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Biomedical subjects

Toshihiko Shibata

Publications and source records attributed to Toshihiko Shibata.

At least 19 recordsLinked to original sources

Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction.

BACKGROUND: Multilineage developmental capacity of the CD34+ cells, especially into cardiomyocytes and smooth muscle cells (SMCs), is still controversial. In the present study we performed a series of experiments to prove our hypothesis that vasculogenesis and cardiomyogenesis after myocardial infarction (MI) may be dose-dependently enhanced after CD34+ cell transplantation. METHODS AND RESULTS: Peripheral blood CD34+ cells were isolated from total mononuclear cells of patients with limb ischemia by apheresis after 5-day administration of granulocyte colony-stimulating factor. PBS and 1x10(3) (low), 1x10(5) (mid), or 5x10(5) (high) CD34+ cells were intramyocardially transplanted after ligation of the left anterior descending coronary artery of nude rats. Functional assessments with the use of echocardiography and a microtip conductance catheter at day 28 revealed dose-dependent preservation of left ventricular function by CD34+ cell transplantation. Necropsy examination disclosed dose-dependent augmentation of capillary density and dose-dependent inhibition of left ventricular fibrosis. Immunohistochemistry for human-specific brain natriuretic peptide demonstrated that human cardiomyocytes were dose-dependently observed in ischemic myocardium at day 28 (high, 2480+/-149; mid, 1860+/-141; low, 423+/-9; PBS, 0+/-0/mm2; P<0.05 for high versus mid and mid versus low). Immunostaining for smooth muscle actin and human leukocyte antigen or Ulex europaeus lectin type 1 also revealed dose-dependent vasculogenesis by endothelial cell and SMC development after CD34+ cell transplantation. Reverse transcriptase-polymerase chain reaction indicated that human-specific gene expression of cardiomyocyte (brain natriuretic peptide, cardiac troponin-I, myosin heavy chain, and Nkx 2.5), SMC (smooth muscle actin and sm22alpha), and endothelial cell (CD31 and KDR) markers were dose-dependently augmented in MI tissue. CONCLUSIONS: Human CD34+ cell transplantation may have significant and dose-dependent potential for vasculogenesis and cardiomyogenesis with functional recovery from MI.

Animals↗

Mycotic aneurysm of the distal aortic arch caused by Aspergillus.

We describe an unusual case of a thoracic aortic aneurysm caused by Aspergillus. A 70-year-old man underwent prednisolone and Ara-C treatments for a myelodysplastic syndrome. Blood examination revealed pancytopenia. Under these treatments, an aneurysm presented at the distal aortic arch. He underwent resection of the aneurysm with a graft repair covered by a pedicled omentum flap, followed by prolonged administration of micafungin and itraconazole for a mycotic aneurysm. The postoperative course was favorable without complications. Serum C-reactive protein became negative and he was discharged 2 months after the surgery. However, 4 months after the surgery, he died from worsening of the myelodysplastic syndrome. The prognosis for patients with mycotic aneurysms is poor due to their immunocompetent condition arising from underlying diseases. Therefore, in addition to prompt treatment with antifungal agents combined with surgical debridement, control of the underlying disease is essential for improving the outcome.

Aged↗

Homemade endovascular treatment of postoperative aortobronchial fistulas.

Successful treatments of aortobronchial fistulas were achieved in two cases using a homemade endovascular stent graft. In one, a 75-year-old man was operated on for a distal arch aneurysm 11 years previously. In the other, a 73-year-old woman was operated on for a ruptured type B aortic dissection 2 months previously. In both cases, the chief complaint was repeated hemoptysis, and the communication between the aorta and the airway tract was at the distal anastomotic site in the descending aorta. To minimize risks associated with reoperation, endovascular stent grafting was selected electively. Postoperative courses were uneventful and there were no recurrences of hemoptysis.

Aged↗

Activation of mitogen-activated protein kinases, activator protein-1, and nuclear factor-kappaB during acute rejection after heterotopic heart transplantation in rats.

