Koichi Shinmyozu

Complete response to twice-a-day interferon-beta with standard interferon-alpha therapy in acute hepatitis C after a needle-stick

A 25-year-old male physician with acute hepatitis C after needle-stick injury was treated with combination therapy including twice-a-day interferon-beta (IFN-beta) and standard interferon-alpha (IFN-alpha). The infecting strain was of genotype 1b. Pretreatment hepatitis C virus (HCV) RNA levels were high. Because severe paresthesias occurred with initial daily administration of 5 million units (MU) of lymphoblastoid IFN-alpha, the dose was reduced to 3 to 6 MU of IFN-alpha2b three times a week. However, HCV RNA was not cleared from serum after 20 weeks of standard IFN-alpha2b treatment. A 4-week course with IFN-beta, at the dosage of 3 MU twice daily i.v. drip, was then started and followed by an 18-week course with IFN-alpha2b, 6 MU thrice weekly. After IFN-beta treatment, HCV RNA was cleared from serum without severe adverse effects, including paresthesias. Total amounts of IFN administered were 20 MU of lymphoblastoid IFN-alpha, 648 MU of IFN-alpha2b, and 252 MU of IFN-beta. Complete response and avoidance of chronic HCV infection were achieved. Thus, combination therapy with twice-a-day IFN-beta and standard IFN-alpha was effective in treating an acute hepatitis C patient with a high viral load and sensitivity to adverse effects of high-dose IFN-alpha.

Polymorphism of Plasminogen in Healthy Individuals and Patients with Cerebral Infarction

Phenotyping of plasma plasminogen (PLG) was carried out by the method of agarose gel isoelectric focusing followed by immunofixation or immunoblotting. The allele frequencies calculated from healthy Japanese individuals (n = 795) were as follows: PLG*1 = 0.9440, PLG*2 = 0.0189, PLG*A = 0.0076, PLG*A2 = 0.0006, PLG*B = 0.0138, PLG*B2 = 0.0013, and PLG*C = 0.0138. The PLG phenotype distribution in a group of patients with cerebral infarction (n = 125) was also studied. The allele frequencies were PLG*1 = 0.960, PLG*2 = 0.016, PLG*A = 0.012, and PLG*B = 0.012. No statistically significant association was found between PLG types and cerebral infarction.

Anti-viral and immunomodulatory effects of interferon-α on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP)

In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.

Schwartz-Jampel syndrome associated with von Willebrand's disease

SummaryWe report a very rare case of Schwartz-Jampel syndrome associated with von Willibrands disease. This association might be coincidental because of the different modes of inheritance of the two disorders. However, we speculate that there might be some link between the two disorders, for example in the locus of the affected gene.

Pathophysiological analysis of the blood coagulation and fibrinolytic systems following intracerebral hemorrhage in a case with hemophilia A

血友病Aに合併した脳出血に伴う凝血病態の推移を検討した.症例は51歳男性.脳内出血発症約13時間後より濃縮第VIII因子補充療法を開始した.最も鋭敏なthrombin産生・作用の指標であるfibrinopeptide A (FPA) は補充療法開始前には全く増加しておらず, また補充療法開始とともに血中VIII : Cレベルは充分に維持されたにも拘らず第2病日までは殆ど増加しなかった.これに相応して脳内血腫量も著しく増大し病状も進行した.第3病日になってようやく明らかなFPAの増加がみられた.脳出血発症後のthrombin活性の発現の遅延は血友病に伴う二次止血機転の発動の障害を反映し血腫の増大と強く関連したことが示唆され, 本症例のように緊急的止血を要する重篤な出血性発作を保存的に管理する場合, 第VIII因子補充療法のみでは即時的止血機転の発動は生じ難く, thrombinや活性化第X因子を含有する活性型第IX因子製剤との併用療法が有効である可能性が推定された.

Studies on the blood coagulation and fibrinolytic system in patients with cerebrovascular disease at chronic stage

脳血管障害慢性期 (1ヵ月～1年以内) の患者について凝固系因子としてantithrombinIII (ATIII), 線溶系因子としてPlasminogen (PLG), α2-Plasmin inhibitor (APL) を測定し血液凝固線溶系の動態を検討した.脳出血患者ではATIII, PLG, APLのいずれも有意な変動を認めなかった。しかしながら脳梗塞患者を抗血小板剤投与の有無で比較した場合, 抗血小板剤非投与群ではATIII, PLGの有意な低下を認めた.性別では男性患者で, 年齢別では70歳以上でより有意に低下しており, また脳梗塞を主幹動脈系梗塞と穿通枝系梗塞に大別した場合前者において有意に低下していた.APLは正常範囲の変動であった。ATIII, PLGの変動は脳動脈硬化の進展とよく一致し動脈硬化性病変における凝固系の活性化, さらに線溶系の発動を反映しているものと推定される.また抗血小板剤投与群ではATIII, PLGは正常範囲の変動であり, 抗血小板剤の有効性が示唆された.