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Biomedical subjects

Shigefumi Suehiro

Publications and source records attributed to Shigefumi Suehiro.

At least 19 recordsLinked to original sources

Nicorandil elevates tissue cGMP levels in a nitric-oxide-independent manner.

The K(+) channel opener nicorandil is a hybrid compound that contains nitrate in its structure. It has been reported that nicorandil can relax vascular tissue in vitro via a mechanism that involves activation of K(ATP) channels and stimulation of soluble guanylyl cyclase. However, it is not known whether the increase of cGMP levels occurs through an elevation of nitric oxide (NO). The aim of the present study was to determine whether NO release was a direct effect of nicorandil. We reported here that nicorandil did not generate NO using ozone chemiluminescence detection methods in human or rat liver microsomes (P450-rich fractions) with addition of NADPH. However, nicorandil elevated cGMP levels in rat liver, aorta, and human coronary smooth muscle cells in vitro. The elevation was not inhibited by the NO trapping agent carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO). These results suggest that nicorandil elevates cGMP without NO generation.

Animals↗

Early and midterm results of off-pump coronary artery bypass grafting.

BACKGROUND: Early outcomes of off-pump coronary artery bypass grafting have been documented by numerous studies. However, there have been few reports concerning midterm outcomes after off-pump coronary artery bypass grafting. METHODS: We retrospectively reviewed the records of 602 consecutive patients (24.8% female) who underwent isolated off-pump coronary artery bypass grafting between April 2001 and July 2004. Mean age was 66.7 +/- 9.3 years. Mean Canadian Cardiovascular Society score was 2.5 +/- 0.9. Early postoperative angiograms were evaluated during the same period of hospitalization. Midterm outcomes, including overall patient survival, freedom from cardiac death, and freedom from the combined endpoint of cardiac events, were evaluated. RESULTS: The average number of distal anastomoses per patient was 3.6 +/- 1.4. The average operation time was 286.1 +/- 72.1 minutes. Long segmental reconstruction of the left anterior descending coronary artery was performed in 218 patients (36.2%). Total arterial grafting was performed in 466 patients (77.4%). Thirty-day mortality was 0.5%. Overall patency rate for all grafts and anastomoses was 97.5% and 97.6%, respectively. Mean follow-up time was 2.9 +/- 1.0 years. Cumulative patient survival at 5 years was 87.9% +/- 2.4%. Freedom from cardiac death was 97.7% +/- 0.6% at 5 years. Freedom from the combined endpoint of cardiac events was 83.8% +/- 2.3% at 5 years. CONCLUSIONS: Early and midterm outcomes after off-pump coronary artery bypass grafting have acceptable mortality and cardiac events rates, with favorable early graft patency rates.

Aged↗

Clinical value of serum cytokeratin 19 fragment and sialyl-Lewis x in non-small cell lung cancer.

BACKGROUND: This study aimed to establish the clinical significance of preoperative serum cytokeratin 19 fragment (CYFRA21-1) and sialyl-Lewis x (SLex) as prognostic markers. METHODS: The study involved 272 patients (181 male, 91 female; median age 69 years; range, 32 to 92) with non-small cell lung cancer (NSCLC) who underwent pulmonary resection with mediastinal lymph node dissection. Tumor markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYFRA21-1, and SLex were examined. RESULTS: A log-rank test revealed that age, gender, performance status, CEA, SCC, CYFRA21-1, and SLex were associated with the survival rate. By multivariate analysis, age, gender, performance status, CYFRA21-1 (risk ratio, 2.42) and SLex (risk ratio, 6.18) were independent prognostic factors. For patients positive for both markers, the relative risk was 6.10 compared with patients negative for both markers. The patients were divided into three groups: negative for both CYFRA21-1 and SLex (n = 97); positive for either marker (n = 136); and positive for both markers (n = 39). The 1-, 3-, and 5-year survival rates were the following: 98%, 82%, and 75% in the first group; 90%, 63%, and 49% in the second group; and 62%, 31%, and 25% in the third group (p < 0.001). Sixty-four percent of patients positive for both markers were histologic stage III/IV, and 68% of patients negative for both markers were stage I. CONCLUSIONS: Serum CYFRA21-1 and SLex were prognostic markers for NSCLC. Their combination should contribute to the classification of NSCLC patients. Preoperative staging should be carefully performed in patients positive for both tumor markers.

