Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor

To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.     

Evaluation of Disposal Stability for Cement Solidification of Lime Waste

The Korea Atomic Energy Research Institute (KAERI) obtains UO₂ powder using the ammonium uranyl carbonate (AUC) wet process. Hydrated lime (Ca(OH)₂) is used to neutralize liquid wastes produced from the AUC process, and the resulting byproduct is known as lime waste. The purpose of this study is to determine optimum operating conditions for cementation of radioactive lime waste produced from the AUC process, and to evaluate the structural stability and leaching stability of cement waste form. The waste acceptance criteria (WAC) of a waste disposal facility in Korea were used to evaluate the cement waste form samples. The maximum lime waste content guaranteeing the shape stability of cement waste form was found to be 80 wt.% or less. Considering the economic feasibility and error of the cementation process, the optimum operating conditions were achieved at a lime waste content of 75 wt.% and a water-to-cement (w/c) ratio of 2.0. The compressive strength of cement waste form samples prepared under optimal operating conditions was 61.4, 76.3, and 61.0 kgf/cm² after the thermal cycling test, water immersion test, and irradiation, respectively, satisfying the compressive strength of 35.2 kgf/cm² specified in WAC. A leaching test was performed on the samples, and the leachability indexes (LX) of Cs, Sr, and Co nuclides were 7.63, 8.02, and 10.89, respectively, which are all higher than the acceptance criterion of 6. The results showed that the cement waste forms prepared under optimal operating conditions satisfied the WAC in terms of structural stability and leaching stability. As such, the proposed cement solidification method for lime waste disposal can be effective in solidifying lime waste powder produced during the neutralization of liquid wastes in the AUC process.     

Effects of Dietary Fat to Carbohydrate Ratio on Obesity Risk Depending on Genotypes of Circadian Genes

Although the impacts of macronutrients and the circadian clock on obesity have been reported, the interactions between macronutrient distribution and circadian genes are unclear. The aim of this study was to explore macronutrient intake patterns in the Korean population and associations between the patterns and circadian gene variants and obesity. After applying the criteria, 5343 subjects (51.6% male, mean age 49.4 ± 7.3 years) from the Korean Genome and Epidemiology Study data and nine variants in seven circadian genes were analyzed. We defined macronutrient intake patterns by tertiles of the fat to carbohydrate ratio (FC). The very low FC (VLFC) was associated with a higher risk of obesity than the optimal FC (OFC). After stratification by the genotypes of nine variants, the obesity risk according to the patterns differed by the variants. In the female VLFC, the major homozygous allele of CLOCK rs11932595 and CRY1 rs3741892 had a higher abdominal obesity risk than those in the OFC. The GG genotype of PER2 rs2304672 in the VLFC showed greater risks for obesity and abdominal obesity. In conclusion, these findings suggest that macronutrient intake patterns were associated with obesity susceptibility, and the associations were different depending on the circadian clock genotypes of the CLOCK, PER2, and CRY1 loci.     

Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects

OBJECTIVE: Our objective was to evaluate the effect of the CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers. METHODS: Nineteen healthy male volunteers were divided into 3 groups on the basis of the genetic polymorphism of CYP3A5. The groups comprised subjects with CYP3A5*1/*1 (n=5), CYP3A5*1/*3 (n=7), or CYP3A5*3/*3 (n=7). After a single oral 1-mg dose of alprazolam, plasma concentrations of alprazolam were measured up to 72 hours, together with assessment of psychomotor function by use of the Digit Symbol Substitution Test, according to CYP3A5 genotype. RESULTS: The area under the plasma concentration-time curve for alprazolam was significantly greater in subjects with CYP3A5*3/*3 (830.5+/-160.4 ng . h/mL [mean+/-SD]) than in those with CYP3A5*1/*1 (599.9+/-141.0 ng . h/mL) (P=.030). The oral clearance of alprazolam was also significantly different between the CYP3A5*1/*1 group (3.5+/-0.8 L/h) and CYP3A5*3/*3 group (2.5+/-0.5 L/h) (P=.036). Although a trend was noted for the area under the Digit Symbol Substitution Test score change-time curve (area under the effect curve) to be greater in subjects with CYP3A5*3/*3 (177.2+/-84.6) than in those with CYP3A5*1/*1 (107.5+/-44), the difference did not reach statistical significance (P=.148). CONCLUSIONS: The CYP3A5*3 genotype affects the disposition of alprazolam and thus influences the plasma levels of alprazolam.     

