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.     

Purification and characterization of a peanut-agglutinin-binding pancreatic-cancer-related serum mucus glycoprotein

A high-molecular-weight (approximately 3.5 x 10(3) kDa) peanut agglutinin (PNA)-binding glycoprotein was previously identified as a tumour marker in pancreatic cancer sera. In the present study the density of this glycoprotein has been estimated and further analysis performed using sequential lectin blotting combined with serial mild acid hydrolysis followed by repeated Smith degradation. This has allowed partial in-situ characterization of the carbohydrate side-chains. The PNA-binding glycoprotein variably expresses the blood group H and sialylated Lewis a antigens. H and sialyl Lea expression disappeared after mild acid hydrolysis and T (PNA acceptor) disappeared after the first Smith degradation step. T (beta gal(1-3)alpha galNAc) expression reappeared after a second Smith degradation, suggesting that the backbone regions of the mucin side-chains with this core sequence are built up by the further addition of at least 2 monosaccharides. A model has been constructed showing the minimum variations in side chain structure that would explain the results of the serial degradation and lectin blotting. Purification and caesium chloride density gradient centrifugation show that the intact PNA-binding glycoprotein has a density of greater than 1.48 g/ml, characteristic of a mucin. The development of assays using a panel of monoclonal antibodies (MAbs) or lectins directed against the different carbohydrate epitopes expressed on this mucin may provide better diagnostic accuracy for pancreatic cancer than current marker assays which rely on detection of a single epitope.     

Radioimmunoimaging of experimental thrombi in dogs using technetium-99m-labeled monoclonal antibody fragments reactive with human platelets

Monoclonal antibody 50H.19, which reacts with human platelets, was converted to fragments, pretinned, and made into kits for subsequent radiolabeling with 99mTc. The antibody, which cross-reacts with dog platelets, was used to evaluate in vitro binding to blood clots and in vivo in experimental thrombi in dogs. After radiolabeling, 97.4 +/- 6.4% of the 99mTc was antibody-associated. The preparations retained immunoreactivity, as determined by: binding studies using whole blood and determining the ratio of cell-to-plasma radioactivity (ratios of 57.6-61.2) and binding of the antibody to clots (clot/serum ratios were 57.2-74.6%). Approximately 50% of the radioactivity was cleared from the blood in 3-6 min and 18-24% was excreted in urine within 3 hr. Experimental thrombi in dogs could be visualized consistently within 2-3 hr postinjection in peripheral veins and arteries, pulmonary arteries, and the right ventricle. In addition, damage to blood vessel intima without visible thrombi could also be detected. This method has the following advantages: short and simple pre-imaging preparation, and rapid visualization of thrombi with no need for blood-pool subtraction or delayed imaging.     

Autoradiographic localization of thyrotropin releasing hormone receptors in human brain

We used quantitative autoradiography to localize thyrotropin releasing hormone (TRH) receptors in human brain. Highest concentrations of TRH receptors were localized within the cortical, basal, and lateral nuclei of the amygdala and the molecular layer of the hippocampus. Low levels were found in the cortex, diencephalon, and basal ganglia. The radioligand bound with similar affinity and pharmacology to pituitary gland as to brain. These data suggest that authentic TRH receptors in the hippocampus and amygdala may mediate the putative effects of TRH on the human brain.     

Response of male acne to antiandrogen therapy with cyproterone acetate

The antiandrogen cyproterone acetate, which is known to suppress sebum production, but is not a standard therapy, was given in combination with tetracycline to 63 young unmarried men who had failed to respond to 6 months' tetracycline therapy alone. Fifty-seven patients responded and the mean time to clearance was 5.2 months' therapy. The main side effects were nodular sub-nipple breast swellings, which occurred in 13 cases (21%). Such side effects were reversible and cleared after 3-4 months following cessation of therapy. Eighty-eight percent of patients relapsed within 3 months of discontinuing therapy.     

Reversal of colchicine-induced mitotic arrest in Chinese hamster cells with a colchicine-specific monoclonal antibody.

The ability of a high-affinity colchicine-binding monoclonal antibody to reverse the effects of colchicine on Chinese hamster ovary cells was investigated. Using flow cytometry, a complete mitotic blockade was demonstrated after 16 hours with 2.5 x 10(-7) mol/l (molar) colchicine. Colchicine-induced changes were reversible when equimolar antibody was added simultaneously with or up to 6 hours after colchicine. With further delay in addition of antibody, a progressive irreversible increase in mitotic blockade and increase in mean cell size was observed. Prolonged colchicine exposure, without antibody reversal, led to polyploidy and structural chromosome breakage. Early antibody reversal restored cells to the diploid state, whereas delayed reversal resulted in a time-dependent increase in polyploidy. Colchicine-induced polyploidy and chromosomal aberrations may be the basis for both colchicine toxicity and the time-dependent increase in irreversibility of colchicine effects.     

Fixed partial denture design and construction for missing mandibular molars by using an osseointegrated implant for an abutment

This article presented a technique in the design and construction of a fixed partial denture by using a Synthes type E, ITI osseointegrated implant as a distal abutment in the mandibular arch. The technique may be altered to accommodate other forms of implants and uses methods and materials familiar to most dentists.     

Specific Immunoassays for Quinine and Quinidine: Comparison of Radioimmunoassay and Enzyme-linked Immunosorbent Assay Procedures.

Antisera have been raised against quinine and against quinidine, both CINCHONA alkaloids of economic importance. The antisera have been used to set up RIA's, after synthesis of appropriate radiolabels, and ELISA's of the indirect, double antibody format. Characterisation of the two methods show the antisera to be specific for the stereochemistry of the particular hapten. The ELISA's have several advantages over the RIA's, including showing greater specificity and sensitivity, and being quicker and technically easier to perform.