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BackgroundGenome-wide association studies (GWASs) have identified 29 disease-associated single nucleotide polymorphisms (SNPs) for systemic sclerosis (SSc) in non-human leukocyte antigen (HLA) regions (1-7). While these GWASs have clarified genetic architectures of SSc, study subjects were mainly Caucasians limiting application of the findings to Asians.ObjectivesThe study was conducted to identify novel causal variants for SSc specific to Japanese subjects as well as those shared with European population. We also aimed to clarify mechanistic effects of the variants on pathogenesis of SSc.MethodsA total of 114,108 subjects comprising 1,499 cases and 112,609 controls were enrolled in the two-staged study leading to the ever-largest Asian GWAS for SSc. After applying a strict quality control both for genotype and samples, imputation was conducted using the reference panel of the phase 3v5 1,000 genome project data combined with a high-depth whole-genome sequence data of 3,256 Japanese subjects. We conducted logistic regression analyses and also combined the Japanese GWAS results with those of Europeans (6) by an inverse-variance fixed-effect model. Polygenicity and enrichment of functional annotations were evaluated by linkage disequilibrium score regression (LDSC), Haploreg and IMPACT programs. We also constructed polygenic risk score (PRS) to predict SSc development.ResultsWe identified three (FCRLA-FCGR, TNFAIP3, PLD4) and four (EOMES, ESR1, SLC12A5, TPI1P2) novel loci in Japanese GWAS and a trans-population meta-analysis, respectively. One of Japanese novel risk SNPs, rs6697139, located within FCGR gene clusters had a strong effect size (OR 2.05, P=4.9×10-11). We also found the complete LD variant, rs10917688, was positioned in cis-regulatory element and binding motif for an immunomodulatory transcription factor IRF8 in B cells, another genome-wide significant locus in our trans-ethnic meta-analysis and the previous European GWAS. Notably, the association of risk allele of rs10917688 was significant only in the presence of the risk allele of the IRF8. Intriguingly, rs10917688 was annotated as one enhancer-related histone marks, H3K4me1, in B cells, implying that FCGR gene(s) in B cells may play an important role in the pathogenesis of SSc. Furhtermore, significant heritability enrichment of active histone marks and a transcription factor C-Myc were found in B cells both in European and Japanese populations by LDSC and IMPACT, highlighting a possibility of a shared disease mechanism where abnormal B-cell activation may be one of the key drivers for the disease development. Finally, PRS using effects sizes of European GWAS moderately fit in the development of Japanese SSc (AUC 0.593), paving a path to personalized medicine for SSc.ConclusionOur study identified seven novel susceptibility loci in SSc. Downstream analyses highlighted a novel disease mechanism of SSc where an interactive role of FCGR gene(s) and IRF8 may accelerate the disease development and B cells may play a key role on the pathogenesis of SSc.References[1]F. C. Arnett et al. Ann Rheum Dis, 2010.[2]T. R. Radstake et al. Nat Genet, 2010.[3]Y. Allanore et al. PLoS Genet, 2011.[4]O. Gorlova et al. PLoS Genet, 2011.[5]C. Terao et al. Ann Rheum Dis, 2017.[6]E. López-Isac et al. Nat Commun, 2019.[7]W. Pu et al. J Invest Dermatol, 2021.Disclosure of InterestsNone declared

BackgroundThe morbidity of scleroderma renal crisis (SRC) and autoantibodies in systemic sclerosis (SSc) vary by races and regions. Anti-RNA polymerase III is associated with SRC in America and European countries. However, the association of autoantibodies with SRC had not been elucidated in Japan.ObjectivesWe aimed to investigate the association of autoantibodies with morbidity and mortality of SRC in Japan.MethodsThe clinical characteristics and mortality of 330 patients with systemic sclerosis (SSc) at Kyoto University Hospital were retrospectively analyzed, focusing on anti-centromere, anti-RNA polymerase III, anti-topoisomerase I, and anti-U1-RNP. Logistic regression analyses were performed to examine the association of autoantibodies with the development and mortality of SRC. Kaplan-Meier survival analysis was performed comparing the groups classified by autoantibodies.ResultsAnti-centromere (n = 177/318, 56%), anti-topoisomerase I (n = 80/311, 26%), anti-RNA polymerase III (n = 27/204, 13%), and anti-U1-RNP (n = 24/305, 8%) were found in SSc patients (n = 330). SRC was observed in 24 out of 330 SSc patients, including anti-topoisomerase I (n = 12/24, 50%), anti-RNA polymerase III (n = 7/24, 29%), anti-U1-RNP (n = 5/24, 21%), and anti-centromere (n = 3/24, 13%). Anti-U1-RNP (odds ratio [95% confidence interval], 3.63 [1.11–10.2]), anti-RNA polymerase III (3.29 [1.16–8.70]), and anti-topoisomerase I (3.22 [1.37–7.57]) were associated with the development of SRC. All patients with SRC were treated with ACE inhibitors and the 1-year survival rate was 54%. Anti-topoisomerase I was associated with the 1-year mortality of SRC (6.00 [1.11–41.1]). When the survival rate was compared between the patients positive for anti-topoisomerase I (n=12) and negative for anti-topoisomerase I (n=12), the 1-year survival rate was 33% vs 75% (p=0.041), respectively (Figure 1A). Furthermore, the 1-year survival of anti-centromere (100%), anti-RNA polymerase III (83%), and others/not detected (50%) were shown in patients negative for anti-topoisomerase I (Figure 1B).Figure 1.Overall survival of patients with SRC according to the type of autoantibodies.(A) The survival rates in SRC patients who were positive for anti-topoisomerase I (solid line, n = 12) and those who were negative for anti-topoisomerase I (dotted line, n = 12).(B) SRC patients negative for anti-topoisomerase I were classified as patients with anti-RNA polymerase III (dotted line, n = 6), anti-centromere (broken line, n = 2), and others/not detected (chain line, n = 4).ConclusionSpecific SSc-related autoantibodies were associated with the morbidity and mortality in SRC.References[1]Nihtyanova SI, et al. Arthritis Rheumatol 2020;72(3):465-76.[2]Hamaguchi Y, et al. Arthritis Rheumatol 2015;67(4):1045-52.Table 1.Univariate logistic regression analysis for mortality in SRC (n = 24).VariablesOdds ratio (95% CI)P valueAge1.07 (0.99, 1.16)0.08Female sex3.00 (0.32, 66.6)0.38Diffuse/limited (diffuse %)0.25 (0.04, 1.36)0.12BMI0.67 (0.41, 0.93)0.049Modified Rodnan skin score0.95 (0.88, 1.02)0.15Digital ulcer0.52 (0.10, 2.63)0.43Reflux esophagitis0.60 (0.02, 17.1)0.73Pulmonary hypertension7.50 (1.17, 69.2)0.046Pleural effusion7.20 (1.23, 62.0)0.04Glucocorticoid use3.86 (0.65, 32.4)0.16Hemoglobin0.55 (0.25, 1.01)0.09Platelet1.00 (0.98, 1.01)0.44Total protein0.17 (0.02, 0.69)0.04Creatinine0.95 (0.67, 1.24)0.69CRP0.90 (0.67, 1.17)0.46Anti-topoisomerase I6.00 (1.11, 41.1)0.048Anti-centromere7.4x10-9 (--, 0.93)1.00Anti-RNA polymerase III0.36 (0.04, 2.18)0.29Anti-U1-RNP0.74 (0.08, 5.49)0.77Disclosure of InterestsNone declared

BackgroundRapid glucocorticoid (GC) tapering is recommended for lupus nephritis (LN) by 2019 EULAR/ERA-EDTA recommendations [1]. However, slower conventional GC tapering regimen is still common in the real world setting, and it is controversial whether a rapid GC tapering regimen is as effective as the conventional regimen.ObjectivesWe aimed to compare the renal outcomes between rapid and slower GC tapering regimens in patients with LN.MethodsWe retrospectively surveyed the medical records of 27 patients with proliferative LN (class Ⅲ or Ⅳ) at Kobe City Medical Center General Hospital. These patients were divided into two groups (rapid GC tapering group and conventional GC tapering group) according to GC dosage at month 6. Logistic regression analyses were performed to examine the association of GC tapering regimens with achievement of primary efficacy renal response (PERR) and complete renal response (CRR) which were defined by Furie et al. [2] at month 24.ResultsTwenty-seven patients (19 women and 8 men) with class Ⅲ or Ⅳ LN were included. The mean age was 43 years. The mean eGFR and urine protein-to-creatinine ratio at baseline were 66.7 mL/min/1.73m2 and 3.125 g/gCr, respectively. Concomitant class Ⅴ LN was present in 26.0%. The rapid GC tapering group (PSL≦10 mg/day at month 6) and the conventional GC tapering group (PSL>10 mg/day at month 6) were 11 and 16 patients, respectively. Baseline characteristics were balanced between the two groups except for use of cyclophosphamide or mycophenolate mofetil. Mean urine protein-to-creatinine ratio at month 24 were 0.46 g/gCr in the rapid GC tapering regimen group and 1.08 g/gCr in the conventional GC tapering regimen group (p=0.790). Achievements of PERR and CRR at month 24 were 54.0% and 43.8% in the rapid GC tapering group and 54.5% and 25.0% in the conventional GC tapering group, respectively. After adjustment of cyclophosphamide or mycophenolate mofetil usage and urine protein-to-creatinine ratio at baseline, adjusted odds ratio was 1.52 (95% confidence interval [0.126 to 18.29], p=0.743) and 2.99 (95% confidence interval [0.34 to 28.52], p=0.341), respectively.ConclusionOur results suggest rapid GC tapering regimen is as effective as conventional slower tapering regimen for patients with proliferative LN.References[1]Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;79:713–723.[2]Furie R, Rovin BH, Houssiau F, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med 2020;383:1117–1128.Table 1.Baseline patients characteristics.Rapid GC tapering group(n=11)Conventional GC tapering group(n=16)P valueAge – years41.7 ± 14.743.9 ± 16.20.863Female – no. (%)9 (81.8)10 (62.5)0.405Class Ⅲ LN – no. (%)6 (54.5)7 (43.8)0.704Class Ⅳ LN – no. (%)6 (45.5)9 (56.3)0.704Concomitant Class Ⅴ LN – no. (%)4 (36.4)3 (18.8)0.391Induction therapy (use of CY or MMF) – no. (%)10 (90.9)8 (50.0)0.042Serum creatinine – mg/dL1.15 ± 0.721.14 ± 0.800.882eGFR – mL/min/1.73m265.2 ± 39.067.8 ± 34.50.835UPCR – g/gCr3.29 ± 2.963.01 ± 3.250.604C3 – mg/dL41.1 ± 20.145.0 ± 21.50.639C4 – mg/dL6.8 ± 4.710.1 ± 8.00.346GC, glucocorticoid; LN, lupus nephritis; UPCR, urine protein-to-creatinine ratio; CY, cyclophosphamide; MMF, mycophenolate mofetilDisclosure of InterestsNone declared

