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Biomedical subjects

W Church

Publications and source records attributed to W Church.

9 recordsLinked to original sources
PubMed1995

Ascertainment of myotonic dystrophy through cataract by selective screening.

Myotonic dystrophy (DM) almost always results from the expansion of an unstable (CTG)n repeat. The mutation can be detected directly. Affected patients with cataracts may have minimal additional signs of the disorder, but all are at risk of life threatening complications. We have studied the efficacy of detecting new families with myotonic dystrophy by selectively screening cataract patients. Selection criteria were: age under 60 with no obvious precipitating factor (except non-insulin dependent diabetes mellitus (NIDDM)); patients of any age with other signs suggestive of myotonic dystrophy detected by the ophthalmologist. Ninety-six patients were tested prospectively; 17 others under 55 were screened retrospectively. All patients were counselled by a clinical geneticist before testing. The patients' DNA was analysed using the DNA probe/restriction enzyme combinations GB2.6/EcoRI, KB1.4/BglI and polymerase chain reaction (PCR). Six patients have been found to have a mutation, three (3.1%) in the prospective group and three (17.6%) in the retrospective group. Three of these patients had minimal myotonic dystrophy and three had classical DM.

Adolescent↗
PubMed1993

Vitamin K1 metabolism and the production of des-carboxy prothrombin and protein C in the term and premature neonate.

This study investigated the incidences of undercarboxylated (protein induced by vitamin K absence: PIVKA) prothrombin and protein C in 496 neonates across a wide range of gestational ages. These findings are related to vitamin K1 levels (an indicator of cofactor availability) and vitamin K1 epoxide levels (a measure of the efficiency of the hepatic vitamin K cycle). PIVKA protein C was present in at least trace amounts in 27% of infants; whereas, PIVKA prothrombin was present in 7% of infants. PIVKA prothrombin and protein C were present at high plasma concentrations in 2% to 3% of term and preterm neonates and both PIVKA protein C and prothrombin increased with gestational age. Despite elevated plasma concentrations of PIVKA protein C and diminished levels of normally carboxylated protein C, clinical thrombosis was not observed. The mean (+/- SD) vitamin K1 level in the study population was 0.009 +/- 0.02 nmol/L (adult reference interval: 0.3 to 2.6 nmol/L) with no clear relationship between vitamin K1 levels and production of PIVKA protein C or prothrombin. By comparison with adults, the epoxide form of the vitamin comprised an abnormally high proportion of total vitamin K1; this suggests possible inefficiencies in hepatic reductase cycling.

Biomarkers↗
PubMed1991

The UK Northern region genetic register for familial adenomatous polyposis coli: use of age of onset, congenital hypertrophy of the retinal pigment epithelium, and DNA markers in risk calculations.

A polyposis register has been established in the Northern Region of England. A total of 48 families with 71 living affected subjects has been identified during the first three years of operation, a prevalence of 2.29 x 10(-5). Indirect ophthalmoscopy identifies the majority of gene carriers by showing multiple areas of congenital hypertrophy of the retinal pigment epithelium (CHRPE). The absence of this sign in families limits its value where a relative with CHRPE has not been identified. Combining eye examination with data on age of onset and linked DNA markers is highly effective in carrier exclusion; 38% of 528 first, second, and third degree relatives had their carrier risk reduced to less than 1 in 1000. Even with such assurance many subjects will request continued bowel screening at a reduced frequency. Little interest has been shown in prenatal diagnosis. The principal value of a genetic register with domiciliary nurse visiting is the reduction in early mortality among unrecognised gene carriers.

Adenomatous Polyposis Coli↗
PubMed1990

Active site-specific immunoassays.

