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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 163 records · Page 9Linked to original sources
PubMed1993

Human peritoneal mesothelial cells synthesize interleukin-8. Synergistic induction by interleukin-1 beta and tumor necrosis factor-alpha.

The present study demonstrates the synthesis and secretion of the neutrophil-activating peptide/interleukin-8 (IL-8) by cultured human peritoneal mesothelial cells (HPMC) and examines the regulation of its production by other cytokines. Unstimulated HPMC under growth-arrested conditions released IL-8 in a constitutive and time-dependent manner. Stimulation of HPMC with IL-1 beta or TNF-alpha resulted in a time- and dose-dependent IL-8 generation; after 24 hours the levels induced by IL-1 beta and TNF-alpha (both at 1000 pg/ml) were (mean +/- SEM, n = 5) 101 +/- 26.6 (z = 2.023; P < 0.01) and 35 +/- 8.09 (z = 2.023; P < 0.01) respectively. This release was inhibited following coincubation with the relevant anti-cytokine antibody or preincubation with either cycloheximide or actinomycin D. Treatment of HPMC with IL-1 beta or TNF-alpha resulted in increased levels of IL-8-specific mRNA. Stimulation of HPMC with combinations of IL-1 beta and TNF-alpha resulted in a synergistic increase in IL-8 release. This effect was significant at combined doses of IL-1 beta (50 pg/ml) and TNF-alpha (500 pg/ml) and above, when the release of IL-8 was 88 +/- 27% above the additive IL-8 release values (z = 2.201; P < 0.01). Western blot analysis using specific anti-IL-8 antibody demonstrated the presence of two major immunoreactive bands between 9 and 10 kd, in HPMC culture supernatants. These data demonstrate that HPMC synthesize IL-8 and that its release can be regulated as a result of induction of mRNA expression and de novo protein synthesis by other cytokines.

Base Sequence↗
PubMed1992

Isolation and characterization of a membrane protein from rat erythrocytes which inhibits lysis by the membrane attack complex of rat complement.

The membrane attack complex (MAC) of complement in humans is regulated by several membrane-bound proteins; however, no such proteins have so far been described in other species. Here we report the isolation and characterization of a rat erythrocyte membrane glycoprotein of molecular mass 21 kDa which inserts into cell membranes and is a potent inhibitor of the rat MAC. This protein, here called rat inhibitory protein (RIP), was first partially purified by column chromatography from a butanol extract of rat erythrocyte membranes. Monoclonal antibodies (Mabs) were raised against RIP and used for its affinity purification. Affinity-purified RIP was shown to inhibit in a dose-dependent manner the cobra venom factor (CVF)-mediated 'reactive' lysis of guinea pig erythrocytes by rat complement. Conversely, the anti-RIP MAbs 6D1 and TH9 were shown to markedly enhance the CVF-mediated lysis of rat erythrocytes by rat complement. RIP acted late in the assembly of the MAC (at or after the C5b-8 stage) and was releasable from the membranes of rat erythrocytes by phosphatidylinositol-specific phospholipase C. These features, together with its size, deglycosylation pattern and N-terminal amino acid sequence, lead us to conclude that RIP is the rat homologue of the human MAC-inhibitory protein CD59 antigen.

Amino Acid Sequence↗
PubMed1992

Flush aortic tie versus selective preservation of the ascending left colic artery in low anterior resection for rectal carcinoma.

The effects of two methods of colonic vascular ligation were studied in 143 consecutive patients who underwent low anterior resection with total mesorectal excision and full mobilization of the splenic flexure. Either the ascending left colic artery (ALCA) was selectively preserved (n = 52) or a flush aortic ligation was performed (n = 91). In those with a protective colostomy, the radiological leak rate was 12 per cent when the ALCA was preserved (n = 41) and 10 per cent when a flush aortic tie was performed (n = 60) (P greater than 0.95; 95 per cent confidence interval (c.i.) for difference -10 to +15 per cent). In those without a colostomy, the clinical leak rates of 9 per cent when the ALCA was preserved (n = 11) and 19 per cent when a flush aortic tie was performed (n = 31) were not significantly different (P greater than 0.10; 95 per cent c.i. for difference -12 to +32 per cent). Proportional hazards analysis showed no association between the method of vascular ligation and the risk of tumour recurrence and death. Anastomotic leak rates, tumour recurrence and survival were not related to the method of vascular ligation.

