TAKEMATSU, H., ISONO, N., KATO, T. and TAGAMI, H. Normal HumanEpidermal Keratinocyte-Derived Neutrophil Chemotactic Factor. Tohoku J. Exp. Med., 1990, 162 (1), 1-13-Human epidermal keratinocytes constitutively produce a variety of cytokines, including neutrophil chemotactic peptide named epidermal cell-derived thymocyte-activating factor, which has been later confirmed to be interleukin 1 (IL-1). Because recombinant IL-1 lacks chemotactic activity, in the present study, we examined the exact nature of the neutrophil chemotactic peptide in the culture supernatant of normal human epidermal keratinocytes. Normal human epidermal keratinocytes produced a neutrophil chemotactic factor, which was also chemotactic for T lymphocytes. Molecular sieve chromatography revealed an approximate molecular size of 11, 000 daltons. The activity was retained after heating at 100°C for 10min, and at a pH between 4 and 11, but was partially inactivated at pH 3, or by trypsin treatment. The chemotactic activity was not inhibited by the treatment with anti-IL-1 antibody. Its production by keratinocytes was stimulated by IL-1 and lipopolysaccharide but not by UV irradiation, tumor necrosis factor-α or by interferon-γ. The neutrophil chemotactic activity in vivo was confirmed by the intradermal injection of the factor into guinea pigs. Blocking study with monoclonal antibodies against NAP-1/IL-8 confirmed that the neutrophil chemotactic factor is IL-8.
SUZUKI, K. Clinical Features of Sustained Ventricular Tachycardia amongVarious Underlying Heart Diseases. Tohoku J. Exp. Med., 1990, 162 (1), 15-26 - Clinical findings of 52 patients with sustained ventricular tachycardia (VT) were analyzed to assess the importance of the underlying etiology. Among patients with organic heart diseases, no differnces were found in the VT rate, the incidence of syncope, and the number of patients who required DC shock, regardless of the difference of the underlying organic heart diseases. Patients without organic heart disease had usually more benign clinical presentations. The electrophysiologic findings of VT such as inducibility, a mode of induction and incidence of pleomorphism were similar in patients who had organic heart disease of various causes. Neither the incidence of pleomorphism nor occurrence of acceleration of VT rate was found in patients with idiopathic VT, and the incidence of VT induction was low in patients with idiopathic VT of RV origin. Patients with organic heart diseases often died suddenly, and patients when their VT rate was 200/min or higher, developed syncope, even who had normal LV function.
OTA, K., KIMURA, T., SHOJI, M., INOUE, M., SATO, K., OHTA, M., YAMAMOTO, T., TSUNODA, K., ABE, K. and YOSHINAGA, K. Effects of IntracerebroventricularAdministration of Adrenoceptor-Agonists on the Regulation of Renal Water andElectrolytes Handling through Endocrine, Renal and Hemodynamic Function. Tohoku J. Exp. Med., 1990, 162 (1), 27-39-In order to assess the roles of central adrenoceptors in the release of atrial natriuretic peptide (ANP), aldosterone (ALD), vasopressin (AVP) and renin as well as in the regulation of renal and cardiovascular functions, either norepinephrine (NE; 0.07μg/kg/min), guanabenz (GB; α2-agonist; 0.4μg/kg/min), methoxamine (MET; a1-agonist; 0.4μg/kg/min), or isoproterenol (ISO; β-agonist; 0.07μg/kg/min), dissolved in the artificial cerebrospinal fluid (ACSF), was intracerebroventricularly (i.c.v.) administered at a rate of 10μl/min for 30min in anesthetized dogs. In the control study, the drugs were omitted. NE decreased mean arterial pressure (MAP), urinary osmolality (Uosm) and plasma ALD and AVP concentrations, and increased urine flow (UF). GB increased UF and urinary K excretion without any changes in urinary Na excretion, but decreased plasma ALD and AVP, heart rate, and Uosm without changes in MAP. ISO decreased MAP and plasma ALD, and increased Na and K output, renal plasma flow and UF with decreased Uosm. MET and ACSF failed to affect any of these parameters. Glomerular filtration rate, plasma ANP concentration and renin activity did not change in any of the studies. The present results suggest that central α2- and β-adrenoceptors may attenuate ALD and/or AVP release without changes in ANP and renin release, and decrease blood pressure, thereby causing a diuresis and natriuresis.
