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Biomedical subjects

O Tokunaga

Publications and source records attributed to O Tokunaga.

At least 55 records · Page 3Linked to original sources
PubMed1996

Suppression of adjuvant arthritis in rats by induction of oral tolerance to mycobacterial 65-kDa heat shock protein.

Oral administration of mycobacterial 65-kDa heat shock protein (HSP) given daily for 5 days prior to immunization with Mycobacterium tuberculosis (Mt) suppressed the development of adjuvant arthritis (AA) in rats. AA was significantly suppressed by 30 and 300 micrograms HSP, and variably by 0.3, 3 micrograms or 1 mg. Histological analysis of joint samples obtained from control and test rats confirmed the suppression of AA in the fed group. Feeding Mt or hen egg lysozyme (HEL) failed to affect AA, indicating that the suppression was HSP specific. The oral administration of 30 micrograms HSP decreased both delayed-type hypersensitivity (DTH) reactions and proliferative responses to HSP and Mt. In addition, the proliferation of lymph node cells (LNC) from Mt-sensitized rats was inhibited by the addition of spleen cells (SPC) from HSP-fed animals, possibly by the secretion of transforming growth factor (TGF)-beta. Spleen cells obtained from tolerized donors were capable of transferring the tolerance to naive recipients. These results demonstrate that feeding HSP is an effective way to suppress AA and that the suppression of AA may be mediated by regulatory T cells generated following oral administration of mycobacterial 65-kDa HSP.

Administration, Oral↗
PubMed1996

Vanadate causes synthesis of endothelium-derived NO via pertussis toxin-sensitive G protein in pigs.

The effects of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, on the endothelial nitric oxide (NO) pathway were studied in vitro. Vanadate caused endothelium-dependent relaxations in isolated porcine coronary arteries, which were abolished by N omega-nitro-L-arginine methyl ester. The relaxations were also abolished by pertussis toxin, an inhibitor of certain G proteins. Tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the vanadate-induced relaxations. Vanadate also caused pertussis toxin-sensitive, endothelium-dependent relaxations in isolated porcine renal and femoral arteries and jugular veins. Immunoblots, using an antibody to phosphotyrosines and to c-Src in native porcine aortic endothelial cells, respectively, showed that vanadate induced an elevation of phosphotyrosine proteins and a decrease in the amount of the active form of c-Src family kinases; both changes were markedly suppressed by cotreatment with ST-638. These results indicate that in porcine blood vessels, vanadate causes a synthesis of endothelium-derived NO for which endothelial tyrosine kinases and pertussis toxin-sensitive G protein are considered to be closely involved.

Animals↗
PubMed1995

Time-dependent thickening of the intima in aortocoronary saphenous vein grafts: clinicopathological analysis of 24 patients.

The present study was undertaken to investigate histological changes in aortocoronary saphenous vein grafts (SVGs) and the relationship between intimal thickening of the SVGs and the interval after grafting. The SVGs were divided into five groups according to the degree of intimal thickening and associated luminal narrowing: minimal thickening (0%-10% stenosis), slight thickening (11%-25% stenosis), slight-to-moderate thickening (26%-50% stenosis), moderate thickening (51%-75% stenosis), and severe thickening (76%-100% stenosis). SVGs showing minimal thickening had been implanted for 0-3 weeks, those with slight thickening for 2-13 weeks, those with slight-to-moderate thickening for 5-13 weeks, those with moderate thickening for 30-52 weeks, and those with severe thickening for 30-83 weeks. Thickening of the intima in SVGs (intimal hyperplasia) was time-dependent, and began as early as 2 weeks after the graft surgery. The change was diffuse and concentric, and observed from an aortic root to a coronary site. The major cell type involved in the intimal hyperplasia was the smooth muscle cell.

Aged↗
PubMed1995

Ten-year survey of incidence of infection as a cause of death in hematologic malignancies: study of 90 autopsied cases.

