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Biomedical subjects

K Nakamoto

Publications and source records attributed to K Nakamoto.

At least 19 recordsLinked to original sources
PubMed2006

Resistance of infant leukemia with MLL rearrangement to tumor necrosis factor-related apoptosis-inducing ligand: a possible mechanism for poor sensitivity to antitumor immunity.

Malignant cells generally acquire some immune escape mechanisms for clonal expansion. Immune escape mechanisms also contribute to the failure of graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (allo-SCT). Infant leukemias with mixed-lineage leukemia (MLL) rearrangement have a remarkably short latency, and GVL effect after allo-SCT has not been clearly evidenced in these leukemias. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)- and FasL-mediated cytotoxic pathways play important roles in cytotoxic T-lymphocyte- and natural killer cell-mediated antitumor immunity and optimal GVL activity. We investigated the in vitro sensitivity of MLL-rearranged acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) cells to TRAIL- and FasL-mediated cytotoxicity. Most of cell lines and primary leukemia cells were highly resistant to TRAIL primarily owing to low cell-surface expression of death receptors in ALL and simultaneous expression of decoy receptors in AML. Nearly half of cell lines and majority of primary leukemia cells showed low sensitivity to FasL. These results suggest that resistance to death-inducing ligands, particularly to TRAIL, could be one of the mechanisms for a rapid clonal expansion and a poor sensitivity to the GVL effect in infant leukemias with MLL rearrangement.

Drug Resistance, Neoplasm↗
PubMed2003

Measurement of soluble Fcgamma receptor type IIIa derived from macrophages in plasma: increase in patients with rheumatoid arthritis.

FcgammaRIII (CD16) is found in two alternative forms, a transmembrane FcgammaRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcgammaRIIIb present on neutrophils. Previously, we measured soluble FcgammaRIIIa (sFcgammaRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcgammaRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcgammaRIIIb and FcgammaRIIIa. The level of sFcgammaRIIIa, as well as the total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcgammaRIIIa(M)(phi) in plasma with a newly developed anti-FcgammaRIII MoAb, MKGR14 (mIgM), which recognizes FcgammaRIIIa(M)(phi) specifically. From the recovery of purified sFcgammaRIIIa(M)(phi), the amount of sFcgammaRIIIa(M)(phi) present was about half that of sFcgammaRIIIa(NK), and that of sFcgammaRIIIa was about 50 times lower than that of sFcgammaRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcgammaRIIIa(M)(phi) in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcgammaRIIIa(M)(phi) and sFcgammaRIIIa levels were increased as proportionally as the Lansbury Index. The sFcgammaRIIIa, but not sFcgammaRIIIa(M)(phi) levels, were increased directly proportional to C-reactive protein. sFcgammaRIIIa(M)(phi) may be a novel marker of disease activity in RA.

Adult↗
PubMed2001

Increased expression of a nucleolar Nop5/Sik family member in metastatic melanoma cells: evidence for its role in nucleolar sizing and function.

F10 and BL6 cells of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells can metastasize to lungs after subcutaneous injection. Differences in gene expression between the two cell lines were examined, and a greater expression of the Sik-similar protein (Sik-SP) gene was found in BL6 cells. Structurally, Sik-SP belongs to the nucleolar Nop5/Sik family whose members play central roles in ribosome biogenesis; however, the function of Sik-SP has not been examined. Cytology with green fluorescent protein-fused proteins showed that Sik-SP was localized to the nucleolus. To examine whether Sik-SP is involved in ribosome biogenesis, two parameters were measured: magnitude of ribosomal RNA synthesis per nucleus and magnitude of protein production from the same amount of mRNA of an exogenous luciferase gene. Both values and, in addition, nucleolar size were larger in COS-7 monkey kidney cells overexpressing Sik-SP and BL6 cells than in mock-transfected COS-7 and F10 cells, respectively. Sik-SP seemed to promote ribosome biogenesis in the nucleolus. Furthermore, the expression of Sik-SP seemed to confer a greater cell growth response to serum, because such a response was greater in BL6 cells and F10 cells overexpressing Sik-SP than in untreated and mock-transfected F10 cells. Sik-SP may render melanoma cells more competent to survive through augmenting the activity of nucleolus.

