MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes

Herein we describe a new test system to produce a standardized partial muscle-tendon junction (MTJ) stretch injury. In anesthetized rabbits the tibialis anterior (TA) muscle-tendon unit is unilaterally shortened using a custom designed clamp roller system. An angular displacement (average velocity of 450 degrees x s[-1]) is applied about the foot to plantarflex the ankle 90 degrees while the lower extremity is fixed. During ankle rotation the TA muscle is tetanically stimulated to generate an eccentric stretch injury at the MTJ. Forty-eight hours after injury, isometric torque deficit (injured/sham) was measured. Two groups of animals (N = 6 in each group) were tested with the only difference between the two groups being the initial tendon shortening. In Group 1 (tendon shortening = 1.2 cm. N = 6) the torque deficit was 36.7+/-5.9% (mean+/-SD). In Group 2 (tendon shortening = 1.5 cm. N = 6) the torque deficit was 58.7+/-7.4% (mean+/-SD). No order effect was suggested by the data (P = 0.6062), but the difference in torque deficit between the two groups was highly significant (P = 0.0001). For all tests in which the tendon was temporarily shortened before muscle stimulation and stretch (N = 12) there was a visible hematoma at the MTJ similar to the injury that is common in athletic injuries. Histological evaluation 48 h after injury revealed both fiber tearing and inflammation at the MTJ. In addition, there was focal fiber damage in the muscle belly for both groups. The damage and inflammatory process, however, were more severe in the group with greater initial tendon shortening.     

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.     

A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex

Amrubicin is a novel, completely synthetic 9-aminoanthracycline derivative. Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA-protein complex formation and double-strand DNA breaks in CCRF-CEM cells and KU-2 cells. In this study, we found that ICRF-193, a topo II catalytic inhibitor, antagonized both DNA-protein complex formation and double-strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF-193. Taken together, these findings indicate that the cell growth-inhibitory effects of amrubicin and amrubicinol are due to DNA-protein complex formation followed by double-strand DNA breaks, which are mediated by topo II.     

IL-12 promotes the adhesion of NK cells to endothelial selectins under flow conditions

This study examined the adhesive interactions of peripheral blood NK cells with P- and E-selectin and analyzed the effect of IL-12 on the binding of NK cells to these selectins. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on most resting and IL-12-activated NK cells. However, the percentage of resting NK cells bound to P-selectin-IgG was 15%, and that of activated NK cells bound to P-selectin-IgG was 65%. Furthermore, the number of IL-12-activated NK cells bound to P-selectin-transfected Chinese hamster ovary cells was significantly higher than that of resting NK cells under flow conditions. These interactions were abolished by the incubation of these NK cells with anti-PSGL-1 (PL-1) mAb. Thus, PSGL-1/P-selectin interaction is important in the binding of resting and activated NK cells to P-selectin. NK cells express sialyl-Lewis(x) (sLe(x)) structure recognized by anti-sLe(x) mAb (KM-93), and IL-12 activation of NK cells increased the mean fluorescence intensity of KM-93-reactive NK cells. Adhesion of IL-12-activated NK cells to E-selectin-transfected Chinese hamster ovary cells was stronger than that of resting NK cells under flow conditions. These interactions were reduced markedly by incubation with anti-sLe(x) mAb. Thus, sLe(x) is the major ligand of resting and activated NK cells for E-selectin. These findings indicate that IL-12 stimulation of NK cells promotes their adhesion activity to endothelial selectins.     

Health-related quality of life varies with personality types: a comparison among cancer patients, non-cancer patients and healthy individuals in a Japanese population

In an attempt to examine differential effects of personality on health-related quality of life (HRQoL) without regard to disease type, we used the HRQoL-20, a general questionnaire (Japanese original scale) we developed (comprising 20 questions related to physiological, psychological or social HRQoL) and the Eysenck Personality Questionnaire (EPQ), which measures personality traits of extraversion (E), neuroticism (N) and psychoticism (P). The subjects (399 males and 429 females), stomach cancer patients, non-cancer patients (who had received acupuncture or moxibustion treatment) and healthy controls, were classified into three personality types. The results indicated that the HRQoL score of the tolerable/tolerant type (high E, low N and high P scorers) was greater than the intolerable/intolerant type (low E, high N and low P scorers) and also the unclassified type (neither of above scorers). The HRQoL correlated positively with the E and P scales and negatively with the N scale, in the case of all subjects, with the exception of N in male cancer patients and E in male non-cancer patients. The results supported the hypothesis that the HRQoL varies with personality variables, in that each patient, in different treatment settings, strives for the situation that is congruent with his/her personality to attain a better HRQoL.     

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.     

Divergent consequences of success and failure in Japan and North America: An investigation of self-improving motivations and malleable selves.

Self-enhancing and self-improving motivations were investigated across cultures. Replicating past research, North Americans who failed on a task persisted less on a follow-up task than those who succeeded. In contrast, Japanese who failed persisted more than those who succeeded. The Japanese pattern is evidence for a self-improving orientation: Failures highlight where corrective efforts are needed. Japanese who failed also enhanced the importance and the diagnosticity of the task compared with those who succeeded, whereas North Americans did the opposite. Study 2 revealed that self-improving motivations are specific to the tasks on which one receives feedback. Study 3 unpackaged the cultural differences by demonstrating that they are due, at least in part, to divergent lay theories regarding the utility of effort. Study 4 addressed the problem of comparing cultures on subjective Likert scales and replicated the findings with a different measure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of 2,4,6,8-tetramethyldecanoic acid on the hydrolysis and acylation of phospholipid by lipase in isooctane

The effect of an unusual natural fatty acid, 2,4,6,8-tetramethyldecanoic acid (TMDA), on the hydrolysis and acylation of phospholipid by lipase in isooctane was studied. Lipases examined were fromRhizopus delemar, Candida cylindracea andPseudomonas sp. The lipase was dispersed in isooctane by dioleoylphosphatidylethanolamine (DOPE) with or without the fatty acid and decanoyl-lysophosphatidylcholine (LPC). The effect of TMDA on both the hydrolysis of DOPE and the acylation of LPC was compared with that of decanoic acid (DA) by varying the water content. At the higher water content, the hydrolysis of DOPE was enhanced or trace amount of phosphatidylcholine was produced. Hydrolysis was enhanced more by the addition of TMDA than by DA. The effect of TMDA on the acylation of LPC was similar to that of DA.     

New type drill with three major cutting edges

Drilling performance of a new type twist is described. The new type drill has three major cutting edges, three chisel edges and three flutes. This drill is an efficient means of making a hole with high accuracy and no reaming. Recently, some research on drill materials including surface coating, drill point geometry, cutting forces and tool life have been carried out in order to increase the cutting performance of drills. All the drills used in these experiments were ordinary drills with two major cutting edges. The authors calculated the point geometry of the new type drill, and also examined the cutting characteristics of the drill with respect to cutting forces, hole accuracy and tool vibration. The experimental results showed that the whirling vibration which frequently occurs in an ordinary drill with two major cutting edges disappears when the new type drill is used, and thereby rifling marks do not results on the hole surface. Consequently, a hole with high roundness and straightness is obtained.