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Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 55 records · Page 3Linked to original sources
PubMed2001

Skin-homing interleukin-4 and -13-producing cells contribute to bullous pemphigoid: remission of disease is associated with increased frequency of interleukin-10-producing cells.

Although evidence is accumulating that type 2 cytokines play a part in the pathogenesis of bullous pemphigoid, little information is available concerning characterization of the cellular source of these cytokines involved in the pathogenesis of bullous pemphigoid. By using multiparameter flow cytometry, we investigated T cells capable of producing interleukin-2, -4, -10, and -13, interferon-gamma, and tumor necrosis factor-alpha and their correlated expression of skin-homing receptor (cutaneous lymphocyte-associated antigen) in peripheral blood and skin blister of patients with bullous pemphigoid. In peripheral blood of bullous pemphigoid patients, significantly increased frequencies of interleukin-4- and interleukin-13-producing cells were found as compared with those of healthy controls, and the majority of these type 2 cells was found in the cutaneous lymphocyte-associated antigen-positive population. The frequency of interferon-gamma-producing cells was also increased as compared with healthy subjects; however, the majority of this subset was found in the cutaneous lymphocyte-associated antigen-negative population. In the skin blister, the frequencies of interleukin-13- and interleukin-4-producing cells were much higher than those in the peripheral blood of bullous pemphigoid, whereas that of interferon-gamma producing cells was significantly lower. Furthermore, in bullous pemphigoid patients after therapy with systemic corticosteroids, the frequency of cutaneous lymphocyte-associated antigen-positive, but not cutaneous lymphocyte-associated antigen-negative, interleukin-13-producing cells was significantly decreased accompanied by an increased frequency of interleukin-10-producing cells, which was associated with clinical improvement. Thus, our results suggest that bullous pemphigoid is a unique organ-specific autoimmune disease characterized by an expansion of skin-homing interleukin-13-producing cells. In addition, corticosteroids may control such type 2 biased inflammatory responses in bullous pemphigoid by promoting the expansion of interleukin-10-producing cells.

Adrenal Cortex Hormones↗
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

Myxoid liposarcoma metastatic to the thoracic epidural space without bone involvement: report of two cases.

Myxoid liposarcoma can frequently metastasize to extrapulmonary sites. We present two cases of myxoid liposarcoma metastatic to the epidural space. Both patients complained of back pain, but plain radiography revealed no abnormality. MR imaging clearly demonstrated metastatic tumors in the epidural space, but no involvement of vertebra. When patients with myxoid liposarcoma complain of back pain, metastasis in the epidural space should be considered even in patients without bone involvement.

Adult↗
PubMed2001

Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease.

The AMPLICOR CMV (qualitative DNA assay by PCR), COBAS AMPLICOR CMV Monitor (quantitative DNA assay by PCR), and antigenemia assay were tested for their ability to diagnose cytomegalovirus (CMV) infection in 115 immunocompromised patients. The AMPLICOR qualitative assay and the antigenemia assay were positive for all nine patients with a clinical diagnosis of CMV disease. The AMPLICOR quantitative assay was negative for one of the nine patients. In 106 patients without CMV disease, the AMPLICOR qualitative test was positive in 22, the quantitative test was positive in 23, and the antigenemia test was positive in 55 patients. The AMPLICOR qualitative and quantitative assays had specificities of 79% and 78% in patients without CMV disease, while that of the antigenemia assay was 48%. Diagnostic efficiencies were 79% for the AMPLICOR qualitative assay, 69% for the AMPLICOR quantitative assay, and 48% for the antigenemia assay. All three tests yielded positive results before, or at the same time as, the onset of CMV disease in most cases, which suggests they can be used to predict disease before the onset of symptoms. During antiviral treatment, test results tended to decrease quantitatively and finally became negative; negative results were followed by remission of symptoms. This suggests that the AMPLICOR quantitative assay and the antigenemia assay could be useful for monitoring therapeutic efficacy. The AMPLICOR qualitative and quantitative assays, as well as the antigenemia assay were considered effective for all of the following: diagnosing CMV disease, predicting the onset of disease, and evaluating the effectiveness of antiviral chemotherapy. The antigenemia assay was at times difficult to perform in the case of severely neutropenic patients, whereas the AMPLICOR assays could be used in such cases.

Antigens, Viral↗
PubMed2001

[Secondary eosinophilia in a patient with hypereosinophilic syndrome after allogeneic bone marrow transplantation from a sibling donor].