Supplemental Material for Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus by K Kitagori, H Yoshifuji, T Oku, T Ayaki, A Kuzuya, T Nakajima, S Akizuki, R Nakashima, K Murakami, K Ohmura, Y Hirayama, R Takahashi and T Mimori in Lupus

Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B , IL6 , IL10 , TNFA , IL1RN , SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN , the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls ( p =0.0067), and A allele at rs4251981 in 5′ upstream of IL1RN with borderline significance (p =0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40–10.8, p =0.0057). For SCN1A , no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A , the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance ( p =0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

Percentage finger systolic blood pressure (%FSBP) in response to finger cooling is used to assess vascular components of the hand-arm vibration syndrome and the measurement method is under discussion for standardization. It has been suggested that measurement circumstances including room temperature may affect %FSBP. We investigated the effect of room temperature on %FSBP response to finger cooling in healthy subjects. Six healthy male subjects who were medical students volunteered for the study. Multi-channel plethysmograph was used for simultaneous multi-finger FSBP measurements. The examination room was kept at 21 +/- 1 degrees C and 25 +/- 1 degrees C, and the subjects were randomly assigned. Percentage finger systolic blood pressures for the index, middle, ring and little fingers at 15 degrees C and 10 degrees C cuff-water temperatures were calculated. Four-way analysis of variance was performed to determine the independent effect of subject, room temperature, finger and cuff-water temperature factors on %FSBP. The room temperature as an independent factor affecting %FSBP was statistically significant (P0.01). From the results, it can be concluded that %FSBP response to finger cooling in healthy subjects may be affected by room temperature. Therefore, room temperature is expected to be controlled when assessing peripheral vascular components of the upper extremities using %FSBP response to finger cooling.

Adsorption kinetics of Sb onto the Si(1 1 1) surface has been modified by incorporation of a Si(1 1 1)–In(√3×√3) surface phase (θ In = 1 3 ML) . In contrast to Sb adsorption on the clean Si surface, the formation of Sb nano-size clusters with good crystalline quality was observed below ≈200°C. Hemispherical clusters grow up to the saturation coverage of about 3 ML and stabilize in the average diameter and height of 40 and 5 nm, respectively, occupying approximately 15% of the surface (cluster density is estimated at 1.2×10 10 clusters/cm 2 ). The structure of clusters is determined to be a double-domain rhombohedral with (0 0 0 1) stacking. Both structure and lattice parameters of the clusters coincide with those of bulk Sb. The inter-cluster surface is covered with a Sb(2×1) surface phase ( θ Sb =1 ML). Using reflection high-energy electron diffraction and scanning tunneling microscopy techniques it has been found that indium acts as a surfactant providing layer-by-layer growth of Sb clusters. By increasing the coverage of initial In layer, the higher cluster density can been achieved.

We investigated the hemopoietic progenitors in fetal liver (FL) compared with those in adult bone marrow (BM) for their ability to differentiate into T, B, and myeloid cells. Lineage marker-negative (Lin-) c-kit+ cells isolated from FL and BM were used as the source of progenitors. No apparent difference was observed between FL and BM progenitors in their ability to generate B and myeloid cells when these progenitors were cultured on a monolayer of a BM-derived stromal cell line. In marked contrast, FL progenitors were able to generate T cells much more rapidly than BM progenitors in both in vivo intrathymic cell transfer and fetal thymus organ culture systems. The same type of FL progenitors were also found in the FL of congenitally athymic nu/nu mice, indicating that these progenitors arise in FL independently of the fetal thymus. The present study have provided circumstantial evidence suggesting the presence of T cell lineage-committed progenitors in FL.

