永井 良三

Pulmonary nocardiosis during immunosuppressive therapy for idiopathic pulmonary fibrosis MAENO Y, SANDO Y, UBUKATA M, MAENO T, TAJIMA S, HOSONO T, SATO M, TSUKAGOSHI M, SUGA T, KURABAYASHI M, NAGAI R. Respirology, 2000: 5 393-395 Nocardiosis is a subacute or chronic suppurative infection caused by Nocardia species. Although it is more common in immunocompromised hosts, idiopathic pulmonary fibrosis (IPF) has not been recognized as a predisposing factor for nocardial infection. We report a case of IPF, in which pulmonary nocardiosis developed during treatment with prednisolone and cyclophosphamide. The risk of pulmonary nocardiosis may be increased in cases of IPF on immunosuppressive therapy. Since IPF often accompanies lung carcinoma, it is important to correctly differentiate nocardiosis from carcinoma.

Neuroblastoma is a tumor that is derived from the neural crest. Recent studies demonstrated that several human neuroblastoma cell lines exhibit at least three morphologic types: neuroblastic (N)-type, substrate-adhesive (S)-type and intermediate (D-type cells. However, the origin of the S-type cells has not been clearly identified. In this study, the expressions of smooth muscle-specific proteins (desmin, α-smooth muscle actin, basic calponin and the smooth muscle myosin heavy-chain isoforms of SM1 and SM2) in three parent and four cloned neuroblastoma cell lines, composed of S-type cells, were examined by indirect immunofluorescence, Western blot and/or by reverse transcription-polymerase chain reaction (RT-PCR). Desmin was found in two of the seven cell lines, and α-smooth muscle actin and basic calponin were detected in all of seven of the cell lines. In three parent cell lines and one cloned cell line composed of N-type cells, none of three smooth muscle-specific proteins were detected. In smooth muscle myosin heavy-chain isoforms, SM1 was detected in two parent cell lines composed of S-type cells (MP-N-MS and KP-N-YS) by immunofluorescence, Western blot and/or by RT-PCR, whereas the SM2 isoform was detected in one parent cell line (MP-N-MS) by RT-PCR. These findings indicate that S-type cells have either the immature or mature smooth muscle cell phenotype, and neural crest cells very likely have the ability of to differentiate into smooth muscle cells in the human system.

This study was designed to evaluate the effects of an Na+/H+ exchange inhibitor, SM-20550, on ischemia-reperfusion injury in the skeletal muscle. Male Sprague-Dawley rats were exposed to ischemia and reperfusion by clamping and releasing clamps both at the abdominal aorta and the bilateral femoral arteries. Rats were divided into three groups; the sham, the SM-20550 treated (SM), and the untreated control (Control) groups. In the SM and control groups, rats were exposed to 5-hr ischemia and 5-hr reperfusion. In the sham group, vessel isolation only was performed. SM-20550 (2.8 mg/kg/hr) in the SM group or vehicle in the sham and control group was continuously administered during ischemia and reperfusion periods. The wall thickness of the vessels were significantly (p<0.01) decreased in the control group than any other group. The internal diameter was significantly (p<0.01) higher in the control and SM group than in the sham group. The wall thickness/internal diameter ratio was significantly (p<0.05) lower in the control group than in the SM group. Thus, an Na+/H+ exchange inhibitor, SM-20550, ameliorated the morphological change due to ischemia reperfusion. These findings provide a clue into the mechanism of ischemia reperfusion injury.

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.

