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Biomedical subjects

W Takahashi

Publications and source records attributed to W Takahashi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of ovarian hormones on beta-adrenergic receptor-mediated relaxation in the female rabbit bladder.

The effects of ovarian hormones on beta-adrenergic receptor-mediated responses in female rabbit detrusor smooth muscles were investigated. Ovariectomized mature female New Zealand white rabbits were untreated or treated with estrogen and/or progesterone for 2 weeks. The contractile responses to carbachol and KCl in the detrusor strips were not significantly different in all groups. As compared with dobutamine and GS-332, isoproterenol and procaterol significantly relaxed the detrusor strips derived from all groups on KCl-induced tonic contractions. Combined with estrogen treatment, isoproterenol, procaterol and GS-332 caused a significant increase in this muscle relaxation. Furthermore, estrogen treatment caused a significant increase in relaxation as a result of forskolin and the cyclic AMP (cAMP) production that was induced by isoproterenol, procaterol and GS-332. However, estrogen treatment did not affect the relaxant response to dibutyryl cyclic AMP. Progesterone treatment did not affect beta-adrenergic receptor-mediated responses. These results suggest that estrogen treatment causes the increased relaxant responses mediated by beta2- and beta3-adrenergic receptor subtypes, which may be related to the increased cAMP content in female rabbit detrusor smooth muscles.

Adrenergic beta-Agonists↗
PubMed2000

Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle.

OBJECTIVE: To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ-bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated. RESULTS: Carbachol (0.001-10000 micromol/L) caused concentration-dependent contractions in human detrusor smooth muscles. Tolterodine (0.01-10 micromol/L), vamicamide (0.01-10 micromol/L), temiverine (0.01-1 micromol/L) and atropine (0.001-1 micromol/L) caused parallel shifts to the right of the concentration-response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atropine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 micromol/L) significantly inhibited the maximum contractions. Tolterodine (0.001-1 micromol/L) and vamicamide (0.01-10 micromol/L) did not inhibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01-10 micromol/L) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 micromol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 micromol/L) significantly inhibited the contractions. CONCLUSION: Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium-antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.

Aged↗
PubMed2000

Application of positron emission tomography imaging to cancer screening.

Whole-body positron emission tomography (PET) with(18)F-fluorodeoxyglucose (FDG) is a diagnostic modality that can noninvasively survey the entire body and sensitively detect various cancers. In this study, we examined the potential application of whole-body PET for cancer screening in asymptomatic individuals. PET was performed in conjunction with conventional examinations including physical examination, laboratory study, ultrasonography and chest computed tomography. Between September 1994 and March 1999, 3165 asymptomatic individuals participated in 5575 screening sessions (2017 men and 1148 women; mean +/- SD age, 52.2+/-10.4 years). Follow-up periods were no less than 10 months. PET results were compared with the screening outcomes. Within 1 year after screening, malignant tumours were discovered in 67 of the 3165 participants (2.1%). PET findings were true-positive in 36 of the 67 cancers (54%). Most of the 36 patients underwent potentially curative surgery; thus a wide variety of cancers were detected by PET at potentially curable stages. However, PET findings were false-negative in 31 of the 67 patients (46%). 14 of these 31 (45%) were of urological origin. FDG PET imaging has the potential to detect a wide variety of cancers at potentially curable stages. However, PET imaging is not suited to screening test of general population because PET examination involves substantial cost.

Adult↗
PubMed2000

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↗
PubMed2000

Inducible nitric oxide-mediated myocardial apoptosis contributes to graft failure during acute cardiac allograft rejection in mice.

The mechanism through which nitric oxide (NO) mediates cardiac myocyte death during acute cardiac rejection has not been fully delineated. We sought to determine whether NO promotes myocardial apoptosis and contributes to graft failure during acute cardiac rejection in a murine model. Heterotopic cardiac transplantation was performed from Balb/c (H-2d) to C3H/He mice (H-2k). Recipients were treated with aminoguanidine (AG) at 400 mg/kg every day after surgery. As references, we used isografts in Balb/c mice with and without AG treatment (400 mg/kg/day). Graft survival, histological changes and serum NO levels were assessed. Intra-graft apoptosis was evaluated using a DNA fragmentation detection assay (TUNEL method) and DNA laddering. Significant prolongation of graft survival was observed in allografts treated with AG in comparison with nontreated allografts. Serum NO levels, which peaked on day 7 in nontreated allografts, were significantly decreased in AG-treated allografts. AG treatment decreased the number of apoptotic cells and lowered the ratio of the apoptotic cardiac myocytes in contrast to that of the apoptotic infiltrating cells. DNA laddering was clearly detected in nontreated allografts but was suppressed in AG-treated allografts. Inhibition of NO production by AG prolonged murine cardiac allograft survival. The decrease in intra-graft apoptotic activity paralleled histological improvement. Cardiac myocyte death which occurs through an apoptotic process mediated by NO contributes to graft failure during acute cardiac rejection.

