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S Weir

Publications and source records attributed to S Weir.

15 recordsLinked to original sources
PubMed1992

Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; III: Sample matrix effects.

Using a set of 13 basic solutes (including a quarternary ammonium compound) with controlled pKa, log P and plasma protein binding, the factors which influence the extraction of these compounds from plasma by reversed-phase liquid-solid extraction have been studied. Direct analysis of plasma, avoiding deproteination, etc., is possible providing the sample is applied to the cartridge under the appropriate conditions. These conditions are dictated by the degree of plasma protein binding and are controlled and predicted from the lipophilicity of the compound. Plasma samples containing lipophilic compounds (log D(pH 7.4) > 2.03) require acidification and samples containing more polar compounds (log D(pH 7.4) < 0.9) should be applied untreated. Failure to use the appropriate conditions can result in significant losses from the cartridge on application or washing. In the intermediate lipophilicity range the optimal application conditions cannot be predicted. The effect of various aqueous-organic wash solvents have been investigated, and it was found that the cationic but not the proteinaceous components of plasma also affect the extraction process. This phenomenon which is probably due to an attenuation of the secondary cation exchange mechanism, results in more facile elution than when compounds are applied in water.

Atenolol↗
PubMed1992

Identification of type 4 pili in Kingella denitrificans.

Kingella denitrificans is an occasionally pathogenic member of the family Neisseriaceae and is a member of the normal respiratory flora. Electron microscopy, colony morphology types, DNA transformation patterns, and immunoblots suggest that K. denitrificans and K. kingae have type 4 pili. This was confirmed by N-terminal amino acid sequencing for K. denitrificans.

Amino Acid Sequence↗
PubMed1991

The determinants of response to diltiazem in hypertension.

We examined factors (blood pressure, plasma renin activity, and age) influencing the antihypertensive response in essential hypertensive patients given 240 mg/day of slow-release diltiazem in an unblinded study after a placebo run-in period. Subjects provided a range of diastolic blood pressures (90 to 115 mm Hg), of age (31 to 70 years), and of plasma renin activity (0.1 to 2.7 ng angiotensin I/ml/hr) on a 70 to 150 mEq sodium diet. Blood pressure, plasma renin activity, and plasma diltiazem concentrations were measured after the first (n = 21) and final dose (n = 19) of 120 mg diltiazem, twice daily for 4 weeks. Multiple linear stepwise regression of change in blood pressure versus age, plasma renin activity, and baseline blood pressure showed baseline blood pressure was the only predictor of response (p = 0.0002). For each increase of 10 mm Hg in baseline pressure there was a 7 mm Hg greater decrease in diastolic blood pressure. We conclude that patient age and plasma renin activity are not clinically significant predictors of antihypertensive response to diltiazem in hypertension.

Adult↗
PubMed1990

Pili (fimbriae) of Branhamella species.

PURPOSE: Pili (fimbriae) have frequently been found to be involved in the attachment of bacteria to mucosal epithelial cells, an important initial step in the disease process. The purpose of this study was to determine if Branhamella catarrhalis expresses type 4 pili. MATERIALS AND METHODS: Piliated B. catarrhalis phenotypic characteristics of colony morphology, agar corrosion, twitching motility, competence for deoxyribonucleic acid (DNA) transformation, autoagglutination, and pellical formation were observed. DNA was isolated from Branhamella spp. and used in genomic Southern hybridizations with a Moraxella bovis pilin gene as a probe. Electron microscopy of negatively stained bacteria was carried out to visualize pili. RESULTS: B. catarrhalis has several (but not all) of the phenotypic characteristics that are related to the presence of type 4 (MePhe) pili in closely related Moraxella spp., including competence for DNA transformation, autoagglutination, pellicle formation, colony morphology, and pitting of agar. The one phenotype we have not found that is generally characteristic of type 4 piliated bacteria is twitching motility. Genomic Southern hybridization analysis using a cloned M. bovis Q pilin gene as a probe reveals DNA homologous to the Q pilin gene in B. catarrhalis, Branhamella ovis, Branhamella caviae, and Branhamella cuniculi. Examination of B. catarrhalis strain ATCC25240 by electron microscopy reveals two different kinds of pili. One kind appears similar to other type 4 pili, whereas a second class is short pili extending outward from all portions of the bacteria. CONCLUSION: Phenotypic, electron-microscopic, and hybridization data are all consistent with type 4 pili being present on some B. catarrhalis strains.

