Skin age in Down's syndrome: a note on the findings of Murdoch and Evans.
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Biomedical subjects
Publications and source records attributed to J H Edwards.
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Five hundred and fourteen individuals from an isolated NewFoundland population have been typed and haplotyped for HLA and Factor B (Bf locus). The Bf gene frequencies were: S0.704, F0.226, F1 0.052 and S1 0.018. Tracing the haplotypes backwards on the various pedigrees it was shown that 202 HLA/Bf haplotypes had been introduced into the study population. Some HLA alleles always appeared in association with particular Bf alleles and vice versa. Bf S1 had entered the population four times, always with HLA--A9, B12. Bf F1 had entered three times, always with HLA--B18. There were 17 entries of HLA--Al, B8 that had given rise to the 78 such haplotypes that were now present in the population; all were Bf S. There were 68 family units informative for Bf. They accounted for 240 children and 304 informative meioses. There were three recombinants in the HLA region but none could be shown to have occurred between the HLA-B and Bf loci.
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Placental lead levels were studied in a series of Birmingham births classified by stillbirth, neonatal death, or survival beyond one week. There was an appreciable range of lead levels even in normal births (0.15-3.56 microgram/g) but nevertheless average results showed a pronounced excess of lead in those who failed to survive both birth and the neonatal period. There was no association of placental lead with impaired birthweight among survivors but, in common with other authors, we noted a seasonal variation. The placentae from Indian women had similar lead levels to those from European women and lower values were found in the normal sibs of stillbirths and neonatal deaths. The possibility is discussed that under conditions of impaired fetal health in late pregnancy the placenta may concentrate lead.
Mouse peritoneal macrophages in culture exposed to mouldy hay dust, Micropolyspora faeni or glycopeptide or protein/glycoprotein fractions from this organism show marked biochemical changes. For comparison the interaction of cultured macrophages with zymosan has been investigated. All these agents induce the release of hydrolytic enzymes from macrophages, even in the absence of serum in the medium. The release is time- and dose-dependent and is not associated with loss of the cytoplasmic enzyme lactate dehydrogenase or any other sign of cell death. The parallelism between the capacity of these agents to activate the complement system via the alternative pathway and to induce inflammatory responses in vivo and selective lysosomal enzyme secretion from cultures of macrophages is discussed. The in vitro phenomena seen with mouldy hay dust, M. faeni, the protein/glycoprotein and the glycopeptide derived from it, may be relevant to understanding the role of mononuclear phagocytes in the disease farmer's lung and other inflammatory reactions.
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Materials associated with the induction of farmer's lung were incubated with fresh normal human serum in the presence of magnesium ethylene glycol tetra-acetic acid (MgEGTA) or ethylene diamine tetra-acetic acid (EDTA) and results compared with material known to activate the alternative pathway of complement--zymosan. Results show that Micropolyspora faeni organisms are as active as zymosan in reducing complement (C) levels in the presence of MgEGTA, with a 50% reduction in CH50 at approximately 140 mug/ml. Thermoactinomyces vulgaris organisms produced a 50% CH50 reduction at approximately 1-25 mg/ml and two samples of respirable mouldy hay dust (MHD) at approximately 5-6 mg/ml whereas extracts of M. faeni and T. vulgaris reduced the CH50 titre by 17% and 39% respectively at 16 mg/ml in the presence of MgEGTA. Organisms and extracts did not reduce the CH50 titre in the presence of EDTA even at the maximum concentration quoted by more than 3%, thus it is considered that alternative pathway activation was responsible for C utilization in the presence of MgEGTA. Respirable MHD used less than 4% available C at 4 mg/ml in the presence of EDTA but at 8 mg/ml dust 11% and 28% available CH50 were used compared with 79% and 81% respectively in the presence of MgEGTA. The elution of immunoglobulin binding material from MHD may be responsible for apparent CH50 consumption in the presence of EDTA.
The cellular sequence of events evoked by the intratracheal injection of both respirable mouldy hay dust and zymosan in unsensitized rats and rabbits was markedly similar and contained many features seen in lung biopsies from farmer's lung cases. It is considered that a combination of ability to activate the alternative pathway of complement and the particulate nature of mouldy hay dust and zymosan produced the pulmonary response seen and as such, considerable insight has been gained into mechanisms by which unsensitized individuals respond to dust inhalation. It is suggested that alternative pathway activation may produce an attack of farmer's lung in the absence of precipitins or other forms of hypersensitivity to the dust or its components and that cases designated as 'pulmonary mycotoxicosis' are more rationally explained by this mechanism.
Data on centromeric linkage for trisomies 13 and 18 are presented. There is no substantial evidence that any of these loci studied are on either chromosome. There is weak evidence relating the locus defining the Kidd groups to chromosome 18.