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T Haneda

Publications and source records attributed to T Haneda.

At least 37 records · Page 2Linked to original sources

Mechanical stretch activates a pathway linked to mevalonate metabolism in cultured neonatal rat heart cells.

It is not certain whether activation of the Ras/mitogen-activated protein (MAP) kinase pathway is involved in cardiac hypertrophy. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, prevent farnesylation of the Ras protein, which is critical for Ras's membrane localization and function. Therefore, the present study was undertaken to investigate the role of the Ras pathway, which is linked to mevalonate metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Myocytes isolated from 1- to 2-day-old rats were cultured at 4.1 x 10(6) cells per well in a deformable silicon dish and incubated with serum-free medium for 7 days. The cultures were stretched by 15% on culture day 4. Stretch increased the RNA/DNA ratio by 20% to 26% on culture days 5 and 6 and the protein/DNA ratio by 18% to 20% on culture days 6 and 7. Stretch accelerated rates of protein synthesis by 24% on culture day 6. Stretch increased protein kinase C (PKC) activity, MAP kinase activity, and c-fos mRNA expression. A selective PKC inhibitor, calphostin C (1 x 10(-6) M), prevented the stretch-induced increase in PKC activity, but lovastatin (7.5 x 10(-6) M) did not. Lovastatin as well as calphostin C partially but significantly inhibited the stretch-induced increases in MAP kinase activity, c-fos mRNA expression, and protein synthesis. Pretreatment with both lovastatin and calphostin C completely inhibited the increases in these variables caused by stretch. Lovastatin as well as calphostin C prevents stretch-induced cardiac hypertrophy. These results suggest that mechanical stretch may activate the Ras pathway, which is linked to mevalonate metabolism, in cultured neonatal rat heart cells.

Animals↗

[Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose metabolism and quality of life in elderly patients with essential hypertension].

The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.

Adrenergic beta-Antagonists↗

Versatility of the free anterolateral thigh flap for reconstruction of head and neck defects.

OBJECTIVE: The anterolateral thigh flap has many advantages in head and neck reconstruction. However, it has not yet come into widespread use because of the anatomic variations of its perforators. Herein, we describe a safe operative technique related to the patterns of the perforators and discuss its wide versatility. SETTING: A national cancer center hospital. PATIENTS: Thirty-eight anterolateral thigh flaps were transferred. Confirmation and dissection of the flap pedicle were simultaneously performed with tumor resection. The design and elevation of the flap were carried out immediately after the tumor resection was completed. RESULTS: From the study of the anatomic variations of the perforators, septocutaneous patterns were recognized in 10 cases (26.3%) and musculocutaneous patterns in 28 cases (73.7%). All flaps were easily and safely elevated with our techniques. Thirty-six flaps survived. Partial necrosis was noted owing to excessive thinning procedure in one patient and total necrosis was noted owing to venous thrombosis at the anastomosis part in another patient. CONCLUSIONS: We found that the anterolateral thigh flap has numerous advantages. It is possible to perform the flap elevation and the tumor resection simultaneously. The flap is generally thin and is suitable for reconstruction of intraoral defects. Combined flaps with neighboring tissues and other, distant flaps can be used. Furthermore, since our technique minimizes the problems of confirmation and dissection of the perforators, we conclude that this flap can be successfully used to repair a variety of large defects of the head and neck.

Adult↗

cAMP-mediated c-fos expression in pressure-overloaded acceleration of protein synthesis in adult rat heart.

OBJECTIVES: The aim was to determine whether proto-oncogene c-fos expression and acceleration of protein synthesis by acute pressure overload to the heart were coupled with a cAMP- and protein-kinase-A-dependent system in adult rat heart. METHODS: Isolated adult rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. In the pressure-overloaded group, aortic pressure was raised from 60 to 120 mmHg for the time indicated. Agents that increase cAMP were added to the perfusate at an aortic pressure of 60 mmHg. Furthermore, a selective protein kinase A inhibitor (H-89) or a selective protein kinase C inhibitor (calphostin C) was administered before the elevation of aortic pressure or the addition of the agents. cAMP content or rates of protein synthesis were measured by RIA or the incorporation of [14C]phenylalanine into total heart protein, respectively. c-fos mRNA expression was determined by Northern blot analysis. RESULTS: Elevation of aortic pressure in beating hearts and arrested hearts increased cAMP content at 2 min of perfusion by 36 and 41%, induced c-fos mRNA expression at 30-60 min of perfusion by 4.8- and 2.0-fold, and accelerated rates of protein synthesis during the 2nd hour of perfusion by 39 and 41% over control levels, respectively. Glucagon, forskolin or IBMX mimicked increases in these parameters by elevated aortic pressure. H-89 prevented these changes by elevated pressure overload or exposure to forskolin or IBMX in arrested hearts. On the other hand, calphostin C prevented the pressure-induced increases in c-fos expression and protein synthesis rates in arrested hearts. CONCLUSIONS: These results suggest that c-fos expression induced by acute pressure overload may be coupled with increased cAMP content and protein kinase A activity in addition to increased protein kinase C activity in adult rat heart.

