Human cDNA probe detects RFLP on chromosome 12, OL 202 (HGM8 designated no. D12S9).
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Biomedical subjects
Publications and source records attributed to M Higuchi.
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Murine peritoneal macrophages elicited with a streptococcal preparation, OK-432, produced as much of a cytotoxic factor after stimulation with lipopolysaccharide (LPS) as BCG-elicited macrophages did. Proteose peptone-elicited macrophages produced a very small amount, if any, of the factor, and resident peritoneal macrophages did not release it at all even after LPS-stimulation. A newly established macrophage hybridoma, D/O-3.3, produced the factor after LPS-stimulation, but another hybridoma, D/O-3.2, did not. Experiments using these peritoneal macrophages and macrophage hybridomas demonstrated that macrophages can be divided into three subpopulations with regard to stages of activation for production of the cytotoxic factor. The first is fully activated macrophages which produce the factor after stimulation with LPS or MAF-C alone, the second is partially activated macrophages which produce the factor only after stimulation with a combination of recombinant interferon-gamma (rIFN-gamma) and LPS or rIFN-gamma and macrophage activating factor for cytotoxicity (MAF-C), and the third is nonactivated macrophages which cannot produce the factor at all.
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Neutralization test and DNA restriction endonuclease analysis were performed in strains of adenovirus types 19 (Ad-19) and 37 (Ad-37) isolated from patients with acute conjunctivitis in Sapporo, Kao-Hsiung (Taiwan) and Pusan (Korea) in the period of 1979 and 1984. Although Ad-19 and Ad-37 were differentiated, they were related to each other in neutralization test. There was no difference between prototype strain and isolates in Ad-19 and Ad-37 strains. By DNA restriction endonuclease analysis Ad-19 isolates were clearly distinct from Ad-19 prototype strain (AV-587) and Ad-37 strains. And it was suggested that these Ad-19 isolates from East Asia were as same as isolates from Europe named Ad-19a. Ad-37 isolated strains were as same as Ad-37 prototype strain (GW) by SmaI, SacI, SalI, BamHI, EcoRI, XhoI, HindIII restriction analysis. But some strains were distinct from prototype strain by only HindIII restriction analysis, and they were new subtype of Ad-37 which had never been reported.
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Developmental process of fetal rabbit lung was studied biochemically and morphologically as a model of human fetal lung. The results are follows: The mean wall thickness of terminal air spaces at 27 days of gestation became closer to that at term (31 days). Surface area of terminal airspaces in a unit volume of the lung acinas however reached the peak at 29 days of gestation. The differentiation of alveolar epithelial cells and the release of lamellar bodies into potential airspaces were prominent at gestational age from 29 to 30 days. Glycogen content in lung tissue decreased significantly at 28 days and total lecithin concentration in lung tissue increased markedly at the same age. Concentration of disaturated lecithin (DSL) in lung tissue and amniotic fluid rose prominently at the age from 29 to 30 days of gestation. The ability of surfactant secretion into potential airspaces after 1 hour respiration reached the maximum at 29.5 days, which was closely the same as that at term. The cortisol/cortisone ratio in fetal plasma increased significantly at 28 days. The biochemical and morphological lung maturation of fetal rabbit was concluded to be established on 29.5 days of gestation. The possibility of assessment of the functional maturation of human fetal lung was investigated using the measurement of surfactant concentration in amniotic fluid and the analysis of fetal breathing movements by real time ultrasonic B-scanner.(ABSTRACT TRUNCATED AT 250 WORDS)
Heterologous membrane antigen (HM Ag) is discovered to be incorporated into membranes of cultured human cells grown in media containing fetal calf serum (FCS). To know the characteristics of HM Ag, we investigated the dynamics of HM Ag on cell membrane, distribution of HM Ag and humoral immune response to HM Ag in pregnancy and gynecologic malignancies. The following results were obtained. HM Ag disappeared from the cell membranes of M14 grown in media with fetal calf serum (FCS) after the cells were transferred into whole human serum (12 days) or into a gamma human serum (18 days). M14 cells grown in human serum reincoporated HM Ag into their membranes within 48 hours after transfer to medium with 20% FCS. HM Ag was detected in FCS, adult bovine serum, cow's milk and erythrocytes homogenate of ox and sheep. The natural anti-HM Ag antibody appeared frequently in pregnant women, patients with gynecologic malignancies and healthy persons. These findings suggest that HM Ag must be excluded in immunologic studies of cultured human cancer cells by changing the medium from FCS to human serum or by absorbing anti-HM Ag antibody with cells carrying HM Ag.
