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J Andrews

Publications and source records attributed to J Andrews.

At least 19 recordsLinked to original sources
PubMed1992

DNA sequence analysis of the gene encoding the HTLV-I p21e transmembrane protein reveals inter- and intraisolate genetic heterogeneity.

DNA sequence analysis was performed on a 235-bp region of the p21 e transmembrane protein gene of the human T-cell lymphoma/leukemia virus type I (HTLV-I) which encompassess the putative immunosuppressive peptide. Polymerase chain reaction-based amplification was used to generate multiple molecular clones from isolates derived from fresh or cultured cells from 19 individuals. A dendrogram was constructed using the p21e DNA sequence information to compare the sequences among isolates in the current study and other previously published HTLV-I isolates including strains from Africa and Papua New Guinea. Examination of multiple clones from individual isolates revealed the presence of multiple genotypes in patients with tropical spastic paraparesis/HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma. These findings suggest that HTLV-I, like HIV, may be present as a quasispecies in vivo. Our studies, however, failed to identify specific sequence motifs that segregated exclusively with the lymphoproliferative or neurological forms of the disease.

Base Sequence↗
PubMed1992

In vitro activity of RU 29246, the active compound of the cephalosporin prodrug ester HR 916.

The in vitro activity of RU 29246 was compared with those of other agents against 536 recent clinical isolates. The MICs of RU 29246 for 90% of members of the family Enterobacteriaceae tested (MIC90s) were less than 2 micrograms/ml except those for Morganella spp. (16 micrograms/ml) and Proteus spp. (8 micrograms/ml). RU 29246 was active against Staphylococcus aureus (MIC90, < or = 8 micrograms/ml) and against Staphylococcus saprophyticus and coagulase-negative staphylococci (MIC90s, < or = 2 micrograms/ml). Streptococci and Neisseria gonorrhoeae were highly susceptible to RU 29246, and the activity of the agent against isolates of Streptococcus pneumoniae (MIC90, < or = 0.5 micrograms/ml), Haemophilus influenzae (MIC90, < or = 2 micrograms/ml), and Moraxella catarrhalis (MIC90, < or = 2 micrograms/ml) was comparable to those of the other cephalosporins tested. RU 29246 was insusceptible to hydrolysis by the common plasmid-mediated beta-lactamases (TEM-1 and SHV-1). However, hydrolysis by the new extended-spectrum beta-lactamases (TEM-3, TEM-5, and TEM-9) was detected. Results of the study suggested that RU 29246 should be investigated clinically for use in the treatment of a wide range of infections.

Bacteroides fragilis↗
PubMed1992

Haemodynamic and metabolic effects of short term administration of synthetic sex steroids in humans.

Synthetic sex steroid administration is a major cause of iatrogenic hypertension but little is known of the haemodynamic or metabolic consequences of these steroids. This study examined the short term blood pressure, volume and metabolic consequences of 5 day administration of synthetic androgen to normal men and synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6 men) on a constant diet took part in each of 3 studies. Males received testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol 0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8 mmHg) systolic pressure but the other steroids did not alter blood pressure. All 3 treatments increased body weight. There were no consistent changes in plasma electrolytes or glucose with any steroid, and no urinary sodium retention or changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid significantly increased plasma volume (measured as volume of distribution of 125I human serum albumin). Renin substrate and cortisol rose and renin concentration fell on ethinyloestradiol. These studies suggest that the progestogen component may contribute to the blood pressure raising effects of oral contraceptives.

Adult↗
PubMed1991

Laser-assisted versus mechanical recanalization of femoral arterial occlusions.

