Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 91 records · Page 5Linked to original sources

PubMed2000

Primary malignant melanoma of the male urethra.

BACKGROUND: We describe a rare case of malignant melanoma originating from the male urethra. METHODS/RESULTS: This case, which presented a tan-colored lesion at the distal urethra on urethroscopy, was considered as transitional cell carcinoma by transurethral biopsy. Pathologic examination of widely resected urethra revealed scattering cells, which included melanin granules in cytoplasm, and then immunohistochemical stains established the diagnosis as amelanotic melanoma. Although partial penectomy and inguinal lymph node dissection were subsequently performed, 7 months later, total cystourethrectomy was required because of multifocal recurrence at the residual urethra. CONCLUSIONS: In cases of amelanotic melanoma, it should be noted that a lack of melanin granules in tumor cells may lead pathologists and urologists to a misdiagnosis due to the histologic non-specific appearance. With respect to surgical management, of significance is the fact that malignant melanoma may progress multifocally along the total urethra; therefore, total urethrectomy should be considered as radical surgery for the primary site, even if the tumor is confined to the distal urethra.

Humans↗

PubMed2000

Nucleocytoplasmic shuttling of the aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that acts in concert with the AhR nuclear translocator (ARNT), and alters gene expression in response to environmental contaminants such as 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We have previously shown that AhR contains both a nuclear localization signal (NLS), AhR(13-39), and a nuclear export signal (NES), AhR(55-75), in its NH(2)-terminal region. In this study, we obtained direct evidence for the nucleocytoplasmic shuttling of AhR and show the biological significance of the shuttling in terms of the transcriptional activation of its target gene, CYP1A1. When AhR(13-75) fused with glutathione S-transferase (GST)-green fluorescent protein (GFP) was microinjected into the nucleus of a polykaryotic of BHK21 cell, the GST-AhR(13-75)-GFP migrated from one nucleus to the other. This event, nucleocytoplasmic shuttling, was completely inhibited in the presence of leptomycin B (LMB). The interaction between chromosome region maintenance 1 (CRM1) and endogenous AhR was shown by immunoprecipitation with antibodies to AhR followed by immunoblot analysis with antibodies to CRM1. The inhibition of the nuclear export of AhR by LMB repressed the transcriptional activation of the CYP1A1 gene. The findings suggest that nuclear-cytoplasmic shuttling of AhR is essential for the inducible expression of the CYP1A1 protein.

Animals↗

PubMed2000

Regional and temporal profiles of phorbol 12,13-dibutyrate binding after myocardial infarction in rats: effects of captopril treatment.

Phosphoinositide turnover and protein kinase C (PKC) mediate the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). To determine whether PKC is activated after MI, rat hearts after MI were subjected to in vitro quantitative autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu), which is highly selective for PKC. [3H]PDBu binding in the infarcted area increased significantly compared with the non-infarcted region 7 and 21 days after MI, but not 1 and 3 days and 10 months after MI. [3H]PDBu binding in the noninfarcted area was similar to that in the sham-operated rats. Immunohistochemical analysis revealed that abundant macrophages (7 days after MI), fibroblasts, and myofibroblasts (7 and 21 days after MI) occupied the infarcted region. To investigate whether myocardial [3H]PDBu binding is affected by captopril, hearts were subjected to in vitro autoradiography with [3H]PDBu after 1- or 3-week captopril treatment or no treatment. Captopril treatment significantly suppressed [3H]PDBu binding in the infarcted area 3 weeks after MI, but not 1 week after MI nor in the noninfarcted areas. These results suggest that PKC is upregulated during the healing and fibrogenic process after MI and that captopril treatment suppresses the upregulation in the infarcted area.

Analysis of Variance↗

PubMed2000

Interaction between L-type Ca2+ channels and sarcoplasmic reticulum in the regulation of vascular tone in isolated rat small arteries.

A dysfunction of the sarcoplasmic reticulum (SR) causes an increase in the myogenic tone of rat skeletal muscle small arteries (A(SK)), but not that of mesenteric small arteries (A(MS)). We hypothesized that the difference depends on the activity of voltage-dependent Ca2+ channels in these vessels. To test this, we measured the membrane potential of these vessels and examined ryanodine-induced constrictions by manipulating the activity of voltage-dependent Ca2+ channels. The isolated vessels were cannulated to control the transmural pressure. To assess the vascular tone, the inner diameter was measured with a video-digitizing system. The membrane potential of A(SK) was more depolarized between 20 to 100 mm Hg of transmural pressure. A(MS) was not constricted by the Ca2+ channel agonist Bay K 8644 (1 nM(-1) microM) alone, but substantially constricted in the presence of ryanodine (1 microM). Ryanodine also augmented the KCl (20 mM)-induced constriction. In A(SK), the Ca2+ channel blocker nisoldipine fully dilated the ryanodine-induced constriction: however, the ryanodine-induced constriction was less susceptible to nisoldipine than was the myogenic and phenylephrine-induced constriction caused mainly by increased Ca2+ influx. In conclusion, the contribution of the SR function to Ca2+ metabolism depends on the activity of dihydropyridine-sensitive Ca2+ channels. The dysfunction of SR by ryanodine may impair the Ca2+ extrusion rather than increase Ca2+ influx in rat small arteries.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2000

Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer.

Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17beta-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was significantly associated with the incidence of breast or squamous cell carcinoma of the lung. On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was significantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17beta-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers.

Adenocarcinoma↗

PubMed2000

Ferroelectric phases in a chiral bent-core smectic liquid crystal: dielectric and optical second-harmonic generation measurements

We report unambiguous evidence for ferroelectricity in a chiral bent-core liquid crystal. This evidence includes (i) a single current peak in the polarization reversal current, (ii) a strong dielectric response that is suppressed by applying a bias electric field, and (iii) strong optical second-harmonic generation in the absence of electric field even at normal incidence. We propose a phase structure that is anticlinic in tilt and ferroelectric in polar order, i.e., smectic-C(A)P(*)(F).

Journal Article↗

PubMed2000

Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin.

TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization concentration-dependently at 1 - 100 microM with IC50 values of 2.2 +/- 0.6 and 2.3 +/- 0.7 microM, respectively. VLB, VCR and VDS inhibited microtubule polymerization at 1 - 3 microM with IC50 values of 2.7 +/- 0.6, 1.6 +/- 0.4 and 1.6 +/- 0.2 microM, respectively, but showed a slight decrease in inhibitory effect at concentrations of 10 microM or more. TZT-1027 also inhibited monosodium glutamate-induced tubulin polymerization concentration-dependently at 0.3 - 10 microM, with an IC50 of 1.2 microM, whereas VLB was only effective at 0.3 - 3 microM, with an IC50 of 0.6 microM, and caused so-called "aggregation" of tubulin at 10 microM. Scatchard analysis of the binding data for [(3)H]VLB suggested one binding site (Kd 0.2 +/- 0.04 microM and Bmax 6.0 +/- 0.26 nM / mg protein), while that for [(3)H]TZT-1027 suggested two binding sites, one of high affinity (Kd 0.2 +/- 0.01 microM and Bmax 1.7 +/- 0.012 nM / mg protein) and the other of low affinity (Kd 10. 3 +/- 1.46 microM and Bmax 11.6 +/- 0.83 nM / mg protein). [(3)H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by VLB. [(3)H]VLB was completely displaced by dolastatin 10 and TZT-1027. Furthermore, TZT-1027 prevented [(3)H]VLB from binding to tubulin in a non-competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentration-dependently inhibited both [(3)H]guanosine 5'-triphosphate (GTP) binding to and GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin concentration-dependently to a lesser extent than TZT-1027, but no inhibitory effect of VLB on [(3)H]GTP binding to tubulin was evident even at 100 microM. Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect on tubulin polymerization and differed from vinca alkaloids in its mode of action against tubulin polymerization.

Animals↗

PubMed2000

CD3+, CD4-, CD8-, TCR alpha beta-, TCR gamma delta+ granular lymphocyte proliferative disorder without lymphocytosis and clinical symptoms.

Granular lymphocyte-proliferative disorder is characterized by a proliferation of large granular lymphocytes (LGLs). It is often associated with neutropenia, rheumatoid arthritis (RA), and pure red cell aplasia (PRCA). Phenotypic analysis has demonstrated that in most cases, the LGLs show a clonal rearrangement of the TCR alpha beta rearrangement. We are reporting a patient with TCR gamma delta LGL proliferation without clinical findings and lymphocytosis. The patient showed an expansion of the CD3+, CD16+, CD56+, and CD57+ LGL populations which involved coexpression of TCR gamma delta with TCR J gamma and J delta 1 gene rearrangement. Autoimmune manifestations, including RA and PRCA, have not appeared and the results of laboratory examinations have not changed for 1 year after the diagnosis.

Aged↗

PubMed2000

Preparation and characterization of poly(ethylene glycol) hydrogels cross-linked by hydrolyzable polyrotaxane.

