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Abstract: Analysis of seismic anisotropy in the crust and mantle wedge above subduction zones gives much information about the dynamic processes inside the Earth. For this reason, we measure shear wave polarization anisotropy in the crust and upper mantle beneath central and southwestern Japan from local shallow, intermediate, and deep earthquakes occurring in the subducting Pacific slab. We analyze S phases from 198 earthquakes recorded at 42 Japanese F-net broadband seismic stations. This data set yields a total of 980 splitting parameter pairs for central and southwestern Japan. Dominant fast polarization directions of shear waves obtained at most stations in the Kanto–Izu–Tokai areas are oriented WNW–ESE, which are sub-parallel to the subduction direction of the Pacific plate. However, minor fast polarization directions are oriented in NNE–SSW directions being parallel to the strike of the Japan Trench, especially in the north of Izu Peninsula and the northern Tokai district. Generally, fast directions obtained at stations located in Kii Peninsula and the Chubu district are oriented ENE–WSW, almost parallel to the Nankai Trough, although some fast directions have NW–SE trends. The fast directions obtained at stations in northern central Honshu are oriented N–S. Delay times vary considerably and range from 0.1 to 1.25s depending on the source depth and the degree of anisotropy along the ray path. These lateral variations in splitting character suggest that the nature of anisotropy is quite different between the studied areas. Beneath Kanto–Tokai, the observed WNW–ESE fast directions are probably caused by the olivine A-fabric induced by the corner flow. However, the slab morphology in this region is relatively complicated as the Philippine Sea slab is overriding the Pacific slab. This complex tectonic setting may induce lateral heterogeneity in the flow and stress state of the mantle wedge, and may have produced NNE–SSW orientations of fast directions. The ENE–WSW fast directions in Kii Peninsula and the Chubu district are more coherent and may be partly induced by the subduction of the Philippine Sea plate. The N–S fast directions in northern central Honshu might be produced by the trench-parallel stretching of the wedge due to the curved slab at the arc–arc junction. [Copyright &y& Elsevier]

Objectives: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA)., Methods: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used., Results: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively., Conclusion: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.

Fibrolamellar hepatocellular carcinoma (FLHCC), which is quite uncommon in Japan, is known to be frequently associated with lymph node metastasis in Western countries. Herein, we describe a case of a 25 year-old Japanese woman with recurrent FLHCC in the lymph nodes after undergoing right hepatic lobectomy. She underwent a second operation for removal of a recurrent celiac lymph node tumor 23 months after the initial operation. In Japan, the frequency of lymph node metastasis in ordinary hepatocellular carcinoma is only 1.6%, whereas 3 out of 9 (33%) reported domestic FLHCCs including this case had lymph node metastasis. The surgical management of lymph node metastasis in FLHCC is discussed.

This article reviews the evolution of functional testing of the pancreas in Japan for the diagnosis and treatment of chronic pancreatitis (CP), contrasting the pre- with the postsecretin test (S test) era. In the pre-S test era, the diagnosis was based on symptoms, clinical findings, fasting serum diastase levels, and the vagostigmin- and ether-stimulation test unless morphologic evidence was available. The S test and CCK-pancreozymin (PZ) test (PS test) were introduced into Japan around 1963 and have been used as the gold standard of the exocrine pancreatic-function test. Through a series of attempts at standardization in 1971, 1985, and 1987, the method was standardized to collect duodenal juice for 60 min through a double- or triple-lumen tube after a bolus or during a continuous i.v. injection of secretin (100 U). The S test, however, is an invasive and cumbersome procedure. As a result, N-benzoyl-L-tyrosal-p-aminobenzoic acid (BT-PABA) testing and fecal chymotrypsin testing were introduced into Japan in the middle and late 1970s, respectively. Although simple and noninvasive, these two methods were found have lower sensitivity and specificity than the conventional S test. These two methods, therefore, are presently used more often for monitoring the course of disease and therapeutic effects. Additionally, the glucose tolerance test can be performed to detect endocrine pancreatic insufficiency.

Recent molecular studies on the Rh blood group system have shown that the Rh locus of each haploid RhD-positive chromosome is composed of two structural genes: RHD and RHCE, whereas the locus is made of a single gene (RHCE) on each haploid RhD-negative chromosome. We analyzed the presence or absence of the RHD gene in 130 Japanese RhD-negative donors using the PCR method. The RhD-negative phenotypes consisted of 34 ccEe, 27 ccee, 17 ccEE, 26 Ccee, 19 CcEe, 1 CcEE, and 6 CCee. Among them, 36 (27.7%) donors demonstrated the presence of the RHD gene. Others showed gross or partial deletions of the RHD gene. These results were confirmed by Southern blot analysis. Additionally, the RHD gene detected in the RhD-negative donors seemed to be intact through sequencing of the RhD polypeptide cDNA and the promoter region of RHD gene. The phenotypes of these donors with the RHD gene were CC or Cc, but not cc. It suggested that there is some relationship between the RHD gene and the RhC phenotypes in RhD-negative individuals. In Caucasian RhD-negative individuals, the RHD gene has not been found outside of the report of Hyland et al. (Hyland, C.A., L.C. Wolter, and A. Saul. 1994. Blood. 84:321-324). The discrepant data on the RHD gene in RhD-negative donors between Japanese and Caucasians appear to be derived from the difference of the frequency of RhD-negative and RhC-positive phenotypes. Careful attention is necessary for clinicians in applying RhD genotyping to clinical medicine.

