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Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.

Dermatopontin (DPT), a regulator of tumoral invasiveness and metastasis, is down-regulated in oral squamous cell carcinoma (OSCC); however, the DPT regulatory mechanism is poorly understood. Epigenetic alterations of chromatin such as histone acetylation do not alter the DNA sequence but modify the chromatin architecture and its accessibility, resulting in repressed gene transcription.

Dentinogenic ghost cell tumors (DGCTs) are extremely rare, accounting for less than 0.5% of all odontogenic tumors. DGCTs were described initially as solid neoplasms of calcifying odontogenic cysts (COCs). In the 2005 WHO Histological Classification of Odontogenic Tumors, COCs were classified as tumors and renamed as calcifying cystic odontogenic tumors (CCOTs). The term of DGCT was retained and histologically defined as a locally invasive neoplasm characterized by ameloblastoma-like islands of epithelial cells in a mature connective tissue stroma, aberrant keratinization comprised of ghost cells, and an association with dysplastic dentin. DGCTs were subdivided into two variants: intraosseous (central) and extraosseous (peripheral). Generally, peripheral DGCTs occur less frequently than central ones. We report a rare case of a peripheral DGCT in a 60-year-old man with a well-circumscribed nodule in the left canine region of the maxilla. The lesion measured about 11 millimeters in diameter. No bone involvement was observed radiographically. Based on clinical and radiographic findings, the tumor was provisional diagnosed as benign. Consequently, it was enucleated completely, and a histopathological diagnosis of DGCT was made. The patient has remained disease-free for 18 months postoperatively. The biologic behavior of central DCGTs is considered to be more aggressive and require radical treatment. In contrast, peripheral DGCTs have been reported to be non-aggressive, because local bone resorption or recurrences have not yet been reported. There are no differences in the histopathologic features between the central and peripheral variants. Accordingly, accurate preoperative evaluation is crucial to differentiate between these lesions including other odontogenic tumors.

The solution treatment after nitriding (STAN) was performed to stabilize the γ- phase in a metastable austenitic stainless steel, type 304, and to improve the strength of type 304 by the solid solution of nitrogen. Plasma nitriding was conducted at 500°C for 8.5h, and then solution treatment was performed at 1200°C for 1h. As a result, the static strength and the hardness were improved by the STAN. Rotary bending fatigue tests were performed on the specimens with STAN (solid solution strengthened) together with the untreated and the nitrided ones in laboratory air and in 3%NaCl solution. In laboratory air, the fatigue strength of the solid solution strengthened specimen increased compared to that of the untreated specimens, where fatigue limits were 340MPa and 290MPa for the solid solution strengthened and the untreated, respectively. However, the fatigue limit of the solid solution strengthened specimen was lower than that of the nitrided specimen, that is, 380MPa. On the other hand, in 3%NaCl solution, the fatigue strengths of the nitrided specimens and the solid solution strengthened specimens decreased significantly compared to those in laboratory air. After the fatigue tests at the stress level of fatigue limit in laboratory air, the strain-induced martensitic transformation was examined by XRD. In the solid solution strengthened specimens, the strain-induced martensitic transformation was not detected during fatigue tests until 3x107 cycles, indicating that the γ- phase was stabilized by the solid solution of nitrogen.

High cycle fatigue properties and failure mode in high strength steel tempered at low temperature were studied. The material used was Ni-Cr-Mo steel, JIS SNCM439, which was tempered at 453 K. After heat treatment, round bar specimens with hourglass shape were machined. Fatigue tests were performed using two kinds of specimens with two surface conditions, i.e., as-ground specimen and buff-finished specimen. Tests were conducted under rotating bending and axial loading. Under rotating bending, in as-ground specimens, fatigue failure took place in high cycle region above 107 cycles and failure mode was surface-related. On the other hand, buff-finished specimens exhibited the step-wise S-N curve, i.e., the subsurface fracture with a fish-eye was observed. However, under axial loading, even in buff-finished specimens the subsurface fracture didn’t occur due to small nonmetallic inclusions. Based on the results, the fatigue limit was estimated by the statistics of extremes. The prediction gave the conservative values.

