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Diabetic nephropathy, included in diabetic kidney disease (DKD), is the primary disease leading to end-stage renal disease (ESRD) or dialysis treatment, accounting for more than 40% of all patients with ESRD or receiving dialysis. Developing new therapeutics to prevent the transition to ESRD or dialysis treatment requires an understanding of the pathophysiology of DKD and an appropriate animal model for drug efficacy studies. In this study, we investigated the pathophysiology of diabetic kidney disease with type 2 diabetes in uninephrectomized db/db mice. In addition, the nephrectomized db/db mice from 10 weeks to 42 weeks were used to assess the efficacy of long-term administration of the angiotensin-II–receptor antagonist losartan. The blood and urinary biochemical parameters and the blood pressure which is a main pharmacological endpoint of the losartan therapy, were periodically measured. And at the end, histopathological analysis was performed. Uninephrectomized db/db mice clearly developed obesity and hyperglycemia from young age. Furthermore, they showed renal pathophysiological changes, such as increased urinary albumin-creatinine ratio (UACR) (the peak value 3104±986 in 40-week-old mice), glomerular hypertrophy and increased fibrotic areas in the tubulointerstitial tubules. The blood pressure in the losartan group was significantly low compared to the normotensive Vehicle group. However, as expected, Losartan suppressed the increase in UACR (829±500) indicating the medication was sufficient, but the histopathological abnormalities including tubular interstitial fibrosis did not improve. These results suggest that the uninephrectomized db/db mice are useful as an animal model of the severe DKD indicated by the comparison of the efficacy of losartan in this model with the efficacy of losartan in clinical practice.

Background:Eosinophilic fasciitis (EF) is a rare disease that causes inflammation and fibrosis mainly in the fascia of the extremities with eosinophilia. It has been reported that the hypertrophied fascia in EF shows inflammatory cell infiltration by the lymphocytes and eosinophils and increased expression of fibrosis-related cytokines genes in fibroblast [1]. However, its pathophysiology in the fascia remains unresolved.Objectives:Therefore, we focused on fascial fibroblasts and aimed to determine the role of interleukin-4 (IL-4) in eosinophil and helper T cell infiltration and fibrosis in fascial fibroblast in EF.Methods:Fascial fibroblasts were obtained from fascia biopsy of a patient with EF, and were stimulated with pre- and post-treatment serum of a patient with EF and healthy control, followed by microarray to analyze gene expression. Fascial fibroblasts were stimulated with IL-4 10 ng/mL, and gene expression of IL-4 receptor and CCR3 ligands, CCL7 and CCL11 were measured by qPCR. Transforming growth factor (TGF) -β and periostin in the pre- and post-treatment serum of a patient with EF and conditioned medium of fascial fibroblasts stimulated with IL-4 were measured by ELISA. To examine the role of IL-4 in proliferation, we performed in proliferation assays using fascial fibroblasts treated with IL-4. CCR3-positive T cells in the fascial tissue of EF, dermatomyositis, and polymyositis patients were evaluated by immunostaining.Results:By microarray analysis, CCL7 and CCL11 expression of fascial fibroblasts stimulated with pre-treatment EF serum was higher than that in post-treatment EF serum and control serum. CCL7 and CCL11 mRNA in IL-4 stimulated facial fibroblasts were increased by 5.1-fold and 7.3-fold, respectively. TGF-β and periostin in IL-4 stimulated facial fibroblast conditioned medium were also increased. In addition, TGF-β and periostin in EF serum were gradually decreased by treatment for 4 and 10 weeks, compared to before treatment. Finally, fascial fibroblast proliferation was significantly increased by stimulation with IL-4. Furthermore, infiltration of CCR3-positive T cells was specific to the fascial tissue of EF.Conclusion:In EF, IL-4 enhances the production of CCR3 ligands, TGF-β, and periostin from fascial fibroblasts. As a result, it promotes the migration of eosinophils and CCR3-positive T helper cells to the fascia and fibrosis. These results suggest that inhibition of IL-4 pathway could be a novel strategy for eosinophilic fasciitis.References:[1]Igarashi A, Nashiro K, Kikuchi K, et al. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J Invest Dermatol. 1996 Apr;106(4):729-33.Disclosure of Interests:None declared

