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S Ward

Publications and source records attributed to S Ward.

At least 181 records · Page 10Linked to original sources
PubMed1993

Metabolism of gestodene in human liver cytosol and microsomes in vitro.

The metabolism of the progestogen gestodene has been studied in human liver cytosol and microsomal incubations. Extraction with diethyl ether was followed by radiometric HPLC analysis. Metabolites were identified by co-chromatography with authentic standards and mass spectrometry (electron impact and chemical ionization). All the cytosolic incubations (n = 4 livers) produced dihydrogestodene as the major metabolite, with lesser amounts of a tetrahydro derivative. It was not possible to separate the 5 alpha- and 5 beta-isomers of dihydrogestodene on the chromatographic system used. Values of Km and V(max) for the delta 4 reductase were determined. Androstenedione (Ki = 2.85 +/- 1.5 microM; n = 4) and cortisol (ki = 24.1 +/- 8.9 microM; n = 4) both inhibited the delta 4-reductase. In contrast desogestrel showed virtually no inhibition at concentrations up to 200 microM. The major microsomal metabolite of gestodene was a hydroxylated derivative although mass spectral analysis was unable to determine the position of insertion of the hydroxyl moiety. The hydroxylation of gestodene (1 microM) was markedly inhibited by ketoconazole (IC50 < 0.1 microM), and also by cyclosporin. This suggests that the cytochrome P450 isozyme CYP3A4 is important in gestodene metabolism. Theophylline and tolbutamide (substrates of CYPIA and CYP2C, respectively) did not affect gestodene metabolism at concentrations up to 100 microM. In conclusion, the major biotransformation of gestodene (A-ring reduction) occurs in the cytosolic fraction of human liver. Microsomal hydroxylation appears to be catalysed by CYP3A4.

Adolescent↗
PubMed1993

The Caenorhabditis elegans spe-6 gene is required for major sperm protein assembly and shows second site non-complementation with an unlinked deficiency.

Caenorhabditis elegans spermatozoa move by crawling. Their motility requires thin cytoskeletal filaments assembled from a unique cytoskeletal protein, the major sperm protein (MSP). During normal sperm development the MSP is segregated to developing sperm by assembly into filaments that form a paracrystalline array in a transient organelle, the fibrous body-membranous organelle. Mutations in the spe-6 gene cause sterility because they lead to defective primary spermatocytes that do not form spermatids. In these mutant spermatocytes the MSP fails to assemble into fibrous body filaments. Instead, the unassembled MSP distributes throughout the cytoplasm and nucleus. Thus, the spe-6 gene product is necessary for normal MSP localization and assembly during sperm development. In addition to their MSP assembly defect, spe-6 mutant spermatocytes arrest meiosis at diakinesis although their spindle pole bodies still replicate and separate. This results in spermatocytes with four half-spindles surrounding condensed, but unsegregated, chromosomes. All four spe-6 alleles, as well as a chromosome III deficiency that deletes the spe-6 gene, fail to complement two small overlapping chromosome IV deficiencies, eDf18 and eDf19. This non-allele-specific second site non-complementation suggests a concentration-dependent interaction between the spe-6 gene product and products of the gene(s) under eDf18 and eDf19, which include a cluster of sperm-specific genes. Since MSP filament assembly is highly concentration-dependent in vitro, the non-complementation might be expected if the sperm-specific gene products under eDf18 and eDf19 were needed together with the spe-6 gene product to promote MSP assembly.

Animals↗
PubMed1993

Competency for the endoscopy team.

To ensure the delivery of quality patient care during endoscopic procedures, competency of all the team members must be ensured. The physician community deals with this differently than the other members of the perioperative team. Using questionnaires and skill checklists to conduct thorough assessments is essential. Developing programmed learning tools, levels of competency, and performance standards are some examples described in this article. The issue of competency must be managed on a regular basis to continually ensure that quality care is delivered.

Clinical Competence↗
PubMed1993

Conflict of interest in medical research and development.

