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Biomedical subjects

Masao Nakagawa

Publications and source records attributed to Masao Nakagawa.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients.

Reactivation of latent varicella-zoster virus (VZV), presenting as localized zoster or as disseminated infection, is a common and potentially serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence hemagglutination method after HSCT and also studied VZV DNA by real-time PCR during clinical VZV reactivation using cryopreserved serum samples. No significant difference was found between anti-VZV titers in 13 patients with VZV infection (localized zoster in 11 patients and disseminated zoster in 2 patients) and in 13 subjects without VZV infection at each time point after HSCT. Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than those of localized zoster cases (P=0.10). Serum VZV DNA copy numbers at the onset of disseminated zoster cases tended to be higher than those of localized zoster cases (P=0.09). A strong inverse correlation was found between preexisting anti-VZV titer and serum VZV DNA at onset (r=-0.90, P=0.006). In HSCT recipients, preexisting antibody does not prevent the development of VZV reactivation but may contribute to decreased viral load at onset, resulting in a mild clinical course.

Adult↗
PubMed2006

In vitro model for mouse coronary vasculogenesis.

To analyze the molecular mechanisms of coronary vessel formation, we performed in vitro experiments on explant cultures of proepicardial organs (PEOs) excised from embryos taken from 9.5-day pregnant mice. When plated on coverglasses coated with rat tail collagen I, fibronectin, or laminin, PEO cells spread and formed an epithelial sheet. When PEOs were cultured on collagen gel in the presence of fetal calf serum (FCS), small projections were seen around the explants 3 days after plating. Around day 6, cord-like structures began to grow from the explants, gradually elongating, increasing in number, and forming a branching network. Histological sections demonstrated that the cells migrated into the gel and formed tube-like structures similar to the vascular channels of the embryonic heart. The cells lining the lumen of the tube-like structures were positive for platelet endothelial cell adhesion molecule (PECAM). Reverse transcriptase-polymerase chain reaction analyses demonstrated that the expression of PECAM, basic fibroblast growth factor (bFGF), and smooth muscle 22-alpha (SM22alpha) was upregulated in association with the tube formation, whereas the expression of Flk-1, Flt-1, and hepatocyte growth factor (HGF) was gradually downregulated. Vascular endothelial growth factor (VEGF) was continuously expressed during the culture. These changes were not observed when PEOs were explanted without FCS. Furthermore, addition of any one or combinational addition of the growth factors, including bFGF, VEGF, or HGF, did not induce tube formation. These results suggest that PEOs contain precursor cells of coronary vasculature and that vasculogenesis may be simultaneously regulated by multiple factors.

Animals↗
PubMed2005

Association of aortic arch anomalies and subclavian artery supply disruption with neurofibromatosis.

We report an 8-year-old Japanese girl with von Recklinghausen disease, who presented with aortic arch anomalies and left hemilateral oculo-otolaryngeal abnormalities including strabismus, blepharoptosis, a dysplastic external ear and hearing loss. The aortic arch anomalies including subclavian artery obstruction that appeared to be a consequence of the neurofibromatosis, and the hemilateral oculo-otolaryngeal abnormalities could be explained by disruption of the subclavian artery supply during embryogenesis.

Abnormalities, Multiple↗
PubMed2005

MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10.

MALT1, BCL10 (B-cell lymphoma 10), and API2 (apoptosis inhibitor 2)-MALT1 are key molecules in mucosa-associated lymphoid tissue (MALT) lymphomagenesis. We previously reported that MALT1 and API2-MALT1 were localized only in cytoplasm, where we suggested that both molecules were likely to be active. In the study presented here, we further examined the localization-determining region by generating various mutants and were able to demonstrate that there were nuclear export signal (NES)-containing domains in the MALT1 C-terminal region. The use of leptomycin B, an NES-specific inhibitor, demonstrated that both MALT1 and API2-MALT1 were predominantly retained in the nuclei, indicating that these molecules were shuttling between nucleus and cytoplasm in an NES-dependent manner. It was also found that MALT1 was involved in the nuclear export of BCL10, which is originally localized in both nucleus and cytoplasm. These results correlate well with the nuclear BCL10 expression pattern in both t(1;14) and t(11;18) MALT lymphomas. The nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor kappaB (NF-kappaB) pathway but also in other biologic functions in lymphocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2005

API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation.

t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-kappaB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-kappaB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-kappaB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-kappaB activation.

