FUKUSHIMA, Y., FUKUDA, M., YOSHIDA, K., YAMAGUCHI, A., NAKAMOTO, Y., MIURA, A.B., HARADA, T. and TSUCHIDA, S. Serum Erythropoietin Levels andInhibitors of Erythropoiesis in Patients with Chronic Renal Failure. Tohoku J. exp. Med., 150 (1), 1-15-The role of various factors in erythropoiesis was studied in 13 predialysis patients and 41 hemodialysis patients. Serum erythropoietin (ESF) was measured by the fetal mouse liver cell bioassay in vitro. The effect of uremic sera on heme synthesis and erythroid progenitor cell (CFU-E) formation was examined using normal human bone marrow cultures. Serum ESF levels in both predialysis (99.9±945.0mU/ml) and dialysis (141.2±109.7mU/ml) patients were significantly higher than those in normal controls (42.0±25.8mU/ml), although the titers were not sufficiently increased to correct the anemia. Serum ESF concentrations did not correlate with hemoglobin level or inhibition of both heme synthesis and CFU-E formation. Bone marrow CFU-Es in uremic patients were normal in the number, the responsiveness to ESF and the percentage in S-phase. Significant decrease in heme synthesis was observed in dialysis patients. The degree of inhibition of CFU-E formation showed a relationship to hemoglobin levels in uremic patients. By the CFU-E formation assay, the difference in inhibitory effects of the sera obtained from dialysis patients immediately before and after a hemodialysis was significant only under a low ESF concentration(0.125U/ml) but not under a high concentration (1.0U/ml). In conclusion, inhibition of heme synthesis and CFU-E formation, in addition to inadequate ESF production, plays an important role in renal anemia.
ISHIZUKA, J., TOYOTA, T., ONO, T., SASAKI, M., YANAIHARA, C. and YANAIHARA, N. Inhibitory Effects of Rimorphin and Dynorphin on InsulinSecretion from the Isolated, Perfused Rat Pancreas. Tohoku J. exp. Med., 1986, 150(1), 17-24-In order to settle the question about whether or not opioid peptides stimulate or inhibit insulin secretion, we studied effects of rimorphin and dynorphin, two members of the preproenkephalin B group, on glucose-induced insulin secretion in the isolated, perfused rat pancreas. These peptides (3.95×10-8 M), like morphine (3.95×10-8M), significantly inhibited the glucose-induced insulin secretion. The inhibitory effect of rimorphin was attenuated by naloxone (1.2×10-6M) and phentolamine (10-6M), suggesting an involvement of adrenergic alpha receptors in the inhibition of glucose-induced insulin secretion mediated through specific opiate receptors. Rimorphin also inhibited glucose-induced insulin secretion even in the cysteamine-treated rat pancreas from which somatostatin had been depleted. Thus, somatostatin does not appear to play a major regulatory role in the insulin secretion in the pancreas.
ISHIZAWA, E. and HORIUCHI, T. Postoperative Growth of the Left SubclavianArtery in a Case after a Modified Blalock-Park Procedure. Tohoku J. exp. Med., 1986, 150 (1), 25-30-Various kinds of operations for coarcation of the aorta in infancy are life saving, but they still carry a high operative mortality rate and are followed frequently by residual or recurrent coarctation. Fifteen years ago we performed a modified Blalock-Park procedure on a 12 month old male infant with preductal coarctation, a large VSD and PDA. Recently a follow-up study was performed on this patient. Aortography revealed a normally developed aortic arch without any sign of stenosis. The intraaortic pressure tracings revealed no pressure gradient through the aortic arch and thoracic aorta. These findings suggest that this procedure is recommendable for the treatment of infants with severely hypoplastic aortic isthmus.
FUJITA, M. and NAKAMURA, R. The Effect of PNF Position of the UpperExtremity on Rapid Knee Extension. Tohoku J. exp. Med., 1986, 150 (1), 31-35 -Premotor time (PMT) and maximum tension (Fmax) produced by isometric contraction of the left and the right quadriceps femoris for rapid knee extension were examined in 10 normal male subjects at two positions of the left upper extremity, neutral and facilitating position for the triceps brachii. Compared to the neutral position, PMT of the both sides decreased and Fmax increased at the facilitating position, while the contraction time did not change. It is assumed that the facilitating position brings about generalized activation of the central nervous system resulting in behavioral alertness.