In order to improve the efficiency of automobile engines and to reduce their weight, there is a move toward the use of conventional stainless steel sheets and pipes for exhaust manifolds to replace cast iron, the traditional material for this application. The exhaust manifold is used in an environment that includes engine vibrations as well as heating and cooling cycles caused by the travel pattern. Therefore, among high-temperature characteristics, thermal fatigue resistance is an important one that affects the life span of an exhaust manifold. Generally, austenitic steels have higher strength at high temperature than ferritic steels. However, type 304, a typical austenitic stainless steel, has less thermal fatigue resistance than type 430, a typical ferritic stainless steel. This is because austenitic steels have higher coefficient of thermal expansion than ferritic steels. Therefore, to obtain a material with excellent thermal fatigue resistance, it would conceivably be best to attempt to increase the high temperature strength of ferritic stainless steels. The present study centered on improvement of the high-temperature proof strength of ferritic stainless steels. The mechanism of high temperature strengthening by Nb addition, which was shown to be one of the most effective methods to improve proof strength at highmore » temperature, was discussed.« less

To simulate the field for the actual scale explosion experiments is sometimes very difficult. From the reasons of safety-space, schedules, and human factor the number of actual field explosion experiments has been strictly limited. Therefore a small scale shock wave generator is considered to be very useful for experimentally simulating the explosion phenomena[1]. This study deals with the blast effects by using laser -induced micro shock wave. A plasma and a shock wave, which generated by a focusing pulsed CO2 laser beam into a two-dimensional acrylic resin structure model by a cylindrical lens, have been visualized by the schlieren method. Moreover, the numerical simulation for compressible and inviscid flow with thermal equilibrium has been conducted to clarify the propagation characteristics of the laser induced shock wave.

A novel type of PLZT light valve fabricated by a green sheet process has been developed, and a prototype image projector incorporating this light valve was investigated. A PLZT matrix with internal electrodes was fabricated by a tape casting technique, and the feasibility of high definition was verified. The light valve exhibits no crosstalk-related problems, is easy to fabricate, and has a high-response speed. >

We report a case of remnant cystic duct carcinoma with widespread invasion along the common bile duct wall. Thin-slice dynamic computed tomography showed circumferential wall thickening of the extrahepatic bile duct (from the common hepatic duct to the intrapancreatic common bile duct) and the remnant cystic duct. Pathologically, the extrahepatic bile duct wall was thickened due to submucosal tumor infiltration by cystic duct papillary adenocarcinoma.

Coxl7p was first cloned as a cytoplasmic copper chaperone from yeast mutant and recent works suggested the existence of mammalian homologues. Previous report has shown that a gel filtration fraction of heart extract containing porcine Coxl7p peptide promoted the survival of NIH3T3 fibroblast cells. In the present study, we first cloned DNA fragments of the mouse COX17 gene. The mouse COX17 spans approximately 6kb and consists of three exons. It was mapped to the center of chromosome 16, using a radiation hybrid-mapping panel. The major transcription start site is 80 bp upstream of the ATG initiation codon as determined by rapid amplification of cDNA ends (5'-RACE) analysis. Two potential polyadenylation sites are 3233 and 3293 bp downstream of the termination codon, respectively. Transient transfection of reporter plasmids containing portions of the mouse COX17 5'-flanking region into AtT-20 and NIH3T3 cells allowed the localization of the essential promoter to a 0.8 kb region upstream of the transcription starting site. Furthermore, the transfected luciferase activity was much higher in AtT-20 than NIH3T3. According to sequence analysis of the approximately 0.8kb 5'-flanking region, GC rich segments including consensus sequences for binding of the transcription factor Sp1, but no TATA/CAAT boxes, exist in the region of the transcription start site. Besides the GC box, binding sites for NRF-1 and 2 known as specific transcription factors for COX subunits are also localized around the transcription starting site.

