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S Ray

Publications and source records attributed to S Ray.

At least 55 records · Page 3Linked to original sources
PubMed1991

Synthesis and pregnancy-inhibiting activity of 7-substituted androst-5-ene derivatives.

Synthesis of 7-aryl/allyl-substituted androstene derivatives 3a through 3g has been carried out by Grignard reaction on 3 beta,17 beta-diacetoxyandrost-5-en-7-one (2) with aryl/allyl magnesium bromide. Isomeric mixture of products 3b and 3c/3e and 3f/3h was separated by column chromatography. Stereochemical assignment at C-7 has been made on the basis of 13C nuclear magnetic resonance studies and chemical considerations. Compounds 6a and 6b were synthesized by alkylation of compound 5 with beta-(N,N-diethylamino)ethyl chloride hydrochloride and 1-(2-chloroethyl)pyrrolidine hydrochloride, respectively. Compound 3g (isomeric mixture) prevented pregnancy in 60% of rats at 10 mg/kg daily dose administered orally on days 1 to 7 of pregnancy; however, its only isolable 7 beta-hydroxy isomer, 3h, was inactive at this dose.

Androstenes↗
PubMed1991

Sequence variation between alleles reveals two types of copy correction at the 27-kDa zein locus of maize.

In many inbred lines of maize, two 27-kDa storage protein (zein) genes are found within tandem duplications of 12 kb. Both genes of the duplicated allele from the maize inbred line A188 were sequenced and compared to a similar duplicated allele in another inbred line, W22, and to a single-copy allele in the inbred line W64A. The comparisons reveal interesting patterns in the distribution of sequence changes between these alleles. Differences between the two duplicated alleles that are conserved between the two genes of each allele are found exclusively in the 5' region. In contrast, differences between the individual genes of each allele in the 3' region are conserved between the two alleles. The first case is indicative of an intraallelic copy correction mechanism, whereas the second may result from interallelic copy correction. These may be mediated by gene conversion processes, as previously described for other multigene families.

Alleles↗
PubMed1991

Cooperative assembly of simian virus 40 T-antigen hexamers on functional halves of the replication origin.

The cofactor ATP stimulates the formation of T-antigen double hexamers on the simian virus 40 core origin of replication (I. A. Mastrangelo, P. V. C. Hough, J. S. Wall, M. Dodson, F. B. Dean, and J. Horwitz, Nature [London] 338:658-662, 1989). We report here the pathway for the assembly of hexamers and double hexamers on the core origin. ATP triggers the cooperative assembly of hexamers on the early and late halves of the origin even when they are completely isolated. Hexamer assembly nucleates at T-antigen recognition pentanucleotides in the early half of the origin. In intact origins, assembly of the first hexamer on the early half of the origin cooperatively stimulates the assembly of a second hexamer on the adjacent late half of the origin. Thus, monomer-monomer and hexamer-hexamer interactions of T antigen, allosterically activated by ATP, constitute two distinct types of cooperative interaction with the origin. Finally, we show that the assembly of T-antigen hexamers on isolated half origins leads to the same array of structural changes that T antigen induces in intact origins. We conclude that the origin is divided into complementary halves that each promote the assembly of functional T-antigen hexamers.

Adenosine Triphosphate↗
PubMed1991

The zinc finger region of simian virus 40 large T antigen is needed for hexamer assembly and origin melting.

Simian virus 40 large T antigen contains a single sequence element with an arrangement of cysteines and histidines that is characteristic of a zinc finger motif. The finger region maps from amino acids 302 through 320 and has the sequence C-302 L K C-305 I K K E Q P S H Y K Y H-317 E K H-320. Previous genetic analysis has shown that the cysteine and histidine sequences and the contiguous S H Y K Y region in the finger are important for DNA replication in vivo. We show here that representative mutations in either of these elements of the finger prevent the assembly of large T antigen into stable hexamers in vitro. These same mutations have a characteristic effect on the interaction of T antigen with the simian virus 40 core origin of replication. The mutant T antigens bind to the central pentanucleotide domain of the core origin but fail to melt the adjacent inverted repeat domain and to untwist the adenine-thymine domain. These defects would prevent the formation of a replication bubble and the initiation of DNA replication. Finger mutations have lesser effects on the helicase function of T antigen and no observable effect on binding of T antigen to the mouse p53 protein. We propose that the zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication and that hexamers are needed for subsequent alterations in the structure of origin DNA. We cannot exclude the possibility that the zinc finger region also makes specific contacts with components of origin DNA.

Amino Acid Sequence↗
PubMed1991

Pharmacokinetics of 18F-labeled fluconazole in rabbits with candidal infections studied with positron emission tomography.

