Brachiocephalic vein perforation on three-dimensional computed tomography.
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Aged↗
Biomedical subjects
Ichiro Hisatome
Publications and source records attributed to Ichiro Hisatome.
Delayed onset of beating and decreased expression of T-type Ca2+ channel in mouse ES cell-derived cardiocytes carrying human chromosome 21.
The mouse ES cell line hcgp7/#21, which carries a human chromosome 21 (hChr.21), was used as an in vitro model to examine the effects of hChr.21 on cardiomyocyte differentiation. Cardiomyocytes derived from hcgp7/#21 showed a significant delay in the onset of spontaneous beating. The number of Nkx2.5/GFP(+) cardiac progenitor cells was comparable to that in control ES cells and they also expressed comparable mRNA levels for mesodermal markers, cardiac specific transcription factors, contractile proteins, and L-type Ca(2+) channels. However, cells from hcgp7/#21 expressed significantly reduced levels of mRNA for Cav3.1 and Cav3.2, which was consistent with the decreased number of cells expressing T-type Ca(2+) channels and decreased T-type Ca(2+) channel currents. These findings suggest that the presence of human chromosome 21 suppresses expression of T-type Ca(2+) channels in cardiomyocytes during differentiation, which may be responsible for delayed onset of spontaneous beating.
Animals↗
Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering.
A cardiac biological pacemaker (BP) has been created by suppression of the inward rectifier K(+) current (I(K1)) or overexpression of the hyperpolarization-activated current (I(h)). We theoretically investigated the effects of incorporating I(h), T-type Ca(2+) current (I(Ca,T)), sustained inward current (I(st)), and/or low-voltage-activated L-type Ca(2+) channel current (I(Ca,LD)) on 1) creation of BP cells, 2) robustness of BP activity to electrotonic loads of nonpacemaking (NP) cells, and 3) BP cell ability to drive NP cells. We used a single-cell model for human ventricular myocytes (HVMs) and also coupled-cell models composed of BP and NP cells. Bifurcation structures of the model cells were explored during changes in conductance of the currents and gap junction. Incorporating the pacemaker currents did not yield BP activity in HVM with normal I(K1) but increased the critical I(K1) conductance for BP activity to emerge. Expressing I(h) appeared to be most helpful in facilitating creation of BP cells via I(K1) suppression. In the coupled-cell model, I(st) significantly enlarged the gap conductance (G(C)) region where stable BP cell pacemaking and NP cell driving occur, reducing the number of BP cells required for robust pacemaking and driving. In contrast, I(h) enlarged the G(C) region of pacemaking and driving only when I(K1) of the NP cell was relatively low. I(Ca,T) or I(Ca,LD) exerted effects similar to those of I(st) but caused shrinkage or irregularity of BP oscillations. These findings suggest that expressing I(st) most effectively improves the structural stability of BPs to electrotonic loads and the BP ability to drive the ventricle.
Action Potentials↗
Extension of the inferior vena cava into the posteroinferior right atrium.
BACKGROUND: The inferior vena cava (IVC) is obliquely connected to the right atrium (RA), and often a low-voltage area is observed in the posteroinferior RA. OBJECTIVES: The purpose of this study was investigate the size of the IVC extension into RA and its anatomic background. METHODS: We investigated 30 human hearts [11 men and 19 women; mean age 79 +/- 10 years; 7 cardiac deaths (group A) and 23 noncardiac deaths (group B)]. After obtaining macroscopic measurements around the RA-IVC junction, serial sections were cut and examined histologically. We defined a horizontal baseline at the level of the cavotricuspid isthmus and measured (1) the length of IVC extension, which was defined as the distance from the baseline to the top of the RA-IVC junction, and (2) the width of the RA-IVC junction at the baseline level. RESULTS: The top of the RA-IVC junction was always located in the posteroinferior RA. The mean length of the IVC extension was 17.6 +/- 6.6 mm, and the mean width was 29.6 +/- 7.5 mm. The IVC extension was wider in group A than in group B (35.8 +/- 9.0 mm vs 27.5 +/- 5.9 mm; P = .0277). The right and left borders of the RA-IVC junction corresponded to the reflection of the pericardium. Histologic examination showed no myocardium in the IVC extension. CONCLUSION: The IVC extension into the posteroinferior RA always exists and varies in size. Because this area lacks myocardium, it is important to consider when analyzing catheter mapping from this area.
