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Biomedical subjects

G M Smith

Publications and source records attributed to G M Smith.

At least 163 records · Page 9Linked to original sources
PubMed1988

A clinical, microbiological and pharmacokinetic study of ciprofloxacin plus vancomycin as initial therapy of febrile episodes in neutropenic patients.

Forty-six episodes of fever in 34 patients with neutropenia and haematological malignancy were treated empirically with a combination of ciprofloxacin and vancomycin. Improvement or temporary improvement was seen in 86% of evaluable episodes, and 75% of bacteraemias improved. There was no difference in the response rate between infections due to Gram-negative and those due to Gram-positive organisms, despite the fact that MICs for ciprofloxacin for Gram-negative organisms were generally much lower. Pharmacokinetic data were obtained from five patients while receiving iv ciprofloxacin and after conversion to the oral form of the drug. The mean plasma half life on 200 mg iv was 5.7 +/- 1.7 h and mean plasma clearance 389 ml/min. The peak serum level after 750 mg orally was 3.6 +/- 2.2 mg/l and occurred between 1 and 3 h.

Adolescent↗
PubMed1987

Directly observed 15N NMR spectra of uniformly enriched proteins.

The proteins cytochrome c2, cytochrome c', and ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum were enriched in 15N by growth of the organism on 15NH4Cl. The proteins were purified to homogeneity and studied by 15N NMR. Longitudinal and transverse relaxation times as well as the nuclear Overhauser effects were determined for various groups of the proteins which vary in molecular weight from 13,000 to 114,000. The values of these parameters for the amide resonances or for groups thought to be rigid were consistent with the molecular weights of the proteins. Relaxation times of the amino-terminal alpha-amino groups and the side chain nitrogen atoms of arginine and lysine were consistent with much more rapid motion. Nitrogen atoms having bound protons were generally found to be decoupled from the protons by chemical exchange. Demonstrable 1H-15N coupling was taken as an indication that exchange was hindered, either by hydrogen bonding interactions or by inaccessibility of the group to solvent. Histidine side chain nitrogen atoms, which experience a large chemical shift upon protonation/deprotonation, were often found to be broadened beyond detectability by chemical exchange and tautomerization. Strategies for improving sensitivity and for obtaining specific peak assignments are also discussed.

Cytochrome c Group↗
PubMed1987

Pre-operative assessment of fitness score.

Death within 30 days or survival after a major operation depends on three things: the severity of the disease and the operation, the technical proficiency of the surgeon and the ability of the patient to withstand both disease and operation. The first of these can be estimated by reference to published figures, the second can only be guessed at and the third has in the past been a matter of subjective judgement. With the aim of producing an objective assessment of the likelihood of survival, we have constructed a score system comprising 26 items including age, chronic disease and acute presenting disease. These items are each given a weight of 1 to 4 and the total fitness score for any patient ranges from 0 (fit) to 10 (unlikely to survive). We have validated this score prospectively in 1517 consecutive patients undergoing emergency or elective major abdominal operations (excluding appendicectomies and hernia repairs). In 492 operations in which the patient scored 0 or 1, one patient died (0.2 per cent); in 290 with scores of 2 or 3, one died (0.3 per cent); in 313 with scores of 4 or 5, five died (1.6 per cent). It was when the score rose to 6 or over that the chances of survival progressively declined: 16 died of the 105 patients who scored 6 (15.2 per cent) as did 74 of the 191 who scored 7 or 8 (38.7 per cent) and 70 of the 126 who scored 9 or 10 (55.6 per cent). We now use the score as part of our audit and enquire particularly closely into the death of any patient with a pre-operative score of less than 6.

Abdomen↗
PubMed1987

Phospholipid studies of marine organisms: 14. Ether lipids of the sponge Tethya aurantia.

The novel unesterified alkyl glycerol monoethers, (2S)-1-(hexadecyloxy)-2,3-propanediol (1), (2S)-1-(16-methylheptadecyloxy)-2,3-propanediol (2) and (2S)-1-(15-methylheptadecyloxy)-2,3-propanediol (3) were isolated from the marine sponge Tethya aurantia and were characterized by spectroscopic methods. These three saturated ethers as well as a series of alk-1'-enyl glycerol monoethers were also encountered in the phospholipids of the same sponge after reduction with LiAlH4. Incorporation experiments with dissociated cells of T. aurantia indicated that [1-14C]-hexadecanol was incorporated into the unesterified alkyl glycerol monoethers.

Animals↗
PubMed1987

Cerebral toxoplasmosis in a patient with Hodgkin's disease.

