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Biomedical subjects

G M Smith

Publications and source records attributed to G M Smith.

At least 199 records · Page 11Linked to original sources
PubMed1984

31P nuclear magnetic resonance studies of the fermentation of glucose to ethanol by Zymomonas mobilis.

High resolution 31P nuclear magnetic resonance spectroscopy has been employed to study the fermentation of glucose to ethanol by Zymomonas mobilis, strain ZM4, a bacterium which uses the Entner-Doudoroff pathway. The levels of nucleoside triphosphates, sugar phosphates, UDP-sugars and Pi in intact fermenting cells have been studied with a time resolution of 1 min. It is suggested that a pH gradient is established across the cell membrane during fermentation and that the intracellular pH does not rise above approximately 6.4. 31P resonances from most phosphorus-containing intermediates in the Entner-Doudoroff pathway, as well as adenosine and uridine nucleotides and a number of other intracellular metabolites, have been assigned in perchloric extracts of fermenting cells by means of a number of techniques, including two-dimensional homonuclear J-resolved and two-dimensional homonuclear shift-correlated spectroscopy. Quantification of these metabolites in spectra of extracts of fermenting cells indicates that the rate-limiting steps in the Entner-Doudoroff pathway in Z. mobilis are the conversions of glucose 6-phosphate to 6-phosphogluconate and of 3-phosphoglycerate to 2-phosphoglycerate.

Ethanol↗
PubMed1984

Increased vasopressor responsiveness to angiotensin II in type 1 (insulin-dependent) diabetic patients without complications.

The blood pressure response to infused angiotensin II (0.3 to 3 ng X kg-1 X min-1) was investigated in six normotensive patients with Type 1 (insulin-dependent) diabetes free of complications and in six healthy subjects matched for age, sex and weight. Basal blood pressures (111/68 and 114/72 mmHg) and basal plasma angiotensin II levels (18.0 +/- 5.2 and 14.1 +/- 2.4 pmol/l; mean + SD) were similar in the diabetic and control groups as were 24 h urinary excretions of sodium (157 +/- 88 and 154 +/- 84 mmol/24 h). Equal increments in plasma angiotensin II were produced during the infusions in the two groups. Increases in both diastolic and systolic blood pressure were significantly greater in the diabetic patients throughout the infusion. Mean diastolic increments were: 6.7 versus 1.3 mmHg (0.3 ng dose), 11.0 versus 6.9 mmHg (1 ng dose) and 16.7 versus 12.3 mmHg (3 ng dose) (p less than 0.001). Corresponding figures for systolic pressure were: 8.7 versus 1.3 mmHg, 10.3 versus 3.7 mmHg and 15.3 versus 8.7 mmHg (p less than 0.001). Vasopressor responsiveness to angiotensin II is thus increased in Type 1 diabetic patients without complications; it may, therefore, be a consequence of the diabetes rather than of the presence of microvascular disease or hypertension.

Adult↗
PubMed1984

Comparison of the actions of 11.9 epoxymethano PGH2 and 9.11 azo PGH2 on rat aorta and stomach strip preparations.

Two synthetic thromboxane A2 agonists were compared on two isolated smooth muscle preparations, the rat aorta and stomach-strip using a superfusion cascade. 11.9 epoxymethano-PGH2 contracted both preparations in a concentration dependent manner. Cumulative concentration-response curves showed that azo PGH2 was twice as active as 11.9 epoxymethano PGH2 on the aorta and nearly four times Statistical analysis of the agonist concentration-response curves showed a significant difference when responses to azo PGH2 were compared on the two preparations and when responses to azo PGH2 and 11.9 epoxymethano PGH2 were compared on the aorta preparation. When EPO45, a thromboxane receptor antagonist was used the PA2 values obtained were not significantly different using the two agonists on the two preparations. The pA2 values indicate that both agonists act on the same receptor but the comparison of the concentration-response curves suggest that azo PGH2 may be acting at another receptor as well as the thromboxane receptor in the stomach-strip.