A randomized clinical trial was performed to test the hypothesis that a laser-heated probe is superior to standard techniques to reopen occluded femoral arteries. Twenty patients were treated with a standard guidewire and balloon dilation method. In a second group of 20 patients, the laser probe was initially used as a nonheated mechanical device. If the probe was unsuccessful in mechanically reopening the artery, an Argon laser was activated to heat the probe. The mean length of occlusion was 15.9 +/- 10.3 cm. The success rate for the laser probe was 15 of 20 (75%), which was not significantly different from the standard method, 19 of 20 (95%). Most of the success in the laser-probe group was due to the probe's mechanical properties. The laser probe was successful as a cold, mechanical device in 13 of 15 (87%) arteries. It was necessary to heat the probe in 5 patients. When heated, the laser probe assisted recanalization in 2 but perforated the artery in 3 cases. The results of this randomized trial do not support the hypotheses behind the use of the thermal laser probe. The laser probe functions primarily as a mechanical device. The thermal activation does not significantly improve the success rate without increasing the risk of perforation. This small additional benefit does not justify the large cost of current thermal laser devices. This controlled study also demonstrates a higher success rate in long occlusions than previous reports of mechanical balloon recanalization. This is due to a combination approach of retrograde and anterograde probing of the occluded segment.

Adult↗
PubMed1991

Inhibitors of ADP-ribose polymerase decrease the resistance of HER2/neu-expressing cancer cells to the cytotoxic effects of tumor necrosis factor.

Four human ovarian and breast tumor lines expressing the HER2/neu oncogene were resistant to the cytotoxic and DNA-degradative activity of TNF. The resistance was not associated with altered TNF receptor function because Scatchard analysis of 125I-rTNF binding to HER2/neu-expressing target cells revealed receptors with normal binding parameters. Furthermore, the TNF receptors on the resistant lines were capable of signal transduction as evidence by the induction of ADP-ribose polymerase activity and MHC expression. TNF resistance was not reversed by coincubation with drugs that interrupted the glutathione redox cycle. In addition, although coincubation of HER2/neu-expressing targets with cycloheximide resulted in significant TNF-induced lysis, when compared to HER2/neu-nonexpressing targets similarly treated with cycloheximide, a significant relative resistance was still present. To investigate the role of ADP-ribosylation in the resistance of these targets, we used nontoxic concentrations of two inhibitors of ADP-ribose polymerase, 3-aminobenzamide, and nicotinamide. Both inhibitors completely reversed the resistance of HER2/neu-expressing targets to TNF-mediated cytotoxicity and DNA injury in a concentration-dependent fashion. These inhibitors of ADP-ribose polymerase did not act by down-regulating expression of HER2/neu oncogenes. In contrast, aminobenzamide and nicotinamide significantly diminished TNF-induced cytotoxicity of L929 targets. These data suggest that the activity of ADP-ribose polymerase may play a pivotal role in determining the fate of the target cell during exposure to TNF.

Cytotoxicity, Immunologic↗
PubMed1991

Transzygomatic approach to tumours of the parasellar region. Technical note.

A simple transzygomatic approach to the middle fossa centered on the inferior retraction of the temporal muscle hinged on the transected zygomatic arch is described. This approach allows a very low basal exposure of the middle and temporal fossa minimizing the amount of temporal lobe retraction needed to approach intra and extradural lesion in this location. The upper portion of the infratemporal fossa is also reached after removal of the middle fossa skull base. This approach is simple, easily performed, does not require extensive skull base removal, and still offers excellent visualization of the middle fossa and of the upper infratemporal fossa.

Chondrosarcoma↗
PubMed1991

Production of mutant dihydrofolate reductases of Lactobacillus casei for nuclear magnetic resonance spectroscopy.

Seven mutations (L4P, W21L, D26E, D26N, R57H, R57K and T63Q) affecting residues of dihydrofolate reductase of Lactobacillus casei, suspected of being important in substrate, inhibitor, or cofactor binding, were made by gapped-duplex site-directed mutagenesis. Expression of the L. casei dhfr gene required the removal of nucleotide sequences flanking the coding region. Temperature-inducible expression from the lambda pL promoter of plasmid pPLc28 allowed synthesis and subsequent affinity purification of five mutant proteins in amounts and purity sufficient for nuclear magnetic resonance (NMR) spectroscopic analysis (100 mg or more) from 10-liter cultures. W21L required the growth of 40-liter batches, and L4P was not found. Using a two-plasmid system with pcI857 providing lambda repressor and pMAC5-14 expressing the mutant gene, any auxotrophic strain of Escherichia coli can be used as a host, allowing isotopic labelling of each amino acid of any protein for rapid NMR peak assignment.