The introduction of laparoscopic cholecystectomy via nontraditional methods opened Pandora's box regarding issues of cost effectiveness, diagnostic need, safety, and efficacy. This article discusses one of many ethical concerns related to new-procedure introduction, conflict of interest in medical research and development. Conflict of interest is defined and suggestions of how to implement conflict of interest rules are discussed. As new procedures and modalities continue to be introduced at a rapid rate, it will be important to manage them appropriately.

Biomedical Research↗
PubMed1993

Coping process theory: a tool to reduce stress and cardiovascular disease.

1. Associations exist between stress and cardiovascular disease. This article presents the coping process theory as a possible strategy to reduce the incidence of cardiovascular disease. 2. The occurrence of coronary heart disease may be reduced by using the coping process to manage stress in the workplace. If the disease is present, coping with the stress of having the disorder diminishes its recurrence. 3. Social support is a valuable coping resource; its association with cardiovascular disease is demonstrated.

Adaptation, Psychological↗
PubMed1992

Analysis and elimination of protein perturbation in infrared difference spectra of acyl-chymotrypsin ester carbonyl groups by using 13C isotopic substitution.

I.r. spectroscopy has been applied to the study of hydrogen-bonding of the unique ester carbonyl group of acylchymotrypsins in the oxyanion hole of the enzyme. This catalytic device provides electrophilic stabilization of negative charge in the transition states and tetrahedral intermediates along the reaction pathway. The use of 13C isotope substitution of the ester carbonyl group reinforces the previous observation [White & Wharton (1990) Biochem. J. 270, 627-637] that the ester carbonyl group is significantly polarized in the ground state by hydrogen bonding in the oxyanion hole. I.r. difference spectra of [carbonyl-12C]-minus [carbonyl-13C]-cinnamoyl-chymotrypsin as well as each of these acylenzymes minus free enzyme are reported. These spectra show that the contribution of protein perturbation (i.e. spectral features that arise from the enzyme which is distorted on acylation) in [carbonyl-12C]cinnamoyl-chymotrypsin minus free enzyme spectra is significant. The contribution of the perturbation components of the spectra is pH-dependent and can represent up to 50% of the total absorbance in the spectral region from 1690 to 1740 cm-1. Use of the isotopic difference method has allowed problems associated with protein perturbation to be eliminated. Similar difference spectra are presented for dihydrocinnamoyl-chymotrypsin. In this case the effect of perturbation is very marked and leads to the cancellation of the band assigned to the non-bonded conformation of the acyl group which has previously only been observed at higher pH. The isotopic difference method again proves reliable and shows that the frequency difference previously used to calculate the ground-state electronic strain induced by the oxyanion-hole catalytic device is not affected by the perturbation, although the amplitudes of the spectral features are different. A study of the deacylation of cinnamoyl-chymotrypsin in water and deuterium oxide using both u.v. and i.r. spectroscopies has confirmed that the use of deuterium oxide as solvent has no serious effect on the deacylation behaviour of the enzyme. I.r. bands assigned to nonproductive and productive conformers decline identically during deacylation, which shows that the conformers are in dynamic exchange on the reaction time-scale.

Acylation↗
PubMed1992

Opioid and cannabinoid receptor inhibition of adenylyl cyclase in brain.

Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatum, kappa-opioid inhibition in guinea pig cerebellum, and cannabinoid inhibition in cerebellum. The inhibition of adenylyl cyclase by both cannabinoid and opioid agonists was typical of G-protein-linked receptors: they required GTP, they were not supported by non-hydrolyzable GTP analogs, and they were abolished (in primary neuronal cell culture) by pertussis toxin treatment. The immediate targets of this system were determined by assaying protein phosphorylation in the presence of receptor agonists and App(NH)p, a substrate for adenylyl cyclase. In striatal membranes, opioid agonists inhibited the phosphorylation of at least two bands of MW 85 and 63 kDa, which may be synapsins I and II, respectively. Other experiments determined the long-term effects of this second messenger system. In primary neuronal cultures, opioid-inhibited adenylyl cyclase attenuated forskolin-stimulated pro-enkephalin mRNA levels, thus providing a feedback regulation of opioid synthesis. Finally, in cerebellar granule cells, both cannabinoid and opioid receptors may exist on the same cells. In these cells, agonists which bind to different receptor types may produce similar biological responses.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety-five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression-free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression-free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression-free interval (P less than 0.0001). Vascular invasion was less effective in these predictions (0.05 less than P less than 0.10). Both measurements were reasonable reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.

