A5062297208- Proteoglycans and glycosaminoglycans research
- Ocular Surface and Contact Lens
- Corneal Surgery and Treatments
- Glycosylation and Glycoproteins Research
- Corneal surgery and disorders
- Osteoarthritis Treatment and Mechanisms
- Protein Tyrosine Phosphatases
- Cell Adhesion Molecules Research
- Genomic variations and chromosomal abnormalities
- Connexins and lens biology
- Protease and Inhibitor Mechanisms
- melanin and skin pigmentation
- Glaucoma and retinal disorders
- Genomics and Rare Diseases
- Cancer-related molecular mechanisms research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hemophilia Treatment and Research
- Blood Coagulation and Thrombosis Mechanisms
- Pharmacological Effects and Toxicity Studies
- Folate and B Vitamins Research
- Genetic Syndromes and Imprinting
- Epilepsy research and treatment
- Tendon Structure and Treatment
- Eosinophilic Disorders and Syndromes
- Shoulder Injury and Treatment
University of Manchester
2012-2014
Manchester Academic Health Science Centre
2014
Cardiff University
2004-2013
University Hospital of Wales
2011
Wessex Regional Genetics Laboratory
2005
St. Mary's Hospital
2002
Sydney Children's Hospital
1994
Human HtrA1 belongs to a widely conserved family of serine proteases involved in various aspects protein quality control and cell fate. Although has been implicated the pathology several diseases, its precise biological functions remain be established. Through identification potential targets, studies presented herein propose that within context arthritis contributes cartilage degradation. Elevated synovial levels were detected fluids obtained from rheumatoid osteoarthritis patients, with...
RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused constitutional dysregulation RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup p.Val55Met) in RRAS, gene encoding small monomeric GTPase controlling cell adhesion, spreading migration, underlying rare (2 subjects among 504 individuals...
The small leucine-rich proteoglycans (SLRPs) modulate tissue organization, cellular proliferation, matrix adhesion, growth factor and cytokine responses, sterically protect the surface of collagen type I II fibrils from proteolysis. Catabolism SLRPs has important consequences for integrity articular cartilage meniscus by interfering with their homeostatic functions. were dissociatively extracted total knee hip replacements, menisci macroscopically normal fibrillated mature age-matched...
Background Congenital sideroblastic anemias are rare disorders with several genetic causes; they characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic anemia is defect the X-linked 5-aminolevulinate synthase 2 gene but this not always present. Recently, variations for carrier SLC25A38 were reported to severe type autosomal-recessive anemia. Further evaluation importance was...
Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted sulfated glycosaminoglycans (GAGs). The major GAG cornea is keratan sulfate (KS), which N-linked to one of three PG core proteins. To ascertain the importance carbohydrate chain sulfation step KS functionality, we generated a strain mice targeted gene deletion Chst5, encodes an N-acetylglucosamine-6-O-sulfotransferase that integral chains. Corneas homozygous mutants were...
Kabuki syndrome (KS) is a rare multi-system disorder that can result in variety of congenital malformations, typical dysmorphism and variable learning disability. It caused by MLL2 point mutations the majority cases and, rarely deletions involving KDM6A. Nearly one third remain unsolved. Here, we expand known genetic basis KS presenting five patients with condition, all whom have novel mutation types- two mosaic small deletions, whole-gene deletion, multi-exon deletion an intragenic...
purpose. Recently, gene-targeted strains of mice with null mutations for specific proteoglycans (PGs) have been used investigations the functional role these molecules. In present study, corneal stroma mouse was examined to provide some baseline PG morphologies in this species. methods. Monoclonal antibodies glycosaminoglycan (GAG) chain sulfation patterns were characterize composition extracts by SDS-PAGE and Western blot analysis identify their tissue distribution immunofluorescence...
purpose. To evaluate the use of neoepitope monoclonal antibody BKS-1, which recognizes keratanase-generated keratan sulfate (KS) stubs on proteoglycans in human cornea, limbus, and sclera. methods. BKS-1 specifically a [N-acetyl-glucosamine-6-sulfate (GlcNAc-6-S)] at nonreducing terminal corneal skeletal KS glycosaminoglycan chains. It was produced by using keratanase-digested peptides from bovine cartilage aggrecan as immunizing antigen. used conjunction with 5D4 to analyze distribution...
To investigate structural remodeling of the developing corneal stroma concomitant with changing sulfation patterns keratan sulfate (KS) glycosaminoglycan (GAG) epitopes during embryogenesis and onset transparency.Developing chick corneas were obtained from embryonic day (E)12 to E18 incubation. Extracellular matrix composition collagen fibril spacing evaluated by synchrotron x-ray diffraction, hydroxyproline assay, ELISA (with antibodies against lesser more highly sulfated KS), transmission...
Summary Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level an important determinant of bleed number development arthropathy . The aim this study was compare the haemophilia health score ( HJHS ) Gilbert severity, age, thrombin generation TG underlying mutation in a cohort had minimal access haemostatic replacement therapy. Ninety‐two individuals were recruited from Pakistan. Age, age at first bleed,...
Two sibs with non-deletional alpha thalassaemia and mental retardation (ATR-X) have been ascertained showing variable neurological features. The proband had a complex picture recurrent apnoea, partial seizures, prolonged periods of semiconsciousness between 12 17 months age. Episodes spontaneous laughter were also feature. An EEG was initially normal. Hb H inclusions present but rare in this family. sole genital anomaly deficiency the foreskin, feature not previously described ATR-X.
DOI 10.1002/ajmg.a.30747 In the Results and Discussion section, first paragraph read “Clinical findings on patients are summarized in Table I. Patients 4, 10, 16 have been previously reported [Costello, 1971, 1977, 1996; Feingold, 1999; Gripp et al., 2000].” The second sentence should read: “Patients 3, authors regret error.