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Biomedical subjects

H Imamura

Publications and source records attributed to H Imamura.

At least 109 records · Page 6Linked to original sources

Acute effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in sedentary young women.

1. The aim of the present study was to examine the effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in seven sedentary young women under controlled conditions. 2. The subjects exercised on separate days for 30 or 60 min at an intensity of 60% of maximal oxygen uptake on a cycle ergometer. Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein-cholesterol, apolipoproteins A-I, A-II and B were measured in the serum at the end of the 60 min rest period before each exercise, immediately after the performance of each exercise and at 30 min and 1, 2 and 24 h after each exercise. 3. The results showed that there were no significant differences between the pre- and postexercise samples for any of the parameters tested. 4. The results of the present study suggest that a single bout of exercise designed to simulate a typical training workout has no noticeable effect on serum lipids, lipoproteins and apolipoproteins in normal sedentary young women who have normal lipid profiles, are in the follicular phase of their menstrual cycle and who consume a relatively low-fat diet.

Adult↗

Aggressive surgical approach to recurrent tumors after hepatectomy for metastatic spread of colorectal cancer to the liver.

BACKGROUND: Liver resection is currently accepted as the only potential cure for patients with metastases of colorectal tumors in the liver. However, cancer will recur in more than 70% of patients. METHODS: In the 7 years to December 1997, 60 patients underwent liver resections for colorectal metastases at our institute. Of these, 20 patients had repeated surgical resections for recurrent disease of the liver and other organs. Another 2 patients had undergone previous hepatectomy elsewhere. The clinical data for these patients were reviewed. RESULTS: The median interval between the 2 resections was 16 months. Eighteen hepatectomies, 6 lung resections, and 1 pancreatoduodenectomy were performed in 22 patients. Operative mortality and complication rates were 0% and 18%, respectively. At a median follow-up of 25 months after repeated resection, the survival rate in these patients was 73% at 2 years (12 of 16 evaluable patients are surviving) and 22% at 5 years (2 of 10 evaluable patients are surviving); the median survival time was 44 months. CONCLUSIONS: Repeated resections for recurrent colorectal metastases yield comparable results to first liver resections in operative mortality and morbidity rates, survival time, and pattern of recurrence. Although the number of patients surviving more than 5 years is still limited, the absence of other proven treatments supports the concept of an aggressive resectional approach for these patients.

Adult↗

Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results.

OBJECTIVE: To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. SUMMARY BACKGROUND DATA: The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. METHODS: Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. RESULTS: The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). CONCLUSIONS: Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.

Adenocarcinoma↗

Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism.

Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term positive inotropic effect (PIE) in the myocardium under nonischemic conditions. IGF-I also conferred cytoprotection against ischemia and reperfusion injury in various organs. IGF-I may, therefore, facilitate the recovery of postischemic cardiac function. Isolated and crystalloid-perfused rat heart was subjected to 25 min of normothermic ischemia followed by 30 min of reperfusion. IGF-I produced PIE in a dose-dependent manner at concentrations ranging between 1 and 100 nM under nonischemic conditions. Although 1 nM isoproterenol produced much greater PIE and myocardial energy conversion efficiency (MECE) than did 65 nM IGF-I in this condition, the same concentration of IGF-I administered during reperfusion conferred better recovery of left ventricular function and MECE compared with isoproterenol. The improved cardiac performance by IGF-I was associated with lower release of creatine kinase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile function and inhibition of CK release in the postischemic heart. We conclude that IGF-I administered during reperfusion accelerates recovery of cardiac performance and mitigates myocardial injury through a wortmannin-sensitive mechanism.

