SASAKI, A., HANEW, K., SATO, S. and YOSHINAGA, K. Evidence for EndogenousDopaminergic Regulation of Thyrotropin (TSH) Secretion in Man. Tohoku J. exp. Med., 1983, 139 (1), 1-7 - In order to clarify the dopaminergic influence on TSH secretion in normal subjects, the effects of a dopaminergic agent, L-dopa, and an anti-dopaminergic agent, sulpiride, on TSH secretion were studied in 28 normal subjects. Improving a commercially available radioimmunoassay (RIA) kit, we developed a high sensitivity RIA method for human TSH (assay sensitivity 0.15μU/ml; 50% B/Bo value 3.47μU/ml). Plasma TSH levels decreased significantly after an oral administration of dopamine agonist, L-dopa, and the mean percent decrease of plasma TSH was significantly greater in male than in female. Dopamine antagonist, sulpiride, induced a significant increase in plasma TSH in female, but a slight elevation in male. The mean percent increase in plasma TSH with sulpiride was significantly greater in female than in male. These results suggest that dopamine exerts physiologically tonic inhibition on TSH secretion and the dopaminergic tone on TSH secretion is higher in female than in male.
KATO, T. Renal Transport of Lysine and Arginine in Cystinuria. Tohoku J. exp. Med., 1983, 139 (1), 9-16 - To study the defective transport mechanism of cystinuria, renal tubular reabsorption of lysine or arginine in normal and cystinuria subjects was investigated by increasing the filtered load employing intravenous amino acid infusion. In the normal group the amino acid reabsorption rose with increases of the filtered load and reached a maximum (Tm). In the cystinuria group the elevation of amino acid reabsorption was poor at low filtered loads and some of the reabsorption rates fell below zero, whereas the tubular transport proceeded at a normal rate with a great increase of the filtered load. This might be explained as follows: At low filtered loads the filtered amino acid in the tubular lumen in patients with cystinuria is not absorbed into the cell because of a transport defect of the luminal membrane of the tubular cell, causing a large amount of urinary amino acid excretion. At high filtered loads the accumulated intraluminal amino acid permeates the tubular cell by a passive diffusion and is transported to the capillary across the intact basolateral membrane, which in turn only brings about a small urinary loss of amino acid. The infusion of lysine or arginine depressed the percentage of tubular reabsorption of other dibasic amino acids in both groups. In the cystinuria group the percentage of the dibasic amino acid reabsorption dropped sharply with an initial load of the inhibitor, but no more depression of the percentage of reabsorption occurred with further loads of the inhibitor.
NONOMURA, A., KURUMAYA, H., OHMORI, K., OHTA, G., KATO, Y. and KOBAYASHI, K. Immunoregulatory T Cell Function in Patients with PrimaryBiliary Cirrhosis. Tohoku J. exp. Med., 1983, 139 (1), 17-25 - Both concanavalin A (Con A)-induced suppressor cell activity and autologous mixed lymphocyte reaction (AMLR) were significantly decreased in patients with primary biliary cirrhosis (PBC) in comparison with those of healthy subjects (p<0.001 and p<0.001, respectively). Factors inhibiting lymphocyte transformation by Con A and PHA were demonstrated in sera from a majority of the patients with PBC. In approximately half of these patients, some serum factor(s) also induced a decrease of Con A-induced suppressor cell function of lymphocytes from healthy subjects. These results suggest that patients with PBC have impaired immunoregulatory lymphocyte function which may be related to some factor(s) present in serum.
