Biomedical subjects

R Nagai

Publications and source records attributed to R Nagai.

At least 253 records · Page 14Linked to original sources

PubMed1999

Increased severity of viral myocarditis in mice lacking lymphocyte maturation.

The role of lymphocytes in the pathogenesis of viral myocarditis is controversial. To better understand how lymphocyte maturation controls a virus-induced myocarditic process, a murine model of viral myocarditis was utilized. Encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and recombination activity gene (RAG)-2 knockout 129/SV mice. The RAG2 participate in the maturity of T and B lymphocytes. Survival rate, heart weight (HW), HW to body weight (BW) ratio, viral genome, cardiac inflammation and myocardial necrosis were evaluated after EMCV (500 plaque forming unit/mouse) inoculation. On post-inoculation day 10, the survival rate of C57BL/6, 129/SV and RAG2 knockout mice were 42, 90 and 0%, respectively. Myocardial viral titer was significantly (P<0.05) higher in C57BL/6 and RAG2 knockout mice than in 129/SV mice. In situ hybridization demonstrated the EMCV genome in the myocardium of RAG2 knockout and C57BL/6 mice, but not in 129/SV mice. At day 8, HW and HW/BW ratios were elevated (P<0.05) in RAG2 knockout mice as well as C57BL/6 mice compared with 129/SV mice. Myocardial necroses were more severe in RAG2 knockout mice than in wild-type 129/SV mice. In conclusion, matured lymphocytes protect the development of viral myocarditis which includes viral replication and myocardial apoptosis.

Animals↗

PubMed1999

Hormone replacement therapy in postmenopausal women with essential hypertension increases circulating plasma levels of bradykinin.

Hormone replacement therapy (HRT) reduces the incidence of cardiovascular disease (CVD) in postmenopausal women (PMW). Recently, it has been reported that HRT declines angiotensin converting enzyme (ACE) activity, which may be one of the factors protecting against CVD. We measured the plasma levels of bradykinin, which would be expected to increase because the bradykinin-degrading enzyme (kinase II) is the same as ACE. Treatment with conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/ day) was given for 3 months as HRT to 19 hypertensive and 19 normotensive PMW. Plasma bradykinin and ACE activity levels were measured at baseline and after 3 months of HRT. The plasma levels of ACE activity in both the hypertensive and normotensive PMW were significantly reduced by HRT. The plasma levels of bradykinin in the hypertensive PMW were significantly increased by HRT, whereas the administration of HRT tended to increase plasma levels of bradykinin in the normotensive PMW. The increased bradykinin levels with a concomitant decrease of plasma ACE activity by HRT in hypertensive PMW seem to be beneficial for reducing the risk of CVD.

Aged↗

PubMed1999

Production of radioactive endovascular stents by implantation of 133Xe ions.

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the renarrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.

Angioplasty, Balloon, Coronary↗

PubMed1999

Reduced production of nitric oxide during haemodialysis.

OBJECTIVE: To examine the influence of systemic nitric oxide (NO) synthesis on blood pressure in patients with chronic renal failure undergoing haemodialysis, since nitric oxides are susceptible to renal excretion or are dialysed, a different indicator that is unaffected by renal function, such as the level of exhaled NO was evaluated. We examined the levels of the endogenous NO before and after a haemodialysis session. DESIGN AND METHODS: We evaluated the serum concentrations of nitrite/nitrate and the rate of nitric oxide release into exhaled air in 10 patients with hypertension who were receiving maintenance haemodialysis. RESULTS: The serum concentrations of nitrite/nitrate before haemodialysis were significantly higher than those in 10 normal controls (183 +/- 151 microM vs 42 +/- 17 microM, P < 0.05). These levels decreased significantly by the end of haemodialysis (42 +/- 26 microM). Because the amount of nitric oxide in the deepest expirate correlated well with the duration of exhalation, we were able to derive the rate of release of NO. The rate of NO release was 0.034 +/- 0.012 nmol/sec before haemodialysis, similar to that in normal controls (0.031 +/- 0.013nmol/sec). The rate was significantly reduced after dialysis (0.023 +/- 0.010 nmol/sec) (P < 0.05). The mean pre-dialysis mean blood pressure (109 +/- 11 mm Hg) and the post-dialysis blood pressure (106 +/- 9 mm Hg) were the same. CONCLUSIONS: These data indicate that NO production does not appear to have a critical role in control of arterial blood pressure across haemodialysis in patients with chronic renal failure.

