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Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 343 records · Page 19Linked to original sources

Scottish cocaine users: wealthy snorters or delinquent smokers?

Ninety-two cocaine users were interviewed in Scotland. Most were middle-class nasal users, also used other drugs and generally gave cocaine a positive rating. One half of them had at some time used cocaine more than once a week. For some, this period lasted some months, when as much as 30 'lines' of cocaine were used per day of cocaine use. More of these heavy users reported adverse effects of cocaine than was the case for light users. Nonetheless, most heavy users had reduced their use by themselves to the point that their current cocaine use was no different from that of light users. Possible explanations for this apparently spontaneous reduction are discussed.

Adolescent↗

Duplex scanning alone before carotid endarterectomy: a 5-year experience.

The role of duplex scanning and arteriography as a means of assessing patients for carotid endarterectomy has been reviewed for the period 1984 to 1988 when 98 carotid endarterectomies were performed. Of these 44 were selected for surgery on the basis of duplex assessment alone, 48 after carotid angiography and duplex scanning and six after angiography alone. No difference between the groups of patients was observed for either perioperative or follow-up complication rates, although all late deaths occurred in patients who had been examined by angiography. By the end of the study period angiography was requested for less than 30% of all patients undergoing carotid endarterectomy. It is argued that the change in our practice is safe provided that certain criteria are met. These include angiography in cases of suspected aortic arch or proximal vessel disease and in those symptomatic patients with a duplex diagnosis of complete occlusion.

Adult↗

Do doctors and patients agree? Views of the outcome of transurethral resection of the prostate.

In an attempt to establish the extent to which patients and doctors agree on the outcome of health care, the pre- and postoperative states of health of 388 men undergoing transurethral resection of the prostate for benign disease were studied. Generally, high levels of concordance (greater than 70%) were obtained. The strongest agreement was for clearly defined events, such as episodes of acute retention (95%); the weakest agreement occurred over the most subjective symptoms, prognostic expectations, and ambiguous terms (around 60%). The level of agreement was not associated with any characteristics of the patient, surgeon, or treatment.

Cystoscopy↗

Vitamin E supplementation and periventricular hemorrhage in the newborn.

In a randomized controlled trial preterm babies received 20 mg vitamin E/kg im soon after birth (day 0) and at 24 and 48 h. The mean +/- SD plasma vitamin E level on day 0 was identical in supplemented and control groups (9.98 +/- 4.88 mumol/L) and rose progressively only in supplemented babies reaching a peak of 69.2 +/- 21.36 mumol/L at 72 h. Supplemented babies had a lower incidence of intraventricular hemorrhage (IVH) diagnosed by ultrasound (9/102, 8.8%) than the control group (37/108, 34.3%; 95% CI for difference in incidence, 15-36%). In a subsequent uncontrolled study using the same vitamin E preparation, a single dose of 20 mg/kg was given soon after birth to preterm babies. The peak mean +/- SD plasma level was 32.97 +/- 13.47 mumol/L at 48 h. The incidence of IVH (16/121, 13.2%) was lower than in historical control from the randomized trial (95% CI for difference; 10.2-31.8%) in spite of the single-dose group having more clinical risk factors for IVH. We conclude that vitamin E protects against IVH in preterm babies.

Birth Weight↗

A double-blind comparison of amlodipine and placebo added to open enalapril in patients with moderate to severe essential hypertension.

The antihypertensive efficacy and tolerability of amlodipine in combination with enalapril were assessed in this two-center study. Patients with moderate to severe hypertension and with diastolic blood pressure > 95 mm Hg after 4 weeks of treatment with open-label enalapril 5-10 mg daily were randomized to receive amlodipine 10 mg daily or placebo, double-blind for a further 4 weeks, in combination with open-label enalapril. There were significantly larger falls in mean supine and standing blood pressure in patients treated with enalapril plus amlodipine than in those treated with enalapril plus placebo. There was no clinically or statistically significant difference between treatment groups in pulse rate, ECG, or body weight. Side effects were generally mild or moderate with a similar incidence in both treatment groups. The study showed once-daily amlodipine to be effective and well tolerated when administered as add-on therapy to enalapril.

Adult↗

Mutations in the aphA-2 gene of transposon Tn5 mapping within the regions highly conserved in aminoglycoside-phosphotransferases strongly reduce aminoglycoside resistance.

