Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis

AIM: to evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis(UC).METHODS: Bio-Three tablets, each containing 2 mg of lactomin(Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used as probiotic therapy.Sixty outpatients with UC in remission were randomly assigned to receive 9 Bio-Three tablets/day(BioThree group) or 9 placebo tablets/day(placebo group)for 12 mo in addition to their ongoing medications.Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication. Fecal samples were collected to analyze bacterial DNA at baseline and 3-mo intervals. Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora.RESULTS: Forty-six patients, 23 in each group,completed the study, and 14 were excluded. The relapse rates in the Bio-Three and placebo groups were respectively 0.0% vs 17.4% at 3 mo(P = 0.036), 8.7%vs 26.1% at 6 mo(P = 0.119), and 21.7% vs 34.8%(P = 0.326) at 9 mo. At 12 mo, the remission rate was 69.5% in the Bio-Three group and 56.6% in the placebo group(P = 0.248). On cluster analysis of fecal flora, 7 patients belonged to cluster Ⅰ, 32 to cluster Ⅱ,and 7 to cluster Ⅲ.CONCLUSION: Probiotics may be effective formaintaining clinical remission in patients with quiescent UC, especially those who belong to cluster Ⅰ on fecal bacterial analysis.

Clinical Phenotype of Japanese Patients with Dermatomyositis—Classification Based on Dermatomyositis-Specific Autoantibodies

Objectives: To correlate the precise specificity of autoantibodies in Japanese dermatomyositis (DM) patients with their clinical phenotypes. Methods: Serum samples from 94 adult DM patients (67 with classical DM and 27 with clinically amyopathic dermatomyositis, CADM) were screened for autoantibodies using immunoprecipitation assays. Patients with antibodies against aminoacyl transfer RNA synthetase (ARS), Mi-2 or who had other autoantibodies were assessed for clinical symptoms and laboratory findings. Results: Sera from 27 of 94 DM patients (29%) were found to have anti-ARS antibodies. Nineteen (20%) had anti-CADM-140/MDA5, 5 (5%) had anti-Mi-2, and 8 (6%) had anti-p155/TIF1-γ. Anti-MJ/NXP-2 was not found in our series of adult DM. Seventeen patients with anti-ARS had fever and 22 had arthritis and interstitial lung disease (ILD), compatible with a diagnosis of anti-ARS syndrome. Seventeen of 19 (89%) with anti-CADM-140/MDA5 had ILD, 16 (84%) of whom developed rapidly progressive ILD (RP-ILD). Four of 5 (80%) with anti-Mi-2 had heliotrope rash and/or Gottron’s sign/papules, and 2 (40%) had V-sign and/or shawl-sign rash, whereas no ILD or malignancy was detected. As seen with anti-Mi-2-positive patients, a low frequency of ILD (13%) was found in patients with anti-p155/TIF1-γ but 6 of 8 (75%) had malignancy during their course. The frequency of ILD was significantly higher in patients with anti-ARS or anti-CADM-140/MDA5 compared with anti-Mi-2 or anti-p155/TIF1-γ (81% and 89%, respectively). It should be noted that anti-CADM-140/MDA5-positive patients suffered significantly more RP-ILD compared to patients with anti-ARS (84% vs. 7%, P < 0.0001). On the other hand, anti-p155/TIF1-γ positive patients had a significantly higher rate of malignancy compared with anti-ARS-, anti-CADM-140/MDA5-and anti-Mi-2-positive patients (75% vs. 7%: P = 0.0004, 5%: P = 0.0006, 0%: P = 0.02, respectively). Conclusions: These results indicate that in addition to antibodies previously identified as specific for DM, autoantibodies newly found in these patients are useful for stratifying them into clinical subgroups.

