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Biomedical subjects

L Andrew

Publications and source records attributed to L Andrew.

10 recordsLinked to original sources
PubMed1998

A genome-wide screen for susceptibility loci in ankylosing spondylitis.

OBJECTIVE: To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS). METHODS: One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis. RESULTS: When only the MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422. CONCLUSION: The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.

Chromosome Mapping↗
PubMed1997

Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.

There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.

Adolescent↗
PubMed1996

Inhibition of nitric oxide: effects on interleukin-1 beta-enhanced ovulation rate, steroid hormones, and ovarian leukocyte distribution at ovulation in the rat.

The ovulatory process resembles an inflammatory reaction with an infiltration of leukocytes, production of inflammatory mediators such as cytokines, and a general edema and hyperemia. Nitric oxide (NO), a potent vasodilator and the main mediator of macrophage tumoricidal and bacteriocidal activities, is known to participate in inflammatory reactions and has been shown to mediate the interleukin-1 beta (IL-1 beta)-directed tissue-remodeling events within the ovary. The regulation by NO of ovulation rate, leukocyte distribution, and steroid release in the rat ovary was investigated through use of a combination of in vivo and in vitro models of ovulation and a competitive inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), of the NO synthase (NOS) enzyme. Subcutaneous L-NAME (1.5 x 10(-4) mol/kg) administration significantly reduced the in vivo ovulation rate of eCG/hCG-primed rats (L-NAME-treated: 10.6 +/- 1.8 [mean +/- SEM] oocytes per ovary [O/O], 11.0 +/- 1.2 rupture sites per ovary [RS/O]; saline-treated: 18.0 +/- 1.8 O/O, 19.4 +/- 1.1 RS/O; p < 0.01) at 20 h post-hCG. These results were reflected in vitro, where addition of L-NAME (3.5 x 10(-5) mol/L) to LH (0.1 microgram/ml)-perfused ovaries decreased ovulation rate from 8.2 +/- 1.6 to 2.7 +/- 1 ovulations per ovary (p < 0.05) and simultaneously decreased nitrite accumulation at the completion of perfusions from 16.5 +/- 1.9 to 4.1 +/- 0.5 nmol/ml (p < 0.001). The addition of L-NAME to LH+IL-1 beta (4 ng/ml)-perfused ovaries decreased ovulation rate from 15.2 +/- 2.4 to 0.8 +/- 0.8 ovulations per ovary (p < 0.001) and simultaneously decreased nitrite accumulation at 22 h from 22.8 +/- 2.2 to 1.9 +/- 0.6 nmol/ml (p < 0.001). Studies analyzing and manipulating perfusion flow rate indicated that the L-NAME effects on ovulation rate are primarily due to a reduction in flow rate resulting from inhibition of NO, which may be a consequence of the known vasoconstrictor effects of NOS inhibitors. The observed reduction of in vivo ovulation rate by NO inhibition at 20 h post-hCG was associated with a significant reduction in thecal MCA149+ neutrophils at 12 h post-hCG, the expected time of ovulation (L-NAME-treated: 98.4 +/- 9.2 cells per thecal area; saline-treated: 211.5 +/- 11.5 cells per thecal area; p < 0.001), while ED1+ monocytes/macrophages underwent similar but nonsignificant changes. Plasma (20 h post-hCG) and perfusate progesterone were not different with L-NAME treatment, while perfusate estradiol levels were markedly reduced upon addition of L-NAME, suggesting a role for NO in ovulation but not in the process of luteinization. In summary, deprivation of NO by use of the competitive inhibitor, L-NAME, led to fewer ovulations, reduced accumulation of nitrite, a decreased neutrophil count in the theca of preovulatory follicles, and reduced estradiol secretion, while progesterone release remained unaffected. The NO pathway may therefore play an important role in the regulation of ovulation and the mediation of IL-1 beta's pro-ovulatory effects. There are likely to be primarily vascular effects, but also a nonvascular component, to the NO regulation of ovulation, with both components indirectly affecting ovulatory leukocyte distribution and steroid secretion.

Animals↗
PubMed1995

Characterisation of bovine lipopolysaccharide binding protein and the in vivo acute phase response to Pasteurella haemolytica Type A.

