The v‐erbB gene is an oncogene of the avian erythroblastosis virus encoding a protein that is a truncated version of the epidermal growth factor receptor. The v‐erbB protein was expressed alone or as polyhedrin‐ erbB fusion proteins using the Bombyx mori nuclear polyhedrosis virus vector. The expression level of the fusion protein whose polyhedrin portion consisted of only 8 amino‐terminal amino acids was more than ten times higher than that of the non‐fusion protein. Studies with tunkamycin showed that the recombinant v‐ erbB proteins were glycosylated. The recombinant protein autophosphorylated tyrosine residues, and phosphorylated a synthetic tyrosine‐containing peptide and lipocortin I. These observations indicate that functional v‐ erbB protein can he expressed in silkworm‐derived cells, and furthermore, that this system can be used for large‐scale production.
Summary We evaluated the antithrombotic effects of DX-9065a, a specific factor Xa inhibitor, using tissue thromboplastin-induced DIC (TP-DIC) and the arterio-venous shunt (AV shunt) in rats. Intravenous TP injection reduced the platelet counts and fibrinogen concentrations in blood. In the TP-DIC model, an intravenous dose of DX-9065a 0.23 mg/kg 1 min before TP injection suppressed the consumption of platelets and fibrinogen to 57% and 66%, respectively, and the production of FDP almost completely. In the AV shunt model, DX-9065a inhibited thrombus formation to 51% on intravenous administration of 0.23 mg/kg and to 60% when given orally at 23.3 mg/kg. Intravenous administration of 2.33 mg/kg of DX-9065a did not affect the bleeding time. These results suggest that Xa inhibition may be an appropriate approach for suppressing thrombosis without impairing haemostasis.
Aims: Effects of DPP-4 inhibitor or SGLT2 inhibitor on human β-cell function are not well understood, and there is no report showing the difference between the two agents. The aim of this study is to compare the effects of these drugs on β-cell function in patients with type 2 diabetes. Methods: The study protocol was approved by the IRB of Kawasaki Medical School (No. jRCTs061190008). A total of 103 patients met the inclusion criteria (age; 20 to 79 years, HbA1c; ≥7.0% and <9.0%). Subjects were randomly assigned to luseogliflozin (L) group (n=49) or teneligliptin (T) group (n=54) and received 24 wks of intervention followed by 1-2 wks of drug washout. The primary endpoint was the change in log-transformed (Ln) disposition index (DI) 0-120 from baseline. Subjects underwent 75gOGTT before and after treatment. Results: The main baseline backgrounds of L and T groups were as follows; age: 60.8±11.1 vs. 62.6±11.2 years (p=0.4), diabetes duration: 10.1±7.9 vs. 9.2±7.6 years (p=0.6), BMI: 27.0±4.2 vs. 27.2±5.4 kg/m2 (p=0.8), HbA1c: 7.6±0.4 vs. 7.5±0.5 % (p=0.5), DI 0-120: 0.80±0.60 vs. 0.92±0.59 (p=0.1). HbA1c levels were significantly decreased in both groups, but the amount of change was greater in the T group (-0.2%, p=0.02). Body weight was significantly decreased only in the L group, with a group difference of -2.5 kg (p<0.001). Ln DI 0-120 were improved in both groups: -0.46±0.66 to -0.15±0.59 (p=0.01) in L group and -0.26±0.60 to -0.02±0.60 (p=0.003) in T group. The change in Ln serum proinsulin/CPR ratio, a marker of β-cell dysfunction, was reduced in L group (1.63±0.63 to 1.56±0.68, p=0.16), but rather increased in T group (1.70±0.75 to 1.90±0.51, p=0.01), with significant difference between the 2 groups (-0.27; p=0.004). Conclusion: Improvement effects on DI 0-120 were almost identical between luseogliflozin and teneligliptin. On the other hand, burden on β-cells was mitigated only in luseogliflozin group. Disclosure M.Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. A.Obata: None. T.Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. F.Kawasaki: None. F.Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. S.Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T.Mune: None. K.Kaku: Advisory Panel; Novo Nordisk, Consultant; Sanwa Kagaku Kenkyusho, Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H.Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc., Abbott, Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Y.Katakura: Speaker's Bureau; Abbott. M.Iwamoto: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Boehringer Ingelheim Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd. Y.Kimura: None. T.Anno: None. H.Isobe: None. Y.Iwamoto: Speaker's Bureau; Kowa Company, Ltd. Y.Fushimi: None. J.Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd. Funding Taisho Pharmaceutical Holdings Co., Ltd.
