Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.

Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that copes with oxidative stress. However, changes in HO-1 expression and their association with human diseases have not been studied. To test the hypothesis that the capacity to upregulate HO-1 in response to oxidative stress is an intrinsic marker for susceptibility to coronary atherosclerosis, we assessed stimulation-induced change in HO-1 expression in blood cells in 110 patients who underwent coronary angiography, comparing the results with the extent of coronary atherosclerosis and (GT)(n) repeat polymorphism in the HO-1 gene promoter region, which is believed to affect the gene expression level. The extent of coronary atherosclerosis was assessed by coronary score. Mononuclear cells were incubated with 10 micromol/l hemin or vehicle for 4 h to maximally stimulate HO-1 expression, then the HO-1 expression level was determined by real-time polymerase chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and vehicle-treated cells (DeltaHO-1 mRNA) was taken as an index of the capacity to upregulate HO-1 mRNA. The coefficient of variance of DeltaHO-1 mRNA was 7.2%. Consistent with previous studies, DeltaHO-1 mRNA was significantly lower in patients carrying a long (GT)(n) repeat. DeltaHO-1 mRNA negatively and significantly correlated with the coronary score (r(2)=0.50, p<0.01). In conclusion, the capacity to upregulate HO-1 expression may be determined, at least in part, by genetics, and reduced ability to induce HO-1 may be involved in the mechanism of coronary atherosclerosis.     

Application of the Human Hepatitis B Virus Core Antigen from Transgenic Tobacco Plants for Serological Diagnosis

Background and objectives: The aim was to produce HBcAg from plants more cheaply than can be done by other currently available means, and to apply such antigen to immunoassay procedures for pretransfusion testing of donor blood. Materials and methods: Transgenic Nicotiana tabacum cv. SR-1 plants expressing the human hepatitis B virus (HBV) core antigen (HBcAg) gene were generated by Agrobacterium-mediated transformation. The recombinant product, called tHBcAg, can assemble itself into a spherical particle with a diameter of 25 to 30 nm, and can maintain two antigenic determinants of HBcAg, namely HBc/α and HBc/β. Partly purified tHBcAg was used in the hemagglutinationinhibition (HI) test, as routinely used by the Japanese Blood Center, to test a panel of 524 blood units taken from HBV-positive donors. Results: In the HI test, tHBcAg showed serologic properties comparable to that from Escherichia coli, the standard antigen used in the Japanese Blood Center. Conclusions: Transgenic plants can produce reagents for serologic testing and perhaps even such medical materials as oral vaccines.     

Association of interleukin-10 promoter single nucleotide polymorphisms -819 T/C and -592 A/C with aging

Increased inflammatory activity is known to accompany aging. Single nucleotide polymorphisms of inflammatory mediator genes might therefore affect the aging process. Relation of eight SNPs (tumor necrosis factor-alpha [TNF-alpha] -1031 T/C, interleukin-10 [IL-10] -819 T/C, IL-1beta -511 C/T, IL-6 -634 C/G, IL-18 -607 A/C, transforming growth factor-beta [TGF-beta] +869 C/T, matrix metalloproteinase-1 [MMP-1] -1607 1G/2G, and MMP-3 -1171 5A/6A) with age or gender was evaluated in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) by the chi-square test. There was a significant association of IL-10 -819 T/C with age (p =.0026). The association remained significant after multivariate logistic regression analysis (odds ratio for an age interval for 1 year, 1.009; 95% CI, 1.002-1.016). Furthermore, the genotype distribution of IL-10 -819 T/C was completely consistent with that of -592 A/C. These data suggest that IL-10 -819 T/C and -592 A/C may be a promising candidate for an aging-related gene in a Japanese population.     

Clinical usage of serum ferritin to assess liver fibrosis in patients with non‐alcoholic fatty liver disease: Proceed with caution

Serum ferritin was recently reported to have low diagnostic accuracy for the detection of advanced fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). To corroborate these findings, we investigated the diagnostic accuracy of serum ferritin levels for detecting liver fibrosis in NAFLD patients utilizing a large Japanese cohort database. A total 1201 biopsy‐proven NAFLD patients, seen between 2001 and 2013, were enrolled into the Japan Study Group of NAFLD. Analysis was performed on data from this cohort comparing between serum ferritin levels and hepatic histology. Serum ferritin increased with increasing histological grade of steatosis, lobular inflammation and ballooning. Multivariate analyses revealed that sex differences, steatotic grade and fibrotic stage were independently associated with serum ferritin levels (P < 0.0001, <0.0001, 0.0248, respectively). However, statistical analyses performed using serum ferritin levels demonstrated that the area under the receiver–operator curve for detecting fibrosis was not adequate for rigorous prediction. Several factors including sex differences, steatosis and fibrosis were found to correlate with serum ferritin levels. Therefore, serum ferritin may have low diagnostic accuracy for specifically detecting liver fibrosis in NAFLD patients due to the involvement of multiple hepatocellular processes.     

Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study

Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH.