HEMMI, H., KITAME, F. and ISHIDA, N. Inhibition of Sterol and DNASyntheses in Phytohemagglutinin-Stimulated Human Lymphocytes by7α-Hydroxycholesterol. Tohoku J. exp. Med., 1985, 145(2), 105-113-Sterol and DNA syntheses were induced in human peripheral blood lymphocytes stimulated with phytohemagglutinin (PHA). DNA synthesis in the PHA-stimulated lymphocytes was suppressed by 7α-hydroxycholesterol (7α-HC). The maximum suppression of DNA synthesis was observed when 7α-HC was added in the culture within 6hr of PHA stimulation to the lymphocytes. However, as the concentration of fetal bovine serum (FBS) in the culture medium was increased, the inhibitory effect of 7α-HC on the syntheses of sterol and DNA were decreased. Furthermore, low and high density lipoproteins completely reversed the inhibition of DNA synthesis by 7α-HC. These results suggest that cholesterol is an essential requirement of lymphocyte blastogenesis regardless of whether the source of the sterol is exogenous or endogenous.
UENO, N., TONO-OKA, T., MATSUMOTO, T., OHKAWA, M., SHIKANO, T. and MATSUMOTO, S. Impairment of Opsonic Function in Children with HematologicMalignancy during Remission Induction Therapy. Tohoku J. exp. Med., 1985, 145(2), 115-123-The activity of complement-mediated opsonin was measured by the whole blood chemiluminescence method in 17 children with hematologic malignancy (including 6 with ALL, 7 with ANLL and 4 with non-Hodgkin's lymphoma) during remission induction therapy. The activity of opsonin, which was at the normal level before chemotherapy, decreased in all of the children during the therapy. This phenomenon was especially marked in the children treated with L-asparaginase. Although no clear relationship was found between the decrease in opsonin activity and the susceptibility to infection, it was confirmed that in 4 children having an episode of sepsis or septic fever, the infection started when the granulocyte decreased to the nadir, and simultaneously the activity of opsonin decreased. Therefore, it may be reasonable to suspect the decrease in opsonin activity when treating children with such infections.
OGAWA, K., MATSUNAGA, M., NAGAI, H., HARA, A., KOIDE, H., PAK, C.H., HIRAKAWA, A. and KAWAI, C. Effects of Enalapril Maleate (MK-421) onRenovascular Hypertension. Tohoku J. exp. Med., 1985, 145(2), 125-135-The effects of enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied on 5 patients with renovascular hypertension(RVH) due to unilateral renal artery stenosis. The therapeutic dosage was increased when the blood pressure (BP) was not controlled for more than 3 days. Blood sampling was performed before, and 5hr and 24hr after the first administration, and on the 3rd day with each dosage. The BP was normalized on 5mg/day in 1 case, 10mg in 1 case, 20mg in 2 cases, and 40mg plus mefruside in 1 case. Plasma renin activity (PRA) was significantly increased after 5hr and recoverd after 24hr with 2.5mg of the enalapril maleate, when the BP was not affected. This indicates that the increase in PRA is likely due to the reduced negative feedback of angiotensin II. When the blood pressure was lowered, PRA was increased and plasma aldosterone concentration (PAC) was decreased significantly. This rise of PRA may depend not only on the reduced negative feedback but also on the fall of BP. It is also considered that the PAC was decreased through the decrease in plasma angiotensin II. A fall of the glomerular filtration rate in one case and also a fall of the perfusion of the kidney of the stenotic side in another case were observed by radioisotope renograms. MK-421 administration was a useful treatment for RVH, and clearly normalized the BP of all the patients studied. However, there was a risk of a fall of renal function on the stenotic side due to the decrease in perfusion pressure.