Background:Hepatocyte growth factor (HGF) binds to the receptor tyrosine kinase c-Met and is a multifunctional cytokine that promotes processes such as cell proliferation, survival, differentiation, migration and angiogenesis [1]. We previously reported that HGF is produced by inflammation in the RA synovium, and activates monocyte migration to the synovium and promotes bone destruction through its own chemotactic effect and enhanced chemokine production in the synovium [2].Objectives:Therefore, we next aimed to determine the role of HGF in RA angiogenesis.Methods:The expression of HGF / c-Met in the serum and synovial tissues (STs) of RA patients and controls and human umbilical vein endothelial cells (HUVECs) was evaluated by ELISA and immunostaining. The effect of HGF/c-Met signaling on the promotion of CXCL16 production from HUVECs and RA fibroblast-like synoviocytes (FLSs) was determined by ELISA. To examine the role of HGF in angiogenesis, we performed in vitro Matrigel assays using HUVECs treated with HGF.Results:HGF in serum in treatment-naive RA patients was significantly higher than that in controls and HGF in serum in treatment-resistant RA showed a significant positive correlation with CXCL16. c-Met were expressed on vascular endothelial cells of RA STs and HUVECs. Stimulation of HUVECs with HGF dose-dependently increased CXCL16 production. c-Met signal inhibition by SU11274 suppressed TNF-α stimulation-enhanced CXCL16 production by RA FLSs in a dose-dependent manner. Furthermore, HGF induced HUVEC tube formation by 1.8-fold.Conclusion:HGF is produced by inflammation in the RA synovium, and activates angiogenesis through its own potent angiogenic effect and enhanced production of CXCL16 in the synovium. These results indicate that a strategy targeting c-Met signalling may be important for resolving treatment-resistant RA.References:[1]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3.[2]Hosonuma M, Sakai N, Furuya H, et al. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419.Disclosure of Interests:None declared

Background Multi-slice computed tomography (CT) is frequently used to evaluate the morphology, arrangement, and other characteristics of bone. Three-dimensional volume rendering (3D-VR) has made it possible to three-dimensionally visualise tendons and other structures by arbitrarily changing CT values. In deformities of the forefoot region in rheumatoid arthritis (RA), dislocation of the metatarsophalangeal (MTP) joints results in the formation of painful calluses that require surgery; however, the toes can sometimes be displaced inwards or outwards by this dislocation. MTP joint dislocation also causes the flexor tendons to dislocate from their original positions, although the relationship with toe displacement is unclear. Objectives We therefore used 3D-VR to examine the relationship between the flexor tendons and toe displacement in the dislocated toes of RA patients. Methods Thirty-one feet (10 right and 21 left) of 24 patients (5 men and 19 women) were examined. The Tsuboi classification was used to classify MTP joint dislocation into subluxation (Grade 2) or dislocation (Grade 3). CT images taken with no load applied to the feet were used for preoperative evaluation. The mean age of the patients at the time of imaging was 59.0 (36–76) years. A Fujifilm volume analyzer (SYNAPSE VINCENT) was used for 3D-VR reconstruction and CT values were adjusted to visualise the flexor tendons and examine their relationship with the heads of the metatarsal bones. When the flexor tendons were displaced inward or outward from the base of the metatarsal bone head, this was classified as flexor tendon dislocation. Toe displacement was identified when the proximal phalanx was displaced inward or outward from the extended line of the metatarsal axis. Results MTP joint dislocation was seen in 80 toes (63 cases of dislocation and 17 cases of subluxation). The flexor tendons were dislocated in 27 s toes (15 inward and 12 outward), 27 third toes (21 inward and 6 outward) and 16 fourth toes (15 inwards and 1 outward). Of the cases of MTP joint dislocation, toe displacement was seen in 12 s toes (1 inward and 11 outward), 12 third toes (12 outward) and 2 fourth toes (1 inward and 1 outward). The flexor tendons were dislocated towards the displaced toes in all cases. No flexor tendon dislocation was seen in any of the cases of subluxation. Conclusions RA is often accompanied by hallux valgus and toe displacement is affected by retraction of the first toe. The results of this study demonstrate that the toes are displaced inwards in some cases and can become dislocated independent of the influence of the first toe. All the toes were displaced towards the dislocated flexor tendons and MTP arthritis had resulted in loosening of the joint capsule and ligaments and dislocation of the flexor tendons, which was likely to cause displacement. Disclosure of Interest None declared

