ISHIDE, N., WATANABE, H. and TAKISHIMA, T. Effects of High-K Low-Na, Diltiazem, Caffeine and Ba on Spontaneous Fluctuating Contractile Activities inRat Cardiac Muscle. Tohoku J. exp. Med., 1984, 144 (4), 331-341 - The effects of 1) high-K low-Na, 2) caffeine, 3) diltiazem and 4) Ba on spontaneous fluctuating contractile activity were examined in isolated rat trabecular muscles. Intracellular contractile activity was recorded by means of light intensity fluctuation at a point on a magnified image of the muscle illuminated by laser light. Perfusion with a high-K (124mM) low-Na (25mM) solution increased the root mean square (RMS) values of the light intensity fluctuations. Perfusion with the normal solution after this perturbation decreased the RMS values below those in the initial control. Caffeine (above 2.5mM) markedly decreased the RMS values. Diltiazem (0.1mM or 1mM) did not change the RMS values. Ba (2.0mM) without Ca reduced the RMS values. These observations suggest that the spontaneous fluctuating contractile activity is due to oscillating movements of Ca between contractile machinery and sarcoplasmic reticulum, and that Na/Ca exchange modulates these movements but Ca current through the slow channel does not influence these movements during resting periods
KAMEYAMA, J., MOMONO, S., KONNO, Y., SASAKI, I. and SATO, T. Influence ofObstructive Jaundice on Gastric Mucosal Barrier in Dogs. Tohoku J. exp. Med., 1984, 144 (4), 343-349-The influence of obstructive jaundice on the gastric mucosal barrier was studied before and after ligation of the common bile duct using 21 mongrel dogs with a Heidenhain pouch. The gastric mucosal barrier was examined using gastric mucosal permeability of ionic net fluxes of Na+ and H+ (_??_Na+, _??_H+), and transmucosal electrical potential difference (PD) during the irrigation of the pouch with various test solutions. No significant differences in _??_Na+ or _??_H+ during the irrigation with 100mN HCl were found between before and after obstructive jaundice. Almost the same results were observed during the irrigation with 150mN HCl. Obvious increases in _??_Na+ and _??_H+ were found, when 20mM sodium taurocholate (taurocholate) was used in addition to 100mN HCl. No differences were, however, found between before and after obstructive jaundice. The PD during the irrigation with 100 and 150mN HCl showed about the same levels of -50mV. The PD decreased early during the irrigation with 20 mM taurocholate in addition to 100mN HCl, but no differences were found in these values between before and after obstructive jaundice. Dose-response relationships were found between the concentration of taurocholate in addition to 100mN HCl, and _??_Na+, _??_H+ and ∑PD/15min, while no differences in ED50 of taurocholate for _??_Na+, _??_H+ or ∑PD/15min were observed between before and after obstructive jaundice. These results suggest that obstructive jaundice itself exerts no influence on the gastric mucosal barrier with respect to gastric mucosal permeability and PD in dogs.
