A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10

Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder characterized by corneal endothelial abnormalities, which can lead to blindness due to loss of corneal transparency and sometimes glaucoma. We mapped a new locus responsible for PPCD in a family in which we excluded the previously reported PPCD locus on 20q11, and the region containing COL8A2 on chromosome 1. Results of a 317-marker genome scan provided significant evidence of linkage of PPCD to markers on chromosome 10, with single-point LOD scores of 2.63, 1.63, and 3.19 for markers D10S208 (at (circumflex)theta = 0.03), D10S1780 (at (circumflex)theta = 0.00), and D10S578 (at (circumflex)theta = 0.06). A maximum multi-point LOD score of 4.35 was found at marker D10S1780. Affected family members shared a haplotype in an 8.55 cM critical interval that was bounded by markers D10S213 and D10S578. Our finding of another PPCD locus, PPCD3, on chromosome 10 indicates that PPCD is genetically heterogeneous. Guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sib ship, but were absent in the younger generations of the family. Evaluation of phenotypic differences between family members sharing the same affected haplotype raises questions about whether differences in disease severity, including differences in response to surgical interventions, could be due to genetic background or other factors independent of the PPCD3 locus.     

The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.     

Evaluation of combined antibiotic and competitive exclusion treatment in broiler breeder flocks infected with Salmonella enterica serovar Enteritidis.

Strategic medication in breeding flocks of domestic fowl (Gallus gallus), using antimicrobial treatment followed by competitive exclusion, was evaluated in 13 trials between February and September 1993. In each trial, the flock had been confirmed as naturally infected with Salmonella enterica serovar Enteritidis and the effect of treatment was determined on salmonella isolation from tissues. Of 11 trials where enrofloxacin was used, a long-term reduction of salmonella was observed in two and a short-term reduction was measured in birds from another five trials. Salmonella Enteritidis was isolated from birds after treatment in four other trials with enrofloxacin and in two trials of medication with amoxycillin. After treatment with enrofloxacin significant reductions were found in the prevalence of 5. Enteritidis in tissues from birds, and in levels and prevalence of salmonellas in their environment. No salmonella was identified in statutory meconium samples taken from the hatched chicks derived from the flocks after treatment. The programme of antibiotic treatment and competitive exclusion offers an alternative to slaughter, but the approach must be part of a co-ordinated programme which will effect a decrease in the prevalence of 5. Enteritidis over time by contemporary use of disease security measures. The risk of development of antimicrobial resistance is also discussed.     

Visual processing in scotomata

Summary In contrast with other animals, when the occipital cortex is damaged in man, blindness occurs in spite of intact retinal projections to subcortical centers in the midbrain. By a proper selection of stimuli and responses, however, it can be shown that some information about the visual stimulus may be processed in regions of cortical blindness, even though the stimulus is not seen. One striking example of such processing occurs when dark, rather than bright flashes of light are presented in the scotoma. In this case the dark bars may actually be discriminated better in the scotoma than they are in the intact portion of the visual field. The nature of the residual discrimination has the properties of a primitive stereoscopic mechanism that ignores the sign of the stimulus disparity.     

Induction of antibody to asialo GM1 by spermatozoa and its occurrence in the sera of homosexual men with the acquired immune deficiency syndrome (AIDS).

Compared to healthy homosexual and heterosexual men, homosexual men with acquired immune deficiency syndrome (AIDS) possessed significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1 (ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36% possessed levels of this antibody that were at least two standard deviations above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed from serum by adsorption with spermatozoa. Weekly rectal insemination of male rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15 weeks. These results suggest that asialo GM1 is a component of ejaculated spermatozoa and demonstrate that rectal insemination by itself can lead to the production of antibodies to this glycolipid in the rabbit. In addition, asialo GM1 antibodies may be of value as a serological marker for the early detection of individuals with AIDS.     

Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers

Implanted biomaterials are coated immediately with host plasma constituents, including extracellular matrix (ECM); this reaction may be undesirable in some cases. Poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) has been shown to spontaneously adsorb from aqueous solution onto metal oxide surfaces, effectively reducing the degree of non-specific adsorption of blood and ECM proteins, and decreasing the adhesion of fibroblastic and osteoblastic cells to the coated surfaces. Cell adhesion through specific peptide-integrin receptors could be restored on surfaces coated with PLL-g-PEG functionalized with peptides of the RGD (Arg-Asp-Gly) type. To date, no study has examined the effect of surface modifications by PLL-g-PEG-based polymers on bacterial adhesion. The ability of Staphylococcus aureus to adhere to the ECM and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of medical-device-related infections. This study describes methods for visualizing and quantifying the adhesion of S. aureus to smooth and rough (chemically etched) titanium surfaces without and with monomolecular coatings of PLL-g-PEG, PLL-g-PEG/PEG-RGD and PLL-g-PEG/PEG-RDG. The different surfaces were exposed to S. aureus cultures for 1-24h and bacteria surface density was evaluated using scanning electron microscopy and fluorescence microscopy. Coating titanium surfaces with any of the three types of copolymers significantly decreased the adhesion of S. aureus to the surfaces by 89-93% for PLL-g-PEG, and 69% for PLL-g-PEG/PEG-RGD. Therefore, surfaces coated with PLL-g-PEG/PEG-RGD have the ability to attach cells such as fibroblasts and osteoblasts while showing reduced S. aureus adhesion, resulting in a selective biointeraction pattern that may be useful for applications in the area of osteosynthesis, orthopaedic and dental implantology.     

Determination of cortisol and cortisone in urine using high-performance liquid chromatography with UV detection

The application of reversed-phase gradient high-performance liquid chromatography with UV detection to the determination of cortisol and cortisone in 24-h urine samples is described. The method employs Sep-pak C18 cartridges for the part-purification and concentration of the corticosteroids, with sample enrichment at the head of an HPLC pre-column and separation using water/acetonitrile gradient. The internal standard is 6alpha-methylprednisolone. Measurement of both cortisone and cortisol provides further information on adrenocortical function. 24-hour excretion rate data from normal subjects are reported.     

Buprenorphine is an Antagonist at the ϰ Opioid Receptor

The effect of buprenorphine on bremazocine-induced diuresis was tested in the rat to determine the nature of buprenorphine's action at the opioid receptor. Both morphine-tolerant and naive rats were used to account for possible antidiuretic effects of buprenorphine at the µ site. Separate experiments established that the morphine pretreatment caused profound tolerance with respect to the antidiuretic action of µ agonists. Buprenorphine acted as a potent antagonist (ID₅₀ = 11µg/kg) of the diuretic action of the agonist bremazocine (ED₅₀ = l0 µg/kg). The similar potency of buprenorphine as an antagonist of bremazocine in naive and morphine-tolerant rats further supports the hypothesis that buprenorphine exerts it's antidiuresis via an antagonistic effect at sites, rather than as an agonist at the µ sites. The high affinity displayed by buprenorphine at the opioid receptor in vivo is consistent with this conclusion. Hence, buprenorphine can now be classified as a partial agonist at the µ site and as an antagonist at the site against bremazocine induced urine flow, while its action at the site to which it has much lower affinity in vivo remains unknown.     

Audit of admission to medical school: II--Shortlisting and interviews

Analysis of shortlisting of applicants for interview at St Mary's Hospital Medical School showed that factor analysis could reduce the selection criteria to three independent scales--"academic ability," "interests," and "community service"--all of which contributed to the interview decision. Early applicants scored more highly on all three factors but were still at a greater advantage in selection for interview than would have been predicted. The dean's judgment of priority for interview from the UCCA form was found to predict a candidate's chance of acceptance at other medical schools besides St Mary's. Analysis of interviewing showed high correlations among interviewers in their assessments, although there was evidence of influence by the chairmen. Factor analysis showed three major factors--academic suitability, non-academic suitability, and health--of which non academic suitability was the major determinant of interview success. Non academic suitability was related to personality (high extraversion and low psychoticism) and to the choices made on the UCCA form. The system of admission interviews enabled greater emphasis to be put on broader interests and achievements than if selection had been on the basis of UCCA application form alone.