PEG hydrogels cross-linked by a hydrolyzable polyrotaxane were prepared and their hydrolytic erosion characterized in terms of supramolecular dissociation of the polyrotaxane. The hydrolyzable polyrotaxane, in which many alpha-cyclodextrins (alpha-CDs) are threaded onto a poly(ethylene glycol) (PEG) chain capped with L-phenylalanine via ester linkages, was used as a multifunctional cross-linker: the PEG network was covalently bound to hydroxyl groups of alpha-CDs in the polyrotaxane. The contact angle and water content of the hydrogels were varied with the polyrotaxane content in the feed. In vitro hydrolysis study revealed that the time to reach complete gel erosion was shortened by increasing the polyrotaxane content in the feed in relation to the decreased number of chemical cross-links between PEG and alpha-CDs in the polyrotaxane. The hydrogel degradation in a physiological condition was found to be followed by bulk mechanism. These findings suggest that changing the preparative conditions such as polyrotaxane content will make it possible to control programmed gel erosion for tissue engineering.

Biocompatible Materials↗

PubMed2000

Serological diagnosis of idiopathic pulmonary alveolar proteinosis.

Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).

Adult↗

PubMed2000

Pharmacokinetic/pharmacodynamic relationship of eptazocine, a narcotic-antagonist analgesic, in rats.

The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.

Analgesics↗

PubMed2000

Uptake of fractionated heparin by two types of scavenger receptors in isolated rat Kupffer cells.

The uptake of fractionated heparin was examined in the absence and presence of anionic proteins such as acetylated low density lipoprotein (Ac-LDL) and maleylated bovine serum albumin (Mal-BSA) to characterize the scavenger receptors involved in the uptake of fractionated heparin in isolated rat Kupffer cells. The uptake of fractionated heparin was completely inhibited by Ac-LDL and dextran sulfate, but only partially by Mal-BSA. Kinetic analysis revealed that the binding capacity (Bmax) of the Mal-BSA-insensitive receptor was significantly larger than that of the Mal-BSA-sensitive one, though their dissociation constants (Kd) were not significantly different. The apparent internalization rate constant (kint,app) was significantly larger for the Mal-BSA-sensitive receptor than for the Mal-BSA-insensitive one. Thus, the scavenger receptors involved in the uptake of fractionated heparin in Kupffer cells can be classified into two types, in terms of sensitivity to Mal-BSA. Mal-BSA-sensitive receptors have been characterized in macrophages and classified as class A. The Mal-BSA-sensitive one found in Kupffer cells in this study may belong to class A, while the Mal-BSA-insensitive one has been little characterized elsewhere.

Animals↗

PubMed2000

Isolation and characterization of a novel polysaccharide as a possible allergen occurring in wheat flour.

A new polysaccharide with a molecular weight of 5.0 x 10(4) was isolated as a possible wheat allergen from a water-soluble fraction of flour by affinity chromatography and gel filtration. The isolated polysaccharide was found to be a possible wheat allergen, as it bound specifically to IgE antibodies in the sera of patients allergic to the water-soluble fraction of flour. Chemically, the sugar moiety of the polysaccharide consisted of D-glucose and D-mannose with beta-1,4-linkages in a molar ratio of 4.4:1. Since this mannoglucan is thought to be stable in our body, it would act as a remaining allergen to cause a long-lasting allergic reaction to wheat flour.

Allergens↗

PubMed2000

Novel method for producing hypoallergenic wheat flour by enzymatic fragmentation of the constituent allergens and its application to food processing.

A novel method is proposed to produce hypoallergenic wheat flour suitable for patients allergic to wheat. Wheat flour was mixed with a cellulase solution, and the mixture was incubated at 50 degrees C for 1 h to hydrolyze the carbohydrate allergens. The hydrolysate was further incubated with actinase at 40 degrees C for 1 h while gently stirring to decompose the proteinaceous allergens. The product was evaluated for its allergenicity by an enzyme-linked immunosorbent assay, the results of which suggested negative allergenicity in most cases. The product changed to a batter state that was difficult to process by the usual methods. Gelatinization of the starch in the product and the addition of a surfactant were beneficial for food processing.

Allergens↗

PubMed2000

Rifampicin suppresses hepatic CYP2E1 expression and minimizes DNA injury caused by carbon tetrachloride in perivenular hepatocytes of mice.

