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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 217 records · Page 12Linked to original sources

Comparison of 99Tcm-tetrofosmin with 201Tl and 131I in the detection of differentiated thyroid cancer metastases.

The purpose of this study was to assess the detectability of metastatic lesions by 99Tcm-tetrofosmin in differentiated thyroid cancer, and to compare the results with those obtained using 201Tl-chloride and tracer doses of 131I. Twenty-four thyroidectomized patients with metastases were studied. There were 34 metastases, including 16 lung, nine lymph node and nine bone. Radiological studies (chest X-ray, computed tomography and magnetic resonance imaging), serum thyroglobulin assays and histopathological examinations were performed to verify the presence of metastases with positive uptake of the three radionuclides. Increased accumulation of 99Tcm-tetrofosmin was observed in 11 of 16 (68.8%) lung metastases, eight of nine (88.9%) lymph node metastases and eight of nine (88.9%) bone metastases. Increased accumulation of 201Tl and 131I was observed in 11 of 16 (both) (68.8%) lung metastases, eight (88.9%) and three (33.3%), respectively, of lymph node metastases and eight (88.9%) and nine (100%), respectively, of bone metastases. The detectability of thyroid cancer metastases using 99Tcm-tetrofosmin, 201Tl and 131I was 79.4%, 79.4% and 67.6%, respectively. The combined detectabilities of 99Tcm-tetrofosmin and 131I and of 201Tl and 131I were both 88.2%. 99Tcm-tetrofosmin and 201Tl imaging were found to be more sensitive than 131I for the detection of differentiated thyroid cancer metastases, particularly for regional lymph node. The combination of 99Tcm-tetrofosmin and 131I imaging may be a more sensitive and effective method for detecting metastases in differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors.

Caspase-3/CPP32, a member of the Ced-3-family of cysteine proteases, is an important mediator of programmed cell death (apoptosis). Intraductal papillary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intraductally with rare stromal invasion. However, it is not possible to distinguish noninvasive from invasive IPMT preoperatively. To examine whether caspase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell carcinomas (PDC) and 13 IPMT cases. Caspase-3 mRNA was overexpressed in PDC and IPMT with carcinoma when compared with normal pancreatic tissue or IPMT with adenoma. The immunoreactivity of this enzyme was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.

Apoptosis↗

Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.

BACKGROUND: Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia. OBJECTIVE: To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined. RESULTS: Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment. CONCLUSION: Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.

Adenosine Triphosphate↗

Peritoneal and peripheral B-1-cell populations in patients with endometriosis.

OBJECTIVE: The purpose of this study was to investigate the frequency of B-1 cells in the peritoneal cavity and peripheral blood of patients with endometriosis. MATERIALS AND METHODS: We examined 31 patients with endometriosis and 14 normal nonpregnant women. Peripheral blood cells and peritoneal exudate cells (PECs) were stained with FITC or PE-labeled anti-CD5/CD19 monoclonal antibodies. Immunofluorescence analysis was performed using a flow cytometer. The significance of differences between the patient and control groups was determined by the non-parametric Mann-Whitney test. RESULTS: There was no significant difference in the percentages of B-1 cells in the peripheral blood of women with and without endometriosis (median, 22.7%; range, 4.7-92.3% vs median, 20.05%; range, 11.1-12.6%, respectively). Endometriosis patients with antinuclear antibodies (ANAs) demonstrated significantly elevated B-1 cells compared to both endometriosis patients without ANAs and normal controls (p < 0.005 and p < 0.05, respectively). Endometriosis patients demonstrated significantly higher B-1 cell populations (B-1 cells/total B-cell ratio) in PECs than did non-endometriosis patients (p < 0.05). CONCLUSIONS: The peripheral B-1-cell population in patients with endometriosis is related to ANA production. B-1 cells might play important roles in the development of endometriosis through autoantibody production.

Adult↗

Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation.