[4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in normal and infected animals. The biodistribution of fluconazole was determined after administration of the 18F-tracer with/without a pharmacological dose of unlabeled drug by radioactivity measurements on excised tissues. In normal rabbits and rabbits with candidal infection of the thigh, tissue concentrations of drug were determined by serial positron emission tomographic imaging. In rats, coinjection of tracer quantities of [4-18F]fluconazole with a pharmacological dose of unlabeled drug resulted in a relatively uniform distribution of radioactivity in most organs, whereas, when the 18F-tracer was injected alone, spleen, muscle and heart accumulation was decreased and liver accumulation was increased. In rabbits, this effect was less pronounced. Early accumulation of [4-18F]fluconazole was greater in infected muscle. The areas under the 2-hr uptake curves were 4.30 and 6.05 micrograms.hr.ml-1 for normal and infected tissue. A mathematical model was used to summarize the kinetics of fluconazole in normal and infected muscle. The model hypothesizes that fluconazole is compartmentalized in blood and tissue, with rate constants describing the transition between compartments. Direct measurement of the partition coefficient of fluconazole in muscle and predictions of the kinetic model were in close agreement, suggesting that fluconazole enters muscle via a passive transport mechanism. Transport rates of fluconazole, into (Kin) and out of tissue (kout), were increased in infected compared with normal muscle, possibly due to increased capillary permeability (Kin: 0.064 +/- 0.001 vs. 0.0270 +/- 0.0002, kout: 0.063 +/- 0.002 vs. 0.035 +/- 0.001).

Animals↗
PubMed1991

Developmental expression of the embryonic chicken brain DNA polymerase alpha and its binding with monoclonal antibodies against human KB cell DNA polymerase alpha.

Changes in DNA polymerase alpha activity accompanying tissue development have been well established in several systems. In most cases, DNA polymerase alpha activity decreases with development. Here, we report observed changes in DNA polymerase alpha activity throughout embryonic chicken brain (ECB) development. The level of DNA polymerase alpha activity was found to gradually decrease by 60% (2.3 to 0.8 nmol of [3H]dCMP incorporated/mg protein/h) between 9- and 19-day-old ECB. An enzyme-linked immunosorbent assay of DNA polymerase alpha utilizing monoclonal antibody SJK 237-71 (human KB cell DNA pol-alpha binder) also demonstrated a gradual decrease (up to 60%) of antigen over this same range of development. Analysis of DNA polymerase alpha from 11- and 19-day-old ECB by a 10 to 30% glycerol density gradient revealed a high molecular weight peak sedimenting near catalase (11.3 S) with activity at the 11th day being approximately 3-fold greater than activity at the 19th day. A Western immunoblot analysis utilizing monoclonal antibody SJK 237-71 (against human KB cell DNA polymerase alpha) showed a decrease in DNA polymerase alpha from 186 kilodaltons in 9- and 11-day ECB cell-free extracts to 120 kilodaltons in extracts from 13- to 19-day ECB. The conversion of DNA polymerase alpha from a higher to a lower molecular weight form may be a regulatory mechanism in eukaryotic DNA replication.

Animals↗
PubMed1991

A PMA degrading constitutive organomercurial lyase in a broad-spectrum mercury resistant Bacillus pasteurii strain DR2.

A broad-spectrum Hg-resistant strain of B. pasteurii DR2 utilized phenylmercuric acetate (PMA) as sole source of carbon. This bacterial strain contained a constitutive organomercurial lyase which specifically degraded PMA but not other organo-mercurials. This PMA-lyase activity was also stimulated to different extents when this bacterial strain was grown in presence of different organic compounds as sole source of carbon.

Bacillus↗
PubMed1990

Role of arginine 67 in the stabilization of chymotrypsin inhibitor 2: examination of amide proton exchange rates and denaturation thermodynamics of an engineered protein.

We have examined the contribution to protein stability of an interaction involving a charged hydrogen bond from an arginyl side chain (Arg67) in the serine proteinase inhibitor chymotrypsin inhibitor 2 (CI-2), by replacing this side chain with an alanyl residue by protein engineering. Using nuclear magnetic resonance spectroscopy (NMR), we have examined the effect of this mutation on the hydrogen-deuterium exchange rates of several backbone amide protons in the native and engineered proteins at 50 degrees C. These exchange rates provide a localized probe at multiple discrete sites throughout the protein and from comparison of native and mutant exchange rates allow calculation of the difference in free energy of exchange (delta delta Gex) resulting from the mutation. The results show that for the majority of amides observed this mutation results in delta delta Gex of ca. 1.7 kcal mol-1 over the whole CI-2 molecule. However, for two relatively exposed amide protons the exchange rates are found to be far less perturbed, implying that local unfolding mechanisms predominate for these protons. Direct measurement of the stability of both proteins to denaturation by guanidinum hydrochloride shows that the interaction contributes 1.4 kcal mol-1 to the stability of the molecule. This value is comparable to those obtained from the NMR exchange measurements and indicates that the exchange processes reflect the differences in stability between the native and mutant proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1990

Monomer sequence determination of carbohydrates using fast-atom bombardment mass spectrometry of periodate-oxidized acetate ester derivatives.

