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Biomedical subjects

N Kurihara

Publications and source records attributed to N Kurihara.

At least 127 records · Page 7Linked to original sources
PubMed1993

Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine, in airborne particles and diesel-exhaust particles.

A carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP), has been measured in airborne particles, diesel-exhaust particles, and incineration ash from garbage-burning plants. PhIP was found in all kinds of samples. In the light of the present results, together with the previous findings that PhIP was present in cooked foods and cigarette smoke, PhIP is likely to be an ubiquitous environmental pollutant. These observations also suggest that PhIP may be formed through the combustion process.

Journal Article↗
PubMed1993

Production of polyclonal antibodies against 1,1'-ethyliden bis[L-tryptophan] (EBT), a potential contaminant causing eosinophilia-myalgia syndrome (EMS).

Eosinophilia-myalgia syndrome (EMS) is thought to be caused by the intake of contaminated L-tryptophan products. 1,1'-Ethyliden bis[L-tryptophan] (EBT) is one of the contaminants in the L-tryptophan products and is thought to be a possible cause of EMS. In the present study we report that anti-EBT antibodies are generated by immunizing rabbits with the low molecular weight substance, EBT (molecular weight 434). These antibodies may be available tools for elucidating the mechanisms responsible for the outbreak and/or development of EMS.

Animals↗
PubMed1993

Effect of a new leukotriene receptor antagonist, ONO-1078, on human bronchial smooth muscle in vitro.

Peptide leukotrienes (LT) have been postulated to play a major role in the etiology of bronchial asthma. The present study investigated the effect of a new peptide LT receptor antagonist, ONO-1078, on isolated human bronchial smooth muscle in vitro. Helical strips of bronchi were suspended in the organ baths filled with 37 degrees C Krebs solution and mechanical responses were recorded isometrically. ONO-1078 produced dose-dependent relaxations, which suggested that the spontaneous basal tone was in part mediated by LT. ONO-1078 caused dose-dependent relaxations of the tissues which were precontracted with LTC4 or LTD4 (3 x 10(-8) M). Pretreatment of bronchi with ONO-1078 (10(-8) M, 10(-7) M) significantly inhibited dose-dependent contractions induced by LTC4 and LTD4. ONO-1078 (10(-6) M) also significantly reduced the antigen-induced contractions in bronchi passively sensitized with atopic serum from mite-allergic patients. Moreover the combination of an H1-receptor antagonist, diphenhydramine (10(-5) M), and ONO-1078 (10(-6) M) completely abolished the antigen-induced contractions. The present findings demonstrate that ONO-1078 is a potent antagonist of exogenous and endogenous LT in the human airway. The selective LT antagonist such as ONO-1078 may be valuable in the therapy of allergic asthma.

Aged↗
PubMed1993

Nucleic acids induce the formation of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system.

Effects of nucleic acids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in a model system. When a mixture of a certain amount of DNA or RNA, creatinine (1 mmol) and phenylalanine (1 mmol) in 10 ml of 50 mM phosphate buffer, pH 7.4, was heated at 60 degrees C for 4 weeks in a screw-capped vial, PhIP was produced, and the yield of PhIP was dependent on the heating time as well as the dose of nucleic acid added to the mixture. However, PhIP was not detectable in the mixtures without the presence of nucleic acids. Both deoxyribonucleotides and ribonucleotides tested induced the formation of PhIP under the presence of phenylalanine and creatinine, although bases of nucleic acids such as adenine and guanine did not induce PhIP formation. Moreover, we confirmed that 2-deoxy-D-ribose as well as D-ribose induced the formation of PhIP in the presence of creatinine and phenylalanine. These results indicate that nucleic acids can induce the formation of PhIP in the presence of creatinine and phenylalanine in the model system. Our data also suggest that pentose in nucleic acids may participate in PhIP forming reactions.

Carcinogens↗
PubMed1993

Simultaneous quantitative determination of 3H, 14C, 32P, 35S, 51Cr, and 125I on the surface of a paper disc using combustion.

A paper disc that retained 3H, 14C, 32P, 35S, 51Cr, and 125I on its surface was combusted in a flow-type combustion flask filled with oxygen. The combustion products containing five radionuclides, except 14CO2, were collected by washing the inner wall of the flask with 0.5-M hydrogen peroxide containing excess NaHSO3. The 14CO2 that remained in the gas phase of the flask was introduced into another flask for absorption into an organic base solution. By determining the radioactivity of both the solutions containing the respective radionuclides by means of NaI(Tl) and liquid scintillation counters, the six radionuclides in the solutions were quantified. The detection limit of surface contamination with this method was compared with the limit specified by Japanese law for the surface contamination of controlled areas.

