Biomedical subjects

H Toyoda

Publications and source records attributed to H Toyoda.

At least 181 records · Page 10Linked to original sources

PubMed1995

Translocation of protein phosphatase 1 catalytic subunits during 1,25-dihydroxyvitamin D3-induced monocytic differentiation of HL-60 cells.

To elucidate the roles of protein phosphatases type 1 (PP1) and type 2A (PP2A) in 1,25-dihydroxy-cholecalciferol [1,25(OH)2D3]-induced differentiation of HL-60 cells into monocytes, we examined the enzyme activity and the protein and gene expressions of PP1 and PP2A in these cells. Calyculin-A augmented the 1,25(OH)2D3-induced differentiation of the cells. Treatment of the cells with 1,25(OH)2D3 led to a decrease in PP1-like activity in the cytosol fraction, with a concomitant increase in the membrane and nuclear PP1-like activity, as determined when protein phosphatase activity was assayed using myosin light chain as substrate in the presence of 5 nM okadaic acid. Western blot analysis with antibodies specific for PP1 catalytic subunit isozymes (PP1 alpha, PP1 gamma, and PP1 delta) showed that all three PP1 isozymes were expressed but were differentially distributed in each cellular fraction. Subcellular redistribution of PP1-like activity during 1,25(OH)2D3-induced differentiation was mainly attributed to PP1 gamma and PP1 alpha proteins. In contrast, the localizations of PP1 delta and PP2A catalytic and regulatory subunits were not significantly affected by 1,25(OH)2D3 treatment. The gene expressions of PP1 alpha and PP1 gamma appeared to be constant during processes of monocytic differentiation. The correlation between phenotypic and functional changes of HL-60 cells on the one hand and subcellular redistribution of PP1-like activity on the other suggest that the translocations of PP1 alpha and PP1 gamma isozymes may contribute to the 1,25(OH)2D3-induced monocytic differentiation of HL-60 cells.

Calcitriol↗

PubMed1995

Portal vein reconstruction using an internal jugular vein as a graft: report of a case.

We report the case of a 41-year-old man with pancreatic carcinoma invading the portal vein who was successfully treated by portal vein resection combined with pancreatoduodenectomy and reconstruction using an autointernal jugular vein. The internal jugular vein is an ideal graft for portal vein replacement because it has sufficient length, a well-matched diameter, and there is no venous insufficiency after unilateral resection. Nevertheless, this is the first report of portal vein reconstruction using the internal jugular vein as a graft.

Adenocarcinoma↗

PubMed1995

Intercellular adhesion molecule 1 gene associations with immunologic subsets of inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease is characterized by a failure to down-regulate the usual self-limited gut inflammatory response, suggesting that one or more of the predisposing genes could be those that determine the level of the immune response along the inflammatory pathway. The aim of this study was to examine potential associations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with inflammatory bowel disease or subsets of inflammatory bowel disease. METHODS: One hundred eighteen patients with ulcerative colitis (UC) and 130 patients with Crohn's disease (CD) as well as 77 ethnically matched controls were tested for antineutrophil cytoplasmic antibodies (ANCAs) and genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: There was no significant difference between all patients with UC, patients with CD, and controls in either polymorphism. However, when stratified by ANCA status, ANCA-negative UC showed a significantly increased frequency of allele R241 compared with ANCA-positive UC (16.0% vs. 6.6%; P = 0.047, Fisher's Exact Test). In contrast, it was ANCA-positive CD that had an increased allele frequency compared with ANCA-negative CD (19.6% vs. 8.4%; P = 0.027, Fisher's Exact Test). CONCLUSIONS: Because the codon 241 polymorphism is in a functionally important domain III of ICAM-1, we may have identified an actual responsible genetic variation for genetically heterogeneous subsets of both UC and CD.

