Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 109 records · Page 6Linked to original sources

PubMed1998

Extraskeletal Ewing's sarcoma mimicking traumatic hematoma.

We describe the clinical course of a 16-year-old baseball player with a history of recurrent hematoma of the thigh. The lesion was aspirated percutaneously several times and curetted under the diagnosis of traumatic hematoma. Microscopical examination revealed massive hemorrhage, necrosis, and a small number of Ewing's sarcoma cells. He died of multiple metastases. With recurrent hematoma in the soft tissue, neoplastic lesions should be ruled out.

Adolescent↗

PubMed1998

Characterization and chemosensitivity of two human malignant peripheral nerve sheath tumour cell lines derived from a patient with neurofibromatosis type 1.

Two new cell lines, designated NMS-2 and NMS-2PC, were established in vitro from a malignant peripheral nerve sheath tumour (MPNST) in the right thigh and a retroperitoneal lesion of a 30-year-old man with neurofibromatosis type 1 (NF1). The NMS-2 cell line was derived from the first tumour, and the NMS-2PC cell line from a retroperitoneal metastatic tumour detected 9 months later. Cultured NMS-2 cells showed epithelioid features, while NMS-2PC cells showed fibroblast-like features. However, both cell lines were strongly positive for S-100 protein. The transplanted NMS-2 and NMS-2PC tumours showed the same histological features typical of MPNST. Chromosomal analysis revealed that only the NMS-2 cells had a t (1;2) chromosomal translocation. Chemosensitivity tests demonstrated that NMS-2PC cells were far more sensitive than NMS-2 cells to Adriamycin and etoposide, which had been used clinically. All-trans-retinoic acid induced a morphological change in NMS-2PC cells so that they were no longer fibroblast-like, but epithelioid cells. We believe the epitheloid components in the MPNST were derived from typical spindle cells.

Adult↗

PubMed1998

Unusual relapse of adult T-cell leukemia/lymphoma after spontaneous remission.

A 42-year-old man was diagnosed with acute adult T-cell leukemia/lymphoma (ATL/L). Abnormal peripheral blood cells (45% of white blood cells) (Fig. 1a), hypercalcemia, and systemic lymphadenopathy were observed. Flow cytometric analysis (FCM) using peripheral mononuclear cells (PMNC) revealed that the immunophenotype of tumor cells was CD4+ CD8- CD25+ CD45RA- CD45RO+. Nevertheless, he developed a spontaneous remission 6 months later. At remission, the number of CD4-, CD25-, and CD45RO-positive cells decreased, while CD8- and CD45RA-positive cells increased to normal levels as previously reported by Suzuki et al. [1]. He was then referred to the outpatient clinic where he was periodically evaluated and received no therapy. Because of a serious sense of fullness he was re-admitted 30 months after diagnosis. Physical examination revealed ascites and small lymphadenopathy in the right axilla. Atypical lymphoid cells were not observed on microscopic examination of the blood smear. FCM using PMNC revealed that CD4+ CD25+ cells (3%) were within the normal range. Serum calcium was also within the normal range. Abdominal ultrasound examination showed massive ascites. Paracentesis demonstrated that the ascitic fluid had a high white blood cell count (3.15 x 10(9)/l) with a marked increase in abnormal large cells (Fig. 1b). FCM using mononuclear cells in the fluid revealed that 87.3% of the cells were double-positive for CD4 and CD25. Southern blot analysis of the cells confirmed monoclonal integration of human T-lymphotropic virus type 1 (HTLV-1) proviral DNA. The integrated genome was considered to be identical with that detected at initial presentation (Fig. 2). A diagnosis of relapsed ATL/L, with the same clone as was detected at initial diagnosis, was made. Although he was treated with cytotoxic drugs, he did not respond and he died of renal failure 1 month after relapse. Autopsy revealed nodular invasive lesions at the rectovesical pouch, omentum, diaphragm, and pericardium with peritoneal dissemination.

Adult↗

PubMed1998

Clinical significance of granulocyte colony-stimulating factor (G-CSF) receptor expression in acute myeloid leukemia.

We examined granulocyte colony-stimulating factor (G-CSF) receptor (GR) expression on leukemic cells from 44 adults with newly-diagnosed acute myeloid leukemia (AML). GR expression was higher in female patients. G-CSF was administered to AML patients after initial induction therapy without significant acceleration of leukemia, irrespective of GR expression level. G-CSF administration after initial chemotherapy did not adversely influence clinical outcome of GR-positive patients. However, at first relapse, leukemia regrowth was accelerated in 3 of 15 GR-positive patients who received G-CSF after re-induction. It remains to be determined whether leukemia acceleration due to G-CSF contributes to re-induction failure and if G-CSF therapy is a significant risk in relapsed, GR-positive AML patients.

