Laminar-type gratings overcoated with carbon-based materials to enhance analytical sensitivity of flat-field emission spectrograph in the VUV region.

Laminar-type spherical diffraction gratings overcoated with carbon-based materials were designed, fabricated, and evaluated for the purpose of enhancing the analytical sensitivity of the flat-field spectrograph in a vacuum ultraviolet region of 35-110 eV. As the design benchmark for numerical calculations, diffraction efficiency (DE) and spectral flux, which are defined by the product of the DE and numerical aperture and correlate with the analytical sensitivity of the spectrograph, were used. To simplify the feasibility study on the overcoating effects, we assumed a laminar-type grating having a grating constant of 1/1000 mm and coated with a Au layer of 30.0 nm thickness and an incidence angle of 84.0°. The optimized groove depth and duty ratio were 30.0 nm and 0.3, respectively. In addition, the optimum thicknesses of the overcoating layer were 44, 46, 24, and 30 nm for B4C, C, diamond-like-carbon, and SiC, respectively. Based on these results, we have fabricated a varied-line-spacing holographic grating overcoated with B4C with a thickness of 47 nm. For the experimental evaluation, we used the light source of Mg-L and Al-L emissions excited by the electron beam generated from an electron microscope, an objective flat-field spectrograph, and a CCD imaging detector. The experimental results showed that the spectrograph employing a new grating overcoated with the B4C layer indicated almost the same spectral resolution and 2.9-4.2 times higher analytical sensitivity compared with those obtained with a previously designed Au-coated grating having a grating constant of 1/1200 mm and used at an incidence of 86.0°.

Proinflammatory cytokine inhibitor prolongs the survival of rats with heart failure induced by pressure overload.

Although an increased expression of proinflammatory cytokines has been reported in cardiac tissue samples from patients with congestive heart failure (CHF) and in various animal models of CHF, the role of these cytokines in the disease remains to be determined. Dahl salt-sensitive (DS) rats fed a high salt diet develop hypertension, cardiac hypertrophy and eventually CHF. In the present study, DS rats were treated with FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl)pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate), a new low molecular weight inflammatory cytokine inhibitor. Treatment with 10 mg/kg per day of FR167653 significantly prolonged the survival of the animals and also prevented the bodyweight loss associated with heart failure. In conclusion, a non-peptide proinflammatory cytokine inhibitor improved the survival of animals with heart failure.

Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart.

Reperfusion injury is a troublesome and unresolved problem in acute myocardial infarction and is believed to be associated with inflammatory reactions in which various types of cells and cytokines participate, in particular, macrophages and monocyte chemoattractant protein-1 (MCP-1). We designed this study to clarify the role and relationship of macrophages and MCP-1 in ischemic and reperfused heart. The number and distribution of macrophages and MCP-1 messenger RNA (mRNA) in the ischemic and reperfused rat heart were examined with in situ hybridization and immunohistochemistry. Myocardial samples were obtained at several times. In situ hybridization was performed with digoxigenin-labeled antisense RNA probe for rat MCP-1 mRNA, and immunohistochemistry was performed with antimacrophage antibody. Double staining with in situ hybridization and immunohistochemistry was also performed. The number of MCP-1 mRNA-positive cells increased after reperfusion and peaked at 3 hours after reperfusion. Early infiltration of ischemic tissues by macrophages was also observed at the time of the absence of an increase of MCP-1 mRNA-positive cells, and this infiltration was not significantly accelerated by reperfusion, but by ischemia itself. The numbers of both MCP-1 mRNA-positive cells and macrophages increased in the ischemic marginal region over time. From the result of double staining, and based on the cellular morphology and the distribution, the majority of MCP-1 mRNA-positive cells appeared to be activated macrophages. This suggests that macrophages may not be attracted to cardiac tissue only by MCP-1 and that MCP-1 may have some roles other than attracting macrophages into ischemic heart. It also suggests that macrophages and MCP-1 may play an important role in reperfusion injury and that MCP-1 may be one of the key molecules of reperfusion injury. These observations may contribute to the development of a new therapeutic approach to the prevention of reperfusion injury.

