Biomedical subjects

Motoyuki Nakamura

Publications and source records attributed to Motoyuki Nakamura.

At least 37 records · Page 2Linked to original sources

PubMed2005

Quantitative determination of incarvillateine in Incarvillea sinensis by solid phase extraction and high performance liquid chromatography.

Method for rapid quantitative analysis of incarvillateine in Incarvillea sinensis by high-performance liquid chromatography (HPLC) has been developed. The sample preparation involves solid phase extraction (SPE) with a mixed-mode reversed-phase and cation-exchange cartridge. The linear calibration range for incarvillateine was 0.002-0.5 mg/ml. The limit of detection was 0.35 microg/ml (S/N=3). Intra- and interday precisions were less than 0.36% (n=6) and 1.61% (n=18), respectively. The recovery of incarvillateine was 97.61-102.44% with the relative standard deviation (RSD) ranging from 0.63 to 1.93% (n=3). This method was proposed as a simple, rapid and accurate method for quantitative determination of incarvillateine content in various samples of Incarvillea sinensis collected from different areas of China.

Alkaloids↗

PubMed2005

Effort angina in a middle-aged woman with abnormally high levels of serum high-density lipoprotein cholesterol: a case of cholesteryl-ester transfer protein deficiency.

A 54-year-old female was admitted to hospital complaining of oppressive anterior chest pain during exercise. Treadmill exercise ECG testing showed significant ischemic ECG changes, and electron-beam computed tomography demonstrated patchy calcifications in the coronary artery. Coronary angiography revealed a significant stenotic lesion of the right coronary artery. On routine investigations, no classical coronary risk factors were found, although a very high concentration (209 mg/dl) of high-density lipoprotein cholesterol (HDL-C) was detected. The serum concentration of cholesteryl-ester transfer protein (CETP), which plays a central role in the reverse cholesterol transport system, was measured and found to be less than the measurable minimum. The patient showed one of the typical genetic CETP mutations (intone 14 splicing defect), and her lipid profile was improved by administration of probucol for 3 months. A very high concentration of HDL-C with a defect of CETP activity may be a specific biochemical indicator pointing to an increased risk of premature coronary artery disease, and the lipid profile can be improved by use of lipid-lowering drugs.

Angina Pectoris↗

PubMed2005

Plasma B-type natriuretic peptide levels and risk factors for congestive heart failure in a Japanese general population.

This cross-sectional study was performed to establish the rationale for BNP testing for identifying subjects at high risk of congestive heart failure (CHF) in a screening setting. Plasma BNP concentrations were measured in 8,178 community-dwelling residents (mean age, 62 +/- 12 years; 3,194 males). First, in order to determine age- and sex-related reference values for plasma BNP levels, subjects having factors known to influence plasma BNP levels were excluded. The remaining 3,410 subjects were eligible for the reference study. Second, to verify BNP testing for screening for subjects at high risk of CHF, the clinical characteristics of subjects showing abnormally high plasma BNP levels (> or = 97.5 percentile for each age- and sex-specific value of the reference cohort) were examined. In the reference subjects, plasma BNP levels increased with age in both genders, and were higher in women than in men. In the original cohort, age- and sex-specific reference values for high plasma BNP levels were related to the presence of major ECG abnormalities, hypertension, mildly elevated serum creatinine levels, and a history of coronary heart disease. The results of the present study indicate that individuals with high plasma BNP levels in the community have accumulating risk factors for CHF. This suggests that plasma BNP measurement may be a useful screening test for identification of individuals at high risk of CHF within a Japanese general population.

Adult↗

PubMed2005

Comparison of positive cases for B-type natriuretic peptide and ECG testing for identification of precursor forms of heart failure in an elderly population.