Fimbriae, Bacterial↗
PubMed1989

The mechanism of action of endothelin-1 as compared with other agonists in vascular smooth muscle.

The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ([Ca2+]1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or [arg8]vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Receptor-operated calcium-permeable channels in vascular smooth muscle.

The extracellular Ca2+ dependence of agonist stimulation of vascular smooth muscle (VSM) has been investigated in rat cultured aortic smooth muscle cells (SMCs) and isolated mesenteric resistance vessels (MRVs). Agonists such as [Arg8]vasopressin (AVP), angiotensin II (Ang II), and adenosine-5'-triphosphate (ATP) stimulated 45Ca2+ entry into the SMCs that was (a) independent of the extent to which the membranes were polarized, and (b) was not inhibited by organic Ca2+ channel antagonists. Measuring the intracellular Ca2+ concentration [( Ca2+]i) after stimulation with agonists revealed a rapid increase of [Ca2+]i, which was followed by a sustained rise that was insensitive to Ca2+ antagonists. In Ca2+-free medium, only the initial peak of [Ca2+]i was still observed, but the sustained response to the agonists disappeared completely. This observation indicates that the sustained elevation seen in Ca2+-containing medium was the consequence of agonist-induced Ca2+ entry. In MRVs, a corresponding Ca2+-antagonist-insensitive, agonist (norepinephrine and AVP)-induced tonic tension was also identified. Moreover, agonists were able to induce sustained tension in the MRVs regardless of whether the membrane was normally polarized or was previously depolarized (80 mM K+) upon their administration. The agonist-stimulated 45Ca2+ entry in the SMCs could be blocked by the multivalent cations La3+, Cd2+, Mn2+, Co2+, Ni2+, and Mg2+ (in this order of potency). Depolarization-induced 45Ca2+ influx was inhibited by these cations in the same order of potency, but was significantly more sensitive to Cd2+ and significantly less sensitive to La3+ than that stimulated by agonists. Treatment with 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (NCDC, a proposed inhibitor of phospholipase C) reduced both the agonist-induced 45Ca2+ influx and the sustained elevation of [Ca2+]i in the SMCs. NCDC also abolished both contraction and depolarization induced by agonists in the MRVs. The kinase C stimulator phorbol-12-myristate-13-acetate (PMA) inhibited the agonist-induced 45Ca2+ influx and sustained increase in [Ca2+]i in the SMCs, whereas the kinase C inhibitor staurosporine had no effect. In the MRVs, in contrast, PMA had no influence on agonist-induced contractions. Staurosporine (1 microM), however, completely prevented these contractions, as did NCDC, but, unlike NCDC, it did so without affecting the agonist-induced depolarization. These data support an important role of receptor-operated Ca2+-permeable channels in VSM activation by agonists and suggest that these channels may be controlled by intracellular enzymic pathways and second messenger systems.

Animals↗
PubMed1988

Importing khat.

Explore the source record for details and available documents.

Animals↗
PubMed1986

Embryonic chick cartilage produces its own somatomedin-like peptide to stimulate cartilage growth in vitro.

Embryonic chick pelvic cartilages increase in size and weight when incubated in a chemically defined medium in the absence of serum. We addressed the question of whether endogenous production of growth factors by the cartilage was responsible for this growth. We found that conditioned medium, in which pelvic cartilages from 9-day-old chick embryos had been incubated for 3 days, increased cartilage dry weight 32% over weights of cartilages incubated in fresh medium. Increasing concentrations of conditioned medium stimulated cartilage weight and proline incorporation in a dose-dependent manner. To determine the molecular size(s) of potential growth-stimulating factors, conditioned medium was dialyzed at acid pH, lyophilized, and fractioned over HPLC-TSK Spherogel 3000. The collections were pooled into five fractions (greater than 100K, 30-100K, 20-30K, 12-20K, 1-12K, and less than 1K). Each fraction was readded to organ culture, and growth was assessed 3 days later. Only the 1-12K fraction stimulated growth above that of control cartilage. We assayed cartilage and conditioned medium for somatomedin-C (Sm-C) by RIA to determine if Sm-like peptides were present. Although Sm-C was not detectable within the cartilage, it was readily measurable in concentrated medium (248 +/- 35 pg/ml). Since Sm-like peptides might play a functional role in the growth process, we used a monoclonal antibody to Sm-C to determine whether immunoneutralization of the Sm-like peptides would inhibit cartilage growth in vitro. Addition of anti-Sm-C to organ culture of chick cartilage prevented increases in cartilage wet and dry weights (only 16% and 0%, respectively, above preincubation weights). The inhibitory effect of anti-Sm-C could be reversed by the addition of high doses of insulin to the medium. These studies suggest that endogenously produced Sm-like peptides have a functional role in promoting cartilage growth and support the hypothesis that growth factors may regulate growth through autocrine mechanisms.

