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Biomedical subjects

S Wood

Publications and source records attributed to S Wood.

At least 73 records · Page 4Linked to original sources

Identification of an immunodominant IgE epitope of the Parietaria judaica major allergen.

Par j 1.0101 is one of the two major allergens of the Parietaria judaica (Pj) pollen, and its three-dimensional structure was built by three-dimensional structural homology modeling. The resultant model was used to identify putative IgE binding regions. Western blot analysis of gene fragmentation products showed that the 1 to 30 region was capable of binding specific IgE from a pool of sera (n = 30) of patients allergic to Pj pollen. Using the structural model as a guide, deletion and site-directed mutagenesis of the 1 to 30 region was performed, and the amino acids involved in IgE binding were identified. In addition, a synthetic peptide covering the 1 to 30 region was capable of binding human IgE without triggering histamine release from basophils of Pj allergic patients (n = 6) and thus represents a haptenic molecule with potential use as an immunotolerant agent. This epitope is also present on the Par j 2.0101 major allergen representing a common IgE epitope. It is an immunodominant epitope, since it was capable of inhibiting 30% of all specific IgE against the Pj major allergens, and therefore, it might be a candidate for the future development of immunotherapeutics.

Allergens↗

Making mistakes when predicting shifts in species range in response to global warming.

Many attempts to predict the biotic responses to climate change rely on the 'climate envelope' approach, in which the current distribution of a species is mapped in climate-space and then, if the position of that climate-space changes, the distribution of the species is predicted to shift accordingly. The flaw in this approach is that distributions of species also reflect the influence of interactions with other species, so predictions based on climate envelopes may be very misleading if the interactions between species are altered by climate change. An additional problem is that current distributions may be the result of sources and sinks, in which species appear to thrive in places where they really persist only because individuals disperse into them from elsewhere. Here we use microcosm experiments on simple but realistic assemblages to show how misleading the climate envelope approach can be. We show that dispersal and interactions, which are important elements of population dynamics, must be included in predictions of biotic responses to climate change.

Animals↗

Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick hepatocytes.

In earlier studies, treatment with sodium arsenite was shown to decrease total hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting step in heme degradation to biliverdin, was considered responsible for the decrease in CYP. Here we investigated the effect of sodium arsenite on induction of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo hepatocytes. When added simultaneously with inducer, arsenite inhibited phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated increases in CYP1A, as measured enzymatically and immunochemically. Near maximal decreases were observed in these forms of CYP at a concentration of 2.5 microM sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by sodium arsenite were concomitant with increases in heme oxygenase. Sodium arsenite was not toxic at concentrations as high as 10 microM, as indicated by protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite-induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H. Combined treatment with heme and phenobarbital induced heme oxygenase to the same extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H activity was decreased only when the treatment included arsenite. These results suggest that elevated levels of heme oxygenase alone are not responsible for arsenite-mediated decreases in CYP2H.

Animals↗

Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants.

The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among allogeneic bone marrow transplant recipients who are receiving a standard protocol as prophylaxis for CMV infection is unclear. We determined the risk factors for death within 1 year among 103 bone marrow transplant recipients by performing a multivariate analysis. The results of donor and recipient CMV serologies did not predict 1-year mortality, although there was a trend towards higher mortality among CMV-seropositive recipients who received marrow from seronegative donors (P = .077). Multivariate analysis revealed that the factors independently associated with 1-year mortality were the development of CMV antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86), bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30-7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17). Although significant on univariate analysis, advanced underlying disease before BMT and the development of active CMV disease after BMT were not independent risk factors. In conclusion, the development of CMV antigenemia after BMT was associated with increased 1-year mortality, while the development of active CMV disease was not. Reactivation of CMV infection may represent a marker of poor immune reconstitution or may contribute to further immunosuppression after BMT.

Adolescent↗

Renal transplantation following renal failure due to urological disorders.

BACKGROUND: Renal allograft outcome, during an 8 year period (1985-1992), has been assessed in 56 renal transplants performed in 55 patients who had end-stage renal failure as a consequence of urological abnormalities. The abnormalities were: primary vesicoureteric reflux (VUR) or renal dysplasia (26 patients); posterior urethral valves (PUV) (15); neuropathic bladders (6); vesico-ureteric tuberculosis (5); bladder exstrophy (3); and prune belly syndrome (1). Six patients had augmented bladders, and eight transplants were performed in seven patients with urinary diversions. RESULTS: Overall, 1 and 5 year actuarial graft survival was 89 and 66%, with mean creatinine of 154 micromol/l +/- 11 (SE) and 145 +/- 9 respectively. Patients with abnormal bladders or conduits (n = 28) had worse graft function than those with normal bladders (n = 28) although graft survival was not significantly different in the two groups at 1 and 5 years: 93 and 75% with normal bladders vs 86 and 57% with abnormal systems. Symptomatic urinary tract infections were common in the first 3 months after transplantation (63%); fever and systemic symptoms occurred in 39% with normal bladders and 59% with abnormal bladders. Urinary tract infection directly contributed to graft loss in six patients with abnormal bladders, but had no consequences in those with normal bladders. CONCLUSIONS: Abnormal bladders must be assessed urodynamically before transplantation, and after transplantation adequacy of urinary drainage must be re-assessed frequently. Prophylactic antibiotics are now given for the first 6 months and urinary tract infections must be treated promptly. With these measures, good results, similar to those of patients without urological problems, can be obtained.

