Biomedical subjects

Jun Watanabe

Publications and source records attributed to Jun Watanabe.

At least 73 records · Page 4Linked to original sources

PubMed2004

Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma.

The progesterone receptor (PR) has two isoforms, A and B, among which PR-B is mainly involved in regulating proliferation of the uterine endometrium. In this study, immunohistochemical analysis was carried out to investigate the correlation of PR-A and -B expressions with cell cycle-regulatory proteins and clinicopathological parameters in endometrial adenocarcinoma. One hundred and forty-one endometrioid adenocarcinomas [76 with well-differentiated (G1), 35 with moderately differentiated (G2) and 30 with poorly differentiated (G3)] were used. Specimens of formalin-fixed and paraffin-embedded tissue were immunohistochemically stained using the high polymer method (HISTOFINE, NICHIREI). The percentage of positive nuclei of tumor cells observed in three high power fields was expressed as a labeling index (LI). PR-B expression significantly occurred more frequently in G1. It was inversely correlated with p53 gene mutation and p53 over expression, and also with clinicopathological variables, including myometrial and lymph-vascular space invasion and the FIGO stage. Patients with negative PR-B had a poorer prognosis than positive cases. PR-A expression was also significantly higher in G1 and was inversely correlated with Ki-67 expression and myometrial invasion, but not with prognosis. PR-A and -B expressions were significantly correlated with biologically malignant potential. Especially, PR-B expression is useful as a prognostic indicator of endometrial adenocarcinoma.

Adenocarcinoma↗

PubMed2004

Characteristics of the increase in plasma brain natriuretic peptide level in left ventricular systolic dysfunction, associated with muscular dystrophy in comparison with idiopathic dilated cardiomyopathy.

To determine whether the plasma brain natriuretic peptide level increases differentially in muscular dystrophy and idiopathic dilated cardiomyopathy, we investigated the plasma brain natriuretic peptide level and echocardiographic parameters in patients with similarly low left ventricular ejection fraction. The plasma brain natriuretic peptide level was lower, and the left ventricular end-diastolic diameter was shorter in the patients with muscular dystrophy than in those with idiopathic dilated cardiomyopathy. The correlation between the plasma brain natriuretic peptide and left ventricular ejection fraction was shifted downward in the patients with muscular dystrophy compared with those with idiopathic dilated cardiomyopathy. Those between the brain natriuretic peptide and left ventricular end-diastolic diameter were superimposable, although the data from the muscular dystrophy patients were located at the shorter left ventricular end-diastolic diameter side. The plasma brain natriuretic peptide level may differentially increase in the two diseases with similar left ventricular systolic dysfunction. Differences in the left ventricular distension and in the physical activity might explain at least partially the different plasma brain natriuretic peptide levels.

Adult↗

PubMed2004

Clinical evaluation of p53 mutations in urothelial carcinoma by IHC and FASAY.

OBJECTIVES: To assess the clinical benefit of the methods of detection of p53 mutations in human urothelial carcinoma. METHODS: A total of 75 surgical specimens of urothelial carcinoma were analyzed using a yeast functional assay (FASAY) and immunohistochemistry (IHC), in combination with sequencing analysis. RESULTS: Of the 75 specimens, 24 (32.0%) were positive (mutant) by FASAY and 23 (30.7%) were positive by IHC. The sequencing analysis confirmed that all 24 FASAY-positive tumors harbored mutations, and no mutations were detected in any FASAY-negative tumors. In contrast, nuclear accumulation of p53 protein was detected in 9 (17.6%) of 51 tumors with no mutation, and 10 (41.7%) of 24 tumors with mutation showed no positive staining on IHC. The mutations detected by FASAY and IHC were both associated with stage and grade, but null mutations of p53 were not associated with stage. Concerning chemosensitivity, 6 (85.7%) of 7 responders harbored p53 missense mutations in at least one allele (P = 0.01), and only 4 (57.1%) were judged positive by IHC (P = 0.13). CONCLUSIONS: FASAY is more accurate than IHC in detecting the various types of p53 mutations, suggesting that a comprehensive approach for the detection of p53 mutations may be essential to elucidate their clinical significance.