This study was designed to elucidate whether left precordial negative T waves are electrocardiographic indicators for the diagnosis of hypertrophic cardiomyopathy (HCM) even in the presence of complete right bundle branch block (CRBBB). In 7 consecutive patients with CRBBB accompanied by negative T waves in at least one of the left precordial leads (V4, V5, V6, maximal negativity; 1.06 +/- 0.40 mVol) (left precordial negative T wave group) and in 15 randomly selected CRBBB patients without left precordial T wave inversions (control group), echocardiography was performed to rule out underlying diseases causing left ventricular overload and to identify candidates for magnetic resonance (MR) imaging. None had anginal pain indicating ischemic heart disease. When 2-dimensional echocardiography indicated left ventricular hypertrophy with wall thickness > or = 15 mm, the magnitude and distribution of hypertrophy were scrutinized on contiguous left ventricular MR short-axis images. The diagnostic criterion of HCM was the demonstration of hypertrophy with a wall thickness of 20 mm or more on the left ventricular MR short-axis images. All patients in the left precordial negative T wave group had negative T waves in both I (negativity; 0.27 +/- 0.17 mVol) and aVL (negativity; 0.23 +/- 0.14 mVol), whereas none in the control group did. The diagnostic criterion for HCM was fulfilled in six patients in the left precordial negative T wave group. However there were no patients who fulfilled the criterion in the control group. Negative T waves were recorded in the I (negativity; 0.30 +/- 0.17 mVol), aVL (negativity; 0.25 +/- 0.14 mVol), V4 (negativity; 1.03 +/- 0.46 mVol), V5 (negativity; 0.83 +/- 0.37 mVol) and V6 leads (negativity; 0.31 +/- 0.31 mVol) in all patients with HCM, while they were recorded in only 6% of the patients without HCM. In conclusion, the existence of left precordial negative T waves in the presence of CRBBB strongly indicates HCM.

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.

We investigated the role of ceruloplasmin in the antioxidative process in the brain in a patient with hereditary ceruloplasmin deficiency (HCD). Immunohistochemistry revealed an accumulation of N-epsilon-(carboxymethyl) lysine (CML) in basal ganglia of the HCD brain. In vitro study disclosed that ceruloplasmin inhibited CML formation from glycated proteins through the reaction of Fe2+ with H2O2 by Fenton reaction. These data suggest that ceruloplasmin plays an important role in the protection of neurons against oxidative stress associated with iron metabolism.

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.

Chest images of five cases with multicentric Castleman's disease were evaluated. Lymphadenopathy was noted in all five cases. Two of them were suffering from interstitial pneumonia. Retention of pleural effusions were found in the other three cases. The enlarged lymph nodes were usually enhanced with contrast material strongly and homogeneously on computed tomography. In cases with interstitial pneumonia, small densities were scattered mainly in lung basal regions, admixed with small number of nodules up to 1cm in diameter. The bronchovascular bundles and pleura were unevenly thickened. One of these with interstitial pneumonia was diagnosed as lymphoid interstitial pneumonia pathologically.

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.

Dilated cardiomyopathy (DCM) is defined echoeardiographic analysis by a dilated left ventricle with globally reduced systolic function. Echoeardiographic investigation of mitral and tricuspid regurgitation was made in patients with different stages of DCM. The purpose of this study was evaluated the grade of valvula regurgitation by echoeardiographic analysis in 190 patients with DCM. The mean left ventricular end systolic dimension, mean left ventricular end diastolic dimension, and percent of mean left ventricular ejection fraction, were significantly (P&lt 0.05) worse in nonsurvivors than in survivors after 5 year observation. Although the grade of mitral and tricuspid regurgitation were significantly worse in nonsurvivors than in survivors, the regurgitation of aortic or pulmonary value were not different between the two groups. The regurgitation of mitral and tricuspid valve appears to be an important prognostic indicator for patients with DCM. © 1999, The Kitakanto Medical Society. All rights reserved.

To better understand the role of advanced glycation end products (AGEs) in atherogenesis, we developed specific antibodies against different immunological epitopes of AGE structures, including N-epsilon-(carboxymethyl)lysine-protein adduct (CML) and a structure(s) other than CML (nonCML), and demonstrated the immunohistochemical localization of CML- and nonCML-epitopes in atherosclerotic lesions of human aorta, which were obtained at autopsy from 20 nondiabetic patients (12 males and eight females; mean age, 60.8 +/- 16.7 years). Monoclonal anti-CML antibody (6D12) recognized not only AGE-modified proteins, but also CML-modified proteins. On the other hand, polyclonal anti-nonCML antibody reacted to AGE-modified proteins, but not to CML-modified proteins. Both antibodies were unreactive to the early-stage products of glycation, including fructose-modified butyloxycarbonyl-lysine and fructose-epsilon-aminocaproic acid. Atherosclerotic lesions included diffuse intimal thickening (DIT), fatty streaks (FS), atherosclerotic plaques (AP) and complicated lesions. An immunohistochemical analysis showed both CML- and nonCML-epitopes to be found along the collagen fibers in DIT in subjects more than 40 years old, but not in subjects less than 40 years old. CML-epitopes accumulated mainly in the cytoplasm of macrophage/foam cells, while nonCML-epitopes accumulated exclusively in the extracellular spaces in FS. APs showed the CML-epitope stored macrophage/foam cells, and the accumulation of both CML- and nonCML-epitopes in the lipid-rich fibrous area. An immunohistochemical analysis with a monoclonal antibody against oxidized low density lipoprotein (FOH1a/DLH3) showed the presence of this antigen within the cytoplasm of the macrophage/foam cells in atherosclerotic lesions, which were also positive for the CML-epitopes. These findings thus suggest that the heterogeneous localization of AGEs in atherosclerotic lesions depends on their different epitopes, and that a close link, therefore, exists between the peroxidation of LDL and the formation of AGEs in atherosclerotic lesions. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction, Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GrA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.