Substrate specificity of avian influenza H5N1 neuraminidase

AIM: To characterise neuraminidase(NA) substrate specificity of avian influenza H5N1 strains from humans and birds comparing to seasonal influenza virus.METHODS: Avian influenza H5N1 strains from humans and birds were recruited for characterising their NA substrate specificity by using a modified commercial fluorescence Amplex Red assay. This method can identify the preference of α2,6-linked sialic acid or α2,3-linked sialic acid. Moreover, to avoid the bias of input virus, reverse genetic virus using NA gene from human isolated H5N1 were generated and used to compare with the seasonal influenza virus. Lastly, the substrate specificity profile was further confirmed by high-performance liquid chromatography(HPLC) analysis of the enzymatic product. RESULTS: The H5N1 NA showed higher activity on α2,3-linked sialic acid than α2,6-linked(P < 0.0001). To compare the NA activity between the H5N1 and seasonal influenza viruses, reverse genetic viruses carrying the NA of H5N1 viruses and NA from a seasonal H3N2 virus was generated. In these reverse genetic viruses, the NA activity of the H5N1 showed markedly higher activity against α2,3-linked sialic acid than that of the H3N2 virus, whereas the activities on α2,6-linkage were comparable. Interestingly, NA from an H5N1 human isolate that was previously shown to have heamagglutinin(HA) with dual specificity showed reduced activity on α2,3-linkage. To confirm the substrate specificity profile, HPLC analytic of enzymatic product was performed. Similar to Amplex red assay, H5N1 virus showed abundant preference on α2,3-linked sialic acid.CONCLUSION: H5N1 virus maintains the avian specific NA and NA changes may be needed to accompany changes in HA receptor preference for the viral adaptation to humans.

Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility

The azoospermia factor(AZF)region is important for spermatogenesis,and deletions within these regions are a common cause of oligozoospermia and azoospermia.Although several studies have reported this cause,the present research,to the best of our knowledge,is the first large-scale study assessing this factor in Japan.In this study,1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide(PCR-rSSO)method,a newly developed method for Y chromosome microdeletion screening,were included.The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia.Among the 1030 patients,4,4,10,and 52 had AZFa,AZFb,AZFb+c,and AZFc deletions,respectively.The sperm recovery rate(SRR)of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions(60.0%vs 28.7%,P=0.04).In patients with gr/gr deletion,SRR was 18.7%,which was lower than that in those without gr/gr deletion,but was not statistically significant.In conclusion,our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries,and SRR was higher in patients with AZFc deletion.

Pandemic threat posed by H3N2 avian influenza virus

Dear Editor,In the last century,H1N1,H2N2,and H3N2 influenza viruses caused pandemics in 1918,1957,and 1968,respectively.In 2009,a novel H1N1 reassortant jumped from pigs to humans and caused a fourth influenza pandemic.Different lineages of H3N2 influenza viruses are commonly found in animal reservoirs.If a different lineage of H3N2 virus jumps to humans,another human influenza pandemic could occur with devastating consequences.

Third-line therapies in patients with Kawasaki disease refractory to first-and second-line intravenous immunoglobulin therapy

Kawasaki disease(KD)is an acute febrile ilness characterized by systemic vasculitis affecting the small-and mediumsized arteries in children [1,2].One of the most critical complications of KD is the development of coronary artery lesions(CALs)approximately after 12 days of ilness,which may lead to myocardial infarction[3].High-dose intravenous immunoglobulin(IVIG)and oral administration of aspirin have been established as the first-line therapy for KD[4,5].

Circulating immunocompetent cell profiles during oral cyclosporin therapy for immunoglobulin-resistant Kawasaki disease

Although the standard treatment for Kawasaki disease(KD)is intravenous immunoglobulin(IVIG)combined with oral aspirin,18%of 1st IVIG is refractory[1].Recently,the efficacy of immunomodulatory drugs for IVIG-resistant KD,such as prednisolone,infliximab(IFX),and cyclosporine(CsA),has been reported[2-5].However,optimal immunomodulatory therapy for IVIG-resistant KD has not yet been established.