Molecular genetic analysis of BAX and cyclin D1 genes in patients with malignant glioma

INTRODUCTION AND OBJECTIVES: Brain tumorigenesis is a complex process involving multiple genetic alterations. Cyclin D1 and BAX genes are two of the most important regulators in controlling the normal proliferation and apoptosis of cells, respectively. In this study, we analysed the possibilities of involvement of cyclin D1 and BAX genes in the gliomagenesis. METHODS AND RESULTS: In determining gene alterations of exon 4 of cyclin D1 gene and exon 6 of BAX gene, all samples were amplified by polymerase chain reaction (PCR) and subsequently by direct sequencing. Our results showed a frameshift mutation (G base deletion) at nucleotide 82 of codon 28 in exon 4 of the cyclin D1 gene and another frameshift mutation with a deletion of C base at nucleotide 153 of exon 6 of the BAX gene in two separate cases of a glioblastoma multiform (WHO Grade IV) sample. CONCLUSION: These findings suggest that both cyclin D1 and BAX genes alteration are rarely found in brain tumors. However, the alteration might cause a significant effect of the normal protein production and this might contribute to the development of brain tumorigenesis in Malaysian patients.     

Network perspectives on HDM2 inhibitor chemotherapy combinations

The discovery of small molecule inhibitors of HDM2-p53 interaction is considered one of the most significant therapeutic developments in the area p53 research. Intensive work on different classes of HDM2 inhibitors has proven their therapeutic utility as activators of p53 in multiple tumor models. Many laboratories have shown that HDM2 inhibitors can synergize with chemotherapeutic agents resulting in enhanced efficacy through both p53-dependent and independent mechanisms. In our hands HDM2 inhibitor and platinum drug combination showed remarkable antitumor activity that led tumor free survival in one of the most resistant and complex pancreatic xenograft models. Although antitumor efficacy of such combinations has been studied in detail, not much is known on the molecular mechanisms governing this synergy. This is partly due to complexity of multiple pathways modulated by p53 and HDM2. We are of the view that in order to decode this complexity, an integrated approach is needed that considers both HDM2 and p53 as components of a network and not in isolation. This review highlights recent advancements in our understanding of HDM2 inhibitor combination therapy based on network modeling and systems biology driven science. Our recent findings support such a network view as integrated gene expression profiling and pathway network modeling on MI-219-oxaliplatin treated cells revealed activation of multiple and closely knit biological networks. We anticipate that in the near future such network-centric approaches will benefit clinical development of HDM2 inhibitors for genetically predefined subsets of cancer patients and this will be a step towards personalized medicine.     

Bilateral temporal bone xanthoma. Case report

Xanthoma formation is frequently seen over the subcutaneous tissue of extensor surfaces and tendons that have received minor trauma or friction in patients with hypercholesterolemia. However, temporal bone xanthomas with intracranial extension are uncommon. To the best of the authors' knowledge, this is the second report in the literature in which bilateral extension of a xanthoma is described. Xanthomas of the temporal bone are benign lesions, and complete or even partial removal is effective. The predisposing cause of the lesion should also be treated.     

Combined coronary and lower extremity revascularization with thoracotomy: a case report

Patients with the combination of coronary artery disease and peripheral vascular disease have multiple risk factors and manifest widespread vascular disease. Although indications of combined coronary and femoral revascularization are rare, a combined procedure is useful in selected patients. We report a patient who underwent a successful combined coronary and lower extremity revascularization with anterolateral limited thoracotomy.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.     

Brucella glomerulonephritis resulting in end-stage renal disease: a case report and a brief review of the literature

Brucella glomerulonephritis is a rare condition with only a few reported cases. We review the literature, and describe a 24-year-old female who presented with edema and proteinuria. Blood grew Brucella melitensis. Renal biopsy showed diffuse proliferative glomerulonephritis. The patient progressed to end-stage renal disease despite antibiotic and steroid therapy.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Fitness level and body composition indices: cross-sectional study among Malaysian adolescent

Background

The importance of fitness level on the well-being of children and adolescent has long been recognised. The aim of this study was to investigate the fitness level of school-going Malaysian adolescent, and its association with body composition indices.

Methods

1071 healthy secondary school students participated in the fitness assessment for the Malaysian Health and Adolescents Longitudinal Research Team (MyHEART) study. Body composition indices such as body mass index for age, waist circumference and waist height ratio were measured. Fitness level was assessed with Modified Harvard Step Test. Physical Fitness Score was calculated using total time of step test exercise and resting heart rates. Fitness levels were divided into 3 categories - unacceptable, marginally acceptable, and acceptable. Partial correlation analysis was used to determine the association between fitness score and body composition, by controlling age, gender, locality, ethnicity, smoking status and sexual maturation. Multiple regression analysis was conducted to determine which body composition was the strongest predictor for fitness.

Results

43.3% of the participants were categorised into the unacceptable fitness group, 47.1% were considered marginally acceptable, and 9.6% were acceptable. There was a significant moderate inverse association (p < 0.001) between body composition with fitness score (r = -0.360, -0.413 and -0.403 for body mass index for age, waist circumference and waist height ratio, respectively). Waist circumference was the strongest and significant predictor for fitness (ß = -0.318, p = 0.002).

Conclusion

Only 9.6% of the students were fit. There was also an inverse association between body composition and fitness score among apparently healthy adolescents, with waist circumference indicated as the strongest predictor. The low fitness level among the Malaysian adolescent should necessitate the value of healthy lifestyle starting at a young age.