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.

Senile dementia of Alzheimer's type (SDAT) is reported to be less frequent in patients with Diabetes Mellitus. However the, the number of elderly people in still increasing in Japan, an is the incidence of diabetes mellitus, especially in middle-aged and elderly people. Thus, we can expect to encounter more elderly people with diabetes and SDAT. We encountered three patients with diabetes who were treated with insulin and in whom SDAT developed. In all three, control of blood glucose levels gradually worsened, despite increases in the dose of injected insulin. It was later found that they did not inject insulin properly because of SDAT. They lived alone and their dementia was not diagnosed before their admission to the hospital. In its early phase, SDAT can be difficult to diagnose, especially in patients who five alone. SDAT should be considered when the control of blood glucose levels for no apparent reason in elderly patients with diabetes.

The pathobiology of rapid intimal thickening following balloon angioplasty remains unsettled. Proteoglycans (PGs) expressed by smooth-muscle cells (SMCs) are known to participate in vascular responses to injury. In this analysis, patients ranging from age 48 to 79 years (mean = 58), underwent atherectomy for 36 restenotic tissues (taken 64 to 345 days postangioplasty; mean = 108) and for 10 primary atherosclerotic plaques. Tissues were formaldehyde-fixed, paraffin-embedded, and histochemically and immunohistochemically stained to determine the temporal and semi-quantitative contribution of major vessel wall PGs, versican, biglycan, and decorin. Versican was the most striking PG in the neointima of restenotic vessels, including a prominent pericellular pattern corresponding to proliferative SMCs, as well as a large extracellular accumulation. Biglycan was limited to the most loose and proliferative neointima and stained less than in primary plaques. Decorin staining was virtually absent in the most proliferative neointimal tissue, whereas it was quite striking in established primary lesions. Thus the earliest response to balloon injury of a coronary artery includes striking expression of versican protein, but the limited expression of biglycan differs from the prominence of the PG in primary atherosclerosis, Versican expression in restenotic lesions is similar to that seen previously in transplant arteriopathy, but the lack of biglycan in atherectomy specimens from restenosis sites is distinctively different from that seen in rapidly progressive transplant vascular disease. (C) 1998 by Elsevier Science Inc.

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.

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.

Despite the availability of diagnostic modalities such as transesophageal echocardiography, computed tomography or magnetic resonance imaging up to 30% of patients with acute aortic dissection remain undiagnosed before death. A novel immunoassay of serum smooth muscle myosin heavy chain was recently developed as a potential diagnostic tool for the detection of aortic dissection. The immunoassay was applied in two patients with an acute chest pain syndrome but no initial clinical suspicion of aortic disease. In both patients myocardial ischemia was ruled out by laboratory, electrocardiographic and echocardiographic examinations. In the first patient both dilation of the aorta and long-standing arterial hypertension were known; however, it was not before 48 h until dissection was suspected and a spiral-CT was performed demonstrating a localized ascending aortic dissection. At this time (48 h after onset of symptoms) the smooth muscle myosin heavy chain concentration in the serum was close to normal. In the other patient there was neither a suggestive history nor any clinical sign of aortic dissection. Widening of the abdominal aortic wall on an ultrasound examination was the key to the incidental diagnosis of a clinically unsuspected type B dissection. The serum test 12 h after onset of pain revealed elevated (diagnostic) serum levels of smooth muscle myosin heavy chains. Both cases exemplify important gaps in the diagnostic strategy for the detection of acute aortic dissection. A novel immunoassay for smooth muscle myosin heavy chains provides rapid and reliable diagnostic information especially in patients without clinically suspected aortic dissection and may avoid limitations in the diagnostic work-up of patients with acute aortic disease, if used early in the evaluation of patients with chest pain syndromes.