KOKUBO, T., TAKAHASHI, M., FURUKAWA, F., NAGANO, K., HAYASHI, Y. and TAKAHASHI, T. A Comparative Histometrical Analysis of Renal Inner Medulla ofMan, Swine, Dog and Hamster. Tohoku J. exp. Med., 1984, 142 (1), 77-88-Quantitative estimations of the total circumference (in mm) of Henle's thin segment (TCH) and of the collecting tubules (TCC) in the renal inner medulla of man, swine, dog and hamster were made at different distances (X) from the papillary apex. The results were expressed as exponential functions of X, the distance in mm along the medullary ray from the papillary apex to a certain point of the inner medulla, as L=AeBX In man and swine, TCH was greater than TCC towards the external border of the inner medulla. However, in dog and hamster TCH was less than TCC along the entire inner medulla. The exponents of TCH showed nearly constant values (hamster: 0.68, dog: 0.75, man: 0.55, swine: 0.56) but those of TCC had values (hamster: 0.92, dog: 0.57, man: 0.28, swine: 0.26) correlated with the ability for concentration of urine. These findings indicate a good correlation between the ability to concentrate urine and the structure of the collecting tubules of the inner medulla, suggesting that the structure of the collecting tubules in the inner medulla affects the mechanism of urinary concentration. urinary concentration ability ; total circumference of collecting tubules ; exponential function
TAKEDA, S., MATSUZAWA, T. and YAMAURA, H. Brain Atrophy and CerebralInfarction. Tohoku J. exp. Med., 1984, 144 (4), 361-367 - The subjects of the study (109 males, 48 females) were all diagnosed to have cerebral infarction by computerized tomography (CT). The cerebrospinal fluid (CSF) space volume and cranial cavity volume in the normal hemisphere of the patients were estimated using CT at the time from 1 to 3 weeks after the attack of cerebral infarction. The percentage of the CSF space volume to the cranial cavity volume was calculated as an indicator for brain atrophy and called brain atrophy index (BAI): BAI (%)=100 (%)×(CSF space volume/cranial cavity volume). The BAI immediately after the attack of infarction (6.6±2.2, n=15), during which no detectable change occurred on CT examination, was the same as the BAI at the time from 1 to 332 days after the attack (6.6±2.4, n=20). Therefore we compared the BAI in patients without infarction with the BAI in patients with infarction irrespective of secondary atrophy of the brain after the attack. The BAIs in males with infarction were significantly greater than the BAIs in males without infarction in the age of fifties, sixties and seventies. The BAIs in females with infarction were significantly greater than in females without infarction in the age of fifties, sixties and eighties.
OHGAWARA, H., TAKEI, I., MARUYAMA, T., SHINJO, T., WASADA, T. and HIRATA, Y. A Clinical Profile of Insulin-Dependent Diabetes with Islet CellCytoplasmic and Cell Surface Antibodies. Tohoku J. exp. Med., 1984, 144 (4), 369-375 - Both islet cytoplasmic and cell surface antibodies (ICA and ICSA) were studied from the onset of diabetes to the honeymoon in an insulin-dependent diabetic patient. The patient, a 24-year-old male, was admitted to the hospital because of ketoacidotic hyperglycemic precoma. Continuous subcutaneous infusion of a small dose of insulin was carried out for a couple of days followed by NPH-insulin injection. The dose was gradually decreased and on the 45th day after the onset, an oral hypoglycemic agent was substituted for insulin. The patient was followed up after discharge from the hospital and his disease was controlled well by diet and a hypoglycemic agent until he caught a common cold. He was then admitted again to the hospital because of hyperglycemia, and insulin injection was performed. Both ICA and ICSA were found independently of each other during the course of the disease. The ICSA, which was quantitatively determined by immunoassay using 125I-protein A, closely paralleled the clinical profile. However, the levels of quantitative ICSA were higher than normal, even though the patient's diabetes reached the honeymoon stage. These results suggest that quantitative ICSA has a strong association with the clinical profile in IDDM, and it may be a “marker” of islet cell damage during the diabetic period or a parameter for diabetic prognosis.
WATANABE, M., SUGAWA, C., HATAFUKU, T. and MORI, S. The Effect ofIncreased Gastrin Release on Lower Esophageal Sphincter Pressure. Tohoku J. exp. Med., 1984, 144 (4), 377-384 - The present study was performed (1) to induce release of endogenous gastrin from the chronic isolated antrum, and (2) to note the effect of endogenous gastrin on lower esophageal sphincter pressure (LESP). Fifteen mongrel dogs weighing 15-20kg were divided into 3 groups by the type of operation: 5 dogs with antral excision and B-II gastrojejunostomy (Group I); 5 dogs with a denervated antral pouch and B-II (Group II); and 5 dogs with an innervated antral pouch and B-II (Group III). Fasting serum gastrin levels (SGL) and LESP were determined preoperatively (basal) and at 2 and 4 weeks postoperatively. SGL was measured by radioimmunoassay using an antibody to human gastrin I. LESP was determined by pullthrough technique using an assembly of 3 polyvinyl tubes perfused with water at 0.6ml/min and connected to external transducers. The mean SGL at 2 and 4 weeks after operation in Group I and in Group II were not significantly different from basal SGL. The SGL rose significantly at 2 weeks and 4 weeks in Group III (p<0.05). The mean LESP at 2 and 4 weeks did not significantly change from the basal LESP in Group I, Group IT and Group III. The present data show that (1) increased endogenous gastrin was produced only in the presence of an innervated antral pouch, and (2) the increased gastrin level, however, did not affect LESP.
