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Biomedical subjects

Y Takehara

Publications and source records attributed to Y Takehara.

At least 19 recordsLinked to original sources
PubMed1995

Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent.

We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide (O2.-) generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herb Hypericin triquetrifolium Turra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on stimulation-dependent O2.- generation and related enzymes of neutrophils were investigated. Hypericin inhibited O2.- generation of neutrophils induced by PKC-dependent and -independent stimuli in a light- and concentration-dependent manner. Oxygen was required for the light-dependent inhibition by hypericin. NADPH oxidase activity in a cell-free system and TNF-alpha-induced tyrosyl phosphorylation of neutrophil proteins were also inhibited by hypericin in a concentration- and light-dependent manner. However, tyrosine kinase of p60src, an enzyme not bound to a membrane, was not inhibited either in the light or in the dark. Oxygen uptake of neutrophils by photosensitization with hypericin resulted in the formation of singlet oxygen (1O2), O2.-, and hydroxyl radical (.OH) and enhanced lipid peroxidation. The formation of 1O2 was inhibited by azide, a quencher of 1O2, but not by desferrioxamine (DSF), a ferric ion chelator. By contrast, both generation of .OH and lipid peroxidation were inhibited by DSF but not by azide. Furthermore, PMA-induced O2.- generation inhibited by hypericin partially recovered in the presence of azide but not DSF. These results suggested that the light-dependent inhibition of O2.- generation by hypericin might be due to inhibition of tyrosine kinase, PKC, and NADPH oxidase via an oxygen-dependent mechanism, possibly through both Type I and II photosensitization mechanisms.

Anthracenes↗
PubMed1995

Oxygen-dependent regulation of mitochondrial energy metabolism by nitric oxide.

To elucidate the role of nitric oxide (NO) in the regulation of mitochondrial function, the effect of NO on energy transfer reactions was examined under different oxygen tensions. Mitochondrial respiration was remarkably inhibited by NO resulting in the inhibition of ATP synthesis in a concentration-dependent manner. In the presence of succinate, respiration, respiratory control by ADP, and ATP synthesis recovered completely at certain times after adding NO. The inhibitory action of NO continued significantly longer under physiologically low oxygen concentrations (such as the cytosolic level) than at high concentrations. In the presence of various substrates, such as pyruvate malate, succinate, and ascorbate tetramethyl paraphenylenediamine, NO also inhibited the uncoupled respiration in an oxygen- and concentration-dependent manner. The inhibition of respiration by NO was stoichiometrically suppressed by oxyhemoglobin. When added to a mitochondrial suspension, NO rapidly disappeared from the medium particularly at high oxygen tension. However, the rate of NO disappearance was significantly lower under low oxygen tension. Thus, under cytosolic oxygen concentration, NO might play an important role in the regulation of mitochondrial energy metabolism.

Adenosine Triphosphate↗
PubMed1995

Effect of the antiretroviral agent hypericin on rat liver mitochondria.

The photosensitizing effect of hypericin (HY), an antiretroviral agent, on the functions of isolated rat liver mitochondria has been investigated. The respiratory control ratio (RCR), ADP/O and membrane potential of mitochondria were decreased by HY in a light-dependent manner. Uncoupled respiration of mitochondria in the presence of succinate was also inhibited by HY in a light-dependent manner. The ID50 of hypericin for these inhibitions was approximately 0.5 microM. These inhibitory effects of HY were not observed when photosensitization was conducted under anaerobic conditions and were not affected by desferrioxamine (DSF) or superoxide dismutase (SOD). Upon photosensitization of HY, mitochondria consumed oxygen in the absence of respiratory substrate with concomitant formation of thiobarbituric acid reactive substance (TBARS). The amount of oxygen consumed was 100-times greater than that of TBARS formed. The oxygen uptake was partially inhibited by NaN3, and formation of TBARS was inhibited by DSF. Upon photosensitization of HY in the presence of mitochondrial membranes, the electron spin resonance (ESR) signal of 2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxyl (DMPO/.OH) was increased by a mechanism which was suppressed by DSF. An ESR signal for singlet oxygen bound to 2,5-dimethylfuran, 2,2,6,6-tetramethyl-4-piperidone (TEMP) was also detected under light in the presence of mitochondria. This signal of the TEMP-N-oxyl radical (TEMPO) was decreased by azide, which physically quenches singlet oxygen, but was increased by DSF. These results indicate that HY might inhibit mitochondrial functions by a type II photodynamic mechanism but that lipid peroxidation of biological membranes through an active oxygen-mediated photodynamic mechanism is not involved.

