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Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 253 records · Page 14Linked to original sources
PubMed2000

Functional conservation of platelet glycoprotein V promoter between mouse and human megakaryocytes.

OBJECTIVE: In an attempt to clarify the megakaryo-specific regulatory mechanism of GPV gene transcription, we characterized the 5'-flanking region of the mouse GPV gene. MATERIALS AND METHODS: The promotor activity of a -481/+22 5'-fragment of the mouse GPV gene was examined in normal mouse bone marrow cells (BMC) and various human cell lines using two distinct reporter gene assay systems, luciferase and green fluorescence protein (GFP). RESULTS: When a DNA construct consisting of this fragment and a GFP reporter gene were transiently expressed in thrombopoietin-supported mouse BMC culture, GFP was identified only in megakaryocytes. The same construct expressed high levels of GFP in the human megakaryocytic Dami line. When assessed by dual luciferase assay, the full -481/+22 fragment could drive variable promoter activity in human as well as mouse megakaryocytic lines but did not work in non-megakaryocytic cells. Sufficient transcriptional activation of this fragment was restricted to the cells expressing apparent GPV mRNA. A deletion and point mutation study indicated that GATA and Ets motifs, typical cis-acting elements for platelet-specific genes, located of -75 and -46, respectively, were essential for promoter function. CONCLUSION: The GPV promoter has the general characteristics found in platelet-specific genes, and the mechanism for megakaryocyte-specific, maturation-dependent regulation of GPV gene transcription is highly conserved between mouse and human. Analysis of GPV transcription mechanism utilizing human lines as well as BMC should provide new information on the final maturational process of megakaryocytes.

Animals↗
PubMed2000

Globotriaosyl ceramide (CD77/Gb3) in the glycolipid-enriched membrane domain participates in B-cell receptor-mediated apoptosis by regulating lyn kinase activity in human B cells.

The role of CD77 expressed on a fraction of germinal center B cells, also known as glycosphyngolipid Gb3, and as a functional receptor for Shiga toxins (Stx) in B-cell receptor (BCR)-mediated apoptosis was investigated. Using Stx1-sensitive Burkitt's lymphoma Ramos cells as an in vitro model of CD77(+) germinal center B cells, intracellular signaling events mediated by either Stx1 or anti-CD77 antibody were examined immunobiochemically and immunocytologically. We observed prompt activation of Lyn and Syk kinases leading to increased binding of these proteins to surface IgM (sIgM) in Ramos cells after Stx1 treatment. We also observed microscopic colocalization of CD77 and sIgM after stimulation with Stx1. Along with the synergism between the cross-linking of CD77 and that of sIgM in their effect on apoptosis induction, it was highly probable that CD77 cross-linking induces activation of the BCR signaling cascade. Analysis using sucrose density gradient centrifugation suggested that Stx1 binding to CD77 induced recruitment and activation of Lyn in the glycolipid-enriched membrane (GEM) fractions. Once activated, however, Lyn seemed to acquire an increased detergent solubility and moved outside of the GEM fractions. This study describes the participation of the GEM domain in BCR-signaling cascade and suggests a possible role of CD77 as a regulator of BCR-induced apoptosis in human B cells.

Apoptosis↗
PubMed2000

Characteristic expression of Hck in human B-cell precursors.

OBJECTIVE: To identify molecules involved in signaling for early B-cell development, we investigated the expression of signal transduction-related proteins in B-cell progenitors. MATERIALS AND METHODS: [corrected] Normal as well as leukemic B-cell progenitors were examined by immunoblotting and immunofluorescence study. RESULTS: [corrected] In a survey of the expression of a broad range of signal transduction molecules, the Src-family protein tyrosine kinases were found to be differentially expressed in early B-cell differentiation. [corrected] Analysis of freshly prepared precursor-B acute lymphoblastic leukemia cells and B-lineage cell lines showed Hck and Lyn are major Src-family protein tyrosine kinases expressed in this type of leukemic blasts. [corrected] However, heterogeneity of Hck and Lyn expression was found in these cells, and precursor-B acute lymphoblastic leukemia cells subsequently were classified according to the expression pattern of Hck and Lyn as Hck/Lyn dual-negative, Hck-predominant, Hck/Lyn dual-positive, and Lyn-predominant. Further studies on normal B-lineage cells indicated that the Src-family protein tyrosine kinases are expressed sequentially in a differentiation-dependent fashion during B-cell ontogeny and that the predominant expression of Hck is a common feature in B-cell progenitors, whereas Lyn expression is more significant in mature B cells. CONCLUSIONS: Although the biologic significance remains unknown, sequential expression of Src-family protein tyrosine kinases should play a role in regulation of early B-cell differentiation.