Lipopolysaccharide binding protein (LBP) is a liver-derived acute phase protein which is implicated in modulating the host responses to lipopolysaccharide (LPS) from Gram-negative bacteria. LBP interacts with circulatory LPS to form complexes which bind to the CD14 receptor or cells of the monocytic lineage and neutrophils resulting in their activation. This causes the release of mediators and cytokines which are responsible for initiating the acute phase response. LBP-like activity has now been identified in bovine serum and in this study LBP has been purified from acute phase bovine serum using ion exchange chromatography. On sodium dodecyl sulphate polyacrylamide electrophoresis, bovine LBP demonstrated a single band with a molecular mass of 58 kDa. Bovine LBP enhanced the binding of LPS to human monocytes while enzymatic removal of the CD14 receptor abrogated this interaction. Furthermore, bovine LBP increased the sensitivity of monocytes to LPS by at least 100-fold. Depletion of LBP by means of antibodies to bovine LBP inhibited the serum mediated LPS binding to monocytes. Antibodies to rabbit LBP or recombinant human LBP did not cross-react with bovine LBP. Studies on the kinetics of LBP activity in calves during the acute phase response demonstrated a four-fold increase in the serum concentration 36 h after a single intratracheal inoculation of Pasteurella haemolytica A1. The findings of this study indicate that cattle possess a LPS detection mechanism comparable to that described in man and experimental animals in which LBP forms complexes in serum with circulatory LPS enhancing the signal to the immune system to mount a host response. The isolation of LBP will allow further investigations into LBP-mediated responses to LPS in cattle.

Acute-Phase Proteins↗
PubMed1992

Short term treatment of dermatophyte onychomycosis with terbinafine.

OBJECTIVE: To evaluate the effect of short term treatment with terbinafine on dermatophytosis. DESIGN: Multicentre, randomised, double blind placebo controlled trial of 250 mg/day terbinafine for 12 weeks in dermatophyte onychomycosis. SETTING: Eight dermatology centres in the United Kingdom. PATIENTS: 112 patients (mean age 44, range 19-78), 99 with mycologically proved toenail infections and 13 with fingernail infections, of whom eight were subsequently excluded and 19 failed to complete the study. INTERVENTION: Terbinafine 250 mg daily or placebo for 12 weeks. Follow up for 36 weeks after stopping treatment. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical cure at the end of follow up, adverse events, and biochemical and haematological variables at monthly intervals during treatment. RESULTS: After follow up 82% (37/45) (95% confidence interval 68% to 92%) mycological cure and 69% clinical cure were recorded for evaluable patients treated with terbinafine for toenail infection and 71% (5/7) (30% to 96%) mycological cure and clinical cure for those treated for fingernail infection. The corresponding values for those treated with placebo were 12% (3% to 31%) mycological cure and no clinical cure for toenail infections and 33% (1% to 91%) mycological cure and no clinical cure for fingernail infections. On an intention to treat basis for toenail infections the figures were 73% (38/52) (58% to 85%) mycological cure for terbinafine compared with 6% (0% to 30%) for placebo (p less than 0.007). Two withdrawals were related to adverse events with terbinafine, and there were no significant abnormal laboratory test results. CONCLUSION: 12 weeks' terbinafine is effective and safe treatment for nail dermatophytosis.

Adult↗
PubMed1991

Prevention in practice. New developments in asthma management.

Asthma management is turning from controlling symptoms as they occur to enabling sufferers to control their own condition to keep them symptom free. While this may mean asthma clinics increase practices' prescribing costs, calls for emergency nebulisation should decrease, as should asthmatic consultations in general surgery.

Asthma↗
PubMed1987

Neurodevelopment of monitored versus nonmonitored very low birth weight infants: the importance of family influences.

Very low birth weight (VLBW) infants are at increased risk for neurodevelopmental delays. Follow-up programs have been instituted as one form of secondary prevention, to identify delays early and refer affected children to intervention. To examine the relationship between follow-up care and later development, 82 neonates who weighed 1500 g or less at birth were followed to 36 months of age. Effectiveness of care was assessed by neurodevelopmental status of 45 patients who participated and 37 patients who failed to participate in annual post-neonatal intensive care unit (NICU) monitoring service. At the outset, the groups had similar medical and socioeconomic status characteristics. However, by the third year of life, the monitored patients had a 14-point General Cognitive Index (GCI) advantage over the nonmonitored group. Examination of family process variables, family organization styles, and mother-child behaviors revealed significant differences between the groups, and suggested that monitored patients were raised in more normal, supportive home environments. Correlation and stepwise regression analyses indicated that mother-child behaviors and quality of the home environment were most predictive of 3-year intellectual development, with neonatal and biological measures adding to the predictive classification of neurosensory delays. It is suggested that an infant's medical record, mother-child behaviors, and overall quality of home environment be measured prior to hospital discharge, followed by home-based intervention where indicated.

Child Development↗
PubMed1985

Desferrioxamine induced aluminium removal in haemodialysis.

This study evaluates if the use of high flux membranes and the type of dialysate influences aluminium removal in haemodialysis. Aluminium kinetics and dialysance were determined in baseline conditions and after infusion of desferrioxamine. The free diffusible fraction of plasma aluminium correlated significantly with the plasma aluminium post desferrioxamine, independently of the type of membrane or dialysate used. Aluminium removal therefore depends on the plasma concentration reached and the dialysate concentration. High flux membranes do not improve aluminium removal in vivo.

Aluminum↗