Search PubMed⌕ Search

Biomedical subjects

M Niimi

Publications and source records attributed to M Niimi.

At least 19 recordsLinked to original sources
PubMed2001

Operational tolerance induced by pretreatment with donor dendritic cells under blockade of CD40 pathway.

BACKGROUND: Dendritic cells can mount immune response as competent antigen presenting cells. Recently, it has been reported that immature dendritic cells induce prolongation of allograft survival. However, the ability of mature dendritic cells to induce operational tolerance is unclear. Therefore, in this study, we examined the ability of splenic mature dendritic cells to induce operational tolerance to fully allogeneic antigens using mouse heterotopic heart transplantation model. METHODS: CBA (H2k) mice received i.v. injections with donor splenic dendritic cells or B cells in the absence or presence of monoclonal antibody (mAb) specific for CD40 ligand or CD80/CD86 2 weeks before transplantation of a C57BL/10 (H2b) heart. RESULTS: When donor dendritic cells were injected i.v. 2 weeks before transplantation, rejection response was accelerated compared with that of naive mice [median survival time (MST) = 7 and 8 days, respectively]. However, when CD40 pathway was blocked by anti-CD40 ligand mAb, i.v. injection of donor dendritic cells but not B cells induced indefinite graft survival (MST >100 and 20 days, respectively). Mice treated with anti-CD40 ligand mAb alone rejected their grafts with a MST of 18 days. Intravenous injection of donor dendritic cells and B cells in combination with anti-CD80/CD86 mAbs was less effective to induce graft prolongation (MST = 9.5 and 13 days, respectively). CONCLUSIONS: Therefore, under blockade of CD40 pathway, mature dendritic cells were tolerogens in vivo independent of CD80/86 pathways.

Adoptive Transfer↗
PubMed2001

Endoscopic thyroidectomy by the axillary approach.

Neck surgery has recently become one of the newest fields for the application of endoscopic surgery because the resultant scar is small and inconspicuous. Still, some patients feel even a small scar on the neck is not cosmetically acceptable. We therefore have developed a new technique of endoscopic thyroidectomy by the axillary approach that leaves no scar on the neck at all. When this method is used, the small scar in the axilla is completely covered by the patient's arm in a natural manner. The cosmetic result is excellent, and sensory loss in the neck is negligible because the area of surgical dissection is small. We believe that endoscopic thyroid surgery by the axillary approach will find a role in the treatment of thyroid disease.

Axilla↗
PubMed2001

Histamine production by cultured microglial cells of the mouse.

We previously reported that cells other than mast cells or neurons could synthesize histamine in response to lipopolysaccharide (LPS) or interleukin 1beta in the rat brain. To identify the responsible cells, we examined histidine decarboxylase (HDC) activity and the expression of HDC mRNA in GMI 6-3 mouse microglial cells. Both the activity and mRNA for HDC in GMI 6-3 cells were induced by LPS treatment, and the induction was sensitive to calmodulin-dependent kinase II inhibitor, KN62. These findings indicate that microglia is a third cell type producing histamine in the brain.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Laparoscopic partial or cortical-sparing adrenalectomy by dividing the adrenal central vein.

BACKGROUND: We perform laparoscopic partial adrenalectomy without sectioning the adrenal central vein has been described because it is important to preserve this vein in the remnant adrenal gland in order to maintain its function. In this article, we describe our technique for laparoscopic partial or cortical-sparing adrenalectomy by dividing the adrenal central vein. METHODS: The procedures were performed in four patients with aldosterone-producing adenomas (APA) and two patients with pheochromocytomas. RESULTS: There were no postoperative complications. At follow-up, adrenal 131I-adosterol scintigrams showed that remnant adrenal function had been preserved in all cases. CONCLUSION: Since the vascular bed adjacent to the remnant adrenal gland is integral to the preservation of its function, it is important to perform procedures that do not separate the remnant adrenal gland from the retroperitonium space. Because the operative field is clearly visualized on the high-magnification video monitor, this delicate procedure can be performed with a high degree of accuracy via the laparoscopic approach. We consider this operative technique to be useful for selected cases.

Adrenal Cortex↗
PubMed2001

IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo.

We present evidence that donor-reactive CD4(+) T cells present in mice tolerant to donor alloantigens are phenotypically and functionally heterogeneous. CD4(+) T cells contained within the CD45RB(high) fraction remained capable of mediating graft rejection when transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD45RB(low) CD4(+) and CD25(+)CD4(+) populations failed to induce rejection, but rather, were able to inhibit rejection initiated by naive CD45RB(high) CD4(+) T cells. Analysis of the mechanism of immunoregulation transferred by CD45RB(low) CD4(+) T cells in vivo revealed that it was donor Ag specific and could be inhibited by neutralizing Abs reactive with IL-10, but not IL-4. CD45RB(low) CD4(+) T cells from tolerant mice were also immune suppressive in vitro, as coculture of these cells with naive CD45RB(high) CD4(+) T cells inhibited proliferation and Th1 cytokine production in response to donor alloantigens presented via the indirect pathway. These results demonstrate that alloantigen-specific regulatory T cells contained within the CD45RB(low) CD4(+) T cell population are responsible for the maintenance of tolerance to donor alloantigens in vivo and require IL-10 for functional activity.

