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Biomedical subjects

T Takaoka

Publications and source records attributed to T Takaoka.

At least 37 records · Page 2Linked to original sources

Cytolysis of malignant glioma cells by lymphokine-activated killer cells combined with anti-CD3/antiglioma bifunctional antibody and tumor necrosis factor-alpha.

With the aim of developing an effective immunotherapy for malignant glioma, glioma cells were incubated with tumor necrosis factor-alpha (TNF-alpha) to increase their susceptibility to lysis by lymphokine-activated killer (LAK) cells. Treatment with exogenous TNF-alpha induced the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells. In addition, the cytolytic activity of LAK cells toward exogenous TNF-alpha treated glioma cells was significantly greater than LAK cell activity toward untreated glioma cells. This increase in cytolytic activity was blocked by anti-ICAM-1 monoclonal antibodies (MAb). Furthermore, co-treatment with a bifunctional antibody (BFA) composed of anti-CD3 (UCHT1) and antiglioma (G-22) antibodies synergistically increased the cytolytic activity of LAK cells towards TNF-alpha-treated glioma cells. These results indicate that a combination of exogenous TNF-alpha and anti-CD3/antiglioma BFA may provide an effective modified adoptive immunotherapy for patients with malignant glioma.

Antibodies, Bispecific↗

Histological and biochemical evaluation of osteogenic response in porous hydroxyapatite coated alumina ceramics.

We compared the osteogenic response in porous alumni (Al) and hydroxyapatite coated porous alumni ceramic (HA/Al) by grafting rat bone marrow cells with these implants subcutaneously in the back of syngeneic rats. The ceramics did not show any bone formation without marrow, but did when combined with marrow cells. The osteogenesis in HA/Al began directly on the ceramic surface, but in Al began away from the ceramic surface, and fibrous tissue interposition was seen between the de novo bone and its surface. Alkaline phosphatase activity and bone specific bone gla protein content in HA/Al with marrow were both about three times higher than in Al with marrow. These results indicate that HA/Al has excellent osteoconductive properties and that a composite of marrow and HA/Al is clinically applicable osteogenic biomaterial.

Alkaline Phosphatase↗

Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene.

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human gamma-interferon (HuIFN-gamma) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-gamma (reaching more than 5 U/ml) into the culture medium. The HuIFN-gamma produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-gamma gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-alpha monoclonal antibody.

Antibodies, Monoclonal↗

Long-term change of anti-acetylcholine receptor antibody in patients with myasthenia gravis after thymectomy.

Anti-acetylcholine receptor antibody (AChR Ab) plays an important role in the pathogenesis of myasthenia gravis (MG). We investigated the change of anti-AChR Ab titer after thymectomy of 10 MG patients including five patients whose age at onset was younger than 16 years. Anti-AChR Ab titer was increased in four of six patients with remission and three of four patients without remission. Change of anti-AChR Ab titer in individual patients showed an increase occurred 1-4 years after thymectomy. It is likely that thymectomy influences immune response and induces autoreactive lymphocytes and autoantibodies.

Adolescent↗

Prostate cancer-induced oncogenic hypophosphatemic osteomalacia.

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Adenocarcinoma↗

Enhancement of adhesive property of epithelial cell line Mm2T by culture in the presence of methylated vitamin B12.

