OHKOHCHI, K., TORINUKI, W. and TAGAMI, H. Increased Plasma Concentrationsof Complement Modulating Proteins (C1 Inhibitor, C4-Binding Protein, Factor H and Factor I) in Psoriasis. Tohoku J. exp. Med., 1988, 154 (4), 315-321 -By using single radial immunodiffusion we measured the plasma levels of four complement modulating proteins, i.e., C1 inhibitor, C4-binding protein, factor H and factor I in 19 psoriatic patients in comparison with those of healthy controls. Except for C1 inhibitor which was only marginally elevated, they were found to be significantly increased in psoriatic patients. When psoriatic patients were classified into subgroups based on the clinical severity, the levels of factor H and those of factor I showed a close positive correlation with the activity and extent of the skin lesions, whereas such clear relationship could not be found with C1 inactivator or with C4-binding protein. These results offer additional support for the hypothesis that the complement system is involved in psoriasis.
OHE, H., OHNISHI, K., WATANABE, H., ITAKURA, Y. and INABA, T. Accuracyof Digital Palpation for Size Assessment of the Prostate Evaluated by TransrectalSonography. Tohoku J. exp. Med., 1988, 154 (4), 323-328 - In order to clarify how precisely digital palpation gives information on prostatic size, evaluation of the size measurement of the prostate by means of transrectal sonography was performed on 1, 543 subjects with various prostatic disorders. There was little agreement between the assessment of prostatic size by digital palpation and the ultrasonic measurement. The larger the prostate the less accurate was digital palpation. The prostatic size assessed by digital palpation was particularly dispersed widely in the prostate of 'hen's egg' size. It was proved that the size assessment by digital palpation was only effective statistically in a two-step differentiation, 'hen's egg' size and smaller. More complicated size classification was of little clinical value in digital palpation.
MORI, S., ITO, H. and YAMAMOTO, K. Effects of Calcium Antagonists on LowDensity Lipoprotein Metabolism in Human Arterial Smooth Muscle Cells. Tohoku J. exp. Med., 1988, 154 (4), 329-333 - Human arterial smooth muscle cells were used to study the effects of calcium antagonists on cellular interactions with iodinated human low density lipoprotein ([125I] LDL). Both verapamil and nicardipine inhibited the degradation of internalized LDL, and as a result, facilitated the intracellular accumulation of LDL without accompanying the change in receptor binding of LDL. These results suggest that the effectiveness of calcium antagonists in improvement of atherosclerosis might not be due to the improvement of LDL metabolism against atherogenesis.
YOKOYAMA, A. Natural Killer Cells in Dilated Cardiomyopathy. Tohoku J. exp. Med., 1988, 154 (4), 335-344-Dilated cardiomyopathy is associated with various immunological abnormalities, such as decreases in the activity and subsets of suppressor T cells and in the activity of natural killer cells, suggesting the involvement of immunological mechanisms in the pathogenesis of this disease. I assayed several subsets and the activity of natural killer cells in the peripheral blood of 44 patients with dilted cardiomyopathy and compared the results with the clinical course. Compared with normal individuals, the patient group showed increases in cells positive for the subsets Leu 7 and Leu 11. Double staining method revealed that natural killer cell groups were positive for Leu 7, Leu 11 and Leu 15 but negative for Leu 2a. The activity of natural killer cells was decreased in all cases, particularly in the subgroup with mild illness. Addition of interleukin 2 (IL-2) caused no increase in activity in any of the cases. Compared with the mild subgroup, the subgroup with severe illness included more male patients and had a shorter clinical course (p<0.05). Of the 43 patients who underwent gallium 67 (Ga-67) myocardial scintigraphy, four demonstrated an accumulation of the contrast material in the myocardium, and all of whom belonged to the mild subgroup. These results suggest that inhibition of the function or activation of natural killer cells and the pathophysiology of chronic myocarditis are intimately associated with the occurrence of at least the mild form of dilated cardiomyopathy.
KUDO, T., ASAO, A. and TACHIBANA, T. Highly Efficient Procedure forProduction of Human Monoclonal Antibodies. Establishment of Hybrids betweenEpstein-Barr Virus-Transformed B Lymphocytes and Heteromyeloma Cells by Useof GIT Culture Medium. Tohoku J. exp. Med., 1988, 154 (4), 345-355-We describe a method for production of human monoclonal antibody by a combinationof the capacity of Epstein-Barr virus (EBV) to transform human B lymphocytes with somatic cell hybridization, in which a new culture medium, GIT, is used. The transformed B cells from wells positive for anti-purified protein derivative (PPD) fused with a (mouse×human) heteromyeloma line (deficient in hypoxanthine-guanine phosphoribosyl transferase and ouabain-resistant) that had been cultured in GIT medium (Kudo et al. 1987) supplemented with geneticin (antibiotic G418) before cell fusion. The hybrids were selected in GIT medium containing HAT and ouabain (GIT-HAT-O) and cloned by limiting dilution technique by use of GIT medium. According to our method, we obtained higher fusion frequency (1/5.5×103 vs. 1/1.1×104) and higher cloning efficiency (43.3-56.7% vs. 3.3-13.3%) compared with the regular method which used the culture medium containing fetal bovine serum (FBS). Six hybrid clones were consequently obtained and characterized. They produced large amount of specific antibodies (35-170μg/ml) in GIT medium, while establishment of hybrid clones producing specific antibodies by the regular method was unsuccessful. This method will be applicable to any kind of human monoclonal antibody production.
