Purification of antilymphocyte antibody (ALA) from patients with systemic lupus erythematosus (SLE)-immunoabsorption and elution.

Purification of antilymphocyte antibody (ALA) from patients with systemic lupus erythematosus (SLE) was achieved by immunoabsorption and elution. Human tonsil cells or thymocytes were used as absorbents. Complement dependent microcytotoxicity tests showed that, in comparison to the parent sera, the eluate from tonsil cells was eight times, and that from thymocytes four times, more active. Antinuclear activity was eliminated by elution. The ALA was almost entirely IgM, IgG being involved in only a few cases. IgA lacked cytotoxic activity. ALA was directed at both T- and B-cell surface determinants, which suggests that, in SLE, it has a heterogeneous biological composition.</p

The Results of Radiotherapy for T1 Glottic Cancers: Influence of Radiation Beam Energy

We analyzed the influence of various parameters on the results of radiotherapy for T1 glottic cancer by assessing the outcomes of 60 patients with this cancer who received definitive radiotherapy between 1985 and 1994. Seven patients were treated with a cobalt-60 unit, and the other 53 with a linear accelerator (26 patients at 3-MV, 10 at 6-MV, and 17 at 10-MV). Of the 17 patients treated at 10-MV, 4 also received part of their treatment with a cobalt-60 unit. The total radiation dose ranged from 56 Gy to 70 Gy (mean, 61 Gy). The total radiation dose of 51 patients (85%) was 60 Gy. The factors found to influence local control were the strength of the radiation beam energy and whether or not there was gross tumor invasion of the anterior commissure. The local control rate was 71% in the patients treated with a 10-MV linear accelerator, 56% in those treated with a 6-MV linear accelerator and, 97% in those treated with a cobalt-60 unit or a 3-MV linear accelerator (P = 0.0173). The local control rate was 43% in the patients with gross anterior commissure invasion and 88% in those without (P = 0.0075). We conclude that low energy photon beams are more suitable for the treatment of early glottic cancers, especially if the lesion grossly invades the anterior commissure

Property of hepatitis B virus replication in Tupaia belangeri hepatocytes

AbstractThe northern treeshrew (Tupaia belangeri) has been reported to be an effective candidate for animal infection model with hepatitis B virus (HBV). The objective of our study was to analyze the growth characteristics of HBV in tupaia hepatocytes and the host response to HBV infection. We established primary tupaia hepatocytes (3–6-week old tupaia) and infected them with HBV genotypes A, B and C, and all the genotypes proliferated as well as those in human primary hepatocytes (>105 copies/ml in culture supernatant). We next generated a chimeric mouse with tupaia liver by transplantation of tupaia primary hepatocytes to urokinase-type plasminogen activator cDNA (cDNA-uPA)/severe combined immunodeficient (SCID) mice and the replacement ratio with tupaia hepatocytes was found to be more than 95%. Infection of chimeric mice with HBV (genotypes B, C, and D) resulted in HBV-DNA level of 104-106 copies/ml after 8 weeks of infection, which were almost similar to that in humanized chimeric mouse. In contrast, serum HBV level in adult tupaia (1-year-old tupaia) was quite low (<103 copies/ml). Understanding the differences in the response to HBV infection in primary tupaia hepatocytes, chimeric mouse, and adult tupaia will contribute to elucidating the mechanism of persistent HBV infection and viral eradication. Thus, T. belangeri was found to be efficient for studying the host response to HBV infection, thereby providing novel insight into the pathogenesis of HBV

An attenuated vaccinia vaccine encoding the severe acute respiratory syndrome coronavirus-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human angiotensin-converting enzyme 2 transgenic mice from severe acute respiratory syndrome coronavirus-2 and its variants

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2 S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants

