Biomedical subjects

Y Naito

Publications and source records attributed to Y Naito.

At least 91 records · Page 5Linked to original sources

PubMed2000

Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases.

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-deoxy-Delta(12,14)-PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class pi GST isozyme (GSTP1) by 15-deoxy-Delta(12,14)-PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-Delta(12, 14)-PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-Delta(12, 14)-PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-O-tetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-Delta(12, 14)-PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-Delta(12,14)-PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results suggest that 15-deoxy-Delta(12,14)-PGJ2 induces the expression of the rat GSTP1 gene through binding of proteins, including c-Jun, to a specific GPEI.

Animals↗

PubMed2000

Requirements for alternative forms of the activator domain, P5abc, in the Tetrahymena ribozyme.

The role of P5abc domain of the Tetrahymena LSU self-splicing Group I intron is to enhance the activity of the intron via tertiary interactions involving A-rich bulge and terminal loops L5b and L5c. We constructed and examined alternative forms of the domain that accelerate the ribozymatic reaction. The results indicate that the characteristic structure of P5c subdomain plays an important role by forming L2xL5c interaction (P14) and that the region flanking P5c subdomain can be significantly mutable without much affecting the activity of the ribozyme.

Animals↗

PubMed2000

Three-component coupling of acylphosphonates and two carbonyl compounds promoted by low-valent samariums: one-Pot synthesis of beta-hydroxyphosphonates

Three-component coupling of acylphosphonates and two carbonyl compounds leading to beta-hydroxyphosphonates has been achieved with low-valent samariums. Thus, acylphosphonates reacted with aldehydes in the presence of semicatalytic amounts of samarium metal or SmI(2) to give acyloxyphosphonates in good yields. The second coupling reaction of the acyloxyphosphonates with aldehydes or ketones promoted by SmI(2) afforded beta-hydroxyphosphonates instead of olefins. Moreover, these two reactions could be carried out in one pot.

Journal Article↗

PubMed2000

Alpha-tocopherol protects against monocyte Mac-1 (CD11b/CD18) expression and Mac-1-dependent adhesion to endothelial cells induced by oxidized low-density lipoprotein.

Alpha-tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of alpha-tocopherol on expression of Mac-1 (CD11b/CD18) by monocytes after stimulation with oxidized low-density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 microg/ml) increased Mac-1 expression on monocytes, and preincubation with alpha-tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of alpha-tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 microg/ml). There was a decrease in the upregulation of Mac-1 compared with that measured before administration. Adherence of oxidized LDL-stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with alpha-tocopherol, and was also inhibited by an anti-CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac-1 upregulation by alpha-tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, alpha-tocopherol suppressed the upregulation of Mac-1 expression on monocytes by oxidized LDL.

Adult↗

PubMed2000

Inhibition of angiotensin-converting enzyme protects endothelial cell against hypoxia/reoxygenation injury.

Cardiovascular tissue injury in ischemia/reperfusion has been shown to be prevented by angiotensin-converting enzyme (ACE) inhibitors. However, the mechanism on endothelial cells has not been assessed in detail. Cultured human aortic endothelial cells (HAEC) were exposed to hypoxia with or without reoxygenation. Hypoxia enhanced apoptosis along with the activation of caspase-3. Reoxygenation increased lactate dehydrogenase release time-dependently, along with an increase of intracellular oxygen radicals. ACE inhibitor quinaprilat and bradykinin significantly lessened apoptosis and lactate dehydrogenase release with these effects being diminished by a kinin B2 receptor antagonist and a nitric oxide synthase inhibitor. In conclusion, hypoxia activated the suicide pathway leading to apoptosis of HAEC by enhancing caspase-3 activity, while subsequent reoxygenation induced necrosis by enhancing oxygen radical production. Quinaprilat could ameliorate both apoptosis and necrosis through the upregulation of constitutive endothelial nitric oxide synthase via an increase of bradykinin, with the resulting increase of nitric oxide.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Bisphosphonate therapy for bone metastases from breast cancer: clinical results and a new therapeutic approach.