HARANAKA, K., SATOMI, N., SAKURAI, A, and KUNII, O. Role of Lipid A in theProduction of Tumor Necrosis Factor and Differences in Antitumor Activitybetween Tumor Necrosis Factor and Lipopolysaccharide. Tohoku J. exp. Med., 1984, 144(4), 385-396 - The role of lipopolysaccharide (LPS) in the production of tumor necrosis factor (TNF) was examined. Alkaline treatment of LPS greatly reduced the TNF-producing activity of LPS, but TNF was produced when a large amount was injected. Free lipid A and lipid A-mouse serum albumin complex, which were prepared from the acid hydrolyzate, effectively induced TNF. However, the polysaccharide-rich fraction of the acid hydrolyzate was not capable of inducing TNF. Preincubation of LPS with polymixin B largely abrogated the TNF-producing activity of LPS. The differences in antitumor activity between TNF and LPS were also tested. TNF has a direct cytotoxicity against cancer cells in vitro but LPS does not. The activity of TNF was not inhibited by preincubation with polymixin B. Tumor necrosis in vivo was inhibited by preincubation of LPS with polymixin B but not by that of TNF. Galactosamine was found to induce susceptibility to the lethal effects of LPS, but did not influence the action of TNF. Lipid A is largely responsible for the TNF-inducing activity of LPS, but is not essential for the antitumor activity of TNF.
TSUJIKAWA, M., AKIBA, T., OHORI, H., FUJIYAMA, A., MATSUBARA, K. and ISHIDA, N. Virological Classification of Autopsy Livers with Hepatic Disorders. Tohoku J. exp. Med., 1984, 144 (4), 397-408 - Forty six selected autopsy livers with hepatic disorders were classified histologically into three groups, i.e., hepatitis 8, liver cirrhosis 16 and hepatocellular carcinoma 22, chiefly by histological findings. These groups were subdivided into two categories after determining the presence or absence of three HBV associated markers, i.e., the hepatitis B surface antigen (HBsAg), the antibody to hepatitis B surface antigen (anti-HBs) and the antibody to hepatitis B core antigen (anti-HBc) in the sera and liver homogenates. At least one of these markers was found to be present in the sera and homogenates of 38% of the livers with hepatitis, 69% of the livers with liver cirrhosis and 77% of the livers with hepatocellular carcinoma. When the liver tissues were examined for the presence of HBV DNA using Southern blot technique, the majority of them (10 out of 11) which proved to be positive for at least one HBV associated marker were also positive for HBV DNA. However, HBV DNA could not be detected in the other 10 livers which contained no HBV associated markers. These results showed that a HBV associated serological marker was always expressed, when liver tissue HBV DNA was demonstrable. The results of the two detection methods we used in this study were found to be almost equivalent. These results showed no evidence of nucleic acid homology between DNA from the liver of patients with non-B type liver disorders and HBV DNA.
ASAKAWA, H., OTAWA, H., SAITO, H. and NEMOTO, K. Radiation Therapy ofCarcinoma of the Rectum and Sigmoid Colon. Tohoku J. exp. Med., 1984, 144 (4), 409-416 - Radiation therapy combined with some anti-cancer drugs was performed in a total of 79 patients with carcinoma of the rectum and sigmoid colon, consisting of 41 primary, 25 recurrent and 13 postoperatively irradiated ones. Relief of subjective symptoms was observed in 50% or more of primary and recurrent patients. Radiation response of tumor was marked in 23 (56%) of primary ones. Five-year survival rate was 21% in the primary patients without any remote metastasis, 11% in the recurrent and 27% in the postoperatively irradiated. It was concluded that this combination therapy might be valuable for getting a cure in the primary patients with radioresponsive tumor (T1-T4: M0) and the patients with localized residual lesion, and for good palliation in the patients with far advanced and recurrent carcinoma.
