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Biomedical subjects

W Takahashi

Publications and source records attributed to W Takahashi.

At least 19 recordsLinked to original sources

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients.

Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of epsilon2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/107 (6.5%); P < 0.05]. Therefore, our results suggest that the epsilon2 allele/APOE might be a risk factor for diabetes in the Brazilian population.

Aged↗

Regulatory effect of castration on endothelins, their receptors and endothelin-converting enzyme in rat seminal vesicle.

OBJECTIVE: To investigate the effects of castration on the expression of endothelins (ETs), ET receptors and ET converting enzyme-1 (ECE-1) in the rat seminal vesicle (RSV). MATERIALS AND METHODS: Sprague-Dawley rats (3 months old) were surgically castrated or sham-operated, and then killed 7 days after surgery. Biochemical and pharmacological properties and the location of ET receptors in the RSV were determined by a series of binding experiments with [125I]ET-1, using membrane particulates and slide-mounted frozen sections of RSV. Expression levels of ETA and ETB receptor subtypes, ET-1, ET-3 and ECE-1 mRNAs were assessed by relative multiplex reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: The density of total ET receptors increased significantly in the seminal vesicle of the castrated rat. The predominance of the ETA receptor subtype in the RSV did not change with castration. Autoradiographic studies showed the presence of ET receptors on the smooth muscle and epithelium of the RSV. In addition, RT-PCR showed an up-regulation in the expression of ETA and ETB receptor subtypes, ET-1 and ECE-1 mRNAs in the seminal vesicle of the castrated rat. However, castration caused no significant change in the expression levels of ET-3 mRNA. CONCLUSION: These findings suggest a regulatory role for testosterone in the expression of the ET receptor system in the RSV.

Animals↗

The effect of nitric oxide on acetylcholine release in the rabbit bladder.

We evaluated the effects of nitric oxide (NO) on acetylcholine release and the contractile response induced by electrical field stimulation in rabbit bladder smooth muscles using a muscle bath and high performance liquid chromatography coupled with microdialysis. Electrical field stimulation (supramaximum voltage, pulse duration 0.5 ms, frequency 5 and 20 Hz) was applied to a smooth muscle strip isolated from rabbit bladder. With low-frequency (5 Hz) stimulation, pretreatment with Nomega-nitro-L-arginine (L-NNA) (100 microM) significantly increased electrical field stimulation-induced acetylcholine release and contractile response, which were reduced by the addition of L-arginine. Pretreatment with sodium nitroprusside in the absence or presence of L-NNA significantly decreased electrical field stimulation-induced acetylcholine release and contractile response. In contrast, with high frequency (20 Hz) stimulation, pretreatment with L-NNA and sodium nitroprusside had no significant effect on either contractile response or acetylcholine release. Pretreatment with sodium nitroprusside caused no significant changes in carbachol and ATP-induced contractile responses. Sodium nitroprusside and L-NNA had no significant effects on the atropine-resistant part of the contraction induced by electrical field stimulation in rabbit bladder smooth muscles. The results suggest that there is a NO-mediated mechanism inhibiting acetylcholine release from cholinergic nerve endings in rabbit bladder, which may contribute to bladder function.

Acetylcholine↗

Prevention of surgical site infection by antibiotic spraying in the operative field during cardiac surgery.

OBJECTIVE: Despite the many procedures introduced to prevent surgical site infection during cardiothoracic surgery, serious infections still occur. We attempted to reduce surgical site infection by spraying antibiotic solution in the operative field--a procedure since introduced at 4 other Japanese institutions. METHODS: In the latter half of 1990, we began spraying an antibiotic solution of cefazolin (1g) and gentamicin (40 mg)/40 ml of saline placed in a 50 ml syringe and dispensed through an 18 G needle bent at 60 to 80 degrees to clean the wound during surgery. RESULT: No deep surgical site infections or deaths due to infection have occurred among the 502 patients undergoing cardiothoracic surgery under cardiopulmonary bypass at our hospital. This method was used in over 2,100 cases of similar procedures at 4 other institutions. There were 3 deaths due to severe surgical site infection (0.11%). At one institution treating over 1,000 cases a year, the incidence of death due to surgical site infection decreased significantly after this method was introduced. CONCLUSION: These preliminary experiences show that spraying antibiotic solution in the operative field reduces the risk of surgical site infection in cardiothoracic surgery.

