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M Niimi

Publications and source records attributed to M Niimi.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Assessment of QOL and survival for patients undergoing radical cystectomy or bladder preservation for invasive bladder cancer].

PURPOSE: In this study, we have retrospectively compared patient backgrounds, prognosis and QOL (quality of life) in patients with invasive bladder cancer treated by radical cystectomy or by bladder preservation. PATIENTS AND METHODS: This study enrolled recent 30 cases from each institutions, totally 120 cases from four institutions. All patients were diagnosed with invasive bladder cancer in stage T 2 or T 3, N 0, M 0. The patients planned for preserving the bladder were treated with a combination of intra-arterial chemotherapy and radiation as an induction therapy. The questionnaire used to assess QOL was the EORTC QLQ-C 30 (Japanese-language edition). RESULTS: Radical cystectomy was selected as the initial treatment in 60 cases (the planned radical cystectomy group). Bladder preservation was planned but the presence of residual tumors after induction therapy underwent radical cystectomy in 18 cases (the preservation-radical cystectomy group). Bladder preservation was achieved in 42 cases (the preservation group). In a comparison of background factors, histologically grade 3 tumor and cases with histology other than transitional cell carcinoma, were significantly common in the planned radical cystectomy group. Because this study is not an randomized test, it is difficult to compare the outcomes between the patients treated by radical cystectomy or by bladder preservation. However, it is indicated that the candidates for bladder preservation therapy exist among the patients with T 2 or T 3, N 0, M 0 bladder cancer. Quality of life, as evaluated from global QL and from physical, cognitive, and emotional function, tended to be better in the patients with their bladder, although no difference was noted among the groups with regard to life role or social function. Symptoms such as sleep disturbance and diarrhea were common in the radical cystectomy groups, and financial impact, constipation, appetite loss, and dyspnea also tended to more frequently affect patients in these groups. CONCLUSION: Our results indicate that bladder preservation treatment using an induction therapy is one of option of the treatment for clinically T 2 or T 3, N 0, M 0 bladder cancer. We need a prospective randomized study with a long-term follow-up to elucidate true candidates for this treatment.

Aged↗
PubMed1999

[The critical appraisal of QOL questionnaire for prostate cancer patients].

BACKGROUND: Prostate cancer is a common malignancy that affects Japanese elderly men. Its incidence is increasing, recently, and its treatments are various. The measurement of quality of life (QOL) has become important for the evaluation of and selection of treatments. In Japan, however, there is no standard way of measuring QOL for prostate cancer patients, except the Japanese version of the EORTC QOL questionnaire for prostate cancer patients. We examined the validity and feasibility of this translated EORTC QOL questionnaire for prostate cancer patients. METHODS: Sixty-nine prostate cancer patients who were under treatment in 4 hospitals were selected for this study. We applied the content validity, the factorial validity which was analyzed by the oblique principal component cluster analysis, the internal consistency analyzed by the alpha coefficient of Cronbach, the convergent validity which was used GHQ, IPSS and PS as external measures, and the feasibility. RESULTS: This questionnaire showed good internal consistency, as the alpha coefficient was 0.61 to 0.90 in all domains, except for sex life, which was the lowest. This questionnaire was classified into 7 clusters by the oblique principal component cluster analysis. Consequently, the factorial validity was good, except for items regarding sex life. As domains correlate well with external measures except in sex life, the convergent validity was good. It was suggested that only two items were not acceptable in regard to the content validity and the feasibility, and that the translation into Japanese of 2 items was inadequate. CONCLUSIONS: Our study suggests that the Japanese version of the EORTC QOL questionnaire for prostate cancer patients demands improvement for the practical employment in clinical trials, as there is a problem of translation and feasibility.

Aged↗
PubMed1999

[Development of Japanese version of QOL questionnaire for bladder and prostate cancer patients using FACT-Bl and P: pilot study].