1-Methyl-3-isobutylxanthine↗

Efficacy and safety of preoperative percutaneous transhepatic portal embolization with absolute ethanol: a clinical study.

BACKGROUND: Preoperative portal embolization has been performed by using various thrombogenic substances to increase the safety and resectability of liver surgery. We evaluated the clinical safety and efficacy of using absolute ethanol in preoperative portal embolization. METHODS: Our study included 19 patients who had undergone right hepatic lobectomy. According to our criteria for right lobectomy of the liver, seven patients were not appropriate for the operation because of a high risk in each of postoperative liver failure. Those patients received preoperative right portal embolization with 11 to 32 ml absolute ethanol. The remaining 12 patients satisfied our criteria and received no preoperative embolization. RESULTS: Although alanine aminotransferase concentrations increased dramatically after the embolization, all serologic changes reverted within 3 weeks. The mean volume of the nonembolized lobe increased from 320 cm3 to 619 cm3 and 667 cm3 2 and 4 weeks, respectively, after embolization. The mean regeneration rate of this lobe was 21.3 cm3 per day for the first 2 weeks and 11.4 cm3 per day for the first 4 weeks after embolization. All patients underwent right lobectomy of the liver and survived; none of the patients had severe complications associated with embolization or surgery. The postoperative survival periods were not statistically significant between the patients with and without preoperative portal embolization. CONCLUSIONS: According to our criteria for liver surgery, the seven patients should not have undergone major surgery, but each underwent right lobectomy of the liver and all survived, showing that portal embolization with absolute ethanol brings about compensatory hepatic hypertrophy for major surgery and that its extreme effect on liver regeneration could widen the range of patients appropriate for liver surgery.

Adult↗

Protective effect of the angiotensin-converting enzyme inhibitor captopril on postischemic myocardial damage in perfused rat heart.

This study was undertaken to examine whether a sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, captopril, improves postischemic cardiac function and myocardial metabolism in the perfused working rat heart, and to elucidate the mechanism by which captopril protects the myocardium from postischemic damage. Isolated rat hearts were perfused by the working heart technique for 15 min. Ischemia was then induced for 30 min by lowering the afterload pressure and coronary flow to zero. After ischemia, hearts were reperfused for 30 min by returning afterload pressure to 60 mmHg. Captopril, a non-sulfhydryl-containing ACE inhibitor, enalapril, or a type 1 angiotensin II receptor antagonist, DuP 753, was added to the perfusate 5 min before ischemia, and the treatment was continued during the first 10-min period of reperfusion. In all groups there was no significant difference in pressure-rate product, coronary flow, tissue levels of ATP, total adenine nucleotides (TANs), energy charge potential (ECP), or creatine phosphate (CrP) before and during ischemia. During reperfusion following ischemia, captopril significantly improved the recovery of pressure-rate product, coronary flow, and tissue levels of ATP, TAN, ECP, and CrP, but neither enalapril nor DuP 753 had an effect. In conclusion, captopril improved postischemic cardiac function and myocardial metabolism in the perfused rate heart and its effect was independent of the blunting of angiotensin II formation.

Adenine Nucleotides↗

[Clinicopathological study on early recurrent hepatoma and its treatment].

Early Recurrence of Hepatoma: PCNA Labeling Index and DNA Ploidy Pattern Sixty-four cases of recurrent hepatocellular carcinoma (HCC) after hepatectomy were divided into two groups; E-group with recurrence within one year, and L-group with recurrence after 1 year. Clinicopathological features and surgical curability were the same in both groups. E-group had significantly higher positive rates of portal invasion, intrahepatic metastasis and rate of patients with more than 40% on PCNA labeling index. While the similar recurrence mode and the same treatment modalities were done, cumulative survival rates after recurrence in E-group had a poorer prognosis than L-group. These results suggest the possibility of lower response for the treatment on the recurrent lesion would be manifest in the E-group. New modalities for prevention of early recurrence of HCC after resection should be developed.

Aged↗

[Prognosis and preoperative imaging of patients with small hepatocellular carcinoma].

