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Biomedical subjects

R Saini

Publications and source records attributed to R Saini.

At least 37 records · Page 2Linked to original sources
PubMed1994

Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group.

To establish the value of adjuvant dl-sotalol to digoxin for control of the ventricular response in chronic atrial fibrillation, 60 patients were evaluated in a multicenter, randomized, double-blind, parallel, placebo-controlled study. Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day. The combination of digoxin and dl-sotalol, at either 80 or 160 mg/day, resulted in a statistically significant reduction in heart rate at rest and with exercise during both exercise testing and ambulatory monitoring. No significant difference was observed between the two doses of dl-sotalol. There was no significant difference with regard to symptoms or side effects among the three groups. In summary, dl-sotalol was noted to be a safe and effective adjuvant to digoxin for control of the ventricular response in chronic atrial fibrillation.

Atrial Fibrillation↗
PubMed1992

Cerebral artery aneurysms in children infected with human immunodeficiency virus.

More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.

Brain↗
PubMed1991

Lung puncture aspiration in the diagnosis of acute pneumonias.

The present study was carried out in 100 children of acute pneumonia to establish the diagnosis of etiologic agents. Clinico-radiological assessment and routine investigations including sputum, throat swab and blood culture did not help in identifying the offending micro-organisms. The bacteriological examination of lung puncture aspirate was the most satisfactory tool for the etiological diagnosis. Direct smear examination/culture were positive in 50% aspirates. On cytology, definite epithelioid granulomas indicated tuberculous infection. However, in direct smear/culture negative patients, predominant mononuclear cell infiltration in the aspirated material may indicate non-pyogenic infection. Staphylococcus aureus (22%) was the commonest organism causing pneumonia in the present study.

Acute Disease↗
PubMed1990

Factor IXHollywood: substitution of Pro55 by Ala in the first epidermal growth factor-like domain.

Factor IX is a multidomain protein essential for hemostasis. We describe a mutation in a patient affecting the first epidermal growth factor (EGF)-like domain of the protein. All exons and the promoter region of the gene were amplified by the polymerase chain reaction method, and sequenced. Only a single mutation (C----G), that predicts the substitution of Pro55 by Ala in the first EGF domain was found in the patient's gene. This mutation leads to new restriction sites for four enzymes. One new site (Nsi) was tested in the amplified exon IV fragment and was shown to provide a rapid and reliable marker for carrier detection and prenatal diagnosis in the affected family. The factor IX protein, termed factor IXHollywood (IXHW), was isolated to homogeneity from the patient's plasma. As compared with normal factor IX (IXN), IXHW contained the same amount of gamma-carboxy glutamic acid but twice the amount of beta-OH aspartic acid. Both IXHW and IXN contained no detectable free -SH groups. Further, IXHW could be readily cleaved to yield a factor IXa-like molecule by factor Xla/Ca2+. However, IXaHW (compared with IXaN) activated factor X approximately twofold slower in the presence of Ca2+ and phospholipid (PL), and 8- to 12-fold slower in the presence of Ca2+, PL, and factor VIIIa. Additionally, IXaHW had only approximately 10% of the activity of IXaN in an aPTT assay. In agreement with the nuclear magnetic resonance-derived structure of EGF, the Chou-Fasman algorithm strongly predicted a beta turn involving residues Asn-Pro55-Cys-Leu in IXN. Replacement of Pro55 by Ala gave a fourfold decrease in the beta turn probability for this peptide, suggesting a change(s) in the secondary structure in the EGF domain of IXHW. Since this domain of IXN is thought to have one high-affinity Ca2+ binding site and may be involved in PL and/or factor VIIIa binding, the localized secondary structural changes in IXHW could lead to distortion of the binding site(s) for the cofactor(s) and, thus, a dysfunctional molecule.

Alanine↗
PubMed1988

Metal ion blockage of tritium incorporation into gamma-carboxyglutamic acid of prothrombin. Stoichiometry of gamma-carboxyglutamic acid to Gd3+ for the high affinity sites.

Prothrombin possesses two high affinity and four low affinity gamma-carboxyglutamic acid (Gla)-dependent gadolinium binding sites. Earlier work (Price, P. A., Williamson, M. K., and Epstein, D. J. (1981) J. Biol. Chem. 256, 1172-1176) has shown that tritium can be specifically incorporated at the gamma-carbon of Gla in proteins at pH 5. In the present work we show that inclusion of saturating concentrations of Ca2+ in nondenaturing buffer systems ranging from pH 5.5 to 8.5 prevents the exchange of tritium into all 10 Gla residues of prothrombin. Similarly, saturating concentrations of Gd3+ prevent tritium incorporation into Gla at pH 5.5. Positive cooperativity was observed for the binding of Gd3+ to human prothrombin (at pH 5.5) for the two high affinity sites (Kd congruent to 35 nM). The four low affinity sites bind Gd3+ with a Kd congruent to 5 microM. Incubation of prothrombin ranging in concentrations from 10 to 40 microM with 2 eq of Gd3+ at pH 5.5 prevents 5.7 (average of seven determinations) Gla residues from tritium incorporation. Sedimentation velocity experiments conducted at pH 5.5 indicate that prothrombin in the presence of saturating concentrations of Gd3+ polymerizes, most likely, to a trimer. Further, in the presence of 2 eq of Gd3+, calculated percent weight average concentration of monomer prothrombin is congruent to 100% at 10 microM, approximately equal to 95% at 20 microM, and congruento to 80% at 40 microM protein concentration. Thus, it appears that under conditions in which prothrombin primarily exists as a monomer, occupancy of the initial two metal binding sites by Gd3+ involves six Gla residues.

