TANAKA, M. and OHKITA, T. Analysis of Fibrinogen Degradation Product inSevere Liver Disorders by Immunoblotting. Tohoku J. exp. Med., 1987, 153 (3), 179-187 - Increased serum fibrinogen degradation product (FDP) in liver cirrhosis and hepatic carcinoma as measured by latex agglutination was analyze by means of SDS-polyacrylamide gel electrophoresis followed by immunoblotting with anti-fibrinogen antibody. The antibody used in this study reacts with fibrinogen, fragment X, Y, D-D, D and E. The validity of this technique was confirmed by the analysis of the serum samples from patients with definit ediagnosis of disseminated intravascular coagulation. Serum samples of 14 patients out of 18 with elevated FDP values and severe liver diseases were shown to contain no plasmic digest of fibrin or fibrinogen. By using the SDS-gel electrophoresis after disulfide bond reduction, seven serum samples from these 14 patients, who were shown to have no plasmic digest in serum, were found to contain unclottable fibrinogen retained in sera, while the remaining seven samples were revealed to have fibrin monomer in their sera. Four serum samples from the 18 patients were shown to have plasmic digest of fibrinogen, but these patients had additional diseases leading to intravascular coagulation.
YAZAKI, M., OKAJIMA, K., SUCHI, M., MORISHITA, H. and WADA, Y. Increaseof Protein Synthesis by Uridine Supplement in Lectin-Stimulated Peripheral BloodLymphocytes and EB Virus-Transformed B Cell Line of Hereditary Orotic AciduriaType I. Tohoku J. exp. Med., 1987, 153(3), 189-195 - A 2 month-old Japanese girl with hereditary orotic aciduria type I was treated with oral uridine supplement. The activities of orotate phosphoribosyltransferase (OPRT) and orotidine-5'-phosphate decarboxylase (ODC) in erythrocytes were 2.7 and 0.4%, respectively, of those in the controls. Megaloblastic anemia, excessive urinary excretion of orotic acid, lymphopenia and decreased number of OKT3 positive lymphocytes on admission were corrected after the uridine supplement. Peripheral blood lymphocytes (PBL) were cultured for 24hr in RPMI 1640 medium with 10% heat-inactivated fetal calf serum and further stimulated with PHA-P, ConA or PWM in the presence of 10 to 1000μM uridine.EB virus-transformed B cell line (LCL) maintained with an optimal concentration of uridine was cultured for 48hr in uridine free medium and cultured for an additional 48hr with 1 to 1000 μM uridine. The incorporations of leucine in to PHA-, ConA- and PWM-stimulated PBL and into LCL of the patient increased in the presence of uridine over 10μM, although they did not increase in controls. These data suggest that low protein synthesis might correlate with an immune deficiency in heredi taryorotic aciduria type I.
MIZUTANI, N., HAYAKAWA, C., OHYA, Y., WATANABE, K., WATANABE, Y. and MORI, A. Guanidino Compounds in Hyperargininemia. Tohoku J. exp. Med., 1987, 153 (3), 197-205 - Plasma and cerebrospinal fluid (CSF) concentrations and urinary excretion of guanidino compounds were investigated in a patient with hyperargininemia during the treatment with low-protein diet, oral administration of an essential amino acid mixture and sodium benzoate, or enzyme replacement therapy such as exchange transfusion or erythrocyte transfusion. In the patient, α-keto-δ-guanidinovaleric acid (GVA), N-α-acetylarginine (NAA), argininic acid (ArgA) and homoarginine concentrations in plasma were elevated as well as arginine. Urinary excretion of GVA, ArgA, NAA and γ-guanidinobutyric acid (GBA) were also increased. CSF concentrations of ArgA, homoarginine and arginine were also elevated. On the other hand, guanidinosuccinic acid (GSA), which is usually detected in all samples, was not detected in plasma, CSF and urine of the patient. The present results suggest that in patients with hyperargininemia other factors such as arginine and its metabolites including GVA, GAA, ArgA and homoarginine may cause the neurological symptoms. Furthermore, it is suggested that in patients with hyperargininemia, arginine may be catabolized via other pathways and nitrogen may be excreted partially in urine in the form of some of guanidino compounds.
KANOH, T. and SAIGO, K. Phagocytic Myeloma Cells in AsymptomaticMultiple Myeloma. Tohoku J. exp. Med., 1987, 153 (3), 207-210 - A newly observed case of asymptomatic multiple myeloma in which phagocytic myeloma cells were observed is described. Bone marrow aspirates contained 16% myeloma cells, 2% of which engulfed red blood cells, lymphocytes, and platelets. The possibility is discussed that phagocytizing ability may be one of the markers for malignant plasma cells. Nothing is so far known of the phagocytosis by plasma cells in benign monoclonal gammopathy which is strictly defined.