A series of fatigue tests has been conducted to estimate the fracture behavior depending on stacking sequences in quasi-isotropic CFRP laminates. Strips of laminate with four different directions were cut out from the same CFRP plate to prepare the specimens with the four kinds of stacking sequences. Prior to fatigue test, the specimens were impacted with lateral load in order to simulate the damage induced by the fallen tools. During the fatigue tests, the damage developed in the specimen was detected by non-destructive techniques using a scanning acoustic microscope (SAM) and a replicating method. Stacking sequences exerted an influence on fracture behavior of laminate specimens, i.e. the stacking position of the zero degree layers, in which fiber direction was parallel to the loading axis, played an important role in the fracture process. When the zero degree layers are located at the specimen surface, no remarkable damage propagation was observed from the surface. On the other hand, when the zero degree layers are located in the middle of laminates, the damage in the surface layer was found in the fatigue process. Not only the degradation of the equivalent elastic modulus was seen in all specimens, but also the degradation curve varied with the stacking sequences.

Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. We previously demonstrated that blockade of B7/CD28 or CD40/CD40 ligand (CD40L) had a potential preventive effect on EAM, but less therapeutic effect on ongoing EAM. Thus, we searched for the involvement of other costimulatory molecules in EAM. We demonstrated the expression of inducible costimulator (ICOS)/ICOSL molecules in the lymph nodes, spleen, and heart in the EAM rat. We constructed adenovirus vectors containing ICOSIg (Adex1CAICOSIg) to achieve effective inhibition of ICOS/ICOSL interaction, and examined the effects of Adex1CAICOSIg on EAM. Adex1CAICOSIg treatment shortly after the immunization did not inhibit the onset and severity of EAM compared to control rats. On the other hand, delayed treatment with Adex1CAICOSIg significantly inhibited ongoing EAM. The survival rate in rats treated with Adex1CAICOSIg was significantly higher than that of the control group. Furthermore, the affected area ratio of the Adex1CAICOSIg treatment group was significantly lower than that of the control group. This study indicates that ICOS/ICOSL costimulation makes an important contribution to the progression of EAM and that the blockade of this pathway by gene transfer has therapeutic potential for ongoing autoimmune myocarditis.

Numerous reports have examined the relationship between hepatocyte growth factor (HGF) and either the facilitation or suppression of the occurrence of hepatocellular carcinoma (HCC). In this study, we measured serum HGF concentrations of blood samples and conducted prospective studies to examine the long-term outcome of C-viral chronic hepatitis (CH) and cirrhosis in patients. The subjects examined in this study include 99 patients with C-viral CH, cirrhosis, and HCC. The serum HGF level was measured in blood samples within 48 hours of collection using enzyme-linked immunosorbent assay kits. The serum concentrations of HGF were significantly higher in patients with HCC than in patients with CH or cirrhosis. The detection rate of HGF and its mean serum level were significantly higher in patients with a low platelet count than in patients with a high platelet count. All of the patients with serum HGF concentrations of more than 0.6 ng/mL had HCC, irrespective of the levels of α-fetoprotein, vitamin K absence, or antagonist-II in the blood. Serum HGF concentrations increased concomitantly with increases in areas occupied by HCC. The cumulative incidence of occurrence of HCC was significantly higher in patients with high HGF concentrations than in patients with low HGF concentrations. Multivariate analysis revealed that the elevation in serum HGF level is the most important risk factor for the occurrence of HCC. The serum level of HGF represents the degree of the carcinogenic state in the liver of patients with C-viral CH and cirrhosis. Therefore, the determination of serum HGF concentrations may be useful as a third tumor marker of HCC in detection as well as follow-up therapy. Cancer 2002;95:824–34. © 2002 American Cancer Society. DOI 10.1002/cncr.10732