NAITO, A., SHIMIZU, Y. and HANDA, Y. Analyses of Airstepping Movement inAdult Spinal Dogs. Tohoku J. Exp. Med., 1990, 162 (1), 41-48-Airstepping of the hind limbs, which occurred when the adult chronic spinal dog was lifted up vertically, was analyzed by high-speed cinematography and electromyography (EMG). In the film analysis, the amplitude of the step increased with decreasing cycle period of the step. The time courses of changes in the joint angles of the hind limb throughout the step were not changed and the maximum flexion of each joint occurred in the knee, ankle and hip joint in that order at any cycle period. In the EMG analysis, alternating EMG activities of the ankle extensor and flexor, and also of the bilateral knee extensors appeared. The EMG burst durations of the knee and ankle extensors correlated closely with the cycle period of the step, although that of the ankle flexor was independent of changes of the cycle period. Since similar results were observed in analyses of treadmill locomotion in the normal and adult spinal dogs, it was thought that airstepping and treadmill locomotion were regulated by the same central pattern generator existing in the lower spinal cord.
EBIHARA, T. and KOYAMA, S. Functional and Phenotypic Characteristics ofEffusion-Associated Lymphoid Cells Cultured in the Presence of Either RecombinantInterleukin 2 or T-Cell Growth Factor from Malignant Pleural andPeritoneal Effusions in Patients with Advanced Carcinoma. Tohoku J. Exp. Med., 1990, 162 (1), 49-63-Malignant pleural or peritoneal effusion-associated lymphoid (EAL) cells from 17 patients with advanced carcinoma were cultured with autologous carcinoma cells in the presence of either recombinant interleukin 2 (rIL 2) or T-cell growth factor (TCGF). Considerable cytolytic activity of the cells against allogeneic tumor cells, such as K562 and Daudi cells was induced by the cultivation. TCGF-activated EAL cells acquired higher anti-Daudi tumor cytotoxicity than rIL 2-activated EAL cells. The resultant TCGF-activiated EAL cells from cancer patients significantly exceeded lytic activity of TCGF-activated EAL cells from patients with liver cirrhosis for control (p<0.01). Four of 6 cases examined also showed cytotoxic activity against autologous tumor. In facts, viable carcinoma cells co-cultured with EAL cells and TCGF mostly disappeard during 14 days. Similar phenomenon was not observed in rIL 2-activated EAL cells. Thus, it was suggested that more additional lymphokine other than IL 2 was necessary to generate cytotoxic activity against autologous tumor cells. The cell populations responsible for cytolytic activity to allogeneic and/or autologous tumor cells were investigated by two-color flow cytometry. The majority of killer-effector cells against allogeneic cells in rIL 2-activated EAL cells from cancer patients showed CD4+Leu8- phenotype at population level. In contrast, it was suggested that cytolytic activity against allogeneic and/or autologous tumor cells in TCGF-activated EAL cells might be mediated by CD8+ CD11- and CD8+CD28+ effector cells.
TAKEMORI, K., NIHIRA, S., MIKAMI, S. and SASAKI, N. Evaluation of theIndividual Effects of a Health Education Program for Sodium Restriction by aSimple Method for Measuring 24-Hour Urinary Sodium Excretion. Tohoku J. Exp. Med., 1990, 162 (1), 65-72-A simple method for measuring 24-hr urinary sodium excretion was applied to the evaluation of the individual effects of a health education program for sodium restriction in a rural community in Japan. Eighteen subjects (6 males and 12 females) between 35 and 72 years of age were advised to reduce their sodium intake. Twentyfour-hour urinary sodium, potassium excretion, and sodium/potassium ratio were measured using the simple method for seven consecutive days in three periods which were before the sodium restriction, 6 months after the sodium restriction, and 6 months after the end of the program. Mean sodium excretion of 18 subjects significantly decreased (p<0.05) after the end of the program. The reduced level was maintained until six months after the end of the program. Within individual cases, sodium excretion decreased significantly in subjects who had levels higher than 170mmol at the initial stage. The reduced levels of sodium excretion were maintained until six months after the end of the program except for one subject. The subjects who had an initial level lower than 170mmol of sodium, which is the upper limit of present recommendation for Japanese adults, did not change their levels.
