Biomedical subjects

H Yasuda

Publications and source records attributed to H Yasuda.

At least 217 records · Page 12Linked to original sources

PubMed1998

Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts.

Recent studies have demonstrated that ceramide plays an important role as a second messenger in many kinds of cells. However, it is not known whether apoptosis of and bone resorption by mature osteoclasts are mediated via sphingomyelinase (SMase) and ceramide. Thus, we examined the possible involvement of SMase and ceramide in the induction of apoptosis in and bone resorption by rabbit mature osteoclasts. SMase and C2-ceramide inhibited strongly F-actin ring formation of and bone resorption by the osteoclasts. However, the osteoclast apoptosis was not induced by C2-ceramide. The ceramide inhibition of the bone resorption was suppressed by DL-threodihydrosphingosine, an inhibitor of sphingosine kinase. In addition, we observed that sphingosine-1-phosphate is able to inhibit bone resorption by the osteoclasts. These results suggest an important role of the sphingomyelin pathway in bone resorption by rabbit mature osteoclasts.

Actins↗

PubMed1998

Establishment and characterization of an immortal macrophage-like cell line inducible to differentiate to osteoclasts.

Osteoclasts are hematopoietic cells essential for bone remodeling and resorption. To understand the process of osteoclast development, we established a macrophage-like cell line C7 that has the potential to differentiate into functional osteoclasts; multinuclear tartrate-resistant acid phosphatase positive cells capable of forming pits on dentin slices. C7 cells share the characteristics of their cell surface molecules and phagocytic activity with macrophages. Generation of osteoclasts from C7 cells was mostly suppressed by the addition of a function-blocking antibody directed to c-Fms, the receptor for macrophage-colony stimulating factor (M-CSF), or by osteoclastogenesis inhibitory factor (OCIF). These responses correspond well with the osteoclast precursors present in bone marrow and peritoneal cavity. Reagents such as bacterial lipopolysaccharide and granulocyte/macrophage-CSF that are known to act as inducers for other cell lineages rather than osteoclasts abolished the potential of osteoclastogenesis in C7 cells. These phenotypes of C7 cells have been stably maintained for more than 2 years. We believe that the cell line established in this study will provide an important tool for osteoclast biology.

Antibodies↗

PubMed1998

Preventive effects of the deleted form of hepatocyte growth factor against various liver injuries.

The effects of a naturally occurring deleted form of hepatocyte growth factor (HGF) on hepatic disorder were studied in various models of hepatic failure. The pretreatment of rats and mice with the deleted form of HGF prevented the liver injuries and coagulopathy induced by endotoxin, dimethylnitrosamine and acetaminophen and reduced the mortality due to hepatic dysfunction induced by these hepatotoxins. The concurrent administration of the deleted form of HGF also prevented the liver injury and hepatic fibrosis in mice treated with alpha-naphthylisothiocyanate and in rats treated with dimethylnitrosamine. Moreover, the deleted form of HGF normalized the results of the bromosulphalein-clearance test and ameliorated jaundice in rats with periportal cholangiolitic hepatopathy induced by alpha-naphthylisothiocyanate. The deleted form of HGF also reversed the coagulopathy in rats with hepatic disorder induced by dimethylnitrosamine or by 70% resection of cirrhotic liver (induced by carbon tetrachloride). In Long Evans cinnamon rats receiving vehicle, 20 out of 21 animals died within 4 days after the onset of jaundice. After infusion of the deleted form of HGF for 4 days, 7 out of 20 Long-Evans cinnamon rats survived. These results indicate that the deleted form of HGF could have therapeutic potency in patients with severe hepatic failure.

Animals↗

PubMed1998

Hyperalgesia and decreased neuronal nitric oxide synthase in diabetic rats.

To evaluate the role of nitric oxide synthase (nNOS) in the pathogenesis of diabetic neuropathy, we investigated nociception and nNOS expression in dorsal root ganglion (DRG) of rats with streptozocin-induced diabetes. Paw withdrawal threshold to noxious mechanical stimuli was decreased in both L-NAME-treated and diabetic rats. The number of NADPH-diaphorase positive neurons was significantly decreased in untreated diabetic compared with control rats. Decreased expression of nNOS protein was confirmed by immunoblotting. Insulin treatment completely prevented decreases in withdrawal threshold and nNOS expression. Cyclic GMP content paralleled nNOS expression in experimental animals. These results suggest that decreased nNOS-cGMP system in DRG may play a role in the pathogenesis of diabetic sensory neuropathy.

Animals↗

PubMed1998

The G protein beta5 subunit interacts selectively with the Gq alpha subunit.