Abstract: Osteopontin (OPN), a noncollagenous adhesive protein, may possibly be implicated in atherosclerosis, in which macrophages and activated T lymphocytes could have higher OPN levels within the atherosclerotic plaques. However, it is not known whether a higher OPN level is a cause or a result of atherosclerosis or whether it has a promoting or inhibitory effect on atherosclerosis. To clarify the role of OPN in atherosclerosis, we developed a transgenic mouse (OPN-TG) in which the exogenous OPN gene was designed to be expressed by hematopoietic cells, expressing OPN, which carried the immunoglobulin enhancer (Eμ)/SV40 promoter. In OPN-TG, the expression of exogenously transfected OPN RNA was found in lymphoid organs, such as the thymus and spleen, and the kidney. In the present study, OPN-TG mice were assigned into two groups, an atherogenic diet group (15% fat, 1.25% cholesterol) for 3 months or a standard diet group (4% fat), and both groups were compared with wild-type C57BL/6 mice to investigate the relationship between osteopontin and the atherosclerotic lesion. In wild-type mice, OPN mRNA was detected in kidney, but not in lymphoid tissues. In both OPN-TG and wild-type mice fed with control diets, atherosclerotic lesions were not found in the aortic sinus or the thoracic and abdominal aorta. In both OPN-TG and wild-type mice fed with atherogenic diets, a high incidence of atherosclerotic lesions was noted in the aortic sinus. The atherosclerotic lesions were significantly larger in OPN-TG as compared with those in control littermate mice (size: 33.8% ± 23.4% vs 10.9% ± 20.4%, respectively, P < 0.05). Activated foamy macrophages within atherosclerotic plaque in OPN-TG expressed a considerably larger amount of OPN compared with such macrophages in control mice. The OPN protein detected in the atherosclerotic lesions was not due to the deposition of serum OPN, but mainly due to in situ production by the infiltrating macrophages. Thus, these results suggest that OPN is atherogenic and that macrophages expressing OPN can be easily activated and thus promote atheromatous lesions if a high fat diet is consumed.

The present investigation compared the histological findings in the liver of chronic hepatitis C patients who were or were not co‐infected with TT virus (TTV) to determine the histological and clinical characteristics of TTV infection. One hundred eighty patients with chronic hepatitis or liver cirrhosis type C were included in this study. Serum samples were tested for the presence of TTV DNA by a nested polymerase chain reaction. The liver biopsy specimen of each patient was examined, and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; fibrous stage; lymphoid reaction in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage of bile duct; and irregular regeneration of hepatocytes. Sixty‐four (34.4%) of the 180 patients were positive for TTV DNA. The histological features of the liver and the blood biochemical parameters of the TTV DNA‐positive and TTV DNA‐negative patients, did not differ significantly except for the score of irregular regeneration (IR) of hepatocytes. Among those in the F4 stage of fibrosis, the score of IR of the TTV DNA‐positive patients was significantly higher than that of the TTV DNA‐negative patients. In conclusion, chronic TTV infection does not modify the biochemical features of chronic hepatitis type C patients. TTV may be a risk factor, however, for the development of hepatocellular carcinoma in patients with type C liver disease in the F4 stage. J. Med. Virol. 64:74–81, 2001. © 2001 Wiley‐Liss, Inc.

The organ where the GB virus (GBV)-C/hepatitis G virus (HGV) localizes and proliferates is not known. We examined the digestive organs for HGV RNA to determine the localization of the HGV. Two cases of patients with serum-positive HGV RNA were investigated. We embedded surgically excised materials and digestive secretion materials from cases 1 and 2 in paraffin blocks. The tissue specimens investigated included lymph nodes No. 201 and 202, ascending colon (nontumor and tumor area), ileocecum, appendix, liver (nontumor and tumor area) and gall bladder. We made cDNA after extraction of total RNA from thin tissue sections and detected HGV RNA with a reverse transcription polymerase chain reaction method. No HGV RNA was detected in liver, colon and gall bladder tissues. HGV RNA was only detected in the appendix tissue. Comparison of nucleotide sequences of PCR products from serum and appendix was almost the same. Homology between US type (PNF2161) and the serum and appendix PCR products was 92.6 and 93.6%, respectively. These results suggest that HGV proliferates in the appendix and is carried by the portal blood flow to the liver, and may cause a hepatitis reaction in the liver.