Alleles↗

PubMed1995

Transcatheter arterial embolization for massive bleeding from duodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND STUDY AIMS: We evaluated the efficacy of transcatheter arterial embolization (TAE) in patients in whom endoscopic hemostasis of a massively bleeding duodenal ulcer failed. PATIENTS AND METHODS: TAE was performed in 11 patients with endoscopically uncontrollable massively bleeding duodenal ulcers, and the results and long-time outcome were studied. Two additional cases of failed endoscopic hemostasis were treated surgically without TAE. The entire group of 13 patients represented 5% of endoscopically treated duodenal ulcers and 0.6% of all cases with upper gastrointestinal bleeding who underwent emergency endoscopy (n = 2073). All but one of these 13 patients had concomitant disease. RESULTS: Arteriograms performed before TAE revealed extravasation of contrast material around the gastroduodenal artery (GDA), the anterior superior pancreaticoduodenal artery (ASPD), or the posterior superior pancreaticoduodenal artery (PSPD) in six of 11 cases. We failed to stop the bleeding in one patient, in whom only the common hepatic artery side of the GDA bleeding site was embolized; this patient died. TAE was successful in the other ten patients, in whom the long stretch of the GDA, including the ASPD and PSPD, was embolized around the bleeding site. Two surgically treated patients died within a week. CONCLUSIONS: Our findings indicate that TAE may induce hemostasis in 90% of patients with serious concomitant diseases who have endoscopically uncontrollable massive bleeding from duodenal ulcers.

Aged↗

PubMed1995

A compartmentalized bias for T-cell receptor V beta usage in summer-type hypersensitivity pneumonitis.

Several monoclonal antibodies specific to the human T-cell receptor (TCR) variable (V) region were used to examine whether T-cell oligoclonality plays a key role in the development of the T-cell-mediated lung disease, summer-type hypersensitivity pneumonitis (SHP). The usage of TCR V-regions was examined using bronchoalveolar lavage (BAL) and matched peripheral blood lymphocytes (PBL) in patients with SHP. In 18 SHP patients, the majority of lymphocytes in both BAL and PBL was CD3+ cells (94.2 vs. 63.9%, respectively), which was similar to that in normals (n = 7). Of CD3+ lymphocytes in a SHP patient, the percentage of CD4+ cells in BAL was reduced compared to those in paired PBL, whereas the percentage of CD8+ cells was significantly elevated. In contrast, the percentage of CD4+ cells was much higher than that of CD8+ cells in both BAL and PBL of normal subjects. While a majority of CD3+ T cells expressed TCR alpha/beta+ in BAL and PBL from both SHP patients and normal controls, a marked increase of the expression of TCR gamma/delta+ was observed in PBL in 4 out of 18 SHP patients. A markedly increased prevalence (> 3 SD) of specific TCR alpha/beta+ V-region families in BAL was detected in 5 of 18 patients with SHP as compared to normal controls, whereas no specific increase was found in PBL. Increased V beta 8 was detected in 3 cases; V beta 6 was observed in 1 patient, and V beta 5 in another patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Determination of a depolymerized holothurian glycosaminoglycan in plasma after intravenous administration by postcolumn HPLC.

Depolymerized holothurian glycosaminoglycan (DHG) produced artificially from sea cucumber has an anticoagulant and antithrombotic activity. In the present study, we attempted to determine the plasma level of DHG using a chemical procedure. A general method for determination of chondroitin sulfates by forming unsaturated disaccharides with chondroitinase digestion was difficult to apply to DHG, because it was resistant to any chondroitinase digestion. We therefore developed a highly sensitive postcolumn HPLC method for determination of intact DHG. DHG was applied to Asahipak NH2P-50, an amino-bonded column, eluted by alkaline solution and then detected with arginine under a strong alkaline condition as a postcolumn reagent. The limit of detection for DHG was 10 ng. The present method was applicable to the determination of DHG in plasma after intravenous administration.

Animals↗

PubMed1995

[Clinical evaluation of a recurrent mode after treatment in patients with small hepatocellular carcinoma].

A total of 96 patients with small hepatocellular carcinoma (HCC) with a maximal diameter of below 2 cm were analyzed according to recurrent factors and recurrent modes after the first treatment. In this study, recurrences were divided into two groups based on the style of recurrences provisionally: intrahepatic metastases (IM, 35 cases) and multicentric recurrences (MC, 22 cases). In patients with IM, the majority of recurrences were observed within 2 years after the first treatment and the primary HCC lesions had strong relation to the degrees of malignancy. On the other hands, there were no association with recurrent intervals and the degrees of malignancy, although the recurrent rate was high in patients with anti-HCV in MC group. The prognosis after the second treatment in MC group was superior to that in IM group (p < 0.05). These results indicate MC group have a good prognosis if early detection and the second accurate treatment are performed.

Aged↗

PubMed1995

Decreased expression of protein phosphatase type 2A in HL-60 variant (HL-60RAr) cells resistant to induction of cell differentiation by all-trans retinoic acid.

