Search PubMed⌕ Search

Biomedical subjects

Shigefumi Suehiro

Publications and source records attributed to Shigefumi Suehiro.

At least 37 records · Page 2Linked to original sources

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↗

Surgical indications for spontaneous pneumothorax in patients over 50 years of age.

BACKGROUND: Surgery is often required in cases of spontaneous pneumothorax. This situation can pose considerable difficulty with correct preoperative estimate of pulmonary function. Simple indications for surgery are mandatory, especially in aged patients. METHODS: To examine the indications and safety of surgery in patients over 50 years, 23 operations in 22 patients over a 6-year period from 1998 to 2003 were reviewed retrospectively. All 23 cases had a grade 2 or better performance status. In all cases, operations were performed with bullectomy or pneumonorrhaphy by a limited thoracotomy with videothoracoscopy in 5 cases. RESULTS: All patients recovered to the same performance status as before the onset of the pneumothoraces, with the exception of one who died, and changes between pre- and postoperative arterial oxygen or carbon dioxide tension were not significant. Lung-related postoperative complications, including 1 mortality (4%), occurred in three cases who required emergency operation because of massive air leaks with incomplete lung reexpansion, obvious mediastinal emphysema or severe subcutaneous emphysema. CONCLUSIONS: Surgical interventions may be safely performed when the patient's performance status is grade 2 or better, but care must be taken to avoid postoperative complications in preoperative conditions as massive air leaks with incomplete lung reexpansion, obvious mediastinal emphysema or severe subcutaneous emphysema.

Age Factors↗

Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress.

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence). The peak of lipid peroxidation and free radical generation in the heart was reached before tolerance developed. In contrast, vitamin E-deficient hearts had lower P450 expression and higher free radical generation than control hearts. To evaluate other vitamin E-inhibitable mechanisms of nitrate tolerance, we studied the NO-cGMP pathway. NTG markedly reduced the vasodilator-stimulated phosphoprotein (VASP) serine 239 phosphorylation (specific substrate of cGMP-activated protein kinase I; cGK-I) in tolerant hearts. Vitamin E inhibited the depletion of pVASP. In conclusion, because continuous NTG infusion causes vitamin E depletion as well as nitrate tolerance, vitamin E deficiency may further accelerate nitrate tolerance via an increase in oxidative stress, the reduced bioconversion because of decreased P450 expression, and impairment of the NO/cGMP pathway in tolerant heart tissues.

Animals↗

BMP-7 opposes TGF-beta1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2.

Mesenchymal cells, primarily fibroblasts and myofibroblasts, are the principal matrix-producing cells during pulmonary fibrogenesis. Transforming growth factor (TGF)-beta signaling plays an important role in stimulating the expression of type I collagen of these cells. Bone morphogenetic protein (BMP)-7, a member of the TGF-beta superfamily, has been reported to oppose the fibrogenic activity of TGF-beta1. Here, we have addressed the effects of BMP-7 on the fibrogenic activity of pulmonary myofibroblasts. We first established cell lines from the lungs of transgenic mice harboring the COL1A2 upstream sequence fused to luciferase. They displayed a spindle shape and expressed vimentin and alpha-smooth muscle actin, but not E-cadherin. COL1A2 promoter activity was dose dependently induced by TGF-beta1, which was further augmented by adenoviral overexpression of Smad3, but was downregulated by Smad7. Under the identical condition, adenoviral overexpression of BMP-7 attenuated the TGF-beta1-dependent COL1A2 promoter activity. By immunocytochemistry, the ectopic expression of BMP-7 led to the nuclear localization of phospho-Smad1/5/8 and suppressed that of Smad3. BMP-7 suppressed the expression of mRNAs for COL1A2 and tissue inhibitor of metalloproteinase-2 while increasing those of inhibitors of differentiation (Id) 2 and 3. Ectopic expression of Id2 and Id3 was found to decrease the COL1A2 promoter activity. Finally, BMP-7 and Id2 decreased TGF-beta1-dependent collagen protein secretion. In conclusion, these data demonstrate that BMP-7 antagonizes the TGF-beta1-dependent fibrogenic activity of mouse pulmonary myofibroblastic cells by inducing Id2 and Id3.