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Autoperipheral blood mononuclear cell transplantation improved giant ulcers due to chronic arteriosclerosis obliterans.
We report the case of a 74-year-old man with Fontaine stage IV chronic arteriosclerosis obliterans who had been suffering from inveterate giant skin ulcers on the dorsum and heel of the right foot. As conventional medical treatments had not improved these ulcers and surgical treatment was considered unfeasible, amputation of the right lower limb below the knee appeared to represent the only option. The patient was admitted to Tottori University Hospital to attempt a new angiogenic therapy using auto-mononuclear cell transplantation to avoid amputation. On admission, neither right ankle blood pressure nor transcutaneous partial pressure of oxygen at the right toe were detectable. The patient had a history of multiple cerebral infarctions, and collection of mononuclear cells from bone marrow was considered too difficult, so collection of peripheral blood mononuclear cells was selected. Transcutaneous partial pressure of oxygen and skin temperature in the treated limb started to improve from 2 weeks after implantation. Ulcer size was recognizably reduced by 1 month after treatment. Partial auto-skin implantation on the right heel was performed 2 months after treatment, and the giant skin ulcer was finally completely covered. No adverse effects were noted during follow-up lasting 1 year. These results suggest that peripheral blood mononuclear cell implantation may offer a suitable alternative rescue therapy for patients with critical limb ischemia whose general condition is not good.
Aged↗
Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure.
BACKGROUND: Adenosine 5'-triphosphate is catabolized to adenosine 5'-monophosphate (AMP), which is further degraded by 2 pathways: deamination to inosine 5'-monophosphate and ammonia by AMP deaminase, or dephosphorylation to adenosine and inorganic phosphate by 5'-nucleotidase. Because adenosine is believed to be cardioprotective and we have reported that ammonia production decreased after exercise in patients with chronic heart failure (CHF), we determined if plasma adenosine levels after exercise increases in patients with CHF. METHODS AND RESULTS: Maximal ergometer exercise tests with expired gas analysis were performed in 51 patients with CHF (age = 61 +/- 2 years, New York Heart Association [NYHA] class I/II/III = 19/18/14) and 20 age-matched normal controls. Serial changes in both plasma ammonia and adenosine levels were determined. The ratio for delta ammonia to peak work rate became smaller (control, NYHA I/II/III: 0.59 +/- 0.13/0.41 +/- 0.06/0.37 +/- 0.10/0.22 +/- 0.11 microg/dL x watts, respectively) and the ratio for delta adenosine to peak work rate was significantly higher in class III CHF (control, NYHA I/II/III: 0.93 +/- 0.21/0.86 +/- 0.14/1.11 +/- 0.27/2.92 +/- 0.67 nmol/L x watts, respectively). CONCLUSION: In patients with CHF after exercise, the plasma levels of adenosine increased along with the decrease in the plasma levels of ammonia. Considering the physiologic cardioprotective actions of adenosine, the enhanced adenosine production after exercise may be an important adaptive response in patients with CHF.
Adenine Nucleotides↗
Expression of oxidative stress-related molecules in circulating leukocytes and urine in patients with chronic viral hepatitis.