Binding Sites↗
PubMed2005

Teratogenic effects of bis-diamine on the developing cardiac conduction system.

BACKGROUND: Congenital heart defects, including conotruncal anomalies, are often associated with arrhythmias. Bis-diamine induces conotruncal anomalies in embryos when administered to pregnant female rats. To investigate the mechanism of arrhythmia in conotruncal anomalies, we histologically examined the development of the cardiac conduction system in this animal model. METHODS: A single dose of 200 mg of bis-diamine was administered to pregnant Wistar rats on ED 10.5 of pregnancy. The embryos were removed on each day from ED 11.5 to 15.5. Immunoexpression of HNK-1, connexin40, and connexin43 were examined in serial sections. The distribution pattern of TUNEL-positive cells around the conduction system was also examined. RESULTS: HNK-1 immunoreactivity was evident in interventricular septum, in both the control and the bis-diamine-treated embryos from ED 12.5. Although a chain of connexin40-immunoreactive cells from interventricular septum to trabeculae, corresponding to the His bundle and its branches, was demonstrated at ED 13.5 in the control embryos, this chain was first detected at ED 14.5 in the bis-diamine-treated embryos. Immunoexpression of connexin43 in the working myocardium was also less in the bis-diamine-treated embryos than in the control at ED 13.5. The number of TUNEL-positive cells in the interventricular septum was highest at ED 12.5 in the control and at ED 13.5 in the bis-diamine-treated embryos. Furthermore, these TUNEL-positive cells were HNK-1 negative, vimentin-positive, and alpha smooth muscle actin-positive. CONCLUSIONS: Bis-diamine disturbed the normal development of gap junctions and apoptosis of myofibroblasts around the HNK-1-positive conduction tissue through overall poor myocardial proliferation and growth.

Abnormalities, Drug-Induced↗
PubMed2005

Clinical characteristics and diagnosis of double-orifice left atrioventricular valve associated with other congenital heart disease.

Four cases of double-orifice left atrioventricular (AV) valve are reported. Three of the four patients with double-orifice left AV valve had other associated congenital heart diseases, and the fourth had double-orifice left AV valve alone. A patient with associated ventricular septal defect, who presented with pulmonary congestion and hypertension, suffered from severe heart failure. However, these symptoms improved with the spontaneous closure of the ventricular septal defect. The patient with double-orifice left AV valve alone showed no cardiac symptoms. Two-dimensional and Doppler echocardiography did not detect the double-orifice left AV valve in two of the four patients. More recently, the echocardiographic technique has allowed a noninvasive and more frequent detection of this abnormality. But both of these patients had left-to-right atrial shunt and subsequent reduced transmitral flow and left ventricular volume, which may have made it difficult to detect the morphological and hemodynamic characteristics of double-orifice left AV valve. Careful and repeated echocardiographic observation of mitral configuration is required to determine the presence of double-orifice left AV valve when heart disease is associated with a left-to-right atrial shunt.

Cardiac Catheterization↗
PubMed2005

Morphological differences in cardiovascular anomalies induced by bis-diamine between Sprague-Dawley and Wistar rats.

