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Biomedical subjects

O Tokunaga

Publications and source records attributed to O Tokunaga.

At least 73 records · Page 4Linked to original sources
PubMed1993

HTLV-I associated and non-associated primary T-cell lymphoma of gastrointestinal tract.

The gastrointestinal (GI) tract is the common extranodal site for non-Hodgkin's lymphoma (NHL), and primary lymphoma of GI tract are mostly of B-cell origin. We have treated 16 patients with primary lymphoma of GI tract between 1981 and 1991, of whom 10 (62%) were of B-cell origin, while 6 (38%) were of T-cell origin. The incidence of T-cell phenotype in our hospital was considered to be much higher than that of previous reports and these 6 patients with primary T-cell lymphoma of GI tract were carefully studied. The primary sites were stomach in 4, ileocecum in 1, and duodenum in 1 case. Their T-cell nature was confirmed by immunohistochemical methods. All were peripheral T-cell lymphomas; one was CD 3+ 4- 8- and the other 5 were CD 3+ 4+ 8-. The antibody against human T-cell leukemia virus type I (HTLV-I) was positive in 3 cases (HTLV-I associated), but negative in 3 (HTLV-I non-associated). The integration of HTLV-I proviral DNA in HTLV-I associated patients was demonstrated by Southern blot analysis after DNA amplification by means of polymerase chain reaction (PCR). The clinical features of the HTLV-I associated and HTLV-I non-associated primary T-cell lymphoma of the GI tract were quite different. HTLV-I associated patients showed leukemic manifestations and tumor involvement of the skin at a later stage of the disease. These observations indicated that HTLV-I can play an important role in the occurrence of primary T-cell lymphoma of GI tract.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

Localized lymphoid hyperplasia (pseudolymphoma) of the pancreas presenting with obstructive jaundice.

A case of hyperplastic lymphoid lesion of the pancreatic head manifested by obstructive jaundice is presented. A 57-year-old woman who complained of malaise and icterus underwent pancreatoduodenectomy under the clinical diagnosis of pancreatic carcinoma. The lesion was diagnosed as localized lymphoid hyperplasia (pseudolymphoma) based on the presence of hyperplastic follicles with germinal center and mixed infiltration of plasma cells and mature lymphocytes with no significant cytologic atypia. The immunostaining revealed polyclonal origin of the lymphoplasmocytic component. Localized lymphoid hyperplasia occurs in a wide variety of sites; however, to our knowledge, its occurrence in the pancreas has not been documented previously.

Cholestasis↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Rapid Ca2+ refilling system of intracellular store(s) in human vascular endothelial cells.

Using a fura-2 method, cytosolic Ca2+ concentration [( Ca2+]i) was measured in endothelial cell monolayers from human umbilical vein. In the presence of 1.5 mM Ca2+, bradykinin (BK) induced a rapid (within 15 sec) and dose-dependent (10(-8)-10(-6) M) increase in [Ca2+]i, consisting of an initial peak and a subsequent sustained phase. The pretreatment with 3 mM EGTA for 1 min caused a significant reduction in [Ca2+]i levels both of the basal (p less than 0.05) and BK-stimulated initial peak (p less than 0.001). However, the BK-stimulated initial peak was retained in magnitude for at least 5 min under the treatment with EGTA. In contrast, the sustained phase was completely abolished by EGTA treatment. The BK-stimulated Ca2+ transient, once having been completely inhibited by ionomycin (10(-6) M) in the presence of EGTA, was rapidly (within 2 min) recovered to the untreated level by replacing it with fresh medium containing 1.5 mM Ca2+. The present results indicated that BK mobilized Ca2+ from both intracellular and extracellular space(s) and suggest the presence of an extracellular Ca2(+)-dependent rapid refilling system of intracellular Ca2+ store(s) in human vascular endothelial cells.

Benzofurans↗
PubMed1990

The antitumor effects of locally injecting human peripheral blood mononuclear cells treated with OK-432 into the tumor site: the possible role of a tumor growth inhibitory factor (TGIF).

The production of a tumor growth inhibitory factor (TGIF) was induced in human peripheral blood mononuclear cells (PBMC) by a streptococcal preparation, OK-432, in vitro. The antitumor effect of locally injecting PBMC treated with OK-432 into the tumor site was studied. PBMC were collected from patients with gastric cancer 5 to 12 days before their operation, and cultured with OK-432 for 24 hr in vitro. After the culture, the PBMC were washed thoroughly to eliminate the OK-432. The washed PBMC went on producing TGIF for more than 72 hr in vitro in the absence of OK-432. A small number of TGIF-producing PBMC, approximately 10(7) cells, were injected around the lesion under endoscopic observation. A remarkable antitumor effect was observed in 2 out of 10 cases of resectable gastric cancer. Histological examinations indicated that the antitumor effect is due to antitumor cytokines such as TGIF produced by PBMC rather than to the OK-432-activated PBMC themselves.

Adenocarcinoma↗
PubMed1989

Incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type I carriers in Saga, Japan.

Using a population-based cancer registry, we tabulated 69 definite adult T-cell leukemia/lymphoma cases (36 males and 33 females) and 2.20 expected cases (0.95 for males and 1.25 for females) diagnosed from 1981 to 1983 in Saga, Japan. The number of human T-lymphotropic virus type I carriers was computed by applying sex- and age-specific anti-human T-lymphotropic virus type I antibody positive rates among blood donors at the blood center in 1986 to the whole population of Saga Prefecture in 1982. The age-specific incidence rates among male human T-lymphotropic virus type I carriers from 40 to 79 yr of age per 100,000 were significantly higher than those of female carriers (P less than 0.05), and the rates from 60 to 69 yr of age were the highest in both sexes. The annual crude incidence rates among carriers were 115.9 for males and 66.4 for females. The summary incidence rates with 95% confidence intervals were 115.9 (58.4 to 193.0) for males and 65.9 (30.0 to 115.9) for females. The cumulative risks were 4.5% (0.8 to 11.0) for males and 2.6% (0.3 to 7.0) for females. These morbidity figures were assumed to be underestimated partly due to the newly proposed clinical entity of adult T-cell leukemia/lymphoma.

Adolescent↗
PubMed1989

Atherosclerosis and macrophages.

Atherosclerosis is undoubtedly a disease of many facets and in this review we have merely touched one angle of this issue. The best-established cause of the disease is hypercholesterolemia. Since the important role of macrophages in lipoprotein metabolism has been confirmed, current interest is focused on the role of macrophages in atherosclerosis. The origin and tissue distribution of foam cells have been discussed in detail, because they are the principal cells in the earliest lesions, the so-called fatty streaks. Once thought to be derived exclusively from smooth muscle cells, foam cells are now known to originate largely from monocytes that enter the intima and become transformed into macrophages. Exactly how monocytes are recruited and retained in the artery wall is not fully understood, but it is certain that the initial event involves adhesion to the endothelial surface followed by penetration under the influence of a chemotactic factor(s). Hypercholesterolemia contributes much to this phenomenon by affecting both monocyte-macrophages and endothelial cells. Intensive current research is increasing our understanding of the dynamic interaction between macrophages and both lipoproteins and vascular cells, and its immediate relevance to lesion formation. Closer scrutiny of the biology and molecular mechanism of the process of atherosclerosis may ultimately permit intervention in and slowing of the progress of this catastrophic human disease using new modalities.

Arteriosclerosis↗