Animals↗
PubMed1978

The percepton of motion: Michotte revisited.

This paper extends the range of artificial-intelligence vision programs to the domain of moving objects, using the work of Michotte as a source of data for a computer program which purports to 'see' the action types he examined. Given the thesis that internal descriptions of a nonlinguistic type provide the basis for a constructive, knowledge-based theory of perception, the properties of a symbol-manipulating system capable of supporting this are explored as a challenge to the Michotte notion of "direct perception without interpretation".

Association↗
PubMedDate not supplied

Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; I: Ionic interactions.

Seven basic solutes with known and controlled pKa (7.93-9.5) and log P (0.23-6.63) values have been used as test probes to study the mechanism involved in liquid-solid extraction with C2 and C18 bonded silica phases. A limited comparison has also been made with underivatized silica and CN phases. In addition to the reversed-phase mechanism, cation-exchange was shown to play a very significant role in the retention process. Various cations both organic and inorganic were assessed for their elution strength, and the ordering was similar to that for classical ion-exchange chromatography. Control of selectivity in the elution process can be achieved by varying the concentration of cation or methanol in the eluent. The C2 cartridge in combination with an aqueous ammonium acetate-methanol eluent proved to be the most versatile in that all compounds, irrespective of pKa or log P could be recovered in high yield. The optimal eluent in terms of selectivity with respect to related compounds could be predicted from the solute log P. Blocking of silanols by pre-conditioning the cartridges with cations prior to sample applications was also studied. The order of cation strengths although somewhat variable was similar to that established at the elution stage. To achieve quantitative elution with methanol or aqueous methanol solutions however, high concentrations of inorganic cations, equivalent to 1 ml of a 1 M solution were required to pre-condition a 100 mg cartridge.

Ion Exchange↗
PubMedDate not supplied

Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; II: Hydrogen bonding effects.

Anomalies in the elution order of the beta-blockers atenolol and propranolol on reversed-phase liquid-solid extraction cartridges have been studied. The hydrogen bond acceptor properties of the polar ring substituent in atenolol was found to result in greater retention than would be expected from the reversed-phase or cation-exchange mechanisms alone. This hydrogen bonding interaction could be attenuated by inclusion of a strong hydrogen bond acceptor in the eluent or more successfully by increasing the eluent water content. The conclusions from this work have been used to explain previously reported anomalies in the solid-phase extraction of polar basic drugs.

Atenolol↗
PubMedDate not supplied

Fertility and contraceptive use among young adults in Harare, Zimbabwe.

In 1986, a survey of young adults aged 14-24 in Harare, Zimbabwe obtained information about their knowledge, attitudes, and sexual behavior. Most adolescent childbearing took place within marriage, although sexual intercourse was generally initiated before marriage. Knowledge of family planning was high, but contraceptive use lagged behind knowledge. Fewer than half of the respondents had talked to an elder about family planning, sex, or pregnancy. Fourteen percent of young women who were unmarried at the time of first intercourse used contraceptives, compared to 18 percent of young unmarried men. Current contraceptive use among sexually active unmarried youths was 36 percent among women and 29 percent among men. One consequence of low contraceptive use was a high number of unwanted premarital pregnancies. Twenty-nine percent of the women had been pregnant; those not married at the time they got pregnant generally got married soon after. Of the girls who got pregnant while in school, 90 percent had to drop out of school. A second consequence of low contraceptive use is an increased risk of transmission of STDs and AIDS among the youth of Harare.

Adolescent↗