We investigated 90 autopsied cases with hematologic malignancy, including malignant lymphoma (ML), acute leukemia (AL), and adult T-cell leukemia (ATL) peculiar to our district, during the 10-year period 1982-1991 to determine the change in incidence of infection as a cause of death. We divided the cases into two groups representing the first half decade (1982-1986) and the second half decade (1987-1991) and compared the findings made in the two groups. Although infection was the major cause of death in those autopsied cases, the incidence of fatal infections decreased during the latter period. The incidence of fatal bacterial infections decreased, while fungal infections showed a relative increase. Pneumocystis carinii pneumonia and cytomegalovirus (CMV) infection occurred more frequently in patients with ATL than in those with ML or AL. Combined infection by more than three pathogens was observed in 2 cases of ATL. Our study revealed the characteristics of ATL specific to our district, and indicated the need to apply new strategies to prevent and treat fungal and viral infections in patients with hematologic malignancies.

Acute Disease↗
PubMed1995

Massive pericardial effusion in a patient with Hashimoto's thyroiditis: histological examination of underlying cardiomyopathy.

An unusual case of a hypothyroid patient with huge pericardial effusion due to Hashimoto's thyroiditis is reported. Cardiac tamponade occurred during admission. Eight hundred milliliters of pericardial effusion was withdrawn by pericardiocentesis. Even after successful replacement of thyroid hormone, she had recurrent effusion two years later. Refractory pericardial effusion is a rare complication in treated hypothyroid patients. Underlying cardiomyopathy was presented with hemodynamic and histological examinations.

Cardiac Tamponade↗
PubMed1995

Granular cell tumor in the ascending colon.

We describe a case of multiple polypoid lesions that occurred in the colon of a 62-year-old man. Eight of the lesions were demonstrated by barium enema, and five were examined histologically. A small nodule in the submucosa of the ascending colon was histologically identical to granular cell tumor, characterized by nested growth of large tumor cells with ample granular cytoplasm and small round nuclei. Immunohistochemically, the cells were positive for S-100, neuron-specific enolase and vimentin, and negative for alpha-smooth muscle actin and desmin.

Colonic Neoplasms↗
PubMed1995

Extraskeletal chondroma with chondroblastic and granuloma-like elements.

A unique case of extraskeletal chondroma occurring in the right ring finger of a 51-year-old man is reported. The tumor, measuring 4.0 x 2.2 x 1.5 cm, consisted of chondroid, granuloma-like, and chondroblastic cell zones associated with fine calcification. Immunohistochemically, most of the tumor cells except for multinucleated giant cells were positive for vimentin. Cells positive for S-100 protein were scattered throughout the tumor, and cells positive for alpha-1 antichymotrypsin were observed in the chondroblastic cell zone and in the granuloma-like area. Ultrastructurally, the chondroblastic cells had a characteristic microvillous cell border.

Chondroma↗
PubMed1995

Hepatopancreatoduodenectomy for squamous and adenosquamous carcinoma of the gallbladder.

The characteristics of squamous or adenosquamous cell carcinoma of the gallbladder differ quite markedly from those of adenocarcinoma, although the incidence is extremely low. Recently, we encountered both of the former types of gallbladder carcinoma: a 77-year-old man with squamous cell carcinoma and a 70-year-old man with adenosquamous cell carcinoma of the gallbladder. Both had a large mass in the gallbladder fossa region with infiltration to the liver and invasion of the duodenum. Hepatopancreatoduodenectomy was performed on both of these patients. The TNM stage of the former was IV (T4N0M0) and of the latter IV (T4N0M0) and of the latter IV (T4N1bM0). The former has remained well without recurrence for about 1 year and 4 months after the operation, while the latter died of recurrent disease 6 months after operation. The true reason for the difference in the prognosis of these two patients was not known. However, hepatopancreatoduodenectomy is considered to be a most adaptable operative procedure for squamous or adenosquamous cell carcinoma of the gallbladder in view of their mode of spread, and the presence of lymph node metastasis might be a factor of poor prognosis.

Aged↗
PubMed1994

Endothelial cell heterogeneity in experimentally-induced rabbit atherosclerosis. Demonstration of multinucleated giant endothelial cells by scanning electron microscopy and cell culture.