Adoptive Transfer↗
PubMed2001

Induction of hyporesponsiveness to fully allogeneic cardiac grafts by intratracheal delivery of alloantigen.

BACKGROUND: Soluble protein delivered through the mucosal surface can induce immunological unresponsiveness. The purpose of this study was to determine if prior exposure to alloantigen via the trachea could modulate the immune response to subsequent cardiac allografts. METHODS: Hearts from C57BL/10(H2b) mice were transplanted into CBA(H2k) recipients. Recipient mice were given donor 1x10(7) splenocytes into the trachea with or without antibody specific for mouse CD80 (1G10) and/or CD86 (GL1) (100 microg each) 7 days before transplantation. RESULTS: All grafts survived in recipients treated with intratracheal delivery of alloantigen for over 35 days (mean survival time [MST], 56 days), whereas naive control mice and mice treated with syngeneic antigen rejected grafts acutely (MST, 8 and 7 days, respectively). Interestingly, when 1G10, GL1, or both of them were combined with the protocol, the majority of grafts were rejected within 21 days after grafting (MST, 7, 15, and 17 days, respectively). CONCLUSION: Intratracheal delivery of alloantigen induced significantly prolonged survival of fully mismatched cardiac allografts and the effect was abrogated by the blockade CD80 and/or CD86 pathway.

Animals↗
PubMed2001

Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle.

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.

Alternative Splicing↗
PubMed2001

Importance of thymus to maintain operational tolerance to fully allogeneic cardiac grafts.

BACKGROUND: The effectiveness of donor-specific blood transfusion (DST) before transplantation has been established. Anti-CD4 monoclonal antibody (anti-CD4) augments the ability of DST to induce indefinite prolongation. Therefore, we investigated the importance of thymus to maintain the unresponsiveness to alloantigens. METHODS: CBA mice were pretreated with 0.25 mL of DST or two doses of anti-CD4 before transplantation of a C57BL/10 heart. Some mice were thymectomized. RESULTS: Naive CBA mice rejected C57BL/10 grafts acutely with a median survival time of 7 days. When mice were pretreated with anti-CD4 plus DST 4 weeks before transplantation, all grafts survived indefinitely (>100 days), whereas mice treated with DST alone or anti-CD4 alone rejected acutely (median survival time, 7 and 12 days, respectively). To investigate the importance of thymus, mice pretreated with anti-CD4 plus DST 4 weeks before transplantation were thymectomized or underwent a sham operation 1 day before grafting. Mice with the sham operation accepted grafts indefinitely, whereas thymectomized mice rejected the majority of the grafts (median survival time, 20 days). CONCLUSIONS: The thymus is important in maintaining the operational tolerance induced by anti-CD4 plus DST 4 weeks before grafting.

Adoptive Transfer↗
PubMed2001

The technique for heterotopic cardiac transplantation in mice: experience of 3000 operations by one surgeon.

INTRODUCTION: The mouse heterotopic fully vascularized cardiac transplantation model has come into widespread use. However, the technique is still difficult. Therefore, simple anastomosis was introduced. METHODS: The donor ascending aorta was sutured end-to-side to the recipient abdominal aorta and the donor pulmonary artery was anastomosed to the recipient inferior vena cava. The main point was only 4 stitches on 1 side between proximal and distal anastomosis of the recipient aorta and inferior vena cava. RESULTS: When beginners tried to perform the same procedure, they were able to complete the first successful procedure after 11 trials and achieved 90% success after 78 operations. SUMMARY: The simple anastomosis is safe and shortens the operation time.

Anastomosis, Surgical↗
PubMed2001

Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft.

Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 x 10(7) SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 microg/dose, 8 and 7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST= 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.

Administration, Oral↗
PubMed2001

A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303.

This phase II trial was performed to evaluate the efficacy of a new granulocyte colony-stimulating factor (G-CSF)-supported multi-agent chemotherapy protocol, LSG15, for aggressive adult T-cell leukaemia-lymphoma (ATL). Ninety-six previously untreated patients with aggressive ATL were enrolled and grouped as: acute type (58), lymphoma type (28) and unfavourable chronic type (10). Therapy consisted of seven cycles of VCAP (vincristine, cyclophosphamide, doxorubicin and prednisone), AMP (doxorubicin, ranimustine and prednisone) and VECP (vindesine, etoposide, carboplatin and prednisone). G-CSF was administered during the intervals between chemotherapy until neutrophil reconstitution was achieved. Eighty-one per cent of the 93 eligible patients responded [95% confidence interval (CI), 71.1-88.1%], with 33 patients obtaining complete response (35.5%) and 42 obtaining partial response (45.2%). The median survival time (MST) after registration was 13 months and the median follow-up duration of the 20 surviving patients was 4.2 years (range 2.8-5.6). Overall survival at 2 years was estimated to be 31.3% (95% CI, 22.0-40.5%). Grade 4 haematological toxicity of neutropenia and thrombocytopenia were observed in 65.3% and 52.6% of the patients respectively, but grade 4 non-haematological toxicity was observed in only one patient. LSG15 is feasible with mild non-haematological toxicity and improved the clinical outcome of ATL patients. MST and overall survival at 2 years were superior to those obtained by our previous trials.