Animals↗
PubMed2001

Structure, expression and chromosome mapping of MLZE, a novel gene which is preferentially expressed in metastatic melanoma cells.

We isolated a novel gene, termed MLZE, from a B16-BL6 cDNA library after subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by fluorescence in situ hybridization) to 8q24.1 - 2, which contains the c-myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze-positive cases was significantly larger in Clark levels III, IV and V melanomas (6 / 11 = 55%) than in Clark levels I and II melanomas (2 / 15 = 13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.

Adult↗
PubMed2000

The response of Parp knockout mice against DNA damaging agents.

Gene-disruption studies involving poly(ADP-ribose) polymerase (Parp) have identified the various roles of Parp in cellular responses to DNA damage. The partial rescue of V[D]J recombination process in SCID/Parp(-/-) double mutant mice indicates the participation of Parp in the repair of DNA strand break. Parp(-/-) mice are more sensitive to the lethal effects of alkylating agents. Parp is also thought to be involved in base-excision repair after DNA damage caused by alkylating agents. On the other hand, resistance of Parp(-/-) mice to DNA damage induced by reactive oxygen species implicates the contribution of Parp to cell death through NAD depletion. Parp(-/-) mice with two different genetic backgrounds also show enhanced sensitivity to the lethal effects of gamma-irradiation. Parp(-/-) mice show more severe villous atrophy of the small intestine compared to the wild-type counterpart in a genetic background of 129Sv/C57BL6. Other forms of enhanced tissue damage have been identified in Parp(-/-) mice with a genetic background of 129Sv/ICR. For example, Parp(-/-) mice exhibit extensive hemorrhage in the glandular stomach and other tissues, such as the testes, after gamma-irradiation. Severe myelosuppression is also observed in both Parp(+/+) and Parp(-/-) mice, but Parp(+/+) mice show extensive extramedullary hematopoiesis in the spleen during the recovery phase of post-irradiation, whereas the spleen of Parp(-/-) mice exhibits severe atrophy with no extramedullary hematopoiesis. The absence of extramedullary hematopoiesis in the spleen is probably the underlying mechanism of hemorrhagic tendency in various tissues of Parp(-/-) mice. These findings suggest that loss of Parp activity could contribute to post-irradiation tissue hemorrhage.

Alkylating Agents↗
PubMed2000

Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers.

The levels of soluble IL-2Ralpha (sIL-2Ralpha) in serum were measured in HTLV-1 carriers and ATL patients in order to evaluate their possible correlation with clinical status. Mean sIL-2R levels in ATL patients were found to be 9704 U/ml for the acute/lymphoma type, 1961 U/ml for the chronic type and 788 U/ml for the smouldering type. The level for asymptomatic HTLV-1 carriers was 475 U/ml, and 165 U/ml for healthy young adult HTLV-1- controls. The serial measurement of sIL-2R in ATL patients, healthy HTLV-1 carriers, and HTLV-1 carriers with diseases other than ATL showed a good correlation between serum levels of sIL-2R and the pathophysiological status of disease. Furthermore, an increase in the sIL-2Ralpha level in serum indicated the exacerbation of HTLV-1 infection and autoimmune diseases. The measurement of sIL-2Ralpha levels is therefore a very useful parameter for determining disease status.

Adult↗
PubMed2000

Annexin VII as a novel marker for invasive phenotype of malignant melanoma.

Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. While examining the genetic difference between the two sublines, we found a marked reduction of annexin VII expression in BL6 cells. In addition, fusion cell clones of both sublines were as poorly metastatic as F10 cells after subcutaneous injection, and contained the annexin VII message as abundantly as F10 cells. Hence, we examined whether the annexin VII expression was correlated with the less malignant phenotype of clinical cases by immunohistochemistry. Immunoreactivities to anti-annexin VII antibody in melanoma cells were evaluated quantitatively by using skin mast cells as an internal positive control. Eighteen patients with malignant melanoma were divided into two groups: lymph node metastasis-negative and positive groups. The ratio of numbers of patients positive versus negative to the antibody was significantly larger in the former than in the latter group. These results not only indicated that annexin VII serves as a marker for less invasive phenotype of malignant melanoma, but also suggested a possible role of annexin VII in tumor suppression.

Adolescent↗
PubMed2000

Synthesis of sialyl Lewis X-polysaccharide conjugates.