Apical hypertrophic cardiomyopathy and hepatitis C virus infection.

The familial form of hypertrophic cardiomyopathy (HCM) is attributed to mutations in the genes for contractile proteins, but the etiology of non-familial form remains unknown. This study was designed to examine the clinical features, histopathologic changes, and hepatitis C virus (HCV) genomes in patients with HCM associated with HCV infection. Anti-HCV antibody was present in the sera of 9 of 65 patients (13.8%) with HCM versus 2.41% in a control population of voluntary blood donors in Japan, a statistically significant difference (p<0.0001). Among these 9 patients, 6 had ace-of-spades-shaped deformities of the left ventricle with apical hypertrophy. Myocardial fibrosis was found in all patients, and mild cellular infiltration was observed in 5 patients. Type 1b HCV RNA was present in the sera of 5 of the 9 patients. The copy number of HCV was 5.5x10(3)-8.6x10(5) genomes/ml serum, and multiple clones of HCV were detected in the sera of each patient by an analysis of the hypervariable regions using fluorescent single-strand conformation polymorphism. Positive strands of HCV were found in the hearts of 5 patients, and negative strands in the hearts of 2 patients. A high prevalence of HCV infection was found in patients with HCM, particularly of the apical variety, suggesting that HCV is an important causal agent in the pathogenesis of the disease.

Protective role of interleukin-12 in viral myocarditis.

The co-ordinate action of several cytokines determines the nature, severity and duration of myocarditis. Interleukin (IL)-12 mediates a broad range of effects on both innate and acquired immunity. However, the in vivo role of IL-12 in viral myocarditis remains to be elucidated. To clarify the role of IL-12 in viral myocarditis, we treated mice inoculated with the encephalomyocarditis virus (EMCV), with recombinant IL-12 and neutralizing anti-IL-12 antibody. The successive administration of 10 ng of IL-12 from the day of virus inoculation to 5 days thereafter, reduced mortality, myocardial damage and viral replication in the heart tissue. The gene expression of IL-12p35 and IL-12p40 was enhanced in the hearts of EMCV inoculated mice. Treatment with neutralizing anti-IL-12 resulted in increased mortality of mice inoculated with EMCV. In conclusion, endogenous and exogenous IL-12 play protective roles in murine viral myocarditis.

[Viral myocarditis and autoimmunity].

The pathogenesis of viral myocarditis has not been clarified yet especially in the subacute and chronic stages. Recent reports have shown that myocarditis may be caused by autoimmune reactions. Autoantigens and autoantibodies have recently been reported in myocarditis and cardiomyopathy, and most of them may be induced by the cross-reaction between virus and cardiac tissue, molecular mimicry, or by the destruction of immune tolerance. However it is not clear how autoimmune reactions affect viral myocarditis. We have reported that cytokines are increased in the blood of patients with myocarditis and cardiomyopathy. Many kinds of cytokines modulate viral myocarditis in different ways in murine models. Nitric oxide is also recognized as an important factor in viral myocarditis. We have reported that drugs for heart failure modulate cytokine production. Classifying drugs from this point of view may be helpful for developing new therapeutic strategy for patients with myocarditis and cardiomyopathy.

[Evaluation of area at risk by 123I-BMIPP in patients with acute myocardial infarction].

The purpose of this study was to investigate the detection of area at risk of acute myocardial infarction (AMI) by 123I-BMIPP (BMIPP). 99mTc-tetrofosmin (TF) scintigraphy was performed on 13 patients with AMI with total coronary occlusion. BMIPP scintigraphy was done on the same patients within 1 week after successful reperfusion by direct PTCA. Activity of both tracers was scored in 8 basal, 8 midventricular and 2 apical segments, using a four-point grading system as defect score: 3 = defect, 2 = severely low uptake, 1 = slightly low uptake, 0 = normal. Extent score (ES) was defined as a total number of segment which deteriorated of uptake, and severity score (SS) was defined as a total score of defect score. ES of BMIPP was 6.5 +/- 2.4 and that of TF was 7.5 +/- 2.4. ES of BMIPP was smaller than that of TF. A ratio of BMIPP/TF was 0.86 +/- 0.18. SS of BMIPP was 16.2 +/- 6.0 and that of TF was 19.2 +/- 5.6. SS of TF was larger than that of BMIPP. A ratio of BMIPP/TF was 0.83 +/- 0.18. A correlation of ES and SS between TF and BMIPP was excellent. BMIPP showed ischemic area by culprit lesion and infarct area clearly. We concluded that BMIPP could indicate area at risk.