Plasma B-type natriuretic peptide (BNP) levels have been reported to be elevated in various types of cardiac disorders and in precursors of CHF. To elucidate the potential ability of BNP testing to identify individuals with structural cardiac disease (ie, hypertensive heart disease, coronary heart disease, valvular heart disease) among community-dwelling elderly persons, cases which were positive on BNP testing were compared to those positive on ECG testing. In the initial phase, we performed plasma BNP measurements and ECG in 856 participants (age > or = 65 years) selected from a general population. From within this group, subjects with an abnormal ECG (n = 125) were selected according to the Minnesota code. Subjects with elevated BNP were selected independently on the basis of plasma levels (n = 112). In the next phase, subjects in both groups were invited to complete Rose's angina questionnaire and to undergo physical examination and transthoracic echocardiography. In this subject group (positive in ECG testing and/or BNP testing), the two tests had comparable sensitivity (65% versus 59%: NS) and specificity (40% versus 41%: NS) for identifying hypertensive heart disease (n = 17). For coronary heart disease (n = 12), the two tests had also comparable sensitivity (58% versus 42%: NS) and specificity (39% versus 41%: NS). However, for selection of valvular heart disease (n = 7), BNP testing had higher sensitivity than ECG testing (100% versus 14%; P < 0.01) with comparable specificity (43% versus 40%: NS). Several types of structural heart disease, in particular valvular heart disease, could be identified exclusively by BNP testing, suggesting that BNP measurement can make a significant contribution to screening for CHF precursors when used in combination with ECG in elderly populations.

Aged↗

PubMed2005

Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic approaches to patients with end-stage renal disease study.

BACKGROUND: The prevalence of cardiovascular risk factors and the prevalence of comorbidities in adult hemodialysis patients in Japan are not fully understood. METHODS: In "Kaleidoscopic Approaches to Patients with End-stage Renal Disease Study" (The KAREN Study, 2003), trained research stuff examined 1,214 adult hemodialysis patients (mean age, 61.2 years; 779 males and 435 females) of 1,506 patients in northern areas of Iwate Prefecture. Cardiovascular risk factors and the prevalence of comorbidities in hemodialysis patients were compared with those in the general population using direct age-adjustment methodology and standardized morbidity ratios (SMRs). RESULTS: In hemodialysis patients, common causes of end-stage renal disease were chronic glomerulonephritis (29.8%), diabetic nephropathy (24.5%), and other diseases. Prevalence and SMR of myocardial infarction were 5% and 9.6, respectively, and those of stroke were 13% and 5.7. The prevalences of hypertension and diabetes mellitus were 87% and 29%, respectively. Mean systolic blood pressure and mean diastolic blood pressure were 155 mmHg and 85 mmHg, respectively. Mean levels of total serum cholesterol, high-density lipoprotein cholesterol, and albumin in patients with end-stage renal disease were lower than those of the general population (160.6 vs. 203.3 mg/dL, 48.5 vs. 59.7 mg/dL, and 3.7 vs. 4.4 g/dL, respectively). Mean levels of C-reactive protein were higher than those of the general population (3.80 vs. 1.16 mg/L). CONCLUSION: Hemodialysis patients have a high prevalence of cardiovascular risk factors and comorbidities. Levels of nutrition-related markers were lower, and C-reactive protein levels were higher, in hemodialysis patients than in the general population.

Adult↗

PubMed2004

Antitumor effects of fusions composed of dendritic cells and fibroblasts transfected with genomic DNA from tumor cells.

Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell-based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA.

Animals↗

PubMed2004

Muscle metaboreflex is blunted with reduced vascular resistance response of nonexercised limb in patients with chronic heart failure.

BACKGROUND: Exercise-mediated muscle metaboreflex (MMR) activates the sympathetic nervous system afferently and may play an important role in the reduction in blood flow in nonexercised limb, thus enhancing exercised skeletal muscle blood flow (ie, normal regional blood flow redistribution during exercise). However, few data are available to describe the relationship between MMR and peripheral vascular control during exercise in congestive heart failure (CHF). The aim of this study was to determine whether MMR is impaired in CHF, and, if so, whether MMR is related to clinical severity of CHF and to changes in nonexercised limb vascular resistance in CHF. METHODS AND RESULTS: Eleven CHF patients and 9 healthy age- and gender-matched controls were examined. All subjects performed a rhythmic handgrip exercise test at 50% of maximal voluntary contraction for 3 minutes on 2 occasions with and without postexercise upper arm regional circulatory occlusion (RCO/non-RCO). Changes in systolic blood pressure were measured and plotted against protocol time for both RCO and non-RCO. The area under each curve was estimated, and the calculating difference in the area between RCO and non-RCO was regarded as MMR. In addition, changes in calf vascular resistance were measured continuously by plethysmography after the handgrip test and the area differences between the RCO and non-RCO data was taken to represent MMR-provoked resistance changes in the nonexercised limb. During the handgrip exercise, systolic blood pressure increased similarly on the 2 occasions for both groups. MMR was significantly lower in CHF patients than in controls (68.2 +/- 23.1 versus 160.4 +/- 29.6 arbitrary units; P < .05). Decrease in MMR activity was related to clinical severity of CHF (controls, 160.4 +/- 29.6; New York Heart Association class II, 87.6 +/- 29.8; New York Heart Association class III, 34.3 +/- 34.8 arbitrary units; P < .05). The increase in calf vascular resistance between RCO and non-RCO protocols in the control group was significant (+146.5 +/- 38.0 arbitrary units; P < .05), whereas the difference in the CHF group was not significant (-72.9 +/- 126.9 arbitrary units; not significant). CONCLUSIONS: Exercise-induced MMR control in mild to moderate CHF is impaired in association with a blunted increase in nonexercised limb vascular resistance. This suggests that blunted MMR activity impairs regional blood flow redistribution and may contribute in part to exercise intolerance in this disorder.

