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Biomedical subjects

T Oikawa

Publications and source records attributed to T Oikawa.

At least 37 records · Page 2Linked to original sources
PubMed2003

Induction of potent antitumour natural-killer cells from peripheral blood of patients with advanced prostate cancer.

OBJECTIVE: To examine whether antitumour natural-killer (NK) cells can be induced from peripheral blood mononuclear cells (PBMCs) of patients with advanced prostate cancer, as cell therapy using antitumour immune cells is a promising candidate treatment but such patients generally have a suppressed immune response against cancer cells. PATIENTS AND METHODS: PBMCs were obtained from 10 patients (four with stage D2 and six with stage B or C disease). For the NK cell expansion, PBMCs were co-cultured with irradiated HFWT cells, a cell line originating from Wilms' tumour, in RHAM alpha culture medium supplemented with 5% autologous plasma and interleukin-2 (200 U/mL) for 2 weeks. RESULTS: When PBMCs were co-cultured with HFWT cells, lymphocytes from all patients had a 20- to 130-fold expansion after 2 weeks of culture. The CD16+ CD56+ cells constituted >70% of the proliferated lymphocyte population. The induced NK cells had significantly greater cytotoxicity against a prostate cancer cell line (PC-3) than lymphocytes cultured with no HFWT cells. There was no significant difference in growth and phenotypes of lymphocytes and the induced NK cell activity between patients with stage D2, B or C. CONCLUSION: NK cells with potent cytotoxic activity against prostate cancer cell lines from patients with advanced prostate cancer were selectively expanded. Further investigation is needed to determine whether this approach could be a candidate for cell therapy for advanced prostate cancer.

Aged↗
PubMed2002

Evolution of lower-hybrid-driven current during the formation of an internal transport barrier.

Evolution of the lower-hybrid(LH)-driven current profile was measured during the formation of an internal transport barrier (ITB) in a reversed magnetic shear discharge. As the ITB developed, the initially centrally peaked LH-driven current profile gradually turned hollow and was sometimes accompanied by an off-axis peak in the electron temperature profile. These observations indicate the concentration of LH power deposition to the ITB for this case as a result of nonlinear coupling between the LH waves and the target plasma.

Journal Article↗
PubMed2002

Birth of normal calves after intracytoplasmic sperm injection of bovine oocytes: a methodological approach.

Intracytoplasmic sperm injection (ICSI) is advantageous when only very few spermatozoa are available for insemination. Bovine spermatozoa were injected individually into matured oocytes using a piezo electric actuator. Spermatozoa were "immobilized", by scoring their tails immediately before injection, or "killed", by repeated freezing and thawing. About 4 h after ICSI, the oocytes with two polar bodies (activated by sperm injection) were selected and treated 5 min with 7% ethanol before further culture. When examined 19-21 h after ICSI, nearly 90% of the oocytes were fertilized normally (two pronuclei and two polar bodies) irrespective of the sperm treatment (immobilization or killing) prior to ICSI, but subsequent preimplantation embryo development was much superior (cleavage 72%: blastocysts 20%) after ICSI with immobilized spermatozoa than by using killed spermatozoa (cleavage 28%; blastocysts 1%). Ethanol activation of bovine oocytes with two polar bodies 4 h after ICSI improved the cleavage (33% versus 72%) and blastocyst (12% versus 20%) rates markedly (P < 0.05). Five normal calves were born after transplantation of ten blastocysts to ten surrogate cows. These results show that piezo-ICSI using immobilized spermatozoa, combined with ethanol treatment of sperm-injected oocytes, is an effective method to produce bovine offspring.

Animals↗
PubMed2002

Atomic configuration in core structure of Lomer dislocation in Si0.76Ge0.24/Si.

The core structure of a Lomer dislocation in SiGe/Si system has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to the high-resolution image taken with a 200 kV field-emission gun high-resolution electron microscope. The Lomer dislocation has a Hornstra-like core. The contrast of the image simulated on the basis of derived atomic configuration is in agreement with that of the experimental image.

Journal Article↗
PubMed2001

Plasma equilibrium and confinement in a tokamak with nearly zero central current density in JT-60U.