Carcinoma, Squamous Cell↗
PubMed1992

Earliest Homo.

The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far.

Animals↗
PubMed1992

Knowledge of, attitudes toward, and barriers to pharmacologic management of cancer pain in a statewide random sample of nurses.

The knowledge of, attitudes toward, and perceived barriers to pharmacologic management of cancer pain were examined in a random statewide sample of nurses (N = 790), using an 82-item questionnaire. Although only 7% of the nurses reported working in oncology settings, 59% of the nurses reported having worked with patients with cancer in the last 6 months. The scores on the knowledge test ranged from 11% to 93% correct, with a mean percent correct of 56.4% (+/- .92). Nurses reported relatively liberal attitudes toward pain management, yet also reported believing that 22% of patients over report pain. Results are discussed with respect to implications for practice and education.

Adult↗
PubMed1992

Transmission of mitochondrial DNA in Ustilago violacea.

Mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) were used as genetic markers for following mitochondrial transmission in the basidiomycete Ustilago violacea. Yeast-like cells of opposite mating types (a1 and a2) were mated on 2% water agar and were treated with alpha-tocopherol to induce formation of dikaryotic hyphae. Upon depletion of the alpha-tocopherol, the hyphae budded off haploid cells with parental nuclear genotypes. These cells were examined for mitochondrial RFLP phenotype. In progeny expressing the a1 mating type, mitochondria from either parent were observed equally frequently. In progeny with the a2 mating type, mitochondria were almost exclusively (94%) from the a2 parent.

Crosses, Genetic↗
PubMed1992

Kinetic analysis of recombinant antibody-antigen interactions: relation between structural domains and antigen binding.

The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 x 10(9) M-1 and 25 x 10(9) M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.

Antibodies, Monoclonal↗
PubMed1992

The predictive validity and accuracy of a screening test for language delay and auditory perceptual disorder.

Infants (321) who had been screened for language delay and auditory perceptual problems at 9 months of age were evaluated 1 year later. Of these infants 88.6% were correctly classified as at-risk or not-at-risk of delayed linguistic development. The correlation between performance on the screen and on a language scale was 0.49. The great majority of those with receptive and expressive delay continued to show problems at 2 years of age, whereas half of those with expressive delay alone were within normal limits. No evidence was found that a history of fluctuating hearing loss contributed to the development of either language delay or auditory perceptual problems.

Auditory Perceptual Disorders↗
PubMed1992

H2-receptors mediate histamine-induced variations in the permeability of the blood-brain barrier of rats.

Earlier investigations suggested that histamine H2-receptors mediate alterations in cerebrovascular permeability in mammals. The objective of this study was to observe the effects of the H2-receptor antagonist ranitidine on histamine-stimulated alterations in the permeability of the blood-brain barrier (BBB) of rats. Normotensive Wistar-Kyoto (WKY) (control) and spontaneously hypertensive (SHR) rats were premedicated with ranitidine (1 mg/kg), followed by histamine (1.25, 2.5 or 5.0 micrograms/kg) or saline. Animals were anesthetized and permeability of the BBB was evaluated with 99mTc-labeled sodium pertechnetate (TcO4-) or with 131I-labeled human serum albumin (RISA). In both control and hypertensive rats, ranitidine blocked histamine-induced changes in cerebrovascular permeability, but did not inhibit histamine-stimulated systemic hypotension. The alterations in the permeability of the BBB did not correlate with variations in blood pressure produced by histamine.

Animals↗