BACKGROUND: We evaluated the usefulness of bisphosphonate (BIS) monotherapy, the safety of rapid infusion of BIS and the efficacy of BIS-sequential therapy for bone metastases from breast cancer. PATIENTS AND METHODS: Twenty-nine patients with bone metastasis or invasion were treated with BIS monotherapy. Each BIS (pamidronate 30 mg, alendronate 10 mg, or incadronate 10 mg) was infused over 30 minutes every two weeks a median of 12 times. RESULTS: With BIS therapy, five patients (17%) showed partial response of the bone lesions, and eighteen patients (64%) had pain relief. Of the nine patients treated with BIS-sequential therapy, one (11%) showed a partial response of the bone metastases, three (33%) had pain relief, and one (11%) showed a decrease in the serum tumor marker level. CONCLUSION: BIS therapy is effective against bone metastases from breast cancer, and rapid infusion of BIS is both safe and convenient for patients. BIS-sequential therapy can be a unique therapeutic option in some cases.

Adult↗

PubMed2000

Ductal aneurysm of adult patients.

A ductal aneurysm is very rarely diagnosed in adults. We experienced 2 cases of adult ductal aneurysm. Both cases developed hoarseness and computed tomographic scanning demonstrated a typical 'triple star sign' at the aortopulmonary window level. They underwent surgical repair with successful results. During the same period, we experienced 38 operations for true thoracic aneurysm. The ductus origin was found in 5.2% of these patients. The ductal aneurysm may no longer be considered a 'rare' vascular disease with more careful diagnostic procedure.

Aged↗

PubMed2000

St. Jude Medical prosthetic aortic valve malfunction due to pannus formation.

According to the literature, the incidence of pannus formation with the St. Jude Medical prosthetic aortic valve has been reported at 0.03% and 0.14% (per patient-year), with no case report of St. Jude Medical prosthetic aortic valve malfunction due to pannus formation. Between 1980 and 1999, 1,186 patients underwent aortic valve replacement at our institute. We encountered 2 aortic valve malfunctions due to pannus formation, including the case of a 53-year-old woman who suffered a St. Jude medical aortic valve malfunction 13 years after the initial operation. A second aortic valve replacement was successful and the postoperative course was uneventful. The possibility of pannus formation on St. Jude Medical aortic valves must thus be considered and its mechanism clarified.

Aortic Valve↗

PubMed2000

Autologous blood donation with recombinant human erythropoietin for abdominal aortic aneurysm surgery.

We evaluated the efficacy of autologous blood donation using recombinant human erythropoietin for elective abdominal aortic aneurysm (AAA) surgery regarding postoperative recovery. Twenty-five AAA patients who completed surgery without receiving a homologous blood transfusion were divided into two groups, consisting of a control group (n = 12) who did not bank any autologous blood, and a donation group (n = 13) who did bank more than 800 ml of autologous blood with the use of erythropoietin. The hematocrit (Ht) level of the control group decreased from 41.1% +/- 1.2% before the operation to 36.2% +/- 0.9% just afterwards (P > 0.01). In the donation group, however, the Ht did not change significantly during either the donation period or the perioperative period. The postoperative period before oral food intake and natural defecation were both significantly shorter in the donation group than in the control group. The first day of mobilization was also earlier in the donation group. In conclusion, autologous blood donation using erythropoietin for AAA surgery is therefore considered to promote the early recovery of patients.

Aged↗

PubMed2000

Thirteen-week dietary intake of rapeseed oil or soybean oil as the only dietary fat in Wistar Kyoto rats-change in blood pressure.

Wistar Kyoto (WKY) rats were fed a diet containing 10% rapeseed (canola) oil or soybean oil as the only dietary fat for 13 weeks. From week 5 of feeding, systolic blood pressure of the canola oil group became higher than that of the soybean oil group. The 13-week canola oil intake increased plasma levels of Na(+) and lipids, and decreased the level of K(+) compared to those in the soybean oil group. The canola oil group also showed a high density of neutrophils and a low density of platelets compared to the soybean oil group. Moreover, the activities of catalase and superoxide dismutase in the hepatic cytosol were depressed in the canola oil group. The mechanisms for the higher blood pressure are unclear. However, an increase in body fluid via activation of Na(+) pump or Na(+), K(+)-ATPase and/or a blunt endothelium-dependent vasodilation by increased superoxide might have relevance to the elevated blood pressure. The increased plasma lipids and the changes in the densities of platelets and neutrophils appear not to be critical in WKY rats. However, these would tend to promote peripheral vascular lesions in the strains, such as spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats, which are prone to present atheroscrelotic vascular injury.

Animals↗

PubMed2000

Increased cortical activation during hearing of speech in cochlear implant users.

