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Biomedical subjects

K Katoh

Publications and source records attributed to K Katoh.

At least 109 records · Page 6Linked to original sources

Effects of exogenous transforming growth factor-beta 1 on spinal cord injury in rats.

This study was undertaken to examine the effect of transforming growth factor-beta 1 (TGF-beta 1) administered into the subarachnoid space after spinal cord injury (SCI) on the increased production of inducible-nitric oxide synthase (i-NOS) in the injured spinal cord in rats. The expression of i-NOS mRNA after SCI was remarkably down-regulated by TGF-beta 1 in vivo. Rats treated with TGF-beta 1 showed a better outcome regarding hindlimb motor dysfunction in the first 5 days after injury compared to the saline-treated rats. However, the final outcome was not better and fibrous scar formation in the injured spinal cord was more evident, which was demonstrated as increased immunoreactivity of fibronectin in the later stage after SCI. These results provide evidence of both positive and negative contributions of TGF-beta 1 to the pathology associated with SCI.

Animals↗

Determination of bradykinin-(1-5) in inflammatory exudate by a new ELISA as a reliable indicator of bradykinin generation.

We have developed an ELISA for BK-(1-5) (Arg1-Pro2-Pro3-Gly4-Phe5). In rat carrageenin-induced pleurisy, in which a plasma exudation peak was observed 5 h after carrageenin, BK levels in the exudates were negligible (< 60 pg/rat). BK-(1-7) (des-Phe8-Arg9-BK) was detectable (900-400 pg/rat) over the entire course of the inflammation. However, a larger amount of BK-(1-5) was detectable in association with the increase in plasma exudation, showing a peak (8800 +/- 1200 pg/rat) 3 h after carrageenin. Bromelain (10 mg/kg, i.v.) and soy bean trypsin inhibitor (0.3 mg/rat, intra-pleural) significantly reduced BK-(1-5) levels (by 60-93%, 3, 7 and 19 h after carrageenin) and plasma exudation rates (by 61-74%, 3 and 7 h after carrageenin). Dexamethasone (0.3 mg/kg, i.p.) reduced BK-(1-5) levels (by 78%) and decreased plasma exudation (by 70%) 3 h after carrageenin. In nasal allergy patients, antigen challenge of nasal mucosa elevated BK-(1-5) levels and active kallikrein levels in nasal washes. These results verify that BK-(1-5) determined by ELISA is a good indicator for release of kinins in vivo.

Angiotensin-Converting Enzyme Inhibitors↗

Octanoate increases cytosolic Ca2+ concentration and membrane conductance in ovine pancreatic acinar cells.

In order to investigate the cellular mechanisms involved in amylase release in response to stimulation with short-chain fatty acids, changes in intracellular calcium concentration ([Ca2+]i), membrane current and amylase release were measured in pancreatic acinar cells of sheep. Both octanoate and acetylcholine raised [Ca2+]i in acinar cells in a concentration-dependent manner. The rise in [Ca2+]i in response to the stimulation with octanoate (10 mmol.l-1) was reduced in a medium without CaCl2, but was markedly enhanced by reintroduction of CaCl2 into the medium up to 2.56 mmol.l-1. Perfusion of the cells with a medium containing octanoate (5 mmol.l-1) or acetylcholine (0.5 mumol.l-1) immediately raised inward current across the cell membrane at a holding-membrane potential of -30 mV. The inward current became greater as the holding potential became more negative. The equilibrium potential was 1.8 mV and 3.9 mV for octanoate and acetylcholine, respectively, being consistent with that for Cl-. Although intracellular application of octanoate through a patch-clamp pipette also raised inward current after several minutes in some cells (4 out of 12), this possibility was significantly smaller than that for extracellular application. In other cells, even though the intracellular application of octanoate did not cause an increase in current, it always caused responses immediately after introduction of the fatty acid into the medium. Stimulation with fatty acid as well as acetylcholine raised amylase release in a concentration-dependent manner in cells dispersed from tissue segments with crude collagenase and trypsin inhibitor. Without trypsin inhibitor, crude collagenase significantly and selectively reduced the octanoate (10 mmol.l-1)-induced amylase release. Dispersion with crude collagenase and trypsin significantly reduced both responses induced by octanoate and acetylcholine (5.5 mumol.l-1). We conclude that fatty acids and acetylcholine increase [Ca2+]i, which consequently evokes a rise in transmembrane ion (Cl-) conductance and amylase release, and that trypsin-sensitive protein(s) in the cell membrane are involved in secretory processes activated by stimulation with fatty acids in ovine pancreatic acinar cells.

