永井 良三

急性心筋梗塞の診断には,病歴,理学所見,生理機能検査,画像,そして血液生化学的検査を用いて多角的に検討することが重要である.近年の研究の発展によって,日常検査で簡単かつ正確な診断ができる生化学検査が確立されてきた.急性心筋梗塞に対する血清診断は,心筋壊死の有無と壊死量の推定が主要な目的である.心筋壊死を迅速に,より特異的に捉えるマーカーが必要とされる.現在までに確立されてきた多くのマーカーの特徴をよく理解し,目的に応じて使い分けることにより,より正確な病態把握が可能になる.

血管平滑筋細胞は動脈硬化巣や血管再建術後の血管で増殖する。増殖刺激に反応して,平滑筋は収縮型から合成型形質へ変換する.血管平滑筋細胞の形質変換の分子機構の解明は,動脈硬化の成因に基づく新しい治療法の開発に結びつく可能性がある.<BR>胎児型平滑筋ミオシンSMembは平滑筋の脱分化に伴って著明に誘導される.SMemb遺伝子の上流-100bp付近にはGCに富むシスエレメントSE 1が存在する.我々は,サウスウエスタン法によってSMembのSE 1に結合する蛋白として,ホメオドメインを持つ蛋白HexとZn-finger構造を持つKruppel型転写因子BTEB 2のcDNAを単離した.<BR>BTEB 2は大動脈では胎児期に多く発現し,発生に伴って減少する.しかし,傷害動脈の新生内膜で増殖する平滑筋細胞に再発現する.また,BTEB 2は単に胎児型ミオシン重鎖遺伝子の発現を亢進させるだけでなく,組織因子,PDGF,iNOS遺伝子のプロモータも活性化する.さらに,BTEB 2遺伝子のロモータも活性化する.さらに,BTEB 2遺伝子のやEgr-1により誘導される.すなわち,増殖刺激と,血管病変に特有の平滑筋形質変換の間に介在する転写因子であると推測された.

症例は20歳女性. 新生児期より哺乳力弱く筋緊張低下を認め, その後, 肥満, 知能発育遅延, 原発性無月経を認めた. 1996年に尿糖を指摘され, 同年8月肥満精査, 糖尿病治療目的にて当科に入院した. BMI 50.8kg/m²と著明な肥満を認めた. 染色体検査の結果, Prader-Willi症候群 (PWS) と診断した, 頭部MRIにて脳梁の欠損が認められた. 本症例はPWSに脳梁欠損が合併した初めての報告と考えられる. また, FPG 180mg/dl, HbA1c 11.6%, 空腹時IRI 22.8μU/mlと高血糖, 高インスリン血症を認めた. 食事療法を行い, 体重91kgまで減少し血糖値も改善したため退院となった. しかし, 退院後に体重が増加し血糖コントロールが悪化したため, トログリタゾンの投与を開始した. 体重の増加を認めない期間はHbA₁cは順調に低下したが, 体重が増加するのに伴いHbA₁cは再び上昇した. 食事指導を繰り返しながらトログリタゾンを増量したところ, 体重は減少し血糖コントロールも改善した. 本症例より, トログリタゾンの血糖降下作用を継続させるためには食事指導の徹底による体重コントロールが大変重要であると考えられた.

Epidermal nevus syndrome is an unusual neurocutaneous disorder in which epidermal nevi are associated with abnormalities of the skeleton and central nervous system, including the eyes and somtimes the cardiovascular system. We treated a patient in whom the latter included renal artery stenosis. An 18-year-old man with epidermal nevi was diagnosed as having the syndrome based on the additional presence of scoliosis, an arachnoid cyst in the middle cranial fossa, and microphthalmos. Hypertension was diagnosed when the patient was 15 years old. The plasma renin activity (9.7 ng/ml/h) was elevated. Right renal artery stenosis was demonstrated by angiography, and the abdominal aorta was narrowed distal to the ostium of the superior mesenteric artery. The plasma renin activity in the right renal vein (16 ng/ml/h) was higher than contralaterally (10 ng/ml/h). Several cardiovascular manifestations have been reported as a complication of epidermal nevus syndrome. Hypertension in an individual with epidermal nevi and congenital anomalies should prompt a search for a vascular anomaly.