Anastomosis, Surgical↗
PubMed1992

The effects of nifedipine on cyclosporine nephrotoxicity in rats.

We have investigated the effect of nifedipine on cyclosporine nephrotoxicity in the Sprague-Dawley rat employing a repeatable, single-shot, isotopic technique of measuring the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Groups of 10 rats received either cyclosporine 5 mg/kg daily or cremaphor with either nifedipine 0.5 mg/kg daily or its vehicle for 14 days. In the cyclosporine group the GFR (P < 0.001, paired t-test), ERPF and filtration fraction (FF) (P < 0.01) all fell significantly. The cyclosporine plus nifedipine group underwent an increase in the ERPF (P < 0.01), the GFR remained unchanged, and the FF fell significantly (P < 0.0001). In this model, nifedipine completely abolished the renal arteriolar vasospasm produced by cyclosporine. That the FF fell in the cyclosporine plus nifedipine-treated animals indicates that cyclosporine has an effect which is not mediated by arteriolar vasoconstriction. This action may be at the glomerular level and is resistant to calcium channel blockade.

Animals↗
PubMed1992

Criteria for diagnosis of urinary tract infection and evaluation of therapy.

Patients with urinary tract infections are commonly used to study the efficacy of new antibiotics. Some criteria, for example the presence of more than 100,000 organisms of a single species per ml as an indicator of infections, have been accepted for many years but all rules have exceptions. Other criteria such as relapse, re-infection are less clearly agreed. Furthermore, timing of collection of specimens during and after treatment shows great variation in protocols and in definition. These criteria and the methodology of collecting, transportation and examination of urine are discussed.

Humans↗
PubMed1992

In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef.

The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs.

Ampicillin Resistance↗
PubMed1992

An audit of appropriate tests in renal biopsy coagulation screens.

Hematological, biochemical, and clinical data was collected over a 15-month period on all adult (greater than 16 years) patients assessed for percutaneous biopsy of native kidneys in a major renal unit. The frequency, causes, interrelationships, and treatment of the abnormalities, along with factors resulting in delay or cancellation of renal biopsies were subsequently subjected to audit. Overall, 30 of 147 coagulation screens were abnormal. The most common coagulopathy was a prolonged bleeding time (BT), which accounted for 58.6% of these. A prolonged BT was not clearly related to other hematological or biochemical indices, and proved to be treatable with arginine vasopressin (DDAVP). The majority of abnormalities occurred in isolation (23/30), and eight of 30 were related directly to current anticoagulant or antiplatelet medication. All but two patients with abnormalities proceeded to renal biopsy after successful corrective measures, but 21 of 30 were delayed by between 1 hour and 14 days. None of the remaining 117 biopsies were delayed, although seven were cancelled for a variety of reasons. The prothrombin consumption index provided no additional useful management information. Our clotting screen, modified by this audit, should safely and efficiently detect clotting abnormalities before renal biopsy.

Adolescent↗
PubMed1992

Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus.