ASAKI, S., NISHIMURA, T., SATO, A., YAMAGATA, R., OKUBO, S., TOYOHARA, T., SAITO, Y., ITO, S. and MIYAZAKI, S. Multiinstitutional Evaluation of Local Injectionof Absolute Ethanol as the New Hemostatic Method for Upper G-I TractBleeding. Tohoku J. exp. Med., 1985, 145(2), 137-147-Local injection of absolute ethanol was proven effective for hemostasis of gastrointestinal bleeding in our fundamental (Asaki et al. 1983a) and clinical (Asaki et al. 1983b) studies. The purpose of the present paper is to report the results obtained in 258 hemorrhagic foci in 152 unselected cases treated with this method at 6 major hospitals in the Tohoku area in Japan. Sixty (39%) of these 152 cases had shock symptoms due to hemorrhage. Gastric and duodenal ulcers were responsible for the hemorrhage in about 90% of the cases in which our method was applied to hemostasis. Eighty-nine (59%) of the 152 cases had some form of complications such as malignant tumors or liver cirrhosis. Hemorrhage due to postoperative stress ulcer after major surgeries including renal implantation or laryngectomy for resection of cancer was seen in 20 cases (13%). The condition of hemorrhage immediately before the treatment with our technique was classified as spouting hemorrhage for 8 foci (3%), pulsating hemorrhage for 22 foci (9%), adhesion of clot for 179 foci (69%), and hemorrhage from veins and capillaries for 49 foci (19%). In all of these cases temporary hemostasis was obtained. Rebleeding occurred in 17 cases (7%) including 5 cases in which hemostasis was successfully obtained by the repeated use of our method. In 4 of the 17 cases, in which repeated endoscopy was infeasible, emergency surgery was performed. In the remaining 8 lesions in 8 cases, new bleeding or rebleeding occurred more than 1 week after the initial hemostasis had been obtained. Six of these 8 cases died from rebleeding due to DIC syndrome. With our method complete hemostasis was obtained in 144 of 152 cases (95%) including 11 cases (7%) which underwent elective surgical operation.
ASAKI, S., NISHIMURA, T., OHARA, S., SATO, A., SHIBUYA, D., KANAZAWA, N. and GOTO, Y. New Trial of Endoscopic Treatment for Gastric SubmucosalTumors. Tohoku J. exp. Med., 1985, 145(2), 149-159-Recently conservative treatment of gastric submucosal tumors is increasing in spite of the absence of definite criteria for histological diagnosis. We have developed a new method of endoscopical treatment of gastric submucosal tumors that have submucosographically intraluminal Pattern I or II, or partly intramural Pattern III. For such tumors with a maximum diameter less than 5cm, (1) 1st step: partial resection is carried out with the use of high-frequency electric currents, (2) IInd step: for the residual tumor tissue, in vivo tissue solidification is undertaken by local injection of absolute ethanol to induce necrotic exfoliation of the tumor tissue and to prevent of hemorrhage.
HANEW, K., SATO, S., SASAKI, A., SHIMIZU, Y., MURAKAMI, O. and YOSHINAGA, K. Comparative Study on the Responses of Plasma GH to Synthetic GH-Releasing Factor and Other Stimulatory and Inhibitory Agents in Patients withAcromegaly. Tohoku J. exp. Med., 1985, 145 (2), 161-166-Ten patients with active acromegaly received synthetic human pancreatic GH releasing factor (hpGHRF-44), and the GH responses to GHRF were compared with the basal GH levels and with the GH responses to arginine, TRH, LH-RH, somatostatin, and L-dopa. There were no significant relationships between the plasma GH responses to GHRF and the results of the stimulatory and inhibitory tests mentioned above, except that the responses to GHRF showed weak positive or negative correlations with the responses to LH-RH (r=+0.56) or with the basal GH levels (r=-0.57). These results indicate that acromegalic somatotrophs would have GHRF receptors as well as several other receptors to hypothalamic hormones and to dopamine, and that there might be no distinct relationship between the somatotroph sensitivities to GHRF and to other stimulatory or inhibitory stimuli. Further studies are required regarding the weak correlations between the response to GHRF and that to LH-RH or basal GH value.