A 23-year-old man first visited a local hospital in 1998 because of exertional dyspnea. Peripheral blood examination revealed mild leukocytosis with 82% eosinophils, and he was treated with prednisolone. As the eosinophilia did not improve, he was referred to Tokai University Hospital in March 1999 for further diagnosis and treatment. The patient was diagnosed as having hypereosinophilic syndrome (HES) because of unexplained hypereosinophilia persisting for more than 6 months, resulting in cardiac dysfunction. His disease was progressive in spite of immunosuppressive therapy, interferon-alpha and cytotoxic chemotherapy. Since he had an HLA-identical brother, allogeneic bone marrow transplantation (BMT) was performed in October 1999. After completion of the immunosuppressive therapy on day 79 after BMT, the number of eosinophils gradually increased again. Although we suspected recurrence of the disease, DNA fingerprinting revealed that the peripheral granulocytes were 100% donor type. An increase of interleukin-5 (IL-5) produced by peripheral lymphocytes and a decrease of the Th1/2 ratio suggested that the eosinophilia was related to GVHD. The eosinophilia was eventually controlled by cyclosporin. We conclude that DNA fingerprinting and examination of the IL-5 level and Th1/2 ratio are useful for differentiating between relapse and GVHD in cases of eosinophilia occurring after BMT for HES.

Adult↗
PubMed2001

Acute lethal injury of lung and liver in mice transplanted with ex vivo-expanded CTLs.

Clinical application of cytotoxic T lymphocytes (CTL) induced in vitro is extensively used for the treatment of viral infection and malignant diseases. We produced anti H-2d CTL in vitro from C57BL/6 (B6) splenocytes presensitized with (B6 x DBA/2) F1 (BDF1) splenocytes to establish a model system of CTL therapy. The specificity and cytotoxic activity were high enough (E/T ratio 1:1 = 38.8%) to induce graft versus host reaction. Though the total number of B6 splenocytes decreased by 0.27 during the 4 days of culture, the number of CD8+ lymphocytes increased 1.3-fold. When more than 5 x 10(6) cells of H-2d-reactive CTL were transplanted into BDF1 mice, mice died within 2 days postinduction. This lethal effect was not seen in the mice induced with ConA-stimulated T cells. Histological examination of the lungs and liver revealed massive infiltration of neutrophils in alveoli and the necrosis of hepatocytes. Therefore, this protocol was shown to be effective to produce alloantigen-specific CTLs and applicable to in vitro manipulation such as retrovirus-mediated gene transfer.

Animals↗
PubMed2000

HSNF5/INI1 gene mutations in lymphoid malignancy.

hSNF5/INI1 is one of the components of the SWI/SNF multiprotein complex that is necessary for the transcriptional activation of several genes and functions by altering chromatin structure. This gene has been thought to be one of the tumor suppressor genes (TSGs) because deletions or mutations were reported in malignant rhabdoid tumors and atypical teratoid and rhabdoid tumors. To evaluate the hSNF5/INI1 gene as a TSG in lymphoid malignancies, we performed a mutational analysis in 23 patients with non-Hodgkin lymphoma (NHL), 24 with acute lymphoblastic leukemia (ALL), 24 with multiple myeloma (MM), 24 with adult T-cell lymphoma/leukemia (ATLL), and 19 with lymphoid cell lines, by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis. Nonsense and missense mutations were found in 1 NHL case and 2 cell lines. Mutations from this NHL case proved to be somatic in origin. These data indicated that alterations in the hSNF5/INI1 gene might be involved in the pathogenesis of lymphoid malignancies.

Base Sequence↗
PubMed2000

Ferromagnetic, A-type, and charge-ordered CE-type states in doped manganites using jahn-teller phonons

The two-orbital model for manganites with both noncooperative and cooperative Jahn-Teller phonons is studied at hole density x = 0.5 using Monte Carlo techniques. The phase diagram is obtained by varying the electron-phonon coupling and the t(2g)-spins exchange. The insulating CE-type charge- and orbital-ordered state with the z-axis charge stacking observed in narrow-bandwidth manganites is stabilized in the simulations. Its charge gap Delta(CO) is much larger than the critical temperature k(B)T(CO). Metalliclike A-type and ferromagnetic states are also obtained in the same framework, and the phase boundaries among them have first-order characteristics.

Journal Article↗
PubMed2000

Topological scenario for stripe formation in manganese oxides

The spin-charge-orbital complex structures of manganites are studied using topological concepts. The key quantity is the "winding number" w associated with the Berry-phase connection of an e(g) electron parallel transported through Jahn-Teller centers, along zigzag one-dimensional paths in an antiferromagnetic environment of t(2g) spins. From these concepts, it is shown that the "bi-stripe" and "Wigner-crystal" states observed experimentally have different w's. Predictions for the spin structure of the charge-ordered states for heavily doped manganites are discussed.

Journal Article↗
PubMed2000

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Adenocarcinoma↗
PubMed2000

Collagenous fibroma of the arm: a report of two cases.