In adult-to-adult living donor liver transplantation (LDLT), left-lobe grafts can sometimes be small-for-size. Although attempts have been made to prevent graft overperfusion through modulation of portal inflow, the optimal portal venous circulation for a liver graft is still unclear. Hepatic hemodynamics were analyzed with reference to graft function and outcome in 19 consecutive adult-to-adult LDLTs using left-lobe grafts without modulation of graft portal inflow. Overall mean graft volume (GV) was 398 g, which was equivalent to 37.8% of the recipient standard liver volume (SV). The GV/SV ratio was less than 40% in 13 of the 19 recipients. Overall mean recipient portal vein flow (PVF) was much higher than the left PVF in the donors. The mean portal contribution to the graft was markedly increased to 89%. Average daily volume of ascites revealed a significant correlation with portal vein pressure, and not with PVF. When PVP exceeds 25 mmHg after transplantation, modulation of portal inflow might be required in order to improve the early postoperative outcome. Although the study population was small and contained several patients suffering from tumors or metabolic disease, all 19 patients made good progress and the 1-year graft and patient survival rate were 100%. A GV/SV ratio of less than 40% or PVF of more than 260 mL/min/100 g graft weight does not contraindicate transplantation, nor is it necessarily associated with a poor outcome. Left-lobe graft LDLT is still an important treatment option for adult patients.

Transient behavior of the a-Si:H/Si3N4 metal-insulator-semiconductor (MIS) capacitor and its relationship to the performance of a-Si:H based active-matrix liquid crystal displays (AMLCDs) have been analyzed in detail. A relatively slow voltage decay whose time constant is comparable to the frame period of the LCD is observed after applying a voltage pulse that drives the MIS capacitor into the electron accumulation. The voltage decay is due to electron emission from the localized states at the a-Si:H/Si3N4 interface. It is also found that this voltage transient results in a shift in the optimum common voltage for the liquid crystal pixel by changing the temperature and light exposure when an MIS-type capacitor is inserted between the pixel electrode and the adjacent gate bus-line as the storage capacitor. This shift in the optimum common voltage affects the image quality of AMLCDs through image sticking or flicker. A similar effect can occur even without an MIS-type storage capacitor in high resolution AMLCDs, where the gate-source parasitic capacitance of the thin-film transistor is comparable to the net capacitance of the pixel. It is important to take such transient effects of MIS capacitors into consideration in pixel designing

A direct transformation of the g-BC3 phase to a new diamond-like d-BC3 phase was observed in a diamond-anvil cell (DAC) at high temperature, 2033 ± 241 K, and high pressure, 50 GPa. Analysis of the peak positions of the d-BC3, B4C, α-boron, and the boron-doped diamond leads to the conclusion that the positions of the peaks of the d-BC3 are more similar to the peak pattern of the boron-doped diamond rather than that of boron carbide, α-boron. Copyright © 2007 John Wiley & Sons, Ltd.

A lattice Boltzmann method for two-phase immiscible fluids with large density differences is proposed. The difficulty in the treatment of large density difference is resolved by using the projection method. The method can be applied to simulate two-phase fluid flows with the density ratio up to 1000. To show the validity of the method, we apply the method to the simulations of capillary waves, binary droplet collisions, and bubble flows. In capillary waves, the angular frequencies of the oscillation of an ellipsoidal droplet are obtained in good agreement with theoretical ones. In the simulations of binary droplet collisions, coalescence collision and two different types of separating collisions, namely reflexive and stretching separations, can be simulated, and the boundaries of the three types of collisions are in good agreement with an available theoretical prediction. In the bubble flows, the effect of mobility on the coalescence of two rising bubbles is investigated. The behavior of many bubbles in a square duct is also simulated.