A thymic epithelial cell line Mm2T was cultured in a medium containing a high concentration (100 micrograms/ml) of methylated vitamin B12 (CH3-B12). After 19 days, cells were found to have a flat phenotype, to have lost the floating cells which were observed in the control cells at the confluent stage, and to have acquired a resistance to trypsin. However, treatment of the CH3-B12-treated cells with EDTA resulted in a dissociation of cell-to-cell contact and reaggregation was achieved by addition of Ca2+, indicating the involvement of Ca2+ ion in cell-to-cell contact. Electron microscopic analyses revealed that the CH3-B12-treated cells were nearly square in their vertical section, which was in contrast to the dome-shaped feature of the control cells, and their cell-to-cell contact area was significantly widespread, as compared to those of the control, indicating that Mm2T cells acquires an adhesive property by treatment with CH3-B12. Biochemical analyses of both cells indicated that the concentration of glucosylceramide in the CH3-B12-treated cells was higher than that of the control. Free glucose characteristically inhibited the reattachment of cells dissociated with EDTA, suggesting the involvement of glucose in the cell-to-cell adhesion of CH3-B12-treated cells. In addition, WGA-binding glycoconjugates were intensely observed in the boundary region of CH3-B12-treated cells by immunohistochemical staining, but not in that of the control cells. It is suggested that CH3-B12 may affect the morphological alteration of Mm2T by enhancing cell adhesion through elevated expression of the C-type lectin.

Animals↗

Transfection-induced tumor necrosis factor-alpha increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells: continuous expression of intercellular adhesion molecule-1 on the glioma cells.

To develop more effective adoptive immunotherapy, we transfected the human tumor necrosis factor-alpha (TNF-alpha) gene into human glioma cells (U251-SP), which were used as target cells. TNF-alpha is known to increase both the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells and the susceptibility of glioma cells to lymphokine-activated killer (LAK) cell cytolysis. We compared the expression of ICAM-1 induced by TNF-alpha generated by the TNF-alpha gene-transfected cells with that induced by exogenously added TNF-alpha. When the TNF-alpha gene was transfected into U251-SP cells, the expression of ICAM-1 was detected on the cell surface from 3 days after the transfection and continued until at least 9 days. In contrast, it was expressed only transiently in the case of exogenously added TNF-alpha. Also, the cytolytic activity of LAK cells induced by transfection-induced TNF-alpha was significantly stronger than that induced by exogenously added TNF-alpha. The increased susceptibility was quenched by anti-ICAM-1 monoclonal antibody. These data indicated that continuous expression of ICAM-1 induced by TNF-alpha gene transfection of glioma cells resulted in higher cytolytic activity of LAK cells.

Antibodies, Monoclonal↗

Liposomal transfection of human gamma-interferon gene into human glioma cells and adoptive immunotherapy using lymphokine-activated killer cells.

The authors evaluated the effect of liposomal transfection of human gamma-interferon (HuIFN-gamma) gene into human glioma cells and lymphokine-activated killer (LAK) cells, alone and in combination. An HuIFN-gamma gene inserted in a eukaryotic expression vector was entrapped in liposomes bearing positive surface charges. Liposomal gene transfection induced production of HuIFN-gamma and its secretion in culture medium of human glioma cell lines (SK-MG-1 and U-251 MG). At 4 days after transfection, the cells produced 10 to 50 U/ml of HuIFN-gamma in the medium, whereby the major histocompatibility complex (MHC) class I and II antigens, as well as intercellular adhesion molecule-1 (ICAM-1), were induced on the glioma cell surface. The growth-inhibiting effect of transfection-induced HuIFN-gamma was much stronger in comparison with control cultures exposed to 500 U/ml of exogenously added HuIFN-gamma. In addition, 20% to 40% growth inhibition was obtained in the glioma cells when they were treated with LAK cells alone at a 5:1 ratio of effector to target cells. Liposomal transfection of HuIFN-gamma gene into human glioma cells combined with immunotherapy using LAK cells was more effective than either technique alone. The reinforcement of growth inhibition in the case of combined therapy was quenched by anti-ICAM-1 monoclonal antibody, but not by anti-MHC class I or II monoclonal antibodies. These results suggest that the combined effect of liposomal transfection of HuIFN-gamma gene plus LAK cells into human glioma cells is a potentially useful therapy for malignant glioma, and that the mechanisms of the reinforcement of growth inhibition are closely related to the expression of ICAM-1 on the glioma cell surface.