The H genes, encoding an alpha1,2fucosyltransferase, which defines blood groups with the H structure, of four Bombay and 13 para-Bombay Japanese individuals were analyzed for mutations. Four Bombay individuals were homologous for the same null H allele, which is inactivated by a single nonsense mutation at position 695 from G to A (G695A), resulting in termination of H gene translation. The allele inactivated by the G695A was designated h1. The other 13 para-Bombay individuals possessed a trace amount of H antigens on erythrocytes regardless of their secretor status. Sequence analysis of their H genes showed four additional inactivated H gene alleles, h2, h3, h4, and h5. The h2 allele possesed a single base deletion at position 990 G (990-del). The h3 and h4 alleles possessed a single missense mutation, T721C, which changes Tyr 241 to His, and G442T, which changes Asp148 to Tyr, respectively. The h5 allele possessed two missense mutations, T460C (Tyr154to His) and G1042A (Glu348to Lys). The h2, h3, h4, and h5 enzymes directed by these alleles were not fully inactivated by the deletion and the missense mutations expressing some residual enzyme activity resulting in synthesis of H antigen on erythrocytes. Thirteen para-Bombay individuals whose erythrocytes retained a trace amount of H antigen were determined to be heterozygous or homozygous for at least one of h2, h3, h4, or h5 alleles. This clarified that the levels (null to trace amount) of H antigen expression on erythrocytes of Bombay and para-Bombay individuals are determined solely by H enzyme activity. These mutations found in the Japanese H alleles differ from a nonsense mutation found in the Indonesian population. To determine the roles of the H, Se, and Le genes in the expression of H antigen in secretions and Lewis blood group antigen on erythrocytes, the Lewis and secretor genes were also examined in these Bombay and para-Bombay individuals. The Lewis blood group phenotype, Le(alpha- b+), was determined by the combinatorial activity of two fucosyltransferases, the Lewis enzyme and the secretor enzyme, and the secretor status was solely determined by the secretor enzyme activity, not by H enzyme activity. Bombay individuals were confirmed to be homozygous for the inactivated H and Se genes. As expected from the very low frequency of Bombay and para-Bombay individuals in the population, ie, approximately one in two or 300,000, the H gene mutations were found to be very variable, unlike the cases of the point mutations in the other glycosyltransferase genes; the ABO genes, the Lewis gene, and the secretor gene.

The expression of Lewis histo-blood group antigen is determined by the Lewis type alpha(1,3/1,4) fucosyltransferase encoded in Fuc-TIII gene (Le gene) on chromosome 19. Weak hemagglutination reactions are often observed in the Lewis blood typing to cause false-negative reactions. The level of CA19-9 tumor marker, defined as sialylated Le(a) (sLe(a)), is influenced by the Lewis blood phenotype. The sLe(a) antigen is also considered to play a role in hematogenous metastasis of tumor cells. The accurate genotyping of Fuc-TIII gene would be, therefore, necessary for solving above questions. In addition to the two missense mutations previously reported by us, i.e. the T59G and the G508A, further sequence analyses revealed a new single base substitution, the T1067A, changing the Ile356 to Lys in the catalytic region. Polymerase chain reaction-restriction fragment length polymorphism methods were developed for the detection of these three missense mutations and applied in 15 Lewis negative (le/le) and 65 Lewis positive individuals (Le/Le or Le/le). These methods were found to be useful for genetic diagnosis for the Lewis histo-blood typing. All le alleles had the T59G mutation, whereas none of the Le alleles did. The le alleles were divided in two types, le1, having the G508A mutation, and le2, having the T1067A mutation. The T1067A mutation reduced the enzyme activity less than 10%, whereas the G508A mutation in the catalytic domain made the enzyme completely inactive. The frequency of occurrence of Le, le1, and le2 in the Japanese population by random sampling study was found to be 66, 30, and 4%, respectively.

Two Japanese propositi with the rare Gerbich -negative (Ge-) phenotype were found by screening serum of donors for antibodies. These are the first two examples of Ge negative in Japanese. Both had the Gerbich type of Ge-negative phenotype (Ge: -1, -2, -3,), showed some depression of Kell system antigens, and had anti-Ge in their sera. The parents of each of the propositi were first cousins, and one of the propositi had two Ge-negative siblings.

'Naturally occurring' anti-Kell (K1) was found in a Japanese male who has never received a transfusion. The antibody agglutinated K:1 cells suspended in saline at 4 and 22 degrees C as well as cells suspended in albumin and treated with proteolytic enzymes.

Two patients and a healthy blood donor were found to be Lan negative and to have anti-Lan in their sera. These are the first three examples of the Lan-negative phenotype to be described in Japanese. The families of two of the propositi were studied: the parents of both were first cousins and one of the propositi had a Lan-negative sibling. No Lan-negative examples were found in 15,000 Japanese donors screened with anti-Lan.

The antigen corresponding to the 'new' allele Kpc postulated in a Japanese family is the low frequency antigen Levay recognized in England 33 years ago.

Four Kp(a-b-) Japanese sisters, the product of a consanguineous mating, have otherwise normal Kell antigens. Kpc, a 'new' allele of Kpa and Kpb is the most probable background.

Fourteen Jk(a-b-) persons were detected by testing 638,460 Osaka blood donors with an automated 2 M urea technique. Two of these 14 Jk(a-b-) samples were quite different from the hitherto reported Jk(a-b-) phenotype, and a family study showed that the mode of the inheritance was dominant. The red cell membranes of these Jk(a-b-) samples were studied by polyacrylamide gel electrophoresis and unusual protein bands (apparent mw, 67,000 d) were detected.

The low-frequency red cell antigen NFLD was identified in 2 Japanese donors. A family study showed that the antigen is not part of the P1 blood group system. Anti-NFLD was found in serum of several donors (frequency of 0.044%).