frequency of rheumatic antigens in 30 patients with recurrence of rheumatic activity (RRA), 30 of rheumatic heart disease (RHD) patients and 50 controls using alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. These patients were examined at the time of registry and after three months follow up. RRA patients showed higher percentage of lymphocyte positive as compare to RHD and controls. Interestingly, on follow-up RRA patients showed significant decline in positive lymphocyte as compare to first visit whereas no such change was observed in RHD patients. There were 90-93% of RRA and RHD patients positive with these monoclonals. A significant age variation of rheumatic cells was also noticed in all groups of rheumatic patients. We conclude that monoclonals raised from the same ethnic population are highly specific and cost effective to use them to develop an easy field test system such as APAAP, to identify the individual at risk, to develop rheumatic fever. It is also suggested that the alloantigen marker may persist through out life and gets activated after recurrence of the disease.

Adolescent↗
PubMed2001

Involvement of nitric oxide in the antiaggregatory effect of enalapril.

This study was conducted to examine the effects of single dose enalapril (1.6 mg/kg) on platelet aggregation alone and after an intravenous bolus dose of the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (L-NNA; 40 mg/kg). Blood samples were collected before and 1, 2 and 6 h after the administration of drugs in rhesus monkeys. Enalapril was administered via a nasogastric tube while L-NNA was administered by the intravenous route. Platelet aggregation was stimulated with adenosine diphosphate (ADP) in platelet rich plasma (PRP). Enalapril significantly inhibited platelet aggregation with a peak effect at 6 h. Upon administration of L-NNA, there was a significant increase in the percentage of platelet aggregation. This effect was partially antagonized by enalapril. The present study demonstrates that enalapril may possess antiaggregatory effects, which may be mediated via nitric oxide mechanisms.

Adenosine Diphosphate↗
PubMed2001

Arabidopsis thaliana Hsp100 proteins: kith and kin.

Arabidopsis thaliana, the first plant for which the entire genome sequence is available, was also among the first plant species from which Hsp100 proteins were characterized. The Athsp101 complementary DNA (cDNA) corresponds to the gene identification At1g74310 in the Arabidopsis genome sequence. Analysis of the genome revealed 7 additional proteins that are variably homologous with At1g74310 throughout the entire amino acid sequence and significant similarities or identities in the signature sequences conserved among Hsp100 proteins. Although AtHsp101 is cytoplasmic, 5 of the 7 related proteins have predicted plastidial localization signals. This complete description of the AtHsp100 family sets the stage for future research on expression and function.

Amino Acid Sequence↗
PubMed2001

A randomized trial to compare the efficacy, safety, cost and platelet aggregation effects of enoxaparin and unfractionated heparin (the ESCAPEU trial).

OBJECTIVE: To compare the efficacy, safety, cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients. PATIENTS AND METHODS: Ninety-three patients with unstable angina were randomized to receive either unfractionated heparin (UFH) or enoxaparin in an open design clinical trial with blinded end point evaluation. The effects of the heparins on platelet aggregation were also compared. RESULTS: The composite end point of myocardial infarction, cardiac death, recurrent angina and need for intervention was observed in 62% of patients treated with UFH and in 37% of patients treated with enoxaparin (RR 1.7, 95% CI 0.75 to 3.71, p = 0.04). There was no difference in the frequency or severity of adverse events. A cost-effectiveness analysis showed both the heparins to be similar. Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin. CONCLUSIONS: Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety. No difference in costs was detected in this study. The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH.

Adult↗
PubMed2001

Open versus percutaneous dilatational tracheostomy: efficacy and cost analysis.

The economic advantages of percutaneous dilatational tracheostomies versus open tracheostomies in the operating room have been thoroughly evaluated. We are now reporting our comparison of the costs and charges of percutaneous dilatational tracheostomies with those of open bedside tracheostomies at our institution. The current literature comparing the two open techniques and the percutaneous method of placing tracheostomies was reviewed and the charges and costs for these procedures at our institution were compared. Patients were placed into one of three groups for analysis: open tracheostomies in the operating room (Group I), open tracheostomies in the intensive care unit (Group II), and percutaneous dilatational tracheostomies in the intensive care unit (Group III). Based on our own experience and a literature review it is evident that all three approaches to tracheostomies are safe. Economic analysis showed a savings of $180 in cost per procedure and a $658 savings in charges per procedure for the open method at the bedside when compared with the percutaneous method at the bedside. The professional fee for bronchoscopy was not included in this calculation; including this would lead to greater savings with the open method over the percutaneous method. Open tracheostomy in the operating room increased costs over the bedside procedure by $2194 and increased charges by $2871. For the 150 to 180 tracheostomies done each year at our institution utilization of the open technique at the bedside results in a cost savings of approximately $31,500 and a charge savings of $109,000 compared with the percutaneous dilatational tracheostomy. Both the open bedside and percutaneous dilatational methods are reasonable and safe options. However, the open bedside tracheostomy is a better utilization of resources and is more cost effective, and it is the procedure of choice at our institution.