It is known that animals show different responses to the same teratogen between different strains. We examined cardiac malformations in Sprague-Dawley (SD) and Wistar rats induced by bis-diamine, which produced conotruncal anomalies and aortic arch malformations in embryos when administered to the dams, to elucidate the morphological differences and pathogenesis in the two strains. Two hundred milligrams of bis-diamine dissolved in 1% gum-tragacanth was administered to pregnant rats on embryonic day (ED) 9.5, 10.5 and 11.5 in each strain. The embryos were removed on ED 20.5. External appearances, cardiovascular morphology and associated anomalies were examined under a dissecting microscope. An immunohistological study with an anti-N-CAM antibody, an excellent marker for neural crest cells, was performed on ED 12.5 embryos. Isolated aortic arch anomalies were common features of malformations induced by bis-diamine in SD rats and intracardiac defects were found in a small number of the embryos. Wistar rats showed more serious cardiovascular anomalies, such as persistent truncus arteriosus and tetralogy of Fallot, especially when dams were treated on ED 10.5 and isolated arch anomalies were significantly less prevalent than in SD rats. Immunohistology demonstrated that there were fewer N-CAM positive cells in the conotruncal region in Wistar rats than in SD rats. Bis-diamine induced more critical cardiovascular malformations in Wistar rats because neural crest cells, which play an important role in conotruncal septation, were more extensively damaged. Different susceptibility to bis-diamine and/or different time of neural crest cell emigration from the hindbrain might explain those morphological differences.

Abnormalities, Drug-Induced↗
PubMed2005

Evaluation of new Japanese diagnostic criteria for disseminated intravascular coagulation in critically ill patients.

New Japanese diagnostic criteria were prepared for disseminated intravascular coagulation (DIC) in critically ill patients and their usefulness was compared with the criteria of the International Society of Thrombosis and Haemostasis (ISTH) and those of the Japan Ministry of Health and Welfare (JMHW). In a retrospective study of patients with platelet counts of less than 150 x10(3)/mL, 52 cases (33.3%), 66 cases (42.3%), and 101 cases (64.7%) were diagnosed as DIC by the ISTH, JMHW, and new Japanese DIC criteria, respectively. The DIC state as diagnosed by the new Japanese DIC criteria included both DIC states as diagnosed by ISTH or JMHW criteria. Some DIC states diagnosed by the JMHW criteria included those diagnosed by ISHT criteria but this was not universal. The mortality of DIC as diagnosed by the ISTH or JMHW criteria was markedly high, compared to that for DIC diagnosed by the new Japanese criteria. The mortality of patients without DIC by ISTH was also high when they were diagnosed as DIC by the new Japanese criteria. The frequency of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection. The mortality of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection, and the mortality of overt-DIC by ISTH diagnostic criteria was also high in patients without infection.

Critical Illness↗
PubMed2004

Teratogenic effects of bis-diamine on the developing myocardium.

BACKGROUND: Bis-diamine induces conotruncal anomalies and disproportional ventricular development in rat embryos when administered to the mother. To evaluate the mechanisms of disproportional ventricular development in the anomalous heart, we analyzed the morphology of the embryonic heart and investigated cardiomyocytic DNA synthesis and apoptosis. METHODS: A single dose of 200 mg of bis-diamine was administered to pregnant rats Wistar on day 9.5 of pregnancy. The embryos were removed on each embryonic day from 10.5 to 18.5. Expression of cardiotrophin-1 and hepatocyte growth factor was investigated on the sections, and cardiotrophin-1, hepatocyte growth factor and myocyte enhancer factor 2 mRNA expression was examined by reverse transcriptase-polymerase chain reaction. Myocardial DNA synthesis was investigated using 5-bromo-2'-deoxyuridine and the labeling index was calculated for each heart. Apoptosis was also analyzed using TUNEL reaction and electrophoresis of DNA fragmentation. RESULTS: The embryos treated with bis-diamine had conotruncal anomalies associated with thin left ventricular wall in the later stage. The labeling index on embryonic day 15.5 and 16.5 was significantly lower than those in the controls. Hepatocyte growth factor and cardiotrophin-1 mRNA expression was upregulated on embryonic day 12.5 and 15.5 in bis-diamine-treated hearts. Fewer apoptotic cells were detected in the hearts of bis-diamine-treated embryos than in control hearts from embryonic day 14.5 to 16.5. CONCLUSIONS: The ventricular disproportion in the bis-diamine-treated heart may be caused by the early myocardial differentiation delay and poor proliferation and reduced apoptosis associated with anomalous circulatory condition in the later stage.