To investigate the cortical activities while listening to noise and speech in cochlear implant (CI) users, we compared cerebral blood flow in postlingually deafened CI users with that in normal hearing subjects using positron emission tomography. While noise activation in CI users did not significantly differ from that in normal subjects, hearing speech activated more cortical areas in CI users than in normal subjects. A comparison of speech activation in these two groups revealed higher activation in CI users not only in the temporal cortices but also in Broca's area and its right hemisphere homologue, the supplementary motor area and the anterior cingulate gyrus. In postlingually deafened subjects, the hearing of speech coded by CI may be accompanied by increased activation of both the temporal and frontal cortices.

Adult↗

PubMed2000

Functional differentiation of the auditory association area in prelingually deaf subjects.

BACKGROUND: it is believed that the number of neurons of the human cortex increases rapidly in the first postnatal year, and then decreases gradually towards adult level as their functions are revised up to 11 years of age ('synaptic revision'). It is also confirmed that regional cerebral blood flow (rCBF) at rest represents the density of the neurons and decreases in accordance with the synaptic revision in process. If synaptic revision does not occur, rCBF remains at high level. Thus, we can evaluate whether functional differentiation has occurred in the human cortex by measuring rCBF at resting state. OBJECTIVE: to examine functional differentiation of the auditory association area (A2) in prelingually deaf subjects. METHODS: six postlingually and six prelingually deaf subjects who had undergone cochlear implant (CI) were involved in the current study. All prelingually deaf subjects underwent CI over 8 years old. The rCBF in A2 was examined during resting and listening to speech sounds using positron emission tomography (PET) and H2(15)O intravenous injection. Twelve normal subjects' rCBFs were also measured as control. Furthermore, three prelingually deaf subjects underwent follow up PET studies in which cortical activities in A2 for listening and lipreading were examined. RESULTS: in the examination of rCBF at rest, rCBFs of prelingually deaf subjects in A2 showed significantly higher than those of either the postlingually deaf subjects or normal subjects. During listening, rCBFs in A2 increased in postlingually deaf subjects and normal subjects, while there was no significant rCBF increase in the prelingually deaf. High rCBF level in A2 at rest observed in prelingually deaf subjects implied a lack of synaptic revision, and it was suggested that the functional differentiation for auditory processing was little in the A2 of prelingually deaf subjects. In the follow up study for three prelingually deaf subjects, activation of A2 was observed during lipreading but not during listening in two cases, who had developed the skill of lipreading while speech recognition was not improved by CI. In contrast, the other case had not used any visual clues in daily communication prior to CI, and the hearing acuity was well improved by CI. This case demonstrated an activity in A2 during listening, while lipreading induced no activation. CONCLUSION: it is suggested that functional differentiation of A2 should differ according to which of visual and auditory clue is chiefly used during critical periods for speech acquisition. The findings are thought to be important for us to schedule the education and treatment for prelingually deaf children.

Adolescent↗

PubMed2000

Effect of vitamin E on aspirin-induced gastric mucosal injury in rats.

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of alpha-tocopherol (vitamin E-deficient), 2 mg/100 g of alpha-tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of alpha-tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCI created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.

Animals↗

PubMed2000

A new mechanism for anti-inflammatory actions of proton pump inhibitors--inhibitory effects on neutrophil-endothelial cell interactions.

BACKGROUND: Neutrophil-endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal inflammation associated with Helicobacter pylori or nonsteroidal anti-inflammatory drugs. AIM: To investigate the effects of proton pump inhibitors and histamine-2 receptor antagonists (HRA) on neutrophil-endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin-1beta (IL-1beta). METHODS: Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibitors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Neutrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were assessed by flow cytometry and an enzyme immunoassay, respectively. Neutrophil adherence was defined as the ratio of exogenous neutrophils that adhered to the endothelial monolayers. RESULTS: The expression of CD11b and CD18 on neutrophils and neutrophil-dependent adhesion to endothelial cells elicited by HPE were inhibited by lansoprazole and omeprazole at clinical relevant doses, and the expression of ICAM-1 and VCAM-1 on endothelial cells and endothelial-dependent neutrophil adherence induced by IL-1beta were also inhibited by lansoprazole and omeprazole at similar doses. Famotidine and ranitidine had no effect on neutrophil-endothelial cell interactions. CONCLUSIONS: These results indicate that proton pump inhibitors can attenuate neutrophil adherence to endothelial cells via inhibiting the expression of adhesion molecules, suggesting that proton pump inhibitors may have anti-inflammatory activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2000

Protective role of intracellular glutathione against nitric oxide-induced necrosis in rat gastric mucosal cells.