Adult↗

PubMed1999

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration.

BACKGROUND: Ultra-filtration failure is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD). This complication is related to histological changes of the peritoneum, i.e. severe interstitial fibrosis and microvascular sclerosis. Although their pathogenesis has not been elucidated yet, advanced glycation end products (AGEs) have been shown to accumulate in the peritoneal tissue of CAPD patients. METHODS: Peritoneal biopsy specimens from 14 CAPD patients with low ultra-filtration (n = 9) and high ultra-filtration (n = 5) capacity were immunohistochemically investigated using a monoclonal antibody against AGEs (6D12). The severity of peritoneal fibrosis, microvascular sclerosis and intensity of AGE accumulation were semi-quantitatively evaluated. Peritoneal ultra-filtration capacity was evaluated by calculating daily ultrafiltration volume per body weight (UFV/BW) and D/D0 (glucose) of the peritoneal equilibration test. RESULTS: In all patients with low ultra-filtration, AGE accumulated in the peritoneal fibrous tissue and microvascular walls. Remarkably, AGE accumulated more intensely in hyalinized fibrosis of small venular media. Extent of AGE accumulation in peritoneal interstitium and vascular walls correlated with the progression of interstitial fibrosis (rho = 0.727, P = 0.0088) and vascular sclerosis (rho = 0.915, P = 0.001). UFV/BW was inversely correlated to interstitial fibrosis (rho = -0.660, P = 0.0174), microvascular sclerosis (rho = -0.671, P = 0.0155) and microvascular AGE accumulation (rho = -0.678, P = 0.0145). CONCLUSIONS: In CAPD patients, AGE formation in the peritoneum correlates with the development of severe interstitial fibrosis and microvascular sclerosis, which is associated clinically with impaired peritoneal ultra-filtration.

Adult↗

PubMed1999

Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts.

To determine whether ANG II as well as mechanical stress affect the production of tumor necrosis factor (TNF) in the heart, neonatal rat cardiac myocytes and fibroblasts were cultured separately and treated for 6 h with ANG II, lipopolysaccharide (LPS), or cyclic mechanical stretch. LPS induced the production of TNF in cardiac myocytes and fibroblasts. However, TNF synthesis in fibroblasts was 20- to 40-fold higher than in myocytes. ANG II (>/=10(-8) M) and mechanical stretch stimulated the production of TNF in cardiac fibroblasts but not in myocytes. Furthermore, both ANG II and LPS increased the expression of TNF-alpha mRNA in cardiac fibroblasts. Isoproterenol inhibited both LPS- and ANG II-induced production of TNF in cardiac fibroblasts with increasing intracellular cAMP level. Moreover, both isoproterenol and dibutyryl cAMP inhibited LPS-induced TNF-alpha mRNA expression. Thus activation of the renin-angiotensin system, as well as mechanical stress, can stimulate production of TNF in cardiac fibroblasts. Furthermore, beta-adrenergic receptors may be responsible for the regulation of TNF synthesis at the transcriptional level by elevating intracellular cAMP.

Angiotensin II↗

PubMed1999

Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice.

Endothelin (ET)-1 has been shown to have various pathophysiological roles in the lung. Recently, it has been reported that ET-1 and a gene encoding ET-1 (Edn1) might be involved in airway hyperresponsiveness, which is a major feature of bronchial asthma. Meanwhile, it remains unclear whether ET-1 might be involved in airway remodeling in vivo. In the present study, we hypothesized whether ET-1 might play a role in airway remodeling, leading to altered responsiveness. To test this hypothesis, we investigated airway function in vivo and airway wall structure in Edn1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and Edn1(+/+) wild-type mice. In the physiological study, enhanced responses in lung elastance and resistance to methacholine administration were observed in Edn1(+/-) mice, whereas there was no difference in serotonin responsiveness. In the morphometric study, there were no differences in either lamina propria or airway smooth muscle thickness between Edn1(+/-) mice and Edn1(+/+) mice. These findings suggest that ET-1 gene disruption is involved in methacholine pulmonary hyperresponsiveness via functional mechanism, but not airway remodeling, in mice. The ET-1 knockout mice may provide appropriate models to study diseases related to ET-1 metabolism.