1-Carboxyglutamic Acid↗
PubMed1987

Fibronectin binding to glomerular basement membrane is altered in diabetes.

We examined the ability of fibronectin, an extracellular glycoprotein that interacts with cell surfaces and matrix components, to bind to glomerular basement membrane and the effect of diabetes on this binding. 125I-labeled fibronectin binding to rat glomerular basement membrane (GBM) was dose dependent, related to time and amount of basement membrane, and inhibited by unlabeled fibronectin but not by unrelated proteins. Binding was reduced approximately 60% when GBM was pretreated with collagenase and approximately 24% when pretreated with chondroitinase plus heparinase. Treatment with NaCl had little effect on binding, whereas reduction with beta-mercaptoethanol removed approximately 25% of the bound 125I-fibronectin. Binding to samples prepared from rats with streptozocin-induced diabetes was significantly increased compared with that observed with control preparations at all concentrations of fibronectin and of basement membrane tested. The findings provide direct evidence that fibronectin binds to GBM and that this binding, which represents a biologic function of the protein, is enhanced in diabetes.

Animals↗
PubMed1985

Purification and characterization of Escherichia coli xanthine-guanine phosphoribosyltransferase produced by plasmid pSV2gpt.

The enzyme xanthine-guanine phosphoribosyltransferase from Escherichia coli cells harboring the plasmid pSV2gpt has been purified 30-fold to near homogeneity by single-step GMP-agarose affinity chromatography. It has a Km value of 2.5, 42 and 182 microM for the substrates guanine, xanthine and hypoxanthine, respectively, with guanine being the most preferred substrate. The enzyme exhibits a Km value of 38.5 microM for PRib-PP with guanine as second substrate and of 100 microM when xanthine is used as the second substrate. It is markedly inhibited by 6-thioguanine, GMP and to a lesser extent by some other purine analogues. Thioguanine has been found to be the most potent inhibitor. The subunit molecular weight of xanthine-guanine phosphoribosyltransferase was determined to be 19 000. The in situ activity assay on a nondenaturing polyacrylamide gel electrophoresis gel has indicated that a second E. coli phosphoribosyltransferase preferentially uses hypoxanthine as opposed to guanine as a substrate, and it does not use xanthine.

Electrophoresis, Polyacrylamide Gel↗
PubMedDate not supplied

Calcipotriol in vitiligo: a preliminary study.

A large variety of therapeutic agents have been tried for the treatment of vitiligo, but psoralens continue to be the main treatment. Twenty-one patients age 5 to 17 years with vitiligo were enrolled in this study. The children were advised to apply calcipotriol 50 microg/g in the evening and expose themselves to sunlight the next day for 10 to 15 minutes. The patients were followed at 3-week intervals. Initial repigmentation occurred in the majority of children after 6 to 12 weeks of treatment. Marked to complete repigmentation was seen in 10 of 18 patients. Four patients showed moderate improvement while the remaining four patients showed minimal or no improvement. No patient developed new lesions. The repigmentation was cosmetically excellent in the majority of children. All patients tolerated the calcipotriol well except for three patients who complained of mild irritation on application. All of the laboratory investigations, including serum calcium levels remained normal. The rationale for this study originated from recent advances in the understanding of vitiligo at the molecular level. Furthermore, development of hyperpigmentation in patients with psoriasis receiving treatment with PUVA and calcipotriol has been observed. Our results are encouraging and offer a new and potentially efficacious treatment for this pigmentation disorder in children.

Administration, Cutaneous↗
PubMedDate not supplied

Rainfall timing and frequency influence on leaching of Escherichia coli RS2G through soil following manure application.

The time between swine (Sus scrofa) manure application to soil as a crop fertilizer, the first rainfall event, and the frequency of rainfall events should influence leaching potential of fecal pathogens. Soil microcosms were inoculated in the lab with a swine manure isolate of Escherichia coli, strain RS2G, expressing green fluorescent protein, to examine how timing and frequency of rainfall events influences RS2G leaching and survival in soil. Liquid swine manure inoculated with RS2G was applied to intact soil cores (20 cm in diameter x 30 cm long) 4, 8, or 16 d before the first rainfall event (50.8 mm over a 4-h period), and each core received one to three rainfall events. Manure application methods (no-till surface-broadcast, broadcast and incorporated, and tilled before broadcast) had no affect on leaching, although there was greater survival in soils when the manure had been incorporated. Most of the RS2G in the leachate appeared following the first rainfall event and RS2G leaching decreased with increasing time between manure application and the first rainfall, although leachates contained as much as 3.4 to 4.5 log colony forming units (CFU) 100 mL(-1) of RS2G when the first rainfall occurred 16 d after manure application. With increasing frequency of rainfalls there was a decrease in subsequent concentrations of RS2G in the leachate. There was no correlation between leachate RS2G and total coliforms or fecal streptococci concentrations. Soil RS2G numbers were 1 to 10% of the inoculum regardless of the length of time between manure application and the first rainfall. RS2G leaching was mostly influenced by the time between manure application and first rainfall event, and significant leaching and survival in soil was possible even if the first rain occurred 16 d after manure application.

Animals↗