Brain inflammation has been implicated in the development of brain edema and secondary brain damage in ischemia and trauma. Adhesion molecules, cytokines and leukocyte chemoattractants released/presented at the site of blood-brain barrier (BBB) play an important role in mobilizing peripheral inflammatory cells into the brain. Cerebral endothelial cells (CEC) are actively engaged in processes of microvascular stasis and leukocyte infiltration by producing a plethora of pro-inflammatory mediators. When challenged by external stimuli including cytokines and hypoxia, CEC have been shown to release/express various products of arachidonic acid cascade with both vasoactive and pro-inflammatory properties, including prostaglandins, leukotrienes, and platelet-activating factor (PAF). These metabolites induce platelet and neutrophil activation and adhesion, changes in local cerebral blood flow and blood rheology, and increases in BBB permeability. Ischemic CEC have also been shown to express and release bioactive inflammatory cytokines and chemokines, including IL-1beta, IL-8 and MCP-1. Many of these mediators and ischemia in vitro and in vivo have been shown to up-regulate the expression of both selectin and Ig-families of adhesion molecules in CEC and to facilitate leukocyte adhesion and transmigration into the brain. Collectively, these studies demonstrate a pivotal role of CEC in initiating and regulating inflammatory responses in cerebral ischemia.

Animals↗

Effects of paternal lymphocyte immunization on peripheral Th1/Th2 balance and TCR V beta and V gamma repertoire usage of patients with recurrent spontaneous abortions.

PROBLEM: The mechanism of immunotherapy for patients with recurrent spontaneous abortions is not well understood. In order to investigate the suppressor mechanism of paternal lymphocyte immunization, we examined peripheral blood lymphocyte subpopulations and the repertoire of T-cell receptor (TCR) gene segments. METHOD OF STUDY: Twelve patients with recurrent miscarriage were treated with immunization with paternal lymphocyte vaccinations three times during 12-14 weeks. Before and 2 weeks after the final inoculation, lymphocyte subsets and intra-cellular interferon (IFN)-gamma and/or interleukin (IL)-4 production were examined by flow cytometry. TCR V beta and V gamma repertoires were examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found no significant difference in CD4/CD8 ratios, prevalence of CD56+CD3+ or CD57+CD3+ cells (possible extrathymic T cells), gamma(delta)T cells, and CD5+ CD19+ (B-1) cells. However, by in vitro activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, peripheral CD4 cells demonstrated a significant decrease of IFN-gamma-producing T helper 1 (Th1) cells and an increase of IL-4-producing T helper 2 (Th2) cells after immunotherapy. Seven of nine patients who exhibited remarkable decreases in Th1/Th2 ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of the three patients who exhibited an increased or unchanged Th1/Th2 ratio had full-term pregnancies (chi2 < 0.0001). Further, changes in usage of TCR V beta and V gamma gene segments were observed after immunotherapy in six patients examined. CONCLUSION: Our findings suggest a shift of Th1-dominant to Th2-dominant status by vaccination might play important roles in maintaining successful pregnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.

Abortion, Habitual↗

Expression of functional chemokine receptors of human placental cells.

PROBLEM: Chemokine receptors of placental trophoblasts possibly act as co-receptors or alternative receptors of maternal fetal infection by HIV. To clarify their possible expression and the physiological roles of chemokines on human placentae, we studied chemokine chemokine receptor expression and the effects of exogenous chemokines on choriocarcinoma cell lines. MATERIALS AND METHODS: Placental samples were obtained from 13 placentae of various gestational ages. Villous tissue was mechanically dissected from samples. Trophoblasts were enriched by anti-human chorionic gonadotropin (hCG)-coated magnetic beads. Human choriocarcinoma cell lines (JAR, BeWo, JEG-3) were maintained in RPMI 1640 media supplemented with 10% FCS. Expression of chemokine receptors was studied by RT-PCR. The effects of MIP-1alpha, RANTES, MCP-1 on hCG production were estimated by EIA. Effects of chemokines on proliferation of choriocarcinoma cell lines were examined by MTT assay. RESULTS: We observed mRNA expression of CCR-1, 2, 3, 4, 5 and CXCR-1, 2, 4 in 1st trimester placental villi, CCR-I, 2, 4 and CXCR-1, 2. 4 in 2nd trimester placental villi, CCR-1, 2, 4 and CXCR-4 in 3rd trimester placental villi. Using MACS enriched trophoblasts, we observed identical results. A choriocarcinoma cell line BeWo expressed CCR-1, 3, 4 and CXCR-1, 2, 4 while JEG-3 and JAR expressed CCR-1, 3, 4, 5 and CXCR-1, 2, 4. Expression of the CCR-5 and CXCR-4 protein in choriocarcinoma cell lines and MACS-enriched trophoblats were confirmed by flow cytometry. Chemokine MCP-3, MIP-1alpha, RANTES mRNA were expressed by the 1st, 2nd and 3rd trimester placental samples and the three choriocarcinoma cell lines examined. MCP-1 was expressed by 1st and 2nd trimester placental villi. Administration of chemokines up-regulated proliferation (10(-1) - 10 ng/mL) and hCG production (10(-1) - 10(-2)ng/ mL) of the three choriocarcinoma cell lines examined. CONCLUSIONS: Our results suggest possible roles of chemokines/chemokine receptors on placental physiology and their involvement in HIV transmission as alternative receptors.