Androstadienes↗

In vitro activities of novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems with potent activities against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

The in vitro activities of the novel 1beta-methylcarbapenems J-111, 225, J-114,870, and J-114,871, which have a structurally unique side chain that consists of a trans-3,5-disubstituted 5-arylpyrrolidin-3-ylthio moiety at the C-2 position, were compared with those of reference antibiotics. Among isolates of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS), 90% were inhibited by J-111,347 (prototype), J-111,225, J-114,870, and J-114,871 at concentrations of 2, 4, 4, and 4 microgram/ml (MICs at which 90% of isolates are inhibited [MIC(90)s]), respectively, indicating that these agents were 32- to 64-fold more potent than imipenem, which has an MIC(90) of 128 microgram/ml. Although these drugs were less active in vitro than vancomycin, which had MIC(90)s of 1 and 2 microgram/ml for MRSA and MRCoNS, respectively, the new carbapenems displayed better killing kinetics than vancomycin. The potent anti-MRSA activity was ascribed to the excellent affinities of the new carbapenems for penicillin-binding protein 2a of MRSA. Since the new carbapenems also exhibited good activity against gram-positive and -negative bacteria including clinically important pathogens such as penicillin-resistant Streptococcus pneumoniae, Haemophilus influenzae, members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Clostridium difficile, as well as MRSA, the novel carbapenems are worthy of further evaluation.

Anti-Bacterial Agents↗

Effects of bradykinin on prostaglandin I(2) synthesis in human vascular endothelial cells.

The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca(2+) kinetics, cytosolic phospholipase A(2) (cPLA(2)) activity, and mRNA expression of cPLA(2) and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced prostacyclin release from endothelial cells time-dependently, but pretreatment with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release. Bradykinin increased both the influx of extracellular Ca(2+) and Ca(2+) release from the intracellular Ca(2+) storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA(2) to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA(2), PGHS-1, and PGHS-2 was 87, 562, and 47 amol/microg RNA, respectively. With the stimulation of bradykinin, cPLA(2) mRNA increased to 746 amol/microg RNA in 15 minutes, PGHS-1 mRNA increased to 10 608 amol/microg RNA, and PGHS-2 mRNA increased to 22 400 amol/microg RNA in 180 minutes. Pretreatment with cycloheximide superinduced cPLA(2) and PGHS-2 mRNA expression but almost completely inhibited PGHS-1. Pretreatment with EGTA had effects similar to pretreatment with cycloheximide in the case of cPLA(2) and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA(2) activity caused by the increase of intracellular Ca(2+) concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA(2) are different from those regulating PGHS isoforms in endothelial cells.

Bradykinin↗

Correlation between neurotoxic events and intracerebral concentration of tacrolimus in rats.

The neurotoxicity associated with tacrolimus is one of the major limitations for its administration after organ transplantation. This study investigated the correlation between neurotoxicity and the intracerebral concentration of tacrolimus. Rats were given one of three doses of tacrolimus (5, 10, and 20 mg/kg/d) orally twice a day for 2 weeks and neurotoxic events were observed. The rats were sacrificed on either day 7 or 14. The trough values of the whole blood and the corresponding intracerebral concentrations were then measured. None of the rats receiving dosage of 5 mg/kg/d showed any neurotoxic symptoms throughout the two-week test period. In rats receiving a dosage of 10 mg/kg/d, however, all seven surviving rats presented tremors or seizures during the second week. In rats receiving a dosage of 20 mg/kg/d, 40% of the rats presented tremors or seizures during the first week. The threshold concentration of tacrolimus in the brain resulting in neurotoxic events was therefore estimated as approximately 700 ng/g. At concentrations over this threshold value, the intensity of the neurological event increases with the concentrations of tacrolimus in the brain. Using a linear correlation between the whole blood and intracerebral concentrations (r=0.967) of tacrolimus, the pharmacological threshold for the whole blood trough level was estimated as approximately 20 ng/ml, which falls into the same value reported for the incidental threshold of neurotoxicity in renal transplant recipients [Böttiger et al., Br. J. Clin. Pharmacol., 48, 445--448 (1999)]. Therefore, it is suggested that the rat is a good animal model to quantitatively evaluate the risk of neurotoxicity associated with tacrolimus in human, and that frequent measurement of whole blood tacrolimus concentrations is important for predicting and preventing neurotoxic events.

Animals↗

Association of matrix metalloproteinase expression and left ventricular function in idiopathic dilated cardiomyopathy.