BACKGROUND: Activation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38MAPK during acute cardiac rejection is not clear. This study aimed to determine whether MAPKs and transcriptional factors such as activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were involved in acute rejection after cardiac transplantation. METHODS: Hearts from Lewis (LEW) rats (group C) or DA rats (group R) were transplanted into the abdomen of recipients (LEW). Grafts were collected at the 1st, 3rd, or 5th postoperative day (POD). ERKs were measured by Western blot analysis, and JNKs were measured by in-gel kinase assay. AP-1 and NF-kappaB DNA binding activities were determined using an electrophoretic mobility shift assay. We assessed functions of donor hearts using echocardiography. RESULTS: Heart rates and myocardial contraction significantly decreased at POD 5 in group R. Phosphorylated p42ERK and p44ERK in the left ventricular free wall (FW) and septal wall (SW) of group R significantly increased at POD 5 compared to those of group C at POD 1. Activities of p46JNK and p55JNK in the FW and SW of group R also significantly increased at POD 5. AP-1 DNA binding activities in the FW and SW of group R significantly increased at POD 5, and NF-kappaB DNA binding activities of group R significantly increased at PODs 3 and 5. CONCLUSIONS: We conclude that ERK, JNK, AP-1, and NF-kappaB are activated during acute rejection. The MAPK pathways may play an important role in acute cardiac rejection.

Animals↗

Successful surgical treatment of a mycotic right coronary artery aneurysm complicated by a fistula to the right atrium.

We reported successful surgical treatment of a mycotic right coronary artery aneurysm complicated by a fistula to the right atrium in a 60-year-old man admitted to hospital because of acute worsening of renal function and erythroderma. After admission, he suffered from methicillin-resistant Staphylococcus aureus septicemia. Despite administration of vancomycin hydrochloride, a low-grade fever persisted. Subacute cardiac tamponade occurred three months after admission, and acute inferior wall myocardial infarction occurred two weeks after pericardial drainage. An emergent coronary angiography demonstrated a large saccular aneurysm of the right coronary artery forming a fistula to the right atrium and obstruction of the distal right coronary artery. We emergently resected the aneurysm including the right atrial wall and repaired the defect in the right atrium. Pathological examination of the aneurysmal wall revealed its mycotic nature; the postoperative course was uneventful.

Aneurysm, Infected↗

Assembly and deployment of a branched arch stent graft using the transaortic approach.

Transaortic stent grafting is an alternative method for treating distal arch aneurysms. Total arch grafts are too bulky to be inserted into a sheath catheter during usual stent grafting methods. An assembling method that uses a chain stitch enables the deployment of any type of stent graft into the distal aorta without the need for a sheath catheter. We describe how to safely assemble and use a branched arch stent graft. We consider this method to be beneficial in selected cases involving extensive distal arch aneurysms or in patients with highly calcified aortas.

Aorta, Thoracic↗

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery.

OBJECTIVE: The complement cascade and granulocytes are activated in on-pump cardiac surgery. If activation of complement directly regulates granulocytes, granulocyte elastase (GEL) should increase significantly after protamine administration. We examined the effect of protamine on granulocytes by protamine administration and observation of the effect on GEL and C3a. METHODS: Thirty patients who underwent coronary artery bypass grafting were randomly assigned to two groups. In 15 patients, protamine was administered 5 min after the termination of cardiopulmonary bypass, and was administered 35 min after cardiopulmonary bypass in the other 15 patients. All patients were perfused with heparin-coated circuits and received 300 IU/kg heparin and 3 mg/kg protamine. GEL and C3a concentrations were measured at 7 time points. RESULTS: GEL concentrations increased significantly just before aortic declamping and did not increase significantly after protamine administration. C3a concentrations, however, did not increase during cardiopulmonary bypass and did increase significantly after protamine administration. CONCLUSIONS: This study indicates that GEL does not increase after protamine administration and that complement concentration does not directly affect GEL release.

Aged↗

Immunolocalization of platelet glycoprotein IIb/IIIa and P-selectin, and neutrophil-platelet interaction in human coronary unstable plaques.

