Circulating immune complexes in patients with cryptogenic fibrosing alveolitis.

Increased Clq binding levels have been obtained in serum from twenty-one (50%) of forty-two patients with cryptogenic fibrosing alveolitis (CFA) suggesting the presence of circulating immune complexes. There was a low frequency of positive results using a number of other tests for circulating immune complexes. The increased Clq binding levels were observed in six (35%) out of seventeen patients with lone lung involvement and in fifteen (60%) out of twenty-five patients with extrapulmonary connective tissue disorders. There was an especially close correlation between arthritis and elevated Clq binding. A strong correlation between Clq binding levels and levels of circulating rheumatoid factor (RF) and IgG, and enhancement in macrophage radiobioassay tests using RF-containing sera, suggested that RF might be involved in the circulating immune complexes in these patients. DNAase pre-treatment of sera did not influence the findings, and there was no correlation between Clq binding and levels of immunofluorescent ANA, C-reactive protein levels, or platelet counts. A weak correlation between Clq binding and erythrocyte sedimentation rates, and slightly lower binding levels in treated than untreated patients with 'lone' CFA suggested that binding levels may give some indication of disease activity and may in some instances be influenced by treatment.     

Detection of immunoglobulin G to Pasteurella haemolytica capsular polysaccharide by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of immunoglobulin G (IgG) to the capsular polysaccharide (CP) of Pasteurella haemolytica serotype 1. Purified CP was first covalently coupled to poly-L-lysine and then optimally adsorbed at a concentration of 5 micrograms/ml to microtiter plates in the presence of carbonate-bicarbonate buffer (pH 9.8). The ELISA was used to evaluate and compare the CP-specific IgG response of calves vaccinated with different P. haemolytica-derived experimental vaccines. Elevated levels of ELISA IgG titers were detected in postvaccination sera and lung lavage from calves vaccinated intradermally with live logarithmic-phase organisms or the culture supernatants. The ELISA was found to be a rapid, reproducible, and sensitive technique for the detection of CP-specific antibodies and may be useful to delineate the protective role of these antibodies in bovine pneumonic pasteurellosis.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection

With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes for a subject were not independent. In a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. There was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. These data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.     

Changes in performance,maximal oxygen uptake and maximal accumulated oxygen deficit after 5, 10 and 15 days of live high:train low altitude exposure

Nineteen well-trained cyclists (14 males and 5 females, mean initial V˙O_2max 62.3 ml kg^–1 min^–1) completed a multistage cycle ergometer test to determine maximal mean power output in 4 min (MMPO_4min), maximal oxygen uptake (V˙O_2max) and maximal accumulated oxygen deficit (MAOD). The athletes were divided into three groups, each of which completed 5, 10 or 15 days of both a control condition (C) and live high:train low altitude exposure (LHTL). The C groups lived and trained at the ambient altitude of 610 m. The LHTL groups spent 8–10 h night^–1 in normobaric hypoxia at a simulated altitude of 2,650 m, and trained at the ambient altitude of 610 m. The changes to MMPO_4min, V˙O_2max and MAOD in response to LHTL altitude exposure were not significantly different for the 5-, 10- and 15-day treatment periods. For the pooled data from all three treatment periods, there were significant increases in MMPO_4min [mean (SD) 5.15 (0.83) W kg^–1 vs 5.34 (0.78) W kg^–1] and MAOD [50.1 (14.2) ml kg^–1 vs 54.9 (13.1) ml kg^–1] in the LHTL athletes between pre- and post-altitude exposure. There were no significant changes in MMPO_4min [5.09 (0.76) W kg^–1 vs 5.16 (0.86) W kg^–1] or MAOD [50.5 (14.1) ml kg^–1 vs 49.1 (13.0) ml kg^–1] in the C athletes over the corresponding period. There were significant increases in V˙O_2max in the athletes during both the LHTL [63.2 (9.0) ml kg^–1 min^–1 vs 64.1 (9.0) ml kg^–1 min^–1] and C [62.0 (8.6) ml kg^–1 min^–1 vs 63.4 (9.2) ml kg^–1 min^–1] conditions. In these athletes, there was no difference in the impact of 5, 10 or 15 days of LHTL on the increases observed in MMPO_4min, V˙O_2max or MAOD; and LHTL increased MMPO_4min and MAOD more than training at low altitude alone. Electronic Publication     

Variable expression of vision in sibs with albinism

Oculocutaneous albinism is defined by the presence of cutaneous and ocular hypopigmentation, the latter associated with nystagmus, iris transillumination, reduced retinal pigment, foveal hypoplasia, and misrouting of the optic fibers at the chiasm. The visual acuity is variable but almost always reduced. We report on two brothers with oculocutaneous albinism and markedly different visual acuity. One brother has a visual acuity of 20/100, while the second has similar cutaneous pigmentation and visual acuity of 20/20 and had not previously been recognized as having oculocutaneous albinism. Both brothers have foveal hypoplasia and misrouting of the optic fibers at the chiasm. Biochemical analysis suggests that this is a tyrosinase-related type of oculocutaneous albinism. This study demonstrates that careful observation of foveal development in relatives with normal vision is necessary to detect all individuals with albinism in a family. A suspected diagnosis of albinism may be confirmed when the visual-evoked potentials show excessive decussation of the optic fibers at the chiasm.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.