AIMS: Oxidative stress plays a role in pathogenesis of chronic viral hepatitis. Expression of oxidative stress-related molecules remains to be clarified. METHODS: 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase, superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in leukocytes and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in 164 persons, including 130 chronic viral hepatitis patients and 34 normal individuals, by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Hepatic expression of these proteins was immunohistochemically examined in 12 patients with chronic viral hepatitis, compared with three persons without liver damage. RESULTS: The 4-HNE/beta-actin ratios in chronic viral hepatitis were significantly higher than those in normal individuals (P<0.01), and were significantly correlated with asparate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01, each). The catalase/beta-actin and SOD-1/beta-actin ratios in chronic viral hepatitis were higher than those in normal individuals, and were significantly correlated with 4-HNE/beta-actin ratios (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in chronic viral hepatitis was higher than that without liver damage. Urinary excretion of 8-OHdG was not changed in chronic viral hepatitis. CONCLUSIONS: The results of the present study suggest that expression of oxidative stress-related molecules in leukocytes is upregulated in relation to serum aminotransferase levels.
8-Hydroxy-2'-Deoxyguanosine↗
Giant aneurysm of the coronary sinus.
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Coronary Aneurysm↗
Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.
We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ø) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.
3-Iodobenzylguanidine↗
Evidence for proteasomal degradation of Kv1.5 channel protein.
BACKGROUND: The voltage-gated potassium channel Kv1.5 plays a critical role in the maintenance of the membrane potential. While protein degradation is one of the major mechanisms for the regulation of channel functions, little is known on the degradation mechanism of Kv1.5. METHODS AND RESULTS: Kv1.5 was expressed in COS cells and its degradation, intracellular localization, and channel activities were assessed by pulse-chase analysis, immunofluorescence, and patch clamp techniques, respectively. Expressed Kv1.5 had a half-life time of approximately 6.7 h, which was prolonged by the proteasome inhibitors of MG132, ALLN, proteasomal inhibitor 1, or lactacystine, but not by a lysosomal inhibitor chloroquine. MG132 increased the protein level of Kv1.5, as well as the level of its ubiquitinated form in a dose-dependent manner. Similar effects of MG132 on endogenous Kv1.5 were seen in cultured rat atrial cells. Within a cell, Kv1.5 was mainly localized in both the endoplasmic reticulum and Golgi apparatus. MG132 increased the immunoreactivity of Kv1.5 in these compartments and also increased Ik(ur) currents through the cell-surface Kv1.5. Pretreatment with either brefeldin A or colchicine abolished MG132-induced increase in Ik(ur) currents. CONCLUSION: Kv1.5 is degraded by the proteasome. The inhibition of the proteasome increased Ik(ur) currents secondary to stabilization of the channel protein in the endoplasmic reticulum/Golgi apparatus.
Animals↗
Status of endothelial dependent vasodilation in patients with hyperuricemia.
Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.
Adult↗
Dynamical mechanisms of pacemaker generation in IK1-downregulated human ventricular myocytes: insights from bifurcation analyses of a mathematical model.
Dynamical mechanisms of the biological pacemaker (BP) generation in human ventricular myocytes were investigated by bifurcation analyses of a mathematical model. Equilibrium points (EPs), periodic orbits, stability of EPs, and bifurcation points were determined as functions of bifurcation parameters, such as the maximum conductance of inward-rectifier K+ current (I(K1)), for constructing bifurcation diagrams. Stable limit cycles (BP activity) abruptly appeared around an unstable EP via a saddle-node bifurcation when I(K1) was suppressed by 84.6%. After the bifurcation at which a stable EP disappears, the I(K1)-reduced system has an unstable EP only, which is essentially important for stable pacemaking. To elucidate how individual sarcolemmal currents contribute to EP instability and BP generation, we further explored the bifurcation structures of the system during changes in L-type Ca2+ channel current (I(Ca,L)), delayed-rectifier K+ currents (I(K)), or Na(+)/Ca2+ exchanger current (I(NaCa)). Our results suggest that 1), I(Ca,L) is, but I(K) or I(NaCa) is not, responsible for EP instability as a requisite to stable BP generation; 2), I(K) is indispensable for robust pacemaking with large amplitude, high upstroke velocity, and stable frequency; and 3), I(NaCa) is the dominant pacemaker current but is not necessarily required for the generation of spontaneous oscillations.
