Biomedical subjects
Publications and source records attributed to R Sakata.
We evaluated the interaction between hepatitis C virus (HCV) and cigarette smoking on death from hepatocellular cancer in The Japan Collaborative Cohort Study. The odds ratio of death from HCC for smoking was 9.60 (1.50-61.35) and 1.71(0.58-5.08) among anti-HCV positive and negative individuals, respectively.
We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110,688 cohort members (46,399 male and 64,289 female subjects) aged 40-79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31-0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54-1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality.
BACKGROUND: In this study, we investigated the effects of oestrogen on nitric oxide synthase activity and nitric oxide production using the cirrhotic rat liver. MATERIAL AND METHODS: Cirrhosis was induced by dimethylnitrosamine. Estradiol valerate was subcutaneously injected twice at week 4 after dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an oestrogen receptor antagonist, ICI-182.780, was performed 2 days before administration of estradiol valerate. Portal pressure and hepatic blood flow were measured. Nitric oxide synthase activity was assessed by l-citrulline generation. Sinusoidal endothelial cells were isolated from the cirrhotic rat liver and cultured. The cells were incubated with estradiol and/or ICI-182.780 for 24 h. Images for nitric oxide in sinusoidal endothelial cells were obtained using diaminofluorescein-2 diacetate. RESULTS: Cirrhotic rats treated with estradiol valerate showed a significant decrease in portal pressure and a significant increase in hepatic blood flow compared with those of control cirrhosis rats. However, in cirrhotic rats treated with ICI-182.780, the reduction of portal pressure and elevation of hepatic blood flow were completely inhibited. In cirrhotic rats treated with estradiol valerate, nitric oxide synthase activity was increased compared with that in control cirrhotic rats. The fluorescent level of intracellular nitric oxide in estradiol-stimulated, cultured, sinusoidal endothelial cells was higher than that in nontreated sinusoidal endothelial cells. CONCLUSIONS: The present study indicated that oestrogen plays an important role in the enhancement of nitric oxide production in sinusoidal endothelial cells of cirrhotic liver and reduces the portal pressure in cirrhotic rats.
On the basis of the bilateral nature of bullous lesions of the lung, the authors have performed single-stage bilateral video-assisted thoracoscopic surgery (VATS) in the supine position for primary spontaneous pneumothorax in five patients since October 1999. All five patients were males with a mean age of 23 years (range 19 to 29 years). The presenting pneumothorax was ipsilateral (right-sided) in four patients and simultaneous bilateral in the one remaining patient. Apart from the one case of simultaneous bilateral spontaneous pneumothorax (SBSP), all patients had a history of at least one pneumothorax episode requiring tube thoracotomy. Bilateral bullae were confirmed in all patients on preoperative chest computed tomography (CT). Bilateral bullectomy was performed by endo-stapler with no difficulties. Mean operating time was 111 minutes (range 85 to 140 minutes). All patients were returned to the surgical ward in good condition from the operating room immediately after extubation. No complications were observed, and duration of postoperative hospital stay was two to four days. All patients were alive without recurrence of pneumothorax after a mean follow-up period of 25 months (range, 9 to 43 months). Single-stage bilateral VATS in the supine position has shown itself to be an excellent approach for the treatment of bilateral bullous lesions, combining both efficacy and low morbidity.
We performed a figure-L unilateral mini-sternotomy for anterior mediastinal tumor resection in ten patients. Pathological diagnosis among the ten included six thymomas, three mature teratomas including one with a seminoma component, and one thymic cyst. Mean tumor length was 7 x 5 x 4 cm. The required skin incision was 8 cm in mean length. The third intercostal space was transected in six cases, the fourth intercostal space in four cases. Bilateral internal thoracic arteries were preserved in all cases. All tumors were completely resected without complications during the procedure. Mean operating time was 106 minutes (range 85 to 120 minutes). Postoperative hospital stay ranged from three to seven days without any complications. All patients were alive at the end of a mean follow-up period of 39 months (range 3 to 60 months). The figure-L unilateral mini-sternotomy is considered an effective and useful minimally invasive approach for anterior mediastinal tumors.
