Tissue-specific extinguisher loci in the murine genome: A screening study based on a rat/mouse microcell hybrid panel

Extinction of tissue-specific traits in intertypic somatic cell hybrids is a well-known phenomenon. In the past few years, microcell hybrids have been used in attempts to dissect this phenotype genetically, and tissue-specific extinguisher loci have been mapped to two different mouse chromosomes. When transferred from fibroblasts into hepatoma cells by microcell fusion, these loci down-regulate expression of specific liver genes intrans. However, other liver genes that are extinguished in genotypically complete hybrids seem not to be extinguished in monochromosomal hybrids. To assess the generality of monochromosomal extinction phenotypes, we assembled a collection of rat hepatoma/mouse fibroblast microcell hybrids that represent most of the mouse chromosome complement, and we screened them for expression of a large number of liver-specific genes. Phosphoenolpyruvate carboxykinase gene expression was down-regulated in hybrids containing mouse chromosome 7 or mouse chromosome 11, but other extinction phenotypes were not readily apparent. These results indicate that extinction of many liver genes may be a polygenic trait.     

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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official nor as reflecting the views of the United States Air Force     

The future of cardiovascular imaging and non-invasive diagnosis

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.This paper is published simultaneously in the European Heart Journal (2006;27:1750–1753) and in the European Journal of Echocardiography (2006;7:268–273).     

Experimental models of reflex contractile activity in the rabbit bladder

We were able to produce two highly reproducible experimental models (in the rabbit) that demonstrated a high degree of reflex bladder contractile activity. In one model, a somatovesical reflex was induced by touching or pinching the perineal area. This reflex may be organized through a neurogenic reflex at the spinal level. In another model, rhythmic bladder contractions were produced by distal urethral constriction in the absence of bladder distension. These rhythmic contractions were thought to be due to a supraspinal reflex. In both types of contractile reflexes, intravenous administration of hexamethonium inhibited the reflex contractile activity virtually completely, intravenous atropine inhibited over 90% of the induced contractile activity, thus suggesting that these contractions were mediated reflexly through cholinergic stimulation. These two models of reflex bladder contractions should be useful for the study of hyperreflexic bladders.     

Arthroscopy and microfracture technique in the treatment of osteochondritis dissecans of the humeral capitellum: report of three adolescent gymnasts

The aim of this paper is to report on three cases of symptomatic osteochondritis dissecans of the humeral capitellum in adolescent gymnasts, two females and one male. In all the cases arthroscopic surgery was performed. During arthroscopy, loose osteochondral fragments were removed, the defect was debrided and microfractures were performed. All the three patients regained the full range of motion of the affected elbow, and returned to the high-level gymnastics within a period of 5 months. At 12 months follow-up, all the three patients remained symptomless and were participating in high-level gymnastics. A combination of arthroscopy and the microfracture technique is a reliable method with excellent short-term results in the treatment of the osteochondritis dissecans of the elbow.     

Outcomes following liver transplantation for seronegative acute liver failure: experience during a 12-year period with more than 100 patients.

Seronegative hepatitis is a common cause of acute liver failure (ALF) requiring liver transplantation. The primary aim of this study was to examine outcomes following transplantation in this group and to identify factors associated with early (<2 months) mortality. Patients studied were 110 consecutive cases of seronegative ALF transplanted at the Queen Elizabeth Hospital, Birmingham, between January 1992 and January 2004. Univariate analysis of 44 pretransplantation recipient, donor, and operative variables was performed initially to identify factors associated with early posttransplantation mortality. Variables identified as significant or approaching significance were analyzed using stepwise multiple logistic regression analysis. Survival following transplantation for seronegative hepatitis was 83%, 81%, and 73% at 2, 12, and 60 months, respectively. The majority (71%) of deaths occurred within the 1st 2 months and sepsis / multiorgan dysfunction was the most common cause of early death. Univariate analysis revealed 9 variables predicting early death. Subsequent multivariate analysis identified high donor body mass index (BMI; a possible surrogate marker for hepatic steatosis) as the most important predictor of early death (P = .009; odds ratio, 1.2; 95% confidence interval, 1.0-1.3). Recipient age >50 (P = .015; odds ratio, 4.2; 95% confidence interval, 1.3-14.1) and non-Caucasian recipient ethnicity (P = .015; odds ratio, 4.9; 95% confidence interval, 1.2-19.2) were other variables associated with early death on multivariate analysis. This study specifically examined factors that determine the early outcome of transplanted seronegative ALF patients. In conclusion, we found that donor and recipient factors identify patients who have a high chance of early death after transplantation.     

Orthodontic undergraduate education: developments in a modern curriculum.

This paper explores some modern concepts of teaching and learning, including cognitive theory, the zone of proximal development, constructivism, andragogy and learning styles and describes how they have informed the development of an undergraduate orthodontic curriculum. The changes described include student-centred learning, guided self-learning, and the incorporation of problem-based learning concepts. The details of the problem-based learning programme are described together with results of student feedback on the change in teaching and learning style.     

Efficacy of lumiracoxib in relieving pain associated with knee osteoarthritis: a 6‐week,randomized, double‐blind,parallel‐group study

Aim: The aim of the current study was to assess the efficacy, safety, and tolerability of lumiracoxib 200 mg once daily (o.d.) in relieving osteoarthritis (OA) knee pain in patients in China, Taiwan, and South Korea. Methods: Patients of either sex (aged ≥ 18 years) with symptomatic, primary OA of the knee for ≥ 3 months were eligible for inclusion if they had OA pain intensity of ≥ 40 mm (100 mm visual analogue scale [VAS]) in the target knee joint during the previous 24 h. Patients were required to undergo regular non‐steroidal anti‐inflammatory drug therapy for ≥ 6 weeks. After 3–7 days of screening, patients were randomized (1 : 1) to receive either lumiracoxib 200 mg o.d. or celecoxib 200 mg o.d. The primary efficacy comparison between the study groups was overall OA pain intensity (VAS) in the target knee after 6 weeks of treatment. Results: The mean overall OA pain intensity (VAS) in the target knee after 6 weeks decreased from 60.6 mm to 35.7 mm and 60.5 mm to 36.1 mm in the lumiracoxib and celecoxib groups, respectively. Both study groups showed similar results in terms of improvement in both patient's and physician's global assessment of disease activity and functional health status. The percentage of adverse events (AEs) in the lumiracoxib and celecoxib groups (40.3% and 37.9%, respectively) was similar, as was the proportion of treatment‐related AEs (21.0% and 18.2%, respectively). Conclusions: Lumiracoxib 200 mg o.d. provided effective and well‐tolerated pain relief similar to that achieved with celecoxib 200 mg o.d. in knee OA patients.