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Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 361 records · Page 20Linked to original sources
PubMed1991

Hyperdynamic sepsis in baboons: I. Aspects of hemodynamics.

The baboon has a number of advantages as a shock model, as its physiological as well as its biochemical behaviour is similar to man. Therefore we have tried to set up a model to mimic the early hyperdynamic phase of clinical sepsis. Seven baboons, 21-25 kg body weight were kept under EEG servocontrolled anesthesia for 8 hr. During this time live E. coli (ATC #33985) 2 x 10(10) BW/8 hr were continuously infused intravenously. Adequate fluid supply with Ringer's solution (up to 40 ml/kg/hr) was given to keep the pulmonary artery wedge pressure at baseline levels; this procedure resulted in a hyperdynamic response with a cardiac output (CO) 20-35% above baseline and a decrease (20-39%) in mean arterial pressure (MAP), leading to a 50% decrease in peripheral resistance. The pulmonary vascular changes were reflected in an increase of the mean pulmonary pressure (PA) to 42% above baseline and a marked rise in pulmonary vascular resistance (PVR) to 50% above baseline with no additional changes in pulmonary gas exchange. After 8 hr both CO and MAP were inversely correlated (r = 0.9-1) with dramatically increased catecholamine plasma levels (15 times above baseline). With continuous infusion of live E. coli (blood levels 10(5)-10(6) CFU/ml) and massive fluid supply we have successfully mimicked hyperdynamic sepsis with severe organ failure after an 8-hr observation period.

Animals↗
PubMed1991

Comparison of the aortic homograft and the pulmonary autograft for aortic valve or root replacement in children.

To assess late results of aortic homograft and pulmonary autograft valves implanted into the left ventricular outflow tract of children, we reviewed the case histories of 146 patients 18 years of age or younger who underwent aortic valve or root replacement between November 1964 and April 1990. One hundred three patients (mean, 12 +/- 3.9 years) received an aortic homograft and 43 (mean, 14 +/- 4.1 years) had their own pulmonary valve transferred to the aortic position. There were 54 valve and 49 root replacements with homografts and 36 valve and seven root replacements with autografts. Hospital mortality rate was 15.5% (16 patients) in the homograft group and 11.6% (five patients) in the autograft group. Survivors were followed up for a total of 867 (homograft) and 297 (autograft) patient-years. The late mortality rate was 16.7% (1.9% per patient-year) for patients with homografts and 13.2% (4.4% per patient-year) for patients with autografts, whereas the incidence for reoperation per patient-year was 2.9% and 2.0%, respectively. At 15 years actuarial rates for homografts and autografts for freedom from reoperation were 54% +/- 8.1% and 68% +/- 11.1%; freedom from endocarditis, 97% +/- 2.4% and 75% +/- 10.2%; and freedom from any complication, 41% +/- 6.5% and 50% +/- 10.3%. Valve degeneration occurred in 19 homografts (2.2% per patient-year), whereas there was no definite instance of primary tissue failure among the pulmonary autografts. This experience would indicate that either the homograft or the autograft valve can be used with acceptable results in children. However, the pulmonary autograft gives better long-term performance and, if growth potential is realized, may be the ideal valve substitute in children.

Adolescent↗
PubMed1990

Transposition of an antibiotic resistance element in mycobacteria.

Bacterial resistance to antibiotics is often plasmid-mediated and the associated resistance genes encoded by transposable elements. Mycobacteria, including the human pathogens Mycobacterium tuberculosis and M. leprae, are resistant to many antibiotics, and their cell-surface structure is believed to be largely responsible for the wide range of resistance phenotypes. Antibiotic-resistance plasmids have so far not been implicated in resistance of mycobacteria to antibiotics. Nevertheless, antibiotic-modifying activities such as aminoglycoside acetyltransferases and phosphotransferases have been detected in fast-growing species. beta-lactamases have also been found in most fast- and slow-growing mycobacteria. To date no mycobacterial antibiotic-resistance genes have been isolated and characterized. We now report the isolation, cloning and sequencing of a genetic region responsible for resistance to sulphonamides in M. fortuitum. This region also contains an open reading frame homologous to one present in Tn1696 (member of the Tn21 family) which encodes a site-specific integrase. The mycobacterial resistance element is flanked by repeated sequences of 880 base pairs similar to the insertion elements of the IS6 family found in Gram+ and Gram- bacteria. The insertion element is shown to transpose to different sites in the chromosome of a related fast-growing species, M. smegmatis. The characterization of this element should permit transposon mutagenesis in the analysis of mycobacterial virulence and related problems.