Aerosols↗

Protein overexpression and gene amplification of c-erb B-2 in pulmonary carcinomas: a comparative immunohistochemical and fluorescence in situ hybridization study.

Amplification of the c-er bB-2 gene (located on 17q11.2--12) is accompanied by overexpression of its cell surface receptor product, p185(ERBB2). In pulmonary carcinomas, however, there has been disagreement between the reported frequencies of gene amplification and overexpression. To clarify their relationship, the correlation between the cellular expression of p185(ERBB2) and the level of c-erb B-2 gene amplification was studied. A total of 195 pulmonary carcinomas (182 primary and 13 metastatic) were examined immunohistochemically using a polyclonal antibody, which recognizes the internal domain of the human c-erb B-2 protein, and positive tumors were further examined for the gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2--12. By immunohistochemistry, distinct membrane staining was found in an adenocarcinoma, a large cell carcinoma and a metastatic carcinoma from the breast, and cytoplasmic and/or faint membranous staining was observed in 23 non-small cell lung carcinomas. It was in the two primaries and the metastatic carcinoma that more than 8-fold amplification of c-erb B-2 was found by fluorescence in situ hybridization. Especially, in the two primary carcinomas, tumor cells had amplified genes with the signals forming one or two clusters, indicating that the amplified gene was present in homogeneously staining regions. Among the 23 tumors, three tumors showed low-level amplification (less than 3-fold), which was differentiated from polysomy 17 found in the other two. In the 30 non-small cell lung carcinomas selected at random from 151 with negative immunostaining, there were five trisomy 17, but no tumors with the gene amplification. This suggests that although c-erb B-2 amplification in pulmonary carcinoma is rare, it occurs in the form of a homogeneously staining region and is thought to control the overexpression of the protein in the cell membrane. New adjuvant therapy using a humanized antibody to the oncoprotein may be beneficial to patients with these tumors.

Carcinoma, Non-Small-Cell Lung↗

Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome.

Intravenous administration of isoproterenol restored the ST-segment configuration to nearly normal in the right precordial leads and completely prevented spontaneous VF attacks in a patient with Brugada syndrome. The formation of a Brugada-type ECG has been attributed to the transmural dispersion of repolarization of the right ventricular epicardium and related to modulation of the autonomic nervous system. Our case may provide clues to the pathophysiological mechanism of this syndrome.

Adult↗

Two cases of bronchial asthma after treatment with amiodarone.

Amiodarone is a highly effective antiarrhythmic agent for the prevention of life-threatening arrhythmias. Two cases are described of patients who developed bronchial asthma after treatment with amiodarone. The bronchial asthma resolved after the dose of amiodarone was decreased in both patients. To our knowledge, an association between amiodarone and severe bronchial asthma has previously been reported only once in the medical literature. Physicians should note that amiodarone may cause bronchospasm in susceptible patients.

Aged↗

FDG accumulation in aortic walls.

A 65-year-old woman with no symptoms underwent whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for cancer screening. FDG accumulation was detected incidentally in her arterial walls, including the aortic wall. She had no history of inflammatory or cardiovascular disease. Although accumulation of FDG is well recognized in the aortic wall when vasculitis is present, this patient showed no symptoms of active vasculitis during the 22-month follow-up period after the PET study. The aortic wall might be a site where FDG accumulates physiologically in elderly persons.

Aged↗

F-18 FDG uptake in endometrial cancer.

Endometrial cancer, which is one of the most common malignant gynecologic diseases, was detected by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in a 60-year-old woman with abdominal distention. FDG PET revealed heterogeneous and marked accumulation in the endometrium, which was thought to represent endometrial cancer. In addition, focal intense accumulation of FDG in both lungs suggestive of lung metastases were noted. Endometrial cancer and lung metastases were confirmed by endometrial biopsy and computed tomography of the chest, respectively.

Endometrial Neoplasms↗

Tranilast inhibits cardiac allograft vasculopathy in association with p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation model.

