YAMANE, N., ODAGIRI, T., ARIKAWA, J. and ISHIDA, N. Reversed Single-Radial-Immunodiffusion Test: The Method for the Assay of the Antibody to Influenza ANucleoprotein. Tohoku J. exp. Med., 1981, 133 (3), 245-255-The reversed single-radial-immunodiffusion (r-SRD) test using the avian-origin influenza A virus, A/chicken/Germany 'N'/49 (Hav2Neql) disrupted with 1.0% sarkosyl, was established as the quantitative method for the assay of a type-specific antibody, particularly of an anti-nucleoprotein antibody, in human sera. Under the test conditions, human sera produced a definite opalescent zone around the well and the annulus area was found to have a high correlation to the antibody level to type A influenza nucleoprotein. The specificity of the opalescent zone produced in the test plate was confirmed with the specific antisera to each viral polypeptide and the adsorption procedures with the purified nucleoprotein. During an epidemic of H3N2 and H1N1 viruses, the r-SRD test was employed to estimate the infection ratio in junior high school students. The results demonstrated its convenience and high sensitivity in detecting the antibody rise to influenza A nucleoprotein. In addition, the age-distribution of the antibody level to influenza A nucleoprotein was examined and discussed. The results obtained strongly suggested that the r-SRD technique using the avian-origin influenza A virus provided a simple and reproducible method for the assay of the antibody level to influenza A nucleoprotein in a large scale seroepidemiology and in the serodiagnosis of influenza A virus infection.
KUROYANAGI, T. and KURA, K. The in Vitro Development of ImmunoglobulinProducing Cells from the Human Bone Marrow Null Lymphocyte. Tohoku J. exp. Med., 1981, 133 (3), 257-266-The distribution of human bone marrow lymphocyte population was studied on twenty normal adults. The distribution of bone marrow lymphocytes were as follows: null lymphocytes 79.4%, E-RFC 8.9%, Thy+ lymphocytes 0.4%, Tγ 0.9%, Tμ 1.4%, SmIg+ cells 7.8%, EAC-RFC 11.7%, EA-RFC 6.2%, and K cells 2.7%. Bone marrow null lymphocytes were intermediate in their size between small lymphocytes and lymphoblasts. The presence of a lot of short microvilli on null lymphocytes was demonstrated by scanning electron microscopic examinations. The bone marrow null lymphocytes had no cytoplasmic Ig. When the bone marrow null lymphocytes were mixed- lymphocyte-cultured with allogeneic T lymphocytes and then stimulated with PWM, there developed Ig producing cells. Differences between pre-B cells and bone marrow null lymphocytes were discussed.
HIGUCHI, M., HIRANO, H. and MART, M. The Thromboplastic Activity ofLung Surfactant in Amniotic Fluid and Its Application to Prenatal Assessment ofFetal Lung Maturity. Tohoku J. exp. Med., 1981, 133 (3), 267-273 Based on the fact that both tissue thromboplastin and lung surfactant show lamellar structures under the electron microscope and belong chemically to lipoprotein, the thromboplastic activity of lung surfactant in amniotic fluid was studied by measuring plasma recalcification time. The results obtained were as follows: (1) The surfactant fractions isolated from amniotic fluid and rabbit or pig lung showed the thromboplastic activity with dose response. (2) The thromboplastic activity of amniotic fluid increased with advancing gestational age. (3) It was found that the thromboplastic activity determined by plasma recalcification time was parallel with the surfactant concentration of amniotic fluid. (4) The shortening rate of plasma recalcification time in amniotic fluid could estimate well the risk of RDS, and the critical value for RDS was assumed to be about 33%.
MORITA, T., MORITA, R., TAKAGI, S., SHIMOYAMA, N. and NAGAI, K. Specificitiesand Some Properties of Human T and B Lymphocyte Antisera. Tohoku J. exp. Med., 1981, 133 (3), 275-284-Antisera were prepared in rabbits by immunization with either human peripheral blood T lymphocytes (PTL) or tonsil B lymphocytes (TBL). Specificities of sequentially absorbed antisera were examined by cytotoxicity testing, immunoperoxidase staining and absorption study. Anti-PTL serum (ATS) reacted with E rosetting lymphocytes in the normal population. ATS was also reactive with some of lymphoid neoplasms, whether neoplastic cells carried E receptors or not. This serum did not lyse any of myelogenous leukemia cells. When antiserum was used in the immunoperoxidase staining, ATS strongly stained paracortical cells in the lymph node and medullary thymocytes in the thymus. On the other hand, anti-TBL serum (ABS) was reactive with lymphocytes corresponding to the percentage of EAC binding lymphocytes in the normal population. ABS reacted not only with the neoplastic cells earring C3 receptors and/or surface immunoglobulin, but also with non T.non B-acute lymphoblastic leukemia cells and a small number of acute myelogenous leukemia cells. In the immunoperoxidase staining, lymph follicular cells showed positive immunoreactivity with ABS, but paracortical cells did not.