Fires↗
PubMed1993

Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion.

The present study examined the possible interaction of platelet-derived growth factor (PDGF) and atrial or brain natriuretic peptides (ANP and BNP, respectively) on cellular proliferation and secretion of endothelin-1 in cultured rat mesangial cells. PDGF increased cellular proliferation and endothelin-1 secretion. The protein kinase C (PKC) inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, staurosporine, and PKC inhibitor peptide, inhibited such stimulation. Rat ANP-(1-28) and rat BNP-45 exhibited clearly dose-related inhibition of PDGF-stimulated cellular proliferation and endothelin-1 secretion. This inhibition by ANP and BNP was paralleled by an increase in the cellular level of guanosine 3',5'-cyclic monophosphate (cGMP). Results indicate that PDGF stimulates cellular proliferation and endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC and that ANP and BNP inhibit such stimulation through a cGMP-dependent process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Natriuretic peptides inhibit mesangial cell production of endothelin induced by arginine vasopressin.

The present study examined the effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) on endothelin-1 (ET-1) secretion after stimulation with arginine vasopressin (AVP), using cultured rat glomerular mesangial cells. AVP stimulated immunoreactive (ir) ET-1 secretion in a concentration-dependent manner via a receptor-mediated process. Rat ANP-(1-28) and rat BNP-45 potently inhibited this stimulated secretion in a concentration-dependent manner. Inhibition by ANP and BNP of AVP-stimulated ET-1 secretion was paralleled by an increase in the medium level of guanosine 3',5'-cyclic monophosphate (cGMP). The addition of a cGMP analogue, 8-bromo-cGMP, reduced the stimulated ET-1 secretion. CNP was much less effective than rat ANP-(1-28) or rat BNP-45 with respect to inhibiting irET-1 secretion and increasing cGMP levels. High-performance liquid chromatography indicated that the major component of irET-1 in the culture medium corresponds to ET-1-(1-21). These findings indicate that AVP stimulates ET-1 secretion in cultured rat mesangial cells and that rat ANP and BNP inhibit this stimulated secretion, probably through a cGMP-dependent process.

Animals↗
PubMed1993

Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump.

Craniometaphyseal dysplasia (CMD) is a rare craniotubular bone dysplasia transmitted in autosomal dominant or recessive form. This disease is characterized by cranial bone hyperostosis and deformity of the metaphyses of the long bones. Using osteoclast-like cells formed from patient bone marrow cells, we investigated the pathophysiology of CMD in a 3-yr-old patient. Untreated bone marrow cells from the patient differentiated into osteoclast-like cells in vitro. These cells were shown to have vitronectin beta-receptors using a specific monoclonal antibody, i.e., 23C6 (CD51), which reacts with osteoclasts in human bone biopsy samples. However, the number of these osteoclast-like cells formed from the patient's bone marrow was only 40% of the normal controls. 1,25-dihydroxyvitamin-D3, bovine 1-34 parathyroid hormone, recombinant human interleukin-1 beta, recombinant human interleukin-6, or recombinant human macrophage colony-stimulating factor significantly increased, while salmon calcitonin significantly inhibited, the number of osteoclast-like cells. However, these cells could not resorb sperm whale dentin slices and lacked the osteoclast-reactive vacuolar proton pump as evidenced by a monoclonal antibody (E11). Western blot analysis using a monoclonal antibody to pp60c-src (327) revealed that protooncogene c-src expression by the platelets of the CMD patient was comparable to the normal control. These data suggest that: (a) the hyperostosis and the metaphyseal long bone deformity in the present CMD patient might be explained by osteoclast dysfunction due to impaired expression of the osteoclast-reactive vacuolar proton pump; and (b) a protooncogene c-src was not associated with the pathogenesis of the present CMD patient.

Blood Platelets↗
PubMed1993

Increases in glomerular eicosanoid production in rats with bilateral ureteral obstruction are mediated by enhanced enzyme activities of both the cyclooxygenase and 5-lipoxygenase pathways.

Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 hr duration produced significantly greater amounts of prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane B2, and leukotriene B4 than glomeruli isolated from sham-operated control (SOC) rats. To examine the mechanisms underlying the greater production of eicosanoids by glomeruli isolated from rats with BUO, we measured the activities of enzymes related to eicosanoid formation such as cyclooxygenase, 5-lipoxygenase, PGE2 isomerase, and PGI2 and thromboxane synthase in glomeruli isolated from SOC rats and rats with BUO. Glomeruli isolated from rats with BUO had a significantly increased activity of cyclooxygenase with de novo synthesis of this enzyme and a markedly augmented activities of PGE2 isomerase and both PGI2 and thromboxane synthases relative to glomeruli isolated from SOC rats. Similarly, the activity of membrane-bound 5-lipoxygenase, the active location of this enzyme, was significantly greater in glomeruli isolated from rats with BUO than in glomeruli isolated from SOC rats. Thus, BUO of 24 hr duration enhances the glomerular production of eicosanoids via the activation of enzymes in both the cyclooxygenase and 5-lipoxygenase pathways.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Relationship between exercise capacity and the severity of emphysema as determined by high resolution CT.

We investigated the relationship between exercise capacity or exercise-induced hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary emphysema. The patients underwent pulmonary function tests, high resolution computed tomography and incremental treadmill exercise testing. Computed tomography scans were obtained at four levels in the lungs, and emphysema scores were determined by the visual assessment of low attenuation areas as a measure of the severity of parenchymal destruction. The emphysema score correlated significantly with diffusing capacity (r = -0.69) in the pulmonary function tests. Among the exercise test parameters, the emphysema score correlated significantly with the total distance walked (r = -0.74), with maximal oxygen consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r = -0.50) and at the maximum workload (r = -0.58), and with the decrement of arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results suggest that exercise capacity and exercise-induced hypoxaemia are related to the extent of destruction of lung parenchyma in patients with pulmonary emphysema.

Aged↗
PubMed1993

[Intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers].

The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis by gastric cancers was evaluated through experimental and clinical studies. In experimental studies, the effect of sodium thiosulfate (STS) on cytotoxic activity of DDP was evaluated by MTT assay using human gastric cancer cell lines. The cytotoxic activity of DDP was reduced by 50% with 100-fold STS in the area under the curve (AUC), whereas 10-fold STS in AUC did not reduce the cytotoxicity of DDP. In clinical studies, patients were treated with one of three protocols: Group A was treated by the intraperitoneal injection (ip) of DDP at a dose of 70 mg/m2, and group B or C was treated by ip DDP at a dose of 110 mg/m2 with or without STS rescue. The pharmacodynamics and the adverse effects of treatments were evaluated between these three protocols. In group C, the means of AUC of STS were 2.43-, 10.8- and 86.8-fold those of total platinum in the peritoneal cavity, plasma, and urine, respectively. There were 1/5, 1/2 and 2/2 partial responses in peritoneal carcinomatosis patients treated with A, B and C. Renal toxicity was not observed in the patients treated with DDP and STS rescue. STS does not seem to reduce the antitumor activity of DDP in peritoneal cavity and plasma, while the renal cytotoxicity was reduced by STS rescue. The result led us to conclude that intraperitoneal DDP treatment combined with STS rescue would be useful chemotherapy against peritoneal carcinomatosis by gastric cancer.

Adult↗
PubMed1993

Hyporesponsiveness to inhibitory agents of alveolar macrophages and polymorphonuclear leukocytes primed by platelet activating factor.

In this study, it was presented that PAF and LTB4 exert a priming effect on PMNs to promote their superoxide anion production. PMNs preincubated with PAF of normal controls or PMNs from asthmatic patients are activated and their responsiveness to inhibitory stimuli such as antiallergic drugs and corticosteroid are attenuated. In conclusions, inflammatory cells of asthmatics may be activated by various mediators and play an important role in the progress of airway damage.

Adult↗
PubMed1992

Low concentration endothelin-1 enhanced histamine-mediated bronchial contractions of guinea pigs in vivo.

Endothelin-1 (ET-1) represents one of the most potent constrictors of guinea pig bronchial smooth muscle. In our study, various doses of aerosolized ET-1 increased airway resistance. But a very low concentration of ET-1 (10(-12) M) could not change airway resistance. We examined low doses of ET-1 enhanced the sensitivity of bronchial contractions to histamine. ET-1 may play one of the most important roles in contributing directly or indirectly to the pathogenesis of bronchial asthma.

Aerosols↗
PubMed1992

Identification of osteopontin in isolated rabbit osteoclasts.