冠動脈造影にて冠動脈病変を有する214例 (CAD群) と有しない162例 (非CAD群) を対象に, FIRI (空腹時インスリン値) とHOMA-IR (homeostasis model assessmentinsulin resistance) をインスリン抵抗性の指標として比較した. FIRIはCAD群6.5±2.3μU/ml, 非CAD群5.9±1.9μU/ml, HOMA-IRはそれぞれ1.67±0.62, 1.41±0.49とともに前者で高かった (それぞれp<0.01, p<0.001).インスリン抵抗性の高い者 (HOMA-IR≧2.60: 高イ低抗者) の頻度は, CAD群20%, 非CAD群6%と, 前者で有意に高率で (p<0.01) あった.耐糖能別でみると, 高イ抵抗者の頻度は, IGT (WHOの基準) の場合, CAD群24%, 非CAD群7%, 新規DM群 (入院時の75gOGTTにて初めて糖尿病を指摘された者) ではそれぞれ38%, 14%と前者で有意に高率であった (それぞれp<0.01, p<0.05).また, CAD群で高イ抵抗者は, そうでない者に比較してTGは高く, 高血圧は高頻度で (IGT群のみではともに有意差p<0.05), HDLコレステロールは低い傾向にあった.CADを有するIGTおよび新規DM群では, インスリン抵抗性が高く, それらの群におけるCADの危険因子の集簇を認めた.

We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting 201Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced 201Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy.

Cardiac sarcoidosis, the main cause of death among patients with sarcoidosis, frequently becomes clinically apparent when the disease is far advanced. To evaluate the usefulness of the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting cardiac sarcoidosis, 18F-FDG PET was performed in 16 patients with sarcoidosis (13 female, 63 +/- 12 yrs), compared with scintigraphic findings of 99mTc-MIBI and 67Ga. Ten of 16 patients were considered to have cardiac complications on clinical grounds with tissue confirmation such as positive endomyocardial biopsy, severe ventricular arrhythmia, more than second degree atrioventricular block, and echocardiographically proven ventricular dysfunction. Among these patients with cardiac complications, abnormal myocardial uptake of FDG were observed in all (100%), which confirms significantly higher frequency compared to 67Ga scintigraphy (50%) (abnormality of 99mTc-MIBI SPECT were observed in 80%). Although abnormal FDG accumulations were observed in region with decreased uptake of 99mTc-MIBI in many cases, localization of regional abnormality of each tracer was frequently independent. This discrepancy may reflect inflammatory and degenerative process of myocardium in cardiac sarcoidosis. 18F-FDG PET is thought to be a useful noninvasive method in detecting cardiac involvement of sarcoidosis and may provide a useful information on the activity of the disease.

αグルコシダーゼ阻害薬 (α阻薬), インスリン (In) 抵抗性改善薬 (トログリタゾン: TZD), 新型In注入器等, 登場以前の1991年 (前期) に6ヵ月以上通院していた糖尿病外来患者291例と, 登場後の1997年 (後期) の患者394例の血糖コントロール状況を比較した. 全体では前期のHbA1c 7.9±1.7%, 後期7.2±1.5%で, 後期の方が有意に低く (p<0.001) 血糖コントロール良好であった. 前期の経口薬治療138例の内訳は, スルフォニルウレア薬 (SU薬) 97.1%, ビグアナイド薬 (BG薬) 3.6%, 両者併用0.7%であったのに対し, 後期の194例ではSU薬54.1%, BG薬3.6%, α阻薬2.1%, Tr2.1%, 2種以上の薬物併用38.1%と多様化しており, HbA1cは前期8.6±1.7%, 後期7.4±1.3%と有意に低かった (p<0.001). In療法例も前期82例の経口薬併用が6.1%であったのに対し, 後期107例では34.6%と増加し, 注射回数も多く, HbA1cは前期8.6±1.9%, 後期7.9±1.6%と有意に低かった (p<0.01). 治療の多様化で, より良い血糖コントロールが得られていることが判明した.