Acetylcholine↗

Effects of saturated fatty acids on amylase release from exocrine pancreatic segments of sheep, rats, hamsters, field voles and mice.

Stimulatory effects of saturated fatty acids consisting of 4 (butyrate), 8 (octanoate), 12 (laurate) and 16 (palmitate) carbon atoms, as well as acetylcholine on pancreatic amylase release were assessed in tissue segments isolated from sheep, rats, hamsters, field voles and mice. The amount of amylase release induced by the fatty acids (1 mumol.l-1 to 10 mml.l-1) and by acetylcholine (10 nmol.l-1 to 100 mumol.l-1) increased in a concentration-dependent manner, and the maximum response in response to the fatty acids was obtained at the maximal dose used. The maximum increase in amylase release in response to butyrate or octanoate was highly and significantly (r = 0.974, P < 0.001) dependent on the log value of the mean body mass in the following order: sheep > rats > hamsters > field voles > mice. On the other hand, the response to laurate and palmitate was variable among animal species. Addition of atropine (1.4 mumol.l-1) to the medium did not reduce the responses to octanoate stimulation, but significantly reduced acetylcholine-induced responses, implying that the effects of the fatty acids were not mediated through activation of muscarinic acetylcholine receptors. Reduction of calcium ion concentration in the medium significantly inhibited the responses induced by the fatty acids and acetylcholine, suggesting that amylase release depends on extracellular calcium ions.

Acetylcholine↗

Lack of contribution of circulatory kinin elevated by captopril to induce hypotension in normotensive and hypertensive rats.

Captopril (10 mg/kg, i.p.) increased the arterial bradykinin (BK) level (Art-BK) of non-treated Sprague-Dawley rats (SD), determined by an ELISA, from 10.8 +/- 3.2 pg/ml to 32.9 +/- 5.4 pg/ml significantly (p < 0.05, n = 6). Intravenous infusion of BK (100-3000 ng/kg/min) dose-dependently increased heart rate (HR) and decreased mean blood pressure (MBP), the former at lower doses than the latter, and the hypotensive response became significant at 3000 ng/kg/min. Art-BK determined during infusion of the lowest dose of BK (100 ng/kg/min) was 12 times the endogenous Art-BK after captopril administration. In spontaneously hypertensive rats, Wistar Kyoto rats, and deoxycorticosterone acetate-salt treated hypertensive rats, Art-BK (450-1280 pg/ml) determined during intravenous BK-infusion (1000-3000 ng/kg/min), which induced significant hypotension, was 20 to 100 times the endogenous Art-BK (4.5-64 pg/ml) with captopril treatment. These results suggest that the increased Art-BK due to inhibition of kinin degradation by captopril could not account for the hypotension due to this angiotensin converting enzyme inhibitor in normotensive and hypertensive rats.

Angiotensin-Converting Enzyme Inhibitors↗

Novel synthetic peptides from the C-terminal heparin binding domain of fibronectin with heparin binding activity.

To identify a minimal peptide ligand that participates in recognition of heparin, we synthesized peptides extending a 29-kDa fragment in the C-terminal heparin binding domain of fibronectin. We obtained evidence that two peptides (designated D5 and D1) exhibit inhibitory activity on binding of the 29-kDa fragment to heparin-Sepharose CL 6B. It dose inhibitory studies, peptide D5 showed the potent inhibitory activity with IC50 of 210 +/- 37 microM. A new heparin binding site in the C-terminal heparin binding domain of fibronectin is demonstrated and provides a rationale for understanding the mechanism of cell adhesion and spreading.

Binding Sites↗

Multicenter, double-blind study of intravenous milrinone for patients with acute heart failure in Japan. Japan Intravenous Milrinone Investigators.