BACKGROUND: Quality of life (QOL) has been known to be a prognostic factor as well as the endpoint of treatment efficacy in many clinical fields. We have begun a US-Japan collaborative project introducing a QOL questionnaire, the FACT (Functional Assessment of Cancer Therapy), into Japan. We report on the translation process, results of the pilot study, and future plans for translating the Japanese version of the FACT subscales, FACT-Bl (for bladder cancer) and FACT-P (for prostate cancer). METHODS: The FACT translation procedure, which is quite rigorous, follows a four-step methodology. After completing the translations, we tested the translated FACT-G (general questionnaire) and subscales for bladder and prostate cancer patients. The questionnaires were tested on 30 outpatients at Tsukuba University Hospital (15 bladder, 15 prostate). The only eligibility requirement to participate in the study was a confirmed diagnosis of cancer of the bladder or prostate. RESULTS AND DISCUSSION: There was satisfactorily high internal consistency of FACT-G of both bladder and prostate cancer patients. FACT-Bl study included patients having undergone radical cystectomy as well as those who had not. Because not all items were answered by all patients, the Cronbach's alpha coefficient for the FACT-Bl subscale could not be computed. Further evaluation of the FACT-Bl concerning the surgical procedures affecting QOL is needed. We are currently planning to make the further refinement of the questionnaire in order to make it more suitable for bladder cancer patients. FACT-P subscale had an alpha coefficient of 0.82 and was determined to be useful in its present form.

Aged↗
PubMed1999

[Leptin].

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Humans↗
PubMed1999

[Current issues and perspectives in Japan Clinical Oncology Group].

Clinical trials can be classified either as "sponsored trials (sponsored by industries)" or "non-sponsored trials (funded by government etc.)". The former is for the application of the commercialization/import of new drugs by the government, and the latter basically seeks to establish and improve the "State of the Art" of medical treatments/prevention in certain disease fields. We present an overview of the Japan Clinical Oncology Group (JCOG), which is a cooperative group funded by government for conducting non-sponsored cancer clinical trials, and the fundamental procedures managed by our JCOG Data Center. The problems and difficulties concerning data management in our trials, our roles and limitations as a non-commercial data coordinating center, future perspectives and issues on local data management are also discussed.

Clinical Protocols↗
PubMed1998

Donor resting B cells induce indefinite prolongation of fully allogeneic cardiac grafts when delivered with anti-immunoglobulin-D monoclonal antibody: evidence for tolerogenicity of donor resting B cells in vivo.

BACKGROUND: Resting B (rB) cells have been shown to induce T-cell anergy in vitro and to prolong the survival of skin and cardiac grafts mismatched for minor histocompatibility antigens. However, rB cells were unable to modulate the rejection response when grafts mismatched for major histocompatibility complex antigens were transplanted. We reasoned that donor antigens, which presented via the indirect pathway by recipient antigen-presenting cells, in particular B cells, might influence the ability of rB cells to induce unresponsiveness. To explore this hypothesis, we used an anti-immunoglobulin (Ig)-D monoclonal antibody (mAb) specific for recipient B cells to deplete these cells, thereby decreasing the potential for indirect presentation in vivo. METHODS: CBA mice were pretreated with 1 x 10(7) donor rB or activated B (aB) cells 7 days before transplantation of a C57BL/10 cardiac graft in the absence or presence of anti-IgD mAb. RESULTS: Naive CBA mice rejected C57BL/10 grafts acutely (median survival time [MST]=8 days). Pretreatment with rB cells alone resulted in a modest prolongation of graft survival (MST=11.5 days). In marked contrast, when rB cells were delivered with anti-IgD mAb, indefinite graft prolongation (MST>100 days) was observed in all recipients. Interestingly, aB cells produced only a small prolongation of graft survival when delivered with anti-IgD mAb (MST=15 days). Recipients treated with anti-IgD mAb alone rejected C57BL/10 cardiac allografts acutely (MST=8 days). CONCLUSION: These data suggest that depletion of recipient B cells in vivo can augment the ability of donor rB cells to induce indefinite prolongation of fully allogeneic cardiac grafts. Thus, IgD+ B cells in the recipient may influence the development of unresponsiveness in vivo.