Animals↗
PubMed2004

Rate-dependent QRS prolongation during exercise testing associated with hyperkalemia.

The present case showed gradual increase of QRS duration from 100 ms up to 180 msec during an ergometer exercise test along with the heart rate increase. After exercise, QRS duration shortened and normalized. Laboratory test showed hyperkalemia (K = 8.0 mEq/l). T1 myocardial scintigraphy revealed exercise-induced transient ischemia in posterolateral region of left ventricle. Coronary angiography showed significant stenosis in the distal portion of left circumflex coronary artery. The increase of QRS duration was possibly due to the combination of hyperkalemia and the effect of mexiletine. The rate dependent blocking effect on sodium channel of mexiletine might be intensified under hyperkalemia.

Aged↗
PubMed2004

Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts.

The mechanism responsible for cardiac depression in septic shock remains unknown. The present study examined whether nitric oxide (NO) overproduced by inducible NO synthase (iNOS) can inhibit aerobic energy metabolism and impair the myocardial function in endotoxin-treated rat hearts. Lipopolysaccharide (LPS) significantly decreased systolic blood pressure (BP) to 44% of control during the 48 h treatment. Hearts from control and LPS-treated rats were perfused in a Langendorff apparatus. After LPS injection, left ventricular (LV) developed pressure (LVDP) was significantly depressed, plasma NO2-/NO3- (NO(x)) concentration was markedly increased, and myocardial adenosine 5'-triphosphate (ATP), creatine phosphate (CrP), and the ratio of ATP/adenosine 5'-diphosphate were progressively decreased with time. Immunological examination showed a significant expression of iNOS protein in the LPS-treated myocytes. Aminoguanidine, an inhibitor of iNOS, significantly attenuated these LPS-induced functional and metabolic changes. Myocardial cyclic guanosine 3',5'-monophosphate (cGMP) content was significantly increased after LPS injection. Methylene blue, an inhibitor of soluble guanylate cyclase, blunted this increase in cGMP and significantly restored the LPS-induced contractile dysfunction 6 h after LPS injection. In addition, there was a significant negative correlation between LVDP and myocardial cGMP levels as well as a significant negative correlation between LVDP and plasma NO(x) levels. In contrast, 48 h after LPS injection, methylene blue no longer affected cardiac performance, and there was a significant positive correlation between LVDP and myocardial ATP content. Furthermore, the normalized activities (as a ratio of the citrate synthase activity) of mitochondrial NADH-CoQ reductase, succinate-CoQ reductase, and ATPase, were significantly inhibited, and the swelling or disruption of mitochondria cristae was seen in the 48 h LPS treatment. These LPS-induced functional and morphological disorders in the mitochondria were significantly improved by aminoguanidine. The findings suggest that sustained production of NO by iNOS leads to contractile dysfunction via cGMP in the early stage, but that it can directly impair the mitochondrial function, lower myocardial energy production, and contribute significantly to the myocardial dysfunction in the later stage of septic shock.

Adenosine Diphosphate↗
PubMed2004

Coronary artery obstruction due to membranous ridge of the right sinus valsalva associated with Tetralogy of Fallot: syncope mimics anoxic spell.

We report an infant with Tetralogy of Fallot who had suffered from repetitive attacks of syncope without obvious cyanosis. Careful observation by means of echocardiography and angiography revealed that the attacks resulted from acute coronary artery obstruction due to membranous ridge covering the sinus Valsalva. Surgical resection of the abnormal ridge and repair of Tetralogy of Fallot successfully improved the patient's symptoms. Syncope in children should be extensively investigated to exclude obstruction of the coronary arteries.