Adult↗

PubMed2004

Polymorphism within the cyclin D1 gene is associated with an increased risk of carcinoma in situ in patients with superficial bladder cancer.

OBJECTIVES: To evaluate the prognostic value of CCND1 polymorphism in superficial and invasive transitional cell cancer of the bladder. METHODS: CCND1 polymorphism of blood DNA from patients with transitional cell cancer of the bladder was evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: No statistically significant difference was found in the recurrence-free survival of patients with superficial (pTa-T1) transitional cell cancer after transurethral resection among different genotype groups (AA versus GG, P = 0.746; GA versus GG, P = 0.979). In patients with superficial bladder cancer, the occurrence of primary carcinoma in situ was significantly greater in patients with the AA genotype compared with those with the GA or GG genotypes (P = 0.006, chi-square test). No statistically significant difference was found in disease-specific survival after radical cystectomy among the different genotype subgroups (AA versus GG, P = 0.245; GA versus GG, P = 0.649). CONCLUSIONS: Although CCND1 polymorphism is not able to serve as a prognostic marker for bladder cancer, the CCND1 variant A allele may recessively increase the risk of carcinoma in situ incidence in patients with superficial bladder cancer.

Aged↗

PubMed2004

Intermittent catheterization time required after interstitial laser coagulation of the prostate.

OBJECTIVES: To evaluate and minimize the duration of clean intermittent catheterization (CIC) required after interstitial laser coagulation of the prostate in patients with benign prostatic hyperplasia. METHODS: Patients who did not show sufficient improvement in lower urinary tract symptoms or voiding dysfunctions with alpha-1 adrenergic blockers, and who agreed to undergo interstitial laser coagulation of the prostate, were enrolled in this study. Postoperatively, the indwelling Foley catheters were removed by the next morning. Patients were then required to undertake CIC with alpha-1 adrenergic blockade therapy until the postvoid residual urine volume decreased to less than 100 mL. RESULTS: Seventy-nine patients underwent interstitial laser coagulation of the prostate, and 70 underwent catheter-free trials by postoperative day 1. The mean age and preoperative prostate volume of these 70 patients was 70.3 years (SD 8.7) and 49.6 cm3 (SD 34.8), respectively. Forty-three patients experienced postoperative urinary retention, and 37 of these underwent CIC. The median postoperative catheterization time was 3 days (range 0 to 31), and all patients eventually became catheter free. Univariate analysis showed that postoperative urinary retention was associated with a preoperative prostate volume of 30 cm3 or larger, a maximal flow rate of less than 6 mL/s, and a postvoid residual urine volume of 100 mL or greater. Multivariate analysis showed that a preoperative prostate volume of 30 cm3 or larger was the most significant predictor of postoperative urinary retention. CONCLUSIONS: More than 60% of the patients experienced urinary retention after interstitial laser coagulation of the prostate. However, the results of the present study suggested that CIC and alpha-1 adrenergic blockade therapy could manage post-treatment urinary retention with a relatively short catheterization time.

Adrenergic alpha-Antagonists↗

PubMed2004

Reduction of allergic airway eosinophilia by dietary raffinose in Brown Norway rats.

Oral administration of raffinose, a naturally occurring indigestible oligosaccharide, has reportedly ameliorated atopic dermatitis in human subjects although the mechanism is unknown. The present study investigated the effect of dietary raffinose on allergen-induced airway eosinophilia in ovalbumin-sensitised Brown Norway rats as an atopic disease model. Brown Norway rats were immunised by subcutaneous injection with ovalbumin on day 0 and fed either a control diet or the diet supplemented with raffinose (50 g/kg diet). The rats were exposed to aerosolised ovalbumin on day 20, and broncho-alveolar lavage fluid was obtained on the next day. The number of eosinophils in the fluid was significantly lower in the rats fed the raffinose diet than in those fed the control diet. Dietary raffinose significantly reduced IL-4 and IL-5 mRNA levels in lung tissue and tended to lower ovalbumin-specific Ig E levels. Suppression of eosinophilia by dietary raffinose was still observed in caecectomised and neomycin-administered rats, suggesting little contribution by the colonic bacteria to the effect of raffinose. Intraperitoneal administration of raffinose also suppressed eosinophilia. Significant concentrations of raffinose were detected in portal venous and abdominal arterial plasma after the intragastric administration of raffinose. Overall, the findings suggest that dietary raffinose ameliorates allergic airway eosinophilia at least partly via post-absorptive mechanisms in Brown Norway rats.

