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Biomedical subjects

B McKenna

Publications and source records attributed to B McKenna.

15 recordsLinked to original sources

Cell Culture Evaluation of the Semliki Forest Virus Expression System As a Novel Approach for Antigen Delivery and Expression in Fish.

Heterologous gene expression by Semliki Forest virus (SFV) expression vectors was investigated in fish cell culture. Experiments performed using an infectious strain of SFV, replication-defective SFV particles, and recombinant SFV RNA constructs encoding the Escherchia coli LacZ or firefly luciferase reporter genes indicated that levels of SFV-mediated expression in fish cells were dependent on cell type and temperature. Maximal expression levels were observed in the two salmonid-derived cell lines CHSE-214 and F95/9 at 25 degrees C and 20 degrees C. As the temperature was lowered to 15 degrees C or below, levels of reporter gene expression were reduced up to 1000-fold, indicating that the SFV replication complex functioned inefficiently at low temperatures. The ability of SFV expression systems to function in fish cells was further investigated by analyzing the expression of the protective VP2 antigen of infectious pancreatic necrosis virus (IPNV) from the various constructs, including a novel DNA-based SFV plasmid. The VP2 protein produced in CHSE-214 and F95/9 cells transfected or infected with the recombinant SFV-IPNV VP2 constructs appeared to be synthesized in an antigenically correct form, as evidenced by the ability to react with several conformation-dependent IPNV-specific monoclonal antibodies. Whether the temperature-restricted replication and expression displayed by SFV-based constructs in fish cell culture also occurs in vivo remains to be determined.

Journal Article↗

Continuous infusion cyclosporine and nifedipine to day +100 with short methotrexate and steroids as GVHD prophylaxis in unrelated donor transplants.

Unrelated donor marrow transplantation is associated with an increased incidence of graft-versus-host disease (GVHD) compared with sibling donor transplants. Forty-one patients undergoing unrelated donor transplants were treated with a GVHD prophylaxis regimen that consisted of continuous infusion cyclosporine from day -1 to 100 days post transplant along with nifedipine, glucocorticoids and short-course methotrexate. The regimen was well-tolerated in this cohort with mostly high risk disease. Fifty-one percent of patients developed acute GVHD, which was grade III-IV in 22% of patients. Six of 22 patients at risk for chronic GVHD developed extensive chronic GVHD, five of whom were adults. In patients <18 years of age, there was a >40% chance of 2 year disease-free survival. Use of continuous infusion cyclosporine with nifedipine as an immunosuppressant and protectant against cyclosporine-induced toxicities in unrelated donor transplants is well-tolerated, and results in acute GVHD incidence favorable to that reported with bolus cyclosporine.

Adolescent↗

Bridging the theory-practice gap.

In New Zealand, there is a festering debate over a "theory-practice gap" in nursing. Joint appointments may be a potential solution to this issue. Joint appointments refer to a variety of arrangements whereby concurrent employment occurs within an educational institution and a clinical setting. Advantages for the appointees include job satisfaction and professional growth. Clinical credibility for nurse educators enables improved facilitation of student learning. In clinical areas, benefits in patient care are associated with the marrying of academic rigour with clinical practice. Some appointees assist with staff development, act as consultants on nursing issues and undertake research. Disadvantages in the concept focus on role conflict, i.e. incongruity between the roles and role ambiguity, i.e. lack of clarity concerning expectations. Success depends upon the personal attributes of appointees; realistic expectations; flexibility to allow the concept to evolve; and support from colleagues and management. This research describes a case study of a joint appointment between a nurse lecturer and a staff nurse in an acute forensic psychiatry unit. Advantages, disadvantages and reasons for success are discussed in relation to the literature findings. (See p15-15) The discussion focuses on the need to develop research methodology to further clarify potential benefits and advantages.

Clinical Competence↗

Clinical pathway development: the Overlake Model.

