KANO, E., FURUKAWA, M., KANEKO, I., YOSHIKAWA, S., TSUBOUCHI, S., KONDO, T. and YAMAGATA, K. Device of Anoxic Chamber System and Repair ofPotentially Lethal Damage of Anoxic Cells in Vitro. Tohoku J. exp. Med., 1986, 148 (1), 1-13-In order to study radiation responses of anoxic plateau phase cells in vitro, an air-tight anoxic chamber was devised in which Chinese hamster V-79 or Swiss mouse NIH3T3 cells were deoxygenated by replacing the air with saturatedly humidified N2 gas. The cells as adhered on the culture plate, which was contained in the anoxic chamber, were x-irradiated. The deoxygenated condition in the anoxic chamber was maintained as long as necessary. Oxygen enhancement ratio obtained by the anoxic chamber was about 2.6. Repair of potentially lethal damage of the anoxic plateau phase cells was observed to the same extent of that of the oxic cells.
AKIBA, T., YOSHIKAWA, M., KINODA, M., OTAKI, S., KOBAYASHI, Y. and SATO, T. Assessment of Cardiac Performance by First Pass Radionuclide Angiocardiographyin Infants and Children with Normal Heart and Endocardial Fibroelastosis. Tohoku J. exp. Med., 1986, 148 (1), 15-23-Peak to peak time from the right and to the left ventricle (PPT), left ventricular ejection fraction, left ventricular peak ejection rate and left ventricular peak filling rate were measured by first pass radionuclide angiocardiography in 27 infants and children with normal heart and in 8 patients (18 studies) with endocardial fibroelastosis. In normal subjects, the PPT significantly correlated with heart rate (r=-0.87, p<0.001). A PPT corrected by the heart rate (cPPT) was calculated by rotation of the regression equation relating the variables: cPPT=PPT+0.018×(heart rate)-2.1. The cPPT averaged 3.0±0.0 (mean+S.E.) sec. Consequently, there was no significant correlation between the cPPT and heart rate, but the cPPT and body surface area are significantly correlated (r=0.41, p<0.05). Left ventricular ejection fraction, peak ejection rate and peak filling rate averaged 68±2%, 4.2±0.3/sec and 4.8± 0.3/sec, all of which were independent of the heart rate and body surface area. In patients with endocardial fibroelastosis, the cPPT was prolonged (4.7±0.4sec), and left ventricular ejection fraction, peak ejection rate and peak filling rate were all reduced (28±4%, 1.7±0.2/sec and 1.8±0.2/sec). These results indicate that parameters obtained from the radionuclide angiocardiography are useful for evaluating cardiac performance in patients with endocardial fibroelastosis.
ETO, M., WATANABE, K., IWASHIMA, Y., MORIKAWA, A., OSHIMA, E., SEKIGUCHI, M. and ISAHII, K. Apolipoprotein E Phenotypes and Plasma Lipidsin Young and Middle-Aged Subjects. Tohoku J. exp. Med., 1986, 148 (1), 25-34-The relationsphip between apolipoprotein (apo) E phenotypes and the levels of plasma lipid, lipoprotein and apo E in young (mean, 21 years of age) and middle-aged (mean, 49 years of age) subjects was investigated. Apo E phenotypes were determined by a rapid flat gel isoelectric focusing method that we had developed previously. Young subjects with apo E3/2 and E4/3 had significantly higher levels of plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG and VLDL-cholesterol than those with apo E3/3. Middle-aged subjects with ap oE3/2 (54.5%) and E4/3 (39.1%) had higher frequency of hyperlipoproteinemia (mainly type IV) than those with apo E3/3 (25.8%). Furthermore, the middleaged subjects with apo E3/2 had significantly higher levels of plasma TG, VLDL-TG and apo E, and significantly lower levels of plasma high density lipoprotein-cholesterol than those with apo E3/3. These results indicate that apo E phenotype E3/2 and E4/3 are associated with lipid abnormalities even in young subjects, which may be caused by impaired functions of apo E2 and E4.