日本睡眠歯科学会口腔内装置診療ガイドライン作成委員会の活動報告

Oral appliance therapy was approved by national health insurance in Japan in 2004 and oral appliances（OAs）have since been widely used in the treatment of obstructive sleep apnea（OSA）. We herein described the process of making clinical practice guidelines by the task force of the Japanese Academy of Dental Sleep Medicine as a work report. In Japan, OAs are covered by national health insurance. In consideration of the balance between medical treatment fees and the price of technical materials, we used a single-piece（monoblock）OA that advanced the mandible forward and limited mouth opening in OSA patients in Japan. The Japanese Academy of Dental Sleep Medicine（JADSM）focused on OAs frequently used for the treatment of OSA in Japan, and considered an evaluation of their effects to benecessary. Clinical practice guidelines were developed using the Grading of Recommendations, Assessment, Development, and Evaluation（GRADE）system. We recommend OAs that advanced the mandible forward and limited mouth opening for patients with OSA.However, CPAP should be used by patients for whom it has been indicated. OAs are desirable for those who cannot use CPAP（GRADE 1B, strong recommendation/quality of evidence, “Moderate quality”）. The long-term effects and side effects, OSA severity, and comorbidities of OA therapy were not examined, which represented a limitation to the present study. In future studies, the Japanese Academy of Dental Sleep Medicine plan to update clinical practice guidelines for oral appliances used in OSA

Studies on the immunological abnormalities in patients with Behcet's disease. Part 2. Autoantibodies and immune complexes in patients with Behcet's disease.

The incidence of various autoantibodies and immune complexes in 66 patients with Behcet's disease was studied. (1) Antilymphocyte antibody(ALA) was detected in 17(54.8%) out of 31 cases, antinuclear antibody(ANA) in 9(13.6%) out of 66 cases, antithyroglobulin antibody (TGHA) in 2(6.1%) out of 33 cases, antimicrosomal antibody(MCHA) in 5(13.9%) out of 36 cases and rheumatoid factor(RF) in 1(1.5%) out of 66 cases. These antibodies tended to be found in the incomplete type of Behcet's disease. (2) Immune complexes were detected in 1(5.3%) out of 19 cases by Clq solid-phase radioimmunoassay and in 8(42.1%) out of 19 cases by conglutinin solid-phase radioimmunoassay, demonstrating a considerable difference in sensitivity depending on the assay system. (3) Antinuclear antibody was found often in the cases without steroid therapy. The staining pattern was speckled, and the titer was low, up to 32 fold. (4) Antilymphocyte antibody was of a lower titer than SLE but. showed the same titer as the patients positive for HBs antigen. The immunoglobulin class was mainly IgM, and 6 out of 15 cases showed cytotoxicity against T cell. ALA was not inversely proportional to the peripheral blood lymphocyte count and showed low values in patients administered steroid hormone. Autoantibodies such as ALA and immune complexes were detected in patients with Behcet's disease, suggesting that the autoimmunization mechanism existed in patients with Behcet's disease. ALA was found at the high incidence of 72.2% in the incomplete type of Behcet's disease. Thus, it appears necessary to restudy this disease from the standpoint of viral infection

Studies on the immunological abnormalities in patients with Behcet's disease. Part 1. Complement system in patients with Behcet's disease.

In a study of the complement system in patients with Behcet's disease, hemolytic activity of CH50 and ACH50 and the complement components C4, C3, C5, C8, C9 and factor B were assessed and compared to the CRP, α2-globulin level and erythrocyte sedimentation rate which are parameters of inflammation. As the controls, those suspected of having Behcet's disease and those with diabetes mellitus and rheumatoid arthritis were compared with those having Behcet's disease. (1) In Behcet's disease, both CH50 and ACH50 were high. Of the complement components, not only C4 and C3 but also C5, C8, C9 and factor B showed an increase. Particularly, the increase of C9 and factor B were conspicious. (2) The complement components showed an acute phase protein charactor which was stronger in C5, C8 and C9 than in C4 and C3. It appeared that the strongest was C9 among the complement components studied. (3) The definite type of Behcet's disease showed higher values of CH50, C5 and C9 than the probable type of Behcet's disease. This fact will be helpful in differentiating one from the other