Animals↗
PubMed1984

Structure-activity, theoretical, and X-ray studies on the intramolecular interactions in a series of novel histamine H2 receptor antagonists.

The furan ring of the histamine H2 receptor antagonist 3-amino-4-[[2-[[[5-[(dimethylamino)methyl]-2-furanyl]-methyl] thio]ethyl]amino]-1,2,5-thiadiazole 1-oxide (1a) was replaced by thiophene, pyridine, benzene, and pyrrole. The relative receptor affinities of these analogues were estimated by in vitro and in vivo techniques. A theoretical model for the stacking interaction, observed by single crystal X-ray analysis of 1a, was developed, and the ability to enter into this type of interaction was estimated. The X-ray analysis of the pyridine analogue of 1a revealed no intramolecular stacking interaction. The theoretical studies were evaluated in light of the observed receptor affinities, and the relevance of the solid-state geometry of 1a to the receptor-bound geometry was assessed. It is suggested that the stacked geometry found in the X-ray structure of 1a does not represent a conformation that is relevant to that bound at the histamine H2 receptor.

Animals↗
PubMed1984

In vivo platelet aggregation in the rat: dependence on extracellular divalent cation and inhibition by nonsteroidal anti-inflammatory drugs.

Using the Technicon Autocounter, the mechanisms involved in collagen-induced platelet aggregation in vivo have been studied without the interference of an anticoagulant. Extracellular divalent cation was essential for in vivo platelet aggregation. Non-steroidal anti-inflammatory drugs completely inhibited the aggregation induced by collagen in platelet-rich plasma in in vitro or ex vivo studies. In vivo only a maximum of 50% inhibition was achieved when release of thromboxane A2 (TXA2) was completely inhibited. Therefore in vivo, collagen causes aggregation through more than one pathway which operate independently of each other and which are all dependent on extracellular divalent cation. In vivo, when different doses of collagen were compared, aggregation produced by low doses of collagen was more dependent upon prostaglandin endoperoxide/TXA2 formation.

Anesthesia↗
PubMed1984

Effects of deletions in transposon Tn7 on its frequency of transposition.

Deletions in transposon Tn7 either abolished transposition or reduced transposition frequency. Except for a deletion in the right-hand terminus, these deletions could be complemented in trans. A 2.1-kilobase fragment of Tn7 encodes a diffusible gene product which stimulates transposition above the wild-type frequency. No cointegrate formation was detected.

Chromosome Deletion↗
PubMed1984

Secretion of erythropoietin-like activity by clones of human renal carcinoma cell line GKA.

Human renal carcinoma cell line GKA was derived from a patient with the paraneoplastic syndrome of erythrocytosis and secretes erythropoietin-like activity into its growth medium (Sytkowski, A. J., Richie, J. P., and Bicknell, K. A. Cancer Res., 43: 1415-1419, 1983). In order to derive homogeneous sublines with higher secretory rates, we cloned line GKA. Over 100 clones were generated, and 21 secreted erythropoietin-like activity, up to 6-fold higher than the uncloned line. This activity stimulated the growth and differentiation of CFU-E derived colonies in plasma clot culture. However, the secreted erythropoietin-like activity did not cross-react in a sensitive radioimmunoassay utilizing highly purified 125I-labeled human urinary erythropoietin and heterologous anti-human urinary erythropoietin antiserum. These results suggest that line GKA secretes an erythropoietic stimulating factor distinct from the hormone erythropoietin.

Cell Line↗
PubMed1983

Prevention of extension of ischaemic damage following acute myocardial ischaemia by dazoxiben, a new thromboxane synthetase inhibitor.

