Is a Type A behavior pattern associated with falling among the community-dwelling elderly?

The aim of this report is to investigate the relationship between Type A behavior patterns and the likelihood of falling among community-dwelling elderly, and to compare differences in the prevalence, reasons, locations, injuries and frequency of falls between Type A and non-Type A personalities. Persons aged 60 or older living in 3 communities of Nanjing, China participated in a baseline survey conducted in 2000 (n=879), and falling incidents were followed for 1 year. The survey employed a self-administered questionnaire designed to elicit demographic data, current health problems and medications taken, intake of alcohol, exercise habits, physical function, environmental hazards and Type A behavior patterns. Several factors associated with falling such as health condition, physical function and environmental factors did not differ between the Type A and non-Type A groups except in the male tendency toward heart disease and their inability to walk fast. The results of logistic regression analyses showed that a Type A behavior pattern was independently associated with falling in males but not in females. Findings in the present study suggest that a Type A behavior pattern might play an important role in the rate of falling incidents in elderly males, since some characteristics of this personality pattern might lead to risk-taking behavior. More studies are needed to evaluate the association of certain behavior patterns with falling incidents.     

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6 mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4–12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h. The mean maximal serum drug concentration (mean C_max) of MTX attained at 1–2 h after ingestion of the first capsule was 0.215 and 0.252 μM, respectively, in the first and the follow-up week. The mean C_max after ingestion of the third capsule was 0.223 μM and 0.357 μM. The mean C_max of 7-OH MTX was 0.0334 and 0.0289 μM for the first capsule, and 0.0495 and 0.0672 μM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6 mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5 mg per week.     

Noninvasive positive pressure ventilation in patients with acute exacerbations of pulmonary tuberculosis sequelae]

To clarify whether noninvasive positive pressure ventilation (NPPV) is effective in patients with acute exacerbations of pulmonary tuberculosis sequelae (PTS), 50 PTS patients (66 episodes) without long-term domiciliary noninvasive ventilation were studied, retrospectively. The average values (SD) of their pulmonary function tests and arterial blood gases were as follows; %predicted VC = 31.4 (8.4)%, pH = 7.29 (0.06), PaCO2 = 91.8 (19.7) mmHg, and PaO2 = 64.2 (20.3) mmHg. The probability of avoiding endotracheal intubation and recovering from an acute exacerbation with NPPV (NPPV success rate) was 92% as a whole. NPPV success rates according to the causes of deterioration were as follows; 96% in 26 episodes with only a simple right heart failure, 93% in 29 episodes with airway infectious diseases, 75% in eight episodes with pneumonia and/or acute respiratory distress syndrome. Moreover, the NPPV success rate of eight episodes in coma or semicoma was 88%. Most patients were treated in respiratory wards rather than intensive care units. Out of 46 patients who recovered from an acute exacerbation, 41 finally received domiciliary NPPV. In facilities where staff are well-trained for an acute NPPV, patients with exacerbations of PTS can be treated as successfully with NPPV as patients with COPD.     

A murine model of acute liver injury induced by human monoclonal autoantibody

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.     

Age-related expression analysis of mouse liver nuclear protein binding to 3′-untranslated region of <Emphasis Type="Italic">Period2</Emphasis> gene

In mammals, both circadian rhythm and aging play important roles in regulating time-dependent homeostasis. We previously discovered an age-related increase element binding protein, hnRNP A3, which binds to the 3′-untranslated region (UTR) of blood coagulation factor IX (FIX). Here, we describe other members of this protein family, hnRNP C and hnRNP H, which bind to the 3′-UTR of the mouse circadian clock gene Period 2 (mPer2). RNA electrophoretic mobility shift assays using a ³²P-labeled Per2 RNA probe coupled with two-dimensional gel electrophoresis followed by MALDI-TOF/MS peptide mass fingerprint analysis was used to analyze these proteins. Western blotting suggested that the total expression of these proteins in mouse liver cell nuclei does not increase with age. Two-dimensional gel electrophoresis analysis of age-related protein expression showed that many isoforms of these proteins exist in the liver and that each protein exhibits a complex age-related expression pattern. These results suggest that many isoforms of proteins are regulated by different aging systems and that many age regulation systems function in the liver.     

Impact of CYP2C19 polymorphism on clinical outcome following coronary stenting is more important in non-diabetic than diabetic patients

Objective

The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM).

Methods

CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n = 249), and non-DM (n = 270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele.

Results

The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501 +/− 1668 versus 3691 +/− 1714AUmin, P < 0.01; events, 32/178 versus 2/92, P < 0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P = 0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P = 0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P = 0.618).

Conclusion

The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents.     

Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation

Introduction

There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.

Material and Methods

We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n = 154) and non-CKD (n = 177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status.

Results

The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P = 0.016) and non-CKD groups (34.3% versus 3.7%; P < 0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P = 0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P = 0.013) and there was no significant difference in the CKD group (log-rank test: P = 0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P = 0.043).

Conclusions

CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.     

Serum levels of soluble adhesion molecules as prognostic factors for acute liver failure

Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF.     

Natural variation in a polyamine transporter determines paraquat tolerance in Arabidopsis

Polyamines (PAs) are ubiquitous, polycationic compounds that are essential for the growth and survival of all organisms. Although the PA-uptake system plays a key role in mammalian cancer and in plant survival, the underlying molecular mechanisms are not well understood. Here, we identified an Arabidopsis L-type amino acid transporter (LAT) family transporter, named RMV1 (resistant to methyl viologen 1), responsible for uptake of PA and its analog paraquat (PQ). The natural variation in PQ tolerance was determined in 22 Arabidopsis thaliana accessions based on the polymorphic variation of RMV1. An RMV1-GFP fusion protein localized to the plasma membrane in transformed cells. The Arabidopsis rmv1 mutant was highly resistant to PQ because of the reduction of PQ uptake activity. Uptake studies indicated that RMV1 mediates proton gradient-driven PQ transport. RMV1 overexpressing plants were hypersensitive to PA and PQ and showed elevated PA/PQ uptake activity, supporting the notion that PQ enters plant cells via a carrier system that inherently functions in PA transport. Furthermore, we demonstrated that polymorphic variation in RMV1 controls PA/PQ uptake activity. Our identification of a molecular entity for PA/PQ uptake and sensitivity provides an important clue for our understanding of the mechanism and biological significance of PA uptake.