Adolescent↗

Field sensitivity of targeted neonatal hearing screening using the Nottingham ABR Screener.

OBJECTIVE: A population of children having bilateral moderate to profound hearing impairment was investigated to find out the number who passed (false negatives) and who failed (true positives) a screening test based on the auditory brain stem response (ABR). DESIGN: This study of the ABR is a parallel report to Lutman, Davis, Fortnum, and Wood (1997), where the transient evoked otoacoustic emission was examined on a similar but not identical population of at-risk neonates. Hearing screening was undertaken in at-risk neonates (targeted screening) at seven hospitals in the UK using the Nottingham ABR Screener. During the period from January 1988 to December 1993, a total of 6983 neonates had been tested. Assessment of audiological records from the participating centers ascertained that 201 children born between January 1988 and December 1993 had hearing threshold levels in both ears of 50 dB or more, averaged over the speech frequencies 0.5, 1, 2, and 4 kHz. Of these, 51 had completed the ABR screening test. Examination of the ABR records, which included both machine and visual scoring, indicated whether they had passed or failed the screening test. RESULTS: Forty-six of the 51 hearing impaired babies failed the neonatal ABR screen either on one or both ears (five false negatives), and 42 failed the test on both ears (nine false negatives). This resulted in field sensitivities of 90% and 82%, respectively. Two cases of suspected progressive hearing loss have been included in the numbers of false negative results. The percentage of babies passing the screen on both ears and subsequently having normal hearing (specificity) is typically 93%. CONCLUSIONS: Neonatal hearing screening in an at-risk population using a highly automated ABR test is a viable and effective tool for identification of hearing impairment. Although the field sensitivity of the test is high, it is unable to identify all babies with a criterion level of hearing loss. There are a number of possible explanations as to the origin of false negative results: configuration of the pure-tone audiogram, a progressive hearing loss, acquired sensorineural or conductive loss, retrocochlear deafness, or an incorrect interpretation of the screening test. Passing a neonatal screening test, therefore, does not exclude the possibility of subsequent hearing impairment and highlights the need for further surveillance.

Auditory Threshold↗

Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition.

BACKGROUND: Reticuloendothelial system function is impaired in humans receiving lipid regimens. AIMS: To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function. METHODS: Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn's disease who were not receiving intravenous nutrition, and 50 healthy controls. RESULTS: Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p<0.001) than in healthy controls (0.6%) and in patients with Crohn's disease (0.9%). No difference was found between healthy controls and patients with Crohn's disease. There was a correlation (r=0.50; p<0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p<0.01) and healthy volunteers (17.8%, p<0.001). An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition (r(s) =-0.44, p<0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12 months. CONCLUSIONS: Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection.

Adult↗

Apathy, depression, and cognitive performance in HIV-1 infection.

The authors examined the relationship between apathy, depression, and cognitive performance in 48 HIV-1-seropositive and 21 seronegative (control) subjects, using reaction time (RT) and working memory tasks. Apathy, but not depression, was associated with working memory deficits among HIV-seropositive subjects. The cognitive-affective component of the Beck Depression Inventory (BDI), but not apathy, was associated with slowing and decreased accuracy on a choice RT task. The BDI cognitive-affective component was more closely associated than the BDI somatic component with both RT slowing and apathy. Results suggest that prominent symptoms of apathy, independent of depression, may be an important indicator of CNS involvement in HIV infection. Total BDI scores showed a less consistent relationship with neurocognitive performance, suggesting that somatic symptomatology is diagnostically ambiguous among HIV-infected subjects.

AIDS Dementia Complex↗

Anomalous screening outcomes from click-evoked otoacoustic emissions and auditory brainstem response tests.

Transiently evoked otoacoustic emissions (TEOAE) and auditory brainstem response (ABR) tests were used in parallel to screen 862 neonates with risk factors for hearing loss. Seven neonates (0.81%) passed on TEOAE screen yet failed on ABR in one ear (six neonates) or both ears (one neonate). This combination of results has been termed 'anomalous'. Examination of audiometric results obtained on follow-up shows that in one ear of one neonate the result was consistent with the later confirmed audiogram shape. The explanation for the anomalous results in the remaining ears is unclear although neural maturation and the effects of hyperbilirubinaemia are possibilities. There were no instances of progressive or retrocochlear hearing loss identified. None of the seven neonates had better ear hearing loss of > or = 40 dB on long term follow-up.

Acoustic Stimulation↗

Juvenile rheumatoid arthritis in a Canadian First Nations (aboriginal) population: onset subtypes and HLA associations.