BACKGROUND: Rifampicin has been shown to increase during activities of serum transaminases and to decrease in cytochrome P-450-mediated monooxygenase activities in livers of mice treated with carbon tetrachloride (CCl4). Although these findings suggest that rifampicin prevents hepatocyte damage caused by CCl4, detailed information on the protective effects is not available. METHODS: We injected first rifampicin and then CCl4 into mice and examined denaturation and fragmentation of hepatocyte DNA by in situ nick translation, in situ end labeling, and in situ hybridization. Furthermore, expressions of p53, a cytoplasmic marker for apoptosis, and bcl2, an anticell death factor, were examined immunohistochemically. In addition, a major ethanol-inducible P-450 isoform in liver homogenates or microsomes, CYP2E1, was examined by Western blotting, because the enzyme metabolizes CCl4 and forms free radicals to injure perivenular hepatocytes in which the enzyme is restrictedly expressed. RESULTS: Rifampicin prevented the denaturation and fragmentation of DNA caused by CCl4 in perivenular hepatocytes except for those located within two or three cell layers surrounding the central venule. Furthermore, CYP2E1 decreased in liver homogenates or microsomes from rifampicin-treated animals. It is therefore likely that rifampicin suppresses expression of CYP2E1 and protects CCl4-mediated DNA damage of hepatocytes by inhibiting formation of free radicals. In addition, perivenular hepatocytes except for those surrounding the venule showed negative immunoreaction for p53 and bcl2 in rifampicin+CCl4-treated animals. CONCLUSIONS: The drug did not alter the mechanism of cell death from necrosis to apoptosis and did not promote recovery of hepatocytes from CCl4-mediated damage.

Animals↗

PubMed2000

[Papillary adenocarcinoma of the prostate: report of 3 cases].

We report here 3 cases of papillary adenocarcinoma of the prostate. In all 3 cases, the tumors were discernible on cystourethroscopy and transurethral biopsy established the diagnosis, whereas no significant finding was found on digital rectal examination. Although androgen deprivation therapy was administered in all cases, different surgical procedures were employed according to the stage in each case. In case 1, since the papillary tumor was confined within the prostatic urethra, complete resection was accomplished by transurethral resection (TUR). In case 2, since pelvic lymph nodes metastases were found, local radiation therapy was added. In case 3, since the patient had vesical invasion of tumor total cysto-prostatectomy was performed. Papillary adenocarcinoma of the prostate originates from the prostatic duct, resulting in existence at the "central portion" of the prostate gland. Cystourethroscopy and transurethral biopsy is helpful for diagnosis of this disease, whereas rectal digital examination is useless. As a surgical procedure for the primary site, TUR may be efficient for tumors confined within the prostatic urethra, although more extensive surgery may be necessary for those with a more invasive profile.

Adenocarcinoma, Papillary↗

PubMed2000

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). I. Susceptibility distribution].

The frequencies of bacterial isolation and susceptibilities to antimicrobial agents were investigated on 538 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1998 to May 1999. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.3% and Gram-negative bacteria accounted for 69.7%. Susceptibilities of several isolated bacteria to antimicrobial agents were as follows; against Enterococcus faecalis isolated from patients with UTIs, vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) had strong activities. Among E. faecalis strains, those with low susceptibilities to all drugs have increased in 1998, compared with those in 1997. VCM showed the highest activity against MRSA isolated from patients with UTIs. The MICs of VCM for all 34 strains were equal to or lower than 2 micrograms/ml. Arbekacin (ABK) was also active against MRSA with the MIC90s of 2 micrograms/ml. Against Escherichia coli and Klebsiella pneumoniae, all drugs except penicillins were active. Particularly, meropenem (MEPM) showed the highest activity with the MICs of 0.125 micrograms/ml or below. Almost all the drugs except minocycline (MINO) showed high activities against Proteus mirabilis. Against Pseudomonas aeruginosa, all drugs were not so active, with the MIC90s of 16 micrograms/ml or above. MEPM, IPM and gentamicin (GM) showed high activities against Serratia marcescens. Generally, it seemed that resistant strains of S. marcescens had decreased since 1996.

Anti-Bacterial Agents↗

PubMed2000

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). II. Background of patients].

Clinical background was investigated on 449 patients with urinary tract infections (UTIs) from whom 591 bacterial strains were isolated in 9 hospitals during the period from June, 1998 through May, 1999. About distribution of age and sex of patients and type of infections, among males, patients less than 50 years old were few, and uncomplicated UTIs without indwelling catheters was most frequent. Among females, patients less than 20 years old were few, and uncomplicated was most frequent. Escherichia coli was the most frequently isolated in uncomplicated UTIs, and the higher the ages of patients, the higher were became the isolation frequencies of Enterococcus faecalis, Proteus spp. and Klebsiella spp. In complicated UTIs with indwelling catheters and without indwelling catheters, the types of pathogens had no relation with ages. The complication of infections had decreased E. coli but that had increased Proteus spp., Pseudomonas aeruginosa and Staphylococcus aureus. Until last year, use of antibiotics had decreased pathogens isolated from patients with uncomplicated UTIs drastically in our study. But, pathogens isolated after antibiotics had increased in 1998. As for surgical procedures and types of causative organisms in UTIs, E. faecalis were more isolated when surgical procedures were experienced, and E. coli were more isolated when they were not in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, types of causative organisms had no relationship with surgical procedures.

Adult↗