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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 55 records · Page 3Linked to original sources
PubMed1999

Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.

BACKGROUND: Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans. METHODS AND RESULTS: Subjects (n=116; age, 52+/-1 years; male:female ratio, 100:16) underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and duplex scanning of the carotid arteries. These individuals had no symptoms of coronary or peripheral artery disease and were taking no medications. Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Sigma glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise regression analysis revealed that plasma ADMA levels were significantly correlated to the intima-media thickness of the carotid artery (as measured by high-resolution ultrasonography). CONCLUSIONS: This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.

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

Long- and short-term histological observations of congenital nevi treated with the normal-mode ruby laser.

OBJECTIVE: To evaluate histologically the long- and short-term changes associated with cosmetic improvement or failure of normal-mode ruby laser treatment of patients with congenital nevi. DESIGN: A biopsy of the laser-treated lesions of 10 patients with good or poor cosmetic results was performed at periods up to 8 years 10 months after treatment (mean, 4 years 9 months). Short-term findings were evaluated in 3 patients. SETTING: Ueda Setsuko Clinic and the Dermatology Unit of the Kyushu University, Fukuoka, Japan. PATIENTS: Of the 85 Japanese patients with relatively large congenital nevi who had been treated with the normal-mode ruby laser since 1990, 13 gave informed consent for biopsy and histological examination of the treated area. RESULTS: A long-term follow-up study of the 8 patients with good cosmetic results showed the presence of residual nevus cells 1.11 +/- 0.35 mm (mean +/- SD) (range, 0.63-2.05 mm) below the skin surface. Above these cells was a layer of connective tissue that formed a subtle microscopic scar that preserved the normal structure of the papillary dermis. Hair follicles were damaged at the base, and the hairs were attenuated. However, in the 2 patients with poor cosmetic results, nests of pigmented cells were commonly seen in the epidermis, and melanin was relatively abundant in basal keratinocytes. No malignant changes were observed in any patient. A short-term study in 3 patients showed damage to pigmented cells in the epidermis and upper dermis as observed following electrodesiccation. CONCLUSIONS: Multiple treatments with the normal-mode ruby laser produced immediate thermal damage to the superficial nests of nevus cells and a subsequent remodeling of the superficial connective tissue. When the thickness of the subtle microscopic scar reached 1 mm, it masked the underlying residual nevus cells and achieved a good cosmetic result. Follow-up for at least 8 years after laser treatment showed no evidence of malignant change in the treated areas.

Adolescent↗
PubMed1999

Histopathological features of liver damage induced by laser ablation in rabbits.

BACKGROUND AND OBJECTIVE: Possible mechanisms that promote or interfere with the effects of laser ablation of the liver have not been clarified. The aim of this study was to define the chronological alterations in the normal rabbit liver at early stages after laser ablation. STUDY DESIGN/MATERIALS AND METHODS: Rabbit livers were ablated with a laser via an optical fiber and then analyzed histopathologically by immunostaining for heat shock protein 70 (HSP70) and by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. RESULTS: The lesions increased in size progressively over the 24 h that followed ablation and the area of the lesion coincided with the area that had been heated above 43 degrees C. TUNEL-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes at 6 h, and such cells were in contact with each other at 24 h. CONCLUSIONS: Injury to hepatocytes induced by laser ablation increases for 24 h and dying cells express nuclear HSP70, with subsequent fragmentation of DNA.

Animals↗
PubMed1999

Chondroid chordoma: fine-needle aspiration cytology with histopathological, immunohistochemical, and ultrastructural study of two cases.

Chondroid chordoma is a controversial and confusing entity that was originally described by Heffelfinger et al. (Cancer 1973; 32:410-420) as a biphasic malignant neoplasm possessing elements of both chordoma and cartilaginous tissue. Fine-needle aspiration (FNA) cytology of chondroid chordoma has not been described. The aim of our investigation was to characterize the chondroid area of chondroid chordoma and to compare the FNA features with those of well-differentiated chondrosarcoma. Clival and cervical spine chondroid chordomas were studied with light microscopy, immunohistochemistry, and electron microscopy. Chondroid chordomas demonstrated an epithelial nature by immunohistochemistry and ultrastructural studies. The FNA smears showed low cellularity, with loosely arranged or dispersed round cells in a myxoid background. Although the smears were similar to those of well-differentiated chondrosarcomas, they showed a positive reaction for epithelial markers. These findings reveal that chondroid chordoma is a variant of chordoma which possesses a hyaline matrix. Immunohistochemical demonstration of epithelial markers is useful to distinguish it from chondrosarcoma. Diagn. Cytopathol. 1999; 21:335-339.