Overlake Hospital Medical Center has developed a multi-faceted Care Management Model to improve clinical and fiscal outcomes for selected patient populations. The Clinical Pathway Component of this model has been applied to high-volume, high-loss DRG groups. Success of the program can be attributed to the unique multidisciplinary problem solving approach, team building and a focus beyond the inpatient hospital stay.

Chief Executive Officers, Hospital↗

CEA-like material in cytosols from human breast carcinomas. Correlation with biochemical and pathologic parameters.

CEA-like material was found in 51 of 62 primary human breast carcinomas and in only 2 of 12 fibroadenomas. Levels of carcinoma CEA-like material correlated weakly with cytoplasmic estradiol receptor levels, total cytosol estrogens, and cytosol progesterone. Levels of CEA-like material showed no significant correlation with carcinoma stage, grade, cellularity, size or histologic type. Levels, however, correlated inversely with lymphocyte infiltration.

Adenofibroma↗

The role of methionine in the intracellular accumulation and function of folates.

It is suggested that mammalian cells have evolved to respond to methionine deficiency since in such circumstances vital methylation reactions are put at risk, due to decreased levels of S-adenosyl-methionine. Enzymatic changes occurring as a result of decreased methionine, S-adenosylmethionine and S-adenosylhomocysteine, optimize the remethylation of homocysteine to methionine by decreasing homocysteine catabolism and channelling cellular folates into 5-methyltetrahydropteroylglutamate (5-CH3-H4 PteGlu). The latter, in addition to optimising the remethylation cycle, directs the folate cofactors away from purine and pyrimidine biosynthesis and decreases the rate of proliferation of rapidly dividing cells thus reducing competition for methionine incorporation into proteins. Decreased cellular homocysteine, as a result of decreased methionine, would also restrict cell division by decreased conversion of plasma 5-CH3-H4PteGlu into intracellular polyglutamates. Cobalamin deficiency, either nutritional or due to exposure to the Co (I) cobalamin inactivating agent nitrous oxide, prevents the demethylation of 5-CH3-H4PteGlu, which even in the presence of adequate amounts of homocysteine and methionine prevents rapidly proliferating cells from converting enough of the plasma 5-CH3-H4 PteGlu into folylpolyglutamate forms to permit normal DNA biosynthesis and cell replication. This, together with the trapping of the cellular folate cofactors in the 5-CH3-H4PteGlu form, results in megaloblastic changes occurring in tissues such as the marrow. The vital role of the methylation reactions was demonstrated by exposing monkeys to nitrous oxide which inactivated their methionine synthetase. The resultant ataxia and severe demyelination was prevented and diminished by methionine supplementation. When methionine synthetase was similarly inactivated in mice it was shown that while 5-CH3-H4PteGlu enters mammalian cells, it is not converted into a polyglutamyl form and subsequently leaves the cell unmetabolised. In similar experiments in rats methionine was found to have only a small effect in restoring folylpolyglutamate biosynthesis, contrary to previous reports using nutritionally cobalamin deficient animals. It was found that a decrease in the deoxythymidine salvage pathway by methionine, under the experimental conditions used, has led others to the mistaken conclusion that methionine has an 'anti-folate' effect in bone marrow, i.e. that it decreases folate availability for thymidylate synthetase.

Animals↗

Emergent cervical cerclage: predictors of success or failure.

Emergent cervical cerclage is a procedure not commonly performed in general clinical practice. The outcome of pregnancies requiring emergent cerclage is based on limited information. The factors that predict success are not well known. Previous studies have suggested that advanced cervical dilation, significant cervical effacement, and the presence of prolapsed membranes are correlated with cerclage failure. We present a retrospective review of maternal characteristics predictive of perinatal survival. Analysis showed the presence of membrane prolapse to be the strongest predictor of poor outcome. Analysis also reveals a significant association between initial white blood cell count and perinatal outcome. This information may be helpful in decision making regarding adjunctive procedures such as amniocentesis and counseling patients regarding the likely outcome.

Adult↗