NAKAMURA, R., ISAGODA, A. and CHIDA, T. The Interference Effect ofSimultaneous Vocalization on Manual Reaction Time. Tohoku J. exp. Med., 1981, 133 (3), 285-288-Simple reaction times (RTs) of the left or right hand with or without simultaneous vocalization were examined in 14 right-handed subjects. RTs of the simultaneous tasks were longer than those of the single tasks and slowing of RT was larger on the manual than vocal response, particularly on the right side. The results are interpreted as reflecting a different mode of processing in the left and right hemispheres.
TAKEDA, T. and MATSUURA, N. The Effect of L-Asparaginase on CholesterolBiosynthesis. Tohoku J. exp. Med., 1981, 133 (3), 289-291-The liver from the Wistar rat was incubated either in the solution of 1μCi acetate-1-14C or 0.1 μCi mevalonic acid-2-14C, and incorporations of radioactivity to phospholipid and cholesterol were estimated respectively. The incorporation of labeled acetate to cholesterol in the L-asparaginase-treated rat was significantly lower than that in the controls. However, there were no differences of the incorporation into the mevalonic acid between the study group and the controls. These results suggest that the inhibitory mechanism may exist between the steps of acetate and mevalonic acid.
MOTOMIYA, M., SATO, H., ARAI, H., NAGAI, H., ITO, M., SATOH, K., KUMANO, N. and KONNO, K. Chemical and Biological Properties of Subfractions ofHot-Water Extract from Delipidated BCG. Tohoku J. exp. Med., 1981, 133 (3), 293-300-A hot-water extract from delipidated Mycobacterium bovis strain BCG was fractionated by precipitation with ethanol. The chemical and biological properties of the subfractions thus obtained were investigated. A subfraction precipitated at 20% ethanol contained less neutral sugar and more ninhydrin-positive substance than other subfractions. Only the guinea pigs that were treated with 20% ethanol-precipitate showed no humoral antibody response to egg white albumin, despite positive skin reaction. The subfractions precipitated at low concentrations of ethanol exhibited a significant antitumor activity in ddY and C3H/He mice inoculated intraperitoneally with tumor cells. These results suggest that the hot-water extract from delipidated BCG consists of subfractions with different chemical and biological properties.
KOIZUMI, F., ISHIMORI, A., NAKANOME, C., MITA, M., TAIMA, T. and TSUDA, K. Mucosal Secretin of the Duodenum in Peptic Ulcer Disease. Tohoku J. exp. Med., 1981, 133 (3), 301-305 Mucosal secretin content of the duodenum was measured using bioptic specimen in healthy controls and patients of peptic ulcer. Immunoreactive secretin in the duodenal mucosa was found greater in healthy controls (7.73±2.71ng/mg dry wt., mean±s.D.) than in gastric ulcer patients (5.76±3.51ng/mg dry wt.) and duodenal ulcer patients (5.54±2.48ng/mg dry wt.), but the difference was not significant. There was no significant relationship between mucosal secretin and acid output in these patients.
ADACHI, K. and HAYASHI, M. An 18p- Syndrome due to 15/18 Translocationwith Facial Palsy and Deafness. Tohoku J. exp. Med., 1981, 133 (3), 307-311 -A case of translocation between chromosomes No. 15 and 18 was described. Phenotype of the patient was almost consistent with that of the 18p- syndrome. In addition to the typical feature of 18p- syndrome, he had perceptive deafness, and abducens nerve and facial nerve palsies. Giemsa-banding technique demonstrated patient's karyotype to be 45, XY, -15, -18, +t (15; 18) (p12: p11).