Myocardial remodeling is an important predictor for the development of dilated cardiomyopathy (DCM). Matrix metalloproteinases (MMPs) are the family of proteins responsible for extracellular remodeling, and tissue inhibitors of metalloproteinases (TIMPs) tightly control their activity. In the present study, the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was determined by immunohistochemistry in right ventricular endomyocardial biopsy samples from 16 patients with idiopathic DCM, and its clinical significance was evaluated by comparison with parameters of cardiac function. To obtain a semi-quantitative assessment of MMP and TIMP expression, the average number of positive cells per high power field was counted. The left ventricular ejection fraction (LVEF) significantly correlated with the expression of both MMP-2 (r=-0.68) and TIMP-2 (r=-0.58). Patients were classified into 2 groups according to the degree of MMP-2 expression: strongly positive and weakly positive. LVEF, left ventricular (LV) end-diastolic pressure, right ventricular end-diastolic pressure, pulmonary capillary wedge pressure and the plasma norepinephrine level were significantly greater in the strongly positive group (p<0.05). In conclusion, the expression of MMPs and TIMPs in the cardiac matrix of patients with idiopathic DCM is closely associated with myocardial remodeling and subsequent deterioration of LV performance. These findings suggest new therapeutic targets for patients with idiopathic DCM.

Adult↗

Pulmonary hypertension as a result of asymptomatic portosystemic shunt.

This report describes a patient with severe pulmonary hypertension accompanied by a congenital intrahepatic portosystemic shunt. Primary pulmonary hypertension was suspected initially because none of the classic symptoms of a portosystemic shunt were present. Physicians should note that disorders of the portal system may cause pulmonary hypertension even in the absence of symptoms suggesting liver disease.

Female↗

Creation of aortic dissection model in swine.

The use of mongrel dogs for experimental purposes was recently restricted and this report presents the experience of creating an aortic dissection model in swine. All the swine in group 1 were anesthetized without pentobarbital and the descending aorta was side-clamped during the creation of the aortic dissection. The false lumen of the completed dissection was patent in the long term despite not having the anchoring suture that the previous canine model required to stabilize the opening of the entry tear. All the swine anesthetized with pentobarbital (ie, group 2) died of heart failure either during cross-clamping of the descending aorta or postoperative aortography. In conclusion, creation of a thoracic aortic dissection is possible in swine, but cross-clamping of the thoracic descending aorta and pentobarbital anesthesia should be avoided.

Aortic Dissection↗

Transient left ventricular aneurysm and hypertrophy accompanied by polymorphic ventricular tachycardia in a patient suspected of acute myocarditis.

A 75-year-old woman presented with recurrent ventricular tachycardia (VT) compatible with torsades de pointes (TdP) based on sinus bradycardia and QT prolongation. Previously she had received pirmenol, at a serum concentration within therapeutic range, for her paroxysmal atrial fibrillation. Emergent cardiac catheterization identified a ventricular aneurysm of the anteroapical and inferior wall along with angiographically normal coronary arteries. A right ventricular endomyocardial biopsy revealed postmyocarditic change. The left ventricular contraction improved after 5 weeks of conservative treatment. A follow-up echocardiogram revealed transient thickening of partial left ventricular wall consistent with the segment of the aneurysm. Several months later, almost all abnormal findings had improved except for sustained deep negative T waves in precordial leads. Acute myocarditis was primarily suspected as the cause of her clinical presentation.

Acute Disease↗

Successful resection of intracardiac invasive thymoma with right ventricular inflow tract occlusion.

A 72-year-old man presenting with the superior vena cava syndrome and intracardiac mass was admitted to our hospital. The mass was resected and confirmed to be invasive thymoma. Three years later, he was re-admitted with recurrence into the intracardiac space without any changes in the anterior mediastinum mass. The mass occupied the right atrial cavity and protruded into the right ventricle, causing right ventricular inflow tract obstruction. He underwent re-operation and irradiation. His postoperative course was uneventful, and he has remained alive. Invasive thymoma with intracardiac extension is extremely rare.

Aged↗

Acute cervical cord injury without fracture or dislocation of the spinal column.