Aims This study was performed to determine whether or not the kinetics of action potential duration restitution during double premature stimuli (S3 )d iffer from that during single premature stimuli (S2) in the human intact right ventricle. Methods and Results A monophasic action potential (MAP) was simultaneously recorded from the right ventricular apex (RVA) and outflow tract (RVOT) during programmed ventricular pacing in 11 patients with symptomatic bradyarrhythmias (five males, six females, mean age 58 years). In the five most recent patients, the RV pressure and its dp/dt were also obtained during the protocol. A substantial difference in the restitution of the MAP duration (MAPD) between S2 and S3 was observed at short diastolic intervals (

We investigated the developmental potential of hemopoietic progenitors in the aorta-gonad-mesonephros (AGM) region, where the definitive type hemopoietic progenitors have been shown to emerge before the fetal liver develops. By using an assay system that is able to determine the developmental potential of individual progenitors toward the T, B, and myeloid lineages, we show that not only multipotent progenitors but also progenitors committed to the T, B, or myeloid lineage already exist in this region of day 10 fetuses. Bipotent progenitors generating myeloid and T cells or those generating myeloid and B cells were also detected, suggesting that the commitment to T and B cell lineages is in progress in the AGM region. The numbers of these progenitors, however, were only 1/200-1/1000 of those in fetal liver of day 12 fetuses. Such small numbers of progenitors suggest that hemopoiesis has just started in the AGM region of day 10 fetuses. Although most of T cell lineage-committed progenitors in the AGM region generated only a small number of immature T cells, some were able to generate a large number of mature T cells. The detection of various types of lineage-committed progenitors strongly suggests that the AGM region is not only the site of stem cell emergence, but also the site of hemopoiesis, including lineage commitment. The T cell progenitors found in the AGM region may represent the first immigrants to the thymus anlage.

To investigate the cellular communication in the liver, nitric oxide (NO) production by sinusoidal cells and hepatocytes by stimulation with cytokines and Kupffer cell-conditioned medium was quantitatively analyzed. NO production by the cells was measured by the Griess reaction, and nitric oxide synthase (iNOS) transcription level by a competitive RT-PCR assay using mutant iNOS mRNA as a standard. NO production and iNOS mRNA transcriptional levels in Kupffer cells were markedly increased by stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), and moderately by interleukin-1beta (IL-1beta). NO production by hepatocytes was not significantly enhanced by LPS, but was markedly enhanced by IL-1beta or the combination of tumor-necrosis factor-alpha (TNF-alpha) and IFN-gamma. Hepatocyte NO production and iNOS mRNA levels were markedly enhanced by the LPS-activated Kupffer cell conditioned medium, but these effects were reduced by heat treatment or anti-TNF antibody. Although NG-monomethyl-L-arginine acetate and dexamethasone reduced NO production by the cells, the iNOS mRNA level was reduced by dexamethasone only. Gel-shift assay showed NF-kappaB activation in hepatocytes during this activation. These data reinforce the importance of cellular communication between sinusoidal cells and hepatocytes.

In this study, we introduce a novel research methodology, the evaluation of mRNA expression of cells contacting with polymeric materials using reverse transcription-polymerase chain reaction (RT-PCR) analysis HL-60 was used as a model of the macrophages. The expression of interleukin-1 beta (IL-1 beta) mRNA, a cytokine secreted by macrophages, was selected to estimate the extent of inflammation. The expression of IL-1 beta mRNA in the HL60 cells cultured on various substrates and in various conditions was studied. Expression of IL-1 beta could be successfully determined by RT-PCR analysis. A 48 h incubation period was necessary to clarify the expression of IL-1 beta mRNA. It became clear that lipopolysaccharide stimulation was not necessary in this analysis because of the high sensitivity of RT-PCR analysis. It is concluded that RT-PCR analysis is a powerful tool for studying cell-polymer interaction, and is a complementary method for ELISA.

A rare case of juvenile secretory carcinoma (SC) associated with juvenile papillomatosis (JP) is described. Tumor biopsy and fine needle aspiration cytology (FNAC) were performed in a 12-year-old girl who had noticed a painful right breast mass. One of the two types of tumor cells found on FNAC smears formed mainly sheets or clusters, intercellular spaces within the sheets and intracytoplasmic vacuolation. These cells, a few of which had a signet-ring cell appearance with completely disordered and randomly arranged nuclei, were considered to be SC cells. Cells of the other type were found in scattered papillary clusters and had well-defined cytoplasmic borders, uniform cell and nuclear size, and an orderly nuclear arrangement, suggesting a benign papillary lesion. Histologic examination of the tumor biopsy and breast quadrantectomy specimens revealed SC with JP. The cytologic, histologic and electron microscopic features of SC are described, and the relationship between SC and JP is discussed.

We experimentally observed the spatiotemporal velocity field of modulated waves (quasiperiodic mode) in a Couette-Taylor system for Reynolds number 9≤R/R c ≤28. A power spectrum averaged over four axial wavelengths showed clear evidence of the coexistence of two quasiperiodic modes for a wide range of Reynolds number and the first azimuthal wave mode disappeared at R/R c ≃18

To clarify the pathogenetic mechanisms in acute gastric lesions induced by vibration (VIB), the effects of VIB (3.0 G, 10 Hz, 90 min) on changes in gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA) as well as ulcer formation were compared with those of forced water immersion stress (FWI). While the VIB increased the GMBF during the exposure, the FWI decreased it during and after the stress. No difference in the severity of ulcer formation between the VIB groups was seen. Although both VIB and FWI increased the COR and CA, the degree of increased in the COR by the VIB tended to be less than that by the FWI. The truncal vagotomy inhibited the reduction of the GMBF and ulcer formation by the FWI, but promoted the reduction of the GMBF by the VIB. These results suggest that ulceration induced by VIB is caused primarily by its direct, mechanical and specific actions and not through the central nerve system.