Sialyl Lewis X (SLeX) is well known as a ligand of the cell adhesion molecule E-selectin which is specifically expressed at inflammatory lesion sites. We have synthesized several SLeX-polysaccharide conjugates and examined their potential for drug delivery to inflammatory lesions. The AUC (area under the blood concentration-time curve) 0-24 h of SLeX-CMCht (1), SLeX-CMPul (2) and SLeX-DSH (3) at the inflammatory lesion was about 60-, 300-, and 30-fold higher than that of the monovalent SLeX (7), respectively. Moreover, 1 showed 2-fold higher accumulation in the inflammatory lesion than SLN-CMCht (4), and 2 showed 2.5-fold higher accumulation than SLN-CMPul (5).

Animals↗
PubMed2000

[Is more really up?: experimental evidence for orientational metaphor].

The purpose of this study was to provide experimental evidence for orientational metaphors based on the UP-DOWN image schema. Two experiments were conducted to examine the effects of the image schema on the picture-word comparison tasks. In the experiments, subjects were required to judge if the location of kanji-target matched the word printed at the center of a reference square. Under the condition in which the location and the metaphorical orientation of the kanji-target disagree, it took longer time for judgment. These results are interpreted in terms of accessibility and availability of the image schema.

Adult↗
PubMed1999

Isolation and sequence of the GCR3 homologue from Candida albicans by complementation of (delta)gcr3 strain of Saccharomyces cerevisiae.

To study the function of GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, a Candida albicans gene which complements the growth defect of the (delta)gcr3 mutant was isolated. Transformants of this gene also recovered the glycolytic enzyme activities. Its DNA sequencing predicted an 886 amino acid protein with 30.4% identity to the Gcr3p of S. cerevisiae.

Amino Acid Sequence↗
PubMed1999

[Stent intubation for the airway stenosis under PCPS].

Placement of stents for the tracheal or carinal stenosis have a meaning of maintaining the airway. Failure of the stenting causes death. In cases of severe airway stenosis and low pulmonary function, the pulmonary support method should be performed instead of intubation and mechanical ventilation. Generally, PCPS (percutaneous cardio-pulmonary support system) is used as a pulmonary support. This method was very useful to place stents for airway stenosis. We concluded that PCPS was useful in emergency cases, and in cases of severe fixed type airway stenosis and low pulmonary function it had be on stand-by.

Cardiopulmonary Bypass↗
PubMed1998

Tissues exhibiting inhibitory [correction of inhibiory] and repulsive activities during the initial stages of neurite outgrowth from the dorsal root ganglion in the chick embryo.

To elucidate the mechanisms underlying the projection of dorsal root ganglion (DRG) axons into the dorsal root entry zone in the dorsolateral region of the spinal cord, we examined tissue interactions which affect neurite outgrowth from DRG. We cultured explants or dissociated cells of DRG from embryonic day 4 (E4) chick embryos in combination with E3 spinal cord, notochord, and dermomyotome in three-dimensional collagen gels. The ventral spinal cord, notochord, and dermomyotome, which are located close to the initial projection pathway of DRG but do not receive direct innervation, strongly inhibited DRG neurite outgrowth and repelled DRG neurites. These inhibitory/repulsive cues appear diffusible in nature, because this activity was observed in the absence of direct contacts between tissue explants and DRG neurites. Furthermore, in heterochronic cultures, E9 DRG lost its responsiveness to inhibitory/repulsive factors from E3 ventral spinal cord, while retaining responsiveness to E3 notochord and dermomyotome, suggesting that the E3 ventral spinal cord may secrete a different inhibitory/repulsive signal than notochord and dermomyotome. Putative inhibitory/repulsive signals secreted from tissues along the axonal pathway may serve to guide growing DRG axons to the dorsal root entry zone.

Animals↗
PubMed1998

Levels of cyclooxygenase-1 and -2 mRNA expression at various stages of acute gastric injury induced by ischemia-reperfusion in rats.