We conducted a retrospective study on the relation of the preoperative imaging patterns to the prognosis of patients with small HCC after hepatectomy. Forty patients with small HCC less than 2 cm in diameter without vascular invasion were enrolled in this study. There were no significant differences in the signal intensity of T1WI on MRI, and angiographic findings such as neo-vascularity or tumor stain. Ultrasonographical images of the internal of tumor were classified into two groups. Six cases with homogeneous pattern were significantly worse in cumulative survival rate than 28 cases with heterogeneous pattern (p = 0.0012). The same results were obtained with respect to limitation of cases treated by relative curative operation (p = 0.0041). It was concluded that histopathological grading and malignant potential of small HCC could be evaluated by classification of the pattern of internal ultrasonographical images, and complete locoregional therapy, and that intense course observation for cases with ultrasonographical homogeneous pattern would be important.

Carcinoma, Hepatocellular↗

Renin-angiotensin system in stretch-induced hypertrophy of cultured neonatal rat heart cells.

Although it is well known that mechanical load to cardiac muscles causes cardiac hypertrophy, little is known about how mechanical load is transduced into the activation of intracellular signals which are linked to cell growth. We investigated whether the cardiac renin-angiotensin system was involved in stretch-induced hypertrophy of cultured neonatal rat heart myocytes. Myocytes were cultured with serum-free medium in a deformable silicon dish. Stretch of cardiac myocytes significantly increased the protein/DNA ratio at culture days 6 and 7, and the RNA/DNA ratio at culture days 4 and 5. Stretch significantly accelerated rates of protein synthesis by 15%. c-fos mRNA expression was significantly increased after stretch. The stimulatory effects of cell stretch on these parameters were significantly inhibited by the angiotensin converting enzyme inhibitor, captopril, or the type 1 angiotensin II receptor antagonist, losartan. The concentrations of angiotensin I and angiotensin II in culture media were significantly increased by stretch. Stretch did not change the angiotensin converting enzyme activity. These studies demonstrate that mechanical stretch activates the cardiac renin-angiotensin system in a autocrine and paracrine system which acts as an initial mediator of the stretch-induced hypertrophic growth.

Angiotensin I↗

A pharmacological pilot study: application of an intermittent schedule of oral uracil and ftorafur (UFT) for hepatocellular carcinoma patients.

Patients with hepatocellular carcinoma (HCC) are highly compromised by failing liver function. To retain good compliance in the administration of uracil and ftorafur (UFT) in such patients, an intermittent schedule for oral administration of UFT was expected to have the same effect as daily continuous use without affecting liver function. A pharmacological pilot study was carried out to confirm the efficacy of this schedule. Sixteen patients with HCC who underwent hepatectomy were given UFT 200 mg b.i.d. for five consecutive days. Blood samples were drawn before the last administration of UFT and at the operation (2 days after the last administration of UFT), and the tumor and adjacent liver tissue were collected. The concentration of ftorafur (FT), 5-fluorouracil (FUra) and uracil (Ura) in serum and liver tissue were measured. Oral administration of UFT 200 mg b.i.d. resulted in a trough level of FT, FUra and Ura in serum of 9.4 micrograms/ml, 13.3 ng/ml and 64.2 ng/ml, respectively. At the operation, FT and FUra in serum had decreased significantly. However, FUra in tissue was still higher than that in serum, in contrast to the results for FT and Ura. There was no difference in the concentration of FUra between the tumors and adjacent liver tissues. No side effect was noted in any of the patients. These results indicated that an intermittent schedule for the administration of oral UFT is not only tolerable but also effective because a sufficient concentration of FUra in the liver tissue is reached and maintained.

Adult↗

[The effects of preoperative transcatheter arterial chemoembolization (TAE) for the recurrence of hepatocellular carcinoma (HCC) from the viewpoint of consecutive tumor necrosis effect].

From 1990 to 1994, seventy-seven patients with HCC below 10 cm in tumor diameter underwent hepatic resections after TAE. They were divided into two groups: group C, complete necrosis (over 90% histologically at the maximum cutting surface of the specimen): group I, incomplete necrosis (under 90%). There were no significant differences in clinical background of patients, histopathological features and total disease-free survival rate (DFR) between the two groups. Nevertheless, DFR of patients in group C was significantly better than that of patients in group I, limiting the patients for curative resection. It was suggested that the recurrence of HCC after resection might be inhibited by curative operation following preoperative TAE with complete necrosis of tumor.

Adult↗

[Role of reservoirs in intraarterial chemotherapy for recurrent hepatocellular carcinoma after hepatectomy].

We conducted a retrospective study on the role of reservoirs in intraarterial chemotherapy for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Ninety-two out of 170 patients with HCC who underwent hepatectomy from 1987 to 1992 in our institute were enrolled in this study. HCC recurred in 55 patients. A rate of good patency of the catheter of the reservoir at the time of recurrence was found in 72.7% of the patients. Transcatheter arterial embolization (TAE) for recurrent tumor was not feasible in 3 patients, because of occlusion of the hepatic artery (3.3% of patients with reservoir, 5.5% of patients with recurrence). Eleven patients were treated by intraarterial chemotherapy using the reservoir and TAE or TAE and PEIT (group R), and 11 patients were treated only with TAE and/or PEIT (group NR). Although there were no significant differences between the two groups in the number of recurrent lesions and operative procedures, tumor-free interval was shorter in group R. Cumulative survival rates after recurrence were not significant. The frequency of TAEs was lower in group R, which shortened the hospitalization for postrecurrence therapy. Thus, intraarterial chemotherapy using reservoir contributed to improvement of the quality of life of patients with recurrent HCC.