This study describes a process by which serine proteases that contain an S-1 arginine subsite and active site histidine may be inactivated and subsequently quantitated using a combination of peptidyl chloromethylketone chemistry and immune recognition technology. Active site labeling and inactivation of proteases is attained by modification of the active site histidine with a peptidyl chloromethylketone. In the specific illustrations demonstrated, we used the compound biotinyl-epsilon-aminocaproyl-phenylalanylprolylarginyl chloromethylketone. This reagent reacts quantitatively and specifically with the active site histidine of a wide variety of proteases that are elaborated in the coagulation and fibrinolytic system. The inactivated enzyme(s) may be quantitated by combinations of antiprotein antibodies and avidin binding technology using the biotin moiety on the peptide inhibitor. We have demonstrated the capability of capture of inactivated enzyme products directly on to solid-phase avidin with subsequent quantitation of bound protein using specific antibodies. In the converse system we have captured specific proteases using antiprotein antibodies in the solid phase and have quantitated bound enzyme by using avidin. Subsequent detection and quantitation has been achieved using the enzymatic activity of horseradish peroxidase conjugated either to the antibody or to avidin. Both types of assays are feasible, with avidin capture being the preferred mode when enzyme is evaluated in the presence of excess zymogen, as would be common in the evaluation of most blood-clotting enzymes. Assays are illustrated for tissue plasminogen activator, plasmin, thrombin, factor Xa, and activated protein C, which can measure protease concentrations as low as 50 pmol/L. Specific applications of the assays are provided in studies of the activation of prothrombin by the prothrombinase complex and of factor X with Russell's viper venom factor X activator. These assays measure the mass of active site present in the reaction mixture and are relatively independent of subspecies of enzyme or the environment in which the activity is generated. These assay systems provide powerful tools for elucidating product-precursor relationships in multienzyme feedback reactions involving zymogen activation.

Animals↗
PubMed1990

Intracranial calcification and seizures: a case of central neurofibromatosis.

Periventricular calcification was found in an eight-year-old boy with seizures. The diagnosis of tuberous sclerosis was considered, but (like his mother) he has central neurofibromatosis. This condition must be considered in the differential diagnosis of children with intracranial calcification and seizures.

Brain↗
PubMed1989

Congenital hypertrophy of retinal pigment epithelium: a sign of familial adenomatous polyposis.

Families of people known to have familial adenomatous polyposis are screened for signs of the disease by yearly examination of the bowel. Multiple areas of congenital hypertrophy of the retinal pigment epithelium have been described in patients with familial adenomatous polyposis. To assess the reliability of this marker 40 patients with familial adenomatous polyposis, representing all 25 pedigrees with living affected members in the Northern region's polyposis registry, were examined for hypertrophy of the retinal pigment epithelium. All had multiple lesions, ranging in number from two to over 40. None of the 35 controls had more than two lesions. Ocular examination is valuable for detecting carriers of the gene for familial adenomatous polyposis before their symptoms develop.

Adenomatous Polyposis Coli↗
PubMed1986

Purification of six human vitamin K-dependent proteins in a single chromatographic step using immunoaffinity columns.

The major human vitamin K-dependent proteins were purified from plasma using immunoadsorbents made with antibodies specific for each protein. Monoclonal antibodies to Factor VII, Factor IX, Factor X, Protein C, and Protein S were prepared from mice immunized with isolated vitamin K-dependent antigens. Purified monoclonal antibodies and a purified burro polyclonal anti-prothrombin immunoglobulin were individually coupled to Sepharose and used in a tandem series of columns to purify each of the vitamin K-dependent proteins from eluates of barium citrate precipitates of plasma. The proteins were eluted from the columns by sodium thiocyanate and retained functional activity following dialysis. Prothrombin, Factor VII, Factor IX, Factor X and Protein C were essentially homogeneous as judged by NaDodSO4-PAGE; Protein S was isolated as a Protein S-C4b binding protein complex. These results indicate the utility of monoclonal antibody immunoadsorbents for purifying the human vitamin K-dependent proteins and represent a considerable simplification over other purification schemes.

Antibodies, Monoclonal↗