家族性大腸腺腫症(FAP)は,常染色体優性遺伝疾患であり,若年から高率に大腸癌を発症するとともに,特徴的な大腸外病変を来たす.FAP家系のサーベイランスと予防的大腸切除術の普及により,大腸癌罹患率は減少し,死因に占める大腸癌の割合も減少してきている.反面,FAP患者の生存期間の延長とともに,大腸外病変の重要性が増加してきた.本稿では,デスモイド腫瘍に代表される腸管外病変について概説した.デスモイド腫瘍は,FAP患者の死因の第二位を占め,FAP患者の約10%に発症する.病因としては遺伝子的要因,手術,性ホルモンの関与が報告されている.腹壁のデスモイド腫瘍には切除術が第一選択とされるが,腹腔内のデスモイド腫瘍に対しては切除術よりも保存的治療が優先される.他の腸管外病変として,甲状腺腫瘍,網膜色素上皮肥大(CHRPE),肝芽腫,脳腫瘍などを取り上げ,若干の知見を紹介した.Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disease predisposing to colon cancer. Surveillance of the pedigree and widespread use of prophylactic colectomy have resulted in a reduction in the incidence of colon cancer in FAP patients. Thus, a greater percentage of morbidity in FAP patients appears to be attributable to extracolonic manifestation of the disease. In this article, the characteristics of extra-intestinal manifestation, as represented by desmoid tumors, are reviewed. Desmoid disease is a second cause of death in FAP patients, and it is associated in approximately ten percent of cases. Trauma, sex steroids, and an inherited defect have been implicated in the etiology of desmoids. Surgery is accepted as the first-line treatment for abdominal wall desmoids, while intraabdominal desmoids should be treated medi-cally. We also reviewed extra-intestinal manifestations, such as thyroid tumors, congenital hypertrophy of retinal pigment epithelium (CHRPE), hepatoblastomas, and brain tumors.

A total of 290 Shigella strains consisting of 180 imported strains and 110 domestic strains isolated during 1995-1999 in Tokyo were examined regarding their species and serovar-distribution and their drug-resistance. In both groups, S. sonnei (70.0% in the imported strains, 80.9% in the domestic strains) was found to be the most prevalent species, followed by S. flexneri (20.0% in the imported strains, 19.1% in the domestic strains). S. dysenteriae and S. boydii were only isolated in the imported cases. Among the S. flexneri serovar, 1b, 2a, 6, 2b, and 3a were predominant in the imported strains, whereas 1b and 2a were predominant in the domestic strains. Provisional new serovar Shigella strains were isolated from 11 imported cases and 2 domestic cases. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 92.2% of the imported strains and 94.5% of the domestic strains were resistant to some of the drugs tested. Drug-resistance patterns of the resistant strains varied in 25 types. Among those, a triple drug-resistance type with TC.SM.ST was found as the most frequent pattern in both groups. None of the strains were resistant to NFLX.

A case of a 5-year-old boy who fulfilled all the criteria for Kawasaki disease (KD) was described. He had associated bilateral coronary artery aneurysms. Our study revealed the isolation of Yersinia pseudotuberculosis in stool cultures, and the elevation and seroconversion of the agglutination antibody titres, and hence he was diagnosed as Y. pseudotuberculosis infection-positive. We also demonstrated the positive mitogenic activity of the culture supernatant of the isolated bacterium from the patient and detected Y. pseudotuberculosis-derived mitogen by PCR. This case therefore suggests that Y. pseudotuberculosis might be closely related to the cause of KD.

The localized electronic density of states gL(E) at the hydrogenated amorphous silicon/silicon nitride (a‐Si:H/Si3N4) interfaces is evaluated by transient voltage spectroscopy (TVS). The gL(E) at the a‐Si:H/Si3N4 interface is found to have a broad peak and a deep minimum, respectively, around 0.9 and 0.47 eV below the conduction‐band edge. The positive fixed charge at the interface makes the flatband voltage of the a‐Si:H/Si3N4 system negative and, hence, there is a finite band bending at the interface even at the gate bias of 0 V. The gL(E) of different samples fabricated under various preparation conditions varies from sample to sample, whereas threshold voltages of a‐Si:H thin‐film transistors are almost independent of their preparation, suggesting the presence of an equilibrium mechanism between the positive fixed charge and the defect density. A modification of gL(E) at a‐Si:H/Si3N4 interfaces by bias annealing is definitely observed using TVS. The overall results obtained by TVS seem to support the ...