Cost Savings↗
PubMed2000

A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.

OBJECTIVE: The current study was designed to investigate drug utilisation in the management of unstable angina in India and to calculate the costs incurred by patients in the treatment of a single episode of unstable angina. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. Data on the cost of treatment, investigations, income, and family size were collected from the case histories or direct interviews with the patients/relatives. RESULTS: A total of 336 consecutive prescriptions were evaluated. Aspirin was the most frequently prescribed drug (98%) followed by nitroglycerin infusion (90%) and enoxaparin (52%). One of the heparins was used by 89% of all patients and beta-blockers by up to 62% of the patients. Besides antianginals, antihypertensive (49%) and antidiabetic (16%) drugs were commonly coadministered. The mean (+/- SD) cost of treatment of a single episode of unstable angina in the hospital was US $494 (+/- 271) against an annual per capita income of US $245. The mean (+/- SD) cost incurred by the patients due to drugs alone during the hospital stay was US $70 (+/- 18) and enoxaparin accounted for 60% of the expenditure due to drugs. CONCLUSIONS: The results of our study show that low-molecular-weight heparin, enoxaparin, is replacing unfractionated heparin in the treatment of unstable angina. In view of the use of costly new drugs, there is an urgent need for carrying out pharmacoeconomic analysis in developing countries as the treatment of a single episode of unstable angina imparts a considerable economic burden on the patient.

Aged↗
PubMed2000

Characterization of a novel type VII beta-turn conformation for a bio-active tetrapeptide rigin A synergy between theoretical and experimental results.

The conformational analysis of an immunomodulating tetrapeptide rigin (H-Gly-Gln-Pro-Arg-OH), shown to possess diverse immunological activity, has been investigated both theoretically and experimentally for its conformational preferences. Unrestrained molecular dynamics simulation studies in implicit dimethylsulfoxide provide strong support for the existence of a significant population of ordered reverse turn structures for the major trans isomer. Of the three different energy minimized families, generated from computer molecular modelling, only one could be complemented by most of the 1D and 2D 1H NMR parameters obtained in dimethylsulfoxide-d6. A variable temperature NMR experiment in dimethylsulfoxide-d6 revealed that the preferred conformation is not stabilized by an intramolecular hydrogen bonding interaction. An analysis of the 2D ROESY experiment provides evidence in favour of an uncommonly observed, rather ill-defined type VII beta-turn structure. A survey of the observed specific inter-and intra-residue NOE connectivities and their comparison with one of the predicted low-energy conformations, demonstrates synergy between the theoretical molecular modelling and experimentally determined NMR spectral data. The primary structure, rather than long-range interactions, appears to be critical in determining the folding behaviour of the bio-active rigin. The present structural attributes may be valuable in peptide drug design and development of the rigin analogs having more effective stimulating activity.

Hydrogen Bonding↗
PubMed2000

Further observations and characterization of monoclonal antibodies reacting with B cell alloantigens associated with rheumatic fever and rheumatic heart disease.

Elevated levels of B lymphocytes with a unique surface alloantigen have been reported to be characteristic of patients with acute rheumatic fever or rheumatic heart disease. Mouse monoclonal antibodies (mAbs) to this alloantigen have been proposed as being useful in identifying individuals at risk for the development of these sequelae of group A streptococcal infection. However, previous studies have suggested that the discriminating ability of the mAbs was highest when the mAbs were made by using lymphocytes from the same ethnic population. To confirm and extend this observation, additional mouse mAbs were developed and their properties defined. These three mAbs-PG-12A, PG-13A, and PG-20A-reacted with B cells from more than 90% of North Indian patients with acute rheumatic fever or rheumatic heart disease. Each of these three new mAbs identified the highest levels of reactive B cells in patients with active acute rheumatic fever. Lower levels of positive reacting lymphocytes were found in individuals with quiescent chronic rheumatic heart disease, and markedly reduced percentages of reactive cells were observed in normal control subjects. The proportion of reactive lymphocytes in individual patients varied according to which of the three was tested, suggesting the possibility of a spectrum of "rheumatic" epitopes in susceptible individuals. The data further suggested that enhanced discriminatory ability for identifying "at-risk" susceptible patients could be obtained by testing with a combination of mAbs. If reduction in the incidence of acute rheumatic fever can be facilitated by early identification of susceptible individuals, accurate and sensitive detection of a marker antigen would result in more cost-effective public health measures. Additional population studies are required to more precisely define and confirm these detection techniques.