ISHIKAWA, Y., KANZAKI, T., MORISAKI, N., SAITO, Y. and YOSHIDA, S. Inhibitory Effect of FO-1561 (S-Adenosyl-L-Methionine Sulfate Tosylate) onPhospholipase A2. Tohoku J. exp. Med., 1987, 153 (3), 211-215 - The mechanism of the protective effect of FO-1561(S-adenosyl-L-methionine sulfate tosylate) on mitochonidria was investigated using rat heart muscle. FO-1561 stimulated CO2 production from palmitic acid in the mitochondria, indicating an increase in energy production. FO-1561 inhibited mitochondrial swelling induced by Ca2+ added exogenously or by addition of snake venom phospholipase A2. Moreover, FO-1561 inhibited phospholipase A2 activity directly. These results suggested that FO-1561 blocked mitochondrial swelling by inhibiting endogenous phospholipase A2 activity and so preventing decrease in palmitic acid oxidation.
ODA, H. Left Ventricular Responses to Dopamine in Dilated Cardiomyopathy as Assessed by Two-Dimensional Echocardiography and Compared with Findings of Thallium-201 Scintigraphy. Tohoku J. exp. Med., 1987, 153 (3), 217-226 - The effects of dopamine on the left ventricular regional wall motion were studied in 11 patients with dilated cardiomyopathy by use of two-dimentional echocardiography and compared with the findings on the uptake of thallium-201. There were no significant changes in heart rate after dopamine infusion (6μg/kg/min). However, the administration of dopamine significantly reduced PEP/ET and increased the systolic blood pressure, fractional shortening, ejection fraction and mVcf. The percentage of segments with reduced thallium-uptake area was significantly higher in abnormal wall motion segments than in normal wall segments both before and after dopamine administration. The percentage of segments with reduced thallium-uptake area was significantly higher in abnormal wall motion segments after loading than in normal wall segments before loading or in dopamine responding segments. However, in reduced uptake area, the asynergy of the left ventricle was improved significantly after dopamine administration. These results demonstrated that the abnormality of Tl-uptake was correlated roughly to the asynergy of the left ventricle, but that the state of remaining myocardium was not necessarily evaluated correctly by Tl-uptake. Dopamine loading seemed to be useful for more accurate evaluation of myocardial residual function.
NAKAGAWA, S., KOJIMA, M., NAKAO, M. and WATANABE, H. FluorescenceMicroscopic Study on Absorption of Adriamycin through the Rat Bladder Epithelium. Tohoku J. exp. Med., 1987, 153 (3), 227-232 - The absorption of adriamycin (ADM) through the rat bladder epithelium was investigated histologically with a fluorescence microscope. ADM permeated through the epithelium into the lamina propria or the inner layer of the muscle within 15min after instillation, but no further infiltration into the deeper part of the bladder wall was observed thereafter. In addition, fluorescence histological evidence on the uptake of ADM by the endothelial cells of the blood vessels in the lamina propria suggested the systemic diffusion of ADM to the whole body via the circulatory system of the blood. The method reported in the present study is considered to be promising in checking the penetrability of ADM both in the normal bladder wall and bladder tumors.
IMAI, T., YASUDA, K., OHTA, T. and MIURA, K. 13 Trisomy Born to a MotherTreated with Bromocriptine: Incidental or Not? Tohoku J. exp. Med., 1987, 153 (3), 233-238 - A case of 13 trisomy born to a mother treated with bromocriptine is described. She, 27 years old, was treated with bromocriptine (5mg/day) as a galactorrhea amenorrhea syndrome with hyperprolactinemia (basal 34-122ng/ml). After the treatment for about a month, disappearance of galactorrhea and occurrence of menstruation were observed. She became pregnant on the second ovulation. On the 34th week she got a male 13 trisomy (47, XY, +13) baby with premature delivery. The baby died 11hr after his birth. After the first delivery, bromocriptine was readministered. Following the induced abortion on the second pregnancy, she borned a healthy baby on the third pregnancy in spite of taking bromocriptine. This case of 13 trisomy might be incidental. However, the effect of bromocriptine on chromosome should be further evaluated in detail.
NIITSU, Y., KOHGO, Y., NISHISATO, T., KONDO, H., KATO, J., URUSHIZAKI, Y. and URUSHIZAKI, I. Transferrin Receptors in Human Cancerous Tissues. Tohoku J. exp. Med., 1987, 153 (3), 239-243 - The clinical significance of radioreceptor assay for transferrin receptors of human cancerous tissues was evaluated. Fresh surgical specimens from various carcinoma tissues were solubilized with 1% Triton X-100 and the extracts were mixed with 125I-labelled diferric transferrin. The free transferrin and the receptor-bound transferrin were separated by 15% polyethylene glycol precipitation. The % specific transferrin binding to gastric, colonic, lung and mammary carcinoma tissues ranged between 3.9 and 13.9%, whereas those for normal stomach and colon were less than 2%. The concentrations of transferrin receptors in these cancerous tissues ranged between 3.7 and 28.3 pmole/g tissues. It was concluded that the amounts of transferrin receptors were significantly increased in all of the tumor tissue extracts examind and may thereby provide a useful marker for the diagnosis of malignancies.