A derivatization method, adapted from that of Angel et al. (ref. 10), for sequencing sugar residues in partially degraded poly- and oligo-saccharides using positive-ion f.a.b.-m.s. is described. Derivative selection provides sequence information by directing fragmentation exclusively to both sides of glycosidic oxygen atoms and, in the case of opened rings, between glycosidic carbon and ring oxygen atoms. Polysaccharides or oligosaccharides are subjected to sequential periodate oxidation, borodeuteride reduction, and acetylation. The derivatized polysaccharides are then subjected to partial degradation, acetylation, and high-performance liquid chromatography (h.p.l.c.) purification. F.a.b.-m.s. data obtained on model compounds, using 3-nitrobenzyl alcohol as matrix for f.a.b.-m.s., demonstrated direction of fragmentation to both sides of the glycosidic oxygen atom in unoxidized residues, and to both sides of the acetal oxygen atoms in oxidized residues. Oligosaccharide linkage and sequence may thus be determined by observing fragmentation from both the reducing and non-reducing ends of the molecule. Two Salmonella lipopolysaccharides, derivatized by this procedure, were partially hydrolyzed and then acetylated. Analysis of the h.p.l.c.-purified oligosaccharide derivatives by f.a.b.-m.s. demonstrated the applicability of the technique for sequencing nmol quantities of branched structures.

Benzyl Alcohols↗
PubMed1990

A pilot study of quinidine and epirubicin in the treatment of advanced breast cancer.

Thirty-one patients were entered into a pilot study combining oral quinidine with epirubicin 100 mg m-2 as first line chemotherapy in advanced breast cancer. Three patients were treated with quinidine 1 g b.d., and developed symptoms of toxicity. Of eight subsequent patients treated with quinidine 500 mg b.d., two experienced tiredness and nausea and one severe oral toxicity with epirubicin. The remaining 20 patients received quinidine 250 mg b.d.; one developed cinchonism and one malaise, the remainder showing no excess toxicity compared with epirubicin alone. The median nadir WBC was similar with or without quinidine (2.3 vs 1.6 x 10(9) l-1) as was median nadir platelet count (175 vs 157 x 10(9) l-1). There was no evidence of significant cardiac toxicity. The median plasma quinidine level achieved was 5.6 mumol l-1 (range 2.1-22.1), which is within the range of concentrations which is effective in vitro at reversing experimental anthracycline resistance. A randomised controlled study is proposed to assess the impact of this potential modulation on the efficacy of epirubicin in advanced breast cancer.

Adult↗
PubMed1990

Scoliosis in trisomy 18.

Patients with trisomy 18 typically present with multiple congenital anomalies and most die within the first year. However, long-term survivors are not uncommon. Seventeen patients with trisomy 18 were evaluated to study the development of scoliosis associated with this disorder. There were 13 females and 4 males with ages ranging from birth to 22 years. Twelve patients died by age 2. None developed scoliosis or had vertebral anomalies. The five patients who survived beyond age 2 developed scoliosis. Curve progression was demonstrated in the patients who returned for follow-up. Bracing was not well tolerated in two patients with curves of 48 degrees and 58 degrees. Both had poor motor control and sitting ability. One patient with a 30 degree curve was successfully managed by bracing. Another patient with a severe scoliosis was successfully fused with anterior and posterior instrumentation. Patients with trisomy 18 should be carefully evaluated for scoliosis. Scoliosis in the older child, surviving beyond age 2, may be progressive and difficult to manage.

Abnormalities, Multiple↗
PubMed1990

Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer.