Cell Adhesion Molecules↗

[Idiopathic interstitial pneumonia that responded to intermittent intravenous administration of high-dose cyclophosphamide].

A 78-year-old man was admitted to the hospital with exertional dyspnea and fever. Chronic idiopathic interstitial pneumonia (IIP) had been diagnosed a year before. Follow-up chest X-ray examination showed diffuse reticular shadows and progressive shrinkage of both lower lobes. Chest CT scan revealed honeycomb appearance of both lower lung fields. Moderate hypoxemia was found by arterial blood gas analysis. The patient responded to an orally administered corticosteroid. Because tapering of the medicine caused exacerbation of the hypoxemia, methylprednisolone pulse therapy was given with poor response. Then high-dose (750 mg) of cyclophosphamide (CPM) were given intravenously 6 times, every 3 or 4 weeks. After the second administration of CPM, decreases in hypoxemia and in blood LDH levels were observed. This treatment allowed as to taper the dose of oral corticosteroid from 60 mg/day to 15 mg/day. This case suggests that intravenous administration of high-dose CPM may be effective against IIP.

Aged↗

[Mitral valve replacement through right thoracotomy in a patient with a functioning ITA graft].

A 51-year-old male was admitted to our Institution with a complaint of dyspnea on effort. He had undergone coronary artery bypass grafting and mitral valve annuloplasty three years previously. The left ventriculograms showed severe mitral regurgitation. The coronary angiograms revealed an ITA graft and two SVG grafts were fully functioning. Considering the risk of injury of ITA/SVG graft during redo median sternotomy, we approached the heart through right anterolateral thoracotomy. Mitral valve replacement was performed under profound hypothermia without aortic cross clamping. Temporary reduction of perfusion flow was useful in order to obtain a better visual field. His postoperative course was uneventful. Right thoracotomy has an advantage over median sternotomy when reoperation is to be done for patients with a functioning ITA graft.

Coronary Artery Bypass↗

[Pulmonary root reconstruction with a cryopreserved pulmonary allograft for mechanical pulmonary valve thrombosis].

A 58-year-old woman suffering from congestive heart failure caused by a mechanical pulmonary valve thrombosis was operated on with a pulmonary allograft. She had experienced pulmonary valvotomy and resection of infundibular stenotic muscle for congenital pulmonary stenosis at the age of 23 years old. She got congestive heart failure caused by pulmonary regurgitation, and underwent pulmonary valve replacement with a St. Jude Medical (SJM) valve when she was 48 years old. She suffered from episodes of a thrombosed SJM valve in 1984 and 1993. Each time, thrombolytic treatment with urokinase or recombinant tissue-type plasminogen activator was effective. She suffered from the third episode of SJM valve thrombosis in January 1994. As thrombolytic treatment was not effective this time, the thrombosed SJM valve was resected and her pulmonary root was reconstructed with a cryopreserved pulmonary allograft. Postoperative course was uneventful, and she now enjoys her life without anticoagulant therapy.

Cryopreservation↗

[Detection of HTLV-I proviral DNA by PCR method from bronchoalveolar lavage cells of HTLV-I carriers].

To elucidate whether or not human T-lymphotropic virus type I (HTLV-I) infected cells exist in the lungs of HTLV-I carriers, we examined bronchoalveolar lavage (BAL) cells for the presence of HTLV-I proviral DNA by the polymerase chain reaction (PCR) method. The cells were harvested from HTLV-I seropositive individuals with or without various respiratory diseases. The HTLV-I pX region was detected from separated BAL cells by dot blot hybridization after PCR in all 14 HTLV-I seropositive individuals tested. Four out of these 14 individuals were asymptomatic HTLV-I carriers, while the other ten had symptoms, including those of bacterial pneumonia, chronic respiratory tract infection, interstitial pneumonia, atypical mycobacterial infection, bronchitis, mediastinal lymphadenitis and bronchial asthma. HTLV-I proviral DAN was detected in BAL cells from patients with a normal proportion of lavage lymphocytes and a normal CD4/CD8 ratio. These findings suggest that HTLV-I infected cells may commonly exist in the lower respiratory tract and alveolar space without producing characteristic symptoms/signs, and that any causal relation to the pulmonary lesion must therefore be carefully elucidated, in HTLV-I carriers.