We tested the sera of patients with non-A, non-B, non-C, non-G (non-A to -G) hepatocellular carcinoma (HCC) for the presence of TT virus (TTV) DNA and clinicopathologically elucidated the relationship between TTV infection and hepatocarcinogenesis. The study cohort consisted of 19 patients with non-A to -G HCC. Detection of TTV DNA was performed by the nested polymerase chain reaction according to a previously published method. TTV DNA was detected in the sera of 9 (47.4%) of the 19 patients with non-A to -G HCC. The clinical background factors and blood biochemical parameters of the TTV-DNA-positive and -negative HCC patients did not significantly differ. Three TTV-DNA-positive and 2 TTV-DNA-negative patients underwent surgical resection of the HCC. The histological findings in the non-cancerous liver tissue of the TTV-DNA-positive and -negative patients did not significantly differ. In conclusion, TTV infection does not affect the features of non-A to -G HCC.

Abstract: Background: The study of the clinical features of multiple primary cancers (MPC) may provide insight into the pathogenesis of specific cancers, as well as the issue of treatment-related induction of second tumors. Methods: Between 1972 and 1995, 94 of 765 patients with urologic cancer treated at our hospital had MPC. We retrospectively analyzed the clinical features of these patients, and compared them with those of the 671 patients with single primary cancers (SPC). Results: The frequency of MPC among all 765 patients was 12.3%. The average age at diagnosis of urologic cancer in the male patients was significantly higher in the MPC group than in the SPC group. In the MPC group, the organs most commonly involved were the bladder and prostate (urologic cancers), and the stomach and lung (nonurologic cancers). Adenocarcinoma was the most common tumor in the MPC group. The interval between the first and second cancer diagnoses was significantly longer in female patients with MPC than in male patients. No significant difference between the MPC and SPC groups was observed in the distribution of ABO blood groups or in the frequency of history of tobacco or alcohol use. Four MPC patients had second cancers considered to have been induced by the treatment for the first cancer. The prognoses were significantly poorer for the patients with MPC. The rate of death due to urologic cancer was much lower in the patients with MPC than in those with SPC. Conclusions: We found that more than 10% of the 765 patients with urologic cancer whose cases we reviewed had another primary cancer. Because the number of cases of MPC is increasing, it is important to be aware of the possibility of the development of MPC and to therefore carefully follow up cancer patients.

A new type of tetracyclic compounds, cis-transoid-cis- and cis-cisoid-cis-tetracyclo[6.6.0.01,11.03.7] tetradecan-12-ones, having a tetraquinane framework, has been synthesized by the novel acid-catalyzed rearrangement.

By means of the ac calorimetry technique, the ferroelectric transition behavior of vinylidene fluoride/trifiuoroethylene (VDF/TrFE) copolymers was investigated. The data from ac calorimetry were compared with those from adiabatic calorimetry to elucidate the orders of the transition. From the comparison, it was clarified that the ferroelectric transitions of copolymers containing 73 and 65 mol% VDF are of the first order, while the copolymer with 55 mol% VDF shows the second-order character. These results were qualitatively explained using a simple model for rotational transitions. Throughout this work, an important feature of ac calorimetry, i.e., the exclusion of the contribution of latent heat, was confirmed in the measurements of PE and VDF/TrFE copolymers.

Differences between nondissipative and dissipative systems are investigated, which were recently emphasized by Prigogine et al. The reason why the Hamiltonian can be diagonalized by the unitary transformation in nondissipative systems and not in dissipative systems is clarified. On the assumption that the Hamiltonian can be diagonalized by the nonunitary transformation in dissipative systems, the similar result as that of Prigogine et al. is obtained. The ergodicity condition is formulated by making use of the method of orthogonal operators expansion. The condition for an operator to be a constant of the motion is obtained both in nondissipative and dissipative systems. It is shown that the number of constants of the motion in dissipative systems if fewer than that in nondissipative systems.