The contact pressure on 112 normal hip joints and 66 acetabular dysplastic hip joints was analysed using a three-dimensional rigid body spring model. Geometric models were made from conventional anteroposterior radiographs, with the assumption that the acetabular surface was spherical. In normal hips, the distribution of contact pressure was almost even over the joint surface, and the maximum contact pressure was relatively low. However, in a dysplastic hip joint, the pressure was concentrated on the anterolateral edge of the acetabulum and increased enormously not only with the reduction in lateral coverage but also with the reduction in the anterior coverage of the acetabulum. This result indicates that a three-dimensional analysis is indispensable for estimating the mechanical effect on acetabular cartilage.

Castrate resistant prostate cancer (CRPC) is a disease that is resistant to both hormone therapy and chemotherapy. At present, no curative therapy for CRPC has been established. Therefore, it is necessary to determine a novel molecular target for the development of therapeutic agents. We previously reported that AlkB homolog 3 (ALKBH3) is highly expressed in prostate cancer but not in benign prostatic hyperplasia or in normal prostate epithelium and that the expression levels of ALKBH3 protein are significantly correlated with the hormone-independent state of prostate cancer. Moreover, ALKBH3 regulates the invasion of prostate cancer cells via the regulation of matrix metalloproteinase 9. Here, we show that ALKBH3 gene silencing markedly induces apoptosis in hormone-independent prostate cancer cell line DU145 but not in the normal prostate epithelial cell line PNT2. Moreover, the in vivo tumorigenicity of DU145 cells was significantly inhibited by the administration of ALKBH3 siRNA. Furthermore, the anchorage-independent growth of DU145 cells was inhibited by ALKBH3 knockdown and promoted by ALKBH3 overexpression, significantly. ALKBH3 shRNA-expressing prostate cancer cells formed significantly smaller tumors than those of control shRNA transfectants in an in vivo xenograft model. These findings suggest that ALKBH3 is a promising target molecule for the development of CRPC therapeutic agents.

The Rhodococcus erythropolis strain KA2-5-1 was characterized by its ability to cleave carbon-sulfur bonds in the dibenzothiophene (DBT) ring by asymmetrically alkyl substitution, such as C2-DBTs (e.g., dimethyl and ethyl DBTs) and C3-DBTs (e.g., trimethyl and propyl DBTs), which are known to remain in hydrodesulfurization-treated diesel fuels. After treatment by solid-phase extraction (SPE) of solvents from microbial reactions of alkylated DBTs (Cx-DBTs), we used gas chromatography (GC), GC-atomic emission detection, GC-mass spectrometry and 1H nuclear magnetic resonance spectroscopy to identify and quantitatively evaluate the Cx-DBT metabolites. Molar ratios of metabolic isomers of the desulfurization products suggested that resting-cell reactions of KA2-5-1 against these Cx-DBTs occurrs through specific carbon-sulfur-bond-targeted cleavages, yielding alkylated hydroxybiphenyls, and that the manner of the attack on the DBT skeleton is affected not only by the position but also by the number and length of the alkyl substituents.

Cristallisation dans C2 avec a=13,769, b=5,079, c=12,403 A, β=107,25°, Z=2; affinement jusqu'a R=0,047. La structure contient des reseaux tridimensionnels de SiO 4 comportant des anneaux a huit, dix et douze chainons, de tetraedres de SiO 4 avec trois types des atomes O non lies. Les atomes de Zn ont une coordination tetraedrique et sont connectes aux atomes O non lies, formant ainsi des chaines en zigzag de ZnO 4 suivant des axes doubles d'ordre deux. Ce nouveau type de silicate selon la classification Liebau a l'expression: K 2 Zn 2 {oB, 3 ∞ }[ 6 Si 8 O 19 ]. Les atomes de K ont les neuf voisins les plus proches constitues par des atomes O et sont situes dans les cavites de squelettes de Si, Zn et O

Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury.Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI.Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI.Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection.