NAKAYAMA, Y., SHINDO, T., AKIHAMA, T. and MIURA, A.B. Prostaglandin E2Production by Human Bone Marrow Cells: a Comparison with Peripheral BloodMononuclear Cells. Tohoku J. exp. Med., 1984, 144 (4), 417-423 - The amount of prostaglandin E2 (PGE2) in the supernatant of human bone marrow cell cultures was measured by radioimmunoassay. Bone marrow cells were obtained from adult patients without hematological malignancies. Marrow mononuclear cells (BMMNC) (0.5×106) and marrow nonadherent cells (BMNAC) (0.5×106) were cultured at 37°C in 5% CO2 in 0.5ml RPMI 1640 supplemented with L-glutamine, 10% fetal calf serum and 10mM Hepes buffer. The levels of PGE2 in the supernatant of BMMNC after 24 and 48hr incubation were 3, 000±2, 320pg/ml (n=10, mean±S.D.) and 4, 470±3, 510pg/ml (n=12), respectively. The kinetics of PGE2 production by BMMNC was different from that of peripheral blood mononuclear cells. The level of PGE2 in the supernatant of BMNAC after 48hr incubation was only 1/18 when compared to that of BMMNC. These data suggest that the major source of PGE2 in the supernatant of marrow cell cultures may be bone marrow mononuclear phagocytes and that admixed blood mononuclear cells in BMMNC may produce only a small amount of PGE2
SATO, S., HANEW, K., SASAKI, A., SHIMIZU, Y., MURAKAMI, O., FUKAZAWA, H., SAKURADA, T., SAITO, S. and YOSHINAGA, K. Enhanced Prolactin Secretion inPatients with Primary Hypothyroidism during Thyroid Replacement. Tohoku J. exp. Med., 1984, 144 (4), 425-431 - Thyroid hormones are known to exert some influence on prolactin (PRL) secretion indirectly via the hypothalamic dopaminergic system and directly at the level of pituitary gland. In order to study the effect of thyroid hormones on the activity of hypothalamic dopamine neurons, lactotrophs and thyrotrophs, we administered increasing doses of thyroid hormones to patients with primary hypothyroidism, and examined the changes of basal PRL, TSH and PRL responses to a dopamine receptor blocker (sulpiride). Among 24 patients with primary hypothyroidism, hyperprolactinemia was observed in 10 cases (18.0-236ng/ml, mean±S.E. 58.6±20.0ng/ml), while elevated TSH levels were observed in all of them (6.6-972μU/ml, mean±S.E. 231.4±53.9μU/ml). There was a significant negative relationship between plasma T3 or T4 levels and basal plasma TSH levels (p<0.05), whereas a poor correlation was observed between the thyroid hormones and basal plasma PRL levels (r=-0.25, p>0.05). Following the administration of gradually increasing doses of thyroid hormones, plasma PRL showed paradoxical and transient increases, while plasma TSH decreased steadily. Plasma PRL response to sulpiride also became exaggerated during the treatment. The elevated basal PRL level and the enhanced response to sulpiride turned to be within the normal range when the patients became euthyroid by treatment. These results may indicate that thyroid hormones stimulate not only hypothalamic dopaminergic activity, but also the lactotroph activity in a long term hypothyroid state. Regarding the paradoxical elevation of basal PRL, one can postulate that the activation of lactotroph by a small dose of thyroid hormone may be able to overcome the hypothalamic dopaminergic inhibition.
OGAWA, K., KUROSE, T., KUWAHARA, T., ISHIKAWA, K., MATSUNAGA, M., NAKAMURA, Y., PAK, C.H., HARA, A. and KAWAI, C. Successful Treatment of theCrisis of Scleroderma by Enalapril Maleate (MK-421). Tohoku J. exp. Med., 1984, 144 (4), 433-434 - A 74-year-old man has been known to have scleroderma for 5 years. Two months before the hospitalization, his blood pressure was rapidly elevated, and progressive renal impairment and ulcerations of the fingers manifested. Then he was diagnosed to have a crisis of scleroderma. The treatment with a new long-acting angiotensin I converting enzyme inhibitor, enalapril maleate (MK-421), normalized the blood pressure and protected the progress of renal impairment without side effects.