BABA, T., MURABAYASHI, S., AOYAGI, K., SASAKI, K., IMAMURA, K., KUDO, M. and TAKEBE, K. Prevalence of Hypertension in Diabetes Mellitus-Its Relationto Diabetic Nephropathy. Tohoku J. exp. Med., 1985, 145(2), 167-173-The prevalence of hypertension was studied in 374 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 1197 non-diabetic controls. The diagnosis of hypertension was made when the mean systolic pressure of three measurements on different occasions was 151mmHg or greater, or the mean diastolic pressure was 91mmHg or greater. The prevalence was 42.8% in the diabetics and 17.8% in the controls. It showed a significant difference over age 31 (p<0.05). Proteinuria (p<0.001), abnormal ECG (p<0.01), hyperlipidemia (p<0.05) and hypertensive or sclerotic changes of the retina (p<0.001) were more frequently observed in the diabetics than in the controls. Hypertension was found in 71% of those with proteinuria, 48% with diabetic retinopathy, 61% with abnormal ECG and 54% with hyperlipidemia in the diabetics. The incidence of proteinuria was 22.8% in the diabetic hypertensives and was 8.3% in the non-diabetic hypertensives (p<0.001). 24 subjects out of 119 diabetics, who were normotensive at their initial visits, became hypertensive within 10 years (N-H), and 95 remained normotensive (N-N). 38% of N-H showed proteinuria already on their initial examinations and 3% of N-N did. 73% of those who showed proteinuria on their initial examination became hypertensive and 13% of those who were free from proteinuria did (p<0.001). The results suggest that diabetic nephropathy plays an important role in developing hypertension in diabetics.
AIKAWA, J., MUNAKATA, H., ISEMURA, M. and YOSIZAWA, Z. Sulfated Glycopeptides, Containing Desmosine and Isodesmosine, Isolated from Porcine Aorta. Tohoku J. exp. Med., 1985, 145 (2), 175-183-Intima-media of porcine thoracic aorta was digested with pronase, after extraction of saline-soluble matters and fat. A crude sulfated glycopeptide fraction (CSGP) was precipitated with 90% (v/v) ethanol from the 80% ethanol-soluble fraction of the trichloroacetic acid (7%)-soluble fraction of the pronase digest. CSGP was fractionated by DEAE-Sephadex A-25 (Cl- form) column chromatography. Of the resulting 9 fractions, 4 major fractions were further purified by gel filtration on Sephadex G-50, followed by affinity chromatography on concanavalin (Con) A-Sepharose 4B to a homogeneous state in electrophoresis on cellulose acetate membrane. All the purified fractions contained glucosamine, galactose, mannose, and sialic acid as the major sugars, and desmosine and isodesmosine as the unigue constituents. The fractions with affinity for Con A (S1 and S2) contained much more mannose than those without affinity for this lectin (S3 and S4). The latter contained sulfate. The predominant amino acids in the former were glycine, aspartic acid (and/or asparagine), and serine, while those in the latter were glycine, proline, and alanine.
IKAWA, S., KAWASAKI, H., YAMANISHI, Y., MURA, T. and MIYAKE, M. Measurement of the Ratio of Primary to Total Bile Acids in Serum by EnzymaticFluorometric Microassay and Its Clinical Significance in Patients with LiverDisease. Tohoku J. exp. Med., 1985, 145(2) 185-195-An enzymatic fluorometric microassay using 3α-or 7α-hydroxysteroid dehydrogenase was devised to determine serum total or primary bile acids. The present microassay using 50μl of a serum sample was run as a two-step method; the first step is the reaction of substrates with NAD+ and the hydroxysteroid dehydrogenase to produce as much NADH as possible in the incubation system and the second step is that of NADH with resazurin coupled with 1-methoxy phenazinemethosulfate to produce fluorescent resorfin. The assay is specific for 3α-or 7α-hydroxy bile acids, sensitive (a detection limit of 1.5μM with a linear range of 1.5-80μM), reproducible (CV=less than 5%) and inexpensive. As measured by this microassay, the ratio of serum primary to total bile acids (P/T ratio) in 10 normal subjects was 62.1±0.7% and was significantly elevated in the early phase of acute hepatitis (p<0.01), followed by return to the normal level after 4 weeks.