To evaluate the molecular basis for susceptibility of the cell differentiation induced by all-trans retinoic acid (ATRA), we examined biochemical activities and expression of protein phosphatases type 1 (PP1) and type 2A (PP2A) from HL-60 cells that are susceptible to differentiation induced by ATRA and HL-60RAr cells, HL-60 variant cells that are resistant to such induction. One nM of calyculin-A (CAL-A) achieved the enhancement of granulocytic differentiation in ATRA-treated HL-60 (1 microM) cells. ATRA exerted no differential action in HL-60RAr cells, but when used in combination with CAL-A, the differential activity was partly resumed at functional and phenotypic levels without change in morphology. The phosphatase activity in the cytosol from HL-60RAr cells was 50% of that from parental HL-60 cells, but the enzyme activities in either membrane or nuclear fractions showed similar values. The decreased phosphatase activity in the cytosol of HL-60RAr cells was mainly due to the decreased expression of the PP2A catalytic subunit. This low level of PP2A protein was reflected at a relative deficiency in expression of the PP2A beta gene in HL-60RAr cells. The exposure to 1 microM ATRA resulted in downregulation of PP2A catalytic subunit protein in HL-60 cells, but ATRA did not affect PP2A expression in HL60RAr cells. Both cell lines expressed the proteins of each PP1 catalytic subunit isozyme (i.e., PP1 alpha, PP1 gamma, and PP1 delta) at comparable levels. ATRA treatment had no effect on the levels of PP1 isozymes. Our results show a correlation between the extent of PP2A expression and the response of HL-60 and HL-60RAr cells to the differentiative effects of ATRA.

Blotting, Northern↗

PubMed1995

[The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous administration of glycyrrhizin for the patients with chronic liver disease caused by type C hepatitis virus].

Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.

Aged↗

PubMed1994

Expression of the catalytic and regulatory subunits of protein phosphatase type 2A may be differentially modulated during retinoic acid-induced granulocytic differentiation of HL-60 cells.

To elucidate the regulation of protein phosphatases types 1 (PP1) and 2A (PP2A) during all-trans retinoic acid (ATRA)-induced granulocytic differentiation of HL-60 cells, the phosphatase activity, proteins, and gene expressions of PP1 and PP2A were examined. Treatment with 1 microM ATRA caused an 85% decrease in the PP2A activity in extracts from HL-60 cells, while the PP1 activity was constant. This reduction in PP2A activity appeared to parallel phenotypic and functional changes of HL-60 cells induced by ATRA. Western blot analysis showed that the level of PP2A catalytic subunit (PP2A-C) decreased during the course of ATRA-induced differentiation, whereas expressions of A and B (M(r) 55,000) regulatory subunits of PP2A were relatively unaltered. Expressions of PP1 catalytic subunit isozymes (PP1 alpha, PP1 gamma, and PP1 delta) were not significantly affected by ATRA treatment. Northern blot analysis revealed that mRNA levels of PP2A-C beta and A alpha regulatory subunits were decreased following treatment with ATRA, while levels of PP2A-C alpha and B (M(r) 55,000) alpha regulatory subunit transcripts were relatively constant. Selective down regulation of PP2A-C beta preceded the granulocytic maturation induced by ATRA. Expressions of PP2A-C isoforms and A and B regulatory subunits may be differentially modulated during ATRA-induced granulocytic differentiation of HL-60 cells.

Blotting, Northern↗

PubMed1994

Mediation of the physiological response of platelets by interactions of spectrin and protein 4.1 with the cytoskeleton.

Spectrin and protein 4.1 became associated with the Triton-insoluble cytoskeletons during platelet activation. Inhibition of platelet activation by a PGI2 analogue resulted in release of the proteins from the cytoskeletons. Changes in subcellular distributions of the proteins preceded changes in the state of platelet aggregation. These results suggest that interactions of spectrin and protein 4.1 with the cytoskeletons are involved in mediating the physiological response of the platelet.

Actins↗

PubMed1994

Host factors required for internal initiation of translation on poliovirus RNA.

