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B C Sykes

Publications and source records attributed to B C Sykes.

At least 37 records · Page 2Linked to original sources
PubMed1991

Segregation analysis of the structural genes of the major fibrillar collagens provides further evidence of molecular heterogeneity in type II Ehlers-Danlos syndrome.

Type II Ehlers-Danlos syndrome (EDS) is one of a group of disorders characterized by striking abnormalities of the soft connective tissues. The major fibrillar collagens (types I and III) found in these tissues have important stress-bearing functions and abnormal collagen could therefore account for the clinical features of this condition. We have used a number of restriction site dimorphisms, tightly linked to the structural genes of type I collagen (COL1A1 COL1A2) and type III collagen (COL3A1), to investigate the segregation of corresponding alleles in three pedigrees in which type II EDS was clearly inherited as a dominant trait. Discordant segregation of all three collagen genes was seen in a large pedigree that included 17 affected individuals with the typical phenotype of type II EDS. Thus mutations in neither type I nor type III collagen genes were responsible for the disease in this family. In a second small pedigree discordant segregation of the disease with both type I collagen loci was observed while the concordant segregation seen at COL3A1 could easily have arisen by chance (P = 0.5). The third pedigree was uninformative at all three collagen loci because of inability to discriminate between the parental alleles. These results suggest that there may be molecular heterogeneity of type II EDS since abnormalities of type I collagen have been described in other individuals phenotypically similar to those in our study.

Collagen↗
PubMed1987

Segregation of all four major fibrillar collagen genes in the Marfan syndrome.

Linkage markers at or close to the genes encoding the three major fibrillar collagens were used to analyze the segregation of these loci in six pedigrees with dominantly inherited Marfan syndrome. Four pedigrees were discordant at one of the Type I collagen loci (COL1A2), and, of these, two were discordant at the other Type I locus (COL1A1). The Marfan syndrome also segregated independently of the structural loci for Type II and Type III collagen in these two families. This is evidence against the Marfan syndrome being, in general, due to mutations in the major fibrillar collagen genes.

Adolescent↗
PubMed1985

Lethal osteogenesis imperfecta and a collagen gene deletion. Length polymorphism provides an alternative explanation.

A 300 base pair deletion near the 3'-end of the gene encoding Type II (cartilage) collagen has been implicated in the pathogenesis of perinatal lethal osteogenesis imperfecta. We have found similar deletions occurring at a high frequency in normal Asian Indian and West Indian populations generated by a length polymorphism just beyond the 3'-end of the gene. We suggest that this polymorphism provides an alternative explanation of the original results.

Base Composition↗
PubMed1985

Characterization of cells with high alkaline phosphatase activity derived from human bone and marrow: preliminary assessment of their osteogenicity.

Confluent cellular layers are reproducibly obtained (from 21 of 24 specimens) by outgrowth from composite pieces of human trabecular bone and marrow. The cells resemble fibroblasts in terms of morphology, esterase profile, and production of collagen type 1. However, the cells displayed some osteoblastlike features. Both the primary outgrowths and passaged cultures had high alkaline phosphatase activities (37 nmols min-1 X microgram DNA-1) in the range displayed by embryonic osteoblastlike cells. The cellular alkaline phosphatase activity, which showed similarity to the bone isoenzyme on kinetic criteria, was stimulated by 1,25-dihydroxyvitamin D3 but decreased by PTH (1-34). In addition, the cell preparations were shown to increase osteocalcin (bone Gla protein) production in response to 1,25-dihydroxyvitamin D3. The osteogenic potential of the bone and marrow-derived cells has been assessed in an in vivo diffusion chamber assay in which congenitally athymic (nude) mice were used as hosts. None of the 25 chambers examined showed evidence of osteogenesis, although the cells remained viable and fibroblastlike. The alkaline phosphatase activities decreased to less than 1% of the original, high in vitro values. The findings question the hypothesis that bone and marrow-derived cells are osteoblasts or osteoblastlike cells, rather than a mixture of cell lines of the bone and marrow stromal system.

Adolescent↗
PubMed1984

Distribution of laminin, fibronectin, and interstitial collagen type III in soft tissue tumours.

