SummaryAn iodinated derivative of dermatan sulphate was administered by the intravenous, subcutaneous and oral routes to healthy human volunteers in conjunction with unlabelled dermatan sulphate. Following intravenous injection clearance of radiolabel and concentration as measured by competitive binding assay were highly correlated and displayed complex kinetics which were not dose-dependent. Intact 125I-dermatan sulphate was absorbed following both subcutaneous and oral administration, though there appeared to be selective uptake by the gut of a subfraction comprising the smaller or less sulphated molecules. The intact material was subsequently excreted unchanged in the urine. Degradation products of dermatan sulphate were not detected by either gel filtration or affinity chromatography on Polybrene-Sepharose at any time in either plasma or urine, indicating that administered dermatan sulphate is not catabolised by man.

No abstract

The spatial distribution of cells in chimaeric tissues, composed of two genotypes, provides insights into the extent of cell mixing during development and growth. However, direct measurement of patch sizes is not usually meaningful because, when the proportion of one genotype is high, a single patch may encompass several adjacent coherent clones of like genotype (clone aggregation). Two previously used methods of comparing patch lengths were evaluated to overcome this problem. The corrected mean patch length (corrected for the predicted effects of random clone aggregation) is a more useful summary statistic than the median patch length of the minor genotype, because its use is not restricted to grossly unbalanced chimaeras, but its validity has been questioned. The two methods gave almost identical numerical summaries of patch sizes in the retinal pigment epithelium of fetal chimaeras, thereby validating the use of the corrected mean patch length for this tissue. The present study also showed that the corrected patch length was unaffected by the presence of cells hemizygous for the TgN(Hbb-b1)83Clo transgene and that the proportion of pigmented cells in a single histological section was representative of the overall composition of the chimaeric fetus.

A specific binding protein for human corticotrophin-releasing hormone (hCRH), which does not bind to the ovine hormone (oCRH), has recently been demonstrated in human plasma. No such binding protein has been found in sheep plasma. We have investigated the half-life of human and ovine CRH in man and in sheep. Peptides were measured directly in plasma with two-site immunoradiometric assays, as these assays are unaffected by the presence of inactivated peptide fragments. In man, the half-life of hCRH (30.5 +/- 3.3 min; mean +/- S.E.M.) was significantly (P less than 0.001) less than that of oCRH (42.8 +/- 6.4 min). In sheep, there was no significant difference between the half-life of hCRH (46.5 +/- 7.2 min) and that of oCRH (39.8 +/- 10.1 min); these half-lives were also significantly (P less than 0.001) longer than that of hCRH in man. One possible explanation for the shorter half-life of hCRH in man is that the clearance of hCRH is enhanced by CRH-binding protein, although other binding proteins often have the opposite effect. Peak ACTH and cortisol responses occurred earlier in sheep than in man, although no differences were found in the response times to oCRH or hCRH within either species. The responses were more sustained in sheep than in man, and the previously reported biphasic response was only seen in some of the sheep and not in man. Absolute responses to either peptide were greater in sheep than in man; however, in man an 8.1-fold rise in ACTH was measured in response to oCRH, while hCRH gave a significantly (P = 0.043) smaller 4.4-fold response.(ABSTRACT TRUNCATED AT 250 WORDS)