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Biomedical subjects

S Watanabe

Publications and source records attributed to S Watanabe.

At least 343 records · Page 19Linked to original sources

Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time-resolved fluoroimmunoassay.

Time-resolved fluoroimmunoassays (TR-FIA), with europium labeled phytoestrogens as tracers, were developed for the quantitative measurement of genistein, daidzein and enterolactone in plasma and urine for the purpose of screening large populations and studies on possible correlation between the values in biological fluids and the risk of western diseases. The mean values of the three phytoestrogens in plasma as determined by TR-FIA were similar to those obtained by gas chromatography-mass spectrometry (GC-MS). The urinary excretion levels of total individual phytoestrogens were higher than those obtained by GC-MS, with the exception of the daidzein values. However, comparing the assay results obtained by the present method and those obtained by GC-MS, a strong correlation was evident (r = 0.87 - 0.99, p < 0.001). We measured plasma levels of genistein, daidzein and enterolactone in 111 healthy Japanese women The mean and median levels of genistein were 406.8 and 306.3 nmol/l, respectively, and those of daidzein were 118.4 and 76.8 nmol/l, respectively. These levels are higher than those reported for Americans and Western Europeans. Isoflavone intake as calculated from dietary records (genistein: mean, 86.5 mircomol/day and daidzein: mean, 57.4 micromol/day) was correlated with the plasma concentrations observed (genistein: r = 0.287, p < 0.01 and daidzein: r = 0.313, p < 0.01). Plasma enterolactone levels were low in Japanese women (mean, about 10 nmol/l). The levels of urinary excretions of genistein, daidzein were also measured and it was found that, in the majority, the levels ranged between 5-25 and 5-50 micromol/24 h, respectively. In contrast, healthy Finnish women showed very low values of isoflavones (below 10 nmol/l in plasma (n = 87) and below 0.6 micromol/24 h in urine (n = 126) for both compounds) and high levels of enterolactone in both plasma and urine (plasma: mean, 25 nmol/l and urine: majority range, 1-7 micromol/24 h).

4-Butyrolactone↗

Antioxidant activity of soya hypocotyl tea in humans.

Antioxidative activity of isoflavones has not been shown in humans. Newly-developed isoflavone-rich soya hypocotyl tea contains about 12 mg isoflavones per liter. 15 tea drinkers and 23 control young female students were randomly selected from volunteers, and underwent physical examination, blood chemistry and urinary analysis before and after one month of tea drinking. A three-day dietary record was taken before each physical examination. The tea drinkers showed a lower level of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl-ethanolamine hydroperoxide (PEOOH) in the red blood cells and a significant reduction of 8-hydroxydeoxyguanine (8ohdG) in the urine compared to the controls.

8-Hydroxy-2'-Deoxyguanosine↗

Effects of isoflavone supplement on healthy women.

Effects of the isoflavone supplement on hormonal states in young premenopausal women were studied by cross-over study design. Administration of 20 mg or 40 mg isoflavones (IF) by tablets, of which 1 g contained 43.5 mg daidzein, 6.0 mg genistein, 24.0 mg glycitein, to 40 young female students for one month caused a prolonged menstruation in 60% of young women, shortened menstruation in 20% of young women, 17% remained unchanged and 3% became irregular. Larger dose tended to elongate more, but 17beta-estradiol levels in both follicular and luteal phages were not different between 20 mg and 40 mg isoflavone intake. Equor excreters tended to show low plasma progesteron level in the luteal phase. Detailed hormonal analysis on 3 of students by a cross over study design showed decreased level of 17beta-estradiol throughout the menstruation cycle. SHBG significantly increased about 10% in all three. DEAS, androstendione, and testosterone showed different responses according to the follicular or luteal phase. T3 and T4 increased as a result of isoflavone tablet administration in the follicular phase, but it decreased in the luteal phase. These changes suggest that isoflavones influence not only estrogen receptor-related functions but the hypothalamo-hypophysis-gonadal axis.

Androstenedione↗

Low-dose dobutamine radionuclide ventriculography for prediction of myocardial viability: quantitative analysis of regional left ventricular function.