Amino Acid Sequence↗
PubMed1990

Intracellular mechanisms governing the acute phase of beta-endorphin secretion from the corticotrope in vitro.

It is not certain which protein kinase (A, C or both) is involved in the acute phase of beta-endorphin (beta-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated beta-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.

Animals↗
PubMed1990

Inhibition of rate of tumour growth in rodent species by inoculation of herpesviruses and encephalomyocarditis virus.

Inoculation of herpesviruses and encephalomyocarditis virus into subcutaneous tumours in hamsters and mice reduced the rate of tumour growth compared to untreated tumours or secondary tumours which had arisen following surgical excision of the primary tumour; in addition, survival times were increased in animals whose tumours were inoculated with virus. It is suggested that the role of virus in the modification of tumour growth merits further exploration.

Animals↗
PubMed1990

Experiments with kainate and quisqualate agonists and antagonists in relation to the sub-classification of 'non-NMDA' receptors.

1) The KD values for a range of antagonists including DGG, pCB-PzDA, pBB-PzDA, HDC-QXCA, DNQX and CNQX have been determined using a series of non-NMDA receptor agonists in the isolated spinal cord of the neonatal rat. 2) CNQX and DNQX, and, to a lesser extent, DCH-QXCA, were by far the most potent antagonists, although the degree of selectivity did not vary much throughout the whole range of antagonists used. 3) AMPA and domoate were the most and least sensitive agonists, respectively, to the action of all the antagonists. Ionophoretic experiments in the cat spinal cord in vivo confirmed this order of susceptibility in the case of the antagonists CNQX and pCB-PzDA. 4) Acromelic acid A was a more AMPA-like than domoate-like agonist. 5) The results suggest that two receptors contribute to the responses induced by several of the agonists, and that quisqualate and kainate are less selective agonists at these receptors than are AMPA and domoate, respectively.

Animals↗
PubMed1990

Receptor expression and oxidase activity in human neutrophils: regulation by granulocyte-macrophage colony-stimulating factor and dependence upon protein biosynthesis.

Incubation of human bloodstream neutrophils with 50 u/ml recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) "primed" the respiratory burst (as assessed by fMet-Leu-Phe stimulated luminol-dependent chemiluminescence) and resulted in a rapid (within 15 min) up-regulation of expression of CD11b and CD18 (as measured by FACS analysis). This rapid "priming" and modulation of receptor expression was not inhibited by cycloheximide and hence appeared to be independent of de novo protein biosynthesis. When neutrophils were incubated for up to 5 h in culture, the fluorescence distributions of CD11b and CD18 declined indicating the loss of expression of these receptors as the neutrophils aged, but in rGM-CSF treated suspensions receptor expression was maintained. When neutrophils were incubated in the presence of cycloheximide, they progressively lost their ability to generate reactive oxidants in response to fMet-Leu-Phe so that by 5 h incubation with this inhibitor they could only generate about 25% of the oxidative response stimulated in untreated cells, and the expression of CD16 and CD18 was grossly impaired. Similar effects were observed in rGM-CSF treated suspensions except that cycloheximide required longer incubation times (typically 4-5 h) before impairment of function or receptor expression occurred. These data show that de novo protein biosynthesis is required for both the maintenance of neutrophil function and also for the continued expression of some plasma membrane receptors.

Antigens, CD↗
PubMed1990

A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives.