TOMOKUNI, K. Effects of Lead Exposure on the Activity of ErythrocytePyrimidine 5'-Nucleotidase and δ-Aminolevulinic Acid Dehydratase in Mice. Tohoku J. exp. Med., 1983, 139 (1), 27-32 - The effects of lead exposure on the activities of erythrocyte pyrimidine 5'-nucleotidase (Py5N) and δ-aminolevulinic acid dehydratase (ALA-D) were investigated in the mice given ad libitum the drinking water containing lead at 10 to 500ppm for 30 days. The erythrocyte Py5N activity was significantly inhibited in the 250 and 500ppm groups, and the activity in these groups was dropped to 62-81% of that in the control group. In addition, the erythrocyte Py5N activity was shown to have a significant negative correlation with the concentration of lead in blood (r=-0.79). The erythrocyte Py5N activity would be a better indicator than ALA-D in the exposure to relatively high lead concentrations, although the assay of Py5N is more time-consuming as compared with that of ALA-D, while, the erythrocyte ALA-D activity is useful in the evaluation of exposure to low levels of lead. The erythrocyte Py5N was less stable than ALA-D against heating at 60°C.
MAEBASHI, M., IMAMURA, A., YOSHINAGA, K., SATO, T., FUNYU, T., ISHIDOYA, Y. and HIRAYAMA, N. Carnitine Depletion as a Probable Cause ofHyperlipidemia in Uremic Patients on Maintenance Hemodialysis. Tohoku J. exp. Med., 1983, 139 (1), 33-42 - The mechanism of the development of hemodialysis hyperlipidemia was investigated in uremic patients on maintenance hemodialysis. Hemodialysis treatment lost large amounts of carnitine from blood into the dialysate fluid, resulting in the reduction in serum concentration of carnitine. After the treatments were repeated for more than 12 months, the serum concentration of carnitine reduced markedly and the serum triglyceride level increased significantly. In contrast, in patients who had been supplemented with commercial amino acids solution, the serum concentrations of carnitine and lipid were within normal ranges and remained unchanged even after repeated hemodialysis treatments. Carnitine administration also reduced the serum triglyceride level to or towards normal. The results suggest that carnitine depletion induced by hemodialysis treatments has a probable causal relationship to hyperlipidemia in uremic patients on long-term maintenance hemodialysis and that supplementation of carnitine or amino acids prevents carnitine depletion and improves hemodialysis hyperlipidemia.
YAJIMA, Y., OHTA, K., NARUI, T., ABE, R., SUZUKI, H. and OHTSUKI, M. Ultrasonographical Diagnosis of Fatty Liver; Significance of the Liver-KidneyContrast. Tohoku J. exp. Med., 1983, 139 (1), 43-50 - In order to investigate the reliability of ultrasonography in the diagnosis of fatty liver, retrospective evaluation was made of abdominal echograms in 45 patients with various diffuse liver diseases who underwent liver biopsy within 2 weeks after the ultrasound study. Instead of the well-recognized but subjective diagnostic criterion, i.e. the bright liver pattern, liver-kidney contrast is proposed as a new criterion. The liver-kidney contrast is based on the brightness of the liver in comparison to the renal parenchyma where fatty change seldom occurs. Combination of this liver-kidney contrast with two other well-known ultrasonographical findings of fatty liver, vascular blurring and deep attenuation, enables us to grade fatty change semiquantitatively. When fatty change of over 30% in the hepatic lobule was adopted as the definition of fatty liver, the satisfaction of both liver-kidney contrast and vascular blurring presented an ultrasound diagnostic criterion for fatty liver, with sensitivity of 83%, specificity of 100%, and an accuracy of 96%.
ASHIDA, T., YAZAKI, Y., OHUCHI, Y., TANAKA, T. and IKEDA, M. PressorResponsiveness to Vasopressin and Angiotensin II in Spontaneously HypertensiveRats: Effects of Dietary Sodium. Tohoku J. exp. Med., 1983, 139 (1), 51-59 - The effects of dietary sodium on pressor responsiveness to arginine vasopressin (AVP) and angiotensin II (A II) were examined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Sixteen SHR and 19 WKY were divided into two groups, which were maintained on high sodium diets or low sodium diets for four weeks. At the end of the treatment with either diet, the rats were anesthetized with urethane and mean arterial pressure was recorded from the iliac artery. After pretreatment with intravenous phenoxybenzamine, the pressor responses to graded i.v. injections of AVP and A II were determined in each rat. The pressor responses to AVP or A II were significantly higher in SHR than in WKY. Sodium loading significantly increased the pressor responses to A II and significantly decreased plasma renin activity in both SHR and WKY. On the other hand, there was no difference in pressor responses to AVP between sodium loading and restriction in both SHR and WKY. In WKY, plasma concentration of AVP was not affected by dietary sodium, but in SHR, it was significantly higher on high sodium diet than on low sodium diet. Thus, the secretion of AVP was shown to be increased in SHR with high sodium intake. The intravenous injection of an AVP antiserum reduced arterial blood pressure substantially. These results suggest that AVP may function as a direct pressor agent in the maintenance of high blood pressure in SHR.