Opioids are commonly administered to critically ill neonates and infants for general anaesthesia and sedation. However, the clinical safety of these drugs, especially the effects on hypoxic-ischaemic damage of the developing brain, has not been well investigated. The present study was therefore conducted to investigate the effects of continuous morphine infusion on brain damage after hypoxic-ischaemic insults in neonatal rats.Seven-day-old Sprague-Dawley rats were subjected to left common carotid artery ligation followed by a 90-min exposure of 8% oxygen. The rats were administered morphine (0.1, 0.3 or 1 mg/kg/h) or saline continuously for 72 h using osmotic minipumps. Seven days later, the rats were weighed and their brains were morphologically categorized into groups based on the following grades: 0=normal, 1=mild atrophy, 2=moderate atrophy, 3=atrophy with cystic cavitation3 mm and 4=cystic cavitation3 mm. For histological assessment, the ratio of the surviving neurons (ipsilateral/contralateral) was calculated in the cornu ammonis fields, CA1 and CA3, and the dentate gyrus (DG).One week after recovery (P14), the rats in the 1 mg/kg/h group showed significantly poorer weight gain compared with the other groups. However, the morphological score of the brains and the ratio of the surviving neurons in the CA1, CA3 and DG were similar among the groups.Our results indicate that continuous administration of morphine does not worsen brain damage 7 days after hypoxic-ischaemic insults in neonatal rats.

Summary B6C3F1 mice of both sexes that had been exposed transplacentally on day 18 of gestation to 0.5mmole N-nitrosoethylurea (NEU) were fed either normal diets or diets containing di(2-ethylhexyl)phthalate (DEHP) at 6,000ppm beginning at 6 wk of age and continuing to 78 wk of age. At 52 and 78 wk of age, 6–26 mice from each group received a single injection of 5-bromo-2'-deoxyuridine (Brdu) at 200mg/kg i.p. and were sacrificed 1 h later for determination of the levels of renal and hepatic DNA synthesis by the Brdu immunohistochemical technique. No differences occurred in incidences of gross or microscopic renal tubular cell tumors between the NEU (males 15 %, females 21 %) and NEU-DEHP groups (males 10%, females 15 %) at 78 wk. The labelling index (LI) of renal cortical tubular cells was significantly increased at 78 wk (22.3±3.7/mm 2 for males, 21.8 ± 1.2 for females) in mice given NEU and DEHP as compared with NEU alone (9.7 ± 1.0 for males, 6.9 ±0.7 for females). The number and sizes of focal hepatocellular proliferative lesions (FHPL), including hyperplastic foci, hepatocellular adenomas and carcinomas, were quantified by image analysis and stereology. DEHP significantly enhanced the mean volume and volume % of FHPL, including liver tumors, but not numbers of FHPL/liver. Hepatocyte LI was also not affected, at least as detected by the technique used, while FHPL had significantly increased LI (14.5–48.3) as compared with normal hepatocytes (0.5–2.4). This study provides some evidence that enhanced chronic cell replication in the kidney may not always be associated with renal carcinogenesis of tumor promotion, while tumor promotion in liver may be a consequence of increased DNA synthesis in initiated or focus cells rather than in nonproliferative parenchymal hepatocytes, which may not be target cells of some tumor promoters.

Gliomas, the most frequent tumors originating in the human nervous system, are divided into various subtypes. Currently, microscopic examination alone is insufficient for classification and grading so that genetic profiles are increasingly being emphasized in recognition of the emerging role of molecular diagnostic approaches to glioma classification. Glioblastomas (WHO grade IV) may develop de novo (primary glioblastomas) or through progression from lower-grade astrocytomas (secondary glioblastomas), while both glioblastomas show similar histological features. In contrast, they do constitute distinct disease entities that evolve through different genetic pathways, and are likely to differ in prognosis and response to therapy. Oligodendrogliomas (WHO grade II) account for 2.7% of brain tumors and 5-18% of all gliomas. Since this tumor is recognized as a particular subtype of glioma that shows remarkable responses to chemotherapy, a correct diagnosis is of prime importance. The difficulty is that histological differentiation of oligodendrogliomas from diffuse astrocytomas is highly subjective in cases without typical morphological features and there is a lack of reliable immunohistochemical markers. While histological distinction of low-grade gliomas from reactive astrocytes is also often difficult, reactive astrocytes usually lack genetic alterations. More biological and molecular approaches to glioma classification thus appear warranted to provide improved means to achieve correct diagnoses.