A high confinement equilibrium with nearly zero toroidal current in the central region (a "current hole") has been observed for the first time to persist stably for several seconds in the JT-60U tokamak. This observation indicates the possibility of stable tokamak operation without central toroidal current; the central current has previously been believed to be necessary in tokamaks. The radius of the current hole extended up to 40% of the plasma minor radius. It was observed that the current hole was formed by the increase of the off-axis noninductive current.

Journal Article↗
PubMed2001

In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression.

We previously reported that overexpression of PU.1, a member of the Ets family of transcription factors, induces differentiation inhibition and apoptosis associated with c-Myc down-regulation in murine erythroleukemia (MEL) cells. To understand the molecular mechanism by which c-Myc is down-regulated due to overexpression of PU.1, we performed luciferase reporter assays using the mouse c-myc promoter. PU.1 repressed the activities of not only the c-myc promoter but also several other promoters. Experiments with deletion mutants of PU.1 revealed that the C-terminal region spanning amino acids (aa) 123-272 including the PEST and ETS domains but not the activation domain was sufficient for this transcriptional repression. It was unlikely that the repression was due to sequestration of a limited amount of CBP/p300 nor pCAF, because overexpression of these co-activators did not relieve PU.1-mediated transcriptional repression. Instead, it was found that the C-terminal aa 101-272 of PU.1 formed a complex with mSin3A and HDAC1 in vivo, which was speculated to be associated with the repression. The C-terminal region of PU.1 also formed a complex with the basic transcription factor TBP in vitro and in vivo. Our results suggest that overexpression of PU.1 induces transcriptional repression in several gene promoters including the c-myc promoter which may be mediated by its complex formation with HDACs.

Cell Line↗
PubMed2001

Quasisteady high-confinement reversed shear plasma with large bootstrap current fraction under full noninductive current drive condition in JT-60U.

A quasisteady reversed shear plasma with a large bootstrap current fraction ( approximately 80%) has been obtained for the first time in the JT-60U tokamak. The shrinkage of reversed shear region was suppressed by the bootstrap current peaked at the internal transport barrier (ITB) layer and the ITBs at a large radius were sustained, which, by combination with an H-mode edge pedestal, resulted in a high confinement or 2.2 times the H-mode scaling for 6 times energy confinement time or 2.7 s. Furthermore, a full noninductive current drive was obtained by the bootstrap current and the beam driven current.

Journal Article↗
PubMed2001

Pentoxifylline improves in vitro fertilization and subsequent development of bovine oocytes.

The purpose of this study was to examine whether pentoxifylline improves in vitro fertilization and developmental rates of bovine oocytes. In the first experiment, we examined the effects on the fertilization rate of various concentrations of pentoxifylline (0-7.5 mM) combined with heparin (10 IU/mL). In the second experiment, we examined fertilization cleavage and blastocyst rates after frozen-thawed spermatozoa, obtained from four different bulls, were incubated with heparin (10 IU/mL) with or without caffeine (5 mM) or pentoxifylline (5 mM). In the first experiment, a significantly higher fertilization rate was obtained in heparin containing 5 mM pentoxifylline compared to that in heparin alone or in heparin containing 7.5 mM pentoxifylline (86% vs 60% vs 64%, respectively). The percentage of monospermy in 5 mM pentoxifylline (81%) was significantly higher than in heparin alone (57%). In the second experiment, the interactions among Bulls A, B, C, and D; between treatments (pentoxifylline-with-heparin, caffeine-with-heparin and heparin alone), and between bulls and treatments were analyzed for the number of oocytes penetrated, monospermic oocytes, cleaved oocytes and blastocysts. Among bulls, there was a significant difference in the number of oocytes penetrated (P < 0.01), monospermic oocytes (P < 0.05), cleaved oocytes (P < 0.001), and blastocysts (P < 0.001). Between treatments, there was a significant difference in the number of oocytes penetrated (P < 0.001), monospermic oocytes (P < 0.01) and cleaved oocytes (P < 0.001). Interaction between bulls and treatments was observed for the number of oocytes penetrated (P < 0.05). Individually, for Bulls A, C and D, the numbers of oocytes penetrated and monospermic oocytes in pentoxifylline-with-heparin were significantly higher than in heparin alone. For Bull D, significantly higher results were obtained for the number of oocytes penetrated, monospermic oocytes, cleaved oocytes and blastocysts in pentoxifylline-with-heparin compared to caffeine-with-heparin and heparin alone (P < 0.05). These results suggest that treating sperm with 5 mM pentoxifylline in combination with heparin is effective for bovine in vitro fertilization and it that this treatment is effective even for bulls that produce low fertilization and blastocysts after sperm treatment with caffeine-with-heparin or heparin alone.