Aminoglycoside-phosphotransferases contain several conserved amino acid sequence motifs. Using hydroxylamine we have obtained five independent missense mutations within the aphA-2 gene of transposon Tn5. Four of the mutations dramatically reduced antibiotic resistance. Two were identical and included the replacement of His-188 with Tyr. One other resulted from the replacement of Gly-189 with Asp. These three mutations map within the first of the conserved motifs. The replacement of Asp-261 with Asn maps to the third of these structural motifs. A mutation diminishing but not eliminating aminoglycoside resistance resulted from replacement of the conserved Val-36 with Met. By site-directed mutagenesis three additional mutants were obtained: His-188 was replaced with Leu and Ser, and Arg-211 within the second conserved motif was substituted by Gly. All three showed reduced levels of resistance to kanamycin. Our results show that these conserved motifs are essential for the biological activity of aminoglycoside phosphotransferases.

Amino Acid Sequence↗

Site-specific integration of the Streptomyces plasmid pSAM2 in Mycobacterium smegmatis.

A method which allowed the stable integration of DNA fragments at a single site (attB) in the chromosome of Mycobacterium smegmatis was developed using an integrative element from Streptomyces ambofaciens, pSAM2. Vectors containing an Escherichia coli replicon (pBR322), the kanamycin resistance gene from Tn903 for selection in mycobacteria, and a fragment of pSAM2 containing the int gene as well as the attachment site (attP) were constructed and introduced to M. smegmatis by electroporation. Transformants showed stable integration of the plasmid into a single site (attB) of the mycobacterial genome. This approach should be valuable for analyses of gene expression in various mycobacterial species and permit the development of stable recombinant mycobacterial vaccine strains expressing bacterial or viral genes inserted in pSAM2.

Blotting, Southern↗

Public awareness of the symptoms of diabetes mellitus.

A cross-sectional survey by standard questionnaire was conducted to determine the public's knowledge (n = 480) of diabetes and diabetes symptoms. Four hundred and sixty-two (96%) subjects had heard of diabetes, 350 (73%) could give a rudimentary definition of diabetes, but 231 (48%) were unable to name any symptom and only 20 (4%) knew of thirst and polyuria in combination. The public's knowledge of diabetes symptoms is poor. This may possibly contribute to delayed presentation of Type 2 diabetes.

Adult↗

Pulmonary autograft aortic valve replacement: long-term results.

Since 1967, 339 cases of replacement of the aortic valve with the patient's pulmonary valve have been carried out in the National Heart Hospital and the Harley Street Clinic, London. The operation was introduced following the finding of progressive degeneration in previously placed homograft valves. The longest follow-up is 24 years and the cumulative total follow-up is 3,986 patient-years. Overall hospital mortality is 7.4% (25 cases) but with only one death after 1976. Late mortality is 38 patients and actuarial survival is 80% at 20 years. No anticoagulants have been used and there have been no emboli. Bacterial endocarditis occurred in 11 patients. Reoperation was carried out in 33 patients. Freedom from replacement is 85% at 20 years. There is no evidence of calcification or progressive tissue degeneration and the explanted valves show viable tissue. There is also accumulating evidence that the valve can grow in children. The actuarial freedom from all events is 70% at 20 years. With the current low operative risk and absence of progressive degenerative change plus growth prospects, it offers a potentially permanent valve replacement for infants, children, and young adults.

Adolescent↗

Transfer of plasmid RSF1010 by conjugation from Escherichia coli to Streptomyces lividans and Mycobacterium smegmatis.

The plasmid RSF1010 belongs to a class of plasmids (IncQ) that replicate in a range of bacterial hosts. Although non-self-transmissible, it can be mobilized at high frequency between different gram-negative bacterial species if transfer functions are supplied in trans. We report the transfer of RSF1010 by conjugation from Escherichia coli to the gram-positive actinomycetes Streptomyces lividans and Mycobacterium smegmatis. In its new hosts, the plasmid was stable with respect to structure and inheritance and conferred high-level resistance to streptomycin and sulfonamide. This is the first reported case of conjugative transfer of a naturally occurring plasmid between gram-negative and gram-positive bacteria.

Blotting, Southern↗

A survey of the heat shock response in four Streptomyces species reveals two groEL-like genes and three groEL-like proteins in Streptomyces albus.