Chemokines↗

Cutaneous monomorphous CD4- and CD56-positive large-cell lymphoma.

BACKGROUND: Recently, CD56 (NCAM)-positive lymphomas, such as nasal and nasal-type angiocentric NK/T cell lymphoma, aggressive NK cell leukemia/lymphoma and blastic NK cell lymphoma, were described by several authors as a unique group of lymphoma. OBJECTIVE: In this study, we intend to clarify the clinicopathological features of cutaneous CD4+ and CD56+ lymphoma. METHODS: Four patients with cutaneous CD4+ and CD56+ lymphoma were studied. RESULTS: Age at the first examination ranged from 71 to 89 years (mean = 81.2 years). One patient was female and 3 were males. The organ mainly involved at presentation was the skin. Lymphadenopathy, splenomegaly, leukemic spread and central nervous system involvement were observed as the disease progressed. The mean survival time was 12.2 months. Epstein-Barr virus was not detected within the tumor cells. CONCLUSION: This peculiar lymphoma is different from nasal and nasal-type angiocentric NK/T cell lymphoma and aggressive NK cell leukemia/lymphoma. Similar cases have been reported as blastic NK cell lymphoma/leukemia.

Adult↗

Expression of tumor necrosis factor-alpha in cultured human endothelial cells stimulated with lipopolysaccharide or interleukin-1alpha.

Tumor-necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine with a wide variety of biological effects. The most important source of this cytokine is monocytes/macrophages. It is a potent agonist in the activation of endothelial cells; however, the precise role of endothelial cells as a source of TNF-alpha is not known. In the present study, we addressed the possibility that TNF-alpha is produced by cultured human umbilical vein endothelial cells (HUVEC) stimulated with factors such as lipopolysaccharide (LPS) or interleukin-1alpha (IL-1alpha). LPS and IL-1alpha induced expression of TNF-alpha mRNA in HUVEC. IL-1alpha induced expression and secretion of TNF-alpha protein, but LPS did not induce production of TNF-alpha protein. Most of the TNF-alpha protein in cell lysate was found in the membrane fraction. The mRNA for TNF-alpha-converting enzyme (TACE) was expressed in unstimulated HUVEC, and its level was not altered by treatment with LPS or IL-1alpha. Transfection of HUVEC with full-length cDNA encoding the precursor TNF-alpha enhanced secretion of TNF-alpha protein by these cells, and treatment of the cells with a TACE inhibitor reduced the secretion. These results suggest that HUVEC produce TNF-alpha and have TACE activity. Secreted TNF-alpha may be involved in autocrine activation of endothelial cells, and TNF-alpha retained in cell membrane may serve as a juxtacrine system to activate target cells on the endothelial surface.

ADAM Proteins↗

Secretory leukoprotease inhibitor augments hepatocyte growth factor production in human lung fibroblasts.

Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine protease inhibitor, is produced and released into the fluids of mucosal surfaces including human lung. It comprises two domains with homologous amino acid sequences: the N-terminal domain possessing antibacterial activity, and the C-terminal domain with antiprotease activity. Here we report the positive regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to 10 microM). This HGF production by SLPI was unaffected by the addition of interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1beta increased HGF production with an intensity similar to that of human lung fibroblasts. Both the time-course and dose-response studies in human lung fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein occurred in parallel, indicating that the mechanism existed at the steady-state mRNA level. A synthetic elastase inhibitor failed to induce HGF, but alpha(1)-antitrypsin also stimulated HGF production in lung fibroblasts. Inactivation of the antiprotease activity of SLPI or its C-terminal domain by an oxidizing agent (N-chlorosuccinimide) abolished their stimulatory effect on HGF production. These findings demonstrate that SLPI exerts a novel HGF induction and functions as an anti-inflammatory and regenerative factor in addition to its role in protease inhibition.