The diversity in the heterotrimeric G protein alpha, beta, and gamma subunits may allow selective protein-protein interactions and provide specificity for signaling pathways. We examined the ability of five alpha subunits (alphai1, alphai2, alphao, alphas, and alphaq) to associate with three beta subunits (beta1, beta2, and beta5) dimerized to a gamma2 subunit containing an amino-terminal hexahistidine-FLAG affinity tag (gamma2HF). Sf9 insect cells were used to overexpress the recombinant proteins. The hexahistidine-FLAG sequence does not hinder the function of the beta1gamma2HF dimer as it can be specifically eluted from an alphai1-agarose column with GDP and AlF4-, and purified beta1gamma2HF dimer stimulates type II adenylyl cyclase. The beta1gamma2HF and beta2gamma2HF dimers immobilized on an anti-FLAG affinity column bound all five alpha subunits tested, whereas the beta5gamma2HF dimer bound only alphaq. The ability of other alpha subunits to compete with the alphaq subunit for binding to the beta5gamma2HF dimer was tested. Addition of increasing amounts of purified, recombinant alphai1 to the alphaq in a Sf9 cell extract did not decrease the amount of alphaq bound to the beta5gamma2HF column. When G proteins in an extract of brain membranes were activated with GDP and AlF4- and deactivated in the presence of equal amounts of the beta1gamma2HF or beta5gamma2HF dimers, only alphaq bound to the beta5gamma2HF dimer. The alphaq-beta5gamma2HF interaction on the column was functional as GDP, and AlF4- specifically eluted alphaq from the column. These results indicate that although the beta1 and beta2 subunits interact with alpha subunits from the alphai, alphas, and alphaq families, the structurally divergent beta5 subunit only interacts with alphaq.

Animals↗

PubMed1998

Comparison of quantitative coronary angiographic results after directional coronary atherectomy and balloon angioplasty of protected left main coronary stenosis.

We compared the angiographic and clinical outcomes after directional coronary atherectomy (DCA, 13 patients) with those after conventional balloon angioplasty (BA, 21 patients) in patients with protected left main coronary artery stenosis. The initial success rate was 100% in the DCA group and 81% (17 of 21) in the BA group. Restenosis was present in 2 of 11 patients in the DCA group and 9 of 16 patients in the BA group (18% vs. 56%, P < 0.05). DCA and BA improved a minimal lumen diameter. The initial gain after DCA was greater than that after BA. At follow-up, the minimal lumen diameter was larger and the percentage diameter stenosis was smaller in the DCA group than in the BA group. The late loss and loss index were equivalent in both groups. Compared with conventional BA, DCA in protected left main coronary artery stenosis is associated with a higher angiographic success rate and provides a wider luminal diameter with reduced incidence of restenosis.

Angioplasty, Balloon↗

PubMed1998

Administration of IL-4 prevents autoimmune diabetes but enhances pancreatic insulitis in NOD mice.

The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (NOD) mice whose T cells produced relatively low amounts of IL-4. However, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the number of CD45RBlowCD4+ T cells was significantly increased by in vivo administration of rIL-4. By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RBlowCD4+ T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infiltrate of the islets, and overt diabetes was prevented. On the other hand, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mice, all of the recipient mice became diabetic within 8 weeks after transfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the development of Th2-like autoreactive T cells in the islets.

Animals↗

PubMed1998

Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas: report of a case.

The unusual occurrence of an "inside-out" appendix reported here is a case of complete intussusception of the appendix of a 45-year-old woman with Peutz-Jeghers syndrome in whom the diagnosis of intussusception was made preoperatively. At laparotomy, the lead point of intussusceptum was revealed to be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion in the pancreas, and subsequent distal pancreatectomy revealed a cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and two duodenal Peutz-Jeghers syndrome polyps were found via intraoperative endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal wedge resection was performed for the adjoining jejunal polyps. One of the two duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the first report of complete intussusception of the appendix caused by a Peutz-Jeghers syndrome polyp.

Appendiceal Neoplasms↗

PubMed1998

[Reoperation for diffuse supravalvular aortic stenosis with Williams syndrome--extended patch aortoplasty and extra-anatomic bypass from the ascending aorta to the descending aorta in a median sternotomy].

A case of diffuse supravalvular aortic stenosis (SVAS) with Williams syndrome is reported. In this case of severe diffuse SVAS, we performed the diamond-patch aortoplasty in a child. However he has been suffering from residual SVAS. At 9-years old, the myocardial injury was noted by myocardial scintigraphy. Preoperative cardiac catheterization and angiography revealed the hypoplastic ascending aorta and arch with a pressure gradient of 89 mmHg at the distal site from the left subclavian artery. Through only a median stenotomy, an extended patch aortoplasty between the valsalva sinus and distal arch was performed and an extraanatomic bypass from the ascending aorta to the descending aorta was employed using a 10 mm tube graft. We realize this technique is available because this method can relieve the left ventriculus of the pressure load and operate via only median sternotomy.