Exercise↗

PubMed2004

Increased expression of tumor necrosis factor-alpha converting enzyme and tumor necrosis factor-alpha in peripheral blood mononuclear cells in patients with advanced congestive heart failure.

BACKGROUND: Tumor necrosis factor-alpha converting enzyme (TACE) has recently been identified as a metalloproteinase-disintegrin, which converts pro-tumor necrosis factor-alpha (TNF-alpha) to the mature form, and is an important mediator in the pathogenesis of CHF. AIMS: In order to establish the importance of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF-alpha in PBMC obtained from patients with congestive heart failure (CHF). METHODS AND RESULTS: PBMC were obtained from 46 patients with CHF and 22 controls. PBMC were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF-alpha were higher in CHF than in controls (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60, P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was divided into two subgroups by NYHA functional class (I and II vs. III and IV), levels of TACE and TNF-alpha were significantly higher in severe CHF patients (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001; intracellular protein levels: P<0.001). CONCLUSION: These results demonstrate that in patients with CHF, and especially those with severe CHF, TACE expression in PBMC increases with TNF-alpha expression. These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may be a potential target for the inhibition of cellular TNF-alpha production in CHF.

ADAM Proteins↗

PubMed2004

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure.

BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.

Blood Flow Velocity↗

PubMed2004

Toll-like receptor 4 is expressed with enteroviral replication in myocardium from patients with dilated cardiomyopathy.

Expressions of innate immune response proteins, most notably proinflammatory cytokines, against enteroviral (EV) infection have been documented in the heart of human dilated cardiomyopathy (DCM). Toll-like receptor 4 (TLR4) activates signaling pathways leading to the expression of proinflammatory cytokines implicated the etiology of DCM. We sought to determine whether EV replication activates TLR4-dependent immune response in myocardium obtained from patients with DCM. Endomyocardial biopsy tissues were obtained from 56 patients with DCM and 10 controls. Levels of plus- and minus-strand EV RNA and TLR4 mRNA were measured by real-time RT-PCR. Immunohistochemical analysis was performed to identify the cellular source of EV capsid protein VP1 and TLR4. Both plus- and minus-strand EV RNA were detected in 19 DCM patients (34%). Neither strand of EV RNA was detected in controls. TLR4 mRNA levels were higher in DCM patients than in controls (P<0.001). A positive correlation was found between TLR4 levels and each strand type of EV RNA in EV RNA-positive patients (plus-strand vs TLR4: r=0.69, P<0.001; minus-strand vs TLR4: r=0.65, P=0.002). VP1/TLR4 double staining showed extensive colocalization of VP1 and TLR4 proteins in cytoplasm of cardiac myocytes in myocardium obtained from DCM patients. EV RNA-positive patients showed lower systolic function and larger ventricular volume compared with EV RNA-negative patients left ventricular ejection fraction (LVEF): P=0.002; left ventricular end-systolic diameter (LVESD): P=0.004). The DCM subgroup with high TLR4 levels showed lower LVEF and larger LVESD than the subgroup with TLR4 levels (both P<0.001). This study suggests that myocardial expression of TLR4 associates with EV replication in human DCM. EV RNA and TLR4 mRNA levels may correlate with LV dysfunction in DCM. The expression of TLR4 against EV replication may be involved in the pathogenesis of DCM.