Biomarkers, Tumor↗
PubMed1999

Posttraumatic intestinal stenosis presenting as a perforation: report of a case.

A 78-year-old woman was admitted to the hospital after falling into a ditch approximately 1 m deep and sustaining a blunt abdominal trauma with a left femur fracture. On the tenth day after admission, symptoms of a small bowel obstruction occurred. A nasogastric tube was inserted, and the symptoms thus improved. She sometimes complained of abdominal pain during the 12 months after the fall, but recovered with conservative management. The next year, she was readmitted to the hospital for a pin extraction of the left femur bone. During this admission, 15 months since her admission after her fall, she again complained of abdominal pain. Abdominal pain increased with a muscular defense, and abdominal X-rays revealed free air. She was referred to our hospital with a diagnosis of perforative peritonitis, and emergency surgery was performed. Upon laparotomy, circumferential stenoses of the small bowel were recognized in the proximal segments about 40cm, 80cm, and 100cm from the ileocecal region. In addition, a perforation and prominent dilatation of the bowel segment was observed just proximal to the stenosis about 100cm from the ileocecal region. She underwent a small intestinal resection at two sites. There were no findings of an intestinal specific ulcer, such as Crohn's disease, intestinal tuberculosis, or malignancy, based on the results of a histopathological examination.

Abdominal Injuries↗
PubMed1999

Allelic diversity at class II DRB1 and DQB loci of the pig MHC (SLA).

The loci encoding the beta chain of the pig major histocompatibility complex (MHC) class II antigens, SLA-DR and -DQ, have been known to exhibit a remarkable degree of allelic polymorphism. Here, to understand the generation of SLA class II polymorphism, 25 SLA-DRB1 and 24 SLA-DQB genes including newly identified 12 SLA-DRB1 and 7 SLA-DQB genes obtained from miniature pigs were analyzed based on the nucleotide and deduced amino acid sequences. Most of the allelic diversity was attributed to the variable sequences which encode a beta1 domain consisting of a beta-pleated sheet followed by an a helix. In the beta1 domain coding region, there were four GC-rich sequences, which have been considered to involve the intra-exon sequence exchange also in other gene evolutions. The first and second GC-rich sequences were alpha-like sequences, which have been shown to be a putative recombination signal, and were stably conserved among SLA-DRB1 and DQB genes. These alpha-like sequences identified in SLA-DRB1 and SLA-DQB were found to encode the first turning point of the beta-pleated sheet and the boundary between the beta-pleated sheet and the alpha helix. Analysis of clustered sequence variation also suggested intra-exon gene conversions in which the alpha-like sequences act as putative breakpoints. In addition to point mutations and selection mechanism, intra-exon gene conversions must be an important mechanism in the generation of allelic polymorphism at the SLA-DRB1 and SLA-DQB.

Alleles↗
PubMed1999

Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis C associated with autoimmune hepatitis-like serological manifestations.

We report a 70-year-old woman with chronic hepatitis C associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis C virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.

Aged↗
PubMed1999

Comparison of adjuvants with respect to serum IgG antibody response in orally immunized chickens.

We have previously shown that oral immunization with non-replicating antigens hardly induced serum IgG antibody response in chickens and addition of sodium fluoride (NaF) to the immunogen markedly improved their immunological states. In the present study, taurine, lithium and Quillaja saponin (Q-SAP) were compared with NaF with respect to their enhancement of serum IgG antibody response in chickens after oral immunization. The antibody titer of chickens which received Q-SAP as the mucosal adjuvant tended to be higher than that of chickens which received antigen plus NaF. Simultaneous administration of antigen with lithium or taurine elicited a higher antibody titer in chickens compared to those of chickens orally immunized with antigen alone, but the effect of these two adjuvants was less efficient compared with that of NaF. These results suggested that Q-SAP as well as NaF is useful as an oral adjuvant for chickens.

Adjuvants, Immunologic↗
PubMed1999

Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-diamminedichloroplatinum (II).