Using a right-sided supraclavicular approach, we operated on a 15-year-old girl with a posterior mediastinal neurogenic tumor and von Recklinghausen's disease. The encapsulated 95 x 65 x 40 mm neurofibroma was removed safely and completely without thoracotomy. No peripheral neurologic defect such as Horner's syndrome, paralysis of accessory nerve, or palsy of the right upper extremity was observed after operation. The postoperative course was uneventful and the patient was discharged on the third postoperative day with no symptoms. Today, various adaptations of video-assisted thoracic surgery are frequently utilized for many lesions. However, more direct, safer, and less invasive approaches should be selected based on local anatomy, such as the supraclavicular approach without thoracotomy that we utilized.
BACKGROUND: It is known that mechanical stress induces extracellular matrix via transforming growth factor-beta (TGF-beta) synthesis in vascular smooth muscle cells. Activated hepatic stellate cells (HSCs) are an important source of TGF-beta in the liver. However, it remains unclear whether mechanical stress induces TGF-beta in HSCs. The Rho small GTP-binding protein (Rho) has recently emerged as an important regulator of actin and cytoskeleton. We examined whether TGF-beta is expressed in stretched HSCs and whether Rho is involved in stretch-induced TGF-beta synthesis. MATERIALS AND METHODS: A cultured human HSC cell line, LI90, was used for this study. Hepatic stellate cells were cyclically stretched using the Flexercell(R) strain unit. Concentration of TGF-beta in the conditioned medium was estimated by a bioassay using mink lung epithelial cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Transforming growth factor-beta mRNA expression of HSCs was estimated by a reverse-transcription polymerase chain reaction. Replication-defective adenoviral vectors expressing a dominant negative type of Rho was utilized to suppress its effect on HSCs. RESULTS: Transforming growth factor-beta concentration of the conditioned media of stretched HSCs showed time-dependent increases as compared to nonstretched HSCs from 2 h to 24 h. Transforming growth factor-beta mRNA expression in stretched HSCs was increased compared with that in nonstretched HSCs. Transfection of dominant negative Rho inhibited the stretch-induced TGF-beta synthesis. CONCLUSIONS: Mechanical stretch enhanced TGF-beta expression on mRNA and protein level in HSCs. Rho was closely related to stretch-induced TGF-beta synthesis in HSCs.
We report on the case of a 23-year-old man with simultaneous bilateral spontaneous pneumothorax (SBSP), treated with bilateral video-assisted thoracoscopic surgery (VATS) in a supine position. SBSP is a very rare condition that can be life-threatening when therapeutic techniques fail. We performed a unique operative procedure for SBSP using one-stage bilateral VATS in a supine position. This procedure is less invasive, more effective, and safer for the treatment of SBSP.
In this paper, we report on a new technique of Dumon stent placement using a flexible bronchofiberscope. This procedure was used to insert Dumon stents in two bronchial obstruction and two bronchofistula cases. The stenting technique described here can be used through either a tracheostoma or the oral cavity; it presents a very straightforward and safe procedure that does not require the use of a rigid bronchoscope.
Alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) have important roles in the elimination of ingested ethanol. These enzymes have polymorphisms resulting from single-point mutations that cause kinetic differences in their respective enzyme activities. Simultaneous observation of these enzymes would be useful in investigating the association between these enzyme polymorphisms and alcohol-related problems. In this study amplified genomic DNA was amplified from nail clippings with two sets of primers for ADH2 and ALDH2 genes, respectively, in a micro test tube and the accuracy of the amplification was verified by direct sequencing. The PCR products were separated into four distinct bands by single-strand conformation polymorphism analysis. This genotyping method is fast, accurate. reliable and inexpensive, and requires the same amount of template DNA as non-simultaneous methods. In other words, the required amount of template DNA for this method is only half that required for the separate genotyping of ADH2 and ALDH2.
We herein report a case of aortic root replacement using cryopreserved allograft. A 52-year-old man received aortic valve replacement using a mechanical prosthesis for aortic stenosis. He was complicated by postoperative methicillin-resistant staphylococcus aureus mediastinitis involving the ascending aorta. Surgical therapy including debridement, omental transposition, patch closure using pericardium had not achieved satisfied result. Aortic root replacement using cryopreserved allograft was mandatory for refractory aortic infection. He had an uneventful postoperative course. The cryopreserved allograft was effective for a patient with refractory aortic root infection due to postoperative mediastinitis.