Animals↗

Minoxidil, a K(ATP) channel opener, accelerates DNA synthesis following partial hepatectomy in rats.

A large number of studies have reported the action of K(ATP) channel openers in accelerating the proliferation of hepatocytes and many other cell types in vitro. Few studies, however, have examined the proliferative effect of K(ATP) channel openers in vivo. The aim of this study was to determine whether the K(ATP) channel opener minoxidil accelerates liver regeneration after partial hepatectomy (PH) in vivo. Male Wistar rats underwent a 70% partial hepatectomy (PH) after receiving a subcutaneous injection of minoxidil (0.01 mg/kg or 0.03 mg/kg). Some of the rats were intravenously treated with 5-hydroxydecanoic acid (5-HD, 10 mg/kg) just before the minoxidil injection. Seventy-two hours after PH, DNA synthesis was immunohistochemically assessed by bromodeoxyuridine (BrdU) incorporation into the nuclei. Minoxidil induced significant and dose-dependent increase in the BrdU labeling index after PH, and 5-HD reversed this minoxidil-induced change. Minoxidil did not significantly affect the changes in liver weight and liver function after PH. The hepatic levels of prealbumin decreased by about 60% after PH and minoxidil inhibited the decrease. In conclusion, the K(ATP) channel opener minoxidil enhanced DNA synthesis after PH without affecting the liver function.

Alanine Transaminase↗

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↗

Evaluation of blood flow by color Doppler sonography in free jejunal interposition grafts for cervical esophageal reconstruction.

The failure of the vascular anastmoses is a devastating complication in free jejunum transplantation. We used color Doppler sonography to estimate blood flow in free jejunal grafts in 21 patients who underwent radical pharyngoesophagectomy. Fast Fourier transform (FFT) analysis of blood flow, the pulsatility index (PI) as a measure of peripheral vascular resistance, and thickening of the graft wall were evaluated for predictive value. The arterial wave patterns were classified into three types based on systolic-diastolic differences and magnitude of flow. Type I was physiologic flow, type III overtly pathologic, and type II intermediate. The three patients who required vascular reanastomoses intraoperatively had a type II pattern that degenerated to type III within 15 minutes. The PI increased to 3.5 to 4.5 over 1 hour. In the one patient who required retransplantation, the wave pattern became type III by 18 hours and had disappeared by 24 hours, at which point the PI could not be measured. Jejunal thickening increased from 1.0 mm to 5.0 mm after 24 hours, even in healthy grafts. Monitoring blood flow during the 24 hours after surgery is critical. A type III wave pattern or a PI >2.5 is an indication for reexploration. Doppler sonography offers a noninvasive way to measure blood flow in jejunal grafts semiquantitatively and can predict free jejunal graft failure.

Aged↗

Mediastinal malignant fibrous histiocytoma developing from a foreign body granuloma.

A patient with mediastinal malignant fibrous histiocytoma (MFH) apparently developing from a foreign body granuloma is reported. A 72-year-old man was admitted to our hospital complaining of generalized fatigue and palpitations. He had undergone surgery for pulmonary tuberculosis 46 years previously. Radiography and computed tomography of the chest showed a round 5-cm mass with marginal calcification in the right side of the anterior mediastinum. The mass was resected completely via median sternotomy. Intraoperative diagnosis of foreign body granuloma was made, based on gauze fragments found in the mass and intraoperative pathologic findings suggesting benign granulation tissue. The postoperative histopathologic diagnosis was myxoid MFH. To our knowledge, mediastinal MFH developing from a foreign body granuloma has not been reported previously.

Aged↗

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia.

OBJECTIVE: Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. METHODS: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. RESULTS: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. CONCLUSION: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.

Adult↗

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↗

Total arterial myocardial revascularization using composite and sequential grafting with the off-pump technique.

