Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.     

Diverse functions of the p75 neurotrophin receptor

The pan-neurotrophin receptor p75NTR belongs to a large family of receptors, which includes tumor necrosis factor receptors, Fas and approximately 25 other members. The p75NTR is the first receptor to be cloned molecularly. Recent years have seen the emergence of a consensus regarding the signaling pathways activated by p75NTR and its potential biological function, although receptor characterization had not been targeted for some years. We now know that p75NTR has surprisingly diverse effects, ranging from cell death to regulation of axon elongation. This diversity can be explained by the complex formation of p75NTR with other receptors and multiple signaling molecules that interact with the intracellular domain of p75NTR.     

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27⁺ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.     

Detection of the putative E2 protein of hepatitis C virus in human liver

The question was asked whether a predicted envelope protein, considered to be processed from the polyprotein precursor encoded by the putative E2/NS1 region of the hepatitis C virus (HCV) genome, may be observed in HCV-infected humans. Two polyclonal antibodies against recombinant E2/NS1 proteins were prepared and their reactivity tested against liver extracts from HCV-infected patients by immunoblotting analysis. A band corresponding to a size of 44 kDa was detected in liver extracts from patients who were positive for the HCV-specific antibody anti-C100-3 but not in liver extracts from patients who did not have anti-C100-3 antibody. Additionally, no band was detected using preimmune sera or antisera which had been preabsorbed with recombinant E2/NS1 proteins. Deglycosylation studies demonstrated that the 44 kDa protein was a glycosylated form of a 38 kDa protein which corresponds to the predicted molecular weight of the putative E2/NS1 protein. These results suggest that the 44 kDa protein is a product of the E2/NS1 region. Frequent observation of the 44 kDa band in cases of chronic active hepatitis C suggests a correlation between the expression of this protein and the progression of hepatitis. © 1994 Wiley-Liss, Inc.     

Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers

Mass screening for hepatitis C virus antibody was carried out in 875 inhabitants (313 men and 562 women) of a town in Japan with a high rate of hepatitis B virus infection. The overall rate of positivity for anti-HCV was 8.8% (6.4% in men and 10,1% in women). The rate of positivity for hepatitis B virus surface antigen was 11.2%. Five subjects (0.6%) were positive for both markers. HCV-RNA was detected in 65 (88.4%) of 77 individuals who were positive for anti-HCV and in 1 (1.5%) of 60 individuals negative for anti-HCV. The genotype of the HCV genome was determined by PCR analysis using type-specific primers in 60 individuals. HCV type 1b was detected in 51 subjects (85%), type 2a in 3 subjects (5%), and type 2b in 6 subjects (10%). None of the individuals was infected with more than one genotype. The nucleotide sequences of the partial nonstructural 5 region of HCV type 1b genotype obtained from 6 individuals showed at least 92.0% homology in the nucleotide sequence, and 94.8% homology in the amino acid sequence. Homology among these clones was greater than their homology with previously described type 1 b sequences. The findings suggest that there was a specific local origin of HCV infection, although it was not possible to identify any single source of HCV infection. The results also indicate the presence of asymptomatic HCV carriers. © 1995 Wiley-Liss, Inc.     

The role of γδ T cells in priming macrophages to produce tumor necrosis factor-α

The secretion of tumor necrosis factor (TNF)-α from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking γδ T cells [T cell receptor (TCR) δ^?/- mice], which lack the gene encoding the δ chain, produced only small amounts of TNF-α in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR δ-/- mice with γδ T cells from their TCR δ^+/- littermates restored their capacity to produce TNF-α in response to LPS. The priming activity of γδ T cells was in part inhibited by neutralizing anti-interferon (IFN)-γ monoclonal antibodies. Collectively, these results suggest that γδ T cells play a role in priming macrophages to a steady state of activation via IFN-γ secretion, which allows them to produce TNF-α when exposed to LPS.     

Effects of Fucoxanthin on the Inhibition of Dexamethasone-Induced Skeletal Muscle Loss in Mice

Fucoxanthin (Fx) has preventive effect against muscle atrophy and myotube loss in vitro, but it has not yet been examined in vivo. Therefore, we aimed to investigate the effect of Fx on dexamethasone (Dex)-induced muscle atrophy and fat mass in mice. ICR mice were fed with Fx diets from 2 weeks before Dex treatment to the end of the study. Muscle atrophy was induced in the mice by oral administration of Dex. Body weight was significantly lower by Dex treatment. Visceral fat mass in the Fx-treated group were significantly lower than those in the control group. The Dex-induced decrease in tibialis anterior muscle mass was ameliorated by Fx treatment. Fx treatment significantly attenuated muscle lipid peroxidation compared with the control and Dex-treated groups. The phosphorylation of AMPK was significantly higher in the Dex-treated group than in the control group. The expression of cytochrome c oxidase (COX) IV was significantly higher in the Fx-treated group than in the control group. These results suggest that Fx may be a beneficial material to prevent muscle atrophy in vivo, in addition to the effect of fat loss.     

Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms

Neurosurgical Review - The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications...     

Feasibility of a self‐assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self‐assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full‐thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model.     

Validation and reliability of a Japanese version of the Shoulder Pain and Disability Index: A cross-sectional study

BackgroundThe Shoulder Pain and Disability Index (SPADI) is a simple disease specific questionnaire that is used to evaluate the impact of shoulder disorders. The purpose of this study was to translate the SPADI into Japanese (SPADI-Jp) and evaluate its reliability and validity in Japanese patients with shoulder disorders.MethodsCross-cultural adaptation of the SPADI was performed according to international guidelines. A total of 100 patients with shoulder disorders participated in this study. Each participant was asked to finish the SPADI-Jp, Disability of Arm, Shoulder and Hand (DASH), and the Short-Form 36 (SF-36) at the initial visit. Thirty-four patients repeated the SPADI-Jp to assess the test–retest reliability. The test–retest reliability was quantified using the interclass correlation coefficient (ICC), while Cronbach's alpha was calculated to assess the internal consistency. The construct validity was assessed using Spearman's rank correlation coefficients.ResultsInternal consistency in the SPADI-Jp was very high (0.969), as measured by the Cronbach's alpha. The ICC of the SPADI-Jp was 0.930. There was a strong, positive correlation between the DASH and the SPADI-Jp (r = 0.837, p < 0.001). The SPADI-Jp was significantly correlated with most of the SF-36 subscales. The correlations of the SPADI-Jp with physical subscales of the SF-36 were stronger than those with the other subscales.ConclusionsWe demonstrated that the SPADI-Jp is a reliable and valid self-assessment tool. Because cross-cultural adaptation, validation, and reliability of the disease-specific questionnaire for shoulder pain and disability have not been evaluated in Japan, the SPADI-Jp can be useful for evaluating such patients in the Japanese population.