In this report, we will describe the treatment of a 38-year-old man with severe descending necrotizing mediastinitis (DNM) with bilateral empyema. DNM is a rare disease with a high mortality rate, and when accompanied by bilateral empyema, this is particularly serious and potentially fatal. To improve the prognosis of such patients, the establishment of an adequate surgical procedure for satisfactory debridement and drainage is essential. This is the first report on a new combined surgical procedure consisting of right standard posterolateral thoracotomy and left video-assisted thoracoscopic surgery (VATS) for severe DNM with bilateral empyema.
Here, we report on a 30-year-old female with primary chylopericardium who successfully underwent thoracic duct clipping and partial pericardiectomy using video-assisted thoracoscopic surgery (VATS). Recently, a few cases of this disease have been treated utilizing VATS. This is a fully detailed description of the treatment of primary chylopericardium including a description of intraoperative findings and photographs obtained during the course of VATS.
Surgical management of patients with concomitant critical cardiovascular disease and resectable general thoracic lesions is controversial. During a 16-year period (1985 to 2001), 15 patients underwent combined cardiovascular and general thoracic operations, of the 2,459 patients who underwent a cardiovascular operation requiring cardiopulmonary bypass at our institution. Patients had cardiovascular symptoms only and the general thoracic lesions were incidentally found by preoperative chest roentgenograms and/or computed tomography. Because of the cardiovascular disease, a pathological diagnosis was precluded before surgery. All except one descending thoracic aortic operation underwent concurrent pulmonary resection after neutralization of protamine following cardiovascular surgery requiring extracorporeal circulation. Lung pathology consisted of pulmonary bullae (n = 7), primary lung cancer (n = 4), benign lung tumor (n = 2), metastatic lung cancer (n = 1), and thymic cyst (n = 1). The pulmonary operations include bullectomy (n = 7), wedge resection (n = 6), lobectomy (n = 3), and removal of a thymic cyst (n = 1) including 2 staged procedures. The final diagnoses in 4 lung cancer cases were T1. N0M0, stage IA (n = 3) and T2N2M0, stage IIIA (n = 1). All malignancies including metastatic lung cancer, were able to be completely resected. The mean intraoperative bleeding volume for the cases was 997 +/- 221 ml, while mean duration of surgery was 382 +/- 31 minutes. Except for 2 cases required long term ventilatory support, the mean durations of tracheal intubation and ICU stay were 2.2 +/- 0.2 and 3.8 +/- 1.0 days respectively. Except for 1 surgical death, mean survival duration and 5-year survival rate were 59.7 +/- 12.5 (5-177) months and 66.3% respectively. These findings suggest that combined pulmonary resection with cardiovascular surgery is safe and offers a favorable prognosis to a selected group of patients.
The basic helix-loop-helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior-posterior polarity is disrupted. As a result, the somite derivatives such as vertebrae and ribs are severely disorganized. Although expression of Notch and its ligands is not affected significantly, the oscillator and Notch modulator lunatic fringe is expressed continuously throughout the mutant PSM. These results indicate that Hes7 controls the cyclic expression of lunatic fringe and is essential for coordinated somite segmentation.