SERA, Y. and KANG, K.-Y. Asbestos and Cancer in the Sennan District ofOsaka. Tohoku J. exp. Med., 1981, 133 (3), 313-320-The cancer incidence among asbestos workers in the Sennan District and its surroundings of Osaka Prefecture, Japan, and the result of a mass survey in the above area since 1957 were evaluated from view points of epidemiology. During the period from 1953 to 1979, 107 patients with asbestosis were admitted to this Hospital. Twenty-six (24%) of them died of various carcinoma; 21 had lung cancer, 2 pleural mesothelioma and 3 had stomach cancer. Respiratory insufficiency due to pulmonary asbestosis was responsible for 41 deaths (38%). By a cohort survey of the 297 asbestos workers in the same district, 4 cases of lung cancer, and 3 cases of gastric cancer were detected and cases of cohort survey were followed up for 19 years. Fifty-seven (10%) of 556 cases of silicosis and 14 (11%) of 125 cases of pneumoconiosis other than silicosis or asbestosis were found to have lung cancer, but no mesothelioma. These results indicate that lung cancer and mesothelioma are associated more frequently with asbestosis than with non-asbestos pneumoconiosis (p<0.001 as tested by X2-test). The standardized mortality ratio of lung and stomach cancer among the inhabitants of the Sennan District was calculated based on the statistics during the period of 10 years (1968-1977). The ratio of observed death to expected death of both cancers was smaller than 1.1, and there was no significant increase of death of lung and stomach cancer, although the risk of lung cancer tended to increase among male inhabitants. Discussions were made on the problems related to asbestos industry.
YUSA, T. and OBARA, S. Myocardial Oxygen Extraction Rate under GeneralAnesthesia. Tohoku J. exp. Med., 1981, 133 (3), 321-324-Myocardial oxygen extraction rates (R) were measured in dogs anesthetized with eight kinds of anesthetic agents to study the balance between myocardial oxygen consumption and its supply under general anesthesia. The R value for basal anesthesia (pentobarbital), original neuroleptanesthesia (Thalamonal®), modified neuroleptanesthesia (droperidol and pentazocine), morphine anesthesia or halothane anesthesia was not significantly different from each other, and similar to those for conscious dogs reported by Merin or Spencer. On the other hand, the R values for ether anesthesia, methoxyflurane anesthesia and enflurane anesthesia were significantly lower than those for the above mentioned anesthesia.
USUBUCHI, I., KUDO, H. and SATO, T. Histological Studies of the Mode ofOrigin of Tumors. Tohoku J. exp. Med., 1981, 133 (3), 325-330-All of the tubular adenocarcinomas of early gastric cancer in humans showed gentle transitions from surrounding normal to neoplastic epithelium. In mammary carcinomas in C3H/He mice, known as viral tumors, there were also transitional appearances from normal to cancer cells. Furthermore, it was possible in rats to trace gradations between normal fibrocytes and sarcoma cells in marginal areas of tumors induced subcutaneously by 3-methylcholanthrene (MCA). It cannot be explained by the mutation of a few somatic cells that transitions from normal to neoplastic cells were observed not only in viral tumors in mice but also in human carcinomas and in chemically induced tumors in rats. It seems well to think of the mode of origin of all types of tumors as an excessive cellular regeneration to make up for the functional disturbance of cells invaded by oncogenic viruses.
MIZUSHIMA, Y., TAKEICHI, N., MINAMI, A., KASAI, M., ITAYA, T., YAMAGUCHI, H, and KOBAYASHI, H. Relationship between the RadioisotopicFootpad Assay and Other Immunological Assays in Tumor Bearing Rats. Tohoku J. exp. Med., 1981, 133 (3), 331-337-KMT-17, a fibrosarcoma induced by 3-methylcholanthrene in a WKA rat, is a sensitive tumor to various kinds of immunological assays and is a suitable model tumor for the study of the immune status in tumor bearing hosts. The antitumor immune response of KMT-17 bearing rats was studied by a radioisotopic footpad assay (FPA) in comparison with other in vivo and in vitro assays. Delayed hypersensitivity to tumor antigens measured by the FPA was observed from the 8th day after transplantation of KMT-17cells, reached a peak on the 12-15th day, and then declined in the late stage on the 17th day. The kinetics of the FPA correlated well with those of an in vivo Winn assay and of an in vitro lymphocyte cytotoxicity assay (51Cr-release assay). The appearance of an antitumor antibody detected by a complement dependent cytotoxicity test also correlated well with the kinetics of the FPA. A growth inhibition assay (GIA) for non-specific cell-mediated immunity also showed similar kinetics to that of the FPA. The delayed hypersensitivity footpad reaction to tumor cell extracts measured by this FPA was tumor-specific. These results suggest that the FPA is a simple and reliable in vivo assay for evaluating antitumor immunity in tumor bearing hosts.