Aged↗

[Anomalous origin of the left coronary artery from the pulmonary artery: a case report in an adult].

A 37-year-old female with anomalous origin of the left coronary artery from the pulmonary artery was surgically treated by creation of intrapulmonary aorto-coronary tunnel. Postoperative cardiac catheterization showed a minimal pulmonary stenosis at the baffle. But the remarkable preoperative ST-depression in a treadmill exercise test disappeared completely after operation and the normograde blood flow of the left coronary artery was detected from the ascending aorta.

Adult↗

[A case report of surgical treatment in acute aortic dissection: efficacy of retrograde cerebral perfusion and pitfall of image diagnosis].

A 76-year-old man with acute aortic dissection of Stanford type A underwent aortic arch replacement using retrograde cerebral perfusion for 105 minutes. By the preoperative IADSA an entry was detected in the distal arch. There were no neurological complications. But the postoperative IADSA showed that the surgically closed entry was another one from that diagnosed before operation. This case shows us efficacy of retrograde cerebral perfusion which allows more time for arch repair than the technique of deep hypothermia with circulatory arrest and importance of careful and precise evaluation by preoperative image diagnosis.

Aged↗

Prevention of posttransfusional non-A, non-B hepatitis by a screening test for hepatitis C virus antibody of donor bloods.

The preventive effect on posttransfusional non-A, non-B hepatitis (PTH) of screening out HCV-Ab positive blood and the prevalence of HCV-Ab-positive donor blood were examined. The incidence of HCV-Ab-positivity in donor blood A was 0.9% and that in donor blood B was 1.35%. The mean ALT and guanase levels were 11.5 +/- 5.8 and 0.58 +/- 0.24 IU/l in HCV-Ab negative blood and 17.3 +/- 7.9 and 0.84 +/- 0.23 IU/l in HCV-Ab-positive blood. Both levels were significantly higher in HCV-Ab-positive blood. These differences were considered to be nonspecific, but there may be some relationship between the levels of ALT and guanase in donor blood and the HCV carrier status. After adoption the screening test for HCV-Ab positive blood, there was no case of a definite diagnosis of PTH, although 4 patients (6.6%) suspected of developing PTH. So, the incidence of PTH was clearly lower than the lowest incidence before adoption of this test. Therefore, we conclude that screening for HCV-Ab in donor blood should be routinely used for prevention of PTH.

Blood Donors↗

Cytosol type electrolyte medium suitable for long term growth of human cells with very low membrane potential.

Culture media for mammalian cells contain electrolytes at concentrations that approximate those of the extracellular fluid (ECF). However, we observed that HeLa strain cells can grow in a cytosol type, serum-free, high amino acid medium (KN13) in which the concentrations of K+, Mg2+ and Pi were increased to about 10 times those in ECF by replacing NaCl. The Ca2+ concentration of KN13 is 10% of that in ECF. The additions of Mg2+ and Pi are essential to prevent the harmful effect of a high concentration of K+ in the medium. Even an increase in the K/Na ratio to 7 and 9 permitted growth for at least 2 weeks and 4 days, respectively. HeLaP3 cells adapted to KN13 (HeLaK cells) have proliferated (4 fold/week) for 4 years in this medium. The Na,K-ATPase of HeLaK cells was the alpha 1 isoform. HeLaK cells in KN13 medium have a lower membrane potential (-3.0 +/- 6.1 mV) than that of the original HeLaP3 cells in DM160 (-26 +/- 10 mV).

Base Sequence↗