Platelet aggregation at the site of plaque rupture or erosion is a dominant feature in the pathophysiology of plaque destabilization. To elucidate the role of glycoprotein (GP) IIb/IIIa in coronary plaque destabilization, we immunohistochemically studied the presence of GP IIb/IIIa in coronary atherectomy specimens obtained from patients with stable angina (SAP) and unstable angina pectoris (UAP). Moreover, we immunohistochemically investigated the presence of P-selectin, which is known to be a marker of platelet activation, in these specimens. All these patients underwent atherectomy at primary atherosclerotic lesions responsible for SAP (n=25) and UAP (n=23). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, neutrophils, endothelial cells, GP IIb/IIIa and P-selectin. Immunoreactive positive areas for GP IIb/IIIa, P-selectin, and macrophages, respectively, were calculated using computer-aided planimetry, and numbers of neutrophils were also counted. In the culprit lesions of UAP patients, 17 of the 23 lesions (74%) contained GP IIb/IIIa positive platelet thrombi, and all these platelet thrombi were positive for P-selectin. In contrast, in the lesions of SAP patients, 3 of the 25 lesions (12%) showed staining positivity for GP IIb/IIIa and P-selectin. Quantitatively, the percentage of GP IIb/IIIa- and P-selectin-positive area was significantly higher (GP IIb/IIIa, P<0.0005; P-selectin, P<0.0001) in patients with UAP than in patients with SAP. The number of neutrophils was significantly higher (P<0.0005) in patients with UAP than in patients with SAP. Moreover, the percentage of GP IIb/IIIa-positive area showed a significant positive correlation with the number of neutrophils (r=0.66, p<0.0001). These findings strongly suggest that platelet activation and aggregation, leading to formation of platelet thrombi, and the interaction between activated platelets and neutrophils play a pivotal role in the pathogenesis of plaque destabilization in human coronary atherosclerotic lesions.

Blood Platelets↗

Paradoxical cerebral embolism in a patient with Paget-Schroetter syndrome.

A 28-year-old man presented with transient speech disturbance and right hemiplegia. Computed tomography of the brain revealed a low-density area in the right cerebellum. A ventilation/perfusion lung scintiscan detected multiple perfusion defects in the both lungs and catheterization revealed pulmonary hypertension. Venography of the upper extremities revealed obstruction of the left subclavian vein. Furthermore, Doppler echocardiography revealed a right-to-left shunt via a patent foramen ovale. Those examinations demonstrated paradoxical cerebral embolism caused by Paget-Schroetter syndrome, which is a rare complication of the disorder. We hypothesize that the source of thrombi was the left subclavian vein and surgery was needed to prevent further thromboembolic events. At surgery, the upper half of the sternum was incised in the midline, and the left brachiocephalic vein was ligated. No thromboembolic episodes have occurred postoperatively.

Adult↗

The optimal method for recording prosthetic heart valve sounds in clinical situations.

BACKGROUND: Valve sounds are thought to be useful in evaluating the functioning of prosthetic heart valves. In previous reports, two recording instruments have mainly been used, a condenser microphone (instrument A) and an accelerometer (instrument B), respectively. This study aimed to investigate the applicability of these conventional devices in recording mechanical heart valve sounds in daily clinical situations. In addition, two other instruments, namely, a stethoscope including a small microphone in its tube (instrument C) and an electrostethoscope (instrument D), were proposed and examined. METHODS: Mechanical valve sounds were recorded from postoperative patients using each-device and the signal to noise ratio (SNR) of each was calculated. Frequency characteristics of the two newly proposed instruments were also investigated by recording a sweep signal in an anechoic chamber. RESULTS: The SNR values of the new instruments were significantly superior to those of conventional ones (A, sound signals were not defined from noises; B, 0.97 +/- 0.59 dB; C, 11.5 +/- 4.7 dB; and D, 9.4 +/- 3.5 dB, respectively p<0.05). The frequency characteristics of the two newly proposed instruments were also shown to be acceptable (under 10 kHz), though resonance frequency peaks were observed. CONCLUSIONS: Two newly proposed instruments can record mechanical heart valve sounds more noiselessly and with more ease than previous ones, and their frequency characteristics are acceptable.