Carcinoma, Hepatocellular↗

[Relationship between severity of farmer's lung and the level of soluble interleukin 2 receptors in serum].

A 54-year-old woman was admitted to Nayoro City Hospital because of a suspicion of farmer's lung (FL). She had been working on her farm for the previous 16 years. Every April she experienced fever, coughing, and dyspnea. Fine crackles were audible over both lung fields. On admission, arterial blood gas analysis showed hypoxemia, and pulmonary-function testing revealed restrictive lung disease and a low diffusing capacity. A chest X-ray film revealed radio-opacity throughout the lower lung fields. A 67Ga scintigram showed abnormal uptake in the lungs. Examination of bronchoalveolar lavage fluid revealed an abnormally high number of lymphocytes and a high CD4/CD8 ratio in the lymphocytes. Histological examination of a specimen obtained by transbronchial lung biopsy revealed interstitial pneumonitis. A precipitation test was positive for anti-Micropolyspora faeni antibody. After admission, symptoms resolved with no treatment. FL was diagnosed from anamnesis and the results of examinations. On admission, the level of soluble interleukin 2 receptor in serum was twice the upper limit of the normal value, and it decreased over time, a long with the severity of the disease. Serial measurements of levels of this receptor are clinically important for detecting the progression of adult T cell leukemia. This case suggests that they can also be useful for evaluating the severity of FL.

Farmer's Lung↗

Free colon transfer: a versatile method for reconstruction of pharyngoesophageal defects with a large pharyngostoma.

Free transverse colon transfers based on the middle colic vessels were used to reconstruct a pharyngoesophageal defect in 9 patients. In all patients, cancer invaded up to the oropharynx. Resection resulted in a larger pharyngostoma than normally seen following standard total pharyngolaryngoesophagectomy. In such cases, it can be difficult to achieve good swallowing function after reconstruction using the free jejunal transfer. This mainly results from a significant discrepancy between the diameter of the pharyngostoma and that of the jejunum. Compared to the jejunum, the transverse colon has a larger diameter with a longer vascular pedicle and can provide a longer, straight intestinal tube, facilitating easy passage of a food bolus. In our series, all transfers survived well and all patients had good swallowing function postoperatively. We consider that a free colon transfer is more suitable than a free jejunal transfer for pharyngoesophageal reconstruction in patients with a large pharyngostoma.

Aged↗

The role of renal dopamine in the reduction of high blood pressure by beta 1-selective beta-blocker with intrinsic sympathomimetic activity in spontaneously hypertensive rats.

The present experiments were undertaken to clarify the difference of renal dopamine production from beta 1-selective beta-blocker with and without intrinsic sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or 300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50 mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR. Urine output, which was significantly less in control SHR than in control WKY, was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a significant positive correlation between u-DA/u-NA ratio and urine output and a significant negative correlation between the ratio of u-DA/u-NA and change of blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of beta 1-selective beta-blocker may contribute, at least in part, to the antihypertensive effect of this drug.

Adrenergic beta-1 Receptor Antagonists↗

Significance of the right ventricular free wall in dogs with and without pulmonary constriction.

To evaluate the role of the right ventricular (RV) free wall in cardiac function, RV and left ventricular (LV) wall segment lengths were measured by ultrasonic crystals in 10 open chest dogs with the pericardium preserved. Right coronary artery (RCA) was perfused separately by own blood and the flow was reduced stepwise until active shortening (delta L) of the RV segment disappeared or RCA flow became zero (Ischemia). The experiment was repeated with and without pulmonary stenosis (PS). At Ischemia, RV and LV systolic pressures decreased. RV end-diastolic length increased and RV delta L decreased. LV end-diastolic length and LV delta L were reduced. LV stroke volume concurrently fell. These changes became more prominent with PS. The critical level of RCA flow, at which RV delta L began to change, was higher with PS (5.27 +/- 2.85 ml/min, mean +/- S.D.) than without PS (1.44 +/- 1.16, p < 0.01). Based on the relationships between RV delta L and percent changes in RV developed pressure and stroke volume, the degree of the decreases in RV developed pressure and stroke volume at RV delta L of zero were estimated to be about 20%. These results indicate that the RV free wall partly contributes to maintaining the RV function, especially during RV pressure overload.

Animals↗