Allergens↗

PubMed2004

Over expression of thioredoxin-1 in transgenic mice attenuates germ cell apoptosis induced by experimental cryptorchidism.

PURPOSE: Experimental cryptorchidism induces apoptosis in testicular germ cells by generating reactive oxygen species. We investigated the effects of a redox regulating molecule, thioredoxin-1 (TRX1), on testicular damage caused by experimental cryptorchidism. MATERIALS AND METHODS: Unilateral cryptorchidism was surgically induced in TRX1 transgenic (TRX1-Tg) or WT adult C57BL6 mice. The contralateral scrotal testis served as a control. RESULTS: Experimental cryptorchidism decreased testicular weight in WT mice from 4 days after surgery. The decrease in testicular weight was significantly attenuated in TRX1-Tg mice compared with WT mice 7 to 14 days after surgery (p <0.01). However, the difference between the 2 groups was not significant 28 days after surgery. Histological analysis and TUNEL assays demonstrated that apoptosis occurred in germ cells of the cryptorchid testis in each group but the appearance of apoptotic germ cells was delayed by 3 days in TRX1-Tg mice. CONCLUSIONS: TRX1 over expression suppressed apoptosis in testicular germ cells induced by experimental cryptorchidism, indicating that TRX1 intensification may be a useful therapeutic strategy for male infertility associated with heat stress.

Animals↗

PubMed2004

Expression of tumor suppressor gene product p14ARF in endometrioid adenocarcinoma of the uterine corpus.

p14 activates p53 by inhibiting MDM2 expression and arrests the cell cycle in G1 and G2/M. Abnormal p14 expression has been reported in various human cancers. This study investigated p14 expression in endometrioid adenocarcinoma of the uterine corpus in an attempt to clarify its correlation with other cell cycle-regulators and clinicopathologic parameters. The specimen studied consisted of 124 endometrioid adenocarcinomas, 20 normal endometria, and 20 endometrial hyperplasias. Immunohistochemical staining of formalin-fixed and paraffin-embedded tissues was performed using a Catalyzed Signal Amplification System. Cells with >5% positive staining were classified as positive for p14. A staining score of 1 was adopted when the percentage of positive nuclei was <5%, a score of 2 when it was 5 to 50%, and a score of 3 when it was >50%. In normal endometrium, the frequency of positive staining in the proliferative phase and secretory phase was 50% (4/8) and 58.3% (7/12), with staining scores of 1.8+/-0.9 and 1.6+/-0.5, respectively. The frequency of staining in simple hyperplasia (SH), complex hyperplasia (CH), and complex atypical hyperplasia (CAH) was 88.9% (8/9), 25% (1/4), and 42.9% (3/7), respectively; the staining scores were 1.9+/-0.3, 1.3+/-0.5, and 1.4+/-0.5, respectively. Among endometrioid adenocarcinomas, the frequency of staining of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) adenocarcinomas was 69% (49/71), 64% (16/25), and 42.9% (12/28) respectively, with staining scores of 2.1+/-0.8, 2+/-0.9, and 1.8+/-1, respectively. Thus expression levels of p14 were higher in G1 tumors than in normal endometria or endometrial hyperplasias, and the frequency of its staining in endometrioid carcinomas was inversely correlated with histologic grade. The staining score for endometrioid adenocarcinomas also was inversely correlated with the labeling index (LI) of Ki-67, but not with that of cyclin A, cyclin D1, cyclin E, cdk2, p27, p53, or other clinicopathologic parameters. In conclusion, p14 expression correlated with histologic grade and Ki-67, but not other prognostic factors in endometrioid adenocarcinoma. Long-term follow-up studies are needed to analyze the significance of p14 expression in these tumors.

Adult↗

PubMed2004

Effects of sextant transrectal prostate biopsy plus additional far lateral cores in improving cancer detection rates in men with large prostate glands.

