Biomedical subjects
Hitoshi Yoshida
Publications and source records attributed to Hitoshi Yoshida.
Production of human monoclonal and polyclonal antibodies in TransChromo animals.
We have developed TransChromo (TC) technology, which enables the introduction of megabase-sized segments of DNA into cells. We have used this approach to derive mice that carry megabases of human DNA by the use of a human chromosome fragment (HCF) as a vector. TC technology has been applied to the construction of the TC Mouse,trade mark which incorporates entire human immunoglobulin (hIg) loci. TC Mouse expresses a fully diverse repertoire of hIgs, including all the subclasses of IgGs (IgG1-G4). Immunization of the TC Mouse with various human antigens produced antibody responses comprised of human antibodies. Furthermore, it was possible to obtain hybridoma clones expressing fully human antibodies specific for the target human antigen. However, because of the instability of the Igkappa locus-bearing HCF2, the efficiency of hybridoma production was less than one-tenth of that observed in normal mice. An instant solution to this problem was to cross-breed the Kirin TC Mouse carrying the HCF14, which was stable in mouse cells, with the Medarex YAC-transgenic mouse carrying about 50% of the hIgVkappa gene segments as a region that is stably integrated into the mouse genome. The resulting mouse, dubbed the KM Mouse, performed as well as normal mice with regard to immune responsiveness and efficiency of hybridoma production. Another application of TC technology is the production of polyclonal antibodies in large animals such as chickens and cows. To test the efficacy of human polyclonal antibodies derived from TC animals, feasibility studies were performed using antisera and purified gamma-globulin from TC mice immunized with Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), or Japanese encephalitis virus (JEV). The TC mouse-derived antisera and gamma-globulin showed a much higher titer and efficacy in terms of the neutralizing activity of the pathogens in vitro and in vivo than either human serum or gamma-globulin prepared from human blood.
Alpha-2 adrenoceptor activity affects propofol-induced sleep time.
UNLABELLED: alpha(2) Adrenoceptor activity is involved in the mechanism of anesthesia. Clonidine, a alpha(2) adrenoceptor agonist, and yohimbine, a alpha(2) adrenoceptor antagonist, increase and decrease barbiturate-induced sleep times. In this study, we examined the effects of these drugs on propofol-induced sleep time. One-hundred-eighteen male Wistar rats weighing 320-400 g were used. Rats received saline, yohimbine (1, 0.1, or 0 mg/kg), or clonidine (300, 30, 3, or 0 microg/kg) intraperitoneally followed by 60 mg/kg of propofol in various combinations. In two series of experiments, either sleep time or prefrontal cortex norepinephrine release (microdialysis) was measured. One milligram/kilogram of yohimbine decreased propofol-induced sleep time to approximately 70% of control, and this was accompanied by an increase in perfusate norepinephrine of approximately 240% of control. Clonidine increased sleep time approximately 260% (300 microg/kg) and approximately 170% (30 microg/kg), and this was accompanied by a decrease (approximately 60% in both doses) in perfusate norepinephrine. In the present study, we show that the alpha(2) antagonist, yohimbine, decreased and the alpha(2) agonist, clonidine, increased propofol-induced sleep times. These changes were essentially mirrored in both groups by changes in norepinephrine release in the prefrontal cortex. IMPLICATIONS: Central alpha(2) adrenoceptor is thought to be involved in several IV anesthetics-induced sleep. In this study, activation of the receptor increased the propofol-induced sleep time, whereas its inhibition decreased the sleep time. The results provide further evidence that the alpha(2) receptor is a good tool to elucidate the mechanism of anesthetics-induced sleep.
A case of autoimmune pancreatitis responding to steroid therapy. Evidence of histologic recovery.
We report a case of autoimmune pancreatitis without obvious evidence of autoimmunological participation, which responded well to steroid treatment and provided histologic and radiographic evidence for this improvement. A 68-year-old woman presented abdominal fullness, diffuse pancreatic swelling on abdominal computed tomography and ultrasonography, and diffuse narrowing of the main pancreatic duct on endoscopic retrograde pancreatography. Transgastric aspiration needle biopsy of the body of the pancreas performed under endoscopic ultrasonography showed severe atrophy of acinar cells, infiltration of T lymphocytes. She was diagnosed as having autoimmune pancreatitis without obvious evidence of autoimmunological participation. Administration of 30 mg/day of predonisolone was started. Computed tomography showed marked improvement of the diffuse swelling of the pancreas, and endoscopic retrograde pancreatograpy showed amelioration of the narrowing of the main pancreatic duct after the start of treatment. Pancreatic tissue obtained by needle biopsy after the start of treatment with predonisolone revealed marked histologic improvement, including amelioration of the fibrosis, and infiltration of inflammatory lymphocytes, and a substantial increase in the number of pancreatic acinar cells. The present report is the first to demonstrate histologic recovery of autoimmune pancreatitis after steroid therapy.
[A case with severe acute pancreatitis treated by regional arterial infusion of nafamostat mesilate and imipenem via both celiac artery and superior mesenteric artery].
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[Anesthetic management of a patient with dilated cardiomyopathy for left ventricular pacing lead insertion under video-assisted thoracic surgery].
A 54-year-old man with dilated cardiomyopathy treated with diuretics, alpha-beta blockers, antiarrhythmics for the previous 5 years, had the indication for biventricular pacing and was scheduled for placing of pacing leads in his left ventricular wall under video-assisted thoracic surgery. Preoperative tests revealed first degree A-V block with left bundle branch block and left ventricular dilation with an ejection fraction of 0.11 on echocardiography. Anesthesia was induced with ketamine and midazolam. Endotracheal intubation was facilitated by administration of vecuronium. Anesthesia was maintained with oxygen-sevoflurane and fentanyl. One lung ventilation was carried out during surgery and the arterial oxygen saturation was kept satisfactory with the intermittent insuffilation of oxygen to the non ventilated lung. The procedure was completed uneventfully while ventricular tachycardia was observed. Biventricular pacing increased the ejection fraction from 0.11 to 0.27. We conclude that any special monitoring such as TEE would be helpful to evaluate the cardiac function during the operation.
[A case of chronic pancreatitis showing diffuse irregular narrowing of the main pancreatic duct associated with ulcerative colitis and pancreas divisum].
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[Molecular mechanism of cadherin-mediated cell-cell adhesion].
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