The thioredoxin (TRX) system, composed of nicotinamide adenine dinucleotide phosphate (reduced form), TRX, and TRX reductase (TRXR), has multiple biologic functions via thiol-mediated redox control. In this study, we investigated the relationship between intracellular TRXR levels and cellular sensitivity to cis-diamminedichloroplatinum (II) (CDDP). HeLa, a human cervical carcinoma cell line, cultured with CDDP showed a time- and dose-dependent reduction of intracellular TRXR activity, which was well correlated with the decrease in cell viability after exposure to CDDP. In a cell-free system, CDDP was found to directly inactivate the reduced form of purified human TRXR. The CDDP-resistant variants of HeLa cells, established by continuous exposure to CDDP, exhibited an increased expression and activity of TRXR as well as TRX compared with the parental cells. In addition, sodium selenate, an inhibitor of TRXR, was found to increase the susceptibility to CDDP in the CDDP-resistant cells. Moreover, the HeLa cells transfected with an antisense TRXR RNA expression vector to reduce the intracellular enzyme activity displayed an enhanced sensitivity to CDDP. Taken together with previous reports on TRX, these results indicate the possible involvement of TRXR as well as TRX in the cellular sensitivity and resistance to CDDP.

Antineoplastic Agents↗
PubMed1999

Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions.

Human membrane cofactor protein (MCP, CD46) is a 45-70 kDa protein with genetic and tissue-specific heterogeneity, and is expressed on all nucleated cells. MCP consists from N-terminus of 4 short consensus repeats (SCRs), 1-3 serine/threonine-rich (ST) domains, a transmembrane domain (TM) and a cytoplasmic tail (CYT). More than 8 isoforms are generated secondary to alternative splicing due to combinations of various exons encoding the ST, TM and CYT domains. It serves as a cofactor of serine protease factor I for inactivation of complement C3b and C4b. Its primary role is to protect host cells from homologous complement attack by inactivating C3b/C4b deposited on the membrane. It also acts as receptors for measles virus (MV), some kinds of bacteria and for a putative ligand on oocytes. MV infection causes temporal host immune suppression, which may appear secondary to signaling events through MCP on macrophages and dendritic cells. These functional properties of human MCP may facilitate xenotransplantation and may be useful in the generation of animal models of measles by creating human MCP-expressing animals.

Amino Acid Sequence↗
PubMed1999

Two cases of HLA-DR2-negative hypersomnia manifesting sleep-onset rapid eye movement periods in the multiple sleep latency test.

We encountered two cases expressing excessive daytime sleepiness (EDS) and manifesting two or more sleep-onset rapid eye movement (REM) periods in the multiple sleep latency test. Unbearable daytime sleepiness occurred abruptly, which usually led to short-lasting naps, after which the patients felt refreshed. The EDS was successfully reduced by treatment with methylphenidate. In spite of these features similar to narcolepsy, these cases of REM hypersomnia did not present cataplexy or other auxiliary symptoms of narcolepsy, and, furthermore, the class-II human leukocyte antigen DR2 appeared to be negative.

Adult↗
PubMed1999

An autopsy case of hepatoid carcinoma of the ovary with PIVKA-II production: immunohistochemical study and literature review.

A case of hepatoid carcinoma of the ovary in a 61-year-old Japanese woman, who showed high serum levels of alpha-fetoprotein and CA125, is reported. Grossly, the left ovarian tumor, which measured 12 x 9 cm, was solid and multinodular. Histologically, the tumor resembled hepatocellular carcinoma by its architectural and cytological features. Liver cell differentiation was indicated functionally by the immunohistochemical detection of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II (PIVKA-II) and by positive bile production, and the hepatocellular differentiation was structurally in accord with keratin 7, 8 and 18 expression. CA125 expression, commonly present in ovarian surface epithelial carcinomas, suggested that this neoplasm originated from ovarian common epithelial cells. There are only nine such cases in the literature. A review of these cases reveals that hepatoid carcinoma of the ovary occurs exclusively in postmenopausal women (mean age, 62.7 years) and that the prognosis is poor.

Biomarkers↗
PubMed1999

Right intraventricular metastasis of squamous cell carcinoma of the uterine cervix: an autopsy case and literature review.

An autopsy case of squamous cell carcinoma of the uterine cervix, which developed cardiac intracavitary metastasis in a 28-year-old Filipina, is reported. At autopsy, the right ventricle contained a soft, red-purple, cauliflower-like mass. Histologically, this mass was made up of sheets of malignant squamous cells similar to the primary uterine foci. The metastases were extensive and associated with multiple organ involvement. Although this case was stage Ib at operation, vascular invasion at the primary site was characteristic, and the intracavitary tumor of the right ventricle developed without myocardial involvement. The carcinoma of the primary site extended along the inferior vena cava and settled as an intracardiac obstructive mass. A literature review (including the present case) disclosed only 14 uterine cervical carcinomas with right intracavitary metastasis. The mean age of these patients was 46 years of age (range, 28-77 years). The clinical stage was Ib in two cases, IIa in one case, IIb in six cases, and IIIb in two cases. The prognosis of these cases was poor; 13 of the patients died at an average of 19.1 months after diagnosis.

