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Biomedical subjects

O Tokunaga

Publications and source records attributed to O Tokunaga.

15 recordsLinked to original sources

Establishment of animal liver metastatic model for C-1300 murine neuroblastoma and immunotherapy for it using OK-432, streptococcus preparation.

Intrasplenic administration of 1 x 10(6) C-1300 murine neuroblastoma cells induced spleen tumor in 78.6% of mice and liver metastasis in 64.3%. When mice were pretreated with carrageenan, an antimacrophage agent, the incidence of spleen and liver tumors in this system was lower, possibly due to the rebound increase in macrophage activity following the disappearance of the carrageenan effect. Continuous daily intraabdominal injection of 1 KE of OK-432 streptococcus preparation markedly reduced the appearance of liver metastasis (P less than 0.01), whereas the spleen mass was not reduced to such an extent. However, the survival rate of the OK-432-treated group did not differ greatly from that of the nontreated group. These results demonstrate the usefulness of the model of liver metastasis induced by intrasplenic administration of tumor cells and the effectiveness of OK-432 against liver metastasis formation.

Animals

Clear cell odontogenic carcinoma. A case report with massive invasion of neighboring organs and lymph node metastasis.

Clear cell odontogenic carcinoma is a rare and unusual tumor that occurs in the jaws. This tumor is generally considered to be of a low grade of malignancy. We describe a patient with a huge clear cell odontogenic carcinoma that originated in the mandible and exhibited massive invasion into the adjacent tissues and metastases to the submandibular lymph nodes. The ultrastructural and immunohistochemical details are described.

Aged

Abnormalities in platelets and vascular endothelial cells induced by glycated lipoproteins.

We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.

6-Ketoprostaglandin F1 alpha

Induction of fatty streak-like lesions in vitro using a culture model system simulating arterial intima.

In this study a two-compartment culture model of arterial intima was used for the in vitro induction of fatty streaklike lesions. The apparatus consisted of upper and lower compartments separated by a human amnion membrane stretched between them. Human umbilical vein endothelial cells (HUVECs) were cultured to confluence on the stromal surface of the amnion membrane. Maximal migration of blood mononuclear cells (MCs) through the HUVEC monolayer in response to a f-Met-Leu-Phe gradient was observed at 10(-8) mol/l; the migration was 3.29 times greater than that observed under the condition of random migration (control). In the study of MC transformation into lipid-laden cells in the amnion membrane (foam cell formation in 'arterial intima'), 10(6) MCs were incubated, in the presence of freshly prepared low-density lipoprotein (LDL; 100 microgram/ml). The lipid loading of MCs was time dependent. After 12 hours' incubation, 39% of the MCs that migrated into the amnion membrane contained a small number of lipid droplets, whereas the remaining 61% showed no lipid droplets. Only 1.7% of the cells contained a high number of lipid droplets in the cytoplasm and took on the appearance of foam cells. With time, the number of lipid-laden cells and the amounts of intracytoplasmic lipid droplets gradually increased. At 72 hours after incubation, 65.4% of the MCs were loaded with lipid droplets, and 20.9% of them, an eightfold increase over 12 hours of incubation, showed a foamy cell appearance. Because MCs consist of 70% monocytes and 30% lymphocytes, about 93% of the monocytes were filled with lipid after a 72-hour incubation. Ultrastructural examination showed that lipid-laden cells took on macrophage characteristics, such as wide and heterogeneous cytoplasm, indented nuclei, and abundant lysosomes. A minority of the MCs in the amnion were considered lymphocytes; they had scanty cytoplasm, round nuclei with abundant heterochromatin, no lysosomes, and no lipid vacuoles. In conclusion, the formation of an in vitro fatty streaklike lesion is demonstrated, and this is reminiscent of in vivo human atherogenesis.

Amnion

Endothelin. Immunohistologic localization in aorta and biosynthesis by cultured human aortic endothelial cells.

BACKGROUND: Endothelin-1 (ET-1) has been shown to exist in many organs and to have various biologic functions including vasoconstriction. However, an exact location of ET gene expression of the tissues is not fully investigated. Human aortic tissue was examined to elucidate the exact location of ET gene expression. EXPERIMENTAL DESIGN: Human aortas were obtained at autopsy and fixed in either conventional 10% formalin or 3% paraformaldehyde. The aortic thin sections were subjected to examinations of an immunohistochemistry and in situ hybridization of ET-1. Human aortic endothelial cells were cultured by a previously reported method. ET-1 released in the supernatant from the cultured endothelial cells was radioimmunoassayed. RESULTS: Immunohistologic study of ET-1 revealed a linear staining of the endothelial monolayer and diffuse staining in the intimal and medial smooth muscle cells on human aorta except for fetal aorta. In situ hybridization signals were intense in the endothelial cells from the elderly as well as younger subjects as examined with 35S-labeled anti-sense probe RNA. Fetal aortic endothelial cells revealed the least signals that meant developing but still immature gene translation. Smooth muscle cells showed positive but weak in situ hybridization signals. Control immunohistologic and hybridization studies were negative. ET-1 biosynthesis by cultured human aortic endothelial cells was invariably low in the subjects under the age of 50, ranging from 0.23 to 0.40 pmol/1 x 10(5) cells for 3 days. On the other hand, endothelial cells from the elderly subjects generally synthesized a greater amount of endothelin in vitro. CONCLUSIONS: These findings indicate that ET-1 is most highly expressed in endothelial cells, although not as highly but certainly, expressed in intimal and medial smooth muscle cells. This fact gives a new insight into the biophysiologic and pathologic roles of ET. In addition, these methods are applicable to investigate the gene expression of ET-1 in all organs and tissues.