Animals↗
PubMed1998

The role of the CD40 pathway in alloantigen-induced hyporesponsiveness in vivo.

Resting B (rB) cells are known to be incompetent APCs in vitro, which alone can induce specific unresponsiveness to single minor histocompatibility (miH) Ags and, when combined with CD40 pathway blockade, can induce hyporesponsiveness to MHC molecules in vivo. Here we show that anti-CD40 ligand (CD40L) mAb does not prevent the expression of B7-2 on allogeneic rB cells in vivo but did prolong donor-specific cardiac allograft survival. Moreover, pretreatment with professional APCs combined with anti-CD40L mAb induced hyporesponsiveness to alloantigens in vivo. rB cells from CD40 knockout mice were unable to induce unresponsiveness, while graft prolongation was achieved in CD40L knockout recipients pretreated with wild-type rB cells. These data suggest that CD40-CD40L interactions in the recipient play a critical role in the induction of hyporesponsiveness to alloantigens in vivo and that the effect of the CD40 pathway may be independent of its effect on the B7 costimulatory pathway.

Abatacept↗
PubMed1998

Molecular cloning and gene expression of growth hormone-releasing peptide receptor in rat tissues.

We cloned a fragment of the rat GH-releasing peptide (GHRP) receptor homologue and examined the tissue distribution of GHRP receptor mRNA in rats. Sequence analysis showed that the open reading frame is well conserved between rat and human with 96% identity in a 364-amino acid overlap. By reverse transcription-polymerase chain reaction we detected GHRP receptor mRNAs in the rat brain including the hypothalamus, anterior pituitary, and renal pelvis in twenty-eight tissues tested. Microdissection revealed that GHRP receptor mRNAs were localized predominantly in the arcuate nucleus and ventromedial hypothalamus.

Amino Acid Sequence↗
PubMed1998

Effects of adrenalectomy and glucocorticoid receptor antagonist, RU38486, on pituitary growth hormone-releasing hormone receptor gene expression in rats.

We examined the effects of adrenalectomy and a glucocorticoid receptor antagonist, RU38486, on pituitary GH-releasing hormone (GRH) receptor gene expression in rats. GRH receptor mRNA levels were significantly decreased in adrenalectomized rats and replacement of dexamethasone reversed the decrease to normal. GH secretion was inhibited by adrenalectomy, whereas dexamethasone replacement failed to restore the impaired GH secretion. A high dose of RU38486 had an agonistic effect on GRH receptor mRNA levels. These results suggest that endogenous glucocorticoid is necessary for normal expression of pituitary GRH receptor mRNA in rats.

Adrenalectomy↗
PubMed1998

Immunoregulation by CD4 T cells in the induction of specific immunological unresponsiveness to alloantigens in vivo: evidence for a reduction in the frequency of alloantigen-specific cytotoxic T cells in vitro.

Donor-specific unresponsiveness to allogeneic cardiac allografts in mice can be induced by the combined pretreatment with donor alloantigen and anti-CD4 antibody (anti-CD4+DST). We have investigated whether the induction of unresponsiveness in this model is due to the presence of T cells that regulate immune responsiveness towards the allograft. First, we analysed the functional characteristics of splenocytes from pretreated mice at the time of transplantation. A significant reduction in the frequency of donor specific cytotoxic precursor was found only after the anti-CD4+DST treatment. Next, we designed an in vitro assay to identify the phenotype of the splenocyte population responsible. CD4+ and CD4- fractions were purified from mice treated with anti-CD4+DST or anti-CD4 alone (controls) by cell sorting. Interestingly, only the addition of CD4+ cells from anti-CD4+DST treated mice resulted in a selective reduction and a bimodal distribution in the donor specific CTLp response, indicating the presence of a regulatory population. CD4+ cells from controls did not have this effect. These in vitro findings were substantiated by adoptive transfer experiments in vivo. These data demonstrate that CD4+ cells with the ability to regulate immune responsiveness to a cardiac allograft are present at the time of transplantation following pretreatment with donor alloantigen in combination with anti-CD4.