We investigated the aortic endothelial cells of cholesterol-fed rabbits, using scanning electron microscopy and a cell culture technique. Rabbits were given a 1% cholesterol diet intermittently for up to 40 weeks. In these animals, the area of endothelial cells was increased and the cells showed polymorphism in relation to the progression of atherosclerosis. In animals fed the cholesterol diet for 12, 28 and 40 weeks, the average area of the endothelial cells was 436 +/- 15, 762 +/- 153, and 836 +/- 165 microns2, respectively. In the cholesterol-fed 40-week group, in particular, giant endothelial cells, measuring more than 1200 microns2, accounted for 14% of the population. In animals fed a standard diet there was no significant difference in endothelial cell morphology between control 0-week and control 40-week groups; in both, the luminal surface of the thoracic aorta formed a homogeneous sheet covered by small rhomboidal endothelial cells, the area of most being less than 400 microns2. Primary cultured endothelial cells harvested from those control groups were mononuclear typical small cells with a centrally located nucleus; the proportion of binucleated cells was less than 2% and no multinucleated giant cells with three or more nuclei were detected. Endothelial cells from the cholesterol-fed groups, however, contained larger numbers of binucleated cells, with the number increasing in proportion to the duration of cholesterol feeding. The major distinguishing feature of the endothelial cells in the cholesterol-fed groups was the presence of multinucleated giant cells with three or more nuclei; these accounted for 2.3% and 3.3% of the total cell population in the cholesterol-fed 28- and 40-week groups, respectively. No bromodeoxyuridine uptake was found in the nuclei of the cultured multinucleated giant cells. Heterogeneity of endothelial cells, with the concomitant appearance of multinucleated giant cells, emerges with the progression of diet-induced atherosclerosis. The morphological alterations of endothelial cells observed in the present study intimately reflect changes in their function associated with the progression of atherosclerotic lesions.

Animals↗
PubMed1994

Activation and cholesterol accumulation of macrophages induced by hypercholesterolemia. A study using a rat peritoneal macrophage model for extravascular in vivo generation of foam cells.

Intimal infiltration of lipid-filled macrophages (M psi s) is an important event in the pathogenesis of atherosclerosis. To better understand M psi functions, a model for the extravascular in vivo generation of foam cells in rat peritoneal cavities was utilized. Morphologic alterations, intracellular cholesterol accumulation, subpopulation, activation and proliferative properties of M psi from hypercholesterolemic rats (HM psi s) were compared with M psi s from normal rats (NM psi s). HM psi s revealed a significant increase of cholesterol mass in the cytoplasm; 65% of HM psi s were loaded with various amounts of oil-red-O-stainable lipid droplets which were barely identified in NM psi s. Ultrastructurally, accumulated lipid droplets in HM psi s were either membrane-bound or membrane-free in the cytoplasm. Further biochemical analysis revealed that cellular levels of total cholesterol, free cholesterol, and cholesteryl esters in HM psi s were increased 6-, 8-, and 4-fold, respectively. As to the M psi subpopulation, there was a significant increase of Ia-antigen-positive cells in HM psi s (15.8 vs. 8.8%), indicating that these cells were in a state of activation. To investigate the mitotic activity, the proliferative potential of M psi s was determined both in vivo and in vitro using monoclonal anti-bromodeoxyuridine (anti-BrdU) antibody to detect BrdU incorporated into cell DNA. However, both NM psi s and HM psi s showed little proliferation; proliferative indices were less than 2%. This implies that M psi s are barely replicating, and hypercholesterolemia does not stimulate M psi s in this aspect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

In situ demonstration of the HTLV-I genome in the spinal cord of a patient with HTLV-I-associated myelopathy.

Using polymerase chain reaction (PCR) and in situ hybridization, we investigated the HTLV-I genome in the CNS of an HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient with a 20-year disease duration. Neuropathologically, there was severe white matter degeneration throughout the spinal cord, but lymphocytic infiltrates were not evident in any lesion. PCR amplification of the pX region of HTLV-I DNA detected its sequence in the spinal cord and all extra-CNS tissue samples. In situ hybridization using probes complementary to the pX and gag regions detected the HTLV-I genome in the cytoplasm and nucleus of cells in the thoracic cord. The findings indicate a direct involvement of HTLV-I in the neurodegeneration of HAM/TSP.

Aged↗
PubMed1994

Hyperplastic polyps following treatment of acute gastric ulcers.

Although hyperplastic polyps are the most common polyps of the stomach, the etiology of these polyps is not completely understood. We report a 61-year-old woman who developed gastric hyperplastic polyps following acute gastric lesions. She was admitted for endoscopic injection sclerotherapy of esophageal varices. After the end of sclerotherapy, acute gastric lesions developed. For treatment of the lesions, omeprazole was used for 8 weeks followed by famotidine for 8 weeks. At the end of the treatment, she developed multiple gastric hyperplastic polyps, suggesting that acute gastric lesions and/or treatment of the gastric lesions are related to the development of hyperplastic polyps in the stomach.

