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Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

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

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Tumors of peripheral nerves: correlation of symptoms, clinical signs, imaging features, and histologic diagnosis.

OBJECTIVE: To distinguish between benign and malignant tumors in the peripheral nerves. DESIGN AND PATIENTS: The clinical, imaging and histologic findings of 99 benign and 16 malignant tumors in the peripheral nerves were reviewed retrospectively. RESULTS: Preoperative motor weakness was observed in only six of 99 benign tumors and was mild, while slight to severe motor weakness was present in 15 of 16 malignant lesions. Pain at rest was present in five of 99 benign tumors and in 15 of 16 malignant tumors. All benign lesions showed a smooth tumoral margin, while half the malignant lesions showed an invasive margin on CT or MRI. Thirteen of 28 benign lesions on CT and nine of 23 on MRI showed round to geographic central enhancement, but this pattern was not seen in malignant lesions. CONCLUSION: Absence of severe motor weakness and a central enhancement pattern strongly suggest a benign nature, while severe rest pain and invasive tumor margin suggest malignant lesions in peripheral nerve tumors.

Adolescent↗
PubMed1999

Solitary infantile myofibromatosis involving the clavicle.

A rare case of solitary infantile myofibromatosis of bone is reported in the right clavicle of a 15-year-old boy. A radiograph demonstrated an osteolytic lesion with a sharp margin and a sclerotic rim. CT revealed a circumscribed lesion with slight expansion of the cortex. On MRI the lesion appeared isointense to muscle on T1-weighted images, bright on T2-weighted images, and showed marked gadolinium enhancement. The patient was well, without evidence of recurrence or metastasis, 4 years and 5 months following resection.

Adolescent↗
PubMed1999

Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system.

Cell numbers limit the widespread clinical use of cord blood (CB) for gene therapy and marrow replacement in adults; a simple and effective method for ex vivo expansion of CB primitive progenitor cells (PPC) is required. Recently, the combination of thrombopoietin (TPO) and Flk-2/Flt-3 ligand (FL-2) was reported to support slow proliferation of CB-PPC in stroma-free liquid culture. We established a novel culture system in which the murine stromal cell line HESS-5 dramatically supports the rapid expansion of cryopreserved CB-PPC in synergy with TPO/FL-2. Furthermore, while HESS-5 cells directly adhered to human progenitors during culture, the cultured human cells could easily be harvested without contamination by HESS-5 cells. Within 7 days of culture, a 100-fold increase in CD34bright/CD38dim cells was obtained in serum-containing culture. When HESS-5 cells were physically separated from human progenitor cells in the presence of TPO/FL-2, synergy was blocked, suggesting that HESS-5 cells support proliferation of PPC by direct cell-to-cell interaction. The hematopoietic-supportive effects of this xenogeneic coculture system were then assessed in a very short-term (5 days) serum-free culture. Expansion was further enhanced by addition of stem cell factor (SCF) or interleukin-3 (IL-3). As a result, a 50- to 100-fold increase in CD34bright/CD38dim cells was noted. Colony-forming units in culture (CFU-C) and mixed colonies (CFU-GEMM) were enhanced by 10- to 30-fold and 10- to 20-fold, respectively. Moreover, generation of long-term-culture-initiating cells (LTC-IC) from CD34bright/CD38dim cells was amplified by 25-fold. The severe-combined immunodeficient (SCID) mouse-repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. These results indicate that this xenogeneic coculture system, in combination with human cytokines, can rapidly generate PPC from cryopreserved CB.

Animals↗
PubMed1999

Umbilical cord blood T lymphocytes are induced to apoptosis after being allo-primed in vitro.

In this study, the immunity of umbilical cord blood (UCB) T lymphocytes against allo-antigens was investigated by a standard MLC. No significant difference, between the UCB T cells or peripheral blood (PB) mature T cells, was observed in the primary responses (stimulation index (SI), 51.8 +/- 14.8 and 46.5 +/- 15.0, respectively). In contrast, in the secondary response, the SI obtained with the CD4 T cells from UCB decreased dramatically (16.3 +/- 6.4), while it increased with the CD4 T cells from PB (118.5 +/- 21.7). UCB (CD4 and CD8) T cells separately showed much higher frequencies of apoptosis after a primary allo-priming, compared with PB CD4 and CD8 T cells (CD4, UCB 30.5% vs PB 0.8%; CD8, UCB 32% vs PB 1.3%). The higher apoptotic level of the UCB CD4 T cells was confirmed by a second, ELISA-based, Tunel assay (OD values, UCB CD4 1.93 +/- 0.31 vs PB CD4 0.59 0.9; P < 0.01). Those apoptotic steps were not attributed to the amount of cytokine (IL-2, 4 and IFN-gamma) production, which was found to be similar in both cases. In conclusion, UCB lymphocytes are much more likely to be induced to apoptosis by allo-priming than adult lymphocytes. This supports their possible, successful engraftment across barriers of HLA incompatibility.