The cell lines designated KKNS-I and KKNS-II were derived from the metastatic lesions in the lymph nodes of endometrial adenocarcinoma. The KKNS-I cells were small spindle or polygonal in shape and showed a jig-saw puzzle-like arrangement with a tendency to pile up. The KKNS-II cells were polygonal in shape, and larger than the KKNS-I. They appeared to be arranged like a pavement. The modal number of the two cell lines was 46 without marker chromosome. Calculating from the growth curves, the doubling times for the KKNS-I and the KKNS-II cells were 35 hours and 60 hours, respectively. The tumors obtained from the nude mouse inoculated with the KKNS-I and the KKNS-II were a poorly differentiated endometrial adenocarcinoma and a well differentiated endometrial adenocarcinoma in histology, respectively. The volume of estrogen receptor and progesterone receptor in the KKNS-II were more than that in the KKNS-I cells. HLA-ABC antigens were detected in both the cells, but HLA-DR antigens were detected in only some populations of KKNS-II cells. These data suggest a relationship between the HLA-DR antigens and the degree of differentiation of the endometrial adenocarcinoma.
A 31-year-old man with peripheral squamous cell carcinoma is reported. By nature he was very small. On admission he was 140 cm tall, weighed 28 kg, and was complaining of chest pain of five years duration. A giant tumor in the right lung was found to be moderately differentiated squamous cell carcinoma. He also had congenital anomalies, such as crossed ectopic kidney with fusion, café-au-lait spots, inguinal hernia, simian line, etc. He had never been exposed to cancer-causing agents. In conclusion, genetic factors related to intrauterine growth retardation might have been linked to his oncodevelopmental mechanisms.
A sinusoidal fetal heart rate and elevated fetal arginine vasopressin levels were found in two bled fetal lambs. Arginine vasopressin was continuously infused intravenously in chronically instrumented fetal lambs at rates ranging between 1.0 and 90 mlU/kg/min. No sinusoidal heart rate occurred in 21 experiments on six control animals with intact vagal nerves. Atropine at doses less than 0.4 mg had no effect (six experiments on three animals). Higher doses of atropine (greater than 1.2 mg) resulted in sinusoidal heart rate (24 experiments on six animals). Twenty-three infusions were performed in five bilaterally vagotomized fetuses, and the sinusoidal heart rate was successfully induced in 17 experiments. The arginine vasopressin infusion rate was less than 1.5 mlU/kg/min on the six occasions in which the sinusoidal heart rate did not appear. All sinusoidal heart rate patterns were associated with fluctuation of fetal arterial pressure at the same frequency. There was a linear correlation between the amplitude of sinusoidal heart rate and magnitude of arterial blood pressure fluctuation. The amplitude of sinusoidal heart rate increased with the concentration of arginine vasopressin infused. Modification of sinusoidal heart rate pattern was attempted with use of sympathetic agonists and antagonists. The possible etiology and mechanisms of sinusoidal heart rate pattern are discussed.
Schistosome egg granulomas in the livers of thymus-intact (nu/+) mice are large and contain eosinophils and mast cells, while those in nude athymic (nu/nu) mice are small and devoid of eosinophils or mast cells. To investigate the cell sources and cell kinetics of hepatic granulomas of nu/+ mice isolated and grafted into the skin of nu/nu mice, biopsies taken after grafting were examined by light and electron microscopy and autoradiography after 3H-thymidine (TdR) injection of either the donor or recipient mice. At 1 week, the grafted granulomas appeared to be amorphous and were surrounded by leukocytes, and the 3H-TdR-labeled donor cells had disappeared. After 2 weeks, repopulation with macrophages began and by 3-5 weeks, the granulomas morphologically resembled hepatic lesions of nu/+ mice. Injection of recipients with 3H-TdR before grafting, showed that labeled macrophages, eosinophils, and mast cells repopulated in granulomas. No granulomas were seen when nu/nu mice were grafted with schistosome eggs alone, and organ culture of nu/+ granulomas before grafting reduced the number of repopulated granulomas. These findings indicate that nu/+ cells in grafted granulomas are replaced by nu/nu cells. Granulomatous reaction of the grafted sites in nu/nu mice is influenced by a substance in nu/+ granulomas, and cells of nunu mice locally acquire a nu/+ type response.
We investigated the effects of exercise training on the amount of aortic collagen and systolic blood pressure in spontaneously hypertensive rats (SHR). Ten-week old SHR were trained either by forced treadmill running (26.8 m X min-1 -1 h X day-1, five times a week, 0% incline) or by voluntary running in revolving wheels (7,800 m X day-1 at peak) for 8 weeks. Succinate dehydrogenase (SDH) activity measured as a marker of an endurance training effect was 13% higher (P less than 0.01) in the soleus of forced-exercised animals than in that of sedentary ones. (6.56 +/- 0.17 mumol X g-1 X min-1; mean +/- SEM), whereas SDH activity in that of voluntarily-exercised group was found to be at the same level as in sedentary animals. The systolic blood pressure after training increased by 26.4 in sedentary, 21.1 in voluntarily-exercised, and 33.9 mm Hg in forced-exercised rats, when compared with the value of each group at the beginning of the training program. A significant difference was observed in the increment of blood pressure only between the voluntarily- and forced-exercised groups (P less than 0.05). The amount of aortic collagen in voluntarily-trained rats (96.5 +/- 2.0 mg X g tissue-1, 39.8 +/- 0.7 mg X 100 mg protein-1) was significantly less than that in forced-trained rats (P less than 0.05). These results suggest that voluntary, mild exercise training may be more effective in the reduction of collagen accumulation in the aorta associated with the suppression of blood pressure increase than forced, vigorous exercise training in SHR.