Translation of poliovirus RNA is initiated by entry of ribosomes into the nucleotide sequence (internal ribosomal entry site; IRES) within the 5'-untranslated region (5'-UTR). Efficiency of this translation initiation in rabbit reticulocyte lysates (RRL) was very low and was greatly enhanced by addition of the ribosomal salt-wash fraction (RSW) prepared from HeLa cells. This stimulating activity in the RSW was partially purified by gel-filtration column chromatography and its molecular weight was estimated to be higher than 240,000. Several proteins that bind specifically to the poliovirus IRES were detected in the active fraction. Among those, a 57 kDa protein, recognized by antibodies against polypyrimidide tract-binding protein (PTB), was found. In addition, La protein (52 kDa) which is a human antigen recognized by antibodies from patients with autoimmune disorders was also detected. Further purification on a hydroxylapatite column resulted in considerable loss of the stimulatory activity, accompanied by a reduction of the apparent molecular weight of active component(s). These results suggest that fully active HeLa cell stimulatory factors for the translation initiation on poliovirus RNA function in RRL as a large complex consisted of several components including PTB and La protein.

Acrylic Resins↗

PubMed1994

Role of laparoscopic cholecystectomy in treating gallbladder polyps.

Since the application of laparoscopic cholecystectomy (Lap C) to gallbladder polyps has not yet been fully evaluated, we performed Lap C on 26 patients with gallbladder polyps. Pathological examinations showed adenocarcinoma in three patients, adenoma in two, and cholesterol polyp in 21. Preoperative diagnoses of the cases with adenocarcinoma were a cholesterol polyp in one patient and an adenoma in two. Adenocarcinoma was confirmed to reside in the mucosa without any invasion of lymphatic ducts or small vessels in the three patients. This procedure was considered to be sufficient for this grade of cancer, and, therefore, no additional operations were performed. At present, our policy is to resect by Lap C a gallbladder polyp having a maximum size larger than 10 mm and a tendency to grow or presenting with suspicion of adenoma. When cancer is suspected by preoperative examinations, however, traditional surgery may be recommended.

Adenocarcinoma↗

PubMed1994

Forskolin potentiates G-CSF-induced proliferation of a murine myeloblastic leukemia cell line.

The role of the cAMP/A-kinase signaling pathway in G-CSF dependent proliferation of murine myeloblastic NFS-60 cells was investigated. G-CSF treatment resulted in a rapid and transient elevation of cAMP content of NFS-60 cells. G-CSF treatment of NFS-60 cells also resulted in the activation of A-kinase parallel to the increase in cAMP concentration. A low concentration (0.2-10 nM) of forskolin augmented the G-CSF-dependent cell proliferation, although forskolin by itself had no effect on NFS-60 cell growth. Forskolin did not affect the IL-3-induced proliferation of this cell line. Addition of forskolin resulted in further increases in the cAMP level, activation of A-kinase in NFS-60 cells stimulated by G-CSF. Proliferation of NFS-60 cells by G-CSF, but not by IL-3, was blocked by the axial diastereoisomer of adenosine 3',5'-phosphorothioate (Rp-cAMPS), a competitive cAMP antagonist. KT-5720(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexyloxy-8-methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2,7b, 11a-triazadibenzo(a,g) cycloocta(c,d,e)trinden-1-one), an A-kinase inhibitor, inhibited the G-CSF-dependent proliferation. These findings suggest that activation of the cAMP/A-kinase signaling pathway may be involved in G-CSF-mediated cell proliferation of NFS-60 cells, whereas IL-3-dependent proliferation is not mediated in such a manner.

Animals↗

PubMed1994

In situ islet cytokine gene expression during development of type I diabetes in the non-obese diabetic mouse.

Expression of cytokine genes in the islets of non-obese diabetic (NOD) female mice was examined. RNA samples were prepared from the islets and spleens of NOD mice at different time points at prediabetic stages during the natural disease process. Cytofluorometric analyses showed that the majority of lymphocyte infiltrates in the islets at 14 weeks of age consisted of T cells (68%). Of these, 80% of Thy1.2+ cells were CD4+ T cells. Less than 1% of in situ islet immune cells expressed a cell surface marker specific for the macrophage (Mac-1). Results of polymerase chain reaction using RNA (RT-PCR) prepared from spleens, and isolated and purified islets demonstrated that IFN-gamma message was detectable in the islets at 7 weeks of age (an early stage of insulitis). No message for this gene was detected in the spleen at any stage studied (7, 14 and 16 weeks of age). In contrast, TNF-alpha message was detected in both spleen and the islets at all stages, although the level of expression of TNF-alpha in the islets was much higher than that in the spleen. These results suggest that both cytokines are produced by in situ islet T cells, possibly activated T cells, which may be responsible for initiating or perpetuating autoimmune reactions in the islets.