Cardiac allograft vasculopathy is a major complication after cardiac transplantation, often limiting long-term recipient survival. N-(3,4-Dimethoxycinnamoyl)anthranilic acid (tranilast) inhibits cyclin-dependent kinase activity through p21(Waf1/Cip1) induction and arrests vascular smooth muscle cell proliferation in vitro. We tested a hypothesis that tranilast inhibits the vasculopathy characterized by diffuse intimal thickening in a murine heart transplantation model. Hearts from DBA/2 mice were heterotopically transplanted into B10.D2 mice as allografts. Oral administration of tranilast started 3 days before transplantation at doses of 550 or 1040 mg/kg per day until the animals were killed. Cardiac allograft vasculopathy was defined as luminal stenosis caused by neointimal formation. The percentage of luminal stenosis and cardiac rejection were analyzed 14 and 28 days after transplantation. Tranilast administration was associated with a marked reduction in luminal occlusion but with no significant effect on cardiac rejection. Immunohistochemical study of the tranilast-treated graft coronary arteries revealed enhancement of p21(Waf1/Cip1) and decreased expression of proliferating cell nuclear antigen in the neointima. The significant reduction in allograft vasculopathy concomitant with the enhancement of p21(Waf1/Cip1) indicates that tranilast has an antiproliferative effect that could be applicable to clinical treatment of cardiac allograft vasculopathy.

Animals↗

FDG uptake in the morphologically normal thymus: comparison of FDG positron emission tomography and CT.

The purpose of this study was to evaluate the correlation between fluorine-18 fluorodeoxyglucose (FDG) thymic uptake and a normal appearing thymus on CT. Non-attenuation corrected FDG positron emission tomography (PET) data from 94 young persons (mean age 25.4 years, range 18-29 years) with a normal thymus diagnosed on CT were retrospectively evaluated. No subject had clinical symptoms suggestive of thymus-related disease or mediastinal tumour (follow-up period 6-69 months). PET images were visually assessed and the count ratio between the thymus and the lung (T/L ratio) was calculated. Increased FDG uptake occurred in 32 (34%) subjects. In these 32 cases, the T/L ratio was 2.86+/-0.49 (range 2.02-3.99). In 86 subjects whose CT images were available to calculate the CT attenuation of the thymus (CAT), the CAT value was -17.5+/-45.7 HU (range -103.6 HU to 79.9 HU). The T/L ratio correlated with the CAT value (r=0.58). CAT values in subjects with positive PET findings were significantly higher than CAT values in subjects with negative PET findings (p<0.001, unpaired t-test). These results suggest that even in young adults, if the thymus has a relatively high CT attenuation value, the presence of physiological thymic uptake in FDG-PET is a normal variant. In this study, the diagnosis of normal thymus was based on CT appearance and clinical course. Further studies are needed to clarify the relationship between histopathology and FDG uptake in the thymus.

Adolescent↗

18F-FDG PET detection of colonic adenomas.

UNLABELLED: The adenomatous polyp of the colon is clinically important as a precursor of colonic cancer. The aim of this preliminary study was to evaluate the potential usefulness of (18)F-FDG PET for detecting adenomatous polyps of the colon. METHODS: We performed a retrospective study of 110 subjects who underwent both PET study and total colonoscopy. On nonattenuation-corrected PET images, focal distinct FDG accumulation along the large intestine was considered a positive finding, and the PET results were compared with colonoscopic findings. Histology and adenoma size were determined by polypectomy. RESULTS: Fifty-nine adenomatous polyps, 5-30 mm in size, were found in 30 subjects by total colonoscopy. PET findings were positive for 14 of the 59 adenomas (24%). The positivity rate for PET images rose with the increase in size of the adenomas; it was 90% in adenomas (9/10) that were > or =13 mm. The overall false-positive rate was 5.5% (6/110 subjects). CONCLUSION: Increased glucose metabolism is observed in colonic adenomas, and detectability with PET increases with the increase in adenoma size. Adenomas are premalignant lesions, and it is important to realize that colonic adenomas may be found incidentally during an FDG PET study.

Adenomatous Polyps↗

Hemorrhagic shock due to intrathoracic rupture of an osteosarcoma of the rib.