UNLABELLED: We compared myocardial viability evaluated by 18F-deoxyglucose (FDG) SPECT in 14 old myocardial infarction patients with that evaluated by 201TI SPECT and 123I-beta-methyl-iodophenyl pentadecanoic acid SPECT as imaging of fatty acid metabolism. FDG-SPECT was performed after oral administration of glucose. From each SPECT image which was divided into 7 segments, the degree of accumulation of each radioisotope (RI) was visually classified into four grades of defect score (ranging from 0 as normal to 3 as severe defect). The % uptake in the same area was also quantitatively calculated. RESULTS: The degree of accumulation of myocardial Rl relative to regional wall motion. FDG is the most wide for a range of accumulation of Rl of infarct area. Also, at FDG, in the area of wall motion had done a disorder, the degree of accumulation was higher than other two methods. In the infarcted area, the degree of accumulation on FDG-SPECT in the area of decreased wall motion was greater than that on the other two procedures. These results suggest that FDG-SPECT is useful for evaluating myocardial viability.

To assess the prognostic significance of myocardial contractile reserve in patients with idiopathic dilated cardiomyopathy (DCM) without overt heart failure (New York Heart Association functional class I or II), seventy-one patients underwent exercise radionuclide angiography in addition to clinical, radiographic, hemodynamic, and echocardiographic evaluations. Myocardial contractile reserve was assessed as left ventricular ejection fraction (LVEF) during peak exercise minus LVEF at rest (delta LVEF). During an average of 49 months, 18 patients died of the disease. Cox's proportional-hazards regression analysis showed that the delta LVEF was the most powerful and independent discriminator for survival (p = 0.0002). Ejection time (p = 0.0029) and cardiothoracic ratio (p = 0.017) were the second and third most predictive variables, respectively. Evaluation of the delta LVEF, which reflects residual myocardial contractile reserve, can provide important information about the prognosis of patients with DCM and mild symptoms.

We report a case of Rendu-Osler-Weber disease with recurrent brain and renal abscess caused by multiple pulmonary arteriovenous fistula. The patient was a 48-year-old man with the chief complaint of dyspnea. He had two arteriovenous fistulas on pulmonary angiography. Resection was performed for arteriovenous fistula with large drainage arteries. Coil embolization was added for another fistula and the complaint of patient was improved. Pulmonary arteriovenous fistula is an important disease for differential diagnosis in a case of recurrent multiorgan abscess without congenital heart diseases. Moreover, Rendu-Osler-Weber disease should be considered when patient has pulmonary arteriovenous fistulas. Coil embolization for multiple arteriovenous fistulas is a useful procedure because it can spare pulmonary function and be performed repeatedly.

L-arginine (Arg) and related amino acids are involved in the pathophysiology of cardiovascular disease. Endothelium-derived relaxing factor, nitric oxide (NO), is generated by vascular endothelial cells from Arg. In this study, high purity N(ω)-hydroxy-L-arginine (OHArg), an intermediate in the pathway generating NO, was synthesized, and the effects of Arg and OHArg on endothelium-dependent vascular relaxation were examined. OHArg caused a significant relaxation of endothelium-intact rat aortic rings that had been contracted by norepinephrine. OHArg was more potent than Arg at aortic relaxation (OHArg(ED80) = 10-7,4M versus Arg(ED80) = 10-5,5M). Neither OHArg nor Arg relaxed the endothelium-denuded or NO synthase-inhibited aortic rings. These results suggest that OHArg is more potent than Arg at inducing vascular relaxation that is endothelium-dependent and NO synthase-dependent. OHArg may be useful in the treatment of hypertension and in the prevention of atherosclerosis.

A 51-year-old woman was admitted with fever, cough and dyspnea. She had been taking Sairei-to, a traditional Chinese medicine, for 2 months. On admission, chest X-ray revealed a ground-glass appearance in the lung fields bilaterally and serum LDH was elevated. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed that lymphocytes were increased, with a decreased ratio of CD4/CD8 cells. A lymphocyte stimulation test (LST) for Sairei-to using the lymphocytes in BALF was a positive, although a test of peripheral blood was negative. Sairei-to-induced pneumonitis was diagnosed based on the clinical course, laboratory findings, BALF cell analysis and LST of BALF. Only 4 cases of pneumonitis due to Sairei-to have been reported. This case suggests that LST of BALF is useful for diagnosing drug-induced pneumonitis.