To clarify their usefulness as markers for renal cell carcinoma, serum immunosuppressive acidic protein (IAP) and serum immunosuppressive substance (ISS) were evaluated by TIA (turbidometric immunoassay) for IAP and by SRID (single radial immunodiffusion) for ISS. The mean level of IAP and ISS was beyond each upper normal limit (500, 700 micrograms/ml) in every stage, and especially high in the M1 group. The levels of IAP and ISS were significantly correlated with each other. The determination of IAP and ISS levels after treatment showed a good correlation to the clinical course of the disease. The positive rates of IAP and ISS increased as the stages progressed, respectively. When the influences of pretreatment IAP and ISS level on survival period were investigated, the low IAP or ISS level group (less than two times of the upper normal limit) tended to have a better prognosis than the high level group (more than two times of the upper normal limit) in the M1 patients. These findings suggested that IAP and ISS could be used as markers for monitoring a disease and predicting the prognosis in patients with renal cell carcinoma. As for the positive rate in the combination assay for IAP, TPA and ferritin, or ISS, TPA and ferritin, more than 80% of the patients with low stage renal cell carcinoma had at least one positive marker. This suggested that the combination assay of these three markers was clinically valuable as a disease monitor in patients with renal cell carcinoma.

To evaluate the surrogate markers of non-A, non-B hepatitis virus (es) carriage state, the relationship between antibody to hepatitis C virus (HCV) and antibody to HBc/HBs and liver enzyme (ALT) was sought in Saitama prefecture. Out of 36,642 blood donor samples, 410 (1.1%) samples were positive for anti-HCV. Anti-HCV was found in 1.79% of donors with anti-HBs and/or anti-HBc, which is 1.7 fold of the frequency found in donors (1.04%) negative for anti-HBc/HBs. In contrast to the reports from Europe or USA, a poor correlation of anti-HCV with the serological history of hepatitis B infection was observed. These results indicate that hepatitis B and hepatitis C were transmitted independently in the Japanese, which is more homogeneous socioeconomically than the European or American populations. On the other hand, anti-HCV prevalence was in close correlation to ALT level as observed in the USA and in Europe. As we predicted previously, ALT can be expected to reduce the incidence of post-transfusion non-A, non-B hepatitis, however, anti-HBc can not.

Dehydrochlorination of stereoregurally chlorinatedpolyacetylene film was carried out by chemical and electrochemical methods. ER spectra showed that the chlorinated polyacetylene was almost converted to a carbynoid material characterized by IR spectra, while presence of conjugated polyene moiety in the product was confirmed by resonance Raman spectra, suggesting the product being a πconjugated polymer with carbyne and polyene structures. Effect of the orientation of polymer main chain by an uniaxial stretching is investigated by XRD and SEM, but alignment of carbynoid chains in the product could not be confirmed.

Reestablishment of gastrointestinal continuity following resection of pharyngoesophageal carcinoma can be a challenging problem. Recent developments in vascular surgery have made microvascular anastomosis possible and practical. At present free intestinal interposition grafts and revascularization of the proximal end of pedicle grafts offer the surgeon new options. From 1983 through 1989, reconstruction with vascular anastomosis was performed in 18 cases with pharyngoesophageal carcinoma. Patients were 47 to 88 years old, mean 62.1 years. Reconstructive methods included; free jejunal graft in 14, revascularization of proximal end of a pedicled gastric tube in 1, revascularization of proximal end of a pedicled jejunum in 1, interposition of free jejunal graft between a pedicled gastric tube and the pharynx in 1 and interposition of free ileal graft between a pedicled jejunum and the cervical esophagus in 1 case. Modified radical neck dissection was performed in all cases and superior mediastinal lymph node dissection with median sternotomy was added in 5. The internal jugular vein and common carotid artery were the donor vessels of choice, but in the case of severe sclerosis of the carotid artery, another cervical artery was chosen. The vascular anastomosis was performed using interrupted 7-0 Prolene sutures in the anterior wall and running 7-0 Prolene sutures in the posterior wall under 2.25 magnification. The patency of the anastomosed vessels was confirmed by Doppler flowmeter. The postoperative following-up periods ranged from 1 to 73 months with a mean of 16.5 months, and the survival rate was 66.2% at 1 year and 42.6% after 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to detect the influence on the growth and development of the maxillofacial cranium due to anterior crossbite in early childhood. The author observed the morphological changes of the maxillofacial cranium of rats in which of mandible was induced anterior crossbite artificially. Experimental animals used in this study were closed colony bred Wistar Crj rats. A total of 106 rats consisting of 65 in the experimental group and 41 in the control group were used. In the experiment, the appliance which was applied to the mandibular incisors of rats aged 30 days to induce anterior crossbite. X-ray photos of the head were taken in lateral and parietal at the age of 30, 60, 90 and 120 days and the soft X-ray photo of the right mandible isolated by sacrificing and decapitation of several animals at the respective ages. 1. The experimental rats have a tendency to lose weight in accordance with the appliance. The increase rate of weight in experimental group is similar to that in the control group and it was estimated that the appliance affected their weights a little. 2. The lateral cephalometric observation 1) The tip of the nasal bone was modified upwards in its position with advancing age. 2) In the mandibular angular region an inhibition of posterior growth was observed. 3) The dental arch length of maxilla was shorter and of mandibular was longer. 4) The molar changed its position upward, and the height of the upper facial region including the tooth and facial height had a lowering tendency. 3. The parietal cephalometric observation Parietal head X-ray photo showed a widening tendency of the width of anterior facial cranium and the anterior tip of zygomatic arch.