SAITO, K. Effects of Diquat on Cell Growth; and Macromolecule Synthesis inCultured Pneumocytes. Tohoku J. exp. Med., 1986, 148 (1), 35-39-The effects of diquat (DQ) on cell growth and macromolecule synthesis were investigated in cultured rat, feline and human. pneumocytes. DQ at 10-3M and 10-5M showed time- and dose-dependent inhibition of cell growth for 7 days. The incorporation of 3H-thymidine, 3H-uridine and 14C-leucine into DNA, RNA and protein was reduced to 0-47% by 10-3M of DQ, and that of 14C-leucine into protein of A-549 cells was reduced to 67% by 10-5 DQ. Among the cells examined, A-549 cells derived from human lung were the most resistant to the inhibitory effects of DQ on cell growth and macromolecule synthesis. On the other hand, human lung embryonic fibroblast cells and L-2 cells derived from rat lung were the most sensitive to the toxicity of DQ. These results indicate that the inhibitory effects of DQ on cell growth and on macromolecule synthesis are dependent on the concentrations of DQ administrated, and that species differences in the sensitivity to DQ toxicity may exist.
SAITO, K. Effect of Cations and Some Compounds on Paraquat Accumulationinto Cultured Pneumocytes. Tohoku J. exp. Med., 1986, 148 (1), 41-47 -Paraquat and diquat, bipyridilium herbicides, have been shown to be accumulated into pneumocytes of three species in culture. Paraquat at 10-3M was accumulated to a maximum of 3-7nmol/mg protein for 20min. Diquat accumulated more slowly but reached a concentration of 1-6nmol/mg protein for 60min. Differences in the ability of various pneumocytes to accumulate paraquat and diquat appear to exist. It was found that the cations, Ca++, Na+ and K+, reduced the accumulation of paraquat. Valinomycin stimulated paraquat accumulation significantly. On the other hand, paraquat accumulation was inhibited by 2, 4-dinitrophenol. These results indicate that paraquat may be accumulated, in part, as cation species into pneumocytes and also by a energy-dependent process regulated by cellular ATP.
HANEDA, K. and HORIUCHI, T. A Method for Measurement of Total CirculatingBlood Volume Using Indocyanine Green. Tohoku J. exp. Med., 1986, 148 (1), 49-56 - A method of measuring total circulating blood volume (TBV) using indocyanine green (ICG) dye was investigated in 7 dogs and 16 patients. Since concentration of injected ICG decreases exponentially from the circulating system after recirculation, concentration of the dye at the time of appearance (Cta) can be extrapolated by extending the slope of the dye dilution curve transcribed to a semi-logarithmic graph. TBV was calculated using the following formula: TBV=I/Cta, where I is the amount (mg) of ICG injected. Repeat measurements of TBV using ICG demonstrated good reproducibility (average coefficient of variation, 2.0%) and when compared to measurements made with Evans blue dye resulted in a correlation coefficient of 0.98 or more. We conclude that assessment of TBV using ICG is reliable and experimentally and clinically feasible.
MURAI, A., MIYAHARA, T., TANAKA, T. and KAMEYAMA, M. Characterizationof Plasma Lipoproteins in Survivors of Cerebral infarction. Tohoku J. exp. Med., 1986, 148 (1), 57-64 - To characterize the plasma lipoproteins in survivors of cerebral infarction, plasma lipoproteins were ultracentrifugally fractionated into VLDL, LDL, HDL2 and HDL3, and the concentrations of cholesterol, phospholipid, apolipoprotein and triglyceride in each lipoprotein class were determined. Subjects examined were 15 male healthy controls and 15 male survivors of cerebral infarction situated in the distribution of cerebral cortical artery. The concentrations of VLDL-cholesterol and VLDL-triglyceride and the percent content of VLDL-cholesterol were higher in survivors than in controls. The concentration of LDL-triglyceride was higher and the percent content of LDL-cholesterol was lower in survivors than in controls. While the plasma concentration of triglyceride was higher in survivors than in controls, those of HDL, HDL2 and HDL3 were lower in survivors. The concentrations of cholesterol, phospholipid and apolipoprotein in either HDL2 or HDL3 were also reduced in survivors as compared with controls. In either HDL2 or HDL3, the percent content of triglyceride was higher and that of phospholipid was lower in survivors than in controls. These results were in good agreement with those reported for survivors of myocardial infarction, suggesting that the underlying derangement in lipoprotein metabolism is common to myocardial and cerebral infarction.