A recently proposed addition to fibrous tumors in soft tissue was first described as desmoplastic fibroblastoma and later renamed collagenous fibroma. This tumor is clinically and morphologically distinct and benign. However, only a few series have been reported, and the clinicopathologic features are not widely recognized. We present two cases of collagenous fibroma of the arm. Both patients presented with an enlarging, well-circumscribed and mobile soft tissue mass. Magnetic resonance imaging showed areas of low signal intensity on both T1- and T2-weighted sequences. Needle aspiration cytology revealed nondiagnostic samples because of the low cellularity of the tumors. Each of the resected tumors was composed of low-cellular spindle- to stellate-shaped cells in a fibrous matrix with clear margination. After the marginal excisions, no recurrences were observed. Clinicians should be aware of this entity to prevent overtreatment, because imaging findings and cytologic features are similar to those of desmoid tumor.

Aged↗
PubMed2000

Deep-seated segmental neurofibromatosis without café au lait spots.

Segmental neurofibromatosis is a rare disease characterized by neurofibromas with or without café au lait spots localized to one segment of the body. The majority of reported cases have had cutaneous neurofibromas, and patients with deep involvement have rarely been described. We report on two patients with deep-seated segmental plexiform neurofibromatosis and review the literature. All reviewed cases including the present two had no café au lait spots, axillary freckling, Lisch nodules, family history or malignant progression of disease. Differential diagnoses from neuro-fibromatosis 1 (von Recklinghausen disease) and malignant peripheral nerve sheath tumor are important for genetic counseling and avoiding overtreatment.

Adult↗
PubMed2000

Solitary osseous hemangioma outside the spinal and craniofacial bones.

Bone hemangioma is mainly seen in the skull and spine, and rarely occurs in other bones. We report herein four cases of osseous hemangioma arising in rare sites: In two cases, on a rib; a faintly painful mass in one case located on the scapula; and progressive pain in one case located on the ischium. The tumors presented clinically as incidental lesions on radiographs. All cases had an aggressive appearance, such as defect of the cortex, a soft-tissue mass, and a sunburst-like appearance. Markedly high signal intensity on T2-weighted magnetic resonance images was a characteristic finding. Open biopsy resulted in severe blood loss, but needle biopsy was performed safely under computed tomography guidance. It is important to note that bone hemangiomas may be misdiagnosed as malignant tumors.

Adolescent↗
PubMed2000

Intra-abdominal metastases in musculoskeletal sarcomas.

This study examined the incidence, histological type, clinical symptoms, and prognosis in patients with intra-abdominal metastases of musculoskeletal sarcomas. The medical records of 505 patients with musculoskeletal sarcomas were reviewed for examples of intra-abdominal metastases. The incidence of intra-abdominal metastases (excluding lung) was: 4% in the liver (20 patients), 1.2% in gastrointestine (6 patients), 0.8% in pancreas (4 patients), and 0.8% on the peritoneal surface (4 patients). Patients with a previous hisory of lung metastases and those with high-grade liposarcoma tended to show metastasis in the intra-abdominal organs. Most patients with liver metastasis had no symptoms. Patients with gastrointestinal metastasis had abdominal pain, anemia, and melena. Patients with pancreatic metastasis had diabetes and jaundice. Six patients underwent surgical treatment, and two of them survived for more than 2 years. Metastases within the abdomen must be considered as a possible site for dissemination of musculoskeletal sarcomas, especially in patients with advanced disease and those with liposarcoma.

Adolescent↗
PubMed2000

Extensive generation of human cord blood CD34(+) stem cells from Lin(-)CD34(-) cells in a long-term in vitro system.

Human CD34(-) hematopoietic stem cells (HSCs) have been identified as potential precursors of CD34(+) HSCs by using xenogeneic transplantation systems. However, the properties of CD34(+) cells generated from CD34(-) cells have not been precisely analyzed due to the lack of an in vitro system in which CD34(+) cells are continuously produced from CD34(-) cells. We conducted this study to determine whether CD34(+) cells generated in vitro from CD34(-) cells have long-term multilineage reconstitution abilities. Lin(-)CD34(-) population isolated from human cord blood was cultured in the presence of murine bone marrow stroma cell line, HESS-5, and human cytokines, thrombopoietin, Flk2/Flt3 ligand, stem cell factor, granulocyte colony-stimulating factor, interleukin 3 (IL-3), and IL-6. They were analyzed weekly for their surface markers expressions, colony-forming cells, long-term culture initiating cells (LTC-IC), and SCID repopulating cells (SRC) abilities up to 30 days of culture. In this culture system, more than 10(7) CD34(+) cells can be continuously generated from 10(4) CD34(-) cells over 30 days. These CD34(+) cells produce colony-forming units, LTC-IC, and SRC with multi-lineage differentiation, all of which are characteristic features of hematopoietic stem/progenitor cells. These findings suggest that CD34(-) HSCs have extensive potential for the generation of CD34(+) HSCs in vitro. This system provides a novel and potentially useful procedure to generate CD34(+) cells for clinical transplantation and gene therapy.

Animals↗