Adoptive Transfer↗
PubMed1998

Intrathymic administration of B cells induces prolonged survival of fully allogeneic cardiac grafts without prolonged deletion of donor-specific thymocytes.

Intrathymic (IT) injection of alloantigen has been shown to induce unresponsiveness to allografts although the exact mechanisms of tolerance induction remains unclear. C57BL/10 (H2b) cardiac allografts were accepted in C3H/He (H2k) mice pretreated with IT inoculation of donor splenocytes (1 x 10(6)) in combination with a depleting anti-CD4 monoclonal antibody 27 days before cardiac transplantation. To investigate which cell types were responsible for tolerance induction by IT injection of alloantigen, resting B (rB) cells or dendritic cells were used as the thymic inoculum instead of whole splenocytes. IT injection of rB cells induced indefinite graft prolongation in all recipients while only 20% of mice that had received IT injection of dendritic cells accepted grafts for over 100 days. In contrast, IT injection of dendritic cells resulted in significant deletion of donor-specific thymocytes whereas rB cells were relatively ineffective. IT deletion is not essential for the induction of tolerance by IT injection of rB cells; nondeletional mechanisms can be involved.

Animals↗
PubMed1998

Expression of truncated pro-opiomelanocortin gene transcript in human leukemia cell lines.

Although previous studies have suggested that human peripheral blood mononuclear cells (PBMCs) may express pro-opiomelanocortin (POMC) mRNA and synthesize its related peptides, the patho-physiological role of POMC expressed in peripheral cells is not known. In this study, we investigated the POMC gene expression in various types of human leukemia cell lines by Northern blot analysis and the reverse transcribed-polymerase chain reaction (RT-PCR) method. The POMC mRNA was not detected by Northern blot analysis in all cell lines tested except the Jurkat cell line which is derived from T-lymphoblastic leukemia. The POMC mRNA expressed in the Jurkat cells was smaller than that in the human anterior pituitary gland. The RT-PCR method revealed that a truncated-POMC transcript could be detected not only in lymphoblastic leukemia cells but also in erythroid and myeloid cells. Interestingly, two cell lines of monocytic leukemia, J-111 and U937, did not express the truncated-POMC mRNA. Treatment with concanavalin-A stimulated truncated POMC mRNA expression and ACTH-like immunoreactivity in lymphoblastic leukemia cells with T-(Jurkat) and B-(BALL-1) lymphocyte phenotypes. These results confirm that human leukemia cells except for monocytic cells express a truncated-POMC mRNA as well as in the human normal PBMC.

Adrenocorticotropic Hormone↗
PubMed1998

Drug pumping mechanisms in Candida albicans.

Multiple drug resistance is becoming a major problem in the treatment of AIDS patients with oropharyngeal candidosis. Candida albicans strains isolated from candidosis patients who do not respond to fluconazole therapy often show azole drug resistance which usually correlates with the expression of C. albicans CDR1, CDR2 or BENr genes, encoding potential drug efflux pumps. The objective of this study was to develop a yeast secretory vesicle transport assay and use this system to study the pumping function of Cdr1 and Benr. The C. albicans CDR1 and BEN r genes were cloned separately into plasmid pVT101-U, to form plasmids pKY1011 and pKN5001 respectively. Plasmids pVT101-U, pKY1011 and pKN5001 were transformed into Saccharomyces cerevisiae SY1, a sec6-4 mutant with a temperature-sensitive mutation in the secretory pathway. SY1 cells transformed with pKY1011 or pKN5001, were more resistant to fluconazole (MICs in both cases 64 microg/ml) than SY1 cells (MIC 32 microg/ml). In addition, cells transformed with pKY1011 were more resistant to cycloheximide (MIC 16 microg/ml) than SY1 cells (MIC 2 microg/ml). Intact secretory vesicles were isolated from SY1 cells expressing Cdr1 and these vesicles accumulated fluconazole in a time dependent manner. These experiments demonstrated that S. cerevisiae secretory vesicles can be used to examine the mechanism of fluconazole transport by putative C. albicans membrane pumps.