[Diagnostic usefulness of myocardial SPECT with 123I-beta-methyl-iodophenyl pentadecanoic acid and 201Tl in unstable angina].

The purpose of this study is whether 123I-BMIPP detects a culprit lesion in patients with unstable angina. Twenty-six patients with unstable angina underwent 123I-BMIPP (BMIPP) and 201Tl (Tl) imaging at rest. BMIPP image was compared with Tl imaging. BMIPP imaging revealed defects or low uptake corresponding to myocardial ischemic areas predicted by coronary angiography in 19 (73.1%) of 26 patients. Tl imaging showed defects or low uptake corresponding to coronary angiographic findings in 14 (53.8%). BMIPP demonstrated significantly less uptake than Tl (p = 0.001). Severity of reduced BMIPP activity was greater than that of Tl (p < 0.001). We concluded that BMIPP imaging was excellent to detecting of culprit lesions in patients with unstable angina. BMIPP SPECT is a sensitive method for detecting myocardium exposed to transient schemia that cannot be detected by Tl imaging.

[Serial changes of coronary arteries after percutaneous transluminal coronary angioplasty: histopathological and immunohistochemical study].

Intimal hyperplasia due to fibrocellular proliferation, mainly of smooth muscle cells, leads to restenosis after successful percutaneous transluminal coronary angioplasty (PTCA). The mechanism of intimal proliferation of smooth muscle cells was investigated by histological and immunohistochemical studies of necropsied coronary arteries from 13 patients who died between several hours and 1 year 8 months after PTCA. Immunohistochemical examinations clearly revealed smooth muscle cells already migrating from the media into the injured intima after 10 days. Thereafter, significant proliferation of smooth muscle cells was observed on the intimal side of the affected regions, predominantly around the circumference of the lumen at the PTCA site. Arteries from patients with restenosis who died more than 1 month after PTCA demonstrated proliferating cells with a polygonal shape and large bizarre nuclei. Arteries without restenosis showed smooth muscle cells with a spindle shape and rather elongated or oval nuclei. Although these cells were ordered along the luminal surface, the intercellular space still contained abundant ground substances. A case in which death occurred more than 1 year after PTCA showed these cells were analogous to medial smooth muscle cells. In addition, the extracellular matrix volume was extremely reduced, and composed chiefly of collagen as shown by positive Masson's trichrome stain. These histological findings demonstrated completion of repair and stabilization of the lesion caused by PTCA. Immunohistochemical investigation showed proliferating cells stained positive to vimentin but were negative to desmin, irrespective of the lesion age. This study provides pathological support for clinical reports suggesting that restenosis is predominant between 1 and 6 months and decreases beyond 1 year after PTCA.

Survival simulation of hepatocellular carcinoma derived from follow-up studies of 450 patients.

A simulation model to predict the survival probability of individual patients with hepatocellular carcinoma (HCC) after therapy was derived from the results of various therapies and follow-up studies of 450 HCC patients. Twenty-two prognostically important variables were analyzed by Cox's proportional hazards model. The 9 significant variables that were extracted were used to build the simulation. In this model, S(t), the expected estimated survival rate for individual patient at time t (month), is calculated by the following equation: S(t) = (exp (-0.03655t) (exp [0.9479 ([portal vein invasion]-0.222) + 0.3846 ([tumor number]-2.00) + 0.2578 ([tumor size]-3.231) + 0.0742 ([loge AFP]-5.647) + 0.8184 ([metastasis]-0.036) + 0.2810 ([Child's class]-1.689)-0.7088 ([transcatheter arterial embolization]-0.578)-0.9746 ([percutaneous ethanol injection]-0.153)-0.5377 ([hepatectomy]-0.109)]) The validity of the model was assessed using a split-sample technique. This paper does not discuss the superiority or inferiority of the therapies, because some selection bias for prognostic factors among the therapies can not be completely excluded. But this model is proposed as a practical model to predict the survival of patients with HCC.