To evaluate the regional wall motion and the myocardial fatty acid metabolism at hibernating myocardium after revascularization (PTCA or CABG), we performed dual SPECT with 201Tl and 123I-beta-methyliodophenyl-pentadecanoic acid (BMIPP), and left ventriculography (LVG) in 34 patients with coronary artery disease before and 3 to 4 months after revascularization. In the SPECT, regional tracer uptake was estimated qualitatively (visual) and quantitatively (% uptake). Regional wall motion was estimated qualitatively (visual) and quantitatively (shortening fraction). At the 78 hibernating areas, the improvement of regional wall motion was more significantly (p < 0.05) correlated with that of regional tracer uptake of 123I-BMIPP (r = 0.63) than 201Tl (r = 0.39), and also correlated with the improvement of the difference between 201Tl and 123I-BMIPP regional uptake (r = 0.36). These results suggest that the improvement of wall motion at hibernating myocardium is more significantly correlated with the improvement of 123I-BMIPP than 201Tl uptake after revascularization.

The aim of this study was to determine the phenotypic modulation in mesangial cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar-Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in glomerular visceral epithelial cells. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the interstitium, especially around the Bowman's capsules. Manidipine ameliorated the glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in mesangial cells. In conclusion, the mesangial cells changed their phenotypes and expressed alpha-smooth muscle actin and SMemb in the glomeruli during the development of hypertensive renal damage. These phenotypically changed mesangial cells are considered to be activated and to produce various kinds of cytokines and extracellular matrix, which leads to glomerulosclerosis. Manidipine attenuated the glomerular damage and the phenotypic changes. The functional relevance of phenotypic changes in these cells should be elucidated in future studies.

We have previously shown that smooth muscle myosin heavy chain isoforms (SMs), including SM1, SM2, and SMemb, are differentially expressed during vascular development, and in vascular lesions, such as atherosclerosis. The SM1/2 gene is expressed exclusively in smooth muscle cells and generates SM1 and SM2 mRNAs by alternative splicing. Whereas SM1 is constitutively expressed from early development, SM2 appears only after birth. In this study, we have isolated and characterized the 5'-flanking region of the mouse SM1/2 gene. Transient transfection assays using a series of promoter-luciferase chimeric constructs demonstrated that tandem elements of the CCTCCC sequence, located at -89 and -61 bp relative to the transcription start site, were essential for transcriptional activity of the SM1/2 gene in primary cultured rabbit aortic smooth muscle cells and smooth muscle cell lines derived from the rabbit aorta but not in non-smooth muscle cells. Gel mobility shift assays indicated that CCTCCC was a binding site for nuclear proteins prepared from smooth muscle cells. Double-stranded oligonucleotides containing either the CACC box or the Sp1 consensus sequence efficiently competed with the CCTCCC elements for binding the nuclear extracts. Site-specific mutations of CCTCCC elements resulted in a significant reduction of the promoter activity. Moreover, CCTCCC elements are evolutionary conserved between mouse and rabbit. In conclusion, the results of this study indicate an important role for the interaction of the CCTCCC sequence with Sp1 or related factors in activating transcription from the SM1/2 gene promoter.

Romano-Ward syndrome, one of familial long QT syndromes, is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. By linkage analyses, three LQT loci were previously mapped: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, LQT3 on 3p21-24. It was recently brought to light that LQT2 and LQT3 were caused by mutations of the gene encoding cardiac ion channels. Mutations in HERG on chromosome 7q35-36, encoding potassium channels (Ikr), cause LQT2, and block of Ikr is a known mechanism for drug-induced prolongation of cardiac action potentials, which provides a mechanistic link between LQT2 and certain forms of acquired LQT. Mutations in SCN5A on chromosome 3p21, encoding the human heart voltage-gated sodium-channel alpha-subunit, cause LQT3. Mutant channels show a sustained inward sodium current during membrane depolarization, which explains prolongation of cardiac action potentials.