von Willebrand's disease (vWD) is the commonest inherited bleeding disorder in man with an estimated incidence of 1 per thousand of the population. Acquired von Willebrand's disease (AvWD) is rare with less than 70 cases reported. AvWD is usually associated with autoimmune or clonal proliferation disorders and whilst the precise mechanism of acquired deficiency of von Willebrand factor (vWF) is poorly understood, the most likely candidate mechanism(s) are; antibodies inactivate or form a complex with immunologic or functional sites on vWF, or vWF multimers are selectively absorbed by malignant cells. Unlike hereditary vWD, the acquired form of the disease can be exceedingly difficult to manage. We report 4 cases of AvWD diagnosed at our centre over the past 3 yr. There was no evidence of a previous personal or family history of bleeding in any of the patients and AvWD was confirmed by laboratory testing. All 4 patients had a recognised primary medical condition known to be associated with AvWD (Waldenstrom's Macroglobulinaemia in 2 patients, hypothyroidism in 1 patient and monoclonal gammopathy of unknown significance (MGUS) in 1 patient). The acquired haemostatic defect corrected following treatment of the primary condition in 3 patients with the other patient requiring on demand von Willebrand Factor replacement to control spontaneous and surgery induced bleeding.

Aged↗

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Thermolabile methylenetetrahydrofolate reductase (C677T): frequency in the Irish population.

BACKGROUND: The genetic variation which underlies the thermolability and low enzyme activity of 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T) has been extensively studied in many populations, including the Irish population. AIM: To describe the examination of the C677T substitution in two new control samples drawn from the Irish population. METHODS: A collection of 487 serum samples was obtained through the blood transfusion services of both the Republic of Ireland and Northern Ireland and a further 115 samples from volunteers. RESULTS: In both samples, the frequency of the thermolabile/low enzyme activity allele (T) was higher than that previously reported for the Irish population. CONCLUSION: This finding thus supports the need for a greater use of internal control/family-based association studies, as opposed to the classic case control study design, when assessing the contribution of the MTHFR T allele to disease processes.

Adult↗

PubMedDate not supplied

Generation of a variant of human interleukin-4 by alternative splicing.

A second species of interleukin-4 (IL-4) mRNA was identified using both a reverse transcription-polymerase chain reaction and an RNase protection assay. This novel IL-4 mRNA was 48 base pairs smaller than IL-4 mRNA, which is the size of IL-4 exon 2. Sequence data of cloned cDNA demonstrated that this variant contained IL-4 exons 1,3 and 4, with exon 1 spliced directly to exon 3 in an open reading frame. The entire protein encoding region of this variant, named IL-4 delta 2, was identical to IL-4 except for the omission of exon 2. IL-4 delta 2 mRNA was detected in all human peripheral blood mononuclear cells tested and in purified CD3+ T cells. Amounts of both IL-4 and IL-4 delta 2 mRNAs increased upon T cell activation, although IL-4 mRNA increased to a greater extent than IL-4 delta 2 mRNA did. Human IL-3, IL-5, IL-13, and granulocyte macrophage-colony stimulating factor did not use alternative splicing to delete exon 2. We speculate that IL-4 delta 2 may regulate IL-4 function.

Alternative Splicing↗

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Skewing of the CD8+ T-cell repertoire in the lungs of patients with systemic sclerosis.