Induction of a TC1-mediated experimental autoimmune thyroiditis by deglycosylated porcine thyroglobulin

Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v. into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of the thyroid glands and levels of Tg-specific CTL were similar to those found in conventional EAT induced by Tg and adjuvants. In contrast, proliferative responses in native pTg and dgpTg-injected mice could not be detected, and titers of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset and exerted their thyroiditogenic potential through release of IFN-gamma. It was concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl). Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower than that of dgpTg, suggested that the abberant and incomplete glycosylation of the thyroglobulin is responsible for the induction of autoimmune thyroiditis.     

Racial variations in Department of Veterans Affairs ambulatory care use and unmet health care needs

Our objective was to describe racial/ethnic variations in Department of Veterans Affairs (VA) ambulatory care use and its association with the presence of unmet health care needs. Using the 1992 National Survey of Veterans, we examined race/ethnicity and unmet health care need for ambulatory care users of VA and non-VA facilities. Black and Hispanic veterans were more likely to report any VA use. In unadjusted analyses, American Indian/Eskimo, Hispanic, and black veterans were 4.4, 2.5, and 1.9 times more likely, respectively, than white veterans to report an inability to get needed care. Adjusting for VA ambulatory care use diminished the disparity in inability to get needed care between American Indian/Eskimo or Hispanic veterans and white veterans and eliminated the disparity between black and white veterans. Our findings support the VA's role as a medical safety net provider and suggest that VA ambulatory care use is effective in mitigating health-related racial disparities for some veterans. Additional facilitators for reducing unmet need should be explored.     

Effect of background motion on line bisection performance in normal subjects

Previous studies have demonstrated that optokinetic stimulation (OKS) influences line bisection (LB) performance in normal subjects and patients with hemispatial neglect. Since subjects were required to attend to stationary targets on a moving background, prior experimental designs might have induced an illusion of target motion or induced motion (IM) in a direction opposite the background. The current study tested whether the IM affects LB performance in normal subjects and how the speed of targets also influences LB. Thirty-two right-handed normal volunteers (aged 28.0±5.3 years) were asked to bisect stationary lines with a background of horizontal OKS. These stimuli were generated by computer and displayed on a large screen via a beam projector. The OKS was varied according to direction (leftward or rightward) and speed (9.4°/sec or 56.1°/sec), producing 4 different experimental conditions. Mean bisection errors in all conditions were compared with a control condition with no background OKS. For each condition, subjects rated the degree of IM on a 5 point scale. With fast rate OKS, subjects reported minimal IM and LB errors were in the same direction as background motion, a finding that replicates previous studies. Conversely, the slow OKS rate caused subjects to report IM and resulted in deviation of the bisection mark in a direction opposite the background OKS. While this discrepancy between the slow and fast OKS conditions might be related to motion illusion, we did not find a direct correlation between the degree of IM and bisection errors and thus reasons for these results remain unexplained.     

The Texas Medication Algorithm Project Patient and Family Education Program: a consumer-guided initiative

Educating patients with mental illness and their families about the illness and its treatment is essential to successful medication (disease) management. Specifically, education provides patients and families with the background they need to participate in treatment planning and implementation as full "partners" with clinicians. Thus, education increases the probability that appropriate and accurate treatment decisions will be made and that a treatment regimen will be followed. The Texas Medication Algorithm Project (TMAP) has incorporated these concepts into its philosophy of care and accordingly created a Patient and Family Education Program (PFEP) to complement the utilization of medication algorithms for the treatment of schizophrenic, bipolar, and major depressive disorders. This article describes how a team of mental health consumers, advocates, and professionals developed and implemented the PFEP. In keeping with the TMAP philosophy of care, consumers were true partners in the program's development and implementation. They not only created several components of the program and incorporated the consumer perspective, but they also served as program trainers and advocates. Initially, PFEP provides basic and subsequently more in-depth information about the illness and its treatment, including such topics as symptom monitoring and management and self-advocacy with one's treatment team. It includes written, pictorial, videotaped, and other media used in a phased manner by clinicians and consumer educators, in either individual or group formats.