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Biomedical subjects

D Stone

Publications and source records attributed to D Stone.

At least 127 records · Page 7Linked to original sources
PubMed1987

Epidemiology of intraocular pressure in a population screened for glaucoma.

This study evaluated the association between intraocular pressure and various sociodemographic characteristics, ocular findings, and cardiovascular risk factors in a population screened for glaucoma. A total of 2594 subjects older than 40 years residing in three urban areas of southern Israel participated. Of those screened 6.1% had a raised intraocular pressure (IOP greater than or equal to 21). The mean IOP increased with age, was higher among persons born in Africa or Asia than those born in Europe or America, higher among myopes than hypermetropes and among those with an enlarged cup-disc ratio (CDR). Analysis of variance tests indicated that refractive status, CDR, age, country of birth, and diabetes were each independently associated with IOP. In addition, associations between raised intraocular pressure and age, country of birth, myopia, CDR, diabetes, and glaucoma in the family were found.

Adult↗
PubMed1986

The impact of prenatal care on the outcome of pregnancy.

In a 12-months' prospective project all women delivering at the Soroka Medical Center, Beer-Sheba, Israel, were studied with regard to the type of prenatal care (P.C.) and the outcome of pregnancy. The Soroka Medical Center is the sole medical facility providing obstetric and neonatal services to the 300,000 inhabitants of the region. Prenatal care is delivered by a uniform network of 70 community-based stations. The availability, type and quality of services were uniform for all women and were not altered throughout the study period. The project encompassed 7308 deliveries. 2154 Bedouin women were excluded in order to avoid possible bias due to cultural and genetic characteristics. Data regarding 5154 Jewish women were analysed. Perinatal mortality was inversely proportional to the number of prenatal contacts. The uncorrected mortality rates were 12.7% in women entirely lacking P.C. and 6.2%, 1.9% and 1.0% in patients who had 1-6, 7-10 and 11 or more prenatal contacts respectively. The low-birthweight rate was significantly increased in women lacking prenatal care (22.8%) or having rudimentary care (17.4%) as compared to those who had 11 or more prenatal contacts with medical personnel (5.9%). Prenatal care reduced neonatal morbidity as expressed by the length of hospitalization, the frequency of infants with multiple diagnoses and the incidence of specific pathologies such as respiratory distress syndrome, light for dates and asphyxia. The incidence of some complications of pregnancy (abruptio placentae, premature labor, PROM) was significantly increased in women lacking P.C. or having inadequate P.C. (1-6 prenatal contacts). Moreover, lack of prenatal care was clearly connected with high-risk delivery, thus increasing the danger to the baby. It is suggested that many adverse effects of various socio-economic, genetic and general health factors may be diminished by proper prenatal care coupled with adequate obstetric and neonatal services.

Adult↗
PubMed1984

Characterization and amino acid sequence of Neisseria gonorrhoeae dihydrofolate reductase.

Dihydrofolate reductase has been purified from a trimethoprim-resistant strain of Neisseria gonorrhoeae. The enzyme showed a single component on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr = 18,000) and on isoelectric focusing in 5 M urea (pI = 6.8). Although gel electrophoresis under nondenaturing conditions resolved the preparation into two enzymatically active proteins (called form 1 and form 2), they were not genetically determined isozymes. Both had a similar dihydrofolate Km (2 microM), NADPH Km (10 microM), and trimethoprim Ki (20 nM), and form 2 (the slower migrating species) was shown to be generated from form 1 by the electrophoresis conditions. The complete covalent structure of the enzyme has also been determined. It is a single polypeptide composed of 162 residues and containing 4 cysteines. The gonococcal dihydrofolate reductase shares a 35% homology with the chicken liver enzyme and a 40% homology with the Escherichia coli enzyme. Most of these identities are residues that have been implicated in the binding of NADPH and methotrexate to the E. coli and Lactobacillus casei reductases.

Amino Acid Sequence↗
PubMed1984

Species-specific irreversible inhibition of Neisseria gonorrhoeae dihydrofolate reductase by a substituted 2,4-diamino-5-benzylpyrimidine.

Neisseria gonorrhoeae dihydrofolate reductase undergoes a time-dependent, irreversible inactivation by 2,4-diamino-5-[3,5-dimethoxy-4-(p-bromoacetamidophenoxy)benzyl] pyrimidine. The kinetics of inactivation are consistent with the reversible formation of an enzyme-inhibitor complex followed by covalent binding to the enzyme. The reversible component is competitive with dihydrofolate and has an inhibitor binding constant of 10 nM. Irreversible inactivation proceeds as a pseudo first-order process with a minimum inactivation half-time of 20 min and a Ki of 28 nM. Using radiolabeled inhibitor, it was shown that approximately 1 mol of ligand was covalently bound to the enzyme/mol of methotrexate binding site when the enzyme was completely inhibited. Radiolabeled inhibitor remained associated with the enzyme following denaturation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cyanogen bromide cleavage of the 14C-labeled enzyme-inhibitor complex yielded only one radioactive polypeptide, and sequence determinations showed that His-25 was modified by covalent attachment of the inhibitor. When dihydrofolate reductases from Lactobacillus casei, Streptococcus faecium, Escherichia coli, SR-1 rodent lymphoma, and chicken liver were tested with the affinity label, only the L. casei enzyme showed a time-dependent increase in inhibition. These data, along with comparisons of known amino acid sequences and x-ray crystal structures, were used to make predictions concerning the three-dimensional conformation of the gonococcal enzyme.