Adult↗
PubMed1999

Molecular genetic analysis of remains of a 2,000-year-old human population in China-and its relevance for the origin of the modern Japanese population.

We extracted DNA from the human remains excavated from the Yixi site ( approximately 2,000 years before the present) in the Shandong peninsula of China and, through PCR amplification, determined nucleotide sequences of their mitochondrial D-loop regions. Nucleotide diversity of the ancient Yixi people was similar to those of modern populations. Modern humans in Asia and the circum-Pacific region are divided into six radiation groups, on the basis of the phylogenetic network constructed by means of 414 mtDNA types from 1, 298 individuals. We compared the ancient Yixi people with the modern Asian and the circum-Pacific populations, using two indices: frequency distribution of the radiation groups and genetic distances among populations. Both revealed that the closest genetic relatedness is between the ancient Yixi people and the modern Taiwan Han Chinese. The Yixi people show closer genetic affinity with Mongolians, mainland Japanese, and Koreans than with Ainu and Ryukyu Japanese and less genetic resemblance with Jomon people and Yayoi people, their predecessors and contemporaries, respectively, in ancient Japan.

Asian People↗
PubMed1999

Inhibitory mechanism of anti-P30-52 monoclonal antibody against human immunodeficiency virus type 1 (HIV-1) multiplication in infected MT-4 cells.

We have studied the immunological role of human immunodeficiency virus type 1 (HIV-1) p17 because the p17 antibody titer is high in asymptomatic patients and decreases with disease progression. Previously we found that monoclonal antibody (MAb) reactive to the p17-derived peptide 30 to 52 amino acids in length, namely P30-52 MAb, had cross-reactivity to the third variable region of the envelope glycoprotein of HIV-1 (Env V3) and also inhibited the viral multiplication of the supernatant of HIV-1-infected MT-4 cells co-cultured with the MAb. The relation between the cross-reactivity of the P30-52 MAb and the inhibitory mechanism is not clear; however, P30-52 might be useful for the development of therapeutic and vaccination strategies. In the present study, we examined the suppressive mechanism of the P30-52 MAbs, and found that the copy number of HIV-1 RNA in HIV-1-infected MT-4 cells was not reduced by the addition of the P30-52 MAbs, and the expression of RNAs of p17 was slightly enhanced 3 hr after the infection, although that of Env V3 was the same as the control level. In contrast, the expression of cellular p17 DNA and p17 protein was reduced by the addition of the P30-52 MAbs. In conclusion, the P30-52 MAbs did not suppress the HIV-1 mRNA level in the infected cells, but might inhibit DNA synthesis, and consequently bring about a reduction of p17 protein synthesis and a decrease of infectivity of the supernatant. The results demonstrated that the P30-52 MAb could be used as immunotherapeutic substance for HIV-1.

Animals↗
PubMed1999

Anti-P30-52 monoclonal antibody cross-reacted to Env V3 and inhibited the viral multiplication of HIV-1-infected MT-4 cells.

It is well known that the anti-p17 antibody titer decreases with the disease progression among human immunodeficiency virus type 1 (HIV-1) carriers. We previously established several murine anti-p17 monoclonal antibodies (MAbs) to investigate the immunological role of p17, and to further characterize these MAbs, we examined the anti-p17 antibody titer in serum of a patient who was a long-term nonprogressor with hemophilia, and found that the antibody for the p17-derivative peptide from amino acid residues 30 to 52 (P30-52) cross-reacted to the third variable region of the envelope glycoprotein of HIV-1, Env V3. In the present study, we primed mice with P30-52 to establish anti-P30-52 MAbs (P30-52 MAbs), and examined their affinity and whether they suppressed the viral multiplication of HIV-1-infected MT-4 (HTLV-1-transformed CD4+ T-cell line) cells, in a TCID50 assay. At the same time, an anti-Env V3 MAb (Env V3 MAb) was also established and examined as above. The IgM-type P30-52 MAb and Env V3 MAb showed heteroclitic binding, and the IgM-type P30-52 MAb inhibited the viral multiplication. We also found that an increase of fragmented DNA of HIV-1-infected MT-4 cells co-cultured with P30-52 MAbs. Because DNA fragmentation is one of the features of programmed cell death, the viral multiplication may be suppressed by the apoptosis of HIV-1-infected MT-4 cells co-cultured with P30-52 MAbs. Though the relationship between cross-reactivity and the inhibition mechanism of multiplication of HIV-1 is unclear, P30-52 of p17 may well be a useful region of viral proteins for the development of therapeutic and vaccination strategies.

Amino Acid Sequence↗