Adult↗

Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats.

Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. We determined the effects of calorie restriction (CR) on the dynamic aspects of mitochondrial ROS production, UCP2, and the nitric oxide (NO)-cGMP pathway in the cardiovascular tissues of type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Some rats were on restricted diets (30% reduction from free intake) from age 29 to 42 weeks. Blood glucose, hemoglobin A1c, plasma levels of free fatty acid, triacylglycerol, and plasminogen activator inhibitor-1 in OLETF rats were significantly higher than those in nondiabetic control [Long-Evans Tokushima Otsuka (LETO)] rats at 29 weeks. Mitochondrial ROS production and UCP2 expression significantly increased in the heart and aorta of OLETF rats compared with those in LETO rats. A fibrogenic growth factor, transforming growth factor (TGF)-beta1 in the coronary vessels, endothelial nitric-oxide synthase, and aortic nitrotyrosine were increased in OLETF rats at 42 weeks. In contrast, an index of the NO-cGMP pathway, phosphorylated vasodilator-stimulated phosphoprotein, and superoxide dismutase activity in the aorta were significantly diminished. The relationship between UCP2 and ROS production in the cardiovascular function of diabetic rats being fed a calorie-restricted diet is unknown. These abnormalities in OLETF rats were reversed to normal levels by CR. CR significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. A decrease in UCP2 expression by CR may be a compensatory mechanism to counteract decreased intracellular oxidative stress. The data suggest that CR may prevent cardiovascular tissues from oxidative stress provoked by diabetes mellitus.

Animals↗

High serum concentrations of Sialyl Lewisx predict multilevel N2 disease in non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to analyze the clinical significance of serum Sialyl Lewisx (SLX) concentrations as a predictor of N2 disease in patients with non-small-cell lung cancer. METHODS: The study included 272 patients with non-small-cell lung cancer who underwent pulmonary resection in our institution between January 1998 and December 2003. Of 272 patients, the serum concentrations of SLX were measured by using a commercially available radioimmunoassay kit. RESULTS: The 5-year survival rates of patients with concentrations of SLX > 38 U/mL and those with lower concentrations were 32% and 69%, respectively (P < .0001). The median serum concentration of SLX in patients with multilevel N2 or N3, single-level N2, and N0/1 disease were 44, 30, and 27 U/mL, respectively. The concentrations of serum SLX in patients with multilevel N2 disease were significantly higher than those in patients with single-level N2 or those with N0/1 disease (Mann-Whitney U-test; P < .0001). Although the sensitivity of SLX for identifying patients with non-small-cell lung cancer was only 24% in all patients, the sensitivity of SLX increased as the N-factor increased; the sensitivity of N0/1 disease was 15%, that of single-level N2 disease was 22%, and that of multilevel N2 or N3 disease was 71%. CONCLUSIONS: High serum concentrations of SLX predicted multilevel N2 disease and the associated poor outcome. Although the sensitivity of serum SLX is not acceptable for use as a screening tumor marker, we suggest that the serum concentration of SLX is useful as a staging marker to determine the strategy of treatment.

Adenocarcinoma↗

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↗

S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats.

This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.

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↗

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer.

OBJECTIVE: Impacts of mediastinal lymph node dissection on a patient's course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. METHODS: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. RESULTS: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. CONCLUSION: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.

Age Factors↗

Resected case of synovial sarcoma in the pleural cavity.

A 29-year-old female was admitted to our hospital complaining of severe dry cough and low-grade fever. A chest roentgenogram and a chest computed tomographic scan revealed a huge tumor and massive pleural effusion in the left pleural cavity. Pathological examination revealed spindle shaped malignant cells. SYT-SSX fusion gene transcripts were detected, so we diagnosed the tumor as a synovial sarcoma in the pleural cavity. After neoadjuvant chemotherapy we resected the tumor completely. A synovial sarcoma in the pleural cavity is extremely rare. To the best of our knowledge, this is the thirteenth case, and the first case to undergo neoadjuvant chemotherapy and complete resection. Because a synovial sarcoma in the pleural cavity has a poor prognosis and is characterized by a high incidence of recurrence, we must carefully follow up this patient.