Acoustics↗

A new poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit possesses superior platelet preservation and inflammatory suppression efficacy.

BACKGROUND: Poly-2-methoxyethylacrylate (PMEA) is a new coating material, and several studies have revealed that PMEA-coated cardiopulmonary bypass (CPB) circuits have good biocompatibility. This study sought to compare this biocompatibility with those of heparin-coated and noncoated circuits. METHODS: Forty-five patients undergoing coronary artery bypass grafting were randomly assigned to PMEA-coated (group P, n = 15), heparin-coated (group H, n = 15), or noncoated (group N, n = 15) circuit groups. Clinical data and the following markers were analyzed: (1) platelet preservation by number of platelets; (2) complement (C) activation by C3a and C4a levels; (3) inflammatory response by interleukin-6 (IL-6) and interleukin-8 (IL-8) levels. RESULTS: Platelet numbers were significantly preserved in group P compared with groups N and H. Postoperative blood loss did not differ among the groups. During CPB, C3a values were significantly lower in group H (536 +/- 145 ng/mL) than in group P (1,458 +/- 433 ng/mL, p < 0.01) and group N (1,815 +/- 845 ng/mL, p < 0.01). The C4a values did not differ 60 minutes after CPB initiation among the groups. The IL-6 and IL-8 levels were significantly lower in group P and group H than in group N. CONCLUSIONS: The PMEA coating was superior to heparin coating and noncoating in preserving platelets, and was equivalent to heparin coating in terms of the perioperative clinical course and inhibition of inflammatory cytokines, but slightly inferior in reducing complement activation.

Acrylates↗

Sonoclot analysis in cardiac surgery in dialysis-dependent patients.

BACKGROUND: Dialysis-dependent patients have multiple disorders of hemostasis; however, there are no reports of viscoelastic changes during cardiac surgery in such patients. METHODS: Hemostasis in dialysis-dependent patients during cardiac operations was evaluated. Thirty patients who underwent cardiopulmonary bypass (CPB) were studied: 6 with chronic renal failure undergoing dialysis (HD group), and 24 without hemodialysis. Blood samples were obtained at four points: before sternotomy, 30 and 90 minutes after the start of CPB, and after protamine administration. RESULTS: Activated clotting time (ACT) measured with Sonoclot analyzer was significantly correlated with ACT measured traditionally (r = 0.92; p < 0.001; y = 36.1 + 0.95x). Values for ACT measured with Sonoclot analyzer as well as traditional ACT increased significantly during CPB. Values for ACT measured with Sonoclot analyzer in the HD group were significantly longer than those in the control group. Before CPB, both ACT measured with Sonoclot analyzer and traditional ACT in the HD group were significantly longer than those in the control group; however, there were no significant differences in ACT measured with Sonoclot analyzer between the groups after CPB. Clot rates and peak signal values were significantly decreased during CPB in both groups, and returned to preoperative values after protamine administration. There were no significant differences in clot rate and peak signal values between the two groups. There were no differences between the two groups in changes of time to peak. Platelet counts in the HD group were significantly higher (p < 0.05) than those in the control group. There were no differences in platelet counts after CPB between the two groups. Antithrombin III levels decreased below 50% during and after CPB. Antithrombin III in the HD group was significantly lower (p < 0.01) than those in the control group. A significant time-group interaction was observed in antithrombin III levels. CONCLUSIONS: Sonoclot signatures in HD patients showed no significant differences in viscoelastic changes compared with non-HD patients.

Cardiopulmonary Bypass↗

Rectus abdominis myocutaneous flap after unsuccessful delayed sternal closure.