KAGAWA, Y., TABAYASHI, K., SUZUKI, Y., ITO, T., SATO, N. and HORIUCHI, T. Intermediate Term Results of Isolated Mitral Valve Replacement withGlutaraldehyde-Preserved Porcine Xenograft Valve: Clinical and HemodynamicComparison between Hancock Valve and Angell-Shiley Valve. Tohoku J. exp. Med., 1986, 150 (1), 37-50-Clinical and hemodynamic assessments were carried out for 30 cases, who underwent isolated mitral valve replacement with glutaraldehyde-preserved porcine xenograft valve. The cases were divided into two groups, according to the types of prostheses. Group H comprised 23 cases with Hancock 342 valve and group AS, 7 cases with Angell-Shiley valve. Mean (S.D.) follow-up periods were 4.0±0.7 in group H and 4.6±0.6 years in group AS. Incidence of valvular malfunction was 3.3 in group H and 9.3% per patient-year in group AS. Cumulative survival and event-free rates were calculated by actuarial method, which revealed 91 and 83% in group H and 70 and 71% in group AS at 6 years after operation. Hemodynamic assessments were carried out in 20 cases, in which complete data at rest and during exercise were obtained. Valvular function deteriorated during exercise in both groups. Parameters showing valvular function in group AS were worse than those in group H. It is concluded from this study that (1) intermediate late results are satisfactory in group H, (2) incidence of valvular malfunction is high in children and in group AS, (3) thromboembolisms are seen even in cases with recourse to anticoagulant, (4) xenograft valves are stenotic especially in high flow state and (5) valvular function of AS valve is inferior to H valve.
ISAWA, T., TESHIMA, T., HIRANO, T., EBINA, A. and KONNO, K. Effect of OralSalbutamol on Mucociliary Clearance Mechanisms in the Lungs. Tohoku J. exp. Med., 1986, 150 (1), 51-61, The purpose of the study was to investigate whether or not orally administered salbutamol would affect mucociliary clearance function in the lungs. Salbutamol, 4mg, was given orally 3 times a day for 7 days to 10 and 9 patients with various chest diseases in stable stage, respectively; the former were also currently taking other medications and the latter, none. Lung function tests, chest x-rays and radioaerosol inhalation lung cine-scintigraphy were performed before and after the administration of salbutamol. There was little qualitative or quantitative difference in mucociliary clearance function in either group before and after the administration of oral salbutamol, although it induced some increases in VC and FEV1.0 and a decrease in RV/TLC ratio in the former and some increases in FEV1.0, FEV1.0% and MMF in the latter. Oral salbutamol seems little to affect the mucociliary clearance function in the lungs.
KUROBANE, I., INOUE, S., GOTOH, Y-I., KATO, S., TAMURA, M., NARISAWA, K. and TADA, K. Biochemical Improvement after Treatment by Bone MarrowTransplantation in I-Cell Disease. Tohoku J. exp. Med., 1986, 150 (1), 63-68-The first case of successful bone marrow transplantation (BMT) in a patient with I-cell disease is reported. A 8-month-old girl with I-cell disease (N-acetylglucosaminylphosphotransferase deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched brother who has heterozygous level of the transferase activity. The following biochemical and clinical improvements have occurred: the transferase in peripheral lymphocytes increased to donor's level, and lymphocytec α-neuraminidase, β-galactosidase and α-mannosidase increased to normal levels. Plasma acid hydrolase activities, which had been 10 to 60 times higher in the patient than normal control levels, have slowly but steadily decreased from one month after the graft. Such decreases were observed in the activities of α-mannosidase, N-acetyl-β-glucosaminidase, α-fucosidase, arylsulfatase A and acidic β-galactosidase. There was also a marked decrease of vacuolated peripheral lymphocyte after the BMT. Three-months after the engraftment, hepatomegaly gradually decreased in size, corneal clouding has not progressed, and tight skin seems to have improved.
AONUMA, S., ARIJI, F., OIZUMI, K. and KONNO, K. Electron MicroscopicStudy of the Cell Surface of Dibekacin-Treated Pseudomonas aeruginosa. Tohoku J. exp. Med., 1986, 150 (1), 69-75-Electron microscopy of thin sections of Pseudomonas aeruginosa IAM 1007 treated with dibekacin revealed blebs, disintegration of the outer membrane of the cell wall and degenerative features of the cytoplasm. In the next experiment, the cell wall fraction was isolated from the mechanically disrupted cells, incubated with dibekacin and was subjected to electron microscopy, in order to find a clue to the action mechanism of dibekacin on the cell wall of Pseudomonas aeruginosa IAM 1007. As a result, it was found that unidentified substances were released from the surface of the cell wall and that the outer membrane of the cell wall disappeared. The degree of changes of the cell wall ultrastructure was almost proportional to the length of incubation with dibekacin. These findings strongly suggest that dibekacin directly disintegrates the outer membrane of the cell wall of Pseudomonas aeruginosa IAM 1007.