Biological Clocks↗
Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine.
ATP-sensitive K+ channels (K(ATP):SUR2A+Kir6.2) play a pivotal role in cardiac protection against ischemia and reperfusion injury. When expressed in COS cells, Kir6.2 was short-lived with a half-life time of 1.9 h. The half-life time of Kir6.2 was prolonged by proteasome inhibitors MG132, ALLN, proteasome inhibitor 1, and lactacystine, but not at all by a lysosomal inhibitor chloroquine. MG132 also increased the level of ubiquitinated Kir6.2 without affecting its localization in the endoplasmic reticulum and Golgi apparatus. In electrophysiological recordings, MG132 augmented nicorandil-activated K(ATP) currents in COS cells expressing SUR2A and Kir6.2 as well as the same currents in neonatal rat cardiomyocytes. Like MG132, a Na+ channel blocker aprindine prolonged the half-life time of Kir6.2 and augmented K(ATP). Finally, both aprindine and MG132 inhibited the 20S proteasome activity in vitro. These results suggest a novel activity of aprindine to enhance K(ATP) currents by inhibiting proteasomal degradation of Kir 6.2 channels, which may be beneficial in the setting of cardiac ischemia.
Animals↗
Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice.
Inflammatory bowel disease is incurable and relapsing disease. In order to clarify the effect of HGF gene therapy for inflammatory bowel disease, the adenoviral-mediated HGF gene was intrarectally administered into TNBS-colitis-induced Balb/c mice. Adenoviral-mediated gene delivery targetted its expression mainly to intestinal epithelial cells. Mucosal damage of HGF-treated intestine was significantly improved, and compared with LacZ-treated and saline administered mice (P<0.05, each). The mice treated with intrarectal administration of pAxCAHGF showed an increased average of body weight in comparison with that of pAxCALacZ-treated and saline-treated mice (P<0.05, each). The PCNA-positive cells in pAxCALacZ-treated mice were 44.7+/-4.9%, 51.7+/-6.6%, and 53.9+/-4.5% at 10, 15, and 21 days after TNBS administration, however those in pAxCAHGF-treated mice were increased to 74.3+/-5.1%, 67.1+/-2.6%, and 69.2+/-4.6% (P<0.05, each). The TUNEL-positive cells in pAxCALacZ-treated mice were 13.3+/-5.2%, 11.5+/-2.1%, and 7.2+/-5.2%, respectively. However, those in pAxCAHGF-treated mice at 10, 15, and 21 days were significantly decreased to 5.4+/-1.8%, 3.8+/-1.3%, and 5.7+/-2.8% (P<0.05, respectively). Expression of ERK1/2 was stronger in pAxCAHGF mice than in pAxCALacZ. These data suggest that adenoviral-mediated HGF gene therapy via an intrarectal route is a promising therapy for inflammatory bowel disease.
Adenoviridae↗
Ventricular tachycardias and dilated cardiomyopathy caused by Fabry disease.
Women with Fabry disease are considered to have a good prognosis. Here we report the clinical history of a female patient with severe Fabry disease before and after referral to our hospital. She was diagnosed to have a cardiac variant of Fabry disease since a left ventricular endomyocardial biopsy revealed specific features of this disease and that cardiac involvement was the sole manifestation. She developed sustained ventricular tachycardia and dilated cardiomyopathy requiring oral administration of amiodarone and a cardiac defibrillator implant.
Cardiomyopathy, Dilated↗
Acute myocardial infarction in a patient with essential thrombocythemia: successful treatment with percutaneous transluminal coronary recanalization.