Recently, the state of cyclooxygenase (COX) mRNA expression has been reported in an acetic acid-induced chronic gastric ulcer model of mice. However, the time course of COX expression during the developmental stage and the subsequent repair process of acute gastric injury is not well understood at present. In this study, we quantitatively investigated the time course of the level of COX-2 and -1 mRNA expression from the developmental stage through the healing stage in ischemia-reperfusion (I-R)-induced acute gastric damage. COX-2 mRNA was expressed at low or undetectable levels in the normal gastric tissues of control rats. The COX-2 expression between 6 and 48 h following I-R was higher than that of the control gastric tissues; the histological findings were erosion during 1-36 h and transitional appearance from erosion to ulcer at 48 h. The maximum expression of COX-2 mRNA was recorded at 24 h (approximately 200-fold elevation). The COX-2 message was very low or undetectable at 72 h (ulcer stage) and at 96 and 120 h (healing stage of ulcer) after I-R. The level of COX-1 mRNA remained stable through all stages of acute gastric damage. These results are potentially useful for understanding the role of COX and evaluating the effects of drugs on expression of COX at various stages of acute gastric injury.

Animals↗
PubMed1998

Thirty-day operative mortality for thoracotomy in lung cancer.

OBJECTIVE: The 30-day operative mortality for thoracotomy in lung cancer is described herein. METHODS: From January 1994 through December 1994, the Japanese Association for Chest Surgery surveyed the number of thoracotomies for lung cancer by operative procedure, age, and operative mortality. The operative mortality was defined as death within 30 days of operation. RESULTS: The total number of operations was 7099. The overall 30-day operative mortality was 1.3%. By operative procedure, the mortalities were 3.2% for pneumonectomy, 1.2% for lobectomy, and 0.8% for a lesser operation, which showed a significant difference between pneumonectomy and lobectomy (p < 0.01). The mortality by age was 0.4% for patients younger than 60 years, 1.3% for those aged 60 to 69, 2.0% for those aged 70 to 79, and 2.2% for those aged 80 or older, which showed significant differences between the less than 60-year and 60- to 69-year-old groups, and between the 60- and 69-year-old and 70- and 79-year-old groups (p < 0.01 and p = 0.047, respectively). Pneumonia and respiratory failure caused most deaths (51.6%). CONCLUSIONS: The operative mortality in Japan for thoracotomy in lung cancer was satisfactorily low. The results of this study on a large population could serve as a standard when discussing the operative outcome of lung cancer.

Age Factors↗
PubMed1998

The role of endogenous acid in the development of acute gastric ulcer induced by ischemia-reperfusion in the rat.

We investigated the role of endogenous gastric acid in the development of gastric ulcer from erosion induced by ischemia-reperfusion of the celiac artery in the rat. A half-hour clamping of the celiac artery (ischemia) caused acute gastric erosions 1 hour after reperfusion and such acute injuries progressed to ulcers 48-72 hours after reperfusion without any necrotizing agents. Gastric acid secretion decreased immediately after ischemia and didn't recover until 12 hours after reperfusion. Intraperitoneal administrations of cimetidine (100 mg/kg, every 12 hours) or omeprazole (30 mg/kg, every 24 hours) were started at 1, 6, or 12 hours after reperfusion. When administrations were started 1 hour after reperfusion, both drugs significantly decreased the total damaged area and prevented the progression of gastric erosions to ulcers. However, administrations started 6 or 12 hours after reperfusion failed to inhibit the total damaged area and to prevent ulcer formation. These results suggest that endogenous gastric acid may play an important role in the progression of gastric erosions to ulcers although ischemia itself reduces acid secretion. Furthermore, treatment with anti-acid-secretory drugs in the early stage of mucosal damage may be important for the prevention of ulcer.

Acute Disease↗
PubMed1998

Effect of tylosin tartrate (Tylan Soluble) on cellular immune responses in chickens.

Although many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance immune function. Tylosin is a macrolide antibiotic approved for the control of mycoplasmosis in poultry. The purpose of this investigation was to determine the effect of tylosin on cellular immune functions in chickens. There was no significant difference in adherent splenocyte chemotaxis between tylosin-treated and untreated (control) chickens. Tylosin increased splenocyte proliferation and splenocyte conditioned medium (CM) proliferative activity above control levels. Removal of adherent splenocytes before preparation of CM caused a reduction in CM proliferative activity. Tylosin also increased antitumor activity of splenocytes. These data are the first to suggest that the macrolide antibiotic, tylosin tartrate, has a modulatory effect in chickens on the immune parameters studied.

Animals↗