BACKGROUND: It is important to distinguish viable myocardium from necrotic tissue in order to decide upon therapy in patients with ischemic heart disease. HYPOTHESIS: We verified the hypothesis that quantitative analysis of regional left ventricular function using low-dose dobutamine radionuclide ventriculography (RNV) can sensitively predict myocardial viability and compared its usefulness with thallium-201 (201Tl) single-photon emission computed tomography (201Tl-SPECT). METHODS: Radionuclide ventriculography at rest and during low-dose dobutamine infusion (5 micrograms/kg/min), 201Tl-SPECT, and coronary angiography were performed in 51 subjects with severe ischemia-related stenosis of coronary arteries and 3 subjects without coronary artery disease. 201Tl uptake was assessed as normal (control), low perfusion (LP), or defect. We compared the response of regional function to dobutamine with the regional 201Tl uptake. The accuracy of both methods for identifying viable myocardium was investigated in 17 patients who underwent successful coronary revascularization, with a resulting improvement in wall motion. RESULTS: The increase in regional ejection fraction (delta r-EF) in response to dobutamine was significantly greater in the control (12 +/- 6%) and LP (16 +/- 11%) regions than in the defect (5 +/- 10%) regions. The increase in one-third regional ejection fraction (delta r-1/3EF) was also significantly higher in the control (14 +/- 7%) and LP (10 +/- 8%) regions than in the defect regions (5 +/- 6%). We defined myocardial viability as a delta r-EF > 5% or a delta r-1/3EF > 2%. The sensitivity and specificity of the delta r-EF for identification of myocardial viability were 91.4 and 55.5%, respectively. The sensitivity and specificity of the delta r-1/3EF were 91.4 and 66.6%, respectively; the corresponding values for 201Tl SPECT were 74.2 and 77.8%. CONCLUSION: Low-dose dobutamine RNV with quantitative analysis of regional left ventricular function was more sensitive for identification of viable myocardium than 201Tl-SPECT.

Aged↗

Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium.

Treatments for rheumatoid arthritis and other inflammatory arthropathies are often ineffective at preventing joint destruction. Long-term genetic modification of the cells lining the joint space (synoviocytes) in vivo represents a potential method for the treatment of these chronic conditions. However, a vector capable of efficiently transducing synoviocytes in vivo for a persistent period has not been available. The present report describes the genetic modification of synoviocytes in vivo using recombinant adeno-associated virus. High-titer adeno-associated virus encoding the gene for Escherichia coli beta-galactosidase was injected into the knee joints of mice. Synovial tissues were then examined for beta-galactosidase transgene expression by in situ staining and by fluorometry. High-efficiency, persistent transgene expression was observed in the synovium with no evidence of vector-induced inflammation. Expression was observed for at least 7 months and was higher in arthritic than nonarthritic mice. Gene transfer of murine IL-4 to the joints of mice with collagen-induced arthritis led to detectable levels of IL-4 in the joint and protection from articular cartilage destruction. These data suggest that adeno-associated virus may be a useful vector for gene delivery to the synovium for the treatment of inflammatory arthropathies.

Animals↗

Association of bone mineral density with polymorphism of the human calcium-sensing receptor locus.

A strong correlation between bone mass and genetic factors has been shown in twins and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate genes, calcium-sensing receptor (CASR) in the parathyroid gland, regulates calcium homeostasis by sensing decreases in extracellular calcium level and effecting an increase in secretion of parathyroid hormone (PTH) and calcium (Ca) reabsorption in the kidney. We have investigated a possible association between the CA-repeat polymorphism at the human CASR gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into nine groups according to the number of CA repeats present, from 20 to 12. BMD was expressed as the adjusted BMD, which was the body mass index (BMI), and age-adjusted average BMD. The 247 women who had an A3 allele (228 bp, containing 18 repeats of CA) had significantly lower adjusted BMD (mean +/- SD: 0.303 +/- 0.059 versus 0.316 +/- 0.063 g/cm(2); P = 0.0308) than the participants (n = 201) who did not carry an allele of that size. This result suggests that genetic variation at the CASR gene locus is associated with some determinants for BMD in postmenopausal women.

Aged↗

A case report of intravenous leiomyomatosis extending into the heart.

The patient was a 47-year-old woman who underwent total hysterectomy for uterine leiomyoma in 1994. Two years later, intracaval and intravenous tumors were found by ultrasonic cardiography, magnetic resonance imaging, enhanced chest computed tomography, and venography. The patient underwent total removal of these tumors. Pathological findings indicated that these tumors were leiomyomas. After comparing the present findings with those of similar cases in the literature, we concluded that our patient had intravenous leiomyomatosis extending into the heart.

Female↗

Ineffective interferon treatment of chronic hepatitis C-associated porphyria cutanea tarda, but with a transient decrease in HCV RNA levels.

Many patients with porphyria cutanea tarda (PCT) have been reported to be hepatitis C virus (HCV) carriers, suggesting that HCV infection plays a role in the pathogenesis of this type of porphyria. In this study, we report a patient with chronic hepatitis C-associated PCT. Therapy with interferon (IFN) transiently decreased HCV RNA levels, but levels of urinary porphyrins and serum transaminases and ferritin remained unchanged. Serum ferritin and urinary porphyrin levels improved after phlebotomy, but this therapy was not effective in improving serum transaminase levels. Although a physiopathological association between HCV infection and PCT has been suggested previously, IFN was not effective in this patient. The transient decrease in HCV RNA levels was a factor independent of porphyrin metabolism.