OBJECTIVE: To determine onset subtypes and HLA associations of juvenile rheumatoid arthritis (JRA) in a First Nations (aboriginal) population; to determine whether population frequencies of HLA antigens may explain the distribution of subtypes of JRA in this population. METHODS: All patients were children from Manitoba and Northwestern Ontario seen in a single pediatric rheumatology clinic between 1975 and 1996. Patients were identified from a clinic registry. Controls were adults of Algonkian Cree and Ojibway heritage. Class I and II major histocompatibility (HLA) typing was performed for First Nations patients and controls. RESULTS: There were a total of 74 First Nations patients with JRA. The relative frequency of rheumatoid factor (RF) positive polyarticular JRA was higher and that of pauciarticular JRA was lower in First Nations compared with Caucasian patients (42 versus 3% and 22 versus 58%, respectively; p = 0.00000). HLA-DRB1*04 (63%), 08 (43%), and 1402 (25%) were the most common DRB1 antigens among controls. The main subtypes of DRB1*04 were 0404 (33% of controls) and 0407 (23%). HLA typing was performed for 39 First Nations patients; 27 were Cree or Ojibway, 4 were from other tribes, and 8 were part First Nations. Among Cree and Ojibway, 59% of controls and 63% of patients with RF positive polyarticular JRA (n = 16) had HLA-DRB1 antigens bearing the rheumatoid arthritis (RA) shared epitope (OR 1.16, 95% CI: 0.38, 3.48). The OR for polyarticular RF positive JRA in those with DRB1*0802 and 0901 were 0.15, 95% CI: 0.02; and 1.24 and 5.83, 95% CI: 1.58, 28.38, respectively. CONCLUSION: There was a high frequency of the RA shared epitope represented by both HLA-DRB1*0404 and 1402 in this Algonkian population. This high frequency may explain the high frequency of RF positive polyarticular JRA. DRB1*0802 may be protective, whereas DRB1*0901 may increase the risk for this subtype of JRA.

Adult↗

HLA associations of seropositive rheumatoid arthritis in a Cree and Ojibway population.

OBJECTIVE: To determine the HLA associations of seropositive rheumatoid arthritis (RA) in a Cree and Ojibway population; to determine whether specific alleles distinguish juvenile or adult onset. METHODS: HLA-A, B, C, and DRB1 alleles were analyzed in 23 Ojibway and Cree patients with RA seen in a single tertiary care center. Comparisons were made with published results of controls and with results of 18 patients with rheumatoid factor (RF) positive polyarticular juvenile rheumatoid arthritis (JRA) from the same population. RESULTS: Comparisons among patients with RA, patients with RF positive polyarticular JRA, and controls showed increased frequencies of the RA shared epitope in patients with RA and of DRB1*0901 in patients with seropositive polyarticular JRA, while the frequency of DRB1*08 alleles was decreased in patients with RF positive polyarticular JRA. CONCLUSION: In this population, DRB1*0901 may promote while DRB1*08 alleles may protect against a juvenile onset of RA specifically. In contrast, the RA shared epitope may have a greater effect on the risk of adult onset seropositive RA. Due to the small patient numbers, these results require confirmation.

Adult↗

The use of enteral and parenteral feeding.

Nutritional support involves a number of disciplines; collaborative decision-making by a nutrition support team is recommended. Unless factors exist which preclude enteral feeding or make the exclusion of nutrients from the gut appropriate, every effort should be made to feed enterally. Nutritional support involves the provision of safe equipment, treatment protocols and procedures, a training programme for all staff involved in the patient's care, and an audit system.

Enteral Nutrition↗

Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity.

The behavioural and endocrine responses to a 10 min white noise stress have been characterized in female virgin and undisturbed lactating Sprague-Dawley rats. Animals were continuously video-taped and frequent blood samples were collected using an automated sampling system. Noise stress caused hypothalamo-pituitary-adrenal (HPA) activation, as indicated by a rapid increase in plasma corticosterone and ACTH in the virgins: corticosterone concentrations peaked 20 min after initiation of the stress before declining rapidly back to basal concentrations. In contrast, noise stress had no significant effect on either plasma corticosterone or ACTH concentrations in the lactating animals. However, 72 h after weaning the corticosterone response of the ex-lactating rats was of comparable magnitude, but longer duration to that seen in the virgins. Plasma prolactin concentrations were significantly higher in the lactating animals and declined in response to the noise whereas, a transient but reproducible increase was seen in the virgin group. In situ hybridization revealed a significantly lower basal expression of CRF mRNA in the paraventricular nucleus of lactating rats as compared to the virgins, but noise stress had no further effect. Virgin animals showed behavioural responses to the stress, including an increase in the total activity, exploratory behaviours (rearing) and displacement behaviours (grooming). Lactating animals also showed behavioural responses to the noise, but their activities were principally directed towards the pups. These data show that although lactating rats showed normal behavioural reactivity to a psychological stress they showed no statistically significant activation of the HPA axis, suggesting a dissociation of behavioural and neuroendocrine responses to this mild stress.

Adrenocorticotropic Hormone↗