Adult↗

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↗

Clinicopathological implications of immunohistochemically demonstrated mucin core protein expression in hepatocellular carcinoma.

METHODS: We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group). RESULTS: MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358). CONCLUSIONS: In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC.

Adult↗

Multiple thoracoabdominal gunshot wounds with complicated trajectories.

A 41-year-old man was shot three times with a custom-made handgun. There were six small round wounds on the surface from two bullets that went into the body and one bullet found in a wall behind the victim at the scene. The gunshot wound in the left supraclavicular region bled massively. He was transferred to our hospital and soon fell into shock. A chest radiogram showed right hemothorax. Resuscitation and blood transfusion were started, and right thoracic drainage was immediately undertaken. The left subclavicular region was incised, and bleeding from the left subclavian vein stopped. Right thoracotomy was done, and bleeding from the lung was controlled. Laparotomy was needed to look for the missing trajectory. Speculation regarding trajectories of bullets in patients with multiple thoracoabdominal gunshot wounds is difficult, and an emergent operation is often needed to control bleeding or to evaluate possible organ injury.

Abdominal Injuries↗

Thymic small cell carcinoma associated with pulmonary squamous cell carcinoma.

A 63-year-old man presented with dyspnea on effort. Chest computed tomography showed an anterior mediastinal mass and a lung mass in the right lower lobe. Thallium scintigraphy revealed accumulation in the mediastinal mass. Therefore, under diagnosis of invasive thymoma or thymic carcinoma associated with suspected lung cancer, exploratory right thoracotomy was undertaken through a median sternotomy with video-assisted thoracoscopic support. The lung mass was intraoperatively diagnosed as squamous cell carcinoma. Right lower lobectomy and total thymectomy were then carried out without additional incision. Thymic small cell carcinoma was diagnosed; therefore the patient received 50 Gy of irradiation to the mediastinum. Ten months after surgery the patient is alive without recurrence.

Carcinoma, Small Cell↗

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2003 and March 2004].

Tendency of isolated bacteria from infections in general surgery during the period from April 2004 to March 2005 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 645 strains including 17 strains of Candida spp. were isolated from 226 (79.0%) of 286 patients with surgical infections. Three hundred and seventeen strains were isolated from primary infections, and 345 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria and anaerobic Gram-negative bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Citrobacter freundii in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli, E. cloacae, and K. pneumoniae. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both primary infections followed by Bilophila wadsworthia. While the isolation rate of B. fragilis group was also the highest from postoperative infections, the following bacteria were Bacteroides thetaiotaomicron and B. wadsworthia in this order. In this series, we noticed no vancomycin-resistant Gram-positive cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenem-resistant P. aeruginosa but not multidrug-resistant was seen in 13.3 per cents. Also cefazolin-resistant E. coli probably producing extended spectrum beta-lactamase was seen in 7.0 per cents. We should be carefully followed up the facts that an increasing isolation rates of B. fragilis group and B. wadsworthia which were resistant to both penicillins and cephems.

Anti-Bacterial Agents↗

[Changing behavior of estrogen and progesterone receptors with metastasis or recurrence of breast cancer].

Changes in level of estrogen receptor (ER) and progesterone receptor (PgR) and their affecting factors were studied with metastasis or recurrence of breast cancer. Since 1983, from 177 patients, 443 specimens were obtained and 244 simultaneous and 122 sequential pairs were compared. The consistency rate was 81% for both ER and PgR with simultaneous comparison,and 69% for ER and 71% for PgR with sequential comparison, mainly due to positive-to-negative change, and less than 10% of negative-to-positive change. Positive-to-negative change was prominent with intervening endocrine treatment, and it was significant (p=0.015) for ER by multiple regression analysis of age, interval of sampling and from prior surgery, intervening chemotherapy, endocrine therapy and human epidermal growth factor receptor 2 (HER 2). Based on recent data of ER and PgR, feasible treatment seems to be planned, because about 30% of them are different from that of primary lesion.

Antineoplastic Agents, Hormonal↗