PURPOSE: To determine whether additional, far lateral cores improve the diagnostic performance of transrectal sextant biopsy in men with large prostate glands. METHODS: Men with prostate volumes of 50 mL or greater in transrectal ultrasonography who were suspected of prostatic adenocarcinoma were prospectively enrolled. Biopsy criteria were defined as 2.0 ng/mL or greater of serum total prostate-specific antigen and/or abnormal findings on digital rectal examination. Four cores of far lateral biopsies were added to the standard sextant technique. RESULTS: Of 104 patients enrolled in the present study and undergoing biopsy, 14 (13.5%) were diagnosed as having prostate cancer and 27 (26.0%) were diagnosed as having prostatic intraepithelial neoplasia (PIN) or an atypical gland. There were no cases where cancer was only detected in the additional cores, whereas PIN/atypical gland was uniquely detected from the additional, far lateral sites in eight of the 27 patients who were diagnosed with this condition. CONCLUSIONS: Although the number of patients diagnosed as having PIN/atypical gland might increase with the addition of far lateral cores, this additional sampling does not improve cancer detection rates in men with large prostate glands.

Adenocarcinoma↗

PubMed2004

Involvement of P-glycoprotein in blood-brain barrier transport of pentazocine in rats using brain uptake index method.

The involvement of P-glycoprotein (P-gp) in pentazocine (PTZ) transport at the blood-brain barrier (BBB) in rats was evaluated by means of an in vivo study using the brain uptake index (BUI) method. The amount of radioactivity in the brain was estimated at different intervals (up to 240 s) after carotid injection in rats. The apparent elimination rate constant (k(test)) due to efflux of PTZ from the brain was calculated as 0.22 min(-1). The observed BUI values of [(3)H]-PTZ (0.35 microM) were not significantly different between 5 and 15 s after the carotid injection. The concentration-dependent uptake of PTZ by the brain was increased gradually by increasing the concentration (0.01-1 mM) of PTZ in the injection solution. The apparent uptake of PTZ by the brain increased in the presence of P-gp inhibitors such as cyclosporin A, quinidine, verapamil and vinblastine after the carotid injection. These results suggest that the increment of PTZ uptake by the brain could be explained by the saturable efflux transport system involving a P-gp-mediated efflux mechanism of PTZ transport at the BBB.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Expression of the von Willebrand factor in atrial endocardium is increased in atrial fibrillation depending on the extent of structural remodeling.

BACKGROUND: The incidence of stroke in patients suffering atrial fibrillation (AF) is increased when left atrial enlargement occurs. Recently, the platelet adhesive molecule, von Willebrand factor (vWF), located in the atrial endocardium, has been shown to be increased in patients with a variety of heart diseases compared with patients who have no cardiac problems. METHODS AND RESULTS: We investigated the expression of vWF mRNA and protein in the endocardium as a possible prothrombotic alteration of AF in association with atrial structural remodeling. Atrial appendage specimens were obtained during either heart surgery or at an autopsy from AF patients with and without underlying heart disease. The immunohistochemical and in situ hybridization signals for vWF in the endocardium were well correlated and varied widely among the individual atrial appendages examined. The increased expression of vWF in the endocardium was associated with enlarged left atrial dimensions in mitral valvular disease or increased myocyte diameters in the underlying myocardium. Platelet adhesion/aggregation on the endocardium was always found under the fresh thrombi and was colocalized with strong vWF staining, but not necessarily with fibrinogen and/or fibrin staining. CONCLUSIONS: Endocardial overexpression of vWF may occur during the process of atrial structural remodeling contributing to the thrombotic predilection of AF in association with underlying heart disease.

Adult↗

PubMed2004

Analysis of chronic heart failure registry in the Tohoku district: third year follow-up.