We diagnosed a 3-year-old boy as type C Niemann-Pick disease by studies on cultured fibroblasts; sphingomyelinase activity was almost normal, but esterification of exogenously administered cholesterol was deficient. Also sparse cultures of his fibroblasts developed a relatively intense fluorescence with filipin that was not observed either in normal or type B Niemann-Pick fibroblasts. We tried to treat him with dimethylsulfoxide (DMSO), 100 mg-120 mg/day for a year, but it had clinically insufficient effect on our case.

Acetylene derivatives were electrolyzed at + 1.5 V (vs. SCE) in the presence of copper (I) salt and N,N,N',N'-tetra-methylethylenediamine at 40 °C under an argon atmosphere. Phenylacetylene was oxidatively coupled to diphenylbutadiyne quantitatively. In the case of 1,4-diethynylbenzene, soluble poly(phenylenebutadiynylene) was obtained. The electrical conductivity (σ) increased from 10 −14 S cm −1 to 10 −12 S cm −1 after I 2 doping. In the case of acetylene as the substrate, an insoluble black powdery product was obtained. The IR spectrum of the product was similar to that of carbyne reported before.

Acetylene was potentiostatically electropolymerized in the presence of a Cu-TMEDA catalyst in DMF containing LiClO 4 under an argon atmosphere, affording a black filmy product deposited on a Pt cathode. The product was liberated as a free-standing film by a treatment of methanol. The film was found to consist of amorphous trans -rich polyacetylene chains whose degree of polymerization was more than 50 with contaminants such as metals and the electrolyte. SEM analysis of the film surface showed a cauliflower-like morphology without fibliler structures. Electrical conductivity of the film was about 10 S cm −1 upon I 2 doping

The mercury process chlor-alkali cells whose anodes are dimensionally stable electrode have been operated in Mitsui Toatsu Chemicals, Inc. (MTC) since 1970. The control system for the mercury cell process was developed by MTC in collaboration with TOPACS Inc.(software house) for the purpose of optimum operation of electrolysis plant in 1978. The advanced benefits obtained by the system are following; 1) low energy consumption, 2) resource saving, 3) man-power saving and 4) safety operation by controlling the distance between electrodes of the cell optimal. The algorithm of the control logics is based on the mathematical model of electrolytic cell and the determination of optimum cell operation. The characteristics of the algorithm are adaptive control and interacting control for multi-variable system. Especially, on the energy conservation, this control system has realized the best mercury cell process for unit consumption of electric power in the world.

This method is concerned with the utilization of welding cables without using control cables in order to remotely control a-c arc welding. machine. The current of the welding transformer is adjusted by a small d-c motor whose control is carried out by connecting between wedling cables a control box containing half wave dry rectifiers. When the connection of the senses is turned over, the motor can also rotate reversely.The method has the following advantages: (1) Non-use of control cables ; (2) Non-use of relays ; (3) Control box is small, light and not dangerous electrically ; (4) Simpler operation ; (5) Easier maintenance ; (6) Longer life ; (7) Possibility of common use of a control box for many welding machines;(8) Owing to the employment of welding transformer without moving parts, the control motor is small;(9) Possibility of applications to large welding machines and a-c machines of other types.In the paper, the authors state the structure and the characteristics of the control motor, the control box and the welding transformer of new remote control type, and explain the actual control circuit.This, paper was awarded a Prize amounting to 10, 000 Belgian francs as Honourable Mention in the Arcos International Competition 1953.

