A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis

The efficacy of Shosaiko-to (SST) on 222 patients with chronic active hepatitis was studied in a double-blind multicenter clinical study. One hundred and sixteen patients received SST in a daily oral dose of 5.4 g for 12 weeks, followed by the same dose for a further 12 weeks. One hundred and six patients received a placebo containing 0.5 g of SST for 12 weeks, followed by a cross-over to SST for a further 12 weeks. Among the liver tests, serum AST and ALT values decreased significantly with the administration of SST. The difference of the mean value between the SST group and the placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed.     

A single nucleotide polymorphism in Prostate Stem Cell Antigen is associated with endoscopic grading in Kyoto classification of gastritis

The risk allele of a single nucleotide polymorphism (SNP) rs2294008 in the Prostate stem cell antigen (PSCA) gene is strongly associated with gastric cancer. Although the Kyoto classification score is believed to be an indicator of gastric cancer risk, it lacks supporting genetic evidence. We investigated the effect of this risk allele of PSCA SNP on the Kyoto score. Participants without a history of gastric cancer or Helicobacter pylori (H. pylori) eradication underwent esophagogastroduodenoscopy, H. pylori evaluation, and SNP genotyping. The Kyoto score is the sum of scores obtained from endoscopy-based atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The Kyoto score is novel in the light of scoring for gastritis. A total of 323 patients were enrolled (number of individuals with genotype CC: 52; CT: 140; TT: 131, average age: 50.1 years, male: 50.8%). The patient baseline characteristics including age, sex, body mass index, smoking, drinking, family history of gastric cancer, and H. pylori status had no association with PSCA SNP. The Kyoto score was higher in T (CT or TT genotype; risk allele) carriers than in CC carriers. Atrophy, enlarged folds, and diffuse redness scores were higher in T allele carriers (risk allele) than in CC genotype individuals. In multivariate analysis, the Kyoto score was independently associated with PSCA SNP (OR: 1.30, p = 0.012). Thus, the Kyoto score was associated with a genetic predisposition.     

In Vitro Analysis of the Functional Effects of an NLRP3 G809S Variant with the co-Existence of MEFV Haplotype Variants in Atypical Autoinflammatory Syndrome

Purpose

Hereditary periodic fever syndromes have been considered monogenic diseases. However, some recent reports have described patients with co-existence of recurrent fever responsible genes. This study assessed whether a rare variant, found in Japanese children showing atypical autoinflammatory syndrome, located in the leucine-rich repeat domain of Nod-like receptor family, pyrin domain containing 3 (NLRP3) with co-existence of Mediterranean fever (MEFV) haplotype variants may contribute to a proinflammatory phenotype using a systematic approach.

Methods

Cytokine production in serum or from peripheral blood monocytes was measured by ELISA. DNA sequence analysis of genes including NLRP3, MEFV, mevalonate kinase (MVK), and tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) were performed on patient samples. In vitro functional assays determined the effects of the NLRP3 variants and pyrin using NF-κB activation and speck formation assays.

Results

A heterozygous genetic variant of NLRP3, G809S, was found in samples from both patients. Additionally the previously reported heterozygous MEFV variants (P369S-R408Q or E148Q-P369S-R408Q) were also detected in both patients. Serum IL-1ra and sTNFR1 levels increased in the attack phase of the disease in both patients. The production levels of IL-1β from monocytes isolated from both cases were elevated following LPS and IFN-γ stimulation. The NLRP3 G809S variant demonstrated no increase of NF-κB activity following monosodium urate stimulation, whereas it significantly increased speck formation by interacting with apoptosis-associated speck-like protein with caspase recruitment domain.

Conclusions

The phenotype of atypical autoinflammatory disease in patients could be modified by a synergistic effect with two other variants of autoinflammatory-associated genes.     

Replacement of owl monkey centromere satellite by a newly evolved variant was a recent and rapid process

Alpha satellite DNA is a major DNA component of primate centromeres. We previously reported that Azara's owl monkey has two types of alpha satellite DNA, OwlAlp1 and OwlAlp2. OwlAlp2 (344 bp) exhibits a sequence similarity throughout its entire length with alpha satellite DNA of closely related species. OwlAlp1 (185 bp) corresponds to the part of OwlAlp2. Based on the observation that the CENP-A protein binds to OwlAlp1, we proposed that OwlAlp1 is a relatively new repetitive DNA that replaced OwlAlp2 as the centromeric satellite DNA. However, a detailed picture of the evolutionary process of this centromere DNA replacement remains largely unknown. Here, we performed a phylogenetic analysis of OwlAlp1 and OwlAlp2 sequences, and also compared our results to alpha satellite DNA sequences of other primate species. We found that: (i) OwlAlp1 exhibits a higher similarity to OwlAlp2 than to alpha satellite DNA of other species, (ii) OwlAlp1 has a single origin, and (iii) sequence variation is lower in OwlAlp1 than in OwlAlp2. We conclude that OwlAlp1 underwent a recent and rapid expansion in the owl monkey lineage. This centromere DNA replacement could have been facilitated by the heterochromatin reorganization that is associated with the adaptation of owl monkeys to a nocturnal lifestyle.     

Lung miliary micro‐nodules in human T‐cell leukemia virus type I carriers

Human T‐cell leukemia virus type 1 (HTLV‐1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well‐known complication, adult T‐cell leukemia/lymphoma (ATLL). HTLV‐1 associated bronchiolo‐alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV‐1 carriers. The reported clinico‐pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV‐1 carriers showing miliary micro‐nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro‐nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.     

A new protocol for the preparation of superconducting KBi2

A superconducting KBi₂ sample was successfully prepared using a liquid ammonia (NH₃) technique. The temperature dependence of the magnetic susceptibility (M/H) showed a superconducting transition temperature (T_c) as high as 3.6 K. In addition, the shielding fraction at 2.0 K was evaluated to be 87%, i.e., a bulk superconductor was realized using the above method. The T_c value was the same as that reported for the KBi₂ sample prepared using a high-temperature annealing method. An X-ray diffraction pattern measured based on the synchrotron X-ray radiation was analyzed using the Rietveld method, with a lattice constant, a, of 9.5010(1) Å under the space group of Fd$\bar{3}$m (face-centered cubic, no. 227). The lattice constant and space group found for the KBi₂ sample using a liquid NH₃ technique were the same as those reported for KBi₂ through a high-temperature annealing method. Thus, the superconducting behavior and crystal structure of the KBi₂ sample obtained in this study are almost the same as those for the KBi₂ sample reported previously. Strictly speaking, the magnetic behavior of the superconductivity was different from that of a KBi₂ sample reported previously, i.e., the KBi₂ sample prepared using a liquid NH₃ technique was a type-II like superconductor, contrary to that prepared using a high-temperature annealing method, the reason for which is fully discussed. These results indicate that the liquid NH₃ technique is effective and simple for the preparation of a superconducting KBi₂. In addition, the topological nature of the superconductivity for KBi₂ was not confirmed.

A superconducting KBi₂ sample was successfully prepared using a liquid ammonia (NH₃) technique.     

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

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