Adult↗
PubMed2000

Molecular strategies for improving waterlogging tolerance in plants.

Plants, like animals, are obligate aerobes, but due to their inability to move, have evolved adaptation mechanisms that enable them to survive short periods of low oxygen supply, such as those occurring after heavy rain or flooding. Crop plants are often grown on soils subject to waterlogging and many are sensitive to waterlogging of the root zone. The combination of unfavourable weather conditions and suboptimal soil and irrigation techniques can result in severe yield losses. The molecular basis of the adaptation to transient low oxygen conditions has not been completely characterized, but progress has been made towards identifying genes and gene products induced during low oxygen conditions. Promoter elements and transcription factors involved in the regulation of anaerobically induced genes have been characterized. In this paper an account is presented of the molecular strategies that have been used in an attempt to increase flooding tolerance of crop plants.

Adaptation, Physiological↗
PubMed1999

5' splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10.

Missense and splice site mutations in the microtubule-associated protein tau gene were recently found associated with fronto-temporal dementia and parkinsonism linked to chromosome 17 (Poorkaj et al. (1998) Ann. Neurol. 43, 815-825; Hutton et al. (1998) Nature 393, 702-705; Spillantini et al. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 7737-7741). The mutations in the 5' splice site of exon 10 were shown to increase the ratio of tau mRNAs containing exon 10 and thus the proportion of Tau protein isoforms with 4 microtubule binding repeat domains, although how this increase leads to neurodegeneration is presently unclear. The mechanism by which these mutations increase tau exon 10 splicing was not determined, although the mutations were predicted to disrupt a potential stem-loop structure that was likely involved in the regulation of exon 10 alternative splicing. Here we describe in vitro splicing assays and RNA structural analysis that demonstrate that the mutations do indeed act through disruption of the stem-loop structure and that the stability of this secondary structure feature at least partially determines the ratio of tau exon 10+/- transcripts. In addition, we provide evidence that the stability of the stem-loop structure underlies the alternative splicing of this exon in other species.

Alternative Splicing↗
PubMed1999

A novel candidate presenilin-1 interacting protein containing tetratricopeptide repeats.

The yeast two-hybrid system, immunofluorescence and co-immunoprecipitation techniques were used to identify a novel candidate protein with which presenilin-1 (PS-1) interacts. This interacting protein, the gene of which is encoded on chromosome 16, contains two tetratricopeptide repeats (TPR) that are known to mediate interactions between proteins, appears to be primarily localized to the cytoplasm of transfected HEK293 cells, and is expressed in brain. Preliminary yeast two-hybrid data suggests this candidate may interact with both heat shock protein-90 and heat shock protein-70 and thus may be a novel member of TPR-containing proteins which interact with this complex.

Alzheimer Disease↗
PubMed1999

Frequency of tau mutations in three series of non-Alzheimer's degenerative dementia.

Splice-site and missense mutations have been identified in tau associated with frontotemporal dementia with parkinsonism linked to chromosome 17. In this study we assessed the genetic contribution of tau mutations to three patient series with non-Alzheimer's (non-AD) degenerative dementia. The groups included (1) a community-based dementia series from Minnesota, MN; (2) a referral series with clinicopathological tauopathy; and (3) a pathologically confirmed familial frontotemporal dementia series from Manchester, UK. Comparing the three clinical series: in the stringently diagnosed Manchester frontotemporal dementia series, tau mutations were present in 13.6% of cases (three splice-site mutations); in the clinicopathological referral series that used more general inclusion criteria, 3 cases with P301L mutations were observed, which represents a lower mutation frequency of 3.6% (9.4% in familial cases); in contrast, tau mutations were not detected in the Minnesota community-based dementia series, suggesting the occurrence of these mutations in dementia generally is rare (<0.2%). These data identify the prevalence of mutations in three different clinical settings and indicate that this figure is sensitive to the diagnostic criteria used in each patient series.

Adult↗