Decompensation of pressure-overload hypertrophy in G alpha q-overexpressing mice

BACKGROUND: Receptor-mediated activation of myocardial Gq signaling is postulated as a biochemical mechanism transducing pressure-overload hypertrophy. The specific effects of Gq activation on the functional and morphological adaptations to pressure overload are not known. METHODS AND RESULTS: To determine the effects of intrinsic myocyte G alpha q signaling on the left ventricular hypertrophic response to experimental pressure overload, transgenic mice overexpressing G alpha q specifically in the heart (G alpha q-25) and nontransgenic siblings underwent microsurgical creation of transverse aortic coarctation and the morphometric, functional, and molecular characteristics of these pressure-overloaded hearts were compared at increasing times after surgery. Before aortic banding, isolated G alpha q-25 ventricular myocytes exhibited contractile depression (depressed +dl/dt and -dl/dt) and G alpha q-25 hearts showed a pattern of fetal gene expression similar to the known characteristics of nontransgenic pressure-overloaded mice. Three weeks after transverse aortic banding, G alpha q-25 left ventricles hypertrophied to a similar extent (approximately 30% increase) as nontransgenic mice. However, whereas nontransgenic mice exhibited concentric left ventricular remodeling with maintained ejection performance (compensated hypertrophy), G alpha q-25 left ventricles developed eccentric hypertrophy and ejection performance deteriorated, ultimately resulting in left heart failure (decompensated hypertrophy). The signature hypertrophy-associated progress of fetal cardiac gene expression observed at baseline in G alpha q-25 developed after aortic banding of nontransgenic mice but did not significantly change in aortic-banded G alpha q-25 mice. CONCLUSIONS: Intrinsic cardiac myocyte G alpha q activation stimulates fetal gene expression and depresses cardiac myocyte contractility. Superimposition of the hemodynamic stress of pressure overload on G alpha q overexpression stimulates a maladaptive form of eccentric hypertrophy that leads to rapid functional decompensation. Therefore G alpha q-stimulated cardiac hypertrophy is functionally deleterious and compromises the ability of the heart to adapt to increased mechanical load. This finding supports a reevaluation of accepted concepts regarding the mechanisms for compensation and decompensation in pressure-overload hypertrophy.     

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.     

Production of fibroblast proliferative cytokines from T lymphocytes stimulated by a B cell lymphoma line and their functional heterogeneity

Human mononuclear leukocytes (MNL) produced several factors with fibroblast proliferation activity (FPA) for HFL-1, a human lung fibroblast cell line, when MNL were cocultured with irradiated BALL-1, a B cell lymphoma line (BCLL), but not with other BCLL. The cellular source of BALL-1-induced FPA seemed to be CD4-positive T lymphocytes. On isoelectric electrophoresis, major activity of BALL-1-induced FPA was detected in the fractions around pH 4-5, and minor activity was present in the fractions around pH 6-7. Major BALL-1-induced FPA consisted of at least 4 different fibroblast proliferation factors (FPFs) according to their molecular weight; 320-600 kDa (P-I), 50-110 kDa (P-II), 22-38 kDa (P-III) and 4.6-11 kDa (P-IV). P-I had affinity to heparin though the rest had little or no affinity. FPA of P-I was suppressed by an antibody against acidic FGF, and FPA of P-III was suppressed by an antibody against IL-6. On the other hand, FPA of P-II and P-IV was suppressed by none of the antibodies against cytokines with FPA, such as FGF, IL-4, IL-6, IFN-gamma, TGF-beta and TNF-alpha. It was thus suggested that P-I was acidic FGF, that P-III was IL-6, and that P-II and P-IV were different cytokines from those described above. Furthermore, it was found that P-II and P-IV failed to exhibit proliferation activity for human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy

Injury of the normal central nervous system is a major concern in the radiotherapy of brain tumors, but the pathogenesis of injury remains poorly understood. Modulation of the production of growth factors is associated with ischemia and traumatic injury in the central nervous system. Ionizing radiation has been shown to induce basic fibroblast growth factor in endothelial cells and in cells of a human breast carcinoma cell line. The inducibility of basic fibroblast growth factor after irradiation and its potential role in the recovery response of the central nervous system led us to investigate the effects of radiation on the expression of this growth factor in primary cultures of normal rat type 1 astrocytes. Astrocyte monolayers were exposed to ionizing radiation (1 to 10 Gy). Northern blot analysis revealed that doses of 2 to 10 Gy markedly reduced the expression of basic fibroblast growth factor as early as 1 h after irradiation, and that it remained below levels in unirradiated cells for at least 24 h. The effect was not associated with astrocyte cytotoxicity, and it appears to have some specificity for basic fibroblast growth factor since the levels of mRNA coding for ciliary neurotrophic factor and glial fibrillary acidic protein were not affected.     

A 150 ns 16-Mb CMOS SRAM with interdigitated bit-line architecture

Circuit techniques for a reduced-voltage-amplitude data bus, fast access 16-Mb CMOS SRAM are described. An interdigitated bit-line architecture reduces data bus line length, thus minimizing bus capacitance. A hierarchical sense amplifier consists of 32 local sense amplifiers and a current sense amplifier. The current sense amplifier is used to reduce the data bus voltage amplitude and the sensing of the 16-b data bus signals in parallel. Access time of 15 ns and an active power of 165 mW were achieved in a 16-Mb CMOS SRAM. A split-word-line layout memory cell with double-gate pMOS thin-film transistors (TFTs) keeps the transistor width stable while providing high-stability memory cell characteristics. The double-gate pMOS TFT also increases cell-storage node capacitance and soft-error immunity     

Estimation of the future numbers of patients with circulatory diseases in Japan based on the results of national patient surveys]

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.     

Modulator integrated DFB lasers with more than 600-km transmission capability at 2.5 Gb/s

The modulator integrated DFB laser diodes with more than 600-km transmission capability over normal fiber at 2.5 Gb/s, have been reproducibly achieved. The longest transmission length obtained in the experiment is as long as 800 km.     

Placement of the Dumon stent using a flexible bronchofiberscope via tracheostomy

In this paper, we report on a new technique of Dumon stent placement using a flexible bronchofiberscope. This procedure was used to insert Dumon stents in two bronchial obstruction and two bronchofistula cases. The stenting technique described here can be used through either a tracheostoma or the oral cavity; it presents a very straightforward and safe procedure that does not require the use of a rigid bronchoscope.     

On the minimal partial realization of 2D discrete linearshift-invariant systems

The partial realization problem for 2D discrete linear shift-invariant systems is discussed. The authors attempt to establish a reasonable definition of minimality and propose a method for finding the degree and the system function of a minimal realization of a 2D linear system characterized by a given 2D impulse response array. The method used is based on the 2D Berlekamp-Massey algorithm which has a close connection with the 2D Hankel matrix derived from the 2D array. While it compares in efficiency with other methods for identification and approximation of 2D linear systems, it gives a novel approach to the problem in the sense that one does not need any knowledge or assumptions concerning the system degree     

Pb-based ferroelectric thin film actuator for optical applications

Novel PZT thin film actuators for optical applications were proposed. Key issues for realizing the actuators such as PZT thin film processes, mechanical properties evaluation of thin films, and design for laminated structure were described. [1 1 1]-oriented PZT films were obtained by anneal/non-anneal sputtering process. Also for PZT dry etching, it was made clear low pressure and low temperature conditions were advantageous for high selectivity and etch rate. ECR etcher was used and etch rate of 1000 A/min and selectivity of 0.56 to photoresist mask were obtained. Young’s modulus and built-in stress of PZT film, measured by load-deflection method, were 72 GPa, −335 MPa respectively. Using these results, calculated deflection of each actuator was on the order of a few microns to 20 microns. It was confirmed that deflection of actuators would be enough for the application.