OBJECT: It is known that the spinal cord can sustain traumatic injury without associated injury of the spinal column in some conditions, such as a flexible spinal column or preexisting narrowed spinal canal. The purpose of this study was to characterize the clinical features and to understand the mechanisms in cases of acute cervical cord injury in which fracture or dislocation of the cervical spine has not occurred. METHODS: Eighty-nine patients who sustained an acute cervical cord injury were treated in our hospitals between 1990 and 1998. In 42 patients (47%) no bone injuries of the cervical spine were demonstrated, and this group was retrospectively analyzed. There were 35 men and seven women, aged 19 to 81 years (mean 58.9 years). The initial neurological examination indicated complete injury in five patients, whereas incomplete injury was demonstrated in 37. In the majority of the patients (90%) the authors found degenerative changes of the cervical spine such as spondylosis (22 cases) or ossification of the posterior longitudinal ligament (16 cases). The mean sagittal diameter of the cervical spinal canal, as measured on computerized tomography scans, was significantly narrower than that obtained in the control patients. Magnetic resonance (MR) imaging revealed spinal cord compression in 93% and paravertebral soft-tissue injuries in 58% of the patients. CONCLUSIONS: Degenerative changes of the cervical spine and developmental narrowing of the spinal canal are important preexisting factors. In the acute stage MR imaging is useful to understand the level and mechanisms of spinal cord injury. The fact that a significant number of the patients were found to have spinal cord compression despite the absence of bone injuries of the spinal column indicates that future investigations into surgical treatment of this type of injury are necessary.

Adult↗

Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma.

Matrix metalloproteinases (MMP) play an important role in tumor cell invasion and metastasis. We examined the expression of MMPs in hepatocellular carcinoma (HCC) to determine whether they may help indicate the progression of HCC and patient outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP were determined in 37 pairs of HCC and adjacent non-tumor tissue specimens by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The tumor to non-tumor (T/N) ratios for mRNA expression of each MMP were compared with the clinicopathological findings and two-year disease-free survival rates. Immunohistochemical analysis for MMP-1 and -9 was performed in 30 specimens. MMP-1 and -9 expression was significantly higher in tumor tissue than in non-tumor tissue (p=0.001 and 0.0078, respectively). By contrast, the expression of MMP-2 and -7 was significantly lower in tumor tissue than in non-tumor tissue (p=0. 003 and 0.03, respectively). A higher MMP-9 T/N ratio was significantly associated with small HCCs (</=2 cm) and higher serum AFP values (>/=20 ng/ml) (p=0.013 and 0.028, respectively). Immunohistochemical analysis suggested that well differentiated HCC showed stronger immunoreactivity for MMP-9 than moderately differentiated HCC. MMP T/N ratio was not significantly associated with the disease-free survival rates. Overexpression of MMP-9 mRNA (T/N ratio >/=2) may be associated with the progression of small HCC (</=2 cm).

Adult↗

Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes.

HIV protease inhibitors have proven remarkably effective in treating HIV-1 infection. However, some tissues such as the brain and testes (sanctuary sites) are possibly protected from exposure to HIV protease inhibitors due to drug entry being limited by the membrane efflux transporter P-glycoprotein, located in the capillary endothelium. Intravenous administration of the novel and potent P-glycoprotein inhibitor LY-335979 to mice (1-50 mg/kg) increased brain and testes concentration of [(14)C]nelfinavir, up to 37- and 4-fold, respectively, in a dose-dependent fashion. Similar effects in brain levels were also observed with (14)C-labeled amprenavir, indinavir, and saquinavir. Because [(14)C]nelfinavir plasma drug levels were only modestly increased by LY-335979, the increase in brain/plasma and testes/plasma ratios of 14- to 17- and 2- to 5-fold, respectively, was due to increased tissue penetration. Less potent P-glycoprotein inhibitors like valspodar (PSC-833), cyclosporin A, and ketoconazole, as well as quinidine and verapamil, had modest or little effect on brain/plasma ratios but increased plasma nelfinavir concentrations due to inhibition of CYP3A-mediated metabolism. Collectively, these findings provide "proof-of-concept" for increasing HIV protease inhibitor distribution into pharmacologic sanctuary sites by targeted inhibition of P-glycoprotein using selective and potent agents and suggest a new therapeutic strategy to reduce HIV-1 viral replication.

ATP Binding Cassette Transporter, Subfamily B, Mem↗