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Biomedical subjects

K Matsuno

Publications and source records attributed to K Matsuno.

At least 55 records · Page 3Linked to original sources

Hydrothermal circulation of seawater through hot vents and contribution of interface chemistry to prebiotic synthesis.

Synthesizing oligopeptides from glycine and alanine in a flow reactor, which stimulates constant hydrothermal circulation of seawater through hot vents on the primitive Earth, demonstrated that an exponential growth of the products is possible. The initial rapid growth of the product is a consequence of using the products formed in one cycle as the starting materials for the cycle of synthesis.

Alanine↗

Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs.

BACKGROUND: The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. AIM: To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants. METHODS: Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer. RESULTS: In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion. CONCLUSIONS: S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.

Animals↗

Gastric acid secretion in dogs in response to combinations of beer, ethanol and peptone meal--the role of endogenous gastrin.

AIM: To examine the effects of beer, ethanol, peptone meal and combinations of either peptone meal and beer or peptone meal and ethanol on gastric acid secretion in vagally denervated pouch dogs. METHODS AND RESULTS: The oral administration of either 200 mL of beer, 5% ethanol or 10% peptone meal significantly stimulated gastric acid secretion for 60-90 min in these dogs. With 5% ethanol the plasma gastrin concentration was not affected for 90 min. Combinations of 10% peptone and beer (peptone-beer) or 10% peptone and 5% ethanol (peptone-ethanol) potentiated the acid secretion and increased the plasma gastrin level. While a selective cholecystokinin-B/gastrin receptor antagonist, S-0509, had no effect on ethanol-stimulated acid secretion, the compound markedly inhibited both peptone-beer-stimulated and peptone-ethanol-stimulated gastric acid secretion. Famotidine and atropine significantly inhibited gastric acid secretion stimulated by 5% ethanol, peptone-beer and peptone-ethanol. CONCLUSIONS: The mechanisms by which peptone-beer and peptone-ethanol stimulate gastric acid secretion may be mediated not only by increased plasma gastrin, but also by the action of histamine and acetylcholine coupled with the increased plasma gastrin. Ethanol-stimulated secretion appears to be unrelated to circulating gastrin, yet may be related to the acid regulatory mechanism involving histamine and acetylcholine.

Administration, Oral↗

Hybrid radioassay of multiple radionuclide mixtures in waste solutions by using liquid and NaI(Tl) scintillation monitors.

A new analytical technique for radioactive waste solutions has been developed by using a combination of a liquid and a NaI(Tl) scintillation monitor, which enables beta-emitter mixtures to be radioassayed using one calculation process with the method of least squares. This hybrid system can facilitate the analysis of beta-emitter mixtures with very similar liquid scintillation pulse height distributions, such as 3H, 51Cr, and 125I. All that is required for the technique are sets of quench standards of the nuclides to be analyzed and calibration standards for the gamma-emitters. Detection limits for seven nuclides were estimated to be about 0.005 Bq mL(-1), which are sufficiently low compared with the values of authorized safety guidelines.

Chromium Radioisotopes↗

The internalist stance. A linguistic practice enclosing dynamics

Natural dynamics, as manifested in evolutionary processes, refer to material bodies in movement in the present progressive mode. Any interacting material body in the present progressive mode must be sentient to others because there can be no global agency coordinating it to others in a globally synchronous manner. The internalist perspective, or the worm's eye view, referring primarily to the present progressive mode, renders local material bodies, large or small, subject to an inevitable inconsistency among local representations of neighborhood events registered in the local present perfect tense. Any sentient material body experiencing this inconsistency subsequently transforms itself into an inconsistency-free representation. The descriptive scheme unique to the internalist stance is internal and dynamic in the sense that it constantly strives to update constituent local representations, attempting to eliminate any inconsistencies residing within antecedent local representations. Compared to external descriptions of invariable universals grounded upon the Cartesian epistemic split, which are complementary to dynamics, internal description serves as a linguistic means of embodying natural dynamics even without recourse to the notion called forces. This makes our language powerful enough to enclose natural dynamics of material bodies in the empirical domain.

Journal Article↗

Asymmetries of the retinal nerve fibre layer thickness in normal eyes.