Antifungal Agents↗
PubMed1998

[Data management for clinical trials at the data center].

Data Management is a series of procedures and a research field which assure the quality control in clinical trials. Poorly performed data management can cause various biases in the results of clinical trials. Data management is important especially in cancer clinical trials because of their multiple endpoints, dealing with multiple therapeutic drugs and modalities. Data checks performed by data center staff and composed of manual and computer checks are the main procedures in data management. It is most important that all participants of clinical trials, physicians, nurses, biostatisticians and data managers, understand the data management processes and collaborate with one other from the earliest stage of conducting clinical trials.

Biometry↗
PubMed1998

Nuclear matrix protein, tumor necrosis factor-alpha, and nitrite/nitrate levels in patients with multiple organ dysfunction syndrome.

Nuclear matrix protein (NMP), an indicator of apoptosis, was analyzed in patients with multiple organ dysfunction syndrome (MODS). Blood levels of tumor necrosis factor-alpha (TNF-alpha) and nitrite/nitrate (NOx) were also measured in these patients to determine the involvement of these factors in the production of NMP. Forty-six patients with MODS were studied, 21 (45.7%) of whom died. NMP and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). NOx was measured by the Griess's method. Marshall's multiple organ dysfunction score (MOD score) was used as an indicator of organ failure. The severity of organ failure was assessed by use of the acute physiology and chronic health evaluation II score (APACHE II score). The number of organs that failed was found to be significantly correlated with the NMP level. The NMP level was also correlated significantly with MOD score and APACHE II score, as well as with TNF-alpha and NOx levels. NMP and NOx levels in the group that died significantly exceeded those in the surviving group. Results suggest that apoptosis can occur in the presence of MODS, and that its extent increases as the number of failing organs increases. The results also suggest that TNF-alpha and NO are involved in the induction of apoptosis.

Adolescent↗
PubMed1997

Resting B cells as tolerogens in vivo but only for minor histocompatibility antigens: evidence for activation of resting B cells in vivo.

BACKGROUND: Small, resting B cells (rB cells) express major histocompatibility complex (MHC) class II molecules but not the putative costimulatory molecules, B7-1 (CD80) and B7-2 (CD86); they are classified as nonprofessional antigen-presenting cells. rB cells have been shown to be capable of anergizing T cells in vitro and inducing the prolonged survival of skin grafts mismatched for a single minor histocompatibility (miH) antigen, H-Y. The aim of this study was to investigate ability of rB cells to induce unresponsiveness to multiple miH and MHC antigens. METHODS: Mice were pretreated with 1 x 10(7) donor rB cells 14 days before transplantation of cardiac grafts mismatched for either a single or multiple miH and/or MHC antigens in vivo. RESULTS: rB cells induced indefinite prolongation of cardiac grafts mismatched for H-Y antigen (C57BL/10 male to female). Moreover, 50% of grafts mismatched for multiple miH antigens (C3H to CBA) were accepted indefinitely in recipients treated with donor rB cells. In marked contrast, when grafts were mismatched for either a single MHC class I antigen, Kb (CBK to CBA), or multiple MHC and miH antigens (C57BL/10 to C3H), pretreatment with rB cells did not prolong graft survival. To investigate why rB cells were ineffective tolerogens for grafts mismatched for MHC antigens, we examined the fate of the cells in vivo. We demonstrate that, after intravenous injection of rB cells, expression of B7-2 was induced within 24 hr. CONCLUSIONS: These data suggest that rB cells may be less effective at inducing specific unresponsiveness to MHC antigens because of their rapid activation in vivo.

Animals↗