Adult↗
PubMed1999

Clonality analysis of refractory anemia with ring sideroblasts: simultaneous study of clonality and cytochemistry of bone marrow progenitors.

X chromosome inactivation and polymorphism of the human androgen receptor (HUMARA) gene has been applied for analyzing the clonality of blood cells. In the present study, the clonal relationship was investigated between peripheral blood polymorphonuclear cells (PMNCs) and marrow progenitor cells and the origin of ringed sideroblasts in patients with refractory anemia with ring sideroblasts (RARS) by polymerase chain reaction (PCR) of HUMARA gene. The X-inactivation patterns of circulating PMNCs and T lymphocytes as well as individual granulocyte colonies grown in vitro from bone marrow cells were analyzed. The development of ringed sideroblasts in erythroid colonies by iron staining and their X-inactivation pattern were also examined. All three RARS patients showed monoclonal PMNCs. In granulocyte colonies, however, two different X-inactivation patterns were observed in all patients, indicating that non-clonal progenitor cells remained in the bone marrow. All erythroid colonies consisted of ringed sideroblasts exclusively showed one pattern dominant in those of PMNCs. Our findings suggest that non-clonal progenitor cells persist in some RARS cases, that erythroid progenitors show mosaicism, and that ringed sideroblasts may be derived from an abnormal clone involved in the pathogenesis of this disease.

Aged↗
PubMed1999

Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.

Aged↗
PubMed1999

Brain metastases in musculoskeletal sarcomas.

BACKGROUND: In musculoskeletal sarcomas, brain metastases are rare, but severely affect quality of life. METHODS: All patients with musculoskeletal sarcomas who were treated at our institutions from 1975 to 1997 were reviewed for examples of brain metastasis. RESULTS: Of 480 sarcoma patients, 179 had distant metastases, including 20 patients with brain metastases (4.2%). Alveolar soft part sarcoma (3/4), extraskeletal Ewing's sarcoma (2/8), rhabdomyosarcoma (2/13) and bone Ewing's sarcoma (2/18) tended to metastasize to the brain. All 20 patients had distant or local relapses and 16 of the 20 patients had pulmonary metastases. Three patients underwent surgical treatment and two of them survived over 1 year. Mean survival after diagnosis of brain metastasis was 5.1 months. CONCLUSIONS: Patients with alveolar soft part sarcoma, Ewing's sarcoma, rhabdomyosarcoma and pulmonary metastases have a high risk of brain metastasis.

Adolescent↗
PubMed1999

Long-term follow-up results of adult patients with acute lymphocytic leukemia or lymphoblastic lymphoma treated with short-term, alternating non-cross-resistant chemotherapy: Japan Clinical Oncology Group Study 8702. Lymphoma Study Group.

BACKGROUND: Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL. METHODS: Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. RESULTS: Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy. CONCLUSIONS: A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.

Adolescent↗
PubMed1999

Clonality analysis of granulocytes and T lymphocytes in healthy females by the PCR-based HUMARA method.

Clonality analysis utilizing X-chromosome inactivation has been used in the study of various diseases, including hematological malignancies. The human androgen receptor gene (HUMARA) assay is the newest of such methods, and the majority of the female population can be assessed by this relatively simple procedure. One problem in using these clonality analysis methods, however, is that there may be significant variation in Lyonization in blood cells in normal individuals. To determine the diversity in X-chromosome methylation patterns, which reflect Lyonization, assessed by the HUMARA assay in the supposedly normal population, we analyzed granulocytes and T cells from 97 relatively young (18- to 35-year-old) healthy female volunteers. We found that the methylation patterns in the two HUMARA alleles were distributed even more widely, both in granulocytes and in T cells, than previously reported with other methods. We also found that the deviation of methylation in granulocytes and T cells was well correlated. Thus, we conclude that appropriate controls from the same individuals, such as T cells in the case of stem cell disorders, should always be employed to conclusively determine whether certain cells of hematopoietic origin are clonal.

Adolescent↗
PubMed1999

[A case of chordoid meningioma].

Chordoid meningioma is a very rare variant, especially in adults. We report an adult case of chordoid meningioma. A 52-year-old man was admitted to our hospital due to right hemiparesis. MRI revealed a left temporal convexity mass that showed two structures; the cerebral layer was shown as an isointensity area on T1WI and T2WI, and the dural layer seemed relatively hypointense on T1WI and hyperintense on T2WI. The tumor was well enhanced with gadolinium, especially on the dural side. A left external carotid arteriogram showed tumor stains with feeding vessels from the left middle meningeal artery. The tumor was totally removed via fronto-temporal craniotomy. Histological examination of the surgical specimen revealed two different structural components, meningothelial meningioma on the cerebral side, and chordoid meningioma on the dural side, consisting of clustering spindled cells and partly vacuolated ones in the mucoid stroma. In immunohistochemical examination, tumor cells showed positive staining for vimentin and epithelial membrane antigen (EMA), and negative for cytokeratin. From the above findings, this case was diagnosed as chordoid meningioma in an adult, a very rare variant of meningioma.