Animals↗
PubMed1995

Benign renal tumors detected among healthy adults by abdominal ultrasonography.

Renal ultrasonography was performed on 17,941 healthy adults without any signs suggestive of urinary tract malignancies. Diffusely hyperechoic renal masses indicative of angiomyolipoma were found in 41 (0.23%) of them and those with echogenic image suggestive of renal cell carcinoma in 45 (0.25%). Final diagnosis of the former group included 24 angiomyolipoma, 1 renal cell carcinoma, 9 calculus and 7 normal variants. The latter group included 19 renal cell carcinomas, 1 leiomyoma, 1 cavernous hemangioma and 24 normal variants or cysts. In total, 24 (0.13%) angiomyolipomas, 20 (0.11%) renal cell carcinomas, 1 leiomyoma, and 1 cavernous hemangioma were discovered. The results indicate that asymptomatic benign renal tumors mainly consisting of angiomyolipoma are not uncommon.

Adult↗
PubMed1995

Inhibition of stimulus-specific neutrophil superoxide generation by alpha-tocopherol.

Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of alpha-tocopherol, inhibited the superoxide (O2-.) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myrisate 13-acetate (PMA). ID50 for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1microM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 microM). The alpha-tocopherol sensitive O2-. generation was also observed in neutrophils induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by alpha-tocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The alpha-tocopherol content of RPMN was 12 ng/10(6) cells and a linear increase to 200 ng/10(6) cells by addition of alpha-tocopherol to the cell suspension corresponded with an increased inhibition of O2-. generation. These results indicate that both the chemical structure and the content of alpha-tocopherol might be important factors in O2-. generation by neutrophils.

Animals↗
PubMed1995

[Enhanced delineation of the pancreatic duct in MR cholangiopancreatography (MRCP) with a combined use of secretin].

Magnetic resonance cholangiopancreatography (MRCP) is a method that can depict the main pancreatic duct non-invasively; however, its tendency to overestimate ductal stenosis is being noted. The authors used secretin to stimulate the output of pancreatic juice, which increased the signal of the main pancreatic duct and consequently minimized the occurrence of pseudostenosis artifacts in MRCP. MRCP images of 54 patients suspected of having pancreatic disease were visually evaluated by two observers before and after administration of secretin (1 clinical unit/kg). Improved delineation of the main pancreatic duct (68.5-59.3%, p < 0.05) and its side branches (40.7-29.6%, p < 0.05) was obtained with good interobserver agreement (kappa = 0.71-0.68).

Aged↗
PubMed1994

Dysfunction of mouse liver mitochondria induced by 2,2'-azobis-(2-amidinopropane) dihydrochloride, a radical initiator, in vitro and in vivo.

Mouse liver mitochondria were uncoupled in a time dependent by intraperitoneal injection of a radical initiator, 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) (100 mg/kg). State 3 respiration, ADP/O ratio and respiratory control ratio (RCR) were decreased 30 min after injection but there was no effect on state 4 respiration. Lipid peroxidation was increased and oxidative phosphorylation was uncoupled at one hr after drug injection but gradually recovered to normal levels after 14 hr in vivo. State 3 respiration, RCR and ADP/O ratio but not state 4 respiration of isolated mouse mitochondria were inhibited by short term incubation with AAPH in vitro. This inhibitory action was concentration dependent (ID50 = 5 mM) but was not prevented by alpha-tocopherol. AAPH had no effect on electron transport or the membrane potential of these isolated mitochondria. However, mitochondria were uncoupled via lipid peroxidation and swelling by long term incubation with AAPH. These inhibitory effects of AAPH were reduced by its spontaneous degradation not only in vitro but also in vivo. Thus AAPH induces mitochondrial dysfunction by direct action in the early period of treatment and free radicals produced from AAPH mediate mitochondrial swelling via lipid peroxidation in the late period. From these findings, it is concluded that mitochondrial phosphorylation plays an important role in the pathogenesis of liver injury induced by AAPH and that radicals generated by AAPH might be a source of liver injury and mitochondrial dysfunction in vivo.