Binding Sites↗

Catalytic properties for naphthoquinones and partial primary structure of rabbit heart acetohexamide reductase.

The catalytic properties of rabbit heart acetohexamide reductase (RHAR) for naphthoquinones were examined. RHAR efficiently reduced 1,4-naphthoquinone and juglone (5-hydroxy-1,4-naphthoquinone), whereas it had little or no ability to reduce menadione (2-methyl-1,4-naphthoquinone) or plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone). The structural requirements for these four naphthoquinones and one acetohexamide analog, and the kinetic mechanism for the inhibition of acetohexamide reduction by juglone led us to conclude that the 2-methyl group of menadione and plumbagin prevents access of the substrates to the catalytic site of RHAR. Five of six peptides derived from RHAR showed 30-42% residue identities with regions in the amino acid sequence of mouse lung carbonyl reductase (MLCR) belonging to the short-chain dehydrogenase/reductase (SDR) family. The catalytically important residues (Arg-39, Ser-136, Tyr-149 and Lys-153) of MLCR were found in the peptide sequences of RHAR, despite the low residue identities between the two enzymes. RHAR is probably best classified as a member of the SDR family similar to MLCR.

Acetohexamide↗

The inhibition of phenylhydroquinone-induced oxidative DNA cleavage by constituents of Moutan Cortex and Paeoniae Radix.

Moutan Cortex (root cortex of Paeonia suffruticosa ANDREWS) and Paeoniae Radix (root of Paeonia lactiflora PALLAS) are crude drugs used in many traditional prescriptions and have constituents in common. We studied the effects of extracts of these crude drugs and their constituents on oxidative DNA damage caused by phenylhydroquinone (PHQ), a major metabolite of o-phenylphenol. Both drugs suppressed the cleavage of pUC18 DNA induced by PHQ, and scavenged the superoxide and hydroxy radical generated by the chemical. They also inhibited the oxidative DNA cleavage by tert-butylhydroquinone (TBHQ), one of the major metabolites of butylated hydroxyanisole. When constituents were examined with the same system, galloylpaeoniflorin and 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) were found to be the most potent inhibitors of the DNA cleavage. These constituents had oxygen radical scavenging activity. Paeonol also attenuated the DNA cleavage. Paeoniflorin and albiflorin had relatively small inhibitory effects on DNA cleavage. However, catechin enhanced the PHQ-induced DNA cleavage. The suppression of oxidative DNA damage by Moutan Cortex and Paeoniae Radix might be attributable to the additive effects of galloylpaeoniflorin, PGG and other constituents.

Biphenyl Compounds↗

Efficient synthesis of a key intermediate of DV-7751 via optical resolution or microbial reduction.

Two efficient and practical methods of synthesis of the C-10 substituent of DV-7751 (1), a novel quinolone carboxylic acid, were established. The first method utilizes an optical resolution of racemic 8-amino-6-benzyl-6-azaspiro[3.4]octane (13), while the second employs an enantioselective microbial reduction of 6-benzyl-5,8-dioxo-6-azaspiro[3.4]octane (8b). The enantiomeric excess of (S)-8-amino-6-benzyl-6-azaspiro[3.4]octane (11) with each method of synthesis is greater than 96%.

Anti-Infective Agents↗

Polyphenols from Eriobotrya japonica and their cytotoxicity against human oral tumor cell lines.

Three new flavonoid glycosides, together with 15 known flavonoids, have been isolated from the leaves of Eriobotrya japonica, and characterized as (2S)- and (2R)-naringenin 8-C-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosides, and cinchonain Id 7-O-beta-D-glucopyranoside, respectively, based on spectral analyses including two dimensional (2D) NMR techniques. Higher proanthocyanidin fraction in the water-soluble portion of the extract was characterized as a procyanidin oligomer mixture mainly composed of undecameric procyanidin. These polyphenols have also been assessed for cytotoxic activity against two human oral tumor (human squamous cell carcinoma and human salivary gland tumor) cell lines. Selective cytotoxicity of the procyanidin oligomer between tumor and normal gingival fibroblast cells, and its possible mechanism, were also described.

Antibodies, Monoclonal↗

[Competitive binding of some alkyl p-hydroxybenzoates to human estrogen receptor alpha and beta].