Little information is available regarding renal hemodynamics in non-insulin dependent diabetics (NIDDMs), despite their numerical significance to renal support programs. Therefore, simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (expressed to 1.73 m2 surface area) was performed in 110 newly presenting normotensive NIDDMs [mean (SD) age: 52.5 (10.1) years] and compared with 32 normal subjects of similar age range [age: 52.2 (11.3) years]. Mean (SD) GFR, ERPF and filtration fraction (FF) for the NIDDMs were: 117 (22) ml/min (range: 74 to 178), 534 (123) ml/min and 22.4 (3.0)%, and for the normals: 95 (12) ml/min (range: 75 to 119), 472 (70) ml/min and 20.2 (2.2%), respectively. As a group, NIDDMs demonstrated significantly greater GFR (P less than 0.001), ERPF (P less than 0.005) and FF (P less than 0.001). GFR values above 140 ml/min were observed in 16% of the NIDDMs, while 45% had GFRs in excess of mean +/- 2 SD of the normals. NIDDMs demonstrated a positive relationship for GFR with ERPF (P less than 0.001) and an inverse association for both GFR and ERPF with age (P less than 0.001). Multivariable regression analysis revealed ERPF as the strongest explanatory variable for GFR in the NIDDMs (P less than 0.001), followed by age (P less than 0.01). Significant contributions to the regression analysis were not observed for body mass index, systolic or diastolic blood pressures, glycosylated hemoglobin nor fasting levels of plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. Urinary albumin excretion rates were not correlated with GFR, ERPF or FF. Microalbuminuria was detected in 7% of the NIDDMs in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1992

Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991.

Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991. After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys. beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986. There was an increase in the prevalence of non-beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co-amoxiclav (6.1%) compared with 1986 (4%). Whereas fewer H. influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively). In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials. Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav. Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H. influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole.

Chloramphenicol Resistance↗
PubMed1992

Comparative in-vitro activity of azithromycin, macrolides (erythromycin, clarithromycin and spiramycin) and streptogramin RP 59500 against oral organisms.

The in-vitro activities of azithromycin, clarithromycin, spiramycin and RP 59500 were compared with erythromycin against a wide range of oral organisms which have been implicated in oral infections and/or endocarditis (clindamycin was included for oral streptococci). All compounds tested showed good activity against many of these organisms, although some variation was observed with different species. Clarithromycin was the most active of the antibiotics tested against Gram-positive anaerobes, including Actinomyces spp., Propionibacterium spp., Lactobacillus spp. and Bifidobacterium dentium. Azithromycin was slightly less active than erythromycin against these species. In general, RP 59500 had higher MICs than the macrolides, other than spiramycin, against these organisms, but was superior in activity against Peptostreptococcus spp., inhibiting all isolates at 2 mg/L. Azithromycin was, in general, the most active antibiotic tested against the Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp., Wolinella spp., Actinobacillus actinomycetemcomitans, Selenomonas spp. and Mitsuokella multiacida, including those isolates which were insusceptible to erythromycin. Clarithromycin showed similar activity to erythromycin against most Gram-negative species, but was superior against Capnocytophaga ochraceus and Eikenella corrodens. RP 59500 was less active than the macrolides against most Gram-negative anaerobes, but was superior to erythromycin and clarithromycin against Fusobacterium spp. and Leptotrichia buccalis, some strains of which were moderately resistant to erythromycin. The macrolides and clindamycin were about equally active against the oral streptococci, whereas RP 59500 showed lower inhibitory activity. The in-vitro results suggest that azithromycin and clarithromycin may be of value in the treatment of dental sepsis and the prophylaxis of endocarditis. RP 59500 showed useful activity against Gram-positive anaerobes and, because of its bactericidal activity against oral streptococci, may also prove to have a role in these areas.

Anti-Bacterial Agents↗
PubMed1992

The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991.

Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Missing generations of spermatocytes and spermatids in seminiferous epithelium contribute to low efficiency of spermatogenesis in humans.