Abnormalities, Multiple↗
PubMed2004

Usefulness of transthoracic echocardiography to detect coronary aneurysm in young adult: two cases of acute myocardial infarction due to Kawasaki disease.

Transthoracic echocardiography is useful for evaluation of the coronary arteries in infants and children with Kawasaki disease. In adults, however, transthoracic echocardiography often cannot detect or accurately estimate coronary artery lesions. We describe two young adults admitted for a diagnosis of acute myocardial infarction ascribed to Kawasaki disease and treated by angioplasty. Coronary aneurysms were not evident in either patient at the time of angioplasty. However, follow-up transthoracic echocardiography revealed coronary aneurysms at the culprit lesions. On follow-up angiograms, we identified a new coronary aneurysm in the first patient, and a regressed coronary aneurysm in the second, confirmed by intravascular ultrasound imaging. These cases suggest that transthoracic echocardiography plays an important role in the diagnosis and treatment of young adults with acute myocardial infarction due to Kawasaki disease.

Acute Disease↗
PubMed2004

Magnetic resonance imaging differentiated partial from complete absence of the left pericardium in a case of leftward displacement of the heart.

A 44-year-old man was referred to hospital for the evaluation of atypical chest pain. His chest X-ray showed leftward displacement of the heart. During echocardiography, the apical window displaced laterally in the usual left lateral position and characteristic motions of the interventricular septum and left ventricular posterior wall were recognized with postural alterations. We presumed a complete absence of the left pericardium. Magnetic resonance imaging (MRI), however, demonstrated a partial left-sided pericardium. The diagnosis was corrected to partial absence of the left pericardium and we have carefully followed up this case without surgical prophylactic intervention. It is very important to differentiate partial from complete absence of the pericardium, because only in patients with partial absence of the pericardium is there a risk of fatal myocardial strangulation. The features of the chest X-ray and echocardiography of this case, which strongly suggested complete absence of the left pericardium, are possibly not always reliable signs. In cases with these abnormal imaging features, MRI may provide additional useful information, as in this case.

Adult↗
PubMed2004

Idiopathic long QT syndrome with early afterdepolarization induced by epinephrine. Acase report.

A patient with idiopathic long QT syndrome had repeated syncopal episodes. The QTc interval on the electrocardiogram at rest was 530 ms and was prolonged by exercise up to 740 ms with T wave alternation. Intravenous epinephrine (0.1 microg/kg weight per min), but not isoproterenol (0.7 microg/min), produced early after depolarization of the monophasic action potential recorded at the right ventricular apex. Epinephrine prolonged the QTc interval to 710 ms. After the addition of propranolol to the epinephrine, the QTc (580 ms) was longer than at baseline. Methoxamine also prolonged the QTc to 580 ms. The QT interval in long QT syndrome is generally considered to be prolonged by a beta-adrenergic effect, but in the present case alpha-adrenergic stimulation had an additional effect on the prolongation of the QT interval.

Adrenergic alpha-Agonists↗
PubMed2004

Ebstein anomaly associated with unusual conduction delay and sick sinus syndrome.

A 64-year-old man was admitted to our hospital because of palpitation, dyspnea on effort, and facial edema. The echocardiographic diagnosis was Ebstein anomaly. Although the 12-lead electrocardiogram showed an atrial rate of 150 beats/min and no typical flutter wave, the electrophysiological study showed counterclockwise rotation of excitation along the tricuspid annulus. Because of sinus arrest and syncope, a permanent pacemaker was implanted, but the right atrium was not captured by electrical stimulation at 5 V/0.4 ms, except for the orifice of coronary sinus, and the intracardiac P wave was only 0.2 mV or less. This is a rare case of Ebstein anomaly characterized by unusually prolonged conduction in the atrium, the basis of which was global myocardial damage, including the ventricles.

Ebstein Anomaly↗