A survey of the heat shock response was carried out in a series of streptomycetes. Four major heat shock proteins (HSPs) were observed in each of four species (Streptomyces albus, S. lividans, S. parvulus, S. viridochromogenes) after pulse labeling with [35S]methionine and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three corresponded to the major procaryotic HSPs Lon, DnaK, and GroEL on the basis of their apparent molecular masses (94 to 100, 70, and 56 to 58 kDa, respectively). In addition, a smaller protein (16 to 18 kDa) was detected in all species but was most dramatically induced in S. albus. Consequently, studies focused on this species. As in other procaryotic systems, thermal induction (elicited by a shift from 30 degrees C to 41 degrees C) of the 70- and 94-kDa proteins was transient and expression returned to uninduced levels after 60 min. In contrast, the 56- to 58-kDa (GroEL) and 18-kDa proteins (HSP18) remained induced for more than 2 h. Two-dimensional gel electrophoresis allowed resolution of at least eight S. albus HSPs. HSP56-58 was composed of multiple acidic protein species, whereas HSP18 appeared to be basic. In spite of these differences in their physical characteristics, the N-terminal peptide sequence of HSP18 was similar to those of GroEL-like proteins found in other organisms and identical to one of the HSP56-58 species. In fact, N-terminal amino acid analysis of the S. albus 56- to 58-kDa species showed that it was composed of two proteins that differed in 3 of 10 positions, an observation that was supported by the detection of two groEL-like genes by Southern hybridization. The amino acid sequence of one of these proteins was identical to that of HSP18. Pulse-chase experiments did not reveal evidence of posttranslational processing of either HSP56-58 or HSP18.

Amino Acid Sequence↗

Characterization of the groEL-like genes in Streptomyces albus.

Three GroEL-like heat shock proteins (HSP56, HSP58, and HSP18) have been observed in Streptomyces albus (G. Guglielmi, P. Mazodier, C. J. Thompson, and J. Davies, J. Bacteriol. 173:7374-7381, 1991). Here we report the cloning and complete nucleotide sequence of groEL1, which encodes HSP18 and HSP58, and groEL2, which encodes HSP56. Both nucleotide sequences predicted proteins of 56,680 Da that were 70% identical. The 5' nucleotide sequence of groEL1 coded for a protein corresponding to HSP18 that may be a processed gene product. At least two groEL-like genes were present in all 12 Streptomyces species tested; they were not closely linked in the genome. groEL1, but not groEL2, was adjacent to a groES-like gene.

Amino Acid Sequence↗

Effect of misoprostol on concentrations of prostaglandins in synovial fluid.

The effect of misoprostol, a synthetic analogue of prostaglandin E, on prostaglandin concentrations in synovial fluids was investigated in a randomised placebo controlled, double blind study. The synovial fluid concentrations of prostaglandin E1, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were measured at the beginning and end of a 24 hour period in 25 patients with effusions of the knee joint. During this period the patients were treated with diclofenac (50 mg every eight hours) and either misoprostol (400 micrograms) or placebo every 12 hours. The concentrations of prostaglandin E and 6-keto-prostaglandin F1 alpha were not significantly altered during treatment. There was an unexpected significant reduction in thromboxane B2 concentrations in the group treated with misoprostol (within group analysis). Although the mean concentration with misoprostol was about half the mean concentration with placebo, this difference was not statistically significant in the between group analysis. These results indicate that misoprostol is unlikely to exert a proinflammatory effect or to interfere with the prostaglandin mediated effects of non-steroidal anti-inflammatory drugs. The significant decrease in thromboxane B2 concentrations in the misoprostol treated group suggests that misoprostol may exert an anti-inflammatory effect.

6-Ketoprostaglandin F1 alpha↗

Immune inhibition of virus release from human and nonhuman cells by antibody to viral and host cell determinants.

Immune inhibition of release of the DNA viruses, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and surprisingly two herpes viruses, bovine mamillitis and equine abortion, were not inhibited by either anti-viral or anti-host sera. Using the herpes simplex virus model, inhibition of virus release was detected in different cells of human and nonhuman origin with cross-inhibition between cell lines of different origin; thus, this form of immunotherapy may not require antibody to be tissue or organ specific. Evidence of inhibition of virus release from neoplastic and leukemic cell lines suggests possible application of this approach to control of virus-mediated leukoproliferative pathology (e.g. Burkitt's lymphoma or adult T cell leukemia).

Animals↗

Isolation and characterisation of an aminoglycoside phosphotransferase from neomycin-producing Micromonospora chalcea; comparison with that of Streptomyces fradiae and other producers of 4,6-disubstituted 2-deoxystreptamine antibiotics.

The gene (aphA-5c) encoding for aminoglycoside-O-phosphoryl-transferase (APH(3')-Vc) from Micromonospora chalcea 69-683 was cloned by expression in Streptomyces lividans; it showed strong nucleic and amino acid similarities with previously described streptomycetes aph genes. S1 mapping of the 5' region indicated that, as with several streptomycete genes, transcription apparently initiates at the translation start codon, with no extragenic ribosome binding site. Comparison of the flanking sequences of the actinomycete aph genes indicates considerable divergence, which is not consistent with the notion that clustered biosynthetic genes for structurally related (or identical) antibiotics are disseminated in their entirety between microbial species.

Amino Acid Sequence↗