Adult↗
PubMed2001

Clinical significance of tissue blood flow during esophagectomy by laser Doppler flowmetry.

OBJECTIVES: We sought to investigate the effect of tissue blood flow on the incidence of anastomotic leakage during esophagectomy. METHODS: Reconstruction was done with a gastric tube, and all cases involved cervical anastomosis. Tissue blood flow of 43 patients was measured with a laser Doppler flowmeter before emplacement and after anastomosis during surgical intervention. The reconstruction route and tissue blood flow before emplacement and that after anastomosis were analyzed as possible factors influencing anastomotic leakage. RESULTS: Tissue blood flow after anastomosis with leakage was 9.1 +/- 2.0 mL/min per 100 g, and that without leakage was 13.7 +/- 2.9 mL/min per 100 g. Tissue blood flow with leakage was significantly lower than that without leakage (P <.01, unpaired t test). Twenty-one patients had tissue blood flow after anastomosis of greater than 13 mL/min per 100 g, and none of them had leakage, whereas 5 patients had blood flow of less than 10 mL/min per 100 g, and all 5 had leakage. CONCLUSION: Tissue blood flow can be an important and useful indicator of the presence of current anastomotic leakage. Low tissue blood flow after anastomosis may mediate for appropriate surgical or pharmacologic interventions to detect, localize, and counteract leakage.

Anastomosis, Surgical↗
PubMed2001

Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients.

Four Candida albicans isolates, TIMM 3163, TIMM 3164, TIMM 3165 and TIMM 3166, with reduced fluconazole susceptibility were obtained from three AIDS patients in Japan, and the mechanisms of their drug resistance were studied. All isolates showed lower levels of intracellular accumulation of fluconazole than ATCC 10231, a susceptible control strain of C. albicans. Increased amounts of CDR1 and CDR2 mRNA encoding putative ATP binding cassette (ABC) transporters were associated with the azole resistance of all TIMM isolates, apart from TIMM 3164. In addition, increased Cdr1p levels were immunodetected in the cell membrane fractions of all the TIMM strains except for TIMM 3164. Gene amplification was not responsible for CDR1 overexpression and there were no significant differences in the mRNA levels of CDR3 or CDR4 (ABC transporters) in the azole-susceptible and -resistant cells. CaMDR1 (a major facilitator superfamily) gene expression was not observed in any of the resistant isolates or the control strain. These results suggest that energy-dependent drug efflux associated with increased expression of CDR1 and CDR2 is involved in the fluconazole resistance mechanisms in two of the four isolates, TIMM 3165 and TIMM 3166. TIMM 3164 demonstrated energy-dependent drug efflux without overexpression of CDR1-4 or CaMDR1, indicating that some other pump may be operating. Despite showing low levels of drug efflux and overexpression of CDR1 and CDR2, efflux in TIMM 3163 was not energy dependent, suggesting that the expressed Cdr1p non-functional Cdr1p and that other resistance mechanisms may operate in this strain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters.

Analysis of the transport functions of individual Candida albicans plasma membrane drug efflux pumps is hampered by the multitude of endogenous transporters. We have stably expressed C. albicans Cdr1p, the major pump implicated in multiple-drug-resistance phenotypes, from the genomic PDR5 locus in a Saccharomyces cerevisiae mutant (AD1-8u(-)) from which seven major transporters of the ATP-binding cassette (ABC) family have been deleted. High-level expression of Cdr1p, under the control of the S. cerevisiae PDR5 promoter and driven by S. cerevisiae Pdr1p transcriptional regulator mutation pdr1-3, was demonstrated by increased levels of mRNA transcription, increased levels of nucleoside triphosphatase activity, and immunodetection in plasma membrane fractions. S. cerevisiae AD1-8u(-) was hypersensitive to azole antifungals (the MICs at which 80% of cells were inhibited [MIC(80)s] were 0.625 microg/ml for fluconazole, <0.016 microg/ml for ketoconazole, and <0.016 microg/ml for itraconazole), whereas the strain (AD1002) that overexpressed C. albicans Cdr1p was resistant to azoles (MIC(80)s of fluconazole, ketoconazole, and itraconazole, 30, 0.5, and 4 microg/ml, respectively). Drug resistance correlated with energy-dependent drug efflux. AD1002 demonstrated resistance to a variety of structurally unrelated chemicals which are potential drug pump substrates. The controlled overexpression of C. albicans Cdr1p in an S. cerevisiae background deficient in other pumps allows the functional analysis of pumping specificity and mechanisms of a major ABC transporter involved in drug efflux from an important human pathogen.

Acid Anhydride Hydrolases↗