Airway Resistance↗

PubMed1999

C-Reactive protein in dilated cardiomyopathy.

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5-8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1. 05 +/- 1.37 vs. 0.49 +/- 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.

Adult↗

PubMed1999

An interleukin-6-producing cardiac myxoma associated with mediastinal lymphadenopathy.

We report our experience with a patient whose mediastinal lymphadenopathy resolved after resection of a cardiac myxoma that secreted interleukin-6 (IL-6). The patient was a 68-year-old female who complained of nocturnal chest discomfort related to congestive heart failure. An echocardiogram demonstrated a large left atrial mass. A computed tomogram showed not only the left atrial mass but multiple enlarged mediastinal lymph nodes. The serum IL-6 level was markedly elevated at 13.7 pg/ml. After resection of the cardiac myxoma, serum IL-6 returned to the normal range. A repeat computed tomogram showed no mediastinal lymphadenopathy. We believe that overproduction of IL-6 by the cardiac myxoma was the cause of the mediastinal lymphadenopathy.

Aged↗

PubMed1999

Sudden death with malignant hemangioendothelioma originating in the pericardium--a case report.

The authors report a rare case of a malignant hemangioendothelioma (MH) originating in the pericardium. In this case, a metastatic skin lesion was found first, and subsequently the existence of a primary cardiac lesion was confirmed. Generally, primary cardiac tumors grow slowly, and the prognosis of MH is relatively good. In this case, however, the patient died suddenly during the creation of a pericardial window for drainage. An autopsy showed that the MH originated from a pericardial lesion in the right atrium.

Death, Sudden↗

PubMed1999

Loculated pericardial effusion due to congestive heart failure: an unusual case of vanishing tumor--a case report.

Loculation of a pleural effusion within an interlobar fissure as a result of congestive heart failure is a well-known entity. It has been termed "vanishing" or "phantom" tumor because its roentgenographic appearance simulates a pulmonary tumor and resolves with treatment of the congestive heart failure. The authors describe an 89-year-old man with a loculated pericardial effusion on the left cardiac border on chest roentgenogram. This was initially thought to represent an occult metastatic malignancy; however, its etiology became obvious when it disappeared with therapy of heart failure. Loculated pericardial effusion should be included in the differential diagnosis of roentgenographic densities in the chest when seen on the left cardiac border.

Aged↗

PubMed1999

The time from anaerobic threshold (AT) to respiratory compensation point reflects the rate of aerobic and anaerobic metabolism after the AT in chronic heart failure patients.

The significance of the time from anaerobic threshold to respiratory compensation point (RCP-AT time) in patients with chronic heart failure was investigated. Thirty-seven patients with chronic heart failure (New York Heart Association class II or III) were enrolled into the study. Cardiopulmonary exercise testing was performed using breath-by-breath gas sampling. A bicycle ergometer was used, and incremental exercise testing was carried out. Anaerobic threshold, respiratory compensation point (RCP), and the slope of oxygen uptake (VO2) as a function of work rate (deltaVO2/deltaWR) were measured. A positive correlation (r=0.53) between RCP-AT time and deltaVO2/deltaWR was found. RCP-AT time was corrected for the whole exercise period (ramp exercise-RCP point), and the correlation between corrected RCP-AT time and deltaVO2/deltaWR was still present (r=0.46). There was no correlation between RCP-AT time and anaerobic threshold. These findings suggest that RCP-AT time is a new parameter that reflects the rate of the aerobic and anaerobic metabolism after AT.

Anaerobic Threshold↗

PubMed1999

Biopsy-proven cardiomyopathy in heterozygous Fabry's disease.