BACKGROUND: Multiple arterial myocardial revascularizations are increasingly undertaken using off-pump techniques; however, various arterial grafting techniques are utilized. This study aimed to review the outcome of combining arterial composite and sequential grafting with off-pump techniques. METHODS: We retrospectively reviewed the records of 107 consecutive patients who underwent coronary bypass surgery with off-pump and arterial composite grafting techniques between April 2001 and March 2004. The left internal thoracic artery (LITA) was harvested in all patients, and the right internal thoracic artery (RITA), the radial artery (RA), and the gastroepiploic artery (GEA) were harvested in 69 patients, in 83 patients, and in 53 patients, respectively. Early postoperative angiograms were evaluated in 97 patients. RESULTS: There were 488 distal anastomoses, an average of 4.5 per patient. Forty-four in situ LITAs were used as LITA Y-composite grafts with a free RITA (n = 19), RA (n = 24), or free GEA (n = 1). Forty-three in situ RITAs were used as RITA-RA grafts (n = 42) or a RITA-GEA graft (n = 1). Twenty-one in situ GEAs were used as composite grafts with the RA (n = 17) or a free RITA (n = 4). There were no hospital deaths. The patency of the LITA was 100%, and that of the RA was 97.3%, while patencies of both in situ and free RITA and GEA were 100%. During the follow-up period (mean: 22.1 months), there were 3 late deaths, but none were cardiac related. CONCLUSIONS: Total arterial revascularization with composite and sequential grafting is a safe and effective technique in patients undergoing off-pump coronary artery bypass surgery.

Aged↗

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↗

FK778 and FK506 combination therapy to control acute rejection after rat liver allotransplantation.

BACKGROUND: In organ transplantation, several immunosuppressants are currently used to control graft rejection. Clinically, no single immunosuppressive agent can completely prevent posttransplantation immunoreaction; thus, combination therapy is usually performed. Novel agents with more powerful immunosuppressive activity and less toxicity need to be developed. METHODS: Lewis rat livers were orthotopically transplanted into Brown-Norway recipients. FK778 was administered orally from day 0 to day 6 to prevent acute rejection and from day 7 to day 13 to rescue ongoing rejection. To assess the combined effects, recipients were treated with intramuscular injection of FK506 and oral administration of FK778 from day 0 to day 6. Blood chemistry and histopathologic findings were measured to determine the patient's general condition and the graft condition. Allospecific antibodies were measured using enzyme-linked immunosorbent assays. The FK778 trough concentration was examined by using high-performance liquid chromatography. RESULTS: The acute immune response was suppressed by FK778 alone in a dose-dependent manner. The optimal FK778 dosage was determined to be 20 mg/kg per day, because adverse effects (weight loss and intestinal bleeding) occurred at 30 mg/kg per day. FK778 treatment from day 7 to day 13 rescued liver grafts from ongoing rejection. The intramuscular FK506 (0.125 mg/kg per day) injection and the oral FK778 (20 mg/kg per day) gavages suppressed acute liver graft rejection effectively and maintained better graft condition compared with monotherapy. CONCLUSIONS.: FK778 treatment effectively prevented acute rejection and rescued ongoing rejection after liver transplantation. The optimal dosage was determined to be 20 mg/kg per day. Combination therapy with FK506 was more beneficial than FK778 monotherapy.

Acute Disease↗

Correlation between dynamic computed tomographic and histopathological findings in the diagnosis of small hepatocellular carcinoma.

BACKGROUND/AIMS: To determine the characteristic image findings on dynamic computed tomography (CT) for small hepatocellular carcinoma (HCC), we evaluated the correlation of histopathological and radiological findings with respect to the angioarchitecture in small HCCs. METHODS: CT and early- and late-phase dynamic CT findings of 80 small HCCs (< or =3 cm) were divided into iso-, high, low, and mixed density. We studied the correlation between the imaging findings and the histopathological findings as follows: differentiation grade; presence of fibrous capsule; presence of Glisson's sheath, and growth pattern. RESULTS: High-density early-phase CT and low-density late-phase CT correlated significantly with moderately/poorly differentiated HCCs, which have a fibrous capsule, no Glisson's sheath, and an expansive growth pattern. In contrast, well-differentiated HCCs with a Glisson's sheath and a replacing pattern (early HCC) appeared as iso-dense lesions in the early and late phases. Well-differentiated HCCs (non-early wHCC) demonstrated various density images in the early phase and low-density images in the late phase. CONCLUSIONS: Dynamic CT is an economic and simple diagnostic tool for planning treatment of small HCC lesions because of the multistep nature of HCC carcinogenesis and the hemodynamic changes of tumor blood flow.

Adult↗

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↗