Bone remodeling is a complex process coupling bone formation and resorption. Osteoblasts, the bone-forming cells, are known to produce various bone matrix proteins and cytokines; however, little is known about protein factors produced by osteoclasts or bone-resorbing cells. A method utilizing the high affinity of osteoclasts for tissue culture dishes was developed to isolate a large number of pure osteoclasts from rabbit long bones. A cDNA library was then constructed from these isolated osteoclasts, and differential cDNA screening was performed between osteoclasts and spleen cells. Two clones representing osteoclast-specific clones, named OC-1 and OC-2, were isolated. By Northern blot analysis, OC-1 was expressed in osteoclasts and in kidneys, whereas OC-2 was specific for osteoclasts. OC-1 was found to encode osteopontin from its nucleotide sequence, and therefore, osteopontin may have other functions for osteoclastic bone resorption besides osteoclast attachment to bone.

Amino Acid Sequence↗
PubMed1992

Brain natriuretic peptide as a cardiac hormone in essential hypertension.

PURPOSE: A natriuretic peptide, brain natriuretic peptide (BNP), has been isolated from porcine hearts. We performed this study to determine if BNP is secreted from the heart and to identify changes, if any, in the plasma BNP concentration in essential hypertension. PATIENTS AND METHODS: We measured the immunoreactive (ir) BNP concentration at intracardiac sites including the coronary sinus of five patients with heart disease during cardiac catheterization. We examined plasma ir-BNP in 48 hypertensive patients, 15 borderline hypertensive patients, and 25 normotensive subjects. RESULTS: Plasma ir-BNP in the coronary sinus was greater than at other cardiac sites. The concentration was significantly higher in hypertensive subjects than in borderline hypertensive or normotensive subjects. Hypertensive patients with left ventricular hypertrophy (LVH) established by echocardiography had higher plasma ir-BNP levels than those without LVH. In the hypertensive group, plasma ir-BNP was closely correlated with the LV mass index. In these patients, BNP levels were correlated with mean arterial pressure and inversely correlated with the LV ejection fraction, although these correlations were weak. Reverse-phase high-pressure liquid chromatography showed that the major component of circulating ir-BNP in the hypertensive and normotensive subjects corresponded to authentic human BNP-32. CONCLUSIONS: Human BNP-32 was secreted through the coronary sinus from the heart and may act as a cardiac hormone. Plasma BNP was increased in many of the hypertensive subjects with LVH. The increase in BNP seemed to be related to LVH or the cardiac overload associated with LVH.

Adult↗
PubMed1992

Hypoxia modulates mediator responses and neurotransmission in guinea-pig trachea in vitro.

To discover whether hypoxia affects mediator responses and neurotransmission in tracheal smooth muscle, we studied in vitro tracheal segments from guinea-pigs under isometric conditions. Hypoxia itself did not alter the basal tone. The maximum response to acetylcholine and histamine under hypoxia was less than that under oxygenated conditions. The logarithm of 50% effective concentration (log EC50) of the response to acetylcholine under hypoxia was not altered, but the log EC50 of the response to histamine decreased significantly. In contrast to the response to exogenous acetylcholine, the maximum contractile response to electrical field stimulation (EFS) under hypoxia was not different from that under oxygenated conditions, but the logarithm of 50% effective frequency of contractions caused by EFS under hypoxia decreased significantly. On the other hand, non-adrenergic-non-cholinergic relaxation caused by EFS was unaffected by hypoxia. These observations suggest that hypoxia can modulate the responses of tracheal smooth muscle to acetylcholine, histamine and nerve stimulation.

Acetylcholine↗
PubMed1992

Angiotensin II stimulates endothelin-1 secretion in cultured rat mesangial cells.

The present study was designed to test two hypotheses: (1) that angiotensin II (Ang II) stimulates endothelin-1 secretion in cultured rat mesangial cells and (2) that atrial and brain natriuretic peptides (ANP and BNP) inhibit the above-mentioned secretion in these cells. Ang II stimulated immunoreactive (ir) endothelin-1 secretion in a concentration-dependent manner between 10(-8) M and 10(-7) M. The protein kinase C (PKC) inhibitors from two chemical classes, H7 and staurosporine, inhibited secretion following such stimulation. The stimulatory effect of Ang II was also abolished in the PKC-depleted cells. Rat ANP(1-28) and rat BNP-45, which are the respective major circulating forms of ANP and BNP in rats, potently inhibited Ang II-stimulated endothelin-1 secretion in a concentration-dependent manner. Inhibition by ANP and BNP of Ang II-stimulated endothelin-1 secretion was paralleled by an increase in the cellular level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced the stimulated endothelin-1 secretion. Rat ANP(5-25) was less effective that rat ANP(1-28) with respect to inhibiting ir-endothelin-1 secretion and increasing cellular cyclic GMP. These findings indicate that Ang II stimulates endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC, and that rat ANP and BNP inhibit this stimulated secretion through a cyclic GMP-dependent process.

Angiotensin II↗