AIMS: To investigate the variation in the retinal nerve fibre layer thickness in detail in normal eyes with a scanning laser polarimeter. METHODS: The retinal nerve fibre layer thickness (RNFLT) was measured in 94 normal volunteers with a scanning laser polarimeter. The mean RNFLT around a 10 pixel-wide ellipse located concentrically with the disc of 1.5 disc diameters was calculated for 16 sectors each of 22.5 degrees. The symmetry of the RNFLT distribution with respect to the horizontal midline for individual eyes and to the vertical meridian for the two eyes was examined. RESULTS: The RNFLT was thicker on the inferior side than on the superior side for the temporal four pairs of 22.5 degrees sectors, and the differences were significant in two of the four temporal pairs (p<0.007). The RNFLT was thicker in the superior than in the inferior side for the nasal four pairs of the sectors, and the differences were significant in three of the four nasal pairs (p<0.04). The mean RNFLT was significantly thicker in the right eyes than in the left eyes in the four temporal sectors (p<0.02), and significantly thicker in the left eyes than in the right eyes in the inferior two nasal sectors (p<0.01). CONCLUSIONS: Asymmetries of the RNFLT in normal eyes with respect to the horizontal midline and to the vertical meridian for the two eyes were found. These asymmetries should be considered when retinal nerve fibre layer loss is evaluated during the course of a disease process.

Adolescent↗

Time-dependent nephrotoxicity associated with daily administration of cisplatin in mice.

The chronopharmacokinetics and chronopharmacodynamics of cisplatin were studied in a mouse model to reveal the mechanisms of dosing time-dependent nephrotoxicity induced by daily administration. Chronotoxicity was tested by daily intraperitoneal injections of cisplatin (6mg kg(-1)) for 5 days at four time points (04:00, 10:00, 16:00 and 22:00h) in BALB/c mice (n = 6 in each group). After following the changes in body weight, serum concentrations of blood urea nitrogen (BUN) and creatinine obtained on day 6 were compared. The results showed diurnal variations in cisplatin toxicity, with the 04:00 and 16:00h time points the best and the worst, respectively. We then measured platinum concentrations in blood, liver and kidney and compared the results of the 04:00 and 16:00 h groups (n = 4 in each group). Kidney sensitivity to cisplatin alone, lipopolysaccharide (LPS) alone, cisplatin with LPS and saline (control) were also measured using a tissue culture system (a measurement system of interleukin-6 (IL-6) production) between the 04:00 and the 16:00 h groups (n = 4 in each group). These results showed no significant difference in platinum accumulation between the two groups. IL-6 production was higher in the 16:00 h group than in the 04:00 h group after saline injection alone (P < 0.05). Cisplatin treatment alone did not increase IL-6 production. However, IL-6 levels were markedly augmented by cisplatin with LPS. In conclusion, chrononephrotoxicity induced by daily cisplatin administration does not only depend on cisplatin accumulation, but might also depend on kidney sensitivity to diurnal variations in inflammatory reaction without direct cisplatin toxicity.

Animals↗

The suppression of potassium cyanide-induced mortality by the increase of extracellular acetylcholine level in the brain.

We examined whether potassium cyanide (KCN)-induced mortality in mice was regulated by acetylcholine transmission in the brain. Our novel compound, (+/-)-1-(1,2-diphenyl)ethyl-4-[2-(3,4-dimethoxyphenyl)ethyl]piperazine dihydrochloride (SA3251), suppressed KCN-induced mortality in mice. In parallel, SA3251 increased the cortical and hippocampal extracellular acetylcholine level in conscious, freely-moving rats. Interestingly, the time course patterns of these two events induced by SA3251 correlated. These results suggest that the central cholinergic system plays an important role in the suppression of KCN-induced mortality.

Acetylcholine↗

Phenotype-genotype correlation in CD36 deficiency types I and II.