SAITO, Y., UZUKA, Y., TAKAHASHI, H., KOMATSU, M. and ITO, T. TheTreatment of Chronic Myelogenous Leukemia in Blastic Crisis with the ChemotherapyIncorporating Vindesine-Prednisolone. Tohoku J. exp. Med., 1986, 148 (1), 65-72 - Twenty-three patients with chronic myelogenous leukemia (CML) in terminal transformation were teated with regimen incorporating vindesine and prednisolone with or without cytosine arabinoside. Twenty-one patients in blastic crisis (BC) were classified into subgroups on the blast cell morphology. Of these 21 patients, 5 (23.8%) had lymphoid morphology, 12 (57.2%) had myeloid morphology, and 4 (19.0%) had monocytoid morphology. All of five patients with lymphoid morphology and ten of twelve patients with myeloid morphology achieved complete remission (83.3%), while none of four patients with monocytoid morphology achieved complete remission. Two patients in accelerated phase also attained complete remission. Our results indicate that the regimens incorporating vindesine and prednisolone with or without cytosine arabinoside should be the treatment of choice in CML-BC both lymphoid and myeloid morphology and accelerated phase of CML as well.
MUSHA, M., ISHII, A., TANAKA, F. and KUSANO, G. Poisoning by HallucinogenicMushroom Hikageshibiretake (Psilocybe argentipes K. Yokoyama) Indigenousto Japan. Tohoku J. exp. Med., 1986, 148 (1), 73-78-Five cases of poisoning by indigenous mushroom Hikageshibiretake (Psilocybe argentipes) are reported. As this mushroom contains psilocybin, in general, clinical features were similar to those seen by pure psilocybin. Acute toxic stuporous state with complete amnesia in the culminating period occurred in one case, psychedelic state with dreamy consciousness in one case and psychotic adverse reactions with vivid visual hallucinations with consciousness in three cases. There were accompanied with anxiety and panic reactions to subjective experiences. Though these toxic effects were usually short-lived, for management of such patients it is important to recognize that horrible emotional reactions and other harmful behavioral problems can also occur.
MIZUSHIMA, Y, IWATA, M., SATO, M. and YANO, S. Effects of Interleukin-2, OK-432 and Interferon-Gamma on In Vitro Induction of Nonspecific Killer Cellsby Concanavalin A in Mice. Tohoku J. exp. Med., 1986, 148 (1), 79-85 -Human interleukin-2 (IL-2), OK-432 and mouse interferon-gamma (IFN-γ) were evaluated for their beneficial effects on in vitro induction of nonspecific killer cells by concanavalin A (Con A). Nonspecific killer cells could be induced by culturing C57BL/6 spleen cells for 4 days with Con A. Con A activated killer cells showed direct cell-mediated cytotoxicity (DCMC) and lectin-dependent cell-mediated cytotoxicity (LDCC) against natural killer (NK) sensitive YAC-1 cells, and LDCC against NK-resistant EL-4 cells in a 4hr-51Cr release assay. Higher DCMC and LDCC reactivity against YAC-1 cells, and higher LDCC reactivity against EL-4 cells were obtained with spleen cells cultured with Con A plus IL-2, or Con A plus OK-432 than with those cultured with Con A alone. No beneficial effect of IFN-γ and no additive effects of IL-2 plus OK-432, or IL-2 plus IFN-γ were observed in the induction of nonspecific killer cells by Con A.
HIRAI, N., HATTORI, N., GEORGIADES, J., OSTHER, K. and BERG, K. ACytotoxic Substance (CTS-51) Produced by Human Buffy Coat Cultures Stimulatedby Staphylococcal Enterotoxin B: Further Characterization and CombinedAction with Interferon. Tohoku J. exp. Med., 1986, 148 (1), 87-97 - A recently recognized unique cytotoxic substance, CTS-51, was tested for the heat or acid stability, trypsin digestion and dialysis. Moreover, influences of elevated incubation temperatures or serum concentrations of medium on the cytotoxic activity of CTS-51, and the combination effects of CTS-51 and human leucocyte interferon (HuIFN-α (Le)) were investigated. The cytotoxic activity of CTS-51, which is promoted by a small molecule easily passable the dialysis membrane, was found to be very stable to heat (even at 100°C for 30min) or acid (pH 2.0 for 24hr at 4°C) treatments. The treatment with 0.75% trypsin for 1hr did not diminish the CTS-51 activity. The susceptibility of Daudi lymphoma cells to the antiproliferative action of HuIFN-α (Le) was further potentiated by treating the cells with CTS-51 for 16hr. On the other hand, the CTS-51 activity which was revealed to be prescribed by its concentration in the medium, was not potentiated at 39°C when compared to that at 37°C in contrast to HuIFN-α (Le) action, and was reduced according to the increase of the fetal calf serum concentration in the medium.