Adolescent

Alterations in the functional characteristics of macrophages induced by hypercholesterolemia.

Intimal accumulation of monocyte-derived lipid-filled macrophages is an important early event in diet-induced hypercholesterolemia. To better understand the functional alterations in macrophages in hypercholesterolemia, we determined several variables in rat peritoneal macrophages putatively associated with atherogenesis including adhesion to, spreading and locomotion on an endothelial monolayer, migration and phagocytic capacities, and superoxide anion (O2-) production. Compared with macrophages from normal rats (NM0s), macrophages from hypercholesterolemic rats (HM0s) revealed a higher rate of adherence to endothelial cells (ECs) and plastic with more extensive cytoplasmic spreading. Towards a chemoattractant of zymosan-activated serum, HM0s exhibited greater chemotactic migration and more prominent aggregation than NM0s. A computerized film analysis using time-lapse cinemicrophotography disclosed that HM0s moved faster on ECs; the average speed of HM0s was almost twice that of NM0s. HM0 phagocytic activity of fluorescent latex beads was significantly heightened (P less than 0.01). By contrast, there was no significant difference in O2- production between the two groups. These results indicate that hypercholesterolemia may initiate and accelerate the atherosclerotic process, at least in part, by modifying a number of functional properties of macrophages.

Animals

Experimental cerebral atherosclerosis in the rabbit. Scanning electron microscopic study of the initial lesion site.

The development and initial lesion sites of cerebral atherosclerosis were studied in hypertensive rabbits fed 0.5 g/day cholesterol in their diet. The earliest lesions developed at remarkably localized areas of the basilar artery-posterior cerebral artery Y-bifurcation (area A) and vertebral arteries-basilar artery confluence (area B). These findings were obtained from a thorough scanning electron microscopic survey of the dorsal surface of the cerebral artery segment covering from the vertebral arteries to the posterior cerebral arteries. By light microscopy intimal lesions were mainly composed of accumulations of foam cells and smooth muscle cells. Electron microscopically foam cells accumulated in the intima resembled those of a monocyte-macrophage lineage. Early lesions involving only a few endothelial cells with adherent leukocytes occurred at the dividing and confluent portions of the endothelial arrays formed in areas A and B, respectively. The results indicate that hypertension coupled with hypercholesterolemia induces atherosclerosis in particular vulnerable regions of the cerebral arteries.

Animals

Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis.

To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis.

6-Ketoprostaglandin F1 alpha

Autocrine effect of endothelin on DNA synthesis in human vascular endothelial cells.

To elucidate the role of endogenous endothelin on DNA synthesis in endothelial cells, we have investigated the effects of rabbit anti-ET gamma globulin on DNA synthesis in cultured human vascular endothelial cells. DNA synthesis was markedly inhibited by anti-ET gamma globulin in a concentration dependent manner in the presence of fetal calf serum(FCS) (x5000;34%, x2500;54%, x1000;70%), but not in the absence of FCS. These data suggest that endogenous ET modulates FCS-stimulated DNA synthesis in an autocrine fashion.

Animals

Collision tumor of the stomach with carcinosarcoma and tubulo-papillary adenocarcinoma.

The present case is an autopsy case of a 66-year-old male who developed a collision tumor in the stomach which originated from carcinosarcoma of Borrmann type II in the gastric antrum and from papillary adenocarcinoma of Borrmann type III in the corpus. The carcinosarcoma consisted of tubular carcinoma and sarcomatous transformation of stroma from the carcinoma.

Adenocarcinoma, Papillary

The influence of intravenous injection of lidocaine on optokinetic nystagmus in rabbits.

The effects of lidocaine in doses of 2.0--6.0 mg/kg with intravenous injection on optokinetic nystagmus were observed in 21 rabbits. No effect of lidocaine was obtained on the frequency of OKN. On the other hand, the amplitude of OKN in lidocaine groups decreased after the injection. The mode and place of the action of lidocaine on OKN were discussed.

Animals

The influence of linear acceleration on optokinetic nystagmus in human subjects.

The influence of linear acceleration on optokinetic nystagmus (OKN) was studied in human subjects. Linear acceleration was applied to the subjects by means of the parallel swing and also by the transfer of the subjects in one direction, either right or left. The cortical form of OKN increased the frequency, amplitude, and eye speed of the slow phase. Of the three, the increase in eye speed was the most pronounced. The subcortical form of OKN was not only increased but was also disturbed by the linear acceleration. When the compensatory eye movement with linear acceleration and the slow phase of OKN were in the same direction, the nystagmus increased remarkably. Contrarily, when the two directions were opposed to each other, nystagmus was inhibited. These results proved that the otolithic organs are not only able to promote but also to inhibit visual function.

Acceleration

Inhibitory and promoting effects of subliminal pendular rotation on optokinetic nystagmus in man.

The influence of vestibular stimulation by subliminal pendular rotation on the optokinetic nystagmus in normal human subjects is discussed. Cortical OKN with pendular rotation was promoted in three indexes--eye speed, frequency, and total amplitude. The subcortical OKN increased markedly when the slow phase of OHN and the compensatory eye movement resulting from the pendular rotation were in the same direction. However, it was inhibited when the two directions were mutually opposed. From the results obtained in the present experiment and in the previous study by the author, it can be concluded that the vestibular organs' effect on visual function is not only promotive but also inhibitive.

Adult