CHIBA, T. Serum and Urine Amino Acid Analysis in Children with BiliaryAtresia. Tohoku J. exp. Med., 1983, 139 (1), 61-66 - Serum and urine amino acid levels were measured preoperatively and at varying time following successful hepatic portoenterostomy. All of the essential amino acids measured returned to normal levels during the late postoperative period over five years, whereas many of the non-essential amino acids remained in the abnormal range.
TSUCHIYAMA, A., OYANAGI, K., SOGAWA, H., NAKAO, T., OGAWA, K. and FUJITA, S. Normal Activities of Hepatic Pyruvate Dehydrogenase and PyruvateCarboxylase in Leigh's Syndrome. Tohoku J. exp. Med., 1983, 139 (1), 67-72 - A case of Leigh's syndrome (subacute necrotizing encephalomyelopathy, SNE), proven by autopsy, was reported. The persistent elevation of pyruvate and lactate in blood and hyperalanemia suggested an impairment of pyruvate oxidation, but the enzyme activities of pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) in liver tissues of the patient revealed normal. It is postulated that Leigh's syndrome and both enzyme deficiencies are distinct entities.
OHNEDA, A., SAKAI, T., KOBAYASHI, T. and NIHEI, J. Insulin and C-Peptidein Plasma and Tumor of Insulinoma Patients. Tohoku J. exp. Med., 1983, 139 (1), 73-81 - In order to elucidate the heterogeneity in insulin secretion and insulin content of insulinoma tumor, insulin (IRI) and C-peptide (CPR) in plasma and tumor were studied in 11 patients with insulinoma and 14 healthy controls. The fasting levels of plasma IRI and CPR were significantly elevated in insulinoma as compared to the normal controls. The molar ratio of CPR/IRI was markedly decreased in patients with insulinoma, indicating higher increase in plasma IRI than CPR. Exaggerated responses of plasma IRI and CPR to glucose load were observed in insulinoma patients. Insulinoma patients revealed a gradual rise of plasma IRI and CPR in response to glucagon. Furthermore, the patterns of plasma IRI and CPR were extremely deviated from normal in the patients. The content of biologically measured insulin in the tumor tissue was increased in all the insulinoma patients. In contrast, immunoreactive insulin and C-peptide in the tumor scattered widely, indicating a dissociation between biological and immunological activity of insulin in the tumor. Chromatography of C-peptide extracted from the tumor elicited 2 parts with different molecular weight in addition to the part corresponding to the authentic C-peptide. From the present study, it is concluded that, although insulin secretion was exaggerated in the basal state as well as after stimuli, its regulation is abnormal in insulinoma. Furthermore, heterogeneity in biosynthesis and secretion of insulin in insulinoma was suggested by the results obtained from insulin content in the tumor and chromatography of C-peptide extracted from the tumors.