Chordoma↗
PubMed1999

Autografting with peripheral blood CD34-positive cells following high-dose chemotherapy against breast cancer.

We report autologous CD34+ cell transplantation performed in 3 cases of recurrent breast cancer. The hematological recovery in these cases was assessed by comparing with that in the previous cases of autologous hematopoietic stem cell transplantation performed with the same high-dose chemotherapy regimen. Patient 1 was a 32-year-old woman with pulmonary and skeletal metastases; patient 2, a 55-year-old woman with pulmonary metastases; and patient 3, a 48-year-old woman with hepatic metastases. On day 1, cyclophosphamide 1000 mg/m2 and epirubicin 130 mg/m2 were administered concurrently with granulocyte colony-stimulating factor, and peripheral blood stem cells were harvested on days 14-16. These stem cells were processed using anti-CD34 monoclonal antibody and an immunomagnetic bead device, Isolex 300i. The high-dose chemotherapy regimen consisted of cyclophosphamide 2000 mg/m2/day, div, and thiotepa 200 mg/m2/day, div on day -5, -4, and -3. The harvested CD34+ cells numbered 3.9 +/- 2.8 x 10(6)/kg (range: 0.73-7.8/10(6)/kg), and the CFU-GM, 8.3 +/- 5.6 x 10(5)/kg (range: 1.2-15.1/10(5)/kg). After the separation, the percent of CD34+ cells was 81.9 +/- 11.6% (range: 65.8-96.4%), the CD34+ cell yield, 71.8 +/- 30.2% (range: 46.0-129.6%), and the CFU-GM yield, 48.9 +/- 9.1% (range: 35.3-62.0%). At the time of transplantation, the number of nucleated cells was 0.55 +/- 0.31 x 10(5)/kg, and that of CFU-GM, 31.2 +/- 17.8 x 10(5)/kg. Comparison of the hematological recovery in these three cases with that in patients receiving an identical high-dose chemotherapy regimen revealed recovery rates significantly faster than in patients having bone marrow transplants, and approximately identical with that in peripheral blood stem cell transplantation cases.

Adult↗
PubMed1998

Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of graft-versus-host reaction-associated myelosuppression.

The influence of graft-versus-host (GVH) reaction on the host hematopoietic cells clinically manifests itself both as adverse reactions in transfusion-associated GVH disease (GVHD) and as a therapeutic graft-versus-leukemia (GVL) effect in either donor lymphocytes transfusion (DLT) or allogeneic bone marrow (BM) transplantation. We examined the effect of GVH reaction on the host hematopoiesis in the murine parent-into-F1 (P1 --> F1) model of GVHD. The systemic transfer of 5 x 10(7) of C57BL/6 (B6) splenocytes into (B6xDBA/2)F1 mice (BDF1), which results in acute GVHD, reduced the peripheral blood cell counts, the number of BM cells, and colony-forming unit-granulocyte macrophage (CFU-GM), whereas the injection of 10(8) of DBA/2 cells into BDF1, which results in chronic GVHD, did not affect hematopoiesis 2 weeks after the transfer. To clarify the mechanism of such myelosuppression, we examined the Fas expression in both hematopoietic progenitor cells as well as whole BM cells. The Fas expressions in each fraction significantly increased in BDF1 mice 2 weeks after the induction of acute GVHD, whereas no such effects were observed in the BDF1 mice with chronic GVHD. Furthermore, when such BM cells were incubated with anti-Fas antibody (Jo2), which induces apoptosis through Fas, the fraction of apoptotic cells increased and the number of CFU-GM decreased significantly. The in vivo administration of neutralizing anti-FasL antibody into BDF1 mice receiving with B6 spleen cells thus protected the host mice from BM failure. These results indicate that the functional expression of Fas on hematopoietic cells plays an essential role in the myelosuppressive effect of GVHD.

Animals↗
PubMed1998

Isolation of novel human cDNA (hGMF-gamma) homologous to Glia Maturation Factor-beta gene.

A novel full-length human cDNA homologous to Glia Maturation Factor-beta (GMF-beta) gene was isolated. Sequence analysis of the entire cDNA revealed an open reading frame of 426 nucleotides with a deduced protein sequence of 142 amino acid residues. The deduced amino acid sequences of its putative product is highly homologous to human GMF-beta (82% identity) and named for GMF-gamma. Northern blot analysis indicated that a message of 0.9 kb long, but not 4.1 kb of GMF-beta, is predominantly expressed in human lung, heart, and placenta.

Amino Acid Sequence↗
PubMed1998

Origin of bone-forming cells in human osteosarcomas transplanted into nude mice--which cells produce bone, human or mouse?

Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific 'Alu' and mouse-specific 'mouse L1 (m-L1)' genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type 1 collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2-7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers.

Alkaline Phosphatase↗