UEHARA, S. and YAJIMA, A. Morphology of Mouse Embryo Cultured in aNewly Established Culture System Using Collagen Gel Layer. Tohoku J. exp. Med., 1987, 153 (3), 245-258 - A new in vitro culture system of embryo using collagen gel as the substrate was developed, in which mouse blastocysts were cultured. Morphological analyses including electron microscopic observation disclosed that after hatchig, the mouse blastocysts were attached to the collagen gel layer and were satisfactorily developed and differentiated. In the embryo observed on the 3rd or 4th day after culture, cellular processes and villi had penetrated the collagen gel from the mural trophoblast. While there were many vacuoles in the cytoplasm and a large number of destroyed cells in the mural trophoblast mass, some steroid producing cells were also observed. The polar trophoblasts, though having a small number of vacuoles, partially exhibited characteristic activities of steroid production. Between the mural and the polar trophoblasts, a sort of desmosome or intermediate junction was observed. There were no morphological differences among the cells derived from the inner cell mass. From these results, it was concluded that this new embryo culture system using collagen gel layer as the substrate can be of value in studies on development and differentiation of the embryo; moreover, this system can be used to replicate several phenomena similar to those appearing in in utero implantation.
SATO, H., SAITO, T., FURUYAMA, T. and YOSHINAGA, K. Histologic Studies onthe Nephrotic Syndrome in the Elderly. Tohoku J. exp. Med., 1987, 153 (3), 259 -264 - Renal histopathology in 87 patients, aged over 60, with nephrotic syndrome were studied. In 57 patients diagnosed as primary glomerular disease, membranous glomerulonephritis (MGN) was of the most common histologic type (52.6% of the cases), and mesangial proliferative glomerulonephritis (21.1%), membranoproliferative glomerulonephritis (12.3%) and minimal change (12.3%) were the other types of primary glomerular disease. In the remaining 30 patients, nephrotic syndrome resulted from secondary glomerular diseases including diabetic nephropathy and renal amyloidosis. In comparison with the nephrotic syndrome of younger age group (669 cases, younger than 60 years of age), the incidence of MGN, diabetes and amyloidosis were significantly higher in the elderly. In contrast with unfavorable prognosis of diabetic nephropathy and amyloidosis, most cases of MGN and minimal change recovered from the nephrotic state with steroid treatment even in the elderly. Thus, a statistical finding that the prognosis of senile nephrotic syndrome is unfavorable as a whole, appears to be ascribable to the increased incidence of secondary glomerular diseases rather than to “aging” itself. The present results that the incidence of diabetic nephropathy was high and the outcome of MGN was favorable in the elderly, taken together with the results from other studies in Japan, are fairly different from the results of similar studies in the Western world.
NAGAMOTO, N., SAITO Y., IMAI, T., SUDA, H., TAKAHASHI, S., USUDA, K., KANMA, K., SAGAWA, M., OHTA, S., SATO, M., NAKADA, T., SATO, H. and HASHIMOTO, K. Histogenesis and Characterization of Minimal BronchogenicCarcinoma Observed in Heavy Smokers. Tohoku J. exp. Med., 1987, 153 (3), 265-284 - The present article describes the results of observations of 11 lesions in 8 cases of roentgenographically occult in situ or microinvasive squamous cell carcinoma with a size of 4×4mm or less which were detected by detailed histologic investigations of 59 cases of occult bronchogenic carcinoma. The 59 cases were discovered mainly by mass screening for the detection of early lung cancers using chest x-ray combining sputum cytology for heavy smokers. The resected specimens were processed with the method of serial block sectioning. All the serial blocks of these minimal carcinomas were observed in detail to confirm the presence or absence of carcinoma and of morphological changes of the bronchial epithelium contiguous to carcinoma. Adjacent to carcinoma, there were normal bronchial epithelium in three lesions, squamous metaplasia with marked atypia in four, basal cell hyperplasia in two, and markedly atypical basal cells without hyperplasia in two. An inference on histogenesis of bronchogenic squamous cell carcinoma was drawn from the detailed observations as follows: (1) A carcinoma develops in the area of squamous metaplasia with marked atypic; (2) A carcinoma arises from markedly atypical basal cells with or without prior hyperplasia. Even in such small-sized carcinomas, there is a difference in type of invasion within the bronchial wall. One is the creeping type which shows a marked horizontal growth and the other is the penetrating type which shows a marked downward growth.