CD36 deficiency was studied with attention to the phenotype-genotype relationship. The diagnosis of CD36 deficiency was made when CD36 was negative on platelets (type II) or on both platelets and monocytes (type I). Among 827 apparently healthy Japanese volunteers, the type I and II deficiencies were found in 8 (1.0%) and 48 (5.8%), respectively. The T for C substitution at nt478 for Pro90Ser and the insertion of A at nt 1159 constituted the major causes of type I and II deficiencies. The dinucleotide deletion at nt539 had a minor role. In two family studies, we found a previously unreported polymorphic site in the 5'-proximal flanking region and the 3'-untranslated region. Including these new polymorphisms, DNA sequence other than the three known mutations affecting CD36 expression was not observed in the CD36 gene, calling into question the previous hypothesis that a platelet-specific silent allele exists near or at the CD36 gene.

Alleles↗

Onset of the sliding movement of an actin filament on myosin molecules: from isotropic to anisotropic fluctuations.

An actin filament contacting myosin molecules increased the fluctuation intensity of the filamental displacement as the ATP concentration increased. In particular, fluctuations in the filamental displacement in the planar plane in which the sliding movement takes place were isotropic at a low ATP concentration, and became anisotropic as the concentration increased. The build-up of the sliding movement of an actin filament was associated with the transformation from isotropic to anisotropic fluctuations of the filamental displacement.

Actin Cytoskeleton↗

Synthesis of superoxide dismutase derivative that specifically accumulates in renal proximal tubule cells.

Protection of tissues from oxygen toxicity is one of the major prerequisites to aerobic life. Since a wide variety of xenobiotics with prooxidant activity is excreted by the kidney, renal tubule cells should be protected from hazardous oxygen species. Because intravenously injected Cu/Zn-type superoxide dismutase (SOD) is rapidly excreted in the urine in its intact form, effective dismutation of superoxide radicals cannot be achieved in vivo by intravenously administered SOD. To scavenge superoxide radicals and inhibit their toxic effects in and around renal tubule cells, a hexamethylene-diamine (AH)-conjugated SOD (AH-SOD) was synthesized. When injected intravenously into the rat, (125)I-labeled AH-SOD disappeared from the circulation with a half-life of 3 min and accumulated in the kidney. After 30 min of administration, more than 80% of the radioactivity derived from AH-SOD was found to localize in the kidney without being excreted in the urine. Immunohistochemical examination revealed that, 60 min after administration, the major part of AH-SOD localized in renal proximal tubule cells. Kinetic analysis using right-side-out-oriented renal brush border vesicles revealed that AH-SOD bound to their membrane surface by some mechanism which was inhibited by AH but not by heparin and albumin. These results indicated that AH-SOD rapidly underwent renal glomerular filtration, bound to apical plasma membranes of proximal tubule cells, and localized in these cells for a fairly long time without being excreted in the urine. Thus, AH-SOD might permit studies on the role of superoxide radicals in and around renal proximal tubule cells.

Animals↗

Contractile and protractile coordination within an actin filament sliding on myosin molecules.

An actin filament exhibits distortions longitudinally when it slides upon myosin molecules. We observed that the actin filament demonstrated contractile distortions at low ATP concentrations and protractile distortions at high concentrations. Temporal development of such distortions was identified, by tracing each of several speckled fluorescent markers attached to the actin filament. Close association of the sliding movement to the moving distortions of an actin filament suggests the presence of a unitary mechanism regulating the apparently two different modes of dynamic movement.

Actins↗

Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

Matrix metalloproteinase-7 (matrilysin) has been implicated in tumor invasion and metastasis as well as tumor initiation and growth. In this study, we analyzed an association between immunohistochemically detected matrilysin expression at the invasive front in esophageal squamous cell carcinomas and clinicopathological characteristics and determined whether matrilysin predicts recurrence and/or survival Matrilysin expression at the invasive front was detected in 49% of 100 carcinoma tissues and was associated with the depth of invasion (P < 0.0001), advanced tumor stage (P = 0.0159), recurrences (P = 0.0002), and recurrences within the first postoperative year (P = 0.002). Patients with matrilysin-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with a matrilysin-negative one (P < 0.0001). Matrilysin remained a significant predictive value for disease-free and overall survival in multivariate analysis, including conventional clinicopathological factors (P = 0.0007 and 0.0004, respectively). Our results suggest that matrilysin may play a key role in the progression of esophageal carcinoma and that its detection may be useful for the prediction of recurrence and poor prognosis and, possibly, for selecting patients for anti-matrix metalloproteinase therapy.