A case is described of a patient presenting with enlarged lymph nodes and in whom a diagnosis of acute toxoplasmosis was made. The patient later developed Hodgkin's disease for which chemotherapy was started. Reactivation of the quiescent toxoplasma infection took place with devastating results. Prophylactic treatment in such cases is discussed.

Brain Diseases↗
PubMed1987

Diethyl 3,6-dihydro-2,4-dimethyl-2,6-methano-1,3-benzothiazocine-5,11- dicarboxylates as calcium entry antagonists: new conformationally restrained analogues of Hantzsch 1,4-dihydropyridines related to nitrendipine as probes for receptor-site conformation.

The pharmacological activity of rigid analogues of 1,4-dihydropyridine calcium entry antagonists 9-16 is demonstrated by dose-dependent inhibition of the calcium contraction in depolarized rat aortic strips and by a [3H]nitrendipine binding assay in using cardiac sarcolemmal membranes. From the results, a model is proposed as the receptor-bound conformation of the dihydropyridine calcium entry antagonists.

Animals↗
PubMed1987

Regulation of climacteric respiration in ripening avocado fruit.

Ripening of avocado fruit is associated with a dramatic increase in respiration. In vivo(31)P nuclear magnetic resonance spectroscopy revealed large increases in ATP levels accompanying the increase in respiration. Both glycolytic enzymes, phosphofructokinase, and pyrophosphate: fructose-6-phosphate phosphotransferase were present in avocado fruit with the latter activity being highly stimulated by fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate levels increased approximately 90% at the onset of ripening, suggesting that the respiratory increase in ripening avocado fruit may be regulated by the activation of pyrophosphate:fructose-6-phosphate phosphotransferase by an increase in fructose 2,6-bisphosphate.

Journal Article↗
PubMed1987

Sucrose phosphatase associated with vacuole preparations from red beet, sugar beet, and immature sugarcane stem.

The specific phosphatase, sucrose phosphate phosphohydrolase (sucrose phosphatase, EC 3.1.3.24) was present in vacuole preparations from storage tissue of red beet (Beta vulgaris L.), sugar beet (Beta vulgaris L. cultivar Kawemono), and immature sugarcane (Saccharum spp. hybrid, cultivar NCO 310). In red beet vacuole preparations the specific activity of sucrose phosphatase, using the naturally occurring vacuole marker, betanin, as reference, was higher than the specific activity of cytoplasmic markers, phosphoenolpyruvate carboxylase and glucose 6-phosphate dehydrogenase, suggesting that sucrose phosphatase is associated with the vacuoles. High speed centrifugation of lysed vacuoles did not result in precipitation of the enzyme indicating that the enzyme is not tightly bound to the tonoplast. Sucrose phosphatase was more sensitive to inhibition by sodium vanadate and less sensitive to ammonium molybdate than was the nonspecific phosphatase which was also present in the extracts. Sucrose phosphatase might be part of the group translocator proposed recently to operate in the tonoplast of sugarcane and red beet.

Journal Article↗
PubMed1987

Molecular approaches towards an anti-ras drug.

The ras proteins have intrinsic biochemical properties that are similar to those of the guanine nucleotide binding regulatory proteins (G-proteins). Increased oncogenic potential results from amino acid substitutions that, by altering either the intrinsic GTPase activity or the GDP/GTP exchange rate, would lead to an increase in the level of the ras-GTP complex. The functional similarity between the ras oncogene proteins and the G-proteins suggests several mechanisms for an anti-ras drug. Anti-ras drugs could act either by retarding the formation of the biologically active GTP complex of the protein or by preventing the ras protein from interacting with its yet-to-be-identified target. Mutagenesis studies of Harvey (Ha) ras have identified the residues involved in GDP and GTP binding, the residues that constitute the epitope for the neutralizing antibody Y13-259 (63-73) and a region (32-40) that is required for effector action. Computer modeling combined with immunological characterization has suggested some structural properties of this putative 'effector' region.

Antineoplastic Agents↗
PubMed1986

Tn7 transposition: a multigene process. Identification of a regulatory gene product.

Tn7 transposition is abolished by the deletion of a 2.2kb HindIII fragment from the central region of the transposon. Transposition is restored when the fragment is present in trans. When this fragment is present in trans with wild-type Tn7, transposition frequencies are stimulated 10-100-fold. The DNA sequence of this fragment has been determined and found to contain one long open reading frame coding for a protein of molecular weight 61 187. We have visualised this protein using a DNA-directed prokaryotic transcription-translation system. This gene may fill a regulatory role in the mechanism of Tn7 transposition. When present in trans the 2.2kb HindIII fragment alleviates a transcriptional block of promoter activity detected in Tn7.

Amino Acid Sequence↗