Folic Acid Antagonists↗
PubMed1984

Characterization of an R-plasmid dihydrofolate reductase with a monomeric structure.

A plasmid-encoded dihydrofolate reductase that originated in a clinical isolate of Salmonella typhimurium (phage type 179) moderately resistant to trimethoprim has been isolated and characterized. The dihydrofolate reductase (called type III) was purified to homogeneity using a combination of gel filtration, hydrophobic chromatography, and methotrexate affinity chromatography. Polyacrylamide gel electrophoresis under denaturing and nondenaturing conditions indicated that the enzyme is a 16,900 molecular weight monomeric protein. Kinetic analyses showed that trimethoprim is a relatively tight binding inhibitor (Ki = 19 nM) competitive with dihydrofolate. The enzyme is also extremely sensitive to methotrexate inhibition (Ki = 9 pM) and has a high affinity for dihydrofolate (Km = 0.4 microM). The sequence of the first 20 NH2-terminal residues of the protein shows 50% homology with the trimethoprim-sensitive chromosomal Escherichia coli dihydrofolate reductase and suggests that the two enzymes may be closely related. This is the first example of a plasmid encoding for a monomeric dihydrofolate reductase only moderately resistant to trimethoprim, and a resistance mechanism, dependent in part on the high dihydrofolate affinity of the type III enzyme, is proposed.

Amino Acid Sequence↗
PubMed1983

R plasmid dihydrofolate reductase with a dimeric subunit structure.

Dihydrofolate reductase specified by plasmid R483 from a trimethoprim-resistant strain of Escherichia coli has been purified 2,000-fold to homogeneity using dye-ligand chromatography, gel filtration, and polyacrylamide gel electrophoresis. The protein migrated as a single band on nondenaturing polyacrylamide gel electrophoresis and had a specific activity of 250 mumol/mg min(-1). The molecular weight was estimated to be 32,000 by gel filtration and 39,000 by Ferguson analysis of polyacrylamide gel electrophoresis. When subjected to electrophoresis in the presence of sodium dodecyl sulfate, the protein migrated as a single 19,000-molecular weight species, a fact that suggests that the native enzyme is a dimer of similar or identical subunits. Antibody specific for R483-encoded dihydrofolate reductase did not cross-react with dihydrofolate reductase encoded by plasmid R67, T4 phage, E. coli RT500, or mouse L1210 leukemia cells. The amino acid sequence of the first 34 NH2-terminal residues suggests that the R483 plasmid dihydrofolate reductase is more closely related to the chromosomal dihydrofolate reductase than is the enzyme coded by plasmid R67.

Amino Acid Sequence↗
PubMed1982

Steroid receptor proteins in human meningiomas.

Steroid receptor assays play an important role in determining the efficiency of endocrine therapy for patients with breast cancer. Other tumors could also be hormonally dependent and patients with these tumours might also benefit from endocrine manipulation. Thus, patients with meningiomas were tested for the presence or absence of estrogen and progesterone receptors. The results showed that a majority of meningiomas lacked estrogen receptors but contained large amounts of progesterone receptor. Therefore, it should be possible to use antiprogestin therapy in cases where complete surgical resection of meningiomas is not possible.

Adult↗
PubMed1982

Glucocorticoids induce the formation and release of anti-inflammatory and anti-phospholipase proteins into the peritoneal cavity of the rat.

1 Dexamethasone and hydrocortisone induced the release of anti-phospholipase proteins into the peritoneal cavities of rats. 2 Adrenocorticotrophic hormone (ACTH) also releases these proteins in normal but not in adrenalectomized rats. 3 Peritoneal lavage proteins were separated by ion-exchange and size exclusion chromatography. The anti-phospholipase activity occurred in four separate fractions with the major component having an apparent mol. wt. of 40 k. 4 Column fractions containing these anti-phospholipase proteins had anti-inflammatory effects in the rat carrageenin pleurisy model whereas other fractions were inactive. 5 The proteins appear to be identical to macrocortin and lipomodulin, the 'second messengers' of glucocorticoid hormone action on the arachidonate system.

Adrenocorticotropic Hormone↗
PubMed1982

Factors that affect the reproducibility of measurements of left ventricular function from first-pass radionuclide ventriculograms.