Animals↗
PubMed2001

Lineage switch induced by overexpression of Ets family transcription factor PU.1 in murine erythroleukemia cells.

PU.1 is an Ets family transcription factor essential for myelomonocyte and B-cell development. We previously showed that overexpression of PU.1 in murine erythroleukemia (MEL) cells inhibits growth and erythroid differentiation and induces apoptosis of the cells. In an effort to identify target genes of PU.1 concerning these phenomena by using a messenger RNA differential display strategy, we found that some myeloid-specific and lymphoid-specific genes, such as the osteopontin gene, are transcriptionally up-regulated in MEL cells after overexpression of PU.1. We then found that expression of several myelomonocyte-specific genes, including the CAAT-enhancer-binding protein-alpha and granulocyte-macrophage colony-stimulating factor receptor genes, was induced in MEL cells after overexpression of PU.1. B-cell-specific genes were also examined, and expression of the CD19 gene was found to be induced. Expression of the myelomonocyte-specific proteins CD11b and F4/80 antigen but not the B-cell-specific proteins B220 and CD19 was also induced. After overexpression of PU.1, MEL cells became adherent and phagocytic and showed enhanced nitroblue tetrazolium reduction activity. Expression of myelomonocyte-specific and B-cell-specific genes was not induced when a mutant PU.1 with part of the activation domain deleted (a change found to inhibit erythroid differentiation of MEL cells) was expressed. These results indicate that PU.1 induces a lineage switch in MEL cells toward myelomonocytic cells and that its activation domain is essential for this effect. The results also suggest that the pathway of the lineage switch is distinct from that of inhibition of erythroid differentiation in MEL cells.

Cell Adhesion↗
PubMed2001

Chemo-enzymatic D-enantiomerization of DL-lactate.

We investigated the total conversion of racemic lactate, L-lactate, and pyruvate into D-lactate, which is very useful as a starting material for the synthesis of chiral compounds and much more valuable than the L-enantiomer by means of coupling of L-specific oxidation of the racemate with L-lactate oxidase and non-enantiospecific reduction of pyruvate to DL-lactate with sodium borohydride. In this one-pot system, L-lactate was enantiospecifically oxidized to an achiral product, pyruvate, which was chemically reduced to DL-lactate leading to a turnover. Consequently, either DL-lactate, L-lactate, or pyruvate was fully converted to the D-enantiomer. We optimized the reaction conditions: DL-lactate was converted to D-lactate in 99% of the theoretical yield and with more than 99% enantiomeric excess. DL-alpha-Hydroxybutyrate and alpha-ketobutyrate were converted also to D-alpha-hydroxybutyrate in the same way, though slowly.

Borohydrides↗
PubMed2001

Fragmentary form of thermostable leucine dehydrogenase of Bacillus stearothermophilus: its construction and reconstitution of active fragmentary enzyme.

X-ray crystallographic studies revealed that various amino acid dehydrogenases fold into two domains in each subunit, a substrate-binding domain and an NAD(P)(+)-binding domain (Baker, P. J., Turnbull, A. P., Sedelnikova, S. E., Stillman, T. J., and Rice, D. W. (1995) Structure 3, 693-705). To elucidate the function and folding process of these two domains, we have genetically constructed a fragmentary form of thermostable leucine dehydrogenase of Bacillus stearothermophilus consisting of an N-terminal polypeptide fragment corresponding to the substrate-binding domain including an N-terminus, and a C-terminal fragment corresponding to the NAD(+)-binding domain. The two peptide fragments were expressed in separate host cells and purified. When both fragments were mixed, the leucine dehydrogenase activity with a specific activity of 1.4% of that of the wild-type enzyme appeared. This suggests that both peptide fragments mutually recognize each other, associate and fold correctly to be catalytically active, although the activity is low. However, the fragmentary form of enzyme produced catalyzed the oxidative deamination of l-leucine, l-isoleucine, and l-valine with broad substrate specificity compared to that of the wild-type enzyme. The fragmentary enzyme retained more than 75% of the initial activity after heating at 50 degrees C for 60 min. The fragmentary enzyme was more stable on heating than separate peptide fragments. These results suggest that the two domains of leucine dehydrogenase probably fold independently, and the two peptide fragments interact and associate with each other to form a functional active site.