KOGA, S., KOGA, Y. and NAGAI, H. Physiological Significance of Fetal BloodGas Changes Elicited by Different Delivery Postures. Tohoku J. exp. Med., 1988, 154 (4), 357-363-We performed umbilical blood gas analysis for 130 pregnant women in sitting and for 50 in supine position immediately after their deliveries. To elucidate whether fetal blood gas changes were attributed to the maternal postures, we also carried out the maternal blood gas analysis during delivery (n=145) and prior to the onset of labor (n=100) in both positions. Blood gas values of the umbilical vein and artery in the sitting group were significantly higher in pH, PO2, base excess (BE) and oxygen saturation (SO2), and lower in PCO2 than those in the supine group. In contrast, maternal arternal blood gas values (pH, PaCO2, PaO2 and SaO2) did not show significant differences between these two groups in both during delivery and before the onset of labor. Thus, the sitting delivery position can elicit physiologically more beneficial blood gas aspects in fetus compared with the conventional supine delivery position. Umbilical blood gas improvements induced by sitting delivery position do not appear to be a result of the maternal blood gas alteration, but appear to be mediated by other factors.
ENDO, Y., IWAMOTO, K., MAMIYA, S., NIITSU, H., ITOH, T. and MIURA, A.B. ANew Bleeding Tendency Due to Hereditary Hyper α2-Macroglobulinemia. Tohoku J. exp. Med., 1988, 154 (4), 365-373-A heritable elevation in α2-macroglobulin (α2M) was identified in a 9-year-old girl with a severe bleeding tendency and activated partial thromboplastin time (APTT) prolonged to 49.1sec (normal 27-38) as well as recalcification time prolonged to 438sec (<180). The addition of her plasma to normal plasma made APTT prolong from 26.8 to 38.3sec. The plasma α2M levels in her relatives were checked, i.e., proband, her sister, mother, maternal grandmother, father, and paternal grandmother: Their levels were 406, 380, 352, 339, 166 and 236mg/100ml (140-285), respectively. Thus the patient's condition was thought to be an autosomal dominant disease, though her other relatives displayed no apparent clinical symptoms. Of significance was that a possible causal association between her elevated α2M and her prolonged APTT was indicated. The activity of the α2M, determined as trypsin-protein esterase, was 351mg/100ml (197% ). The α2M also demonstrated normal horizontal mobility to anti-α2M plasma with a high precipitin arc (showing the difference of the protein concentration) by crossed immunoelectrophoresis, and a normal horizontal mobility of immunofixation electrophoresis. In addition, after analysis of testing done by SDS-polyacrylamidegelelectrophoresis, we found no qualitative abnormality in the α2M of the patient.
MOJICA, J.A.P., YAMADA, Y. and NAKAMURA, R. Effect of Warning Signal onReaction Time and EMG Activity of the Biceps Brachii Muscle in Elbow Flexionand Forearm Supination. Tohoku J. exp. Med., 1988, 154 (4), 375-380-Using a reaction time (RT) task, the biceps brachii muscle was investigated in five healthy subjects to determine whether EMG in the initial phase of activity is dependent upon the direction of movement, i.e., elbow flexion and forearm supination, and/or influenced by the presence or absence of warning signal. Results showed that in the presence of warning EMG-RT of forearm Supination was faster than that of elbow flexion, and that the reverse occurred in the absence of warning. The warning signal significantly reduced EMG-RT of both movements and the reduction of EMG-RT was larger in Supination than flexion. Compared to forearm supination, large amplitude potentials were observed during elbow flexion. The warning suppressed EMG activities of both movements within 30msec after their initiation. The present study indicates that the biceps brachii muscle exhibits a motor response program specific to the direction of movements and that preparatory set conditioned by warning shortens RT and also suppresses EMG activities.