Daily sperm production per gram parenchyma (DSP/g) in humans is only 25 or 35% of that for most species including rats and nonhuman primates. To explain the low efficiency of spermatogenesis in humans, the number of generations of germ cells (spermatocytes and spermatids) and the number of these germ cells in each generation were determined for each spermatogenic stage in men with varied efficiencies. Testes were obtained at autopsy, fixed by vascular perfusion with glutaraldehyde, further fixed in osmium, and embedded in Epon 812 before 0.5-micron sections were stained with toluidine blue. Tubular cross sections were photographed, and spermatogenic stages were determined by two observers. Testes were divided into three groups on the basis of DSP/g. The number of generations of spermatocytes and spermatids was greater (p < 0.05) in the high (2.01 +/- 0.05) and intermediate (1.77 +/- 0.04) than in the low (1.45 +/- 0.15) DSP/g group. All groups had a lower number of generations of spermatocytes and spermatids compared to the optimum value of three. The number of these generations per cross section was related (r = 0.85; p < 0.01) to DSP/g in these men. The number per cross section of spermatocytes, spermatids, and the combined number of germ cells was higher (p < 0.01) in the high than in the low DSP/g group. The combined number of germ cells per cross section was related (r = 0.85; p < 0.01) to DSP/g. The combined number of germ cells was higher in the high versus the low DSP/g group in stages I through V, but this difference was significant only in stages IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A comparison of injectable anaesthetic regimens in mules.

Three combinations of injectable anaesthetic agents were compared in nine adult mules. The combinations were xylazine/ketamine (X/K), xylazine/butorphanol/ketamine (X/B/K), and xylazine/tiletamine-zolazepam (X/T). Measured variables were heart rate, respiratory rate, systolic blood pressure, arterial blood pH, PCO2 and PO2, recumbency time and number of attempts to stand. Quality of induction and recovery, muscle relaxation and response to stimulus were evaluated subjectively. Recumbency time was significantly (P < 0.05) longer with X/B/K and X/T than with X/K. Mules required significantly more attempts to stand under the influence of X/T than X/K or X/B/K. No statistically significant (P < 0.05) differences in heart rate, respiratory rate, blood pressure or arterial pH, PCO2 and PO2 were detected between groups.

Anesthesia, Intravenous↗
PubMed1992

A comparison of injectable anaesthetic regimens in Mammoth asses.

Xylazine (1.1 mg/kg body weight [bwt])-ketamine (2.2 mg/kg bwt) (X/K) anaesthesia was evaluated, in nine Mammoth asses, for effectiveness and compared with two other injectable anaesthetic combinations: xylazine (1.1 mg/kg bwt)-butorphanol (0.044 mg/kg bwt)-ketamine (2.2 mg/kg bwt) (X/B/K); and xylazine (1.1 mg/kg bwt)-tiletamine-zolazepam (1.1 mg/kg bwt) (X/T). All drugs were given intravenously (i.v.). Heart rate, respiratory rate, systolic blood pressure, arterial blood pH, PCO2, PO2, recumbency time and number of attempts to stand were measured. Quality of induction and recovery, muscle relaxation and response to stimulus were evaluated subjectively. One animal did not become recumbent with X/K. Recumbency times were significantly (P < 0.05) different: the shortest time was with X/K (24 mins) and the longest time with X/T (46 mins), with X/B/K, it was 37 mins. Assess required significantly more attempts to stand with X/T (n = 3) than with X/K (n = 1) or X/B/K (n = 2). No significant differences in heart rate, respiratory rate, blood pressure, arterial PO2 or PCO2 were detected between groups. Arterial pH was significantly lower at 15 mins in the X/B/K and X/T groups than in the X/K group. Although X/K generally produced effective immobilisation, the combinations of X/B/K and X/T, appeared to be more satisfactory and relatively safe, and provided longer recumbency times and increased muscle relaxation compared with X/K.

Anesthesia, Intravenous↗
PubMed1992

Profile of bronchial responsiveness in children with respiratory symptoms.

