Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia–Reperfusion Injury in Diet-Induced Obesity

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia–reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia–reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.     

A case of large neonatal arteriovenous malformation with heart failure. Color Doppler sonography, MRI and MR angiography as early non-invasive diagnostic procedures

We report a case of a large arteriovenous malformation (AVM) of neonatal onset with heart failure. Transfontanel color Doppler sonography revealed abnormal vessels in the early stage of the investigation. Magnetic resonance imaging (MRI) revealed numerous flow voids suggesting abnormal vessels, and magnetic resonance angiography (MRA) disclosed numerous bizarre abnormal vessels. Color Doppler sonography is a convenient and appropriate procedure for the early bedside diagnosis of neonatal AVMs. MRI and MRA can replace cerebral angiography for the diagnosis of neonatal AVMs.     

Prevalence of hepatitis C virus antibody in patients on chronic hemodialysis

Hepatitis C virus antibody (anti-HCV) was studied in 267 patients undergoing maintenance hemodialysis using an anti-HCV enzyme-linked immunosorbent assay. Furthermore, both hepatitis B virus core antibody (anti-HBc) and human T cell leukemia virus type 1 antibody (anti-HTLV-1) were determined in these patients to compare their prevalence rates. Seventy one patients (27%) had positive anti-HCV, 134 patients (50%) positive anti-HBc and 40 patients (15%) positive anti-HTVL-1. Among the 183 patients who had received blood transfusion, the prevalence of these antibodies was 34% for anti-HCV, 56% for anti-HBc and 17% for anti-HTLV-1, respectively. A significance between those with and without blood transfusion was recognized for anti-HCV (p < 0.001) and anti-HBc (p < 0.01). Of 56 patients who had received hemodialysis for over 15 years, the positive antibody was found in 63% for anti-HCV (p < 0.001), 73% for anti-HBc (p < 0.001) and 25% for anti-HTLV-1 (p < 0.05), which was significantly higher than that of patients receiving a less than 15 years hemodialysis. The prevalence rates of anti-HCV and anti-HTLV-1 did not increase with age, while that of anti-HBc increased. These findings suggest that blood transfusions during hemodialysis play a very important role in the infection of hepatitis C virus.     

Expression and activity of cyclin-dependent kinase 5/p35 in adult rat peripheral nervous system

In spite of the clarification in the temporal and spatial expression pattern of a cyclin-dependent kinase (Cdk) 5 and its neuron-specific activator, p35, in the CNS, it remains to be elucidated in the PNS. In addition, it is not known whether Cdk5 activity exists in the PNS. Therefore, we have examined their expression and activity in the PNS by immunoblot analysis, immunohistochemistry, and in vitro kinase assay. Immunoblot analysis indicated the expression of Cdk5 and p35 proteins in dorsal root ganglion (DRG) and sciatic nerve alike in the CNS. By immunohistochemistry, both proteins were shown to be present in the cell body and axon (sciatic nerve) of both DRG neurons and anterior horn cells. A co-immunoprecipitation study indicated the in vivo association between Cdk5 and p35 in both DRG and sciatic nerve. However, Cdk5 kinase activity was found only in DRG, but not in sciatic nerve. These results suggest that Cdk5 kinase activity exists and functions physiologically in the PNS and may be regulated by unknown mechanisms other than the availability of p35 as reported in developing brains.     

Enclosure effects on flame spread over solid fuels in microgravity

Enclosure effects on the transition from a localized ignition to subsequent flame growth over a thermally thin solid fuel in microgravity are numerically investigated by solving the low Mach number time-dependent Navier-Stokes equations. The numerical model solves the two and three dimensional, time-dependent, convective/diffusive mass, and heat transport equations with a one-step global oxidation reaction in the gas phase coupled to a three-step global pyrolysis/oxidative reaction system in the solid phase. Cellulosic paper is used as the solid fuel and is placed in a slow imposed flow parallel to the surface. Ignition is initiated across the width of the sample or at a small circular area by an external thermal radiation source. Two cases are examined; an open configuration (i.e., without any enclosure) and the case with the test chamber used in our previous microgravity experiments. Numerical results show that the upstream centerline flame spread rate for the case with the enclosure is faster than that for the case without any enclosure. This is due to the confinement of the flow field and also thermal expansion initiated by heat and mass addition in the chamber. The confinement accelerates the flow in the chamber, which enhances oxygen transport into the flame. In the three-dimensional configuration with the spot ignition, the flame growth in the direction perpendicular to the flow is significantly enhanced by the confinement effects. The effect of the enclosure is most significant at the slowest flow condition investigated and the effect becomes less important with an increase in imposed flow velocity. The total heat release rate from the flame during a flame growth period increases significantly with the confinement and the enclosure effects should be accounted to avoid underestimating fire hazard in a spacecraft.     

Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis

BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP). METHODS: Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program. RESULTS: Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage. CONCLUSIONS: uPA and its receptor may contribute to the lytic damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-beta, thereby leading to the accumulation of fibrotic tissue.     

State of Utah Performance Information Procurement System Tests

The state of Utah has experienced problems in the procurement of construction. Similar to other states using low-bid, Utah historically has not had construction projects delivered on time and within budget. Faced with critical projects to prepare for the 2002 Olympics, overworked construction project managers, and construction litigation caused by low-bidding contractors, the Division of Facilities Construction and Management tested the Performance Information Procurement System (PIPS) in the fall of 1998 on the University of Utah Housing Project Phase II for the 2002 Olympic Housing. Five other tests were conducted. This article analyzes the differences between the PIPS and the Utah low-bid procurement system, the results of the state of Utah tests, problems, and modifications to the PIPS, and recommendations to future users of the PIPS. Major contributions of this article include the PIPS, Kashiwagi’s Information Measurement Theory, and Zeleny’s Displaced Ideal Model. The objective of this article is to use an information-based business process to procure contractors who deliver on time and on budget and meet quality expectations.     

Inhibition of apoptosis by the actin-regulatory protein gelsolin

Gelsolin is an actin-regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility in vivo through modulation of the actin network. In addition to its actin-regulatory function, gelsolin has also been proposed to affect cell growth. Our present experiments have tested the possible involvement of gelsolin in the regulation of apoptosis, which is significantly affected by growth. When overexpressed in Jurkat cells, gelsolin strongly inhibited apoptosis induced by anti-Fas antibody, C2-ceramide or dexamethasone, without changing the F-actin morphology or the levels of Fas or Bcl-2 family proteins. Upon the induction of apoptosis, an increase in CPP32(-like) protease activity was observed in the control vector transfectants, while it was strongly suppressed in the gelsolin transfectants. Pro-CPP32 protein, an inactive form of CPP32 protease, remained uncleaved by anti-Fas treatment in the gelsolin transfectants, indicating that gelsolin blocks upstream of this protease. The tetrapeptide inhibitor of CPP32(-like) proteases strongly inhibited Fas-mediated apoptosis, but only partially suppressed both C2-ceramide- and dexamethasone-induced apoptosis. These data suggest that the critical target responsible for the execution of apoptosis may exist upstream of CPP32(-like) proteases in Jurkat cells and that gelsolin acts on this target to inhibit the apoptotic cell death program.     

Crack initiation from a sharp notch and stretched zone

The “crack tip COD” at the fracture initiation mainly consists of the stretched zone, the new surface which appeared due to the slip deformation at the notch tip. Therefore, the COD or the stretched zone width at the fracture initiation is a very important parameter which reflects the notch tip behavior until fracture initiation.In the case of fibrous crack initiation, the stretched zone width ($\text{S}{}_{\mathrm{i}}$) and COD ($\text{δ}{}_{\mathrm{i}}$), where $\text{δ}{}_{\mathrm{i}}$ ≈ √2 $\text{S}{}_{\mathrm{i}}$, take almost constant values regardless of temperature, specimen geometry, preloading (if the total $\text{δ}{}_{\mathrm{i}}$ is taken), slit angle (in the case of mixed mode condition) and so on, while, in the case of cleavage fracture initiation, COD and the stretched zone width take various values between the value at the fibrous crack initiation ($\text{δ}{}_{\mathrm{i}}$ or $\text{S}{}_{\mathrm{i}}$) and almost zero, depending on temperature and plastic constraint.