BACKGROUND: Nitric oxide synthase activity is increased in the stomach in association with Helicobacter pylori infection and portal hypertension, but the mechanism by which nitric oxide contributes to mucosal damage remains unclear. AIM: To examine whether nitric oxide injures gastric mucosal cells and whether cellular glutathione affects nitric oxide-induced cytotoxicity. METHODS: A confluent monolayer of RGM-1 gastric mucosal cells was exposed to nitric oxide donors (NOC5 or NOC12). Cell viability was determined by trypan blue dye exclusion, lactate dehydrogenase release and supravital staining with Hoechst 33342 and propidium iodide. The kinetics of the reduced/oxidized forms of glutathione were also measured, as well as the effect of glutathione-depletion or glutathione-precursor treatment on nitric oxide-induced cytotoxicity. RESULTS: Excess exogenous nitric oxide produced by NOC5 or NOC12 induced necrosis in RGM-1 cells in a time- and concentration-dependent manner. The level of reduced glutathione drastically decreased prior to the loss of cell viability and remained low, but oxidized glutathione was not affected. Glutathione depletion increased necrosis of both NOCs in an NOC-concentration-related fashion, while pre-treatment with gamma-glutamylcysteine ethyl ester reduced their necrotic susceptibility. CONCLUSION: Exogenous nitric oxide induced necrosis in gastric mucosal cells, and intracellular reduced glutathione protects gastric mucosal cells from damage by nitric oxide.

Animals↗

PubMed2000

The role of neutrophils and inflammation in gastric mucosal injury.

Gastric inflammation is a highly complex biochemical protective response to cellular/tissue injury. When this process occurs in an uncontrolled manner, the result is excessive cellular/tissue damage that results chronic inflammation and destruction of normal tissue. Current evidence suggests that Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) ingestion are major causative factors in the pathogenesis of gastric mucosal injury in humans. In response to H. pylori infection or NSAID, neutrophils are recruited to the site of inflammation and generate reactive oxygen and nitrogen species and proteases. However, neutrophils are not able to kill the bacteria that live in the gastric mucus, and compounds produced by activated neutrophils themselves may be potentially harmful for normal tissue. It has been shown that leukocyte-vascular endothelial cell interaction is regulated by various cell adhesion molecules, and that this interaction is directly or indirectly modified by many factors, the origin of which is H. pylori and NSAIDs. This review describes the potential role of neutrophils and neutrophil-associated inflammation for gastric oxidative stress and injury induced by H. pylori and/or NSAID.

Animals↗

PubMed2000

Evolution of sequence recognition by restriction-modification enzymes: selective pressure for specificity decrease.

Several type II restriction-modification (RM) gene complexes kill host bacterial cells that have lost them, through attack on the chromosomal recognition sites of these cells. Two RM gene complexes recognizing the same sequence cannot simultaneously enjoy such stabilization through postsegregational host killing, because one will defend chromosomal sites from attack by the other. In the present work, we analyzed intrahost competition between two RM gene complexes when the recognition sequence of one was included in that of the other. When the EcoRII gene complex, recognizing 5'-CCWGG (W = A, T), is lost from the host, the SsoII gene complex, which recognizes 5'-CCNGG (N = A, T, G, C), will prevent host death by protecting CCWGG sites on the chromosome. However, when the SsoII (CCNGG) gene complex is lost, the EcoRII (CCWGG) gene complex will be unable to prevent host death through attack by SsoII on 5'-CCSGG (S = C, G) sites. These predictions were verified in our experiments, in which we analyzed plasmid maintenance, cell growth, cell shape, and chromosomal DNA. Our results demonstrate the presence of selective pressure for decrease in the specificity of recognition sequence of RM systems in the absence of invading DNA.

Cell Division↗

PubMed2000

Paclitaxel-induced remission in docetaxel-refractory anthracycline-pretreated metastatic breast cancer.

Paclitaxel and docetaxel are excellent agents with a high antitumor effect for the treatment of previously anthracycline-exposed metastatic breast cancer. There has been no standard treatment for patients who undergo therapy of a taxan-resistant metastatic breast cancer. Paclitaxel has partial non-cross-resistance in vitro with docetaxel in inhibiting microtubule disaggregation. We present the case of a patient with docetaxel-refractory anthracycline-pretreated metastatic breast cancer who achieved remission with paclitaxel.

Adult↗