Base Sequence↗
PubMed1991

A role for prostaglandins in the suppression of cutaneous cellular immunity and tumour development in benzo(a)pyrene- but not dimethylbenz(a)anthracene-treated mice.

Prostaglandins have been implicated in the immune suppression associated with the development of some tumours. Application of the prostaglandin synthetase inhibitor indomethacin, to murine skin prior to treatment with the chemical carcinogens benzo(a)pyrene (BP) or 7,12 dimethylbenz(a)anthracene (DMBA), restored contact sensitivity responses to 2,4-dinitrofluorobenzene in BP- but not DMBA-treated mice. However, indomethacin failed to restore antibody responses in either group of mice. Prolonged treatment with BP or DMBA led to cutaneous tumour formation. Indomethacin was found to delay the onset and reduce the size of tumours in BP- but not DMBA-treated mice. It is proposed that prostaglandin-induced suppression of cellular cutaneous immunity may play a role in BP- but not DMBA-induced cutaneous carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Value of positive technetium-99m leucocyte scans in predicting intestinal inflammation.

The value of positive scans of autologous 99mTc-labelled leucocytes in the detection of intestinal inflammation was assessed in 29 patients with known inflammatory bowel disease and a high probability of intestinal inflammation and 58 with a low probability of intestinal inflammation comprising 37 with intestinal symptoms and 21 with suspected abscess. Autologous leucocytes were labelled with 99mTc using either of the established methods. In patients with inflammatory bowel disease, 3/13 with ileocaecal and 1/11 with colonic accumulation of 99mTc were incorrectly diagnosed in that there was no histological evidence of inflammation in those regions. In the low probability patients, all 26 positive images were false positives: there were 19 in the ileocaecal and 7 in colonic regions and no differences between the two subgroups. False positives were more common in low probability than high probability patients (p = 0.011). The results were independent of the 99mTc cell labelling technique used. Three false positive patients also had normal scans for 111In-labelled granulocytes. The time of first detection of 99mTc in the bowel was earlier in true than in false positive patients (92% v 33% within 1 h, p = 0.008), the false positive rates in the first hour of imaging being 5% in high and 15% in low probability patients. In 99mTc scintigraphy, the appearance of the isotope in the intestine occurs commonly in the absence of inflammation irrespective of the cell labelling technique used. In high probability patients, imaging at 1 h can more reliably discriminate true from false positives and retain clinical usefulness. In low probability patients specificity remains unacceptable and 99mTc-labelled leucocyte scanning in these patients is of little value as a positive predictor of intestinal inflammation.

Adolescent↗
PubMed1990

Maternal cigarette smoking during pregnancy, adiposity, social class, and perinatal outcome in Cardiff, Wales, 1965-1977.

There have been several reports in which maternal nutritional status has been implicated as either a mediating or moderating factor in the relationship between maternal cigarette smoking and birthweight and perinatal survival. Also, there is evidence that the effects of maternal cigarette smoking on both intrauterine growth and fetal viability are more intense among women of lower social status. The well-maintained data set of the Cardiff Births Survey from 1965-1977 afforded an opportunity to review these issues among over 50,000 births in south Wales (the survey took place in Cardiff City through 1973 and subsequently included suburban areas of South Glamorgan). The major findings were: (1) Smoking was much more common with descending maternal social status; (2) among upper status women, smokers had similar or slightly greater mean Quetelet's indices (kg/m2) than nonsmokers. Among lower status women, smokers were considerably thinner than nonsmokers; (3) the greater the adiposity of the mother, the less the association between cigarette smoking and depressed birthweight; (4) perinatal mortality was significantly higher among heavy smokers (10 or more cigarettes a day) than among nonsmokers; and (5) neither the decrease in birthweight nor the excess mortality associated with smoking was greater among those of lower rather than upper social status, except among class I women, among whom smoking was only minimally associated with depressed birthweight. With the inclusion of the South Glamorgan suburban population in the survey after 1974, the excess mortality associated with heavy smoking dropped from 53 to 16%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