Adolescent↗

PubMed2004

Expression and localization of tumour necrosis factor-alpha and its converting enzyme in human abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is characterized by chronic aortic wall inflammation and loss of matrix components. Proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) are thought to be involved in this inflammatory process and, therefore, to play an important role in the pathogenesis of human AAA. TNF-alpha-converting enzyme (TACE) has recently been purified and cloned as a disintegrin and metalloproteinase that converts TNF-alpha precursor into its mature form. The aim of the present study was to determine whether TNF-alpha and TACE were expressed and localized in aortic tissues in human AAA. Infrarenal aortic tissues were obtained from AAA patients (n=19) undergoing elective aneurysm reconstruction and from autopsy cases without cardiovascular disorders as normal controls (n=5). Internal thoracic artery samples were also obtained from patients with coronary artery disease undergoing coronary artery bypass grafting to represent biopsied conduit vessels (n=5). The AAA specimens were taken from the mid-portion of the aneurysm and from the longitudinal transition zone between the non-dilated aorta and the proximal aspect of the aneurysm. TNF-alpha and TACE mRNA levels were determined by real-time quantitative reverse transcriptase-PCR. Expression levels of both TNF-alpha mRNA and TACE mRNA were significantly greater in the transition zone than in the mid-portion (both P<0.05). Expression levels of both forms of mRNA were significantly higher in AAA samples than in control aortas or atherosclerotic arteries. There was a significant correlation between the expression of TNF-alpha mRNA with that of TACE mRNA in AAA (r=0.54, P<0.005). Immunostaining was positive for both TNF-alpha and TACE in CD68-positive macrophages in the media and adventitia obtained from the transition zone in AAA, whereas neither TNF-alpha nor TACE was expressed in control vessels. In conclusion, the concomitant activation and localization of TNF-alpha and TACE in the media and adventitia of the transition zone in human AAA underlines the importance of this system in the pathogenesis of this disorder.

ADAM Proteins↗

PubMed2004

Post-operative constrictive pericarditis complicated with lymphocytopenia and hypoglobulinemia.

A 71-year-old man who had a history of open chest surgery was admitted due to anasarca and bilateral pleural effusions. Although imaging modalities could not demonstrate any pericardial abnormalities, right-sided cardiac catheterization revealed 'dip and plateau' in diastolic pressure waveform. He was admitted frequently because of the episodic right-sided congestive heart failure and hypoproteinemia due to protein-losing enteropathy. The peripheral lymphocyte count and serum gamma-globulin concentration were gradually decreased, and finally showed lymphocytopenia and hypoglobulinemia. On the last admission, the patient showed extensive cellulitis on both legs, and he developed septicemia, and finally died due to septic shock. Post-mortem examination showed that both visceral and parietal layers of the pericardium adhered tightly with mediastinal fibrosis. This case report suggested that constrictive pericarditis should be considered even if there is a lack of typical abnormal pericardial imaging findings when patients have a history of open chest surgery and recurrent right-sided congestive heart failure. In addition, we should be aware of a serious outcome due to immune compromised conditions such as lymphocytopenia and dysglobulinemia in this disorder.

Agammaglobulinemia↗

PubMed2004

Association between serum C-reactive protein levels and microalbuminuria: a population-based cross-sectional study in northern Iwate, Japan.

OBJECTIVE: The presence of microalbuminuria is a renal marker of vascular endothelial damage, and is an independent and strong predictor of increased risk for cardiovascular mortality and morbidity. Elevated circulating C-reactive protein (CRP) levels have recently been reported to be a novel cardiovascular risk factor, and it has been suggested that this acute-phase protein impairs vascular endothelial function. The aim of the present study was to determine whether serum CRP level is a dependent or an independent risk factor of microalbuminuria in the general population. METHODS: Subjects of this cross-sectional study were apparently healthy individuals drawn from the general Japanese population (mean age, 62; men, 2,236; women, 4,217). Serum CRP levels were determined using a highly sensitive kit and urine albumin-creatinine ratio (UACR) was calculated using a single urine sample. Multivariate logistic regression analysis was used to determine which risk factors (ie, age, hypertension, diabetes, obesity, hypercholesterolemia, smoking, and CRP) might predict the presence of microalbuminuria. RESULTS: In addition to classical cardiovascular risk factors such as age, hypertension, diabetes and obesity, serum CRP levels are also significantly correlated with microalbuminuria in men (odds ratio = 1.42, 95% CI = 1.13-1.79; p < 0.01) and women (odds ratio = 1.25, 95% CI = 1.05-1.49; p < 0.01). When subjects with diabetes were excluded from the analysis, serum CRP levels continued to be a significant predictor for microalbuminuria (odds ratio = 1.35, 95% CI = 1.06-1.73; p < 0.05 for men: odds ratio = 1.23, 95% CI = 1.03-1.47; p < 0.05 for women). CONCLUSIONS: The present study has shown that low-grade inflammation as represented by high sensitivity CRP levels may be significantly related to the presence of microalbuminuria. This suggests that microalbuminuria may be a useful marker representing systemic low-grade inflammation as well as being an established cardiovascular risk factor in apparently healthy individuals.