Animals↗
PubMed2000

Global reduction of cerebral glucose metabolism in persons with symptomatic as well as asymptomatic lacunar infarction.

To clarify the hemodynamic changes in lacunar infarction, we evaluated cerebral glucose metabolism by using positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in patients with asymptomatic and symptomatic lacunar infarction and in persons without cerebral infarction on MRI. Subjects in this study were 27 patients with symptomatic lacunar infarction (SCI group), 73 subjects with asymptomatic lacunar infarction (ACI group), and 134 persons without infarction (NC group). CMRgl in the ACI group was significantly lower than that in the NC group in the cerebral cortex (P < 0.05) and thalamus (P < 0.05). CMRgl in the SCI group was significantly reduced from that in the NC group in the cerebral cortex (P < 0.005), basal ganglia (P < 0.001), thalamus (P < 0.05) and white matter (P < 0.005). The reduction in CMRgl in the SCI group was more severe than that in the ACI group in basal ganglia (P < 0.05) and thalamus (P < 0.05). Our results indicated that glucose metabolism in patients with asymptomatic lacunar infarction is reduced throughout the whole brain as compared with non-infarcted elderly persons. Follow-up and treatment of risk factors if present, may be necessary in such patients.

Aged↗
PubMed2000

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.

Aclarubicin↗
PubMed2000

[An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated cardiomyopathy].

We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with dilatated cardiomyopathy. A 29-year-old male patient first noticed night-blindness at the age of four years. He was pointed out retinitis pigmentosa at the age of six years and developed ataxia, mental retardation, epilepsy and myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum, brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted MRI showed mild high signal intensity in the white matter around the trigones of the lateral ventricles. Autopsy findings showed an abundant accumulation of ceroid-lipofuscin-like lipopigments in most neurons in the central nervous system, and curvilinear bodies and lipofuscin like granules were confirmed by electron microscopy. The heart muscle showed an increase in the accumulation of ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in the myocardium. The peculiar point of this case is NCL3 with dilated cardiomyopathy.

Adult↗
PubMed1999

Pharmacological effects of tolterodine on human isolated urinary bladder.

Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of overactive bladder with symptoms of frequency, urgency and urge incontinence. We investigated the effects of tolterodine and its major active metabolite, DD 01 (PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in human isolated urinary bladder smooth muscles, using the muscle bath technique. Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome region of the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD 01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6) M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(-8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M) caused typical shifts to the right of the concentration-response curves for carbachol, except for higher concentrations (10(-5) M) of oxybutynin and propiverine, which caused a decrease of about 30% of the maximum contractile responses to carbachol. All the slopes of the regression lines of Schild plots were close to unity, and the rank order of pA2 values was: atropine = DD 01 = tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine. Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl-induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)-10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contraction of human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did not inhibit the residual contractions induced by electrical field stimulation at any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M) significantly inhibited the atropine-resistant part of the contractions. The results suggest that the inhibitory effects of tolterodine and DD 01 are mediated only by their antimuscarinic action, which is equal to that of oxybutynin and significantly greater than that of propiverine, and that tolterodine and DD 01 have neither Ca2+ channel antagonist action nor inhibitory effect on the atropine-resistant part of the contractions in human detrusor smooth muscles. These findings support the usefulness of tolterodine as a therapeutic drug for overactive bladder with symptoms of frequency, urgency and urge incontinence.

Aged↗
PubMed1999

Increased FDG uptake in the wall of the right atrium in people who participated in a cancer screening program with whole-body PET.

The purpose of this study was to evaluate the characteristics of patients who showed increased FDG uptake in the wall of the right atrium. We have encountered 10 patients with increased activity in the wall of the right atrium among a total of 2,367 examinees who participated in our cancer screening program with whole-body PET. The mean age of these examinees was 62.9 yr, higher than that of the total population. All suffered from cardiac disorders, especially atrial fibrillation. FDG accumulated almost exclusively in the wall of the right atrium, whereas only slight activity was seen in the wall of the left atrium. Although the average size of the right atria was significantly enlarged, left atria were more severely dilated than right ones. Therefore overload does not seem to account for the FDG accumulation in the wall of the right atrium. In conclusion, the increased activity in the wall of the right atrium was a rare finding that was made in older people who suffered from cardiac disease. Although the mechanism of induction of the high metabolic state of glucose in the wall of the right atrium remains unclear, this unusual activity would be another false positive finding in cancer screening with whole-body FDG PET.

