Serum antibody to poliovirus in patients in a mental deficiency hospital, with particular reference to Down's syndrome.

Neutralization tests for poliovirus antibodies were carried out on 74 patients in an adult mental deficiency hospital: 37 patients with Down''s syndrome and 37 non-Down''s mental defectives. The distribution of antibody titres to poliovirus types 1, 2 and 3 did not differ significantly between the two groups. Most patients had antibody to at least one poliovirus type but less than a third had antibodies at a titre of 1/8 or greater to all three types. The low level of poliovirus immunity in this population may be of epidemiological importance.     

Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds

Determining 3D intermediate structures during the biological action of proteins in real time under ambient conditions is essential for understanding how proteins function. Here we use time-resolved Laue crystallography to extract short-lived intermediate structures and thereby unveil signal transduction in the blue light photoreceptor photoactive yellow protein (PYP) from Halorhodospira halophila. By analyzing a comprehensive set of Laue data during the PYP photocycle (forty-seven time points from one nanosecond to one second), we track all atoms in PYP during its photocycle and directly observe how absorption of a blue light photon by its p-coumaric acid chromophore triggers a reversible photocycle. We identify a complex chemical mechanism characterized by five distinct structural intermediates. Structural changes at the chromophore in the early, red-shifted intermediates are transduced to the exterior of the protein in the late, blue-shifted intermediates through an initial "volume-conserving" isomerization of the chromophore and the progressive disruption of hydrogen bonds between the chromophore and its surrounding binding pocket. These results yield a comprehensive view of the PYP photocycle when seen in the light of previous biophysical studies on the system.     

Variability in clinical laboratory practice in testing for disorders of platelet function: results of two surveys of the North American Specialized Coagulation Laboratory Association

Disorders of platelet function are important causes of abnormal bleeding that require laboratory tests for diagnosis. Currently there are limited guidelines on how to perform clinical testing for these disorders. The goal of our study was to obtain information on how disorders of platelet function are currently evaluated in clinical laboratories. Two patterns-of-practice surveys were distributed to laboratories of the North American Specialized Coagulation Laboratory Association (NASCOLA). The information collected was analyzed to determine practices and common problems. Forty-seven NASCOLA laboratories participated and 54% completed both surveys. The majority of the laboratories that responded performed more than 50 aggregation tests per year, mainly using platelet rich plasma based methodologies. A minority performed testing for platelet secretion and dense granule abnormalities. While platelet aggregation results were reviewed in various ways, laboratories most commonly issued a combined report containing quantitative values (% aggregation and/or slope) and a qualitative interpretation. Although laboratories used similar agonists for aggregation testing, the final agonist concentrations varied widely. Several approaches were also used to obtain reference intervals. Comments offered by the participants indicated that performing, and interpreting platelet function tests were challenging for many clinical laboratories. Although common practices have evolved, there is considerable variability in the diagnostic test procedures used by clinical laboratories to evaluate disorders of platelet function. These patterns-of-practice surveys illustrate a need for guidelines and recommendations for clinical laboratories performing tests of platelet function.     

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.     

Referral patterns in vestibular schwannomas --10 years on

Diagnostic imaging techniques, symptom awareness and education of local sources of referral in vestibular schwannomas, including general practitioners, have all improved in the last 10 years. The referral patterns in vestibular schwannomas in Cambridgeshire in the period 1981-1993 has been reported.(1) A direct comparison was made with regard to referral patterns seen in the last 10 years paying particular emphasis to source of referral, diagnosis at referral and symptoms/size at presentation. The incidence of vestibular schwannomas in the region is compared and discussed. Patients' managed by the 'watch and wait' policy were particularly scrutinized, as they were not discussed previously. Retrospective analysis of computerized database was used. We have demonstrated an increase in the proportion of referrals with known vestibular schwannoma to 90% of all referrals. No significant change in length of history prior to referral, source of referral or principal presenting symptom were found. An overall decrease in tumour size was found but an increase in the percentage with larger tumours (>4.5 cm). We attribute the significant findings to an increase in availability of magnetic resonance (MR) scanners in the country during the past 10 years. It appears that some tumours would still present with no symptoms until late and therefore will elude identification until large in spite of a low threshold for MR scanning.     

4-thiophenoxy-N-(3,4,5-trialkoxyphenyl)pyrimidine-2-amines as potent and selective inhibitors of the T-cell tyrosine kinase p56lck

We have developed a series of 4-thiophenoxy-N-(3,4,5-trialkoxyphenyl) pyrimidine-2-amines as potent and selective inhibitors of p56lck tyrosine kinase activity. In particular, the most potent inhibitor shows cellular activity in T-cell receptor (TCR) stimulated models of cytokine release, which suggests an immunomodulatory role for this class of inhibitor.