A 13-year-old girl presented with dyspnea and chest pain. Chest radiography showed a massive left pleural effusion. Computed tomography revealed a tumor of the fourth rib. A large bloody effusion was drained. Her anemia worsened (hemoglobin: 4.8 g/dl), and hemorrhagic shock ensued. An emergency thoracotomy was performed. Bleeding from the ruptured tumor was identified. The fourth rib, the tumor, and the adjacent tissues were resected. Histopathologic examination revealed a ruptured primary osteosarcoma of the rib with pleural dissemination.

Adolescent↗

[Surgical treatment of chronic pulmonary thromboembolism caused by a cavernous hemangioma at the lower limb].

A 48-years old man complained of dyspnea and was admitted to the hospital. Chest enhanced CT confirmed the presence of the thrombus in the pulmonary artery. Cardiac catheterization showed severe pulmonary hypertension (mean PAP 75 mmHg). ATIII level, protein C and S antigen were within normal range. Anticardiolipin antibody and lupus anti-coagulant determination were negative. He was diagnosed as chronic pulmonary thromboembolism, and underwent pulmonary thromboendarterectomy via median sternotomy under deep hypothermic intermittent circulatory arrest. At the same time IVC filter was inserted. The origin of the thrombus was not detected before operation, but after surgery, MR angiography of total body showed a cavernous hemangioma at left lower limb. We speculated this lesion was the origin of pulmonary embolism.

Chronic Disease↗

Prejunctional alpha-adrenoceptors regulate nitrergic neurotransmission in the rabbit urethra.

We evaluated the effects of prejunctional alpha-adrenoceptors on nitric oxide (NO)-mediated urethral relaxation in rabbits using a muscle bath technique and high-performance liquid chromatography coupled with a microdialysis procedure. The amount of NO(2)(-)/NO(3)(-) released during electrical field stimulation was measured by an NO(2)(-)/NO(3)(-) analyzer based on the Griess method. Pretreatment with phenylephrine (0.01 microM) and yohimbine (0.1-10 microM) significantly reduced the relaxation responses induced by electrical field stimulation. In contrast, pretreatment with clonidine (0.01 microM) and prazosin (0.01-1 microM) enhanced the relaxation responses. Cys-NO-induced relaxations of rabbit urethral smooth muscle were not affected by pretreatment with alpha-adrenoceptor agonists and antagonists. The amount of NO(2)(-)/NO(3)(-) released by electrical field stimulation increased after pretreatment with clonidine (0.01 microM) and prazosin (0.01-1 microM), but decreased after pretreatment with phenylephrine (0.01 microM) and yohimbine (0.1-10 microM). The results suggest that the release of NO from nitrergic nerves in the rabbit urethra is reduced and increased by stimulation of prejunctional alpha(1)- and alpha(2)-adrenoceptors, respectively.

Adrenergic alpha-Agonists↗

Reduced cerebral glucose metabolism in subjects with incidental hyperintensities on magnetic resonance imaging.

OBJECTIVE: To clarify the significance of incidental and asymptomatic hyperintensities on T(2)-weighted magnetic resonance images (MRI) in adults, we examined the relationship between a variety of these lesions and cerebral metabolism evaluated by positron emission tomography (PET) with (18)F-labeled fluorodeoxyglucose ([(18)F]FDG). SUBJECTS AND METHODS: Two hundred and thirty-one persons with hyperintensities on T(2)-weighted MRI but without overt neurological disease (mean age 60+/-9 years) were studied. MR hyperintensities were classified into deep and/or subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs) and hyperintensities in the basal ganglia and/or thalamus (HBGTs). The relationship between these lesions and cerebral metabolic rate of glucose (CMRgl) measured by [(18)F]FDG-PET was investigated. RESULTS: The CMRgl values in white matter and cerebral cortex in the group with severe PVHs were lower than those in the group with mild PVHs (P<0.0001 and P<0.005). Although the severity of PVHs was associated with the numbers of DSWMHs and HBGTs, the results of multivariate analysis showed a significant relationship of PVHs to glucose metabolism in cerebral cortex and white matter. CONCLUSIONS: We conclude that increasing severity of MRI hyperintensities in adults is associated with a deterioration of cerebral metabolism. In particular, involvement of PVHs may be a marker of widespread deterioration of cortical metabolism.

Adult↗