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Biomedical subjects

M Tsuchiya

Publications and source records attributed to M Tsuchiya.

At least 163 records · Page 9Linked to original sources
PubMed1994

Humanization of a mouse anti-human interleukin-6 receptor antibody comparing two methods for selecting human framework regions.

Mouse monoclonal antibody AUK12-20 binds to human IL-6 receptor and inhibits IL-6 functions. It has been humanized by CDR-grafting for therapeutic use. In the design of reshaped human AUK12-20 VL region, the human framework regions (FRs) from the human Bence-Jones protein REI were used. The reshaped human AUK12-20 light chain, in combination with chimeric AUK12-20 heavy chain, bound to antigen as well as chimeric AUK12-20 antibody. In the design of reshaped human AUK12-20 VH region, two sets of the human FRs were chosen and compared. One set was from the consensus amino acid sequence for human VH regions subgroup (HSG)-I and the other set was from human antibody HAX, the most similar human VH region found in a database of human immunoglobulin sequences. The HSG-I-based and the HAX-based reshaped human AUK12-20 heavy chains in combination with the reshaped human AUK12-20 light chain, showed approximately 90 and 100% antigen-binding and competition-binding activities as compared to the chimeric or mouse AUK12-20 heavy chains. Most importantly, these humanized antibodies inhibited the IL-6-dependent tumor cell growth as well as the original mouse antibody suggesting that these humanized antibodies could be efficacious in human patients. Our results show that both approaches for the design of reshaped human antibodies can be used for successful humanization. The approach based on FRs from the most similar individual human antibody, however, seemed to be best for designing a reshaped human antibody that mimicked as closely as possible the original mouse antibody.

Amino Acid Sequence↗
PubMed1994

A cephalometric and electromyographic study of upper airway structures in the upright and supine positions.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep, usually in the supine position. To investigate the relationship between upper airway size and genioglossus (GG) muscle activity, upright and supine cephalograms were obtained in 20 OSA patients and 10 symptom-free control subjects. Tongue electromyographic (EMG) recordings were obtained with surface electrodes, and pressure transducers were placed in the 10 symptom-free controls. The tongue cross-sectional area increased 4.3% (p < 0.05), and the oropharyngeal area decreased 36.5% (p < 0.01) when the OSA patients changed their body position from upright to supine. No changes were observed in the tongue area, but soft palate thickness increased (p < 0.01) when the control subjects changed from the upright to the supine position. Furthermore, the oropharyngeal cross-sectional area decreased 28.8% (p < 0.01) despite a 34% increase (p < 0.05) in resting GG EMG activity. Posterior tongue pressure increased 17% (p < 0.05) with the change from upright to supine. On the basis of these findings, we propose that body posture has a substantial effect on upper airway structure and muscle activity. This postural effect should be taken into account when assessing upper airway size in the erect posture (conventional cephalography) and in the supine position (computed tomography). The vertical and anteroposterior position of the tongue and its relationship to airway size may be more important than soft palate size in the pathogenesis of OSA.

Airway Resistance↗
PubMed1994

Evidence of direct interaction between Kupffer cells and colon cancer cells: an ultrastructural study of the co-culture.

A co-culture study of purified rat Kupffer cells and human colon cancer cells was performed, and the process of the tumor cell injury was observed under an inverted type fluorescence microscope loaded with propidium iodide, and also under an electron microscope. Ultrastructurally there was direct membrane-to-membrane interaction between Kupffer cells and colon cancer cells in time. The interaction occurred 1 h after start of the co-culture, and injured tumor cells were observed closely attached to pseudopodia of Kupffer cells at 6 h. The number of propidium iodide-positive tumor cells with damage increased in time. Pretreatment with NG-monomethyl-L-arginine reduced the number of injured tumor cells without preventing morphological interactions, but superoxide dismutase did not prevent the tumoricidal effect. Pretreatment with trypsin completely inhibited cell interaction and damage to tumor cells. In conclusion, the morphological interaction of Kupffer cells as a first step and the involvement of nitric oxide-derived free radicals as a second step seem to play a significant role in the host-defense mechanism.

Animals↗
PubMed1994

Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity.

Alanine↗
PubMed1994

Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical oxidative injury in hypoperfused rat liver.

This study was designed to investigate the effects of prostaglandin E1 on reductive stress and the subsequent oxidative cell injury in hypoperfused rat liver. The intralobular heterogeneity of hepatocellular redox state, mitochondrial dysfunction, and intracellular hydroperoxide formation were visually monitored by digital microfluorography of pyridine nucleotide autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence, respectively. Under the 25% low flow perfusion, pyridine nucleotide autofluorescence increased time-dependently and reached a steady state at 10 min among the entire lobules. The decrease in mitochondrial membrane potential was > 20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide formation was observed at 40 min in the marginally oxygenated proximal portion of anoxic pericentral regions and the oxidative impact reached a maximum level at 60 min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5-triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor, suppressed the zone-specific oxidative changes without attenuating the increase in pyridine nucleotide autofluorescence and mitochondrial dysfunction. Pretreatment with prostaglandin E1 not only abrogated an early increase in pyridine nucleotide fluorescence and mitochondrial dysfunction induced by hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of this reagent on the hypoxia-induced oxidative cell injury is attributable to the attenuation of mitochondrial dysfunction. These results suggest that, in low flow hypoxia, early reductive stress plays a key role in the initiation of xanthine oxidase-mediated midzonal oxidative changes, which may lead to subsequent centrilobular necrosis.