Chloramphenicol, thiamphenicol and three fluorinated derivatives, Sch 24893, Sch 25298 and Sch 25393, were studied with respect to inhibition of the growth of selected bacterial strains and cell-free translation systems. Thiamphenicol was the least potent inhibitor in the former experiments, but behaved similarly to chloramphenicol and Sch 25298 in the latter, thereby displaying selective inhibition of prokaryotic protein synthesis. Thiamphenicol and Sch 25298 were shown to be like chloramphenicol in inhibiting peptidyl transferase activity specifically on 70 S ribosomes, but the antibiotics bound to their common ribosomal-receptor site with different efficiencies in the order chloramphenicol greater than thiamphenicol greater than Sch 25298. Selected bacterial strains highly resistant to chloramphenicol and thiamphenicol because of chloramphenicol acetyltransferase production were, in contrast, highly sensitive to inhibition by the fluorinated antibiotics. Thus Sch 24893, Sch 25298 and Sch 25393 may have important uses in veterinary and clinical medicine.

Chloramphenicol↗
PubMed1990

Ethics committees and health services research.

Ethics committees in Britain were set up to consider clinical research. Increasingly, however, they are receiving applications for health services research which often involves several or many centres. The performance of 23 ethics committees was examined through a case-study of an application for a multi-centre non-experimental study of prostatectomy. Although all the committees approved the study, long delays occurred (mean 11.5 weeks, range 3-32 weeks), particularly in teaching districts which dealt with large numbers of applications. The composition of the committee and the frequency with which it met were not associated with the time taken to reach a decision. Some delays might be reduced by improving the design of the application forms and ensuring that at least one member of the committee has an understanding of health services research methods. Although such measures might improve the performance of committees, applicants are likely to remain in a logistic trap between funding bodies, clinicians, and ethics committees. In addition, until committees temper their concern for individualistic medical ethics with a collective ethic of the common good, health services research may continue to experience delays and difficulties.

Decision Making, Organizational↗
PubMed1990

Radiological progression in rheumatoid arthritis: do D-penicillamine and hydroxychloroquine have different effects?

We studied 43 patients with active rheumatoid disease of less than 4 years' duration: 23 were given hydroxychloroquine and 20 penicillamine. Efficacy was assessed using clinical and laboratory variables. Radiological progression was measured using Larsen's method for scoring plain radiographs of the hands and feet. Twenty-four patients received 2 years' continuous therapy. Clinically both drugs were effective with falls in articular index and C-reactive protein. Initial radiological damage was less with penicillamine (P less than 0.05 by Wilcoxon rank sum test). By 2 years there were no significant differences between the two drugs; mean increases in Larsen score were 20.3 with penicillamine and 27.5 with hydroxychloroquine. Both groups progressed at a rate likely to give severe joint destruction over 10-20 years.

Arthritis, Rheumatoid↗
PubMed1990

What are antibiotics? Archaic functions for modern activities.

Secondary metabolites are proposed to have played important roles in the evolution of the reactions of living forms on earth, in effecting and modulating reactions during biochemical evolution by chemical and structural interaction with 'receptor' sites in primitive macromolecular templates. For example, in the evolution of the translation system, as the polymerizing reactions became more complex and proteins became involved, the low molecular-weight effectors were functionally replaced by polypeptides, but retained their ability to interact with receptor sites in nucleic acids and proteins. Many of these low molecular-weight effectors now play a different role, that of antagonists, by interacting with the original receptor sites in macromolecular structures; this explains their contemporary activity as antibiotics.

Animals↗
PubMed1990

Aminoglycoside acetyltransferase 3-IV (aacC4) and hygromycin B 4-I phosphotransferase (hphB) in bacteria isolated from human and animal sources.

Members of the family Enterobacteriaceae harboring an enzyme of the aminoglycoside acetyltransferase 3 class (AAC-3-IV) (apramycin and gentamicin resistance) and hygromycin B phosphotransferase 4 (HPH-4-I) (hygromycin B resistance) have been isolated from human clinical sources in Europe. A cluster of genes containing IS140, aacC4, and hphB was found in these strains. We demonstrate by Southern hybridization that this cluster is identical to the operon found in animals that also contains insertion sequences belonging to the ISO family. This provides another example of presumptive transfer of antibiotic resistance genes between bacteria of animal and human origin.

