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Biomedical subjects

A Grover

Publications and source records attributed to A Grover.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Pregnancy following cardiac valve replacement surgery.

OBJECTIVES: To study the outcome of pregnancy in women with artificial heart valves and to compare the maternal and perinatal outcome in mechanical and bioprosthetic valves. METHOD: Retrospective analysis of 34 pregnancies in 29 women who conceived after cardiac valve replacement was carried out. RESULTS: The majority of women (76.4%) delivered within 5 years of valve replacement. Anticoagulants were administered in 79.4% of pregnancies. Maternal mortality was 2.9% and maternal morbidity in the form of heart failure, atrial fibrillation, valve thrombosis, thromboembolism, bleeding complications and non-functioning prostheses were 2.9%, 5.8%, 2.9%, 2.9%, 11.7% and 2.9%, respectively. The incidence of prematurity was 5.8% and small for gestational age babies was 11.7%. There was no case of abortion. Two babies (5.8%) were still born, one of which had malformations. Maternal complications were significantly higher in women with bioprostheses, though the complications were more grave in the mechanical prostheses group. The perinatal outcome was almost similar in both the groups. CONCLUSION: The perinatal outcome was not different in women with bioprosthetic valves from the ones with mechanical prostheses, but the maternal morbidity was more in women with bioprosthetic valves. Coumarin derivatives were safe and effective and did not lead to embryopathy.

Adult↗
PubMed1999

Superantigen-induced T cell responses in acute rheumatic fever and chronic rheumatic heart disease patients.

CD4+ and CD8+ T cells from healthy donors, acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD) patients responded variably to a superantigen from Streptococcus pyogenes--Streptococcal pyrogenic erythrogenic toxin A (SPE-A). In vitro culture of CD4+ T cells from ARF patients (CD4-ARF) with SPE-A exhibited a Th1 type of response as they produced high levels of IL-2, while CD4+ T cells from CRHD patients (CD4-RHD) secreted IL-4 and IL-10 in large amounts, i.e. Th2 type of cytokine profile. The skewing of human CD4+ T cells (in response to SPE-A stimulation) to Th1 or Th2 type reflects the role of the two subsets in a disorder with differing intensities at the two extremes of the spectrum. Moreover, the anergy induction experiments revealed that CD8-ARF and CD8-RHD undergo anergy (to different extents), whereas CD4+ T cells do not, in response to re-stimulation by SPE-A. These results initially demonstrate that both CD4+ and CD8+ T cells respond differentially to SPE-A, and hence it is an important observation with respect to the pathogenesis of ARF/CRHD. Anergy in CD8+ T cells in the presence of SPE-A in vitro goes a step further to show the clinical relevance of these cells and their possible role in suppression of the disease.

Acute Disease↗
PubMed1999

Evaluation of clinical practice guidelines on outcome of infection in patients in the surgical intensive care unit.

OBJECTIVE: In this study, clinical practice guidelines were developed by a multidisciplinary team for patients with infections admitted to a surgical intensive care unit (ICU). DESIGN: A 51-day baseline audit period (Phase I) in a 20-bed (private rooms) surgical ICU was compared with a 34-day period in the same unit after implementation of the guidelines (Phase II). PATIENTS: Phase I included 182 patients (670 patient days), and Phase II included 139 patients (427 patient days). RESULTS: There was no significant difference between patients in the Phase I and Phase II groups regarding age (65.4/19-95 vs. 64.8/18-90 yrs), gender (56% male vs. 55% male), severity of illness (mean Acute Physiology and Chronic Health Evaluation III, 38 vs. 39.1), total infections (respiratory, 8% vs. 4%; urinary tract, 15% vs. 4%; wound, 4% vs. 3%; skin/soft tissue, 3% vs. 7%; sepsis, 5% vs. 3%; intra-abdominal, 9% vs. 17%), and no infection (64% vs. 67%). Clinical outcomes of patients with infections in the Phase I group compared with those in the Phase II group were as follows: clinical improvement or cure, 64% vs. 76%; persistent infection, 17% vs. 11%; clinical failure, 0 vs. 2%; and death, 18% vs. 7% (p = NS). When patients with infections were compared, death rates were 20% in the Phase I group and 5.6% in the Phase II group (p = .02). After implementation of the clinical pathways, antibiotic costs were reduced from $676.54 per patient to $157.88 per patient (p = .001). Length of stay in the ICU was 3.7 days in the Phase I trial and a mean of 3 days in the Phase II trial (p = NS). Specimens of Escherichia coli demonstrated a trend toward a decreased resistance to all antibiotics and Pseudomonas aeruginosa to ciprofloxacin and aminoglycosides (p = NS). CONCLUSIONS: In this study, the use of clinical practice guidelines for patients who were admitted to the surgical ICU was shown to reduce costs, without adversely affecting patients' outcomes. This study has important implications for the use of clinical practice guidelines for the management of patients with infections who are admitted to surgical ICUs.

Aged↗
PubMed1999

Clinical, echocardiographic, and angiographic profile of patients with double-chambered right ventricle: experience with 48 cases.

Forty-eight patients with double-chambered right ventricle (DCRV) were prospectively studied over a 3-year period. Clinical, echocardiographic, hemodynamic, and angiographic studies were done in all. Three patients were studied postoperatively also. Fifteen patients underwent surgery confirming the diagnosis. Echocardiography detected anomalous muscle bundles (AMBs) in 39/41 patients in whom this study was carried out. Angiographically AMBs were best demonstrated in anteroposterior views in a systolic frame. Common associated anomalies found with DCRV were ventricular septal defects (69%), pulmonary valve stenosis (38%), and double-outlet right ventricle (10%).

Adolescent↗
PubMed1998

Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.

Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.

Alternative Splicing↗