MUKADA, T., ITASAKA, K., MIYAZAKI, S., HIRAKAWA, H., KASHIWAGURA, J., SASAKI, Y., ANDOH, S., SHINZAWA, A. and SENDOH, F. Pulmonary HypertensionAssociated with Liver Cirrhosis and Hepatitis-B Antigenemia. Tohoku J. exp. Med., 1983, 139 (1), 83-90 - An autopsy case of pulmonary hypertension in a 29-year-old Japanese female with macronodular, posthepatitic liver cirrhosis and hepatitis-B antigenemia was presented. No recognizable known cardiopulmonary disease or portal thrombosis was obtained. Hepatitis-B antigen was demonstrated in the cirrhotic hepatocytes by a specific peroxidase antiperoxidase method. Characteristic pulmonary arterial changes including plexiform lesions with varying developmental stages were widely observed throughout the lungs. Complication of these two distinct disease processes seems to be rarely encountered in the literature. Discussion was focused on the possible interrelationship between the liver cirrhosis with hepatitis-B antigenemia and pulmonary hypertension. Proposed were presumptive underlying humoral, particularly immunological, abnormalities common to these diseases rather than mere incidental complications.
HANEW, K., SASAKI, A., SATO, S., SHIMIZU, Y., MURAKAMI, O. and YOSHINAGA, K. Foctors Determining the Effectiveness of CB-154 in the Treatment of Acromegaly. Tohoku J. exp. Med., 1983, 139 (1), 91-95 - To predict the effectiveness of CB-154 treatment in patients with acromegaly plasma GH changes induced by CB-154 treatment were compared with GH responses to TRH or arginine tests performed before the treatment. Fourteen patients with active acromegaly (4 males and 10 females, aged 16-68 years) were given 7.5 to 15mg of CB-154 daily for 3 weeks or longer. During the treatment 7 of the 14 cases showed significant GH decreases (20.1 to 86.2%; p<0.05-0.001), and one of the other 7 cases showed a significant GH increase (30.8%;p<0.005) as compared with GH values before the treatment. In the remaining 6 cases no significant GH changes were observed. Before the treatment 12 of the 14 cases showed distinct GH responses (68-7, 033% increase from the basal GH) to the bolus injection of TRH. Ten of these 12 cases also showed an increase in GH to arginine infusion (62-5, 557%). There was a significant relationship between GH changes induced by CB-154 therapy and logarithmic values of the ratio of TRH-induced GH increasevs. arginine-induced GH increase (r=-0.75; p<0.005). Two cases of less responsive type did not show any GH changes to the treatment. It is concluded that CB-154 treatment is effective only in more responsive type of acromegaly, and especially in cases which are more responsive to TRH and less responsive to arginine.
YAZAKI, M., WADA, Y., KOJIMA, Y., TANAKA, A., ISSHIKI, G., KAWAMURA, N. and HIROSE, M. Copper-Binding Proteins in the Liver and Kidney from thePatients with Menkes' Kinky Hair Disease. Tohoku J. exp. Med., 1983, 139 (1), 97-102 - Copper-binding proteins in the tissues from the patients with Menkes' kinky hair disease were examined by gel filtration on a Sephadex G-75 column. In the kidney, major part of copper was found to bind to low molecular weight protein, which corresponded chromatographically to metallothionein. This copper-binding protein contained a large amount of copper and a small amount of zinc. Cu: Zn ratio of this protein was different from that of metallothionein found in the fetal liver. In the liver of the same patient, however, there was no increase of copper bound to this protein.
GOTO, T., ABE, K., OTSUKA, Y., SEINO, M., ITO, T., IMAI, Y., HARUYAMA, T., SATO, M., HIWATARI, M., SATO, K., OMATA, K., KASAI, Y., TAJIMA, J. and YOSHINAGA, K. Active and Inactive Renin after Captopril (SQ 14225) Administrationin Hypertensive Patients. Tohoku J. exp. Med., 1983, 139 (1), 103-111 -The changes in active and inactive renin after oral administration of captopril (SQ 14225) were studied in 29 hypertensive patients. Inactive renin was calculated as plasma renin activity (PRA) after cold storage (total renin) minus PRA before cold storage (active renin). The patients were divided into 2 groups, responders and non-responders, according to the response of active renin to captopril. In 9 responders, the active renin increased markedly, while the inactive renin decreased. On the other hand, in 20 non-responders, both renin activities increased only slightly. Total renin increased markedly in responders; it increased in much smaller degree but significantly in non-responders. These data suggest that captopril promotes the conversion of inactive renin to active one and augments the renin release as a whole.