Antigens, CD↗
PubMed2000

Insufficient diagnostic accuracy of imported serological kits for Helicobacter pylori infection in Japanese population.

Although there are many reports of the high diagnostic accuracy of commercially available serologic kits for Helicobacter pylori infection in Western countries, they rarely has been investigated in oriental population. Accordingly we examined their usefulness in 492 Japanese patients with dyspeptic symptoms. Diagnostic accuracy of 4 imported serologic kits (HEL-p TEST, HM CAP, G.A.P IgG, Helico G2) was investigated using the (13)C-urea breath test as the gold standard. When intermediate results were excluded, the sensitivity, specificity and accuracy of these serologic tests ranged from 88.6% to 97.8%, 67.9% to 85.9%, and 87.9% to 91.4%, respectively, which were comparable with reported median accuracy in the Western population. However, there were many intermediate results in these tests, ranging from 5.3% to 23.0%. Their usefulness seemed to be limited in our patient population because of the large number of intermediate results.

Adult↗
PubMed2000

Effect of viscous additives on drug absorption from the liver surface in rats using phenol red as a model.

The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use.

Absorption↗
PubMed2000

Synthesis and biological activities of the marine bryozoan alkaloids convolutamines A, C and F, and lutamides A and C.

Synthesis of convolutamines and lutamides, new 2,4,6-tribromo-3-methoxyphenethylamine alkaloids isolated from Floridian marine bryozoan Amathia convoluta, was accomplished by a sequence of reactions starting from 3-hydroxyphenethylamines. Cytotoxities of the synthetic lutamides, convolutamines and their de-O-methyl derivatives were examined using drug-sensitive and -resistant P388 as well as KB cell lines. The bioassay suggests that the 2,4,6-tribromo-3-methoxyphenethylamine is an indispensable unit for detection of the activities. Additionally, a reversal of drug resistance by those alkaloids is recognized.

Alkaloids↗
PubMed2000

Efficacy of reduced dosage of rabeprazole in PPI/AC therapy for Helicobacter pylori infection: comparison of 20 and 40 mg rabeprazole with 60 mg lansoprazole.

Proton pump inhibitor (PPI)- based triple therapy has been a recent trend for treatment of Helicobacter pylori infection, with the PPI-amoxicillin-clarithromycin (PPI/AC) regimen being one of the most popular. We have reported the effectiveness of PPI/AC regimens in the Japanese population and have demonstrated that the effectiveness of 40 mg rabeprazole, a recently developed PPI, is similar to that of 40 mg of omeprazole and 60 mg of lansoprazole when used in combination with amoxicillin and clarithromycin. In this study, we focused on whether 20 mg of rabeprazole is effective in our patient population by comparing that dosage with 40 mg of rabeprazole and 60 mg of lansoprazole. In all, 308 H. pylori-infected patients [236 men and 72 women; age (mean +/- SEM) 49.3+/-0.6 years] with peptic ulcer disease (N = 270) or nonulcer dyspepsia (N = 38) were randomly assigned to one of three different PPI/AC regimens for seven days: LAC (N = 104), consisting of lansoprazole 30 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; RAC (N = 104), consisting of rabeprazole 20 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; and the R1/2AC regimen (N = 100), which included rabeprazole 10 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day. Cure of the infection was determined by the [13C]urea breath test one month after completion of the treatment. Intention-to-treat based and per-protocol based cure rates for the LAC, RAC, and R1/2AC regimens were 82.7 (95% CI, 74-89) and 88.7% (81-94), 85.6 (77-92) and 89.8% (82-95), and 87.0 (79-93) and 89.7% (82-95), respectively. Although adverse effects were reported by 20.3% of the patients, these affected compliance in only five patients in the RAC and LAC regimens and none in the R1/2AC group. Overall complete compliance was achieved in 94.7% of interviewed patients. In conclusion, the effectiveness of the PPI/AC regimen with 20 mg of rabeprazole is comparable with and even safer than that of 40 mg of rabeprazole and 60 mg of lansoprazole in our patient population.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Implications of mechanical stretch on wound repair of gastric smooth muscle cells in vitro.