Mitogen activated protein (MAP) kinases are well known serine threonine kinases that modulate gene expression, mitosis, cell proliferation and programmed cell death or 'apoptosis' in response to various stresses. Extracellular stress regulated kinase (ERK), c-jun NH2 terminal kinase and p38 are major members of the MAP kinases, and there is now a body of evidence of their involvement in genesis or sensitivity to chemotherapy of human prostate cancers. In this review, we focus on the molecular roles of MAP kinases and their pathological correlations, with particular attention to novel downstream signals through phosphorylation of the Fas-associated death domain protein that effectively regulates not only apoptosis but also the cell cycle in prostate neoplastic cells.

Multi-component GPR system is developed. It is a part of integrated electromagnetic survey system. The GPR system has four antennas and is able to measure with four antenna patterns. Two field tests are conducted. First test was conducted to analyze the effect of angles between target, steel pipes, and survey line with two directional parallel antennas. Hyperbolic shapes of reflections in data differ by the angles, 0, 30, 60 and 90 degree. Two parallel antennas compensate each result at any survey direction. Summation of two pair of antenna improved the results. Second field was conducted to evaluate the multi-component migration. It is not big different for angle 0 configuration. However two component migration improved the image for angled configuration.

Impurity back diffusion through a UHV pump in reduced-gas-processing chambers has been experimentally studied. A large throughput of process gases severely degrades the main UHV pump capability in dragging impurities, resulting in the back diffusion of impurities to the processing chamber. Such degradation is greatly influenced by the pumping speed of the backing pump. However, we have found for the first time that the impurity level in the chamber can be made even lower than that for the best performance under UHV when the gas flow rate is optimized for the system. The scenario to the gas pumping system optimization is presented.

Seven prepubertal short children with congenital heart disease were treated with recombinant human growth hormone (GH). Although complete surgical correction was performed for their heart disease at least 2 years before the start of GH therapy, improvement in growth was less than expected in these children. They received 0.5 IU kg-1 week-1 of GH daily for 2 years or more. The growth rate increased from a mean of 4.3 cm year-1 before treatment to a mean of 7.8 cm year-1 in the first year and to a mean of 6.3 cm year-1 in the second year of treatment. Their mean standardized height improved from -3.41 +/- 0.78 to -2.54 +/- 0.62 after 2 years. The mean height age difference minus the bone age difference became positive in these children. We conclude that recombinant GH increases the growth rate in children with congenital heart disease and prepubertal growth retardation.

A Cu/low-k dual-damascene process using a novel dissoluble hardmask material, AlO, is developed to suppress ashing-damage to porous/nonporous low-k SiOC. In this process, ArF-resist patterns are firstly transferred to a very thin, typically 30-nm-thick, AlO hardmask layer. After removing the resist, SiOC is patterned using the hardmask. The hardmask remaining after the etching is spontaneously removed during post-etch wet-cleaning. The line-to-line capacitance of 280-nm-pitch, 4-level interconnects using this process is reduced by 10% from that using a conventional resist-mask process.

A novel self-aligned air-gap interconnect process with Cu/FSG structure was proposed. The key feature is the use of an easily removal sacrifice film by dry-etching process with a reducing gas. This process consists of a conventional Cu damascene process with 130 nm node CMOS technology. In this study, a 2 level Cu interconnect was fabricated and the effective dielectric constant of 2.3/spl sim/2.6 has been successfully achieved. These are consistent with the capacitance reduction by 37/spl sim/41% compared with a conventional Cu/FSG structure.

Recent increases in the incidence of primary central nervous system lymphoma (PCNSL), a rare non-Hodgkin's lymphoma arising in the brain, have been noted in both immunodeficient and immunocompetent patients. Compared with lymphomas originating outside the central nervous system, the biology of PCNSL at the molecular or cytogenetic level has not been well characterized, yet it is important to thoroughly understand the etiology of this rare malignant lymphoma if effective therapies are to be developed. This review will focus on the epidemiology, clinical aspects, histopathology, pathogenesis, and molecular genetics of this aggressive, extranodal lymphoma in immunocompetent patients.

Abrasive free polishing (AFP) for 0.13 /spl mu/m node copper damascene interconnects was improved. A CMP process using a modified groove pad design to provide optimized polishing friction force can reduce a metal loss of 20% on Cu wiring, compared to the conventional AFP process. We demonstrated meeting the planarity target for a 0.1 /spl mu/m technology node without extra intermediate oxide polishes.