Aged↗

PubMed2004

Pharmacological modulations of the renin-angiotensin-aldosterone system in human congestive heart failure: effects on peripheral vascular endothelial function.

Elevated peripheral vascular tone has been proposed as one of the detrimental factors causing increased cardiac after load and reduced exercise capacity in patients with congestive heart failure (CHF). A number of studies have shown impaired endothelium-dependent vasodilation in limb resistance and conduit vessels in CHF, suggesting that this is one of the important etiologies of vascular dysfunction. Several clinical trials have shown that pharmacological inhibition of the renin-angiotensin-aldosterone system by angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, or aldosterone receptor antagonists, significantly improves prognosis in this disorder. However, the relationship between the clinical utility of this type of drug and its pharmacological effects on the peripheral vasculature has not been extensively assessed in patients with CHF. The present review summarizes recent reports including our own observations on the pharmacological effects and mechanisms of this type of drug on vascular endothelial function in the peripheral vasculature in human CHF.

Angiotensin II Type 2 Receptor Blockers↗

PubMed2003

The limited value of plasma B-type natriuretic peptide for screening for left ventricular hypertrophy among hypertensive patients.

BACKGROUND: Several reports have suggested that plasma B-type natriuretic peptide (BNP) levels are elevated in hypertensive patients especially with left ventricular (LV) hypertrophy. However, few data have been available concerning the utility of plasma BNP measurement to identify LV hypertrophy in hypertensive patients in a general population screening context. METHODS: We measured plasma BNP concentrations in 1112 volunteers in a health screening program (mean age, 57 years). All subjects underwent electrocardiography, chest X-ray, and echocardiography. Among the sample, 284 subjects were designated as hypertensive because they were on antihypertensive drugs or showed elevated systemic blood pressure. By echocardiography, 36 of the hypertensive patients showed significant LV hypertrophy. RESULTS: There were no significant differences in age and sex between the LV hypertrophy and non-LV hypertrophy groups. Plasma BNP levels in the LV hypertrophy group were significantly higher than in the non-LV hypertrophy group (19.4 +/- 18.9 v 28.2 +/- 28.2 pg/mL; P <.05). However, the ability of plasma BNP levels to discriminate between LV hypertrophy and non-LV hypertrophy patients was not sufficient as the area under the receiver operating characteristic curve was 0.588 (95% CI: 0.528-0.646) with sensitivity of 50.0% and specificity of 69.0%. Positive and negative predictive values for detecting LV hypertrophy among hypertensive patients were 18.9% and 90.5%, respectively. This ability did not improve significantly when the screening was limited to patients with untreated LV hypertrophy or concentric LV hypertrophy. CONCLUSIONS: Plasma BNP testing in a mass screening setting is of limited use for the identification of LV hypertrophy patients among hypertensive patients with heterogeneous etiology.

Adult↗

PubMed2003

Natriuretic peptide measurement as a screening test for overt and subclinical heart failure.