1 Dazoxiben, a new thromboxane synthetase inhibitor, at an infusion rate of 5 mg/kg/h inhibited the ischaemia-induced increase in circulating thromboxane B2 in cats. 2 Dazoxiben also restored the S-T segment of the electrocardiogram toward normal values after the onset of ischaemia, and prevented the rise in plasma creatine kinase activity usually observed during myocardial ischaemia. 3 Associated with the above changes were reduced loss of myocardial creatine kinase activity and amino-nitrogen concentration in the ischaemic region of those cats treated with dazoxiben. 4 No significant effects of dazoxiben were observed on heart rate, mean arterial blood pressure or the product of the two, the pressure-rate index. Therefore, dazoxiben does not protect by reducing myocardial oxygen demand. 5 The mechanism of the protective action of dazoxiben in acute myocardial ischaemia seems to be either due to prevention of the constrictor and cytolytic actions of thromboxane A2 or to metabolic and cellular actions of dazoxiben unrelated to thromboxane synthetase inhibition.

Animals↗
PubMed1983

Responsiveness of platelets and coronary arteries from different species to synthetic thromboxane and prostaglandin endoperoxide analogues.

1--Platelet-rich plasma (PRP) from humans, cats, dogs (after addition of 10 microM adrenaline), rabbits and guinea-pigs aggregated in response to sodium arachidonate or 9,11-azo-prostaglandin H2, while PRP obtained from sheep was unresponsive to either agent. 2--The stable thromboxane (Tx) analogues, carbocyclic TxA2 (CTA2) and pinane TxA2 (PTA2) significantly inhibited these aggregatory responses in platelets from humans, dogs and guinea-pigs, while PTA2 but not CTA2 produced significant inhibition in cat platelets. The aggregatory response of PRP from rabbits was not significantly blocked by either analogue. 3--CTA2 and the endoperoxide analogue 9,11-methanoepoxy PGH2 (U-46619) constricted coronary arteries from cats, dogs, rabbits and guinea-pigs, while sheep vessels were unresponsive to either analogue. 4--Vasoconstrictor responses to U-46619 were significantly attenuated by PTA2 in vessels from all species. However, constriction produced by CTA2 was blocked significantly only in vessels from cats, dogs and guinea-pigs. 5--These results demonstrate the species differences which exist in the responsiveness of platelets and coronary arteries to thromboxane and endoperoxide analogues. Furthermore, the results illustrate the importance of species selection in the study of thromboxane antagonists for potential therapeutic use.

Animals↗
PubMed1983

Properties of MM 13902 and other carbapenem antibiotics in vitro and in vivo.

The carbapenem antibiotics, which include the olivanic acids and the thienamycins, have a broad-spectrum of antibacterial activity but only thienamycin itself shows appreciable activity against Pseudomonas aeruginosa. The zwitterionic nature of thienamycin was reproduced in the olivanic acid series by preparing the deacetyl derivatives of MM 17880 and MM 22380--compounds NA 26975 and NA 26978. The latter derivative showed antipseudomonas activity and had an antibacterial spectrum similar to thienamycin itself. In contrast the O-sulfated analogue, NA 26975, was no more active than the parent compound against P. aeruginosa. Both deacetyl compounds were more stable than the parent natural products to a mouse kidney enzyme preparation and gave higher urinary recoveries in the mouse. Pharmacokinetic studies with MM 13902 in various animal species showed that the compound was rapidly eliminated from the blood and gave only low urinary recoveries. Similar findings were observed also in human volunteers given MM 13902. The nephrotoxicity reported for thienamycin/MK 0787 in the rabbit was not seen with the olivanic acids MM 13902, MM 17880, MM 22382 and MM 22383 when tested under the same conditions.

Adolescent↗
PubMed1982

Nuclear magnetic resonance studies of the nucleotide binding sites of porcine adenylate kinase.