OBJECTIVES: Milrinone is a phosphodiesterase F-III inhibitor with positive inotropic and vasodilating activities. We investigated the hemodynamic response and pharmacokinetics of intravenous milrinone in patients with acute heart failure. DESIGN: Double-blind studies: a prospective, multicenter, double-blind, dose-finding study and a placebo-controlled, double-blind, comparative study. SETTING: Patients with acute heart failure (pulmonary artery occlusion pressure of > or = 18 mm Hg), who were hospitalized in the cardiac care units of 33 institutes in Japan, were entered into the study. PATIENTS: Fifty-four patients with acute or decompensated heart failure in the dose-finding study and 52 patients in the placebo-controlled, double-blind, comparative study. INTERVENTIONS: The present multicenter study consisted of a double-blind, dose-finding study (50-micrograms/kg intravenous loading dose, followed by 0.25, 0.5, or 0.75 microgram/kg/min of a continuous infusion of milrinone for 6 hrs, n = 54), and a placebo-controlled, double-blind, comparative study (50-micrograms/kg loading dose, followed by 0.5 microgram/kg/min of a continuous infusion of milrinone vs. placebo treatment, n = 52). We investigated the effects on cardiovascular hemodynamics, subjective symptoms, physical findings, and the pharmacokinetics of intravenous milrinone in a total of 106 patients with acute heart failure. MEASUREMENTS AND MAIN RESULTS: In the double-blind, dose-finding study, dose-dependent inotropic/vasodilating hemodynamic effects were documented for percent changes in cardiac index (+21.2%, +25.8%, and +30.9%, respectively) and pulmonary artery occlusion pressure (-12.8%, -17.0%, -41.3%, respectively) vs. plasma drug concentration at the equilibrium state (6 hrs after starting continuous infusion; 97 +/- 13, 197 +/- 22, and 284 +/- 28 ng/mL, respectively). Throughout the 6-hr infusion period, subjective symptoms were improved in 40%, 46.2%, and 70% of patients, respectively, for the three continuous infusion rates (0.25, 0.5, and 0.75 microgram/kg/min). In the placebo-controlled, double-blind, comparative study, the milrinone group exhibited marked improvement in cardiovascular hemodynamics (pulmonary artery occlusion pressure: from 26 +/- 6 to 15 +/- 3 mm Hg; cardiac index: from 2.6 +/- 0.9 to 3.3 +/- 1.1 L/min/m2) within 15 mins after starting drug administration. However, the placebo group showed no significant hemodynamic changes. Subjective symptoms and physical findings of acute heart failure improved in 47.6% and 40%, respectively, of patients within 60 mins after starting milrinone. The placebo group, however, showed no improvement providing inotropic/vasodilating (both 0%). CONCLUSION: Continuous infusion of milrinone (0.25 to 0.75 microgram/kg/min) after a 50-micrograms/kg loading dose is effective for inotropic/vasodilating hemodynamic support in patients with acute or decompensated heart failure.

Acute Disease↗

Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis.

Ultrasonography, computed tomography, and magnetic resonance imaging were performed to differentiate preoperatively between schwannomas of the vagus nerve and schwannomas of the cervical sympathetic chain by observing the position of schwannomas in regard to the surrounding blood vessels. Ultrasonography also permitted direct visualization of the vagus nerve, so its position relative to the schwannoma could be examined. In schwannomas of the vagus nerve the schwannoma grew between the common carotid artery and the internal jugular vein or between the internal carotid artery and the internal jugular vein, resulting in an increase in the distance between the artery and vein (separation). In schwannomas of the cervical sympathetic chain, no separation was observed between the internal jugular vein and the common carotid artery or internal carotid artery. Ultrasonography with a 7.5-MHz transducer showed the derivation of the tumor from the vagus nerve in schwannomas of the vagus nerve but showed the vagus nerve on the tumor surface in schwannomas of the cervical sympathetic chain.

Adolescent↗

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

4-Quinolones↗

Macromolecular composition of stress fiber-plasma membrane attachment sites in endothelial cells in situ.

Stress fibers (SFs) are present along the apical (apical SF) and the basal (basal SF) portions of cultured cells. We have recently shown that apical SFs are anchored to the apical plasma membrane (PM) in a manner similar to how basal SFs are attached to focal adhesion sites. We propose calling such apical SF-membrane attachment sites "apical plaques." To study the macromolecular composition of the apical plaque and the focal adhesion in endothelial cells (ECs) in situ, we examined by confocal laser scanning and fluorescence microscopy guinea pig aortae stained with various antibodies against focal adhesion-associated proteins. Basal SFs oriented parallel to the blood flow direction were mainly located in the upstream half of the cell. Thin apical SFs were also observed. Spotty staining patterns were observed in the basal and the apical portions of cells stained with anti-vinculin, anti-talin, anti-paxillin, or anti-fibronectin receptor, indicating the presence of focal adhesions and apical plaques in ECs in situ. Although fibronectin receptors were present in the apical plaque, fibronectin was not detected on the apical cell surface. Our data suggest that the molecules responsible for the SF-PM association are the same between in vitro and in situ cells. Our results appear to support a hypothesis that the SF system is involved in sensing and/or signal transduction of fluid mechanical forces.

Animals↗

Mutually exclusive distribution of the focal adhesion associated proteins and the erythrocyte membrane skeleton proteins in the human fibroblast plasma membrane undercoat.