Animals↗

PubMed1994

Calyculin A and okadiac acid inhibit human platelet aggregation by blocking protein phosphatases types 1 and 2A.

Two potent inhibitors of protein phosphatase type 1 (PP1) and type 2A (PP2A), calyculin A (CAL-A) and okadaic acid (OKA), inhibited human platelet aggregation induced by thrombin, collagen and 9,11-epithio-11,12-methano-thromboxane A2 (STA2). IC50 values of CAL-A and OKA for STA2-induced aggregation were 53 nM and 3.5 microM, respectively. These drugs also inhibited thrombin-induced [14C]serotonin secretion of platelets. CAL-A and OKA elicited phosphorylation of certain proteins with an apparent M(r) (x 10(-3) of 200, 60, 50 and 20 light chain of myosin (MLC). Agonist-induced 47,000 M(r) protein phosphorylation was strongly inhibited by these compounds, whereas phosphorylation of 20,000 M(r) MLC was enhanced. The increase in 50,000 M(r) protein phosphorylation by CAL-A and OKA was observed in the presence of agonists, and the 50,000 M(r) phosphorylation may be involved in the inhibition of platelet activation by these compounds. Subcellular analysis of the phosphatase activity in human platelets showed that MLC phosphatase activity was present mainly (approx. 78%) in the cytosolic fraction. Chromatography of human platelet extract on heparin-Sepharose resolved two peaks of MLC phosphatase activity: PP2A in 0.1 M NaCl eluate and PP1 in 0.5 NaCl eluate. PP2A and PP1 isozymes (PP1 alpha, PP1 gamma and PP1 delta) have also been identified in human platelets, by cross-reactivity with polyclonal antibodies against PP2A and PP1 isozymes, respectively. These results suggest that PP1 and/or PP2A may play an important role in the process of platelet activation by regulating levels of phosphorylation of certain proteins.

Blood Platelets↗

PubMed1994

[Clinical study of retreatment of chronic hepatitis C with interferon (IFN) for non-complete responders on initial treatment].

From August 1990 to May 1993, we treated 23 non-complete responders on initial treatment with interferon and studied the factor which affects the effectiveness in the attempt to verify the factors for the selection of patients who are to receive it. Complete response was achieved in 8 (34.8%) patients, while the other 15 patients did not achieve this degree of response. Three patients were of genotype II and 5 of genotype III in these 8 complete responders. All complete responders were patients with relapse who had had normalized serum ALT levels during the initial administration and undetectable HCV-RNA at the end of the period. No patient who failed to achieve normalization of the serum ALT level on initial treatment achieved a complete response on retreatment. HCV-RNA concentration before retreatment was significantly less than the one before initial treatment in 8 complete responders. Interferon retreatment of patients who do not achieve a complete response may be effective in relapsed cases with undetectable HCV-RNA at the end of initial treatment. Selection of patients to receive interferon retreatment requires careful review and consideration of genotype, HCV-RNA concentration, and the clinical response at initial treatment.

Adult↗

PubMed1994

Retreatment of chronic hepatitis C with interferon.

OBJECTIVE: We analyzed the retreatment of chronic hepatitis C with interferon to get the standpoint for the selection of patients to receive it. METHODS: A complete response was defined as continuous normalization of the serum alanine aminotransferase (ALT) level and continuous disappearance of serum hepatitis C virus RNA (HCV-RNA) during interferon administration and more than 6 months after. Patients without complete response were classified as noncomplete responders. From August 1990 to May 1993, we retreated 23 noncomplete responders on initial treatment with interferon and studied the factors that alter the effectiveness. RESULTS: Complete response was achieved in eight (34.8%) patients; the other 15 patients did not achieve this degree of response. Three patients were of genotype II and five were of genotype III in these eight complete responders. All complete responders were patients with relapse who had had normalized serum ALT levels during the initial administration and undetectable HCV-RNA at the end of the period. No patient who failed to achieve normalization of the serum ALT level on initial treatment achieved a complete response on retreatment. HCV-RNA concentrations before retreatment were significantly less than before initial treatment in the eight complete responders. CONCLUSION: Interferon retreatment of patients who do not achieve a complete response may be effective in relapsed cases with undetectable HCV-RNA at the end of initial treatment. Selection of patients to receive interferon retreatment requires careful review and consideration of genotype, HCV-RNA concentration, and the clinical response on initial treatment.

Alanine Transaminase↗