Between August, 1968 and March, 1985, we treated 27 patients with testicular seminoma. The histopathological type was typical seminoma in 23 (85%) and anaplastic seminoma in 4 (15%). Their clinical stages were classified into stage I for 17 patients (63%), 7 patients (25%) in II and 3 (12%) in III. Tumor markers, alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG-beta), were determined in 16 patients. None of them showed an elevated level of AFP, but 7 (43.8%) had elevated hCG-beta in the peripheral vein. The hCG-beta in the spermatic vein on the tumor side was elevated in 12 out of 14 patients (88.9%). The hCG-beta level in the spermatic vein on the tumor side was significantly higher than that in the peripheral vein in 10 patients with stage I seminoma. This finding suggests that the determination of hCG-beta in the spermatic vein would give us more accurate information on the production of hCG-beta in seminoma. Although the elevation of the hCG-beta level in pure seminoma has been supposed to be a poor prognostic factor, our results indicated that a mild to moderate elevation of hCG-beta in stage I seminoma did not always imply a poor clinical course, first, because none of these 10 patients, even with an elevated hCG-beta, who underwent retroperitoneal lymph node dissection (RPLND), had microscopic metastasis, and second, because none of these have had a recurrence of the disease up to now.(ABSTRACT TRUNCATED AT 250 WORDS)

Nine antibiotics were tested for the control of 11 bacterial genera isolated from boar semen. Of the antibiotics tested, the aminoglycosides dibekacin, amikacin and gentamicin proved fairly effective. Minimum inhibitory concentrations of those antibiotics were low (less than 6.25 micrograms/ml) compared to those of antibiotics commonly used for semen diluents. Seventy-four semen samples were stored at 15 degrees C by means of dialysis in the presence of dibekacin (100 micrograms/ml). After seven days' storage, about 80 per cent of the samples showed no bacterial growth and the mean values for sperm motility an normal acrosomes were 75.4 per cent and 82.7 per cent respectively. Twenty sows which were inseminated with semen stored for up to 14 days produced 16 litters and the average litter size was 9.9.

A retrospective comparative study was done on the management of hepatoma: MMC-mc-chemoembolization therapy (group A; 9 patients) vs. the same therapy in combination with UFT as a maintenance therapy (group B; 8 patients). The six-month survival rate was 44.4% for group A, and 87.5% for group B. Generalized Wilcoxon test for the whole period revealed that the survival was favorable for group B as compared with A (P = 0.048). For adverse reactions in UFT therapy, no subjective signs occurred, but objective ones appeared such as one case of leukocytopenia, one of thrombocytopenia and 3 of increased GOT. However, no cessation of UFT therapy was necessary in these patients. These findings suggested that maintenance therapy with UFT may be favorable in this type of treatment for hepatoma.

Clinical findings and results of various treatments were discussed for 30 patients with nonseminomatous testicular tumor (NSTT) who had been treated from August, 1968 to March, 1985. Radioimmunoassays were positive for AFP in 19 of the 22 evaluated patients (86.4%) and were positive in 14 of the 19 evaluated patients (73.7%). These positive rates are consistent with those reported by others. Abnormal pre-treatment level of hCG-beta did not always indicate poor clinical courses, since in patients under stage III A pre-treatment level of hCG-beta did not correlate to either treatment results or clinical courses, even in patients with bulky metastasis such as stage IIIB1, B2 or C their treatment results and clinical courses seemed to be primarily determined by the size and extent of metastasis. However, pre-treatment measurement of hCG-beta was useful to predict in primary and/or metastatic tumor the presence of choriocarcinoma element which could not be found with conventional histopathological studies. Most of our 14 patients at stage I were subjected to radical orchiectomy and retroperitoneal lymph node dissection followed by post-surgical management with radiotherapy or chemotherapy. With these treatments only one of the stage I patients had a recurrence. However, adjuvant therapy may not be necessary for them because of a low recurrence rate following retroperitoneal lymph node dissection and the high cure rate with intensive chemotherapy including CDDP for the early stage of recurrence, when a close follow-up would be possible. We treated only 2 patients at stage II A. One of these 2 patients became free of the disease by intensive chemotherapy including CDDP (24 months after the start of treatment). In stage II A, a high recurrence rate has been reported, following retroperitoneal lymph node dissection without post-surgical adjuvant chemotherapy, which indicates that these patients should be treated with adjuvant chemotherapy, including CDDP. All 4 patients in stage II B or III treated mainly by chemotherapy without CDDP died of the disease at around one year after treatment. However, the five-year survival rate was improved to 40% in 10 advanced patients with these stages who had been treated mainly with recent chemotherapy regimen including CDDP. The recent development of chemotherapy regimen including CDDP has been able to lead many patients with advanced stage to a curable status. However, the appropriate treatment for some patients with bulky and extensive metastasis remains to be established. More aggressive treatment such as cytoreductive surgery may be necessary for such patients.