The prevalence of heart failure will increase in a number of industrialized countries as the proportion of elderly within the population increases. Despite recent advances in medical and surgical intervention, the prognosis for this disorder has not improved significantly. To make a major impact on the prognosis for heart failure, it would be important to be able to recognize various forms of heart disease before severe heart failure has developed. Chest X-radiography, ECG and echocardiography may not be adequate screening tools for heart failure in large populations. Natriuretic peptides are secreted from the heart in response to various cardiac abnormalities including ventricular dysfunction, volume overload, hypertrophy, and myocardial ischemia. Circulating levels of natriuretic peptides are elevated in various forms of structural cardiac disease regardless of etiology and the degree of ventricular systolic dysfunction. Natriuretic peptides, specifically B-type natriuretic peptide, are practically stable and can be measured without an extraction procedure. We have reviewed the recent status of plasma natriuretic peptide measurement for identification of patients with congestive heart failure, left ventricular dysfunction, and high risk of heart failure, especially in mass screening settings.

Atrial Natriuretic Factor↗

PubMed2003

Expression of Toll-like receptor 4 is associated with enteroviral replication in human myocarditis.

Previous studies have demonstrated that inflammatory cytokine expression associated with enteroviral (EV) infection may play an important role in human myocarditis. However, the mechanism of the host immune response against viral pathogens has not been fully understood. The aim of the present study was to determine whether Toll-like receptor 4 (TLR4) and EV RNA are present in human myocarditis. Endomyocardial biopsy samples were obtained from 44 patients with myocarditis and five controls. Levels of plus- and minus-strand EV RNAs and TLR4 mRNA were measured by real-time reverse transcriptase-PCR. Immunohistochemical analysis was performed to identify the cellular source of TLR4 and the EV capsid protein VP1. EV RNA was present in 21 patients with myocarditis and these patients were defined as having either active viral replication ( n =15) or latent viral persistence ( n =6). Neither strand of EV RNA was detected in controls. TLR4 mRNA expression levels were higher in myocarditis patients than in controls (TLR4/glyceraldehyde-3-phosphate dehydrogenase ratio 1.48+/-0.17 compared with 0.08+/-0.06, P <0.001). A positive correlation was found between EV RNA and TLR4 levels (plus-strand vs TLR4: r =0.66, P <0.001; minus-strand vs TLR4: r =0.48, P <0.001). TLR4 immunostaining was observed in infiltrating cells and myocytes in patients with myocarditis. The EV capsid protein VP1 was also found in myocytes. The myocarditis group with EV replication and high levels of TLR4 showed significantly lower systolic function. The present study has shown that increased expression of TLR4 is associated with EV replication and that these RNA levels are related to cardiac dysfunction in human myocarditis.

Adult↗

PubMed2003

Increased mRNA expression of tumour necrosis factor-alpha and its converting enzyme in circulating leucocytes of patients with acute myocardial infarction.

Tumour necrosis factor-alpha (TNF-alpha) plays an important role in myocardial damage in acute myocardial infarction (AMI). It has recently been discovered that TNF-alpha-converting enzyme (TACE) cleaves precursor TNF-alpha into its mature form. However, it remains unknown whether TNF-alpha expression is related to TACE expression in circulating leucocytes in AMI. Blood samples were obtained from 37 patients with AMI within 24 h of onset and eight healthy controls. Plasma TNF-alpha levels were measured by ELISA. Total mRNA was then extracted from circulating leucocytes, and the expression levels of TACE and TNF-alpha mRNAs were determined by reverse transcriptase-PCR. Plasma TNF-alpha levels were significantly higher in patients with Killip's classes III and IV AMIs (17.1+/-5.0 pg/ml, n =11) than in those with Killip's classes I and II AMIs (13.7+/-4.2 pg/ml, n =26), or controls (13.0+/-1.7 pg/ml, n =8) ( P <0.05). There was a significant increase in expression (arbitrary units) of TACE and TNF-alpha mRNAs in circulating leucocytes obtained from patients with Killip's classes I and II AMIs [TACE/glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 2.770+/-0.303; TNF-alpha/GAPDH, 2.123+/-0.475] compared with controls (TACE/GAPDH, 1.498+/-0.209; TNF-alpha/GAPDH, 1.283+/-0.274) ( P <0.01). This increase was even greater in patients with Killip's classes III and IV AMIs (TACE/GAPDH, 3.086+/-0.354; TNF-alpha/GAPDH, 2.808+/-0.422) ( P <0.01). Moreover, there was a significant positive relationship between these mRNA expression levels ( r =0.60, P <0.01). The TACE-TNF-alpha system in circulating leucocytes is stimulated and may have a negative impact on clinical outcome in AMI.

ADAM Proteins↗