MORIYAMA, M. and SAITO, H. Twenty Four-Hour Urinary Excretion ofSodium, Potassium and Urea in Japanese Children. Tohoku J. exp. Med., 1988, 154 (4), 381-388-The general profile of sodium and potassium intake during childhood was studied by the analysis of excretion in 24-hr urine samples collected from 119 healthy Japanese children at the ages of 1 to 18 years. In order to analyze sodium and potassium excretion under the changing body size and diet during growth, sodium and potassium were further expressed as values relative to creatinine and urea, as the reflection of body muscle mass and protein intake, respectively. Both of sodium and potassium (mEq/24-hr) increased significantly with age. Sodium/creatinine and potassium/creatinine, however, decreased significantly with age, suggesting that the increase in muscle mass exceed that in dietary intakes of sodium and potassium. When urinary sodium and potassium were expressed as ratios to urea-N, sodium/urea-N increased, but potassium/urea-N decreased with age. Sodium/potassium ratio increased with age. Thus, the results suggest that, in the given population of Japanese children, the amount of sodium per calorie or per protein in the diet increase, and that of potassium decrease with age.
SHIMIZU, H., MORISHITA, M., MIZUNO, K., MASUDA, T., OGURA, Y., SANTO, M., NISHIMURA, M., KUNISHIMA, K., KARASAWA, K., NISHIWAKI, K., YAMAMOTO, M., HISAMICHI, S. and TOMINAGA, S. A Case-Control Study of Lung Cancer inNonsmoking Women. Tohoku J. exp. Med., 1988, 154 (4), 389-397-A case-control study of Japanese women in Nagoya was conducted to investigate the significance of passive smoking and other factors in relation to the etiology of female lung cancer. A total of 90 nonsmoking patients with primary lung cancer and their age- and hospital-matched female controls were asked to fill in a questionnaire in the hospital. Elevated relative risk (RR) of lung cancer was observed for passive smoking from mother (RR=4.0; p<0.05) and from husband's father (RR=3.2; p<0.05). No association was observed between the risk of lung cancer and smoking of husband or passive smoke exposure at work. Occupational exposure to iron or other metals also showed high risk (RR=4.8; p<0.05). No appreciable differences in food intakes were observed between cases and controls.
SATO, M., ABE, K., TAKEUCHI, K., MATSUI, K., YASUJIMA, M., FANG, S., KANAZAWA, M., YOSHIDA, K., KIMURA, T. and YOSHINAGA, K. Cyclic GMPAccumulation by Atriopeptins in Cultured Rat Renal and Vascular Smooth MuscleCells. Tohoku J. exp. Med., 1988, 154 (4), 399-411-To-evaluate the role of cyclic guanosine monophosphate (cGMP) in the vascular and renal action of atrial natriuretic peptide (ANP), we compared the effects of atriopeptins (APs) on cGMP accumulation in cultured cells from rat mesenteric vascular smooth muscle (VSM), glomerular mesangium (GM) and renal papillary collecting tubule (RPCT), and also evaluated the relationship between renal sodium or water excretion and urinary cGMP in AP-infused rats. Both AP I and AP III increased intracellular cGMP levels dose-dependently in all types of cells, while they did not affect intracellular cAMP levels or prostaglandin synthesis. AP III was 100 times more potent than AP I. The magnitude change in cGMP levels was largest in GM cells. The sensitivity of VSM and GM cells to AP III were greater than that of RPCT cells. There were significant positive relationships between urinary excretion of sodium or water and that of cGMP levels in AP-infused rats. These results may suggest that GM and VSM cells are the principal targets for ANP to stimulate cGMP synthesis and, possibly, to exert the renal sodium and water excretion, and also support the hypothesis that cGMP mediates the cellular action of ANP.
KEITOKU, M., OKAYAMA, H., SATOH, Y., MARUYAMA, Y. and TAKISHIMA, T. Does Diffuse Intimal Thickening in Human Coronary Artery Act as a DiffusionBarrier to Endothelium-Derived Relaxing Factor? Tohoku J. exp. Med., 1988, 154 (4), 413-414-We investigated the effect of Intimal thickness in human coronary artery on the endothelium-dependent relaxation. Histamine (in the presence of cimetidine), substance P and A23187 potently relaxed arterial rings with intima thinner than 200μm. However, those relaxations diminished progressively in the artery with intimal thickness of 200-400μm, and disappeared at the thickness greater than 400μm. These results suggest that diffuse intimal thickening greater than 200μm may inhibit the diffusion of endothelium-derived relaxing factor.
KEITOKU, M., MARUYAMA, Y. and TAKISHIMA, T. The Receptor Mechanismsfor Histamine Actions in Proximal Portion Differ from Those in Distal Portion inHuman Coronary Artery. Tohoku J. exp. Med., 1988, 154 (4), 415-416-While most distal human coronary arteries markedly relaxed in response to histamine, nearly half the proximal ones contracted only. Thus, we investigated the receptor mechanisms for those heterogeneous histamine actions. After a combination of cimetidine-treatment and endothelial removal, but neither one alone, proximal and distal rings contracted to histamine to the same degree. It is suggested that histamine hypercontractility in proximal human coronary artery is due to a lack of both direct (H2-receptor) and endothelial-mediated (H1-receptor) relaxant actions.