QT延長症候群は致死性不整脈を呈し突然死の危険性が高い.以前より心臓交感神経系の不均衡が原因の一つとして考えられていた.近年,家族性QT延長症候群の原因として心筋イオンチャネルの遺伝子異常が同定された.遺伝子の同定によりQT延長のメカニズムのみでなく,心筋イオンチャネルの生理機能の解明も進んだ.心筋イオンチャネルの生理機能を解明することにより,不整脈治療への応用も期待される.

大動脈の急性障害は,虚血性心疾患に次ぐ突然死の原因となる循環器疾患である.急性の大動脈疾患は臨床症状が多彩で,診断・治療の進歩が日進月歩の今日でも,見落としや,診断の遅れが小なくない.また,致命的な合併症を併発する可能性が高いため,ハイリスク患者の同定や発症後の早期診断は,予後を決定する重要な要因である.この意味でも疾患の予防・早期発見を目標とした遺伝子・生化学的診断法は,最適な手段であり,開発・確立が急がれている.

This study was designed to assess how the glomerular expression of the nonmuscle-type myosin heavy-chain isoform, SMemb, is regulated in rats with focal glomerulosclerosis induced by puromycin aminonucleoside. SMemb was barely detectable in control glomeruli. On day 48 of focal glomerulosclerosis, SMemb was expressed in mesangial area and glomerular epithelial cells. When glomerulosclerosis became prominent on day 80, SMemb stained immunohistochemically in a focal segmental pattern in the sclerotic glomeruli. SMemb-expressing cells did not always express alpha-smooth muscle actin. In Northern blot analysis, SMemb mRNA was not detected in control glomeruli, whereas it was transiently upregulated in glomeruli on day 48 in rats with focal glomerulosclerosis. The mRNA levels of SMemb were thereafter gradually downregulated by day 80; however, they remained higher than those of control glomeruli. These data suggest that glomerular embryonic nonmuscle-type myosin heavy chain is abnormally regulated in glomerulosclerosis and that glomerulosclerosis may be associated with dedifferentiation of not only the mesangial cells, but also the other resident glomerular cells.

Chronic pressure overload is known to increase cardiac mass and expression levels of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs. Although mechanical stretching of cardiac myocytes could cause these changes, humoral factor(s) secondary to pressure overload may also be involved. To dissociate humoral effects from the effects of mechanical loading on cardiac hypertrophic responses, we examined expression of ANP and BNP at both mRNA and protein levels and proportions of myosin isoforms in transplanted cervical hearts that were mechanically unloaded under conditions with or without hypertension by aortic coarctation. Seven days after transplantation, cardiac atrophy that usually occurs in transplanted hearts without hypertension by coarctation was prevented in the transplanted hearts with hypertension by coarctation. The levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts with relative to those without hypertension by coarctation. The plasma level of angiotensin II was higher in rats with than without hypertension by coarctation. Plasma endothelin-1 levels were not significantly different between the two groups. In addition, levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts without hypertension relative to those in the in situ hearts. The proportion of the V3 myosin isoform was also increased in the transplanted hearts without hypertension relative to the in situ hearts. These results indicate that humoral factor(s) secondary to the pressure overload produced by aortic coarctation enhanced the cardiac hypertrophic response and elevated the levels of mRNAs encoding these embryonic markers. Moreover, our findings regarding ANP and BNP expression in the transplanted hearts provide additional evidence that the fetal genes are reexpressed during the process of cardiac atrophy as well as in cardiac hypertrophy.