Alkyl p-hydroxybenzoates such as isobutyl p-hydroxybenzoate (PHBA-iBu), butyl p-hydroxybenzoate (PHBA-nBu), isopropyl p-hydroxybenzoate (PHBA-iPr), propyl p-hydroxybenzoate (PHBA-nPr), ethyl p-hydroxybenzoate (PHBA-Et), and methyl p-hydroxybenzoate (PHBA-Me) are widely used as preservatives, stabilizers and antiseptics for medical supplies, cosmetics, foodstuffs etc. We determined the binding affinity of alkyl p-hydroxybenzoates to human estrogen receptor alpha (ER alpha) and beta (ER beta) by non-RI receptor binding assays. PHBA-iBu had a high binding affinity for ER alpha (IC50: 6.0 x 10(-6) M, the relative binding affinity (RBA): 0.267) and ER beta (IC50: 5.0 x 10(-6) M, RBA: 0.340). These IC50 values and RBA were almost the same as those of bisphenol A. The ranking of the estrogenic potency of alkyl p-hydroxybenzoates for both ERs is different; that is, PHBA-iBu > PHBA-nBu[symbol: see text]PHBA-iPr[symbol: see text]PHBA-nPr > PHBA-Et >> PHBA-Me. Alkyl p-hydroxybenzoates bound with equal relative affinity to both ER alpha and beta proteins. Alkyl p-hydroxybenzoate having a long alkyl side-chain showed a high affinity for ER alpha and beta. These findings suggest that p-hydroxybenzoates may be endocrine disruptors.

Binding, Competitive↗

Cloning and characterization of a gene complementing the mutation of an ethanol-sensitive mutant of sake yeast.

Ethanol-sensitive mutants (esl to es10) were isolated from sake yeast, Saccharomyces cerevisiae SY-32. These mutants were unable to grow at 7% ethanol at which the wild type strain SY-32 does grow. The mutants had a variety of fermentation rates and viabilities in the presence of ethanol. The gene ERG6, complementing the ethanol-sensitive mutation of es5, was cloned from an SY-32 gene library. ERG6 encodes S-adenosylmethionine: delta 24-sterol-C-methyltransferase (EC 2.1.1.41) in the ergosterol synthetic pathway. Mutant es5 had a reduced ability to synthesize ergosterol. An erg6 disruptant was also ethanol-sensitive. These results suggested that ERG6 plays an important role in the ethanol tolerance of S. cerevisiae.

Cloning, Molecular↗

Gonadotropin-releasing hormone analog therapy failed to improve predicted final height in two children with central precocious puberty and microcephalus.

Long-acting gonadotropin-releasing hormone (GnRH) analog treatment for central precocious puberty (CPP) suppresses excessive bone maturation by inhibiting the pituitary-gonadal axis, and usually assures favorable results for growth potential. Recently, we encountered two children with CPP and microcephalus in whom GnRH analog therapy arrested pubertal development, but could not suppress bone age maturation effectively. Eventually, their final height deteriorated rather than improved. The reason why these two cases did not respond to GnRH analog therapy remains unknown. However, microcephalus and minor cerebral anomalies may have some links to deterioration of final height. Our cases suggest that careful evaluation will be required especially for CPP with microcephalus throughout treatment with GnRH analog.

Adolescent↗

Effect of high amniotic fluid pressure on fetal circulation.

The purpose of this study was to investigate the effects of high amniotic fluid pressure (AFP) created by amnioinfusion on fetal circulation. Five pregnant goats whose fetuses had a mean gestational age of 131 +/- 2 days (term 145 days) were used. After a 30 minute control period, 1500 ml of warm saline was infused to the amniotic cavity over a period of 30 minutes. The AFP gradually increased during amnioinfusion and remained 2-3 mmHg above the control level for 3 hours after amnioinfusion. Fetal arterial pH (FpH) tended to decrease, and there was a significant negative correlation between the FpH and AFP (r = -0.723). Fetal arterial pO2 also tended to decrease and negatively correlated to the AFP (r = -0.59). On the other hand, fetal arterial pCO2 tended to increase and positively correlated with the AFP (r = 0.75). Although amnioinfusion is useful for improving the status of a distressed fetus, the fetal condition may be jeopardized at the same time. Therefore, careful monitoring of the AFP and fetal status is recommended during amnioinfusion.

Amniotic Fluid↗