Amino Acid Oxidoreductases↗
PubMed2001

Sebaceous gland metaplasia in intraductal papilloma of the breast.

We report here the first case of sebaceous gland metaplasia arising within an intraductal papilloma of the breast of a 70-year-old female. Several lobules and nests composed of clear cells closely resembling sebaceous glands of the skin were discovered within an intraductal papilloma of the breast. Squamous metaplasia was also noted in certain areas of the tumor. Immunohistochemically, the cells of the lobules and nests stained positively for monoclonal antibodies anti-cytokeratin 14 and epithelial membrane antigen. This study confirms a novel type of metaplasia of the breast.

Aged↗
PubMed2001

Mercury pollution in the Tapajos River basin, Amazon: mercury level of head hair and health effects.

There is increasing concern about the potential neurotoxic effects of exposure to methylmercury for the 6 million people living in the Amazon, even in regions situated far away from the gold mines (garimpos), considered to be the major source of mercury pollution. In November 1998, a spot investigation on mercury contamination was conducted in three fishing villages (Barreiras, Rainha, and Sao Luiz do Tapajos) on the Tapajos River, an effluent of the Amazon, situated several hundred kilometers downstream from the gold-mining areas. A total of 132 fishermen and their families volunteered for the current study. As was anticipated, the total mercury levels in the head hair collected from the fishing villages were relatively high (14.1-20.8 ppm on the average) and the number of subjects with a high total mercury level over 10 ppm (the least upper bound of a normal value) was 103 (78.0%) in total, along with various symptoms, thereby suggesting wide mercury contamination in the Tapajos River basin. Moreover, in view of the absence of other diseases (e.g., alcoholism or malaria), a high intake of fish containing a methylmercury level, and high hair mercury levels in addition to the various symptoms such as sensory disturbance (especially glove-and-stocking type, which is characteristic of Minamata disease), tremor, failure in two-point discrimination, and slight balancing failure, several subjects examined were diagnosed with mild Minamata disease. The findings obtained suggest, thus, that the mercury pollution in the Amazon should be crucially observed for head hair mercury level and health in a much broader region.

Adolescent↗
PubMed2001

Chronic cyclosporin nephropathy: long-term effects of cyclosporin on renal allografts.

Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA-associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long-term outcome of renal transplant patients with biopsy-proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long-term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy-four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow-up: the functioning graft group (n = 30) and the graft-loss group (n = 44). There was no significant difference in severity of CAA grade between the functioning and graft-loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA-associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow-up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non-specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long-term CSA treatment.

Adult↗
PubMed2001

Does infiltration of neutrophils in peritubular capillaries indicate humoral rejection? A case displaying a characteristic lesion of a significantly high amount of neutrophils in peritubular capillaries at 1-h graft biopsy during transplant operation.

We present a case report of a 50-yr-old Japanese woman with a significant accumulation of neutrophils in the peritubular capillaries (PTC) and severe acute tubular necrosis (ATN) at 1-h allograft biopsy during transplant operation from cadaver donor after a cardiac death. Significant accumulation of neutrophils in the PTC is usually valuable diagnostically for acute humoral rejection. However, the patient showed no clinical signs of acute rejection. A second graft biopsy performed on the fifth postoperative day (POD) revealed that both infiltration of neutrophils in PTC and ATN lesions were more aggravated. Neither clinical course nor other morphological findings were compatible with humoral rejection. After the third biopsy of POD 27 revealing acute vascular rejection of moderate degree, acute rejection therapy using methylprednisolone pulse therapy and OKT-3 therapy was performed. Consequently, after a period of delayed graft function requiring haemodialysis for approximately 4 wk, graft function was restored and serum creatinine decreased to 2 mg/dL. Later, we were able obtain information from a paired graft from the same donor. Significant accumulation of neutrophils in the PTC similar to our recipient was also noted in a 1-h biopsy specimen of the paired kidney. This confirmed that the accumulation of neutrophils in the PTC noted in two recipients was transmitted from the donor kidney. The pathogenesis and clinical significance of neutrophils in the PTC has been shrouded in mystery.

Biopsy↗