BACKGROUND: Because the real prognosis of Japanese patients with chronic heart failure (CHF) is still unknown, the aim of the present study was to clarify the prognosis and predictors for mortality of CHF patients using the Chronic Heart failure Analysis and Registry in Tohoku district (CHART). METHODS AND RESULTS: As of February 2003, 1,154 stable CHF patients with optimum standard therapy have been enrolled in the registry since February 2000 and of these, 175 died of some cause during the follow-up period (mean follow-up period, 1.9+/-0.9 years), giving 1- and 3-year all-cause mortality rates of 7.3% and 20.9%, respectively. Multivariate analysis showed that age at entry, diabetes, ventricular tachycardia, plasma concentration of brain natriuretic peptide (BNP), New York Heart Association (NYHA) functional class and rural residence were significantly associated with all-cause mortality (hazard ratio: 1.028, 1.940, 1.650, 1.001, 1.713, and 2.226). The 1-year all-cause mortality rates of CHF patients with a left ventricular ejection fraction <25%, left ventricular end-diastolic diameter > or =60 mm, BNP > or =500 pg/ml, NYHA > or = III, or with underlying coronary artery disease were 15.0%, 11.4%, 16.8%, 16.3%, and 10.8%, respectively. CONCLUSIONS: The prognosis of Japanese CHF patients with these predictors remains poor. A stratified approach is necessary to improve their survival and quality of life.

Aged↗

PubMed2004

Rationale, design, and organization of the Diastolic Heart Failure Assessment Study in Tohoku District (DIAST).

BACKGROUND: High mortality and a high readmission rate characterize diastolic heart failure (DHF), but evidence-based therapeutic strategies have not been established for DHF. METHODS: The aim of a multicenter, randomized open trial (the Diastolic Heart Failure Assessment Study in Tohoku District, DIAST) is to evaluate the safety and prognostic efficacy of the multiple action non-selective beta-blocker carvedilol in 160 patients with DHF (left-ventricular ejection fraction > or =50%). The target dose of carvedilol is 10 mg twice a day and the mean follow-up is estimated to be 2 years. The primary endpoints are to evaluate (1) all-cause mortality or hospitalization, (2) cardiovascular mortality or hospitalization and (3) worsening heart failure. The secondary endpoints are to assess (1) cardiovascular events, (2) the individual components of the above combined endpoints, (3) the duration of hospitalization, (4) the functional class and exercise capacity and (5) the safety and tolerability. All patients' data are processed using an original registration system on an internet homepage. Several substudies to assess neurohumoral factors, heart rate variability, oxidative stress and sleep apnea will clarify the pathophysiology of DHF. CONCLUSIONS: The DIAST will contribute to establish therapeutic guidelines for DHF.

Diastole↗

PubMed2004

Right ventricular systolic function and the manner of transformation of the right ventricle in patients with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is generally considered to be accompanied by both left and right ventricular dysfunction, but most studies only analyze the left ventricular function. METHODS AND RESULTS: Biplane right ventriculography was performed in 13 control subjects and 13 patients with DCM and New York Heart Association functional class II. Three dimensions of the right ventricle (RV) (the long axis dimension (LA), the anterior - posterior dimension (AP), and the septum -free wall dimension (SF)) and 2 dimensions of the left ventricle (LV) (LA and AP) were examined to assess regional function. The group with DCM had a lower stroke volume index and RV ejection fraction. In the RV dimensional analysis, the group with DCM had a smaller SF and a larger AP at end-diastole, and larger AP and LA at end-systole. There was a significant linear negative correlation between SF of RV and AP of LV at end-diastole. CONCLUSION: In clinically well-controlled cases of DCM, RV systolic function is depressed, and the RV is compressed by the LV, becoming less thick than in the controls. This transformation results from some parallel interaction between the RV and a markedly enlarged LV.

Adolescent↗

PubMed2004

A novel method for producing a foodstuff from defatted black sesame seed that inhibits allergen absorption.

A method is proposed to produce a foodstuff that inhibits allergen absorption through the intestinal tract. Defatted black sesame (Sesamum indicum) seeds as a starting material were hydrolyzed with a crude preparation of trypsin at 40 degrees C and pH 8 for 3 hrs while gently stirring to generate an active peptide. The resulting hydrolysate was heated to inactivate the trypsin and make the active components soluble. An extract was obtained by centrifugation and then freeze-dried. Ser-Asn-Ala-Leu-Val-Ser-Pro-Asp-Trp-Ser-Met-Thr-Gly-His (compound 1) as an active peptide, and sesamino1 2'-O-beta-glucopyranosyl-(1-->2)-O-[beta-glucopyranosyl(1-->6)]-O-beta-glucopyranoside (compound 2) and sesamino1 2'-O-beta-glucopyranosyl (1-->2)-O-beta-glucopyranoside (compound 3) were identified as active lignan glycosides in an in vitro model by using Caco-2 cells. Compound 1 was active at 10(-7) M and compounds 2 and 3 at 10(-5) M.