Gastric smooth muscle cells continually receive repetitive physical stretching by food storage, peristalsis and fasting contraction; therefore mechanical stretch can not be disregarded in gastric events. The aim of this study was to clarify the effects of mechanical stretch on wound repair using a rabbit gastric smooth muscle cell sheet. Mechanical stretch was imposed on adherent cells on a flexible membrane in order to increase elongation by an average of 5% and 10%, respectively, at 5 cycles per minute after artificial wounding. Adherent cells not subjected to mechanical stretch served as controls. The restoration process was monitored by measuring wound size for 48 h. Proliferation was assessed by BrdU staining and the influence on the cytoskeletal system was assessed by actin staining. The speed of restoration was highest in controls and lowest in the 10% stretch groups. Proliferation was almost equal to that of controls in the stretch groups. Under the condition of mechanical stretch, stress fibers appeared weakened and the direction of fibers was not consistent but random. In conclusion, mechanical stretch inhibited the migration of gastric smooth muscle cells, leading to cytoskeletal dysfunction. It is suggested that physical stretch, such as mechanical stretch, might be an important factor in the process of gastric wound repair.

Animals↗
PubMed2000

Physiological modeling of altered pharmacokinetics of a novel anticancer drug, UCN-01 (7-hydroxystaurosporine), caused by slow dissociation of UCN-01 from human alpha1-acid glycoprotein.

PURPOSE: The extremely low clearance and small distribution volume of UCN-01 in humans could be partly due to the high degree of binding to hAGP. The quantitative effects of hAGP on the pharmacokinetics of UCN-01 at several levels of hAGP and UCN-01 were estimated in rats given an infusion of hAGP to mimic the clinical situation and a physiological model for analysis was developed. METHODS: The plasma concentrations of UCN-01 (72.5-7250 nmol/kg i.v.) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, were measured by HPLC. Pharmacokinetic analysis under conditions assuming rapid equilibrium of protein binding and incorporating the dissociation rate was conducted. RESULTS: The Vdss and CLtot of UCN-01 (725 nmol/kg i.v.) in rats given an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/ 700 that in control rats. The Vdss and CLtot following 72.5-7250 nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9-688 ml/kg and 3.18-32.9 ml/h/kg, respectively, indicating non-linearity due to saturation of UCN-01 binding. The CLtot estimated by the physiological model assuming rapid equilibrium of UCN-01 binding to hAGP, was six times higher than the observed value while the CLtot estimated by the model incorporating k(off), measured using DCC, was comparable with the observed value. CONCLUSIONS: These results suggest that the slow dissociation of UCN-01 from hAGP limits its disposition and elimination.

Algorithms↗
PubMed2000

Effects of one-lung ventilation on cardiac autonomic nervous activity as evaluated by power spectral analysis of heart rate variability.

The purpose of this prospective study was to evaluate the effects of one-lung ventilation on the activity of the cardiac autonomic nervous system. Ten adult patients who underwent thoracotomy were endotracheally intubated with a double-lumen tube under general anesthesia using isoflurane. After induction of anesthesia, a continuous, 256-sec electrocardiogram (ECG) was obtained during bilateral lung ventilation (control) followed by recordings during one-lung ventilation of each side. Using the R-R interval tachograms obtained for the 256-sec ECGs, low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.40 Hz) bands of the spectral density of the heart rate variability and the HF/LF ratio were analyzed using the fast Fourier transform algorithm. Log(HF), which indicates parasympathetic activity, increased during one-lung ventilation on each side, but did not differ between ventilated sides. Log(LF), which represents sympathetic and parasympathetic activity, increased similarly to log(HF) on both sides. Log(HF/LF), the balance of the sympathetic and parasympathetic activity, did not change during one-lung ventilation. We suggest that one-lung ventilation alone does not substantially affect the cardiac autonomic nervous system.

Adult↗
PubMed2000

Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs.

Transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinases (MMPs) produced by tumor cells play important roles in tumor invasion. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. In this study, we focused on the effects of PSK on invasiveness, TGF-beta1 production, and MMPs expression in two human tumor cell lines, pancreatic cancer cell line (NOR-P1) and gastric cancer cell line (MK-1P3). PSK significantly decreased the invasiveness of both cell lines through Matrigel-coated filters but did not affect cell viability, proliferation, or adhesion. Decreased invasion was associated with the inhibition of TGF-beta1, MMP-2, and MMP-9 at both mRNA and protein levels as assessed by reverse transcriptase-polymerase chain reaction, gelatin zymography, and enzyme-linked immunosorbent assay. Antibody against TGF-beta1 neutralized the MMP activities of both cell lines. PSK also suppressed the expression of urokinase plasminogen activator (uPA) and uPA receptor but did not change plasminogen activator inhibitor-1 (PAI-1) expression. Western blot analysis showed that PSK reduced uPA protein expression but not PAI-1 expression in the both cell lines. These results indicate that PSK suppresses tumor cell invasiveness through down-regulation of several invasion-related factors including TGF-beta1, uPA, MMP-2, and MMP-9.

Adjuvants, Immunologic↗
PubMed2000

Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population.

Low density lipoprotein (LDL) receptor-related protein (LRP) gene polymorphisms located in the 5' region and in exon 3, and the apolipoprotein E (APOE) genotype were determined in 100 Japanese patients affected by late-onset Alzheimer's disease (AD). We matched 246 controls for age and found no association between the polymorphism located in the 5' region of the LRP gene. The distribution of LRP exon 3 genotypes and alleles did not differ between AD and the control groups. However, the frequency of T allele in the Alzheimer's group having APOE-epsilon4 was lower than that in the control group having APOE-epsilon4, but it was only marginally significant (p = 0.022). Age of onset was significantly younger in the patients with CC genotype than those carrying the T allele (p = 0.03), and this trend was more evident among non-APOE-epsilon4 carriers (p = 0.008). These results support the possibility that ApoE and LRP may contribute to the development of AD.

Age of Onset↗
PubMed2000

The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver.

AIMS/BACKGROUND: Among patients with collagen diseases, liver enzyme abnormalities are a relatively common phenomenon. To establish the liver pathology in collagen diseases, detailed pathologic studies were performed on the hepatic diseases in many patients, including various kinds of collagen diseases. METHODS: The livers from 160 patients (120 autopsy and 40 liver biopsy patients) were examined pathologically: 73 with systemic lupus erythematosus (SLE), 32 with rheumatoid arthritis (RA), 18 with polymyositis and dermatomyositis (PM and DM), 15 with systemic sclerosis (SSc), 11 with mixed connective tissue disease (MCTD) and 11 with polyarteritis nodosa (PAN). RESULTS: Liver diseases were divided into three groups: hepatic arteritis, liver diseases associated with collagen diseases (primary biliary cirrhosis, PBC; autoimmune hepatitis, AIH; nodular regenerative hyperplasia of the liver, NRH) and other liver diseases. Hepatic arteritis presenting the features of the PAN type of necrotizing arteritis was found in 27 autopsy patients. The incidence of arteritis in autopsy patients was 100% in PAN and 8.3-25% in other collagen diseases. Primary biliary cirrhosis was observed in 9 patients, 7 of whom (3 with SSc, 2 with RA, 1 with PM and DM, and 1 with MCTD) had antimitochondrial antibodies (AMA)-positive PBC, and 2 SLE patients had AMA-negative PBC. Three patients (2 with SLE and 1 with MCTD) were diagnosed clinicopathologically as having AIH. However, 3 patients (1 with SLE, 1 with MCTD and 1 with PM and DM) with clinical, biochemical and serologic data indicating probable AIH were excluded from the group with AIH association because of the liver histology (no characteristic features of AIH) and clinical course. These results indicated that data without histologic assessments of the liver are not adequate for diagnosing AIH in collagen diseases. Nodular regenerative hyperplasia of the liver was observed in 7 patients (5 with SLE, 1 with SSc and 1 with PAN). CONCLUSION: The present study offers data that are useful for the diagnosis and treatment of patients with collagen diseases and liver abnormalities.

Adolescent↗
PubMed2000

Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression.