Many exercise protocols are in use in clinical cardiology, but no single test is applicable to the wide range of patients' exercise capacity. A new protocol was devised that starts at a low workload and increases by 15% of the previous workload every minute. This is the first protocol to be based on exponential rather than linear increments in workload. The new protocol (standardised exponential exercise protocol, STEEP) is suitable for use on either a treadmill or a bicycle ergometer. This protocol was compared with standard protocols in 30 healthy male volunteers, each of whom performed four exercise tests: the STEEP treadmill and bicycle protocols, a modified Bruce treadmill protocol, and a 20 W/min bicycle protocol. During the two STEEP tests the subjects' oxygen consumption rose gradually and exponentially and there was close agreement between the bicycle and the treadmill protocols. A higher proportion of subjects completed the treadmill than the bicycle protocol. Submaximal heart rates were slightly higher during the bicycle test. The STEEP protocol took less time than the modified Bruce treadmill protocol, which tended to produce plateaux in oxygen consumption during the early stages. The 20 W/min bicycle protocol does not take account of subjects' body weight and consequently produced large intersubject variability in oxygen consumption. The STEEP protocol can be used on either a treadmill or a bicycle ergometer and it should be suitable for a wide range of patients.

Adult↗
PubMed1990

Studies on synergism between penicillins and ambodryl (bromodiphenhydramine HCl), an antihistamine with antimicrobial property.

With respect to 31 different selected test bacteria, all sensitive to benzyl penicillin (Pc), ampicillin (Ap), methicillin (Me), ceporan (Ce), cloxacillin (Cx), streptomycin (Sm), kanamycin (Km), gentamicin (Gm), chloramphenicol (Cm), tetracycline (Tc), polymyxin (Pm) as well as ambodryl [Am; an antihistamine (bromodiphenhydramine HCl) with distinct antimicrobial properties], it was found that Am in combination either with Pc, Ap, Ce or Me consistently showed enhancement of antimicrobial effects resulting from synergism. A combination of Am with either Sm, Km, Gm or Tc, on the other hand, showed only additive effects. An interaction of the activities of Am with Pm also resulted in indifference effects. Determination of the area of inhibition zone, calculated from its diameter for the degree of synergism in case of Am and Pc, showed these synergistic effects to be significant (P less than 0.05) in comparison with their individual effects: this was corroborated by the determination of the fractional inhibitory concentration (FIC) index which was found to be less than 0.5. The synergism of Am-Pc combination was confirmed by in vivo studies by challenging mice with a virulent strain of S. typhimurium and looking for protection.

Bacteria↗
PubMed1990

Acid excretion and serum electrolyte patterns in patients with advanced chronic renal failure.

Hyperchloremic metabolic acidosis can be seen in advanced chronic renal failure (CRF). To study this further, we measured acid excretion under controlled conditions in 19 patients with severe but stable CRF. Twelve patients had a hyperchloremic metabolite acidosis, 3 had an elevated anion gap acidosis ('delta acidosis'), while the 4 remaining patients had a slightly decreased tCO2 with a normal anion gap and serum chloride level ('mild acidosis'). Ammonium excretion was markedly reduced in CRF patients (11 +/- 1 vs. 32 +/- 2 mEq/day in normal subjects, p less than 0.005), and likewise urinary titratable acid was diminished (18 +/- 2 mEq/day in patients, vs. 28 +/- 3 mEq/day in normal subjects; p less than 0.005). When expressed per 100 ml GFR, ammonium and titratable acid excretion were markedly increased in all groups of patients compared to normal subjects. The Tm for bicarbonate was 22.5 +/- 3.7 mEq/l for all CRF patients and 24 +/- 1 mEq/l for the patients with a hyperchloremic metabolic acidosis. We conclude that the hyperchloremic metabolic acidosis in advanced renal failure is due to diminished excretion of ammonium and titratable acid and is not due to an increased bicarbonate leak. As renal failure advances and renal mass declines, the remaining functioning nephrons hypersecrete acid.

Acidosis↗
PubMed1990

Pattern of acute myocardial infarction in a district hospital in Brunei Darussalam--a pilot study.

The objective of the authors was to study the pattern of presentation, risk factors, and natural course of acute myocardial infarction in the general population of Belait District in Brunei Darussalam. A prospective study was done of 100 consecutive cases of acute myocardial infarction admitted to the coronary care beds of a District General Hospital. The patients were followed up to 12 weeks after admission to hospital. There were three times more males than females (75 males, 25 females). Nine cases out of 75 males were below the age of 40 years, 3 being below 30 years. The mean age of the male denominator was 57.4 years while that of the female counterpart was 67.48 years showing a mean difference of 10.08 years. There were significant association with hypertension (31%), smoking (30%) and diabetes mellitus (27%). The majority of the patients had prodromal symptoms, the most common presenting symptoms were chest pain (63%) and shortness of breath (27%). Only 4% of the patients had silent infarction. Acute myocardial infarction is common in Brunei forming 2.6% of all the patients admitted to the medical wards and the relative rate is 3 times higher in males than in females. There is significant association of IHD with 3 main risk factors namely hypertension, smoking and diabetes mellitus.

Adult↗