To investigate the usefulness of severity classification for predicting outcomes in patients with adult-onset Still's disease (AOSD).This was a multi-centre retrospective cohort study. AOSD patients were classified into mild, moderate, and severe groups based on severity classification (Japanese Ministry of Health, Labour and Welfare) during the initial treatment, and clinical features were compared among these groups. The primary endpoints were the AOSD-related mortality and drug-free remission rate. For comparison, the same analysis was performed in parallel for patient groups stratified by the modified Pouchot systemic score.According to severity classification, 49 (35%), 37 (26%), and 56 patients (39%) were classified into mild, moderate, and severe groups, respectively. Patients in the severe group showed higher frequency of severe complications and the use of biological agents. Although AOSD-related survival was not significantly different (p = .0776), four of the five fatal cases were classified into the severe group. The severe group showed a reduced rate of drug-free remission (p = .0125). Patient groups classified by systemic score did not correlate with survival or drug-free remission.Severity classification is useful for predicting outcomes in patients with AOSD.
Abstract Objective Monocytosis is a unique cellular abnormality associated with the Yaa (Y‐linked autoimmune acceleration) mutation. The present study was designed to define the cellular mechanism responsible for the development of monocytosis and to characterize the effect of the Yaa mutation on the development of monocyte subsets. Methods We produced bone marrow chimeras reconstituted with a mixture of Yaa and non‐ Yaa bone marrow cells bearing distinct Ly‐17 alloantigens, and determined whether monocytes of Yaa origin became dominant. Moreover, we defined the 2 major inflammatory (Gr‐1+,CD62 ligand [CD62L]+) and resident (Gr‐1−,CD62L−) subsets of blood monocytes in aged BXSB Yaa male mice, as compared with BXSB male mice lacking the Yaa mutation. Results Analysis of the Ly17 allotype of blood monocytes in chimeric mice revealed that monocytes of both Yaa and non‐ Yaa origin were similarly involved in monocytosis. Significantly, the development of monocytosis paralleled a selective expansion of the resident monocyte subset compared with the inflammatory subset, and the former expressed CD11c, a marker of dendritic cells. Neither monocytosis nor the change in monocyte subpopulations, including CD11c expression, was observed in Yaa ‐bearing C57BL/6 mice, in which systemic lupus erythematosus (SLE) fails to develop. Conclusion Our results suggest that Yaa ‐associated monocytosis is not attributable to an intrinsic abnormality in the growth potential of monocyte lineage cells bearing the Yaa mutation and that the Yaa mutation could lead to the expansion of dendritic cells, thereby contributing to the accelerated development of SLE.
An 18-year-old Japanese girl had received oral minocycline 200mg daily for treatment of acne vulgaris since 16 years old. She had a fever three months before admission, followed by joint pains in her knees, elbows and several proximal interphalangeal joints one month before admission. She was referred to our hospital because of a high serum level of anti-DNA antibody. She had already discontinued oral minocycline five weeks before admission, because she missed her medication refilled. On admission, the arthralgia and fever spontaneously resolved, and there were no laboratory evidence of hypocomplementemia and cytopenia. She had neither erythema nor internal organ involvements. Because her symptoms subsided spontaneously after the cessation of minocycline, she was considered to have drug-induced lupus. Both the arthralgia and fever did not relapse, and anti-ds DNA antibody returned to normal during a follow-up period without treatment. There are few reports of drug-induced lupus caused by minocycline in Japan. This case highlights the importance of considering minocycline-induced lupus.
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