Pulmonary parenchymal involvement in SSc is characterized by alveolitis and interstitial fibrosis, with an increased number of CD8+ T cells in BAL fluids. This study analyzed the diversity of the alphabeta T-cell repertoire in peripheral blood and BAL fluids from seven SSc patients, looking for evidence of antigen-driven selection of T cells in the lungs. A reverse transcriptase-polymerase chain reaction technique was used to amplify rearranged TCR transcripts from unfractionated, CD4+, and CD8+ T cells. Nearly all AV and BV gene families were expressed in SSc patients and most had similar levels of expression in blood and BAL samples. Next, the diversity of TCR junctional region lengths was assessed, using sequencing gel electrophoresis. Many V gene families had a Gaussian distribution of their junctional region lengths. However, some V gene families had an abnormal pattern of junctional lengths, with skewing away from a Gaussian distribution, including predominance of one or two lengths. This suggests selected expansion of T cells expressing those V genes. Alterations in TCR junctional region lengths were most prominent in bronchoalveolar CD8+ T cells, with similar patterns of skewing in several patients and in one patient over time. Sequence analysis of AV14 and BV17 junctional regions confirmed the oligoclonal character of expansion of bronchoalveolar CD8+ T cells.

Adult↗

PubMedDate not supplied

Immune abnormalities in systemic sclerosis.

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Antibody Formation↗

PubMedDate not supplied

Morbidity, rickets and long-bone growth in post-medieval Britain--a cross-population analysis.

BACKGROUND: Vitamin D deficiency rickets is associated with skeletal deformities including swollen rib junctions, bowing of the legs, and the flaring and fraying of the wrist and long-bone metaphyses. There is, however, scarce information on the direct effect of rickets on skeletal growth in either present or past populations. AIM: The study investigated the effect of vitamin D deficiency rickets on long-bone growth in two post-medieval skeletal populations from East London (Broadgate and Christ Church Spitalfields). Subsequently, inter-population growth variations in relation to non-specific environmental stress (dental enamel defects), industrialization, urbanization and socio-economic status during infancy (birth to 3 years) and early childhood (3-7 years) were examined. SUBJECTS AND METHODS: Data on long-bone diaphyseal length dimensions and stress indicators of 234 subadults from Anglo-Saxon, late medieval and post-medieval archaeological skeletal samples were analysed using both linear and non-linear growth models. RESULTS: Rickets had no effect on the growth curves for any of the long bones studied. However, pronounced variations in growth between the four populations were noted, mainly during infancy. The diaphyseal length of long bones of Broadgate were significantly smaller-per-age than those of Spitalfields and the other samples up to the age of 4 years, and were associated with a high prevalence of enamel defects during early infancy. CONCLUSION: Socio-economic status, rather than urbanization, industrialization or rickets, was the central factor behind the observed differences in growth among the post-medieval populations. The observed inter-population growth variations were only significant during infancy.

Bone Development↗

PubMedDate not supplied

Computer users' postures and associations with workstation characteristics.

This investigation tested the hypotheses that (1) physical workstation dimensions are important determinants of operator posture, (2) specific workstation characteristics systematically affect worker posture, and (3) computer operators assume "neutral" upper limb postures while keying. Operator head, neck, and upper extremity posture and selected workstation dimensions and characteristics were measured among 379 computer users. Operator postures were measured with manual goniometers, workstation characteristics were evaluated by observation, and workstation dimensions by direct measurement. Considerably greater variability in all postures was observed than was expected from application of basic geometric principles to measured workstation dimensions. Few strong correlations were observed between worker posture and workstation physical dimensions; findings suggest that preference is given to keyboard placement with respect to the eyes (r = 0.60 for association between keyboard height and seated elbow height) compared with monitor placement with respect to the eyes (r = 0.18 for association between monitor height and seated eye height). Wrist extension was weakly correlated with keyboard height (r = -0.24) and virtually not at all with keyboard thickness (r = 0.07). Use of a wrist rest was associated with decreased wrist flexion (21.9 versus 25.1 degrees, p < 0.01). Participants who had easily adjustable chairs had essentially the same neck and upper limb postures as did those with nonadjustable chairs. Sixty-one percent of computer operators were observed in nonneutral shoulder postures and 41% in nonneutral wrist postures. Findings suggest that (1) workstation dimensions are not strong determinants of at least several neck and upper extremity postures among computer operators, (2) only some workstation characteristics affect posture, and (3) contrary to common recommendations, a large proportion of computer users do not work in so-called neutral postures.

Adult↗