Presenilin 1 (PS1), a polytopic membrane protein, has a critical role in the trafficking and proteolysis of a selected set of transmembrane proteins. The vast majority of individuals affected with early onset familial Alzheimer's disease (FAD) carry missense mutations in PS1. Two studies have suggested that loss of PS1 function, or expression of FAD-linked PS1 variants, compromises the mammalian unfolded-protein response (UPR), and we sought to evaluate the potential role of PS1 in the mammalian UPR. Here we show that that neither the endoplasmic reticulum (ER) stress-induced accumulation of BiP and CHOP messenger RNA, nor the activation of ER stress kinases IRE1alpha and PERK, is compromised in cells lacking both PS1 and PS2 or in cells expressing FAD-linked PS1 variants. We also show that the levels of BiP are not significantly different in the brains of individuals with sporadic Alzheimer's disease or PS1-mediated FAD to levels in control brains. Our findings provide evidence that neither loss of PS1 and PS2 function, nor expression of PS1 variants, has a discernable impact on ER stress-mediated induction of the several established 'readouts' of the UPR pathway.

Alzheimer Disease↗
PubMed2000

Cord blood transplantation and cord blood bank in Japan.

The first cord blood transplantation (CBT) was performed in a 5-year-old boy with acute myelogenous leukemia from his HLA-identical sibling donor in 1994. Since then there have been 17 related and 131 unrelated CBTs in Japan. Overall survival and disease-free survival (DFS) were over 70% in sibling donor CBT. DFS of unrelated CBT in leukemia and other hematological malignancies was 43%, and OS of UCBT in non-malignant diseases was 63%. HLA disparity between the donor and the recipient did not affect the incidence and severity of acute graft-versus-host disease (GVHD) or survival. Cell dose was the most important factor for engraftment and survival both in malignant and in non-malignant diseases. The Japanese government has recently established the nationwide cord blood bank network, and eight local cord blood banks are financially supported by the government. 20,000 units of CB are planned to be collected and stored in the next 5 years by this network.

Blood Banks↗
PubMed2000

Erythema exsudativum multiforme induced by granulocyte colony-stimulating factor in an allogeneic peripheral blood stem cell donor.

We describe a healthy peripheral blood stem cell (PBSC) donor who developed a cutaneous reaction, erythema exsudativum multiforme, during the administration of granulocyte colony-stimulating factor (G-CSF) for mobilization. The cutaneous lesions were located on his hips, apart from the site of G-CSF injection. Treatment with topical corticosteroid was commenced, and the lesions resolved completely within a week. Adverse cutaneous reactions induced by G-CSF have been reported infrequently in healthy donors. Further documentation of cases and their full evaluation will be of great importance for both physicians and PBSC donor.

Adrenal Cortex Hormones↗
PubMed2000

Large scale purification of human blood CD34+ cells from cryopreserved peripheral blood stem cells, using a nylon-fiber syringe system and immunomagnetic microspheres.

Isolation of large numbers of human peripheral blood CD34+ cells could lead to therapeutic applications, including purging of malignant cells from blood cell transplantations, purging of T cells from allogeneic bone marrow, and even blood cell transplantation. This procedure has limitations if there are not sufficient numbers of progenitor cells in the leukapheresis concentrates available for selection after detection of tumor cells in apheresis products. Use of frozen/thawed peripheral blood mononuclear cell (PBMC) samples would make feasible pooling of two or even more stem cell harvests collected at different time points and the total number of CD34+ progenitor cells available would increase. We established an efficient method for purification of CD34+ cells from cryopreserved apheresis products, using a nylon-fiber syringe system and immunomagnetic microspheres. We compared purity, recovery rate and clonogenicity of CD34+ cells purified from fresh (n = 22) and cryopreserved apheresis products (n = 14), using a nylon-fiber syringe system and immunomagnetic microspheres. The purity of CD34+ cells from cryopreserved products was less than that from fresh products (85.9 +/- 14.4% vs 94.6 +/- 10.0%), but the recovery rate of CD34+ cells and colony-forming cells was comparable between fresh and cryopreserved products. One patient underwent grafting with peripheral blood CD34+ cells selected after freezing, with good success. Therefore, these cells are capable of rapidly reconstituting hematopoiesis after high-dose chemotherapy. Bone Marrow Transplantation (2000) 26, 787-793.

Antigens, CD34↗