KANOH, T., HASHIMOTO, M., USUI, T. and UCHINO, T. Auer Rods in MatureGranulocytes and Monocytes. Tohoku J. exp. Med., 1986, 148 (1), 99-102 - In a 73-year-old man with acute myelomonocytic leukemia (M4 on FAB classification) Auer rods were demonstrated in mature granulocytes and monocytes in the blood as well as the bone marrow. Cytochemically, a significant number of leukemic blasts were positive for both alpha-naphthyl-acetate esterase and naphthol-AS-D-chloroacetate esterase. Auer rods in mature granulocytes were associated with immature cytoplasm and not infrequently with pseudo-Pelger anomaly. The significance of these observations is discussed.
ITOH, T., THOMAS, R., FOLTZ, B.D. and DILLARD, D.H. Blood AnestheticLevels during Surface-Induced Deep Hypothermia under Halothane-Diethyl EtherAzeotrope Anesthesia. Tohoku J. exp. Med., 1986, 148 (1), 103-111 - Blood anesthetic concentration and clinical indicators related to anesthetic management during surface-induced deep hypothermia were determined in seven adult mongrel dogs. The azeotrope of halothane and diethyl ether was assayed by gas chromatography. Blood concentration of halothane ranged from a pre-cooling control of 0.74 vol% to 0.11 vol% at 20°C rewarming; ether ranged from 0.06 vol% at 20°C rewarming to 0.22 vol% at 35°C rewarming. Administration of anesthetic was reduced during cooling because of the spontaneous decrease in mean arterial pressure and heart rate. After elective circulatory arrest was induced, anesthetic was not required until after cardiac resuscitation at about 22°C rewarming. Initial clinical signs indicating a need to increase administration of anesthetic included spontaneous respiration and an increase in mean arterial pressure. Blood azeotrope concentration was significantly lower during rewarming than at comparable temperatures during cooling. We conclude that blood concentration of halothane and ether changes as a function of body temperature and that anesthetic demand may be diminished following total circulatory arrest.
KONDO, S., MORITA, T., TSUCHIDA, S., TERUI, M. and TASHIMA, Y. Effect ofDobutamine on Adenylate Cyclase Activity in Rabbit Renal Pelvis and Ureter. 1986, 148 (1), 113-114 - The adenylate cyclase activity in the rabbit renal pelvis and ureter was measured by the method of Salomon et al. (1974). The dobutamine-induced increase of adenylate cyclase activity is more prominent in the renal pelvis including the pacemaker region than in the ureter that is non-pacemaker region in the upper urinary tract. Therefore, it is thought that the pacemaker region is different from other regions in the upper urinary tract with regard to responses to dobutamine.
MIZUTA, K., MORIGA, M., NARUSAWA, H., UCHINO, H. and AONO, M. Effect ofIntracerebroventricular Injection of Vasoactive Intestinal Polypeptide on SystemicBlood Pressure, and Pancreatic and Gastric Secretions in the Rat. Tohoku J. exp. Med., 1986, 148 (1), 115-116 - In order to examine the central effects of VIP (vasoactive intestinal polypeptide) on systemic blood pressure, and pancreatic and gastric secretions in rats, the peptide was given to rats intracerebroventricularly (i. c.v.) through the lateral cerebroventricle. VIP, when given i.c.v., showed no effects on systemic blood pressure, and pancreatic and gastric secretions in rats. The present results indicate that VIP affects these functions not centrally but peripherally. Physiological role of VIP in the brain remains to be elucidated.
NIHEI, M., IMAI, Y., ABE, K., SASAKI, S., MIURA, Y. and YOSHINAGA, K. Ambulatory Blood Pressure Measurement in a Patient with Pheochromocytoma byMeans of a Finger Volume-Oscillometric Device. Tohoku J. exp. Med., 1986, 148 (1), 117-118 - A new device which measures ambulatory blood pressure was used to detect paroxysmal hypertension in patients with pheochromocytoma. The device uses a finger volume-oscillometric technique for the long-term mesurement of indirect arterial pressure at desired intervals. The device clearly detected crises of hypertension of short duration. This device is invaluable for the detection of paroxysmal hypertension in patients with pheochromocytoma.