Aorta↗

PubMed1998

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility.

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 x 10(5) cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing.

Antineoplastic Agents↗

PubMed1998

Localized contribution of N-methyl-D-aspartate receptors to synaptic input-induced rise of calcium in apical dendrites of layer II/III neurons in rat visual cortex.

To examine the role of N-methyl-D-aspartate receptors in the synaptic input-induced increase in Ca2+ in layer II/III neurons of visual cortex, Ca2+ imaging with a relatively low-affinity indicator was carried out simultaneously with whole-cell recordings of synaptic activity in cortical slices of young rats. Electrical stimulation of layer IV elicited excitatory postsynaptic potentials that generated action potentials concomitantly with a marked rise of Ca2+ signal in apical dendrites of 24 pyramidal cell-like neurons. Dendritic regions about 50 microm from the soma (peak regions) consistently showed the strongest increase in signal. The application of an N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovalerate, reduced the Ca2+ signal in peak regions but did not in other regions in nine of the 15 neurons tested. In all the dendritic regions in which Ca2+ signal was measured, the magnitude of the increase in signal was related linearly to the number of action potentials, suggesting that voltage-dependent Ca2+ channels activated by action potentials may also be involved in the increase. In 25 of 33 neurons which were voltage-clamped at 80 mV and perfused with the Mg2+-free solution, layer IV stimulation could induce a local rise in Ca2+ signal in apical dendrites. This rise was blocked by the N-methyl-D-aspartate receptor antagonist almost completely. Such an antagonist-sensitive Ca2+ rise was still seen even when the membrane potential was held at +10 mV when voltage-dependent Ca2+ channels were expected not to be activated by excitatory synaptic inputs. These results suggest that N-methyl-D-aspartate receptors are involved in the synaptic input-induced rise in Ca2+ at postsynaptic sites in apical dendrites of layer II/III neurons, and the increase may be boosted through voltage-dependent Ca2+ channels activated by action potentials.

Action Potentials↗

PubMed1998

Expression and activity of cyclin-dependent kinase 5/p35 in adult rat peripheral nervous system.

In spite of the clarification in the temporal and spatial expression pattern of a cyclin-dependent kinase (Cdk) 5 and its neuron-specific activator, p35, in the CNS, it remains to be elucidated in the PNS. In addition, it is not known whether Cdk5 activity exists in the PNS. Therefore, we have examined their expression and activity in the PNS by immunoblot analysis, immunohistochemistry, and in vitro kinase assay. Immunoblot analysis indicated the expression of Cdk5 and p35 proteins in dorsal root ganglion (DRG) and sciatic nerve alike in the CNS. By immunohistochemistry, both proteins were shown to be present in the cell body and axon (sciatic nerve) of both DRG neurons and anterior horn cells. A co-immunoprecipitation study indicated the in vivo association between Cdk5 and p35 in both DRG and sciatic nerve. However, Cdk5 kinase activity was found only in DRG, but not in sciatic nerve. These results suggest that Cdk5 kinase activity exists and functions physiologically in the PNS and may be regulated by unknown mechanisms other than the availability of p35 as reported in developing brains.

Animals↗

PubMed1998

Interactions of plaunotol with bacterial membranes.

Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of this compound with the bacterial cell membrane. The purpose of the present study was to confirm that plaunotol interacts with the H. pylori membrane. Membrane fluidities were measured using two stearic acid spin labels, namely 5-doxyl-stearic acid (in which the nitroxide group is located in the upper portion of the bacterial cell membrane) and 16-doxyl-stearic acid methyl ester (in which the nitroxide group is located deeper in the bacterial cell membrane), by means of electron spin resonance. The membrane fluidities of plaunotol-treated cells were significantly increased in the measurements made using the two spin labels. We also attempted to isolate plaunotol-resistant H. pylori in vitro by two different methods. To assess the level of resistance that could be reached, H. pylori was passaged five times on an agar plate containing subinhibitory concentrations of plaunotol or metronidazole. To measure the rate of development of resistance, H. pylori was grown with subinhibitory concentrations (0.25 x MIC) of plaunotol or metronidazole, and quantitatively plated on to medium containing 4 x MIC of the compounds. This treatment was repeated once more. No plaunotol-resistant colonies were selected by the two methods. H. pylori developed resistance to metronidazole easily and at a relatively high rate. The mechanism by which plaunotol directly fluidizes and destroys the H. pylori membrane might make it difficult for this organism to develop resistance to plaunotol. It was confirmed that the bactericidal effects of plaunotol were also shown against Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae. No such effect was seen against Escherichia coli and Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

PubMed1998

Current surgical trends in Japan for managing chronic pancreatitis.