Amidines↗
PubMed1994

DNA damage by various forms of active oxygens and its inhibition by different scavengers using plasmid DNA.

The degree of DNA damage by the treatment with various molecular species of active oxygen and its inhibition by pretreatment with different scavengers were evaluated using pUC19 plasmid DNA. DNA damage caused by O2-. generated by xanthine-xanthine oxidase system (X-XOD), .OH by Fenton reactions, and OCl- by NaOCl involved the generation of open circle DNA demonstrating single strand breaks. Catalase (Cat), diethylenetriaminepentaacetic acid (DETAPAC), desferroxiamine (Desferal), dimethyl sulfoxide (DMSO) and ethanol (EtOH) all inhibited 60-80% of DNA damage by the generated O2-.. Superoxide dismutase (SOD) inhibited all DNA damages by O2-.. Cat, DETAPAC and Desferal effectively inhibited DNA break by .OH; complete inhibition of .OH-induced DNA break was achieved by addition of DMSO and EtOH. Desferal and EtOH completely inhibited DNA damage by OCl-. These findings suggested that metal ions are associated with the mechanism of DNA damage by all forms of active oxygen species.

DNA Damage↗
PubMed1994

Expression of antral gastrin and somatostatin mRNA in Helicobacter pylori-infected subjects.

OBJECTIVES: We investigated the gene expression of antral gastrin and somatostatin in Helicobacter pylori-infected subjects. Twelve asymptomatic men with normal endoscopic findings participated in this study, four of whom were infected with H. pylori. METHODS: Biopsy specimens of the gastric mucosa were obtained after subjects had fasted overnight. Serum gastrin levels, antral gastrin and somatostatin content, and antral G- and D-cell densities also were measured. RESULTS: Fasting serum gastrin levels were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. There were no differences between groups in antral gastrin content, G-cell density, or gastrin mRNA levels. Antral somatostatin content, D-cell density, somatostatin mRNA levels, and the somatostatin mRNA:D-cell density ratio were significantly decreased in H. pylori-positive subjects. CONCLUSIONS: Our results suggest that in addition to reduced antral D-cell density, a suppression of somatostatin synthesis in D-cells may have contributed to the decrease in antral somatostatin in H. pylori-infected subjects.

Adult↗
PubMed1993

Reversible priming and protein-tyrosyl phosphorylation in human peripheral neutrophils under hypotonic conditions.

Hypotonic shock enhanced both formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide (O2-.) generation and tyrosyl phosphorylation of cellular proteins including 120-, 115-, 83-, 63-, and 54-kDa proteins of human peripheral neutrophils. The time course of the enhancement correlated with that of tyrosyl phosphorylation of the 115-kDa protein. The "primed state" was reversed to the nonprimed resting state by changing the conditions from hypotonic to isotonic, with a concomitant decrease in tyrosyl phosphorylation. Genistein inhibited the increase in both O2-. generation and tyrosyl phosphorylation of the 120-, 115-, 63-, and 54-kDa proteins. These results suggest the involvement of tyrosyl phosphorylation of a cellular protein(s) in hypotonic shock-induced priming of neutrophils.

Amino Acid Sequence↗
PubMed1992

Case report: MR appearance of a retained surgical sponge.

A case of a retained surgical sponge found in the retroperitoneum is presented with findings on magnetic resonance (MR) imaging, computed tomography (CT), ultrasonography (US) and angiography. Among all the performed modalities, a characteristic internal structure of the gauze granuloma was best visualized on MR imaging. If no radio-opaque marker is seen on plain radiography or CT, the folded fabric inner structure visualized on T2-weighted images can be a most important clue to the correct diagnosis of this iatrogenic mass.

Female↗
PubMed1992

Reperfusion and irreversible myocardial injury: identification with a nonionic MR imaging contrast medium.