A 23-year-old woman with heterozygous Fabry's disease who had acroparesthesia was admitted to hospital for precise examination of the disease before childbearing. She had no cardiac-related symptoms and no abnormality on physical examination. The alpha-galactosidase A activity in her leukocytes was present, but lower than normal. However, the endomyocardial biopsy showed specific changes for Fabry's disease. As Fabry's disease is a rare X-linked recessive inborn error of glycosphingolipid metabolism, heterozygous females are usually asymptomatic, but rarely can be affected as severely as hemizygous males. This is an isolated case of heterozygous Fabry's disease in a female in whom cardiac involvement was detected by endomyocardial biopsy, although she had no cardiac abnormality on physiological examinations. In conclusion, endomyocardial biopsy is useful for evaluation of the cardiac involvement of Fabry's disease even in an asymptomatic case.

Adult↗

PubMed1999

Dietary salt loading increases nitric oxide synthesis in transgenic mice overexpressing sodium-proton exchanger.

We studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.

Animals↗

PubMed1999

Biochemical diagnosis of aortic dissection: from bench to bedside.

Aortic dissection is an acute cardiovascular disease associated with high mortality and morbidity. Although uncommon, recent studies have shown that the incidence of this catastrophic disease is steadily increasing. Unfortunately, the disease is still not well recognized on clinical presentation due to lack of specific signs and symptoms. As early diagnosis and initial management are critical for survival, we focused on developing a biochemical diagnostic approach for this disease given its meritorious properties in use in the acute clinical situation and additional projected combined use with established imaging modalities. Studies using an assay developed against smooth muscle myosin heavy chain, a protein which is released from the aortic medial smooth muscle cells on insult to the aortic wall, showed promising results for use of this assay in the diagnosis of aortic dissection. The background of this pioneering assay in addition to its clinical use are discussed in this review.

Acute Disease↗

PubMed1999

Clinical implication of left precordial T wave inversions in the presence of complete right bundle branch block.

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.

Bundle-Branch Block↗

PubMed1999

Embryonic smooth muscle myosin heavy chain SMemb is expressed in pressure-overloaded cardiac fibroblasts.

Left ventricular hypertrophy (LVH) is a secondary adaptation to increased external load. Various qualitative and quantitative changes in myocytes and extracellular components occur during the development of LVH. It has recently been demonstrated that alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblasts appear in the interstitium of the heart subjected to increased workload suggesting that cardiac fibroblasts as well as myocytes alter their phenotype in response to pressure overload. In the present study, to explore the load-induced response and phenotypic modulation of cardiac fibroblasts, the localization of embryonic smooth muscle myosin heavy chain (SMemb) and alpha-SMA in thoracic aorta-constricted rat hearts was investigated by immunohistochemistry, and the morphology of the SMemb-expressing cells was examined by electron microscopy. In addition, to clarify the mechanisms by which SMemb is induced in pressure-overloaded hearts, mRNA expression of SMemb in aorta-constricted rat hearts and in transforming growth factor-beta1 (TGF-beta1)-treated or mechanically-stretched cultured cardiac fibroblasts was investigated. Enhanced staining of SMemb and alpha-SMA was detected in the interstitial spindle-shaped cells in the fibrotic lesions of the pressure-overloaded left ventricles by immunohistochemistry. These cells were demonstrated by electron microscopy to have features specific for activated fibroblasts such as serrated nuclei or prominent rough endoplasmic reticulum. These cells also had characteristic features of myofibroblasts, i.e. irregularly arranged actin filaments and scattered dense bodies. Northern blot analysis revealed increased mRNA levels of SMemb both in aorta-constricted rat hearts and in cultured cardiac fibroblasts stimulated by TGF-beta1 or by mechanical stretch. These results suggest that SMemb may be a molecular marker both for the detection of activated cardiac fibroblasts that may play important roles in the remodeling of pressure-overloaded cardiac interstitium, and for the identification of the regu latory mechanisms that control the phenotypic modulation of cardiac fibroblasts in response to pressure overload.

Actins↗

PubMed1999

Autoantibody against N(epsilon)-(carboxymethyl)lysine: an advanced glycation end product of the Maillard reaction.

Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure.

Animals↗