Open chest management is one of the best options for severely impaired hearts after open-heart surgery. Reapproximation of sternal edges compresses the heart, so a less compressive method of chest wall reconstruction should be considered when sternal closure must be delayed. We applied a rectus abdominis myocutaneous flap approach in 3 patients after difficulties with delayed sternal closures. Two patients were weaned off intraaortic balloon pumping and survived without respiratory troubles or wound complications. This alternative method of chest reconstruction is useful in patients after an unsuccessful delayed sternal closure.

Aged↗

Mallory - weiss tear complicating intraoperative transesophageal echocardiography.

A Mallory - Weiss tear occurred as a complication of intraoperative transesophageal echocardiography carried out in a 62-year-old man who underwent coronary artery bypass grafting. Left ventricular function was monitored in the transgastric short-axis view. Postoperative esophagogastroscopy revealed a Mallory - Weiss tear at the gastroesophageal junction and erosions in the cardia, presumably secondary to contact pressure by the echoprobe and ultrasonic thermal injury. When not actively imaging, the echoprobe should be left free in the esophagus with the acoustic power off.

Coronary Artery Bypass↗

Small-intestinal bleeding from angiodysplasia after aortic valve replacement.

An association between aortic stenosis and angiodysplasia of the gut has been reported, though this is unproven. In many instances, recurrent gastrointestinal bleeding originating from angiodysplasia has ceased following aortic valve replacement (AVR). A case is reported of massive bleeding from a small-intestinal angiodysplasia after AVR. The diagnosis was made using radioisotope-labeled red cell scintigraphy and selective angiography of the ileocolic artery soon after AVR. Selective embolization using sponge was performed, and bleeding ceased immediately. The time from onset of bleeding to completion of embolization was 6 h. However, signs of peritonitis appeared the next morning, and an emergency resection of the necrotic ileum was performed. Bleeding from angiodysplasia of the gut may occur after AVR, although the etiologic role of aortic stenosis in angiodysplasic hemorrhage is not clear.

Aged↗

Effects of FK506 on acute allograft rejection in transplanted rat heart: the role of mitogen-activated protein kinases, AP-1 and NF-kappaB.

To scrutinize the effect of the immunosuppressant on acute allograft rejection as related to the intracellular signal transduction, heterotopic cardiac transplantation was performed from DA rat to Lewis rat with/without FK506. In the experimental group, recipients were given FK506 intramuscularly for 5 days. The control group received placebo. Allograft survivals were compared between two groups. For the assay of mitogen-activated protein kinase (MAPKs) families, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in the left ventricular free wall (LV) and septum (SEP) of the grafts, rats were sacrificed on POD 5 (n=5 in each group). Extracellular signal-regulated kinase (ERK) and p38MAPK were measured using Western blot analysis. AP-1 and NF-kappaB DNA binding activities were measured by electrophoretic mobility shift assay. FK506 prolonged allograft survival (6.5 vs 31 days), and suppressed activation of myocardial MAPKs (ERK: 66% in LV and 67% in SEP, p38MAPK: 62% in LV and 72% in SEP), AP-1 (24% in LV and 18% in SEP), and NF-kappaB (41% in LV and 20% in SEP) (the mean value of activities in the control group was represented as 100%). These results suggest that the signal transduction pathways may play important roles in acute allograft rejection in rat cardiac transplantation.

Acute Disease↗

Asymptomatic thrombosis as a late complication of a retrohepatic vena caval graft performed for primary leiomyosarcoma of the inferior vena cava: report of a case.

A 63-year-old woman successfully underwent a graft replacement of the retrohepatic inferior vena cava with a ringed polytetrafluoroethylene graft for primary leiomyosarcoma of the inferior vena cava (IVC). Although anticoagulant had been administered, a thrombus was found in the IVC just cranial of the downstream anastomosis 67 months after the operation. The patient remained free of symptoms, and she had no evidence of any tumor recurrence. She underwent a complete resection with a prosthetic reconstruction for leiomyosarcoma of the IVC and has since been able to enjoy a reasonably long-term survival. The occurrence of thrombosis must be kept in mind in the long-term follow-up of such cases.

Blood Vessel Prosthesis Implantation↗