KOYAMA, H., SUZUKI, S. and SATOH, H. Effect of Alcohol Ingestion onUrinary Excretion and Intraerythrocyte Concentrations of Sodium and Potassium. Tohoku J. Exp. Med., 1990, 160 (1), 73-78-Although epidemiologic studies have demonstrated that alcohol consumption is related to increased blood pressure, the mechanism involved has not been fully understood. In the present study the urinary excretion and intraerythrocyte concentrations of sodium and potassium after alcohol ingestion were measured in 7 young adults. Decreases of urinary excretion of sodium and potassium and an increase in intraerythrocyte sodium were observed. The results suggest that alterations of the electrolyte metabolism influenced by alcohol ingestion may be related to alcohol-induced hypertension.
TAKAHASHI, H., FUJITA, S., TSUDA, N., TEZUKA, F. and OKABE, H. ImmunohistochemicalDemonstration of α1-Antichymotrypsin and α1-Antitrypsin in SalivaryGland Pleomorphic Adenomas of Children. Tohoku J. Exp. Med., 1990, 162 (1), 79-93-Twenty-five benign pleomorphic adenomas of salivary glands in children were studied with immunohistochemical techniques in order to characterize the cell types comprising the epithelial and so-called “mesenchymal” regions of the tumors. The antisera against α1-antichymotrypsin (α1-ACT) and α1-antitrypsin (α1-AT) were used to stain in normal salivary gland tissue as well as in pleomorphic adenoma. In normal salivary glands, α1-ACT was localized to the intercalated duct and serous acinar cells. On the other hand, there was positive staining for α1-AT in the intercalated and striated duct cells. Twenty-five cases (100%) of pleomorphic adenomas in children displayed positivity to α1-ACT staining and 22 cases (88%) showed a positive staining for α1-AT. α1-ACT staining was particularly intense in chondrocyte-like cells of 20 cases (80%), in inner tubular cells of 16 (64%) and cyst-lining cells of 12 (52%). The limited number of tumor cells which were called plasmatoid or hyaline cells and squamous epithelial cells, were positive for α1-ACT. None of the outer tubular cells and hyalinous material was positively stained for α1-ACT. A strong positive reaction for α1-AT was observed in chondrocyte-like cells of 15 cases (60%). Inner tubular cells were positive for α1-AT in 12 cases (48%), plasmatoid or hyaline cells in 10 (40%) and cyst-lining cells in 8 (35%). Squamous epithelial cells, clear cells, secretory product and hyalinous material were positive for α1-AT in some cases. Chondroid matrix and myxoid stroma had no reaction with both antibodies. The biological role of α1-ACT and α1-AT with a wide immunohistochemical distribution in pleomorphic adenomas of children may be associated with a self regulating mechanism which inhibits degradation by tissue proteinases.
OHNEDA, A., TSUCHIYA, T., NAITO, H., SASAKI, I., OHNEDA, M. and KAWAMURA, T. Increased Plasma Glucagon-Like Immunoreactivity in Dogs withIleojejunal Transposition. Tohoku J. Exp. Med., 1990, 162 (1), 95-108-To elucidate hormonal and metabolic changes in intestinal adaptation, an experimental study was performed in dogs subjected to ileojejunal transposition. Fasting levels of blood glucose, plasma insulin and gastric inhibitory polypeptide (GIP) did not change significantly throughout 12 weeks. Plamsa glucagon measured with an antiserum specific to the C-terminal portion of glucagon slightly increased and plasma total glucagon measured with a non-specific antiserum gradually increased. Glucose tolerance deteriorated at the 4th week in the transposed group. The response of plasma insulin and GIP to glucose in the transposed group did not differ from that of the sham operated group. Plasma glucagon increased significantly during glucose loading at the 12th week. The response of plasma total glucagon to glucose was most prominent, reaching a peak of 3, 755±742pmol/liter. The value was significantly increased, compared with that of the sham group or normal group (p<0.01). Insulin-induced hypoglycemia enhanced a larger increment of plasma total glucagon in the transposed group than in the sham group (p<0.05). At the 12th week plasma total amino acids were decreased and several amino acids were reduced. It is concluded that ileojejunal transposition elicited an exaggerated response of plasma total glucagon to glucose and several metabolic derangements and that the transposition offers an excellent model for hyperenteroglucagonemia.