The alpha, beta, gamma-tridentate complex of CrATP, a paramagnetic competitive inhibitor of porcine adenylate kinase, increases the longitudinal [1/(fT1p)] and transverse [1/(fT2p)] relaxation rates of a resonance of the enzyme previously assigned by McDonald et al. [McDonald, G.G., Cohn, M., & Noda, L. (1975) J. Biol. Chem. 250, 6947-6954] to the C2 proton of histidine-36. These paramagnetic effects are diminished upon the addition of the substrate MgATP by an amount consistent with the simple displacement of CrATP. The 1/(fT2p) value sets a lower limit of 400 s-1 on the rate constant for dissociation of CrATP from the enzyme. The 1/(fT1p) value at 250 MHz and the correlation time for water protons in the same complex are used to calculate a distance of 12.9 +/- 1.0 A from Cr(III) to the C2 proton of histidine-36. A primary, negative nuclear Overhauser effect is detected on the adenine H2 resonance of enzyme-bound MgATP upon preirradiation of the C2 proton of histidine-36, indicating that these protons are approximately less than 5 A apart. These distances and negative intramolecular Overhauser effects from the ribose protons to adenine H8 of MgATP indicate an extended structure for bound MgATP with an anti conformation about the glycosidic bond. These findings require a different orientation or location of the bound metal-ATP substrate from that proposed based on X-ray studies of the binding of salicylate [Pai, E. F., Sachsenheimer, W., & Schirmer, R.H. (1977) J. Mol. Biol. 114, 37-45]. Other nuclear Overhauser effects from resonances of the protein at 1.8 and 0.9 ppm to both adenine H2 and ribose H1' of bound MgATP indicate the proximity to the substrate of at least one Arg C beta proton (at 1.8 ppm), C gamma proton (at 1.7 ppm), Lys C delta proton (at 1.7 ppm), or Leu C beta proton (at 1.6 ppm) and one or more Leu, Ile, or Val methyl groups (at 0.9 ppm). Entirely different Overhauser effects are observed from the enzyme to the adenine protons of AMP consistent with a distinct site for the other substrate.

Adenosine Monophosphate↗
PubMed1982

Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments.

The atomic environments of 170 phenylalanine-residue aromatic rings from 28 protein crystal structures are transformed into a common orientation and combined to calculate an average three-dimensional environment. The spatial distribution of atom types in this environment reveals a preferred interaction between oxygen atoms and the edge of the planar aromatic rings. From the difference in frequency of interaction of oxygen atoms with the edge and the top of the ring, an apparent net free energy difference of interaction favoring the edge of the ring is estimated to be about -1 kcal/mol (1 cal = 4.184 J). Ab initio quantum mechanical calculations, performed on a model consisting of benzene and formamide, indicate that the observed geometry is stabilized by a favorable enthalpic interaction. Although benzene rings are considered to be nonpolar, the electron distribution is a complex multipole with no net dipole moment. The observed interaction orientation frequencies demonstrate that these multipolar electron distributions, when occurring at the short distances encountered in densely packed protein molecules, are significant determinants of internal packing geometries.

Benzene↗
PubMed1982

Effect of environmental conditions during heating on commercial spore strip performance.

Commercial biological indicator spore strips in glassine envelopes, produced by three manufacturers, were evaluated by fraction-negative procedures after being heated at 121.0 +/- 0.05 degrees C. Only one type of spore strip met the manufacturer's specifications. The strips of one manufacturer were further evaluated by fraction-negative and survivor curve-plate count procedures after being heated under several conditions (enclosed in glassine envelopes, in trypticase soy broth plus 0.0015% bromocresol purple, in Trypticase soy broth alone in Water for Injection, directly); Trypticase soy broth plus bromocresol purple and tryptic soy agar, respectively, were used as recovery media. The heating condition affected the D-value of the spore strip. Recovery procedures also had an effect; in all cases, the D-values obtained from the survivor curve tests were larger than those obtained from fraction-negative tests carried out under the same conditions. To determine if the differences in D-values between the two evaluation procedures were caused by the recovery media, we evaluated, by both methods, one type of spore strip heated directly and in glassine envelopes, using tryptic soy agar plus bromocresol purple and Trypticase soy broth plus 1.5% agar, respectively, as the recovery media. The survivor curve results showed that for both enclosed and unenclosed spore strips, there was a marked difference between the two recovery media; however, there was no difference when fraction-negative tests were used.

Culture Media↗