A postal questionnaire inquiring into the presence of respiratory symptoms was sent to 3698 children aged 7 and 8 years. Those reporting either cough or wheeze were randomised, and a sample invited to attend for skin testing. A total of 192 symptomatic children, half of whom were atopic and half non-atopic, were randomly selected to enter the study. All children performed and recorded best of three peak expiratory flow measurements twice a day and completed a 10 point respiratory symptom score card each day for one year. They also recorded all treatment taken and made a note of relevant life events. Each child was seen monthly for general assessment and for measurement of nonspecific bronchial responsiveness to methacholine. Of the 192 children, 183 successfully completed the study. For six subjects 11 measurements of the provocation dose required to cause a 20% fall in forced expiratory volume in one second (PD20) were available for analysis and on the remaining 177, greater than or equal to 12 measurements. The prevalence and degree of bronchial hyper-responsiveness (PD20 less than 6.4 mumol) and its relationship to atopy was examined by comparing the percentage of members of each symptom group demonstrating bronchial hyper-responsiveness and the number of occasions on which they did so, and by comparison of minimum and median PD20 values. The range of bronchial responsiveness shown during the study period by each child was expressed as doubling doses of methacholine and compared between symptom groups. Atopy and wheeze were both independently associated with an increased prevalence and greater degree of bronchial hyper-responsiveness when compared with non-atopy and cough respectively, all differences being significant a the 0.001 level.. Thirty three per cent of subjects demonstrated a rnge of methacholine responsiveness of >4 and 13.4% of >6 doubling doses during one year.

Bronchi↗
PubMed1992

Estimation of erythropoietin secretion rate in normal and uremic subjects.

We have developed a method for directly estimating the secretion rate of endogenous erythropoietin (EPO) in human subjects. Carrier-free recombinant human EPO was labeled with 125I by the chloramine T method. Human serum albumin was then added prior to removal of free iodide. Seven normal subjects and nine patients with chronic uremia and anemia were studied. Each subject received a bolus of 125I-EPO according to body size and then a constant infusion for 5 h. Secretion rate was calculated as the rate of infusion divided by serum EPO specific activity given by the protein-bound counts divided by the EPO concentration. Serum EPO concentration was significantly higher in the patients than the controls (mean 30.9 pg/ml vs. 11.1 pg/ml, P < 0.05), although all values were within the normal range. Mean EPO secretion rate was 255 in the patients (range 68-1,101) and 190 pg.kg-1 x h-1 in the normal group (range 52-382). This difference was not significant. As the subjects were in a steady state, EPO disappearance/degradation was the same in patients compared with controls despite a relatively hypoplastic marrow.

Adult↗
PubMed1992

Protein kinase C activation modulates tumour necrosis factor-alpha priming of human neutrophils for zymosan-induced leukotriene B4 release.

Neutrophil (PMN) activation by the yeast component zymosan involves the complement receptor type 3 (CD11b/CD18). Recombinant human tumour necrosis factor-alpha (rhTNF-alpha) augmented the zymosan-stimulated leukotriene B4 (LTB4) release from PMN, reaching a fourfold increase at 10(-9) M. Co-incubation of PMN with 10(-9) M rhTNF-alpha and staurosporine resulted in a further dose-dependent increase, which became significantly greater than a purely additive effect at a staurosporine concentration of 10 nM. This synergy was maintained at all doses of staurosporine tested. In addition, doses of phorbol 12-myristate 13-acetate (PMA) that do not activate protein kinase C (PKC) (below 10(-9) M) also augmented the zymosan-stimulated release of LTB4. However, doses of PMA above 10(-9) M progressively inhibited the response to levels below that of zymosan alone. Staurosporine at 50 nM completely prevented, and 10(-9) M rhTNF-alpha partially but significantly (P less than 0.02 at 10(-8) M PMA, P less than 0.01 at 10(-7) M PMA) reversed, this high-dose PMA inhibition. PKC activation thus opposes the priming effect of rhTNF-alpha on neutrophils, while PKC inhibition may enhance the ability of rhTNF-alpha to prime PMN for zymosan activation. The combined effect of rhTNF-alpha and staurosporine suggests an intracellular synergy rather than simply a direct action due to increased zymosan receptor expression. Thus there appear to be mechanisms whereby the responses of neutrophils may be augmented without activating PKC. Indeed, kinase activation may even exert a degree of feedback control that is antagonized by rhTNF-alpha treatment.

Alkaloids↗