OHTSU, H., MUE, S., TAMURA, G., YAMAUCHI, K., ISHIHARA, T., SATO, K. and TAKISHIMA, T. Measurement of SRS-A Activities in Plasma of AsthmaticPatients. Tohoku J. exp. Med., 1985, 145 (2), 197-203-Ethanol extracts of arterial blood from 20 of 29 asthmatic patients during attacks produced sustained contractions of the guinea pig ileum. These contractions were inhibited by FPL 55712, a specific antagonist of slow reacting substance of anaphylaxis (SRS-A). SRS-A activity was significantly higher during attack than during remission. Reverse-phase high pressure liquid chromatography (HPLC) was performed on two extracts which had shown high SRS-A activity with bioassay. One extract showed double peaks, which had retention times identical to those of leukotriene (LT) C4 and LTD4. The other extract showed a single peak, which had a retention time identical to that of synthetic LTC4.
TANAKA, K., KAJIYAMA, K., IMAMURA, T., JIMI, S., WATANABE, T., SATO, H., OKOCHI, K. and INOUE, T. Genetic and Environmental Factors in the Developmentof Behcet's Disease. Tohoku J. exp. Med., 1985, 145(2), 205-213-Analysis of HLA antigens and case control study were performed in 50 patients with Behcet's disease. Frequency of HLA-Bw51 was significantly increased in the patients (52.0%) as compared to that in the control subjects (16.0%). In case control study, the incidence of tonsillitis, and use of public bath and a privy were more frequently seen in the patients than in the controls. The patients were frequently exposed to agricultural chemicals before onset of the disease. Daily ingestion of vegetable salad and milk was less frequent in the patients than in the controls. Heterogeneity of Behcet's disease and results of multivariate analysis for selected variables were discussed.
YASUJIMA, M., ABE, K., TANNO, M., OMATA, K., KASAI, Y., SATO, M., KIMURA, T. and YOSHINAGA, K. Decreased Urinary Active and Inactive Kallikrein byChronic Infusion of Vasopressin in Conscious Rats. Tohoku J. exp. Med., 1985, 145 (2), 215-222-To assess possible interactions of circulating vasopressin with the synthesis or activation of renal kallikrein, we studied the effect of chronic infusion of vasopressin (7.2U/kg/day i.p.) for 6 days on the urinary excretion of total and active kallikrein in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after the treatment with trypsin (200μg/ml). Chronic infusion of vasopressin induced sustained decreases in urinary total, active and inactive kallikrein excretion, but did not affect the ratio of active to total kallikrein. The infusion of vasopressin induced significant increases in circulating levels of vasopressin (248.1±35.2pg/ml in vasopressin-infused rats (n=7) compared to 95.5± 14.6pg/ml in vehicle-infused rats (n=7), p<0.001) and in weight gain (39.6±1.3 g in vasopressin-infused rats (n=7) compared to 29.1±3.3g in vehicle-infused rats (n=7), p<0.05), and also sustained decreases in water intake and urine volume, but it did not induce any change in urinary sodium excretion. Circulating levels of angiotensin II was decreased by chronic infusion of vasopressin. Thus, the present study suggests that the elevation of circulating vasopressin levels induces a decrease in the synthesis of renal kallikrein.
YAMAGUCHI, S., OKUNO, A., ETO, Y. and MAEKAWA, K. Pathochemical Studyof a Case of Hereditary Cerebral Degenerative Disease-Lipopigment Accumulationand Peroxidase Deficiency in Brain. Tohoku J. exp. Med., 1985, 145 (2), 223-229 -Ultrastructural study of autoptic cerebral tissue from a patient with hereditary degenerative disease of the nervous system revealed lipofuscin-like bodies and variable sized osmiophilic granular masses in neurons. Autofluorescent granules were also found in neurons. Biochemical study demonstrated a deficiency of diaminobenzidine peroxidase and the accumulation of lipopigment in cerebral tissue.
SAJIKI, N. and NAKAMURA, R. Motor Time of the Rectus Femoris duringPassive Movements. Tohoku J. exp. Med., 1985, 145 (2), 231-232-Motor time (MT) of 10 normal subjects were examined in three conditions: 1) during passive flexion of the knee (PFLX), 2) during passive extension (PEXT), and without passive movement (STAT). Compared to STAT, MTs of PFLX and PEXT were significantly long. MT tended to be shorter, though insignificant statistically, in PFLX than in PEXT. In conclusion, passive movements are influential in changing the physical state of the muscle including both series-elastic and contractile components.