We developed 0.5 /spl mu/m-pitch Cu-dual-damascene metallization by using very low-k organic SOG (HSG-R7; Hitachi Chemical Co., k=2.9) as the ILD. Interconnects using HSG reduced the interconnect capacitance by 30% compared to that of interconnects using TEOS. Furthermore, the electrical characteristics, such as line and via resistances, show that the HSG-ILD combination is feasible for 0.18-/spl mu/m CMOS applications.

The aim of this study was to evaluate the effect of fluoride-releasing adhesive systems on human decalcified dentin in vitro. Two fluoride-releasing adhesive systems, Reactmer bond (RB, Shofu) and ABF (AF, Kuraray), an experimental system, and a commercial adhesive system without fluoride release, SE bond (SE, Kuraray), were used in this study. The amount of fluoride release from adhesive in deionized water was measured every week for 10 weeks. Class V cavities were prepared on extracted human pre-molars and decalcified dentin was promoted by using a bacterial caries induction system at the cavity floor. The cavities preserving decalcified dentin were restored with resin composite (AP-X, Kuraray) after treatment by each adhesive system. The specimens without treatment by adhesive system and restoration were used for control. The specimens with restoration were then incubated for 4 weeks at 37 degrees C, 100% humidity. Microradiographs of the specimens showed that the radiopacities of the decalcified dentin layers in RB and AF groups with fluoride release were significantly higher than those in SE or control groups without fluoride release. This result suggested that the fluoride-releasing adhesive systems enhanced mineralization of decalcified dentin.

Two versions of the Laser Flowgraphy system are presented in this paper-one version analyzes the bloodstream of the human retina and the other version visualizes the microcirculation map of skin tissue and the gums. The retina is illuminated with a diode laser spot through a retinal camera and the speckle field at the image plane of the spot is scanned by an area sensor. A hardware logic circuit board is used to evaluate the average derivative (AD) or square blur rate (SBR) of the intensity variation at each pixel point. The results are displayed successively on 2-D color maps at a rate of 16 frames/second which allows real-time observation of retinal blood flow. Similarly, the blood flow of the gum is analyzed by scanning the laser line spot across the gum tissue and the spot is imaged onto the line sensor. The blood flow map is obtained for the region of 50/spl times/50 mm in a few seconds with 200/spl times/200 resolution.

We propose a 1-wavelength loop type dielectric chip antenna that meets the demand for antennas with unidirectional radiation patterns for portable communication devices. The structure of the proposed antenna is shown. The radiating element printed loop is on the top of the cube. A feeding strip line is on one of the vertical face of the cube and a shorted plate parallel to the feeding strip line is on the same face. The conductive plane is on the bottom of the cube. By printing all of conductive elements on a ceramic cube this novel antenna is easy to fabricate.

The float buoy ranging system consists of a vessel-mounted pinger, three surveying float buoys which receive the pinger signal and the receiving station on the testing ship. The antenna of the receiving station receives the radio signal for the underwater vehicle's position from three surveying float buoys. At the same time it receives the radio signals for three float buoy's position an the surface of the sea from four GPS satellites. The surveying float buoy processing system in the receiving station tracks down the running locus of the underwater vehicle as the X-Y co-ordinates from the values of the latitude and the longitude. Further, it is possible to carry out the float buoy ranging system's calibration to determine the float buoy position at any time.

Objective: Dentin structure varies with orientation and location. Ultimate shear strength (USS) has also been found in previous studies to vary with location. The present study further explores this relationship between USS and various locations in coronal dentin as well as distance from the pulp. Methods: Stick specimens were prepared from coronal dentin located in the center or under cusps of human molar teeth. These were tested in the shear mode at various distances from the pulp. Results: Median values ranged from 52.7 (range 29.0–73.1) MPa near the pulp to 76.7 (range 53.9–104.0) MPa near the dentino–enamel junction. No differences were found among the buccal, central or lingual locations, however, the USS near the pulp was found to be significantly lower. Significance: The properties of coronal dentin vary with distance from the pulp, which may affect adhesion and other aspects of restorative dentistry.