Alprostadil↗
PubMed1994

Inhibition of Helicobacter pylori urease activity by hydroxamic acid derivatives.

Helicobacter pylori (HP) produces strong urease [EC 3.5.1.5], which is considered to play a role in the pathogenesis of gastritis and peptic ulcers. Inhibitions against this enzyme have been studied with hydroxamic acid (HXA) derivatives of aliphatic or aromatic carboxylic acids, amino acids and dipeptides. A number of HXAs potently inhibited the urease (I50 values were near the order of 10(-6)M), and H-Ile-Gly-NHOH (I50 = 0.20 x 10(-6)M) was the most potent inhibitor among the derivatives. HP urease was inhibited more potently, in general, than Jack bean (JB) urease by HXAs, and a correlation between the chemical structures of HXA derivatives and their inhibitory effects on HP urease was observed, in comparison with JB urease.

Amino Acids↗
PubMed1994

[Application of the Limulus test for practical quality control on endotoxin content in commercial human serum albumin (HSA) products. In comparison with the rabbit pyrogen test].

The bacterial endotoxin content in human serum albumin (HSA) products measured by two different Limulus amebocyte lysate (LAL) test methods, colorimetric and kinetic turbidimetric methods, were compared. So far as endotoxin-specific LAL reagents which do not show a false-positive reaction with (1-->3)-beta-D-glucan are used, a definite correlation was found between the results with the two LAL test methods. Endotoxin added to HSA products was recovered in a quantitative manner showing neither inhibition nor enhancement by HSA to the both LAL test methods. Results of the LAL tests showed a significant correlation with that of the rabbit pyrogen test. The correlation was much improved with endotoxin-added HSA. The present results indicate the practical applicability of the LAL test as an alternative method for the rabbit pyrogen test.

Animals↗
PubMed1994

Gastric mucosal injury: microcirculation and Helicobacter pylori.

The integrity of gastric mucosa is well-balanced by an array of defensive mechanisms which protect the mucosa against external aggressive factors. When excessive stimulation of autonomic nervous system (irritation) is induced, microcirculatory disturbances easily lead to the gastric mucosal damage due to the formation of vasoactive mediators and oxygen radicals. In this review, our discussion has been focused on the co-ordinating function of the autonomic nervous system as well as the microcirculation as an important defense bastion. In this context, Helicobacter pylori represents an important pathogenic factor. In particular, we have discussed the contribution of monochloramine, and active oxidant, which is formed by neutrophils in the presence of ammonia derived from H. pylori to the gastric mucosal injury. Microcirculatory disturbances may be also involved in the pathogenesis of H. pylori-induced mucosal injury. On the basis of these considerations, we should not depend solely on the use of anti-acid secretory drugs for the treatment of gastric mucosal injury, but also should be aware of beneficial effect of mucosal protective drugs which may act on microcirculation and the autonomic nervous system.

Animals↗
PubMed1994

Vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase activity and re-activation of the less-active form by dithiothreitol plus NaCl under anaerobic conditions.

We observed dilution/vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase purified from chicken peripheral polymorphonuclear granulocytes (heterophils) and re-activation of the less active form by dithiothreitol plus NaCl, under anaerobic conditions. The vortex-mixing-induced inactivation of the diluted enzyme was rapid; more than 85% of the enzyme activity was lost with 1-min vortex-mixing at room temperature. When the less-active form of the enzyme was treated with 10 mM dithiothreitol plus 0.2 M NaCl, under anaerobic conditions, more than 50% of the enzyme activity was restored. Putative mechanisms of the vortex-mixing-induced inactivation and dithiothreitol/NaCl-dependent re-activation of the arginine-specific ADP-ribosyltransferase are discussed.

ADP Ribose Transferases↗
PubMed1994

The impact of diabetes mellitus on the prognosis of alcoholics.

In this study, the mortality of clinically treated Japanese alcoholics with diabetes mellitus was analysed. Fifty-one diabetic alcoholics without liver cirrhosis (DM), 23 diabetic and cirrhotic alcoholics (DM.LC), 44 cirrhotic alcoholics without diabetes (LC), and 354 alcoholics without either complication (AL) admitted to the National Institute on Alcoholism in 1985 were studied. Thirty-seven diabetics required insulin treatment, and 12 oral hypoglycemic agents. The 4.4-year survival and drinking status after discharge were studied in 1990. Stepwise logistic regression analysis showed that the estimated odds for death increased 8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcohol misuse after discharge, DM, DM.LC, and LC, respectively. The 4.4-year survival rate of alcoholics who continued misusing alcohol was much lower in DM (26%,P < 0.0005) and LC (35%, P < 0.0001) than in AL (73%). The survival rate of those who stopped misusing alcohol was significantly higher in DM (90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P < 0.0005) than those who continued misusing alcohol. There was no significant difference in the survival rate between the alcoholics with DM.LC who continued misusing alcohol (50%) and those who stopped misusing alcohol (73%). In the dead patients, 56% of DM died unexpectedly or suddenly, whereas 71% of LD died of liver failure after hospitalization. These results suggest that diabetic alcoholics should be intensively educated for abstinence.

Adult↗