Aged↗

Multiple epiphyseal dysplasia--report of two families.

Multiple epiphyseal dysplasia (MED) is a relatively uncommon inherited disorder of epiphyseal maturation. Affected individuals may have a degree of short-limbed dwarfism, short stubby digits, and stiff or painful joints. We report two families of MED and emphasize the variations of joint involvement. Ten out of 34 members in family A and 13 out of 39 members in family B were suspected of having MED by questionnaire. Radiological examination was done for 3 out of the 10 members in family A and 6 out of the 13 members in family B. In both families, the epiphyseal disturbances in the skeleton were bilaterally symmetric and involved several joints. Apparent dwarfism, short stubby digits and spinal involvement were not observed. The degree and the pattern of affected joints were different in the two families and even among members of the same family. In family A, the knee joint was commonly affected, followed by the ankle joint. The deformity of the joints was mild and caused only slight disability. No apparent hip lesion was present. In family B, the hip joint was predominantly affected, followed by the knee and ankle joints, and the deformity was severer than that in family A. These observations suggest that MED is a group of heterogeneous disorders.

Adult↗

Flexibility of saccade adaptation in the monkey: different gain states for saccades in the same direction.

Saccadic accuracy, measured as the ratio of the size of a saccade to the size of the target step that elicits it, i.e., saccade gain, can be altered by jumping the target surreptitiously during the targeting saccade. The gain change produced by this paradigm does not generalize or transfer to saccades of all sizes. Instead, the amount of transfer decreases the more the tested saccade differs in amplitude and direction from that adapted. Here, we tested the limits of this saccade-size specificity by attempting to impose quite different gain states on saccades in the same direction. We altered the saccadic gain by intrasaccadic target jumps of 30% of the initial target step, either forward to produce a gain increase or backward to produce a gain decrease. Three different conditions were studied: (1) saccades to target steps of 20 degrees or 7 degrees were adapted in individual sessions with backward and forward jumps, respectively; (2) saccades to target steps of 20 degrees caused backward target jumps during the same session in which saccades to 7 degrees target steps caused forward steps; (3) the target jumps accompanying 20 and 7 degrees saccades were the same as in (2), but in addition, there were intermediate-sized saccades to 13.5 degrees target steps with no intrasaccadic target jumps. Saccadic gain adaptation was quite flexible. In condition 2, we could simultaneously increase the gain of saccades to 7 degrees target steps while decreasing the gain of saccades to 20 degrees steps in the same direction. Intermediate horizontal saccades to 13.5 degrees target steps experienced gain reductions (average: 6.9%), which were not the sum of gain changes expected from separate 20 degrees gain decreases and 7 degrees gain increases alone, as predicted from condition 1. If adaptation at 20 degrees and 7 degrees occurred while an animal also tracked a non-adapting 13.5 degrees target step (paradigm 3), the gain reduction of saccades to the 13.5 degrees step was reduced considerably (3.4%). Thus, the mechanism that adapts saccade size can support a robust gain increase for saccades of one size while simultaneously supporting a robust gain decrease for saccades only 13 degrees larger. Furthermore, the presence during adaptation of a non-adapted target step with a size intermediate to the two adapting steps reestablishes a nearly normal gain within only 6.5 degrees of a robust gain increase and decrease. These data indicate that saccadic gain adaptation can set very different gain states for saccades with rather similar vectors.

Adaptation, Ocular↗

Effect of mental stress on left ventricular ejection fraction and its relationship to the severity of coronary artery disease.

To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8% +/- 17.7% to 49.8% +/- 16.2% with mental stress (P < 0.0005). Ten of the 20 patients (50.0%) had a > or = 5% decrease in LVEF The remaining ten patients had no or a <5% decrease in LVEF There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r = -0.80, P < 0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of <10 (r = -0.69, P = 0.014) than in the eight patients with a total defect score at rest of > or = 10 (r = -0.94, P = 0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEE It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.

Aged↗

Congenital absence of the horizontal portion of the left portal vein: ultrasound findings.

Congenital absence of the horizontal portion of the left portal vein is very rare and has been very reported sporadically. We present three such cases referred from other hospitals with a diagnosis of intrahepatic vascular anomaly. Color Doppler ultrasound not only confirmed the diagnosis but also allowed a quantitative measurement of blood flow in these cases. Although it is a very rare condition, knowledge of the ultrasound and color Doppler findings helps in establishing the diagnosis of this congenital anomaly.

Congenital Abnormalities↗

Long-standing painless intussusception in adults.