OTOTANI, N. and YOSIZAWA, Z. Inhibitory Activities for Thrombin and FactorXa of Whale Heparin: Comparative Studies on Two Preparations from DifferentSpecies. Tohoku J. exp. Med., 1986, 150 (1), 77-82-Whale intestinal heparin preparations from Balaenoptera physalus L. (Bp) and Balaenoptera borealis L. (Bb) were fractionated by affinity chromatography on a column of antithrombin III (AT)-Sepharose 4B. The yields of high-affinity fractions for AT (HA) from Bp and Bb were 86.8 and 13.3%, respectively, in total. The inhibitory activities for thrombin of Bp and Bb and their HA and those for Factor Xa of the latter were compared in the presence of AT. The results indicated that the inhibitory activities for thrombin of Bp and its HA were higher than those of Bb and its HA, respectively. No noticeable difference in the inhibitory activity for Factor Xa was, however, observed between HA from Bp and Bb. The present observations confirm our previous assumption that the presence of the thrombin-binding regions in addition to the AT-binding regions in heparin molecule are essential for the manifestation of high inhibitory activity for thrombin in the presence of AT.
MATSUBARA, S., OKABE, K., OUCHI, K. and OWADA, Y. Blood Purification ofBilirubin and Bile Acids by Plasma Exchange for Patients with Liver Failure. Tohoku J. exp. Med., 1986, 150 (1), 83-90-To evaluate the efficacy of blood purification by plasma exchange in patients with liver failure, blood levels of total bilirubin and total bile acids, known to be a part of protein-bound toxins, were measured before and after plasma exchange. With one plasma volume exchange the percent reduction was 39 for bilirubin and only 25 for bile acids. The declining of the reduction efficiency appeared to be well correlated with the prolongation of the treatment time for bilirubin and the augmentation of the initial concentration for bile acids. These data suggested that the equilibration between intra-and extra-vascular pool takes place slowly for bilirubin and comparatively rapidly for bile acids, though they are both mostly bound to albumin in the blood. In addition, the presence of protein-bound toxins like bile acids, predominantely accumulated in the tissue, may make it more difficult to support patients with liver failure by only blood purification therapy with plasma exchange.
SASAKI, I., NAITO, H., MATSUNO, S. and SATO, T. Experimental Studies on theInfluence of Simultaneous Ligation of the Bile and Pancreatic Ducts upon GastricAcid Secretion and Gut Hormones. Tohoku J. exp. Med., 1986, 150 (1), 91-99-The influence of simultaneous ligation of the bile and pancreatic ducts on gastric acid secretion and gut hormones, particularly gastrin and secretin, was studied in 5 dogs with a Heidenhain pouch. In addition, the pH of the duodenal content was measured in 2 dogs with a duodenal fistula. Tests in response to a test meal were done during the control and observation periods. In all of the 5 dogs the mean 24 hr-acid output from the Heindenhain pouches showed a significant increase from 199 to 564%. Plasma gastrin levels during the fasting showed no significant change, but the peak response to the test meal significantly decreased from 83.6± 4.4pg/ml (mean±S.E.) before the ligation to 42.1±4.2pg/ml after the ligation. Plasma secretin levels were significantly elevated after the ligation both during fasting and after the test meal. The pH of the duodenal contents after the test meal was lower after the ligation than before. These results suggest that gastric hypersecretion induced by the simultaneous ligation of the common bile and pancreatic ducts is not related simply to release of gastrin, and further hyper-sercretinemia may depend on gastric hypersecretion.
HORII, D. and ISHIBASHI, A. Coronary Dilator Effect of MCI-176, a NewCalcium Channel Blocker, in Dogs. Tohoku J. exp. Med., 1986, 150 (1), 101-102 -Effects of MCI-176, 2-(2, 5-dimethoxyphenylmethyl)-3-(2-dimethyl-aminoethy1)-6-isopropoxy-4 (3H)-quinazolinone hydrochloride, on coronary and aortic blood flows, mean blood pressure and heart rate were investigated in comparison with those of diltiazem in anesthetized dogs. MCI-176, like diltiazem, dose-dependently increased coronary and aortic blood flows and decreased mean blood pressure. In producing these effect MCI-176 was slightly but significantly more potent than diltiazem. Heart rate tended to increase with MCI-176, whereas it tended to decrease with diltiazem.