Five patients with colorectal cancer and unresectable synchronous liver metastases have survived for over five years at this writing. Four of the five had multiple metastases over both lobes, as diagnosed preoperatively, and the other had multiple metastases in the right lobe not evident preoperatively. The primary foci were excised completely in four patients. For one patient with multiple metastases limited to the right lobe, the postoperative cancer chemotherapy prescribed was intravenous mitomycin C (MMC; 12 mg) and oral ftorafur (a derivative of 5-FU) for a total dose of 291 gm over 63 weeks. The remaining four patients underwent postoperative intra-arterial infusion therapy with the average total dose of 20.5 mg of MMC plus 5600 mg of 5-FU; subsequently, they received protracted chemotherapy with oral ftorafur of 354 gm as an average, with little or no side effects. In these four patients, duration of intra-arterial treatment was an average of 3.2 weeks, and the subsequent oral treatment continued for an average of 85 weeks. Recent hepatic echography and CEA determinations show these patients to be free from intrahepatic metastasis.
A mouse macrophage cytotoxic factor was purified to homogeneity from the serum-free culture supernatant of a mouse macrophage hybridoma clone, N/P-7-1, stimulated with lipopolysaccharide by gel filtration, affinity chromatography, anion-exchange chromatography, and polyacrylamide gel electrophoresis. The purified material was judged to be homogeneous as to the criteria of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and has a relative molecular mass of 17,500, as determined by SDS-PAGE, or 55,000, as determined by gel filtration on columns of both Sephacryl S-200 and TSK G3000SW. It has an isoelectric point of 5.0, and is trypsin sensitive, stable at 56 degrees C and labile at pH less than 6. The cytotoxic activity of the purified factor could not be inhibited by various sugars and lectins. The production of the factor from N/P-7-1 triggered by macrophage-activating factor for cytotoxicity, but not by mouse recombinant gamma-interferon. The factor should be synthesized after lipopolysaccharide stimulation because treatment of N/P-7-1 cells with a metabolic inhibitor, emetine or actinomycin D, prevents the production.
Hypersensitivity granulomas induced by infection with Schistosoma mansoni were isolated from the livers of BALB/c mice after 7, 8, 10, and 12 weeks. The parasite egg-granulomas were sequentially extracted with a Tris-buffered saline (soluble fraction) and 2 M KSCN (bound fraction). Fibrinolytic enzyme activity measured with both synthetic substrates and fibrin plates demonstrated an elevated level of plasminogen activator activity in the bound fraction 7-8 weeks after infection when mature granulomas first began to appear, followed by a gradual decrease 10-12 weeks after infection. An electrophoretic enzymography technique revealed multiple molecular species of plasminogen activator at Mr = 95K, 74K, 60K, 45K, and 24K. The bands with Mr = 45K and 24K were found compatible with the electrophoretic pattern of macrophage-plasminogen activator. When the granulomas reached maximum size after 10 to 12 weeks, the plasminogen activator with 45K and 24K diminished, while plasminogen activator activity at Mr = 95K, 74K, and 60K remained unchanged suggesting the presence of both vascular and tissue types of plasminogen activators. There was no urokinase-type plasminogen activator detectable in granulomas at any time. In the soluble fraction no enzymatic activity was found, whereas regulating inhibitor activity for plasminogen activator was consistently detectable.
Cellular damage caused by free radical reactions may play a role in the aging process. A bout of exercise can increase free radical concentration with damage to mitochondria in muscle (Davies et al., 1982). This study was undertaken to determine if muscle adapts to exercise training with an enhancement of enzymatic defenses against free radical damage. A program of running that induced two-fold increases in mitochondrial enzymes in leg muscles of rats resulted in no increase in catalase or cytoplasmic superoxide dismutase (SOD) activities. Mitochondrial SOD activity was increased 37% in fast-twitch red and slow-twitch red types of muscle and 14% in white muscle. Thus, despite an increase in mitochondrial SOD, the ratio of SOD to mitochondrial citrate cycle and respiratory chain enzymes was decreased. It seems unlikely that increased capacity for enzymatic scavenging of superoxide radical is a major protective adaptation against free radical damage in exercise-trained muscle.