Absorption↗

PubMed2004

Isolation of tryptophan as an inhibitor of ovalbumin permeation and analysis of its suppressive effect on oral sensitization.

Tryptophan was isolated from rat feces as an active compound against ovalbumin permeation in an in vitro Caco-2 cell model. Tryptophan dose-dependently inhibited ovalbumin permeation with accompanying increase in transepithelial electric resistance, and its inhibitory activity reached a plateau at 10 mM. Brown Norway rats were sensitized by intragastric administration of ovalbumin together with or without tryptophan. Antibody levels specific to ovalbumin in the sera and proliferative responses of spleen mononuclear cells to ovalbumin were significantly lower in rats administered ovalbumin plus tryptophan than those administered ovalbumin alone. These results suggest that tryptophan suppresses oral sensitization to ovalbumin, probably via suppression of ovalbumin absorption from the intestinal tract.

Administration, Oral↗

PubMed2004

Crossreaction with an anti-Bax antibody reveals novel multi-endocrine cellular antigen.

We found a novel protein that has crossreactivity with a polyclonal anti-Bax antibody (SCBAX antibody). The protein was localized exclusively in the endocrine cells of hypothalamus, pituitary gland, and pancreatic islets. Immunohistochemical (IHC) double labeling revealed that the cells showing crossreactivity with this antibody corresponded precisely to oxytocin neurons and ACTH, alpha-MSH, and glucagon cells in rat and gerbil. By immunoelectron microscopy, the protein was localized predominantly in and just around the secretory granules in the cytoplasm but not in the mitochondria. Double-labeling IHC with the anti-Bax SCBAX antibody and two anti-Bax monoclonal antibodies (MAbs) showed that cells stained with the anti-Bax SCBAX antibody were not stained with anti-Bax MAbs except for very few cells (probably apoptotic cells). Western blotting analysis revealed that the molecular mass of the protein was approximately 55 kD, which differs from that of Bax protein (21 kD). These findings indicate that the anti-Bax SCBAX antibody recognizes not only pro-apoptotic Bax protein (a 21-kD mitochondrial protein) but also an unknown substance present in one endocrine cell group in each endocrine organ. Therefore, the protein is designated as multi-endocrine cellular antigen (MECA). MECA is probably a 55-kD protein secreted from the particular differentiated cell groups of endocrine tissues.

Animals↗

PubMed2004

Effects of tachycardia on regional wall motion in acute ischemic canine heart.

Tachycardia accompanies the preload reduction. Our aim is to assess the effect of the heart rate change on wall motion in ischemic heart. In 8 dogs with occlusion of left anterior descending artery, we changed the heart rate (heart rate 90, 120, and 150 beats/minute) after using UL-FS49, a selective bradycardic agent, with atrial pacing. Preload was changed by inferior vena caval occlusion at a heart rate of 90 beats/minute. With either an increase in heart rate or an inferior vena caval occlusion, the end-diastolic length was decreased, but the end-diastolic length relationships between the non-ischemic and the ischemic region made different lines from those of the heart rate change and inferior vena caval occlusion. When increasing the heart rate, isovolumetric shortening was unchanged in the non-ischemic region with more expansion in the ischemic region. While inferior vena caval occlusion at a heart rate of 90 beats/minute, isovolumetric shortening was increased in the non-ischemic region, with more expansion in the ischemic region. Both in tachycardia and by the inferior vena caval occlusion, ejectional shortenings decreased in the non-ischemic and ischemic regions. Our results suggest that, in ischemic heart, tachycardia changes both in the end-diastolic length relationship between the non-ischemic and the ischemic region and at the isovolumetric contraction phase. The changes seem to be not only due to the inferior vena caval occlusion, but also due to tachycardia itself.

Animals↗