A 65-year-old woman with essential thrombocythemia (ET) was admitted to hospital where she was diagnosed as acute myocardial infarction (AMI). Because of abundant thrombus of right coronary arteries, percutaneous transluminal coronary recanalization by administration of urokinase was selected as the reperfusion therapy, resulting in successful revascularization with Thrombolysis in Myocardial Infarction grade III coronary flow. The maximum creatine kinase reached 507 IU/L, and left ventriculography performed at 1 month after initiation of both anticoagulant and antiplatelet therapies revealed reduced motion in the inferior wall with an ejection fraction of 57%. Despite good recovery of left ventricular function, bleeding complications, such as epistaxis or ecchymoma, which did not require blood transfusion, occurred during the clinical course. Because ET causes not only thrombus formation but also bleeding tendency, it is very important to carefully follow-up any clotting abnormality in AMI patients with ET.
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Subtype switching of T-type Ca 2+ channels from Cav3.2 to Cav3.1 during differentiation of embryonic stem cells to cardiac cell lineage.
BACKGROUND: The developmental changes of Ni(2+)-sensitivity to automaticity of Nkx2.5-positive cells derived from mouse embryonic stem cell have been identified, suggesting developmental regulation of expressing Ni(2+)-sensitive T-type Ca(2+) channel, although the mechanism of the change has not been fully studied. METHODS AND RESULTS: Transcripts of Cav3.2, Cav3.1 and Cav1.2 genes of beating Nkx2.5-positive cells, which encode the Ni(2+)-sensitive T-type Ca(2+) channel, Ni(2+)-insensitive T-type Ca(2+) channel, and L-type Ca(2+) channel, respectively, were investigated by real-time reverse-transcriptase-polymerase chain reaction, and the current density of each channel was measured by patch-clamp techniques at the early and late stages of differentiation. The expression of the Cav3.2 transcript predominated in the early stage whereas those of Cav3.1 and Cav1.2 transcripts were upregulated in the late stage, which was consistent with the change in each current density, suggesting the expression of channel proteins is largely determined at the transcriptional level. CONCLUSION: The results indicate that the mechanism of change of Ni(2+)-sensitivity is partly, if not completely, the subtype switch of T-type Ca(2+) channel from Cav3.2 to Cav3.1 at the transcriptional level, and that the expression of the L-type Ca(2+) channel might have an attenuating effect on Ni(2+)-sensitivity to automaticity in the late stage of differentiation.
Animals↗
Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats.
Angiotensin II (Ang II) has been reported to indirectly influence atrial electrical activity and to play a critical role in atrial arrhythmias in hypertensive patients. However, it is unclear whether Ang II has direct effects on the electrophysiological activity of the atrium affected by hypertension. We examined the effects of Ang II on the action potentials of atrial myocytes enzymatically isolated from spontaneous hypertensive rats (SHRs). The action potentials were recorded by the perforated patch-clamp technique and the atrial expression of the receptors AT1a and AT2 was measured by radioimmunoassay. Ang II significantly shortened the action potential durations (APDs) of SHRs without changes in the resting membrane potentials (RMPs). Pretreatment with selective AT1a blockers abolished the Ang II-induced reduction of atrial APDs of SHRs; however, a selective AT2 blocker did not, which was consistent with the results of the receptor assay. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitor, phospholipase C inhibitor, or protein kinase C (PKC) inhibitor abolished the Ang II-induced shortening of atrial APDs, but pertussis toxin and protein kinase A (PKA) inhibitor did not. To study the effects of chronic AT1a inhibition on Ang II-induced shortening of atrial APD, SHRs were treated with AT1a blocker for 4 weeks. AT1a blocker abolished the Ang II-induced reduction of atrial APDs of SHRs and also significantly lowered their blood pressure. In conclusion, Ang II shortened atrial APDs of SHRs via AT1a coupled with the Gq-mediated inositol triphosphate (IP3)-PKC pathway. Our findings indicated that Ang II caused atrial arrhythmias in hypertensive patients by shortening the effective refractory period of the atrium.
Action Potentials↗