ITABASHI, H., OHNEDA, A. and IIMURA, Y. Thickening of Basement Membraneof Muscle Capillary in Spontaneously Diabetic KK Mice. Tohoku J. exp. Med., 1981, 133 (3), 339-348-In order to clarify the relationship between the thickening of muscle capillary basement membrane (MCBM) and diabetes mellitus, an experimental study was carried out using spontaneously diabetic KK mice. Glucose tolerance tests and the measurements of the width of MCBM were performed in KK mice and DD mice at the age of one week through 16 months. The KK mice, in general, revealed a less increase in body weight, compared with the control mice. Impaired glucose tolerance in the KK mice was observed at the age of 2 weeks and remained for 12 months. The width of MCBM increased in both KK and DD mice with the aging process until 6 months. Thereafter, however, the KK mice revealed a significant increase of the width of MCBM. In both KK mice and DD mice, significant correlations were observed between age and the width of MCBM. In contrast, there was no significant correlation between glucose intolerance figured out as the sum of blood glucose levels and the width of MCBM. The present study suggests that the thickening of MCBM in the KK mice may occur as an aging phenomenon on the one hand and may develop as the consequence of long-term carbohydrate derangement based on genetic disposition on the other hand.
SAITO, T., FURUYAMA, T., KYOGOKU, Y., YAMAKAGE, K., ARAKAWA, M. and YOSHINAGA, K. Focal Glomerular Sclerosis in Aminonucleoside Nephropathy. Tohoku J. exp. Med., 1981, 133 (3), 349-360-In an attempt to establish a model of focal glomerular sclerosis (FGS), 17 male Sprague-Dawley rats were i.m. injected with aminonucleoside of puromycin (AN) in a dose of 1mg/100g body weight for 8 consecutive days as one series. Seven rats were treated through the one series only, and followed up for 4 to 8 months after AN loading (Group I). Two months after the first series, the other 10 were given the same injections as the second series. Four rats were killed within one week after the second series because of their intractable debilitation (Group II-a), and the remaining 6 were kept for 4 to 6 months after the second series (Group II-b). Glomeruli involving sclerotic lesions and/or hyaline deposits were 3.8 to 50.7% (mean±S.E., 23.7±6.3%) for Group I, 3.3 to 41.6 % (21.6±8.2%) for Group II-a and 9.3 to 25.0% (17.5±2.7%) for Group II-b. Glomerular sclerosis was closely associated with irreversible proteinuria in the early stage. But, in Group II-a, hyaline deposit was less frequently observed than that in other long maintained groups. Thus, hyaline deposits in this disease usually appeared lagging in time behind the formation of glomerular sclerosis.
NAKAZAWA, I., OUCHI, E., OUCHI, K, and WAGAI, K. The Effect of OralAdministration of Amphotericin B on the Incorporation of 5-Fluorouracil intoHuman Gastric Cancer Tissue. Tohoku J. exp. Med., 1981, 133 (3), 361-362-Amphotericin B (AmB)-5-fluorouracil (5-FU) combination therapy against cancer was evaluated when both were given orally. Seven gastric cancer patients were treated in this manner, and 4 gastric cancer patients treated with 5-FU alone to serve as the control. AmB syrup and 5-FU syrup were administered orally for 3 days before surgical operation. Then, the drugs were given through a gastric tube into the stomach 4hr before the start of the gastric surgery. Lesion tissues and healthy tissues were collected from each patient and the 5-FU titers were measured by bioassay. It was shown in the majority of the gastric cancer cases that the 5-FU levels in the lesion tissues were substantially higher than those in the surrounding normal tissues, whereas in the gastric cancer patients who received 5-FU alone, most of the lesion tissues showed lower 5-FU content as compared with that of the surrounding tissues.
IMATAKA, K., SEKI, A., Takahashi, N. and Fujii, J. Elevation of SerumCreatine Phosphokinase during Pindolol Treatment. Tohoku J. exp. Med., 1981, 133 (3), 363-364 We observed elevation of serum CPK in hypertensive patients under pindolol treatment. In this report, we showed a representative patient and compared serum CPK values in 56 patients under pindolol treatment to those in 64 patients under propranolol treatment. Mean serum CPK values in the patients under pindolol treatment and propranolol treatment were 117.0±12.6 (S.E.) and 50.8±3.8IU/liter, respectively (p<0.01). Although the mechanism of elevation of serum CPK cannot be well understood, we should be careful in clinical evaluation of serum CPK during pindolol treatment.