The potential of a new nonionic gadolinium complex--gadodiamide injection--to (a) allow distinction between reperfused and occlusive infarction and (b) enable differentiation between reperfused reversible and irreversible myocardial injury was investigated. Three groups of rats were used: 10 with reversibly reperfused myocardial injury, 10 with irreversibly reperfused injury, and 10 with occlusive infarction. Before administration of contrast material, there was no significant difference in signal intensity between normal and injured regions on T1-weighted images. After administration of gadodiamide injection (0.2 mmol/kg), the reversibly injured myocardium was indistinguishable from normal myocardium, while the reperfused irreversibly injured zone showed prominent and homogeneous enhancement. Occlusive infarcts showed three zones of differential enhancement consisting of normal, periinfarction, and infarction regions. Gadodiamide injection provides differential enhancement in reversibly reperfused, irreversibly reperfused, and occlusive infarcts. Thus, it may be useful as a marker of reperfusion and extent of infarction after thrombolytic therapy.

Animals↗
PubMed1992

The role of protein kinase-C in gonadotropin-induced ovulation in the in vitro perfused rabbit ovary.

Tumor-promoting phorbol esters are believed to affect ovarian granulosa cell progesterone and prostaglandin (PG) production and possibly ovulation by activating protein kinase-C (PKC). The effects of phorbol esters and PKC inhibitors on ovulation, progesterone, and PG production were examined in an in vitro perfused rabbit ovary. The effect of tranexamic acid, an inhibitor of the conversion of plasminogen activator to plasmin, on phorbol ester-induced ovulation was also examined. Phorbol 12,13-dibutyrate (PdBU), a PKC stimulator, induced ovulation in a dose-related manner in the absence of gonadotropins (56%, 200 nM PdBU; 0%, 0 nM PdBU; P < 0.05). Perfusate progesterone levels were increased only after 600 nM PdBU treatment, and perfusate PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were increased in a dose-dependent fashion (P < 0.05). Staurosporine, a potent inhibitor of the catalytic domain of PKC, and calphostin-C, a specific inhibitor of the diacylglycerol-binding region, inhibited hCG-induced ovulation in a dose-related manner. Gonadotropin-induced ovulation decreased from 73% without staurosporine to 19% with 1.0 microM staurosporine (P < 0.01). Calphostin-C reduced ovulatory efficiency from 60% to 24% (P < 0.01). However, neither inhibitor decreased progesterone or PGF2 alpha production by ovaries exposed to hCG. hCG-induced oocyte maturation was also unaffected by exposure to either staurosporine or calphostin-C. Tranexamic acid reduced phorbol ester-induced ovulatory efficiency from 67% to 37% (P < 0.05). These findings demonstrate that the calcium-dependent PKC pathway is instrumental in gonadotropin-mediated follicular rupture in the rabbit. Although PGs may play an important role in ovulation, they do not appear to be directly responsible for PKC-mediated follicular rupture.

Animals↗
PubMed1992

Helicobacter pylori infection and gastroduodenal disease: a comparison of endoscopic findings, histology, and urease test data.

To determine the prevalence and significance of Helicobacter pylori (H. pylori) infection, biopsies of the antral mucosa were obtained from 139 patients and 43 asymptomatic volunteers. The specimens were examined by hematoxylin-eosin staining and the ureas test. The detection rate of H. pylori by histologic examination was 91.3% in patients with duodenal ulcer, 75.0% in those with combined duodenal and gastric ulcer, 63.6% in those with gastric ulcer, 22.9% in those with gastric carcinoma, 36.4% in those with gastric adenoma, 14.3% in those with gastric hyperplastic polyp, and 51.7% in those with gastritis, and the respective percentages detected by the urease test were 91.3%, 75.0%, 54.5%, 28.6%, 27.3%, 14.3%, and 44.8%. H. pylori was also detected in 10/43 (23.3%) asymptomatic healthy volunteers by histology and the urease test. The prevalence of H. pylori was significantly higher in the patients than in the asymptomatic healthy volunteers (p < 0.05). H. pylori was detected in 62.9% of patients with endoscopic erosive gastritis and in 97.9% of those with histologically proven chronic active gastritis. The urease test was positive in 77/82 patients who were histologically positive for the organism (sensitivity: 93.9%), and it was negative in 98/100 patients who were negative by histology (specificity: 98.0%). Thus, there was over 90% agreement between the urease test and histology. Our investigations showed that H. pylori was closely related to peptic ulcers and antral gastritis, and that the urease test provides a simple, rapid and accurate diagnosis of H. pylori infection.

Adult↗