To examine which factors affect the reproducibility of ejection fraction (EF), pulmonary transit time (PTT) and segmental wall motion assessed from first-pass radionuclide angiograms (FPRA), 32 patients who had FPRA were randomized for site of injection of isotope (right or left arm) and projection (right or left anterior oblique [RAO or LAO]). The quality of injected bolus was measured from the full width at half maximum (FWHM) of the bolus time-activity curve in the superior vena cava. All patients had two sequential studies on each of two consecutive days, and each study was analyzed independently by two observers. For EF, inter- and intraobserver correlations ranged from 0.94-0.98. EF was higher in the RAO than the LAO projection (mean 47.4% vs 40.3%, p less than 0.001), but neither injection site nor bolus FWHM affected the results. For PTT, interobserver correlations ranged from 0.75-0.93 and intraobserver correlations from 0.61-0.85. Variability in PTT was large, and inter- and intraobserver variabilities were directly related to bolus FWHM (mean 0.60 +/- 0.21 second for interobserver differences in PTT of less than 2.0 seconds, mean 1.55 +/- 0.86 seconds for interobserver differences in PTT of greater than 2 seconds [p less than 0.005]). Differences in FWHM between sequential studies were 0.28 +/- 0.29 second when intraobserver differences in PTT were less than 2 seconds and 1.04 +/- 0.67 seconds when differences in PTT were greater than 2.0 seconds (p less than 0.005). Variations in PTT were not related to differences in projection or injection site. Wall motion was highly reproducible for both projections. In the RAO projection, one of 116 anterior segments (0.9%), one of 116 apical segments (0.9%), and four of 116 inferior segments (3%) were judged normal from one observer's images and abnormal from another. In the LAO view, discrepancies occurred in one of 126 septal segments (0.8%), two of 126 apical segments (1.6%) and four of 126 posterolateral segments (3%). This study shows that EF and wall motion are highly reproducible in any projection, but the choice of projection significantly affects the values for EF from FPRA. PTT measurements are less reliable, highly bolus dependent, and their use in clinical practice depends on quality control of the bolus of injected radionuclide.

Adult↗
PubMed1981

Effect of a single amino acid substitution on Escherichia coli dihydrofolate reductase catalysis and ligand binding.

The two isozymes of dihydrofolate reductase (Forms 1 and 2) from, a Trimethoprim-resistant strain of Escherichia coli (RT500) were separated and purified to homogeneity using a simple procedure based on differential elution from a Methotrexate affinity column. The complete amino acid sequence of the Form 2 isozyme was determined, and it differs from that of Form 1 in only one position. Residue 28 is arginine in Form 2 and leucine in Form 1. However, the isozymes differ greatly in their binding and kinetic properties. Equilibrium dialysis studies showed the Trimethoprim dissociation constants of Form 2 are about 50-fold greater than those of Form 1 in both the binary complex and the ternary complex with NADPH. Similarly, the Methotrexate dissociation constant of Form 2 is about 10-fold greater than that of Form 1. The two isozymes also differ in their turnover numbers at pH 7 (Form 1 is 10-fold more active) and inhibition by divalent cations. Form 1 is extremely sensitive to BaCl2 (50% inhibition at 0.5 mM), whereas Form 2 is much less sensitive (50% inhibition at 60 mM). In the presence of 10 mM BaCl2, Form 1 has the functional characteristics of Form 2. Its turnover number is decreased, its Trimethoprim Ki is increased, and the shape of its pH-activity profile is identical with that of Form 2. The x-ray structures and amino acid sequences of several bacterial dihydrofolate reductases indicate that Asp-27 is important in inhibitor binding and may be involved in catalysis. The present data provide kinetic evidence for this hypothesis, and it is proposed that almost all the unusual characteristics of Form 2 are the direct result of a charge interaction between Arg-28 and Asp-27. A similar interaction between Ba2+ and the Asp-27 of Form 1 can result in an enzyme complex that is kinetically similar to Form 2.

Amino Acid Sequence↗
PubMed1981

Female urethral diverticula: double-balloon catheter study.

A double-balloon catheter was used to evaluate the female urethra in 51 patients. Six different radiographic appearances were identified. Three of the categories are considered variants of normal. One of the categories consisted of eight patients with urethral diverticula. All showed large rounded or lobulated collections of contrast material which were adjacent to the urethra and which persisted on postvoid films. Other abnormalities should be closely correlated with the clinical findings to determine their significance. The diagnosis of urethral diverticulum may be missed, as physical examination and endoscopy can be negative. Therefore, the optimal method for identifying its presence and extent includes both a double-balloon catheter study and a voiding cystourethrogram.

Adult↗
PubMed1980

A monomeric insulin from the porcupine (Hystrix cristata), an Old World hystricomorph.

The insulins of New World hystricomorph rodents exhibit many novel amino acid changes in primary structure when compared with other mammalian insulins. These changes give rise to unusual properties (low potency, failure to self-associate) not shared by other naturally-occurring insulins. We report here on the primary structure, zinc-binding properties and circular dichroism (CD) of porcupine-insulin (Hystrix cristata), the first Old World hystricomorph insulin to be investigated, and discuss the changes in primary structure of the hormone in relation to its properties. Residue B22 is strongly implicated as being responsible for the unusual properties of porcupine insulin.

Amino Acid Sequence↗