The ends of stress fibers in the basal portion of cells (basal stress fibers) are anchored to focal adhesions, and stress fibers in the apical part of cells (apical stress fibers) are attached to the apical membrane, forming a structure (the apical plaque; KATOH, K. et al. (1995). Cell Motil. Cytoskel., 31: 177-195) resembling the focal adhesion. In addition to these two sites, stress fibers also make lateral contact with the plasma membrane but little is known about the molecular composition of this type of stress fiber-membrane interaction sites. Several actin-membrane association types are known, each employing a different set of proteins, and the focal adhesion and the erythrocyte membrane skeleton are the best characterized systems. We investigated by immunofluorescence microscopy if there is any morphological basis for the involvement of the erythrocyte membrane proteins in the stress fiber-plasma membrane association sites in cultured human fibroblasts. Our results indicated that fodrin (nonerythrocyte type spectrin) and ankyrin were generally associated with the plasma membrane, but that they were clearly excluded from the focal adhesion, the apical plaque and the stress fiber. Thus, it appears that the spectrin and the integrin based actin-membrane association systems are mutually excluded in the fibroblast membrane undercoat. Protein localization at the lateral stress fiber-membrane association site was also studied. Our data indicated that, while talin, vinculin, paxillin, fibronectin receptor and integrin beta 1 were present at the three stress fiber-membrane association sites, vitronectin receptor and integrin alpha v were absent from the apical plaque and the lateral association site. While the plasma membrane at the focal adhesion adheres tightly to a solid substrate, the cell surface of the apical plaque is free. Although the lateral association site faces the substrate, the molecular composition of this site is similar to that of the apical plaque.

Actin Cytoskeleton↗

[Effects of retinal intrinsic dopamine on the in in vivo electroretinogram of rabbits].

The effects of intravitreal injection of nomifensine, a potent dopamine uptake blocker, on the electroretinogram (ERG) were investigated in rabbit. Nomifensine enhanced the amplitude of the oscillatory potentials at 100 microM (intravitreal concentration) and 300 microM (p < 0.05), but it attenuated the oscillatory potentials at 1,000 microM (p < 0.01). Nomifensine attenuated the amplitude of the scotopic b-wave at 100 microM and 1,000 microM (p < 0.05), leaving the peak latency of the scotopic b-wave unaltered at all concentrations tested (30, 100, 300, 500 and 1,000 microM). Neither the amplitude nor the peak latency of the dark-adapted a- and b-waves elicited by bright stimuli was altered at any nomifensine concentration tested. 1 microM dopamine and 30 microM nomifensine together, each of which is insufficient to alter either of the scotopic b-wave or the oscillatory potentials when applied alone, reduced the scotopic b-wave and enhanced the oscillatory potentials. These results suggest that intrinsic dopamine release in the retina is large enough to alter the ERG.

Animals↗

[D1 receptor mediates dopamine-induced enhancement of electroretinographic oscillatory potentials].

The inhibitory action of SCH 23390 (SCH, D1-antagonist) or sulpiride (SUL, D2-antagonist) on the dopamine-induced enhancement of the electroretinographic oscillatory potentials was examined in anesthetized albino rabbits. Enhancement of the oscillatory potentials by intravitreal dopamine (50 microM intravitreal concentration) injection was blocked by a simultaneous intravitreal injection of SCH (20 microM) but not by SUL (50 microM, 100 microM). These results suggest that D1-receptor is mainly responsible for the dopamine-induced enhancement of the oscillatory potentials.

Action Potentials↗

[Partial purification of endogenous growth factor(s) of retinal pigment epithelial cells from neural retina].

We attempted to purify endogenous growth factors of chick embryonal retinal pigment epithelial cells from bovine neural retina. Ammonium sulfate precipitation, gel filtration, and anion exchange column chromatography were used. Though only partially purification, bovine retinal extract had two effects, growth and transformation, on chick embryonal pigment epithelial cells. We think that these purified factors may be novel from the estimation of their molecular weight by gel filtration.

Animals↗

[Diffuse B-cell lymphoma associated with hemophagocytic syndrome].

An 84-year-old female was admitted to our hospital because of fever. Physical examination and computed tomography revealed hepatosplenomegaly without lymphadenopathy. Anemia and thrombocytopenia were noted and the serum levels of LDH, IL-6 and sIL-2R were elevated. Bone marrow aspiration showed infiltration of lymphoma cells and proliferation of histiocytes with hemophagocytosis. Southern blot analyses revealed rearrangements of both IgJH and IgJK genes. She received corticosteroids with improvement of her general state but she died on the 110th hospital day. Necropsy of the spleen showed diffusely proliferating large lymphoma cells, immunoreactive for B cell marker L-26, and scattered histiocytes with hemophagocytosis.

Aged↗