Carcinoma, Squamous Cell↗

Selective coupling of mouse brain metabotropic sigma receptor with recombinant Gi1.

Various sigma (sigma) ligands including (+)-pentazocine stimulated [35S]GTPgammaS binding in synaptic membranes from the mouse cerebellum. The (+)-pentazocine-stimulated [35S]GTPgammaS binding was blocked by the treatment of membranes with pertussis toxin (PTX), but completely recovered by the reconstitution of PTX-treated membranes with recombinant Gi1, but not with GoA. These findings suggest that metabotropic sigma receptors are selectively coupled to Gi1 protein.

Animals↗

Presentation of tumor antigens by phagocytic dendritic cell clusters generated from human CD34+ hematopoietic progenitor cells: induction of autologous cytotoxic T lymphocytes against leukemic cells in acute myelogenous leukemia patients.

The use of antigen-presenting dendritic cells (DCs) is currently proposed for tumor immunotherapy through generation of CTLs to tumor antigens in cancer patients. In this study, DCs were differentiated using granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha from CD34+ hematopoietic progenitor cells that had been mobilized into the peripheral blood. To use the phagocytic activity of DCs for processing and presentation of tumor antigens, we established DC clusters containing immature DCs by preserving proliferating cell clusters without mechanical disruption. After an 11-day culture, the developed clusters contained not only typical mature DCs but also immature DCs that showed active phagocytosis of latex particles, suggesting that the clusters consisted of DCs of different maturational stages. These heterogeneous clusters could present an exogenous protein antigen, keyhold limpet hemocyanin, to both CD4+ and CD8+ T lymphocytes. Furthermore, in three acute myelogeneous leukemia patients, clusters pulsed with autologous irradiated leukemic cells could also induce antileukemic CTLs. The mechanical disruption of clusters abrogated the induction of CTLs to leukemic cells as well as to hemocyanin. This observation gives an important information for the use of heterogeneous DC clusters derived from autologous peripheral blood CD34+ cells in the case of immunotherapy for leukemia.

Acute Disease↗

Elongation of oligopeptides in a simulated submarine hydrothermal system.

Oligomerization of a peptide was attempted in a flow reactor that simulated a submarine hydrothermal system. When fluid containing glycine repeatedly circulated through the hot and cold regions in the reactor, oligopeptides were made from glycine. When divalent ions (such as copper ions) were added under acidic conditions, oligoglycine was elongated up to hexaglycine. This observation suggests that prebiotic monomers could have oligomerized in the vicinity of submarine hydrothermal vents on primitive Earth.

Chromatography, High Pressure Liquid↗

Acute and chronic administration of the selective sigma1 receptor agonist SA4503 significantly alters the activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study.

In this study, we examined the effect of the acute and repeated administration of the selective sigma (sigma)1 receptor agonist 1-(3, 4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) on the number and firing pattern of spontaneously active dopamine (DA) neurons in substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male Sprague-Dawley rats. This was accomplished using the technique of in vivo extracellular single unit recording. The intravenous administration of SA4503 (0.01-1.28 mg/kg) did not significantly alter the firing rate or pattern of spontaneously active DA neurons in either the SNC or VTA. A single injection of either 0.1 or 0.3 mg/kg i.p. of SA4503 did not alter the number of spontaneously active SNC and VTA DA neurons. In contrast, a single injection of 1 mg/kg i.p. of SA4503 produced a significant decrease and increase in the number of spontaneously active SNC and VTA DA neurons, respectively. Overall, the firing pattern parameters of spontaneously active SNC DA neurons were altered more significantly than those of spontaneously active VTA DA neurons following the acute administration of SA4503. The repeated administration (one injection per day for 21 days) of 0.3 and 1 mg/kg i.p. of SA4503 produced a significant increase in the number of spontaneously active VTA DA neurons. In addition, the repeated administration of SA4503 produced a greater alteration of the firing pattern of spontaneously active VTA compared to SNC DA neurons. Our results suggest that the administration of SA4503 significantly alters the activity of spontaneously active midbrain DA neurons, particularly those in the VTA following repeated administration.

Animals↗