Acetylation↗
PubMed1990

A new polymorphic probe which defines the region of chromosome 19 containing the myotonic dystrophy locus.

The region of human chromosome 19 which includes the myotonic dystrophy locus (DM) has recently been redefined by the tight linkage between it and the gene for muscle-specific creatine kinase (CKMM), which lies just proximal to DM. Utilizing human/hamster hybrid cell lines containing defined breakpoints within this region, we have assigned a number of new probes close to DM. Two of these probes, p134B and p134C, were isolated from a single cosmid clone (D19S51) and detect the same BglI RFLP; p134C detects an additional RFLP with the enzyme PstI. Analysis of these probes in the Centre d'Etude du Polymorphisme Humain families demonstrates tight linkage with a number of markers known to be proximal to DM. A two-point lod score of 6.34 at theta = .025 demonstrates the linkage of this probe to DM. Analysis of a DM individual previously shown to be recombinant for other tightly linked markers indicates that p134C is distal to DM. This result indicates that both the new probe and the existing group of proximal probes including CKMM and ERCC1 probably flank DM and define the genetic interval into which this mutation maps.

Animals↗
PubMed1990

Amlodipine with enalapril therapy in moderate-severe essential hypertension.

The efficacy and toleration of amlodipine (10 mg once daily) was compared with placebo in a four-week double-blind parallel group two-centre study in 38 patients who were receiving enalapril. Patients were moderate to severe hypertensives whose blood pressure was not adequately controlled by enalapril (5-10 mg once daily) (diastolic blood pressure greater than 95 mmHg after four weeks). Results are expressed as the mean difference, in baseline to final changes, between the two treatment groups. At the end of the double-blind period amlodipine patients had significantly greater decreases in supine (-19.4/-10.2 mmHg, P less than 0.001/P less than 0.001) and standing (-16.2/-10.2 mmHg, P less than 0.005/P less than 0.001) blood pressures than the placebo group. There was a greater fall (P = 0.005) in standing diastolic blood pressure at the UK centre (-17.1 mmHg) than in Denmark (-11.2 mmHg). However, pooling the standing diastolic blood pressure data from the two centres gave an overall significant mean treatment difference (-10.2 +/- 2.4 mmHg/P less than 0.001). There were no clinically or statistically significant changes in mean heart rate. Nineteen out of 20 patients in the amlodipine group compared to seven out of 18 patients on placebo, were assessed as improved by the investigator. Similarly 14 out of 19 patients receiving amlodipine were classified as responding to treatment (supine diastolic blood pressure less than 90 mmHg or reduction from baseline of greater than 10 mmHg after four weeks of double-blind therapy) in contrast to four out of 17 receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Segmentation and the development of the vertebrate nervous system.

1. Recent experiments on the development of neural segmentation in chick embryos are reviewed. 2. Segmentation of the spinal peripheral nerves is governed by a subdivision of the somite-derived sclerotome into anterior and posterior halves. Migrating neural crest cells and outgrowing motor axons are confined to the anterior sclerotome as a result, in part, of inhibitory interactions with posterior sclerotome cells. 3. The sclerotomal distribution of certain molecules known to influence growing nerve cells in vitro, namely laminin, fibronectin, N-CAM, N-Cadherin and J1/tenascin/cytotactin, suggest that these molecules play no critical role in determining the preference of nerve cells for anterior sclerotome. 4. Peanut agglutinin (PNA) recognises cell surface-associated components on posterior cells which, when incorporated into liposomes, cause the abrupt collapse of sensory growth cones in vitro. The PNA receptor(s) may be inhibitory for nerve cells in vivo. 5. The chick hindbrain epithelium is segmented early in its development. Each branchiomotor nucleus in the series of cranial nerves V, VII and IX derives from a pair of segments lying in register with an adjacent branchial arch. Neurogenesis of motor and reticular axons begins in alternate segments, suggesting parallels with insect pattern formation.

Animals↗