Adult↗
PubMed1999

Differential Th1 and Th2 cell regulation of murine cardiac allograft acceptance by blocking cell adhesion of ICAM-1/LFA-1 and VCAM-1/VLA-4.

Administration of anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb) plus anti-lymphocyte function associated antigen (LFA)-1 mAb induces tolerance in murine cardiac transplantation, while anti-vascular cell adhesion molecule (VCAM)-1 mAb plus anti-very late antigen (VLA)-4 mAb administration prolongs graft survival, but leads to tolerance only in some cases. BALB/c mice hearts were transplanted into C3H/He recipients. Each combination of anti-VCAM-1 plus anti-VLA-4 mAbs (100 microg each/day, i.p.) or anti-ICAM-1 plus anti-LFA-1 mAbs (50 microg each/day, i.p.) was administered for 5 days. For control study, third group mice received daily with FK506 administration (1 mg/kg/day). The cardiac allografts and recipients' spleens were harvested on day 7; the expression of cytokines were detected using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR. Th2 cytokines (IL-4 and IL-10) were markedly enhanced and Th1 cytokines (IFN-gamma and IL-2) were suppressed in recipients treated with anti-ICAM-1 mAb plus anti-LFA-1 mAb, while poor Th2 cytokine expression allowed persistent Th1 cytokine expression in recipient mice with anti-VCAM-1 mAb plus anti-VLA-4 mAb treatment. Both Th1 and Th2 cytokine expression was suppressed in FK506-treated mice. It is concluded that immunological tolerance and prolonged graft survival induced by blocking cell adhesion is regulated by different cytokine expression.

Animals↗
PubMed1999

A small breast cancer detected by PET.

A small breast cancer was detected by positron emission tomography (PET) in an asymptomatic individual. Physical examination, mammography and magnetic resonance imaging all failed to identify the tumor. Treatment was partial resection of the breast. Based on the resected specimen, the tumor was 6 mm in diameter. Although previous studies have shown PET to be highly sensitive for the detection of primary breast cancer, detectability of tumors smaller than 1 cm is uncertain. Our case suggests the potential utility of PET for the early detection of primary breast cancer.

Breast Neoplasms↗
PubMed1999

Fluorine-18 fluorodeoxyglucose uptake in the retractile testis.

A 51-year-old man with a palpable mass in his right inguinal region had fluorine-18 fluorodeoxyglucose (F-18 FDG) whole-body positron emission tomography (PET) in our cancer screening program. FDG accumulated in the mass, suggesting a metabolically active lesion that was likely malignant. A pelvic MRI and a urologist's palpation revealed that his inguinal mass was a retractile testis. Because a retractile testis is a benign process with no need for interventional therapy, it would be considered a false-positive finding on the cancer screening program using F-18 FDG PET.

False Positive Reactions↗
PubMed1999

Assessment of myocardial fatty acid metabolic abnormalities in patients with idiopathic dilated cardiomyopathy using 123I BMIPP SPECT: correlation with clinicopathological findings and clinical course.

OBJECTIVE: To determine the clinical and prognostic value of identifying metabolic abnormalities of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy using iodine-123 beta-methyl-iodophenyl pentadecanoic acid (123I BMIPP). SETTING: Cardiac care division in national hospital. PATIENTS: 32 consecutive patients with idiopathic dilated cardiomyopathy in whom both 123I BMIPP and thallium-201 myocardial single photon emission computed tomography were performed. METHODS: The uptake of each tracer was scored visually from 0 (normal) to 3 (defect) in 17 segments (eight basal, eight midventricular, and one apical). A total score for all 17 segments was compared with clinicopathological variables. Prognostic value of mismatches between the two tracers were also evaluated. RESULTS: The 123I BMIPP total score was correlated with pulmonary capillary wedge pressure (r = 0.68, p < 0.001), left ventricular end diastolic pressure (r = 0.65, p < 0.001), percentage fractional shortening at six months' follow up (r = -0.58, p = 0. 001), myocyte diameter (r = 0.66, p < 0.001), and percentage area of interstitial fibrosis (r = 0.69, p < 0.001) measured by morphometry in the biopsy specimens. During a mean (SD) follow up of 20 (11) months, deterioration of the New York Heart Association functional class was observed in 11 of the 32 patients; four of these died. Segments with a greater decrease in 123I BMIPP than thallium-201 uptake (type B mismatching) were often observed in patients with deterioration (88/187, 29% v 58/357, 16%; p < 0.001). CONCLUSIONS: The extent of the abnormality of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy reflects the severity of haemodynamic deterioration and histopathological changes. Type B mismatching is one of the important prognostic indicators in idiopathic dilated cardiomyopathy.

Adult↗