Long-standing painless intussusception in adults is considered to be rare. We report three such cases with an emphasis on color Doppler results. In our three cases the indication for abdominal US was a palpable mass in all these cases, and intussusception was detected by US at a time when the patients had only very mild abdominal discomfort. Persistence of sufficient blood flow, as was suggested by the color Doppler results, was thought to be the most likely pathomechanism of long-standing painless intussusception. The underlying disease was tuberculosis in two of the three cases. Thus, when encountering patients with painless intussusception, tuberculosis must be kept in mind.

Aged↗

alpha-Glutathione-s-transferase as a new sensitive marker of hepatocellular damage in biliary atresia.

Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. alpha-Glutathione-s-transferase (alpha-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum alpha-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 +/- 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum alpha-GST was determined using a specific ELISA. Tissue alpha-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum alpha-GST was significantly higher in group II (20.7 +/- 8.4 ng/ml) than in groups I (4.7 +/- 1.3 ng/ml) and III (8.0 +/- 1.2 ng/ml) (P < 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens alpha-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III alpha-GST was only found in regenerative nodules. We conclude that alpha-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of alpha-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.

Adolescent↗

Severity of hyperemesis gravidarum correlates with serum levels of reverse T3.

To investigate the possible physiological relevance of extra-thyroidal production of reverse T3 (rT3) in hyperemesis gravidarum, measurements of serum rT3, free T3 (FT3), free T4, (FT4), and nonesterified fatty acids (NEFA) were correlated with weight loss of hyperemetic women. All the thyroid hormones, NEFAs and weight loss were significantly higher in hyperemesis gravidarum than in control subjects, and also higher than in those with milder symptoms of morning sickness (p < 0.05). Elevations of FT3, FT4 and NEFAs correlated with the extent of weight loss, the latter taken as the index of the severity of hyperemesis gravidarum (p < 0.05). Only rT3 correlated with both weight loss and the rate of lipolysis, as reflected by elevations of NEFAs (p < 0.05). The data are consistent with a shift from T3 to rT3 as products of 5'-monodeiodination of thyroxine in hyperemesis gravidarum. Because reverse T3 is physiologically inactive a control mechanism may be postulated wherein T3 production is minimized, thereby reducing weight loss and lipolysis in patients with hyperemesis gravidarum.

Fatty Acids, Nonesterified↗

Taurine preserves gap junctional intercellular communication in rat hepatocytes under oxidative stress.

Gap junctional intercellular communication (GJIC) between hepatocytes is important for the maintenance of differentiated liver functions. Taurine is known to be cytoprotective, and is used clinically to improve liver functions. We evaluated the effect of taurine on GJIC in hepatocyte doublets under oxidative stress. Hepatocyte doublets were isolated from female Wistar rats, using a collagenase perfusion technique, and cultured in Leibovitz-15 medium containing fetal bovine serum (10%). H2O2 (2 mM) and/or taurine (0.1-1 mM) were added 2 h after inoculation, and the culture was incubated for 3 h. Fluorescent dye (Lucifer Yellow CH) coupling between adjacent cells was evaluated by microinjection. The distribution and quantity of connexin 32 (Cx32) in hepatocytes were detected using indirect immunofluorescence analysis and Western blotting. Steady state mRNA levels of Cx32 were detected by Northern blotting. The percentage of dye coupling 5 h after inoculation was 88 +/- 6.3% in the control. however, this was decreased to almost half the control value by H2O2. Taurine prevented the decrease caused by H2O2 in a dose-dependent manner. Immunofluorescence analysis for Cx32 demonstrated numerous punctate fluorescent spots along the intercellular plasma membrane in controls, which were significantly decreased by H2O2. Taurine prevented the decrease of Cx32. Western blot analysis also showed the decrease of Cx32 protein levels by H2O2 treatment, which decrease was prevented by taurine. Interestingly, H2O2 and/or taurine treatments did not affect Cx32 mRNA levels. Our findings indicated that H2O2 treatment decreased GJIC between hepatocytes, most likely due to augmenting the degradation of Cx32 proteins, whereas taurine prevented this process. This effect of taurine is beneficial for the preservation of differentiated functions in the liver under oxidative stress.

Animals↗

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats.

Cyclosporin A is an immunosuppressive agent which is well known as a specific inhibitor of calcineurin (protein phosphatase 2B). In this study, we investigated the effects of cyclosporin A on water-immersion stress-induced gastric ulcer formation and gastric acid secretion in rats. We also examined the localization of calcineurin immunohistochemically. Calcineurin was specifically expressed in gastric parietal cells and chief cells of the gastric mucosa. The intraperitoneal administration of cyclosporin A dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion stress and inhibited gastric acid secretion, as assessed by pylorus ligation. These results indicated that calcineurin may play an important role in gastric acid secretion.

Animals↗