The distributions of laminin, fibronectin, and interstitial collagen type III have been investigated in a series of 60 soft tissue tumours by immunochemistry. Positive laminin staining was seen in sites predicted by the distribution of ultrastructurally visible basal lamina. Pericellular laminin was present in all benign tumours of Schwann cell and smooth muscle origin examined, in the two malignant Schwannomas examined, and in six of 13 leiomyosarcomas. It was also evident around nests of cells in an alveolar soft part sarcoma and around malignant endothelial cells in an angiosarcoma. In fibroblastic and fibrohistiocytic tumours it was found only in blood vessel walls. The results of laminin staining led to revision of the original histopathological diagnosis in seven of the 60 cases studied. Fibronectin was abundant in the stroma of most neoplasms, both benign and malignant. It was also found in a distribution parallel to that of laminin. In some tumours this was clearly distinguishable from the distribution of interstitial collagen. Intracellular fibronectin was shown consistently only in mast cell granules. Its demonstration in synovial cells, fibroblasts, and histiocytes was more variable. Interstitial collagen type II had the most irregular distribution of the three proteins. It was as plentiful in tumours of smooth muscle origin as in tumours of fibroblastic origin, but was scanty in fibrous histiocytomas. Its distribution appeared similar to that of laminin and fibronectin in leiomyomas, but differed from these two proteins in Schwann cell tumours and other neoplasms. In one leiomyosarcoma fibronectin, laminin, and type III collagen appeared to be lost concomitantly from tumour cell peripheries.

Collagen↗
PubMed1983

Comparative distribution of fibronectin and type III collagen in normal human tissues.

The distribution of fibronectin (FN) and type III collagen (IIIC) in normal adult human tissues have been directly compared using immunofluorescence and immunoperoxidase techniques on fresh frozen and formalin-fixed paraffin embedded material. Although in many tissues localisation of these two proteins appeared similar, two major differences were identified: (1) Where the ratio of extracellular matrix to cells is high (e.g. in breast, intestinal submucosa), FN was scanty and present predominantly in association with cells, whether of epithelial, endothelial or mesenchymal origin. IIIC was present diffusely throughout interstitial connective tissue. (2) In the highly specialised vascular beds of spleen and renal glomeruli, FN was abundant and accompanied by little or no IIIC. It is postulated that these differences reflect a generalised more intimate association of FN with cell surfaces and basal laminae which is not always discernible by light microscopy. Proximity of FN and IIIC may nevertheless be important for cell-matrix interactions. It was also noted that "reticulin" fibres as defined by silver impregnation do not all have an identical composition.

Adult↗
PubMed1983

Fibronectin and type III collagen in epithelial neoplasms of gastrointestinal tract and salivary gland.

The distribution of fibronectin (FN) and collagen type III (IIIC) have been compared in a series of epithelial neoplasms from the gastrointestinal tract and salivary gland. The difficulty of distinguishing between FN of epithelial and fibroblastic origin is emphasised and evidence is presented for the validity of this distinction. In carcinomas FN was sometimes, but not invariably, lost from epithelial cell surfaces. Both FN and IIIC were increased in reactive connective tissue stroma. It is concluded that loss of cell surface FN is unlikely to be a useful diagnostic marker for malignancy, but that the occurrence of this phenomenon in vivo as in vitro indicates that it is biologically significant.

Adenocarcinoma↗
PubMed1981

The relative amounts of the collagen chains alpha 1(I), alpha 2 and alpha 1(III) in the skin of 31 patients with osteogenesis imperfecta.

1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent alpha 1(III) and alpha 1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the alpha 1(I) to alpha 2 chains of type I collagen has also been measured. 2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio alpha 1(III)/alpha 1(I) was significantly increased (P less than 0.001) and the ratio alpha 1(I)/alpha 2 significantly decreased (P less than 0.005) compared with age-matched control subjects. 3. In three infants with lethal (type II) osteogenesis imperfecta the ratio alpha 1(III)/alpha 1(I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients. 4. The ratio of alpha 1(I)/alpha 2 and of alpha 1(III)/alpha 2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio alpha 1(III)/alpha 1(I) was increased. 5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied. 6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the alpha 1(I) chain rather than of the alpha 2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.

Adolescent↗
PubMed1974

Salt-soluble elastin from lathyritic chicks.

The isolation of a salt-soluble homogeneous elastin from the aortas of lathyritic chicks by chromatography on DEAE-cellulose and salt precipitation is described. These new techniques, as well as some previously published by other workers, were evaluated with the help of antiserum raised in sheep against insoluble chick elastin. The purified elastin was very basic and behaved in a predictable manner in coacervation studies. The protein migrated in sodium dodecyl sulphate-polyacrylamide gels as a single band moving slightly faster than pyruvate kinase (mol.wt. 57000).

Amino Acids↗