STUDY DESIGN: Posterolateral lumbar transverse process fusion in a rabbit model was performed using two different carriers for recombinant human morphogenetic protein-2, one having a porous structure and the other being a Type I collagen sheet. OBJECTIVES: To compare the effectiveness of two different carriers for recombinant human morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: The application of osteoinductive growth factors at various anatomic sites, such as in long bones and spinal segments, has been performed experimentally by many researchers. Although many carriers of osteoinductive factors have been reported, the most effective carrier has not been established. We have reported the efficacy of sintered bovine bone, True Bone Ceramics, which is coated with Type I collagen as a carrier of recombinant human bone morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. True Bone Ceramics is a crystallized form of bone minerals made from sintering bovine bone at high temperatures and possesses natural trabecular structure. The crystalline character of True Bone Ceramics is similar to that of artificial hydroxyapatite. In this study we focused on the structure of two different carriers to facilitate osteosynthesis in lumbar arthrodesis. METHODS: Fifty-four adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into five groups and had implants placed as follows: Group 1, autograft group, harvested autologous corticocancellous bone from the posterior iliac crest; Group 2, TBC group, True Bone Ceramics alone; Group 3, TBC-TBMP group, True Bone Ceramics coated with Type I collagen infiltrated with 100 microg of recombinant human bone morphogenetic protein-2; Group 4, collagen group, Type I collagen sheet; and Group 5, collagen-BMP group, implanted collagen sheet containing 100 microg of recombinant human bone morphogenetic protein-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination at both 3 and 6 weeks after surgery. RESULTS: Radiographs in the TBC-TBMP group showed a continuous trabecular pattern within the intertransverse area at 3 weeks after surgery. The fusion mass in the intertransverse area was more prominent than in the other groups. At 3 weeks after surgery the TBC-TBMP group had higher fusion rates based on manual palpation, and the fusions showed significantly higher tensile strength and stiffness. The histologic findings in the TBC-TBMP group at 3 weeks after surgery showed a cortical bone rim around the edge of the fusion mass, and contiguous new bone appearing between the recipient bone and the matrix of TBC without evidence of foreign body formation. In the collagen-BMP group, less mature bone formation was present within the grafted area and the new bone was not contiguous, even at 6 weeks after surgery. CONCLUSIONS: As a carrier for recombinant human bone morphogenetic protein-2, True Bone Ceramics, possessing a bony or porous structure, was more effective than a Type I collagen sheet in achieving a faster and stronger lumbar spinal fusion in a rabbit model.
To evaluate the in vitro effects of cilostazol, a phosphodiesterase III inhibitor, on platelet responses, we measured platelet aggregation and the levels of soluble P-selectin, a glycoprotein present on the alpha-granule membrane in resting platelets, and cAMP. Platelet-rich plasma and washed platelets from healthy human volunteers were treated with cilostazol (5, 25 and 50 microM). Platelet-rich plasma was stimulated by ADP (1 and 5 microM) or collagen (5 microg/ml). Washed platelets were stimulated by thrombin (4 U/ml) in the presence or absence of 1 microM forskolin. In vehicle-treated samples, soluble P-selectin levels in response to 1 microM ADP-induced primary aggregation were similar to those of circulating levels of healthy volunteers but the levels in response to 5 microM ADP-induced secondary aggregation and collagen-induced aggregation increased markedly compared to those in response to primary aggregation. This result suggests that P-selectin is released from platelets according to the extent of platelet aggregation. Cilostazol inhibited platelet aggregation as well as P-selectin release in a concentration-dependent manner. Cilostazol inhibited completely thrombin-induced aggregation in the presence of 1 microM forskolin, when cAMP levels were two-fold higher than those in the absence of forskolin. Cilostazol, which increases intracellular cAMP in platelets, may be useful in the treatment of arterial occlusive diseases.
Intestinal ischemia and reperfusion (I/R) has been shown to be associated with multiple organ damages. Serotonin (5-hydroxytriptamine; 5-HT), which is synthesized in the enterochromaffin cells in the intestine and stored in platelets, is known to play an important role in platelet aggregation and vasoconstriction and may ultimately enhance such organ injuries. The purpose of this study was to investigate the association between liver damage and 5-HT levels in the liver after intestinal I/R. The entire canine small intestine, isolated on a vascular pedicle that consisted of the proximal superior mesenteric artery and superior mesenteric vein, was subjected to 4-h ischemia by clamping these vessels and the marginal arteries supplying the proximal and distal ends of the small intestine. Hepatic blood flow, liver tissue blood flow, bile flow rate, and hepatic venous ketone body ratio (HVKBR) were measured before and at the end of intestinal ischemia and at 5, 15, and 30 min, and 1 and 2 h after reperfusion. 5-HT levels in plasma of the portal vein and hepatic vein were assayed at the same intervals. Time-matched, sham-operated animals served as controls. Intestinal I/R significantly decreased the liver tissue flow, bile flow rate, and HVKBR. Compared to those in controls, 5-HT levels in the portal vein and hepatic vein were markedly increased after reperfusion. Furthermore, intravenous administration of 5-HT receptor antagonists attenuated the liver dysfunction after intestinal reperfusion. These results suggest that intestinal I/R induces continuous disturbance of hepatic microcirculation, leading to liver dysfunction, and that 5-HT may be implicated as one of the mediators of liver dysfunction after intestinal I/R.