The main aims of surgery for treating chronic pancreatitis are to relieve the patient's persistent pain and to preserve pancreatic functioning. The indications for surgery include treating complications, such as the presence of pancreatic pseudocysts or biliary stenosis associated with chronic pancreatitis or both. A resection, ductal drainage, or both, may commonly be required. Furthermore, some surgeons recommend pancreatic denervation. We analyze the details of 2,936 patients with chronic pancreatitis who were treated surgically and were listed in the 1985 National Statistics in Japan. We have also evaluated the present surgical methods for treating chronic pancreatitis in Japan. In addition, we discuss a new surgical method being used to treat chronic pancreatitis. This is a recently improved technique involving a complete duodenum-preserving resection of the head of the pancreas, which also preserves the biliary and alimentary tracts.

Chronic Disease↗

PubMed1998

Hepatocyte apoptosis and hepatic expression of transforming growth factor-beta1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor.

Hepatocyte apoptosis occurs during involution of hyperplastic liver induced by administration of xenobiotic compounds in rats. With this hyperplasia and involution, hepatic transforming growth factor (TGF)-beta1 is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-beta1 is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-beta1. When rats received an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h after the last injection to 140% of control. This DNA content was significantly decreased at 108 and 180 h after discontinuation of treatment. At 60 h after the last injection, the number of apoptotic bodies positive for nick end-labelling of DNA in hepatocytes was significantly greater in treated rats than in control rats. Hepatocyte apoptosis was also identified electron micrographically. Hepatic TGF-beta1 mRNA levels in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude that hyperplastic liver induced in normal rats by hepatocyte growth factor regresses with hepatocyte apoptosis and suppressed hepatic TGF-beta1 mRNA levels.

Animals↗

PubMed1998

Efficacy of CS-834 against experimental pneumonia caused by penicillin-susceptible and -resistant Streptococcus pneumoniae in mice.

The efficacy of CS-834, a novel oral carbapenem, was assessed by using a murine model of pneumonia caused by penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and was compared with those of oral cephems, i.e., cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil. Intranasal inoculation of 10(6) CFU of penicillin-susceptible or penicillin-resistant S. pneumoniae in the exponential growth phase induced pneumonia and bacteremia in ddY mice within 48 h. For the treatment of infections caused by the penicillin-susceptible strain the antibiotics were administered orally at 0.4, 2, and 10 mg/kg of body weight twice daily for 2 days beginning at 24 h after bacterial inoculation, and for the treatment of infections caused by a penicillin-resistant strain the antibiotics were administered at 2, 10, and 50 mg/kg twice daily for 2 days beginning at 24 h after bacterial inoculation. Among the antibiotics tested, CS-834 exhibited the most potent efficacy against both types of strains. Against infections caused by penicillin-susceptible S. pneumoniae, CS-834 at all doses significantly reduced the numbers of viable cells in both the lungs and blood. Cefpodoxime proxetil at all doses and cefteram pivoxil and cefditoren pivoxil at doses of 2 and 10 mg/kg showed comparable efficacies. Against infections caused by penicillin-resistant S. pneumoniae, CS-834 at doses of 10 and 50 mg/kg showed the most potent efficacy among the antibiotics tested, resulting in the maximum decrease in the numbers of viable cells in the lungs. Comparable efficacies were observed with cefteram pivoxil and cefpodoxime proxetil at doses of 50 mg/kg each. The concentration of CS-834 in the lungs and blood was higher than that of cefdinir and was lower than those of the other antibiotics tested, suggesting that the potent therapeutic efficacy of CS-834 reflects its strong activity against S. pneumoniae.

Animals↗

PubMed1998

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

Amino Acid Sequence↗

PubMed1998

Percutaneous revascularization of lesions with saphenous vein graft failure: influence of chronic total occlusion on early outcome.

The purpose of this study was to evaluate a therapeutic strategy of percutaneous transluminal coronary angioplasty (PTCA) in patients with recurrent angina following coronary artery bypass grafting. The study looked at 112 branches associated with graft failure, excluding new lesions in the native coronary artery (NCA). Chronic total occlusion (CTO) was observed in 50% of NCA (56/112) and in 68% of the grafts (76/112). Thirty-three branches (29%) showed CTO in both NCA and the graft. The overall success rate was 86% (96/112). The success rate on NCA was 98% (44/45) in non-CTO, while in CTO it was significantly lower at 62% (18/29). As to grafts, the success rate was 94% (32/34) in non-CTO, while it was 50% (2/4) in CTO. These characteristics, with respect to lesion morphology and the prevalence of CTO, exerted an influence on the selection of the access vessels for revascularization. Early outcome depended on the result of treatment of CTO.

Acute Kidney Injury↗