Hemostasis of gastric variceal hemorrhage by transileocoecal and transhepatic obliteration.

Obliteration for gastric or duodenal variceal hemorrhage was performed via transileocoecal or transhepatic portal catheterization in 8 patients with portal hypertension. The patients were 6 men and 2 women, whose average age was 59 years. All of the patients had cirrhosis of the liver. The obliteration was performed as an emergency procedure in 6 cases, and 2 patients were electively treated. Transileocoecal obliteration (TIO) and transhepatic obliteration (PTO) were selected for 6, and 2 patients, respectively. Variceal bleeding was successfully controlled in all patients after completion of the therapy. One patient died after 3 months when duodenal variceal bleeding recurred. Elective surgical operations were performed on 2 patients after the initial therapy, because the vein feeding toward the varices remained. Six of the patients have survived to date without bleeding. Transient oliguria and jaundice after the therapy were noticed in 2 patients. Histological examination revealed cast formation of polymerized cyanoacrylate in the obliterated gastric varices of 2 patients. TIO and PTO seem to be safe, effective procedures to stop bleeding from ectopic varices, gastric or duodenal. This therapy is useful either to obtain accurate information about the varices or to obliterate the collateral veins in patients with ruptured ectopic varices.

Obliteration of portal systemic shunts as therapy for hepatic encephalopathy in patients with non-cirrhotic portal hypertension.

The effects of obliteration of portal systemic shunts (PSS) in 5 patients with non-cirrhotic hepatic encephalopathy is reported. All patients had a history of disturbance of consciousness for several years, and examinations revealed large PSS, most of which connecting the left gastric vein to the left renal vein. After the obliteration of PSS, portal vein pressure elevated, the shunt ratio of the portal blood flow decreased, the indocyanine green disappearance rate increased, and serum albumin increased. Blood ammonia (NH3) decreased significantly accompanied by disappearance of hepatic encephalopathy. This treatment may open a way to improve the quality of life in patients with large PSS without severe hepatic injury.

[A case of successful repair of aorto-pulmonary artery fistula secondary to aortic arch aneurysm].

A report of a rare case of successful repair of rupture of an aortic aneurysm into the pulmonary artery. A 55-year-old male was transferred to our hospital because of dyspnea with sudden onset, hemoptysis and palpitation. A loud, continuous, "machine-like" murmur was heard on the anterior wall of the chest. Various examinations revealed an acquired shunt between the thoracic aortic aneurysm and the pulmonary artery and high-output heart failure. Aortic arch replacement was performed expeditiously and the patient recovered, and was able to return to work. 108 cases of rupture of a thoracic aortic aneurysm into the pulmonary artery have been reported in the literature. Operation for repair was performed in only thirteen of these. Only four cases have been reported in the literature in which the patients were successfully treated.

Long-term intermittent administration of interferon-alpha in patients with chronic non-A, non-B hepatitis.

IFN-alpha was administered intermittently over a 6 month period in 39 patients with chronic non-A, non-B hepatitis confirmed by peritoneoscopy and liver biopsy. Three million units of IFN-alpha were administered 3 times a week for the first 6 months then twice, then once a week. In 26 patients (67%), GPT decreased and remained within the normal range during the course of administration, and in 9 patients (23%) GPT remained normal for over 6 months after the discontinuation of IFN-alpha. There was no significant difference of efficacy among 3 groups liver histology groups (CPH, CAH-2A, and CAH-2B), but GPT decreased significantly in patients with sporadic hepatitis compared to patients with a history of blood transfusion. Furthermore, GPT decreased significantly in patients with a history of a blood transfusion within the preceding 2 years compared to patients with a history of a blood transfusion over 7 years ago. GPT increased markedly after an early tapering to 2 doses weekly, but it did not increase after a 6 month administration. In conclusion, the long-term administration of 300 million unit IFN-alpha, 3 times weekly for 6 months, about 2.5 hundred million units in total, is thought to be an effective way to control chronic NANB hepatitis.