Esophageal and Gastric Varices↗
PubMed1993

Primary T-cell lymphoma of the gastrointestinal tract associated with human T-cell lymphotropic virus type I. An analysis using in situ hybridization and polymerase chain reaction.

BACKGROUND: During a population-based local cancer registry, a peculiar type of T-cell lymphoma restricted to the gastrointestinal tract was found in patients living in southwestern Japan. METHODS: Five cases of gastrointestinal (GI) tract T-cell lymphoma were analyzed with immunohistologic examination, ultrastructural analysis, in situ hybridization (ISH), and polymerase chain reaction (PCR). RESULTS: All cases satisfied the criteria of primary GI tract lymphoma at presentation or operation. Four showed a close relationship to human T-cell lymphotropic virus type I (HTLV-I). Those four had positive results for anti-HTLV-I antibody and positive surface markers for CD4, positive hybridization signals by ISH, and HTLV-I gene products by PCR, but they had no lymphoma cells in peripheral blood or bone marrow. The fifth case showed negative signals by ISH and PCR. CONCLUSIONS: These findings suggest that some of the putative adult T-cell leukemia/lymphoma (ATLL) types can be further classified as GI-tract-type lymphoma. The prognosis for the GI tract type is as poor as it is for conventional ATLL.

Aged↗
PubMed1993

Occurrence of primary biliary cirrhosis, CREST syndrome and Sjögren's syndrome in a patient with HTLV-I-associated myelopathy.

We report the occurrence of three autoimmune diseases (primary biliary cirrhosis, CREST syndrome and Sjögren's syndrome) in a patient with HTLV-I-associated myelopathy (HAM). The patient had the depressed cell-mediated immune responses but the infiltration of CD8-T cells was found in the cerebrospinal fluid and liver. The clinical and immunological features of this case are similar to those of chronic graft-versus-host disease.

Biopsy↗
PubMed1993

Monocyte-endothelial cell interactions in vitro, with reference to the influence of interleukin-1 and tumor necrosis factor.

The interaction between monocytes and endothelial cells plays an important role in normal vascular biology and the pathogenesis of several vascular diseases. In the present study, interactions of freshly isolated human monocytes (Mos) and cultured umbilical vein endothelial cells (ECs) were quantitatively analyzed by a time lapse microcinematographic optical video system in vitro, with reference to Mo locomotion, adherence, and cytokine influence on these processes. The interaction between Mos and ECs was found to be a dynamic process. Without any stimulation of ECs, Mos generally possessed higher binding capacity to ECs and more active motile property than neutrophils and lymphocytes. The binding ratio of Mos to ECs varied from 0 to 8. Mos crawled over the surface of ECs or along the intercellular boundary areas of ECs by extending pseudopodia as long as 60 microns in length to traverse several ECs. Mos migrated into the subendothelium and could cause the disruption of the EC monolayer. In contrast, neutrophils or lymphocytes showed less adhesiveness to ECs and exhibited less dislocation when they moved on the ECs. Pretreatment of ECs with either human recombinant interleukin-1 beta (IL-1 beta) or tumor necrosis factor (TNF) (10-20 U/ml for 4-8 h) significantly increased adhesion rates of both Mos and neutrophils. Furthermore, the increased adhesion of neutrophils to stimulated ECs was accompanied by incremental increases in the rate of cellular movements. These phenomena were found to be associated with activation of EC surface adhesion molecules. In addition, by using the Boyden chamber assay, we found that IL-1 and TNF did not produce any chemotactic activity for Mos with a concentration range of 10(-3) to 10(3) U/ml. These results indicate that, in comparison with neutrophils and lymphocytes, Mos exhibited active adhesive and motive properties even on unstimulated EC surfaces, which could potentially interfere with the integrity of ECs. Upon exposure to cytokine stimulation, ECs increase the expression of adhesion molecules thereby enhancing both adhesion and locomotion of leukocytes. The distinctively higher affinity for binding to cultured ECs of blood Mos and their active motility relative to other circulating leukocytes may have great consequences in various physiological and pathological processes in vivo, including atherogenesis.

Cell Communication↗