Jun Okada

Magnetic Resonance Imaging of the Brain in Patients with Migraine

Magnetic resonance imaging (MRI) was studied in 91 patients with migraine and in 98 controls. Risk factors known to cause MRI lesions were carefully examined. In 36 patients with migraine (39.6%), small foci of high intensity on T2-weighted and proton-density-weighted images were seen in the white matter. Of patients with migraine who were less than 40 years old and without any risk factor, 29.4% showed lesions on MRI; this was significantly higher than the 11.2% for the group of age-matched controls (n = 98). The lesions were distributed predominantly in the centrum semiovale and frontal white matter in young patients, but extended to the deeper white matter at the level of basal ganglia in the older age group. The side of the MRI lesions did not always correspond to the side of usual aura or headache. Migraine-related variables such as type of migraine, frequency, duration or intensity of headache or consumption of ergotamine showed no significant correlation with the incidence of MRI abnormalities. Our data indicated that migraine may be associated with early pathologic changes in the brain.

NOS2 polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity.

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. One of several complications of SSc, pulmonary arterial hypertension (PAH) can be refractory to treatment, both novel and established. In the present study we investigated the ratio of circulating nitric oxide to endothelin-1 in patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the nitric oxide synthase 2 gene) are associated with susceptibility to PAH. Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. We confirmed the presence of two single nucleotide polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT) at -2.5 kilobases. There were significant differences in single nucleotide polymorphisms between patients with SSc who had PAH and those who did not, and between patients with both SSc and PAH and healthy control individuals. The CCTTT repeat was significantly shorter in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. Transcriptional activity were analyzed using the luciferase reporter assay. The transcriptional activity of NOS2 was much greater in fibroblasts transfected by a vector with a long allele of the CCTTT repeat than in those transfected by a vector with a short allele. Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH.

Detection of anti-bovine β2-glycoprotein I antibody in sera from patients with antiphospholipid syndrome

We studied and characterized anti-bovine β2 I antibodies (aBβ2-GPI) in sera from patients with antiphospholipid syndrome (APS) by ELISA. Bovine β2-glycoprotein I β2-GPI was purified by heparin affinity and DEAE ion-exchange chromatography, and identified on immunoblots using a monoclonal antibody against human β2-GPI and by amino acid sequence analysis. aBβ2-GPI levels in the sera from 36 APS patients were measured by ELISA using purified bovine β2-GPI as an antigen. The mean±standard deviation level of aBβ2-GPI was 17.4±22.0 units in the 58% of APS patients who were positive. There was a significant correlation (P=0.003) between aBβ2-GPI and anticardiolipin antibody (aCL) levels. aBβ2-GPI from the sera of patients with APS was inhibited by bovine β2-GPI itself. Purified IgG from the sera of patients with APS showed that bovine β2-GPI was capable of acting as a cofactor for aCL. Purified bovine β2-GPI was useful antigen for conventional ELISA. aBβ2-GPI may contribute to the further development of aCL analysis and to the understanding of the pathogenesis of APS.

Prospective study of high-dose intravenous immunoglobulin for the treatment of steroid-resistant polymyositis and dermatomyositis

Abstract High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating many autoimmune and systemic inflammatory diseases. In the present prospective study, we evaluated the efficacy of IVIG for patients with polymyositis (PM) and dermatomyositis (DM) refractory to treatment with high-dose corticosteroids. PM/DM was defined as steroid-resistant when the muscle strength of a patient did not improve despite the administration of more than 50 mg prednisolone per day for more than 4 weeks. A total of 12 patients with biopsy-proven, steroid-resistant PM/DM received one infusion of polyethylene glycol-treated human IgG at a dose of 0.4 g per kg per day for five successive days. Three of the patients received a second infusion. All patients were followed for up to 3 months after the infusion. Finally, 8 patients (6 PM and 2 DM; 5 men and 3 women) aged 29–67 years (mean 48 years) were analyzed. Their clinical response was assessed by changes in (a) subjective signs, i.e., fatigue (visual analog scale, VAS), muscle pain (VAS), activities of daily living (ADL), (b) objective signs, i.e., manual muscle strength (MMT) and serum level of creatine kinase (CK). At 12 weeks after the infusion, the patients showed significant improvement in their scores of muscle strength (from a mean of 67.0 to 81.0) and their ADL scores (from a mean of 27.1 to 39.1). The mean serum CK level decreased significantly from 1287.4 to 612.6 IU/l. In addition, the mean VAS of fatigue decreased significantly from 5.5 to 1.3 cm. The physicians’ assessment showed that 87.5% of patients had improved. The average reduced dose of prednisolone was 47.1 mg/day at 12 weeks after infusion in 7 patients who exhibited improvement. Adverse effects, i.e., asymptomatic myocardial infarction and increased blood urea nitrogen (BUN), were noted with two of the 15 infusion (13%). Overall, IVIG was found to be safe and effective for refractory PM and DM.

出産後にMRSAによるToxic shock syndromeを合併したSLEの1例

We experienced a SLE patient with TSS after delivery. A 32-year-old SLE patient was transferred to our division due to fever, diarrhea, erosive rash, pericardial effusion, myalgia, low blood pressure, thrombocytopenia and hypoproteinemia which appeared two days after transvaginal delivery. At the time of admission, we considered these symptoms as the exacerbation of SLE, and treatment with high doses of steroid was started. It was when TSST-1-producing-MRSA was cultured from the vagina and uterus that TSS was suspected. 2 g/day of vancomycin was administered and her symptoms improved. As observed in this case, it is important to consider TSS as one of the complications seen with SLE patients after delivery.

A CLINICAL AND IMMUNOLOGICAL STUDY ON CENTRAL NERVOUS SYSTEM INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS

SLEの中枢神経障害の病態および発症機序を解明するために,中枢神経障害を合併したSLE (CNS-SLE)について,臨床的ならびに免疫学的解析を行なつた. SLE 58例中20例が中枢神経障害を合併し,そのうち原因がSLEによると考えられたものが14例(24.1%)あつた. CNS-SLEは皮膚硬塞症状,強度のレイノー現象,末梢神経障害およびリウマトイド因子陽性の頻度が高かつたのに対し,腎障害は少なく,かつその程度は軽度であつた.異常脳波はSLEの60%に, CNS-SLEでは90.9%と高率に認められ,その脳波所見は中枢神経障害あるいはSLEの活動性と並行して動いた. CNS-SLEでは腎障害の有無に関係なくDNA抗体価は高値をとり,低補体血症を長期間持続していた. lymphocytotoxinはCNS-SLEの全例で陽性を示し,かつその値も高かつた.髄液中のIgG値およびDNA-DNA抗体結合物はCNS-SLEでは活動期に高く,寛解期に低下する傾向がみられた.以上から, CNS-SLEは特異な病像を形成すること, SLEの中枢神経障害の発症機序として免疫結合物やlymphocytotoxinあるいは両者の関与が推測された.また,本症の中枢神経障害の診断およびその病勢推移の指標として,脳波所見,髄液IgG就中髄液中のDNA-DNA抗体結合物の測定が役立つことを明らかにした.