Acute Disease↗

PubMed1998

Malignant melanoma extending along the ulnar, median, and musculocutaneous nerves: a case report.

We analyzed a case of malignant melanoma that resembled malignant peripheral nerve sheath tumor with marked neurotropism. The subungual tumor in the right ring finger extended along the ulnar nerve for a distance of 30 cm, as well as along the median and musculocutaneous nerves, with lymph nodal metastases. The tumor consisted of interlacing spindle-shaped cells with large nuclei and distinct nucleolei. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein. Five years after forequarter amputation, the patient is alive without disease. Malignant melanoma has the potential of invading several major peripheral nerves and must be distinguished from malignant peripheral nerve sheath tumor, which rarely metastasizes to regional lymph nodes.

Diagnosis, Differential↗

PubMed1998

Truncated c-Myb expression in the human leukemia cell line TK-6.

The c-MYB proto-oncogene encodes a transcription factor which plays an important role in hematopoiesis. We detected truncated c-MYB mRNA (2.0 kb) and c-Myb protein (55 kDa) in the TK-6 cell line, which was established from a patient with chronic myelogenous leukemia in T cell blast crisis. Mutated c-MYB cDNA clone (WTK-1) was isolated from a TK-6 cell cDNA library and sequenced in its entirety. Compared with the wild-type human c-MYB sequence, the WTK-1 sequence diverged at the 3' ends of exons 9. A termination codon was present as the second codon downstream from the point of divergence and was followed by a previously unknown rearranged sequence. The conceptual protein encoded by WTK-1 (Myb(TK-6)) comprises 402 amino acids and lacks the negative regulatory domain of the normal c-Myb, reminiscent of the activated form of Myb protein. Luciferase reporter assay in NIH3T3 cells showed that the expression vector encoding Myb(TK-6) stimulated Myb-regulated mim-1 promoter more effectively than that encoding wild-type human c-Myb, suggesting that Myb(TK-6) is functional as a transcription factor, and thus as a potential transforming protein. Southern blot and mutant allele-specific polymerase chain reaction analyses showed that the same rearrangement of the c-MYB gene in TK-6 was present in late, but not in early, specimens obtained from the patient, indicating that this mutation had been acquired during disease progression.

Adult↗

PubMed1998

A novel variant of B-lymphoid leukemia expressing kappa/lambda light chains.

We studied a patient with an indolent leukemia which behaved similarly to chronic lymphocytic leukemia (CLL). Leukemic cells, however, showed larger cell diameters and lower nuclear/cytoplasmic ratios than typical CLL cells, and contained numerous cytoplasmic vacuoles. The cells also demonstrated some morphologic characteristics of hairy cell leukemia. Furthermore, flow-cytometric analysis demonstrated a distinct population of kappa/lambda double-positive tumor cells, as well as kappa single and lambda single populations. Southern blot analysis confirmed rearranged bands for both light chains with a monoclonal heavy chain rearrangement. Despite a decision not to treat this asymptomatic patient, disease progression was not observed. This case may represent a unique variant of B lymphoid leukemia. Possible mechanisms of abnormal light chain expression are discussed.

Aged↗

PubMed1998

Multiple schwannomas in the peripheral nerves.

Multiple tumours of peripheral nerves are often seen in patients with neurofibromatosis of type 1 or 2. Multiple schwannomas may occur without other manifestations of neurofibromatosis. We have reviewed 12 patients with multiple schwannomas arising from peripheral lesions who did not fulfil the criteria for either type of neurofibromatosis. Four had spinal and one an intracranial lesion in addition to the peripheral tumours. Two patients had one and three café-au-lait spots, respectively, and another had a probable family history. The largest tumours were 45 to 250 mm in size. Three patients had been referred as having von Recklinghausen's disease. The large size of tumours, the difficulties of histological diagnosis on biopsy, and the confusion with neurofibromatosis can lead to overtreatment. Malignant change seldom, if ever, occurs in patients with multiple schwannomas.

Adult↗

PubMed1998

CDKN2 (MTS1/p16INK4A) gene alterations in adult T-cell leukemia/lymphoma.

p16INK4A is a cyclin-dependent kinase inhibitor (CDKI), and regulates the cell cycle negatively. Recently, p16INK4A protein was shown to be encoded by the CDKN2 gene, which is identical to multiple tumor suppressor gene 1 (MTS1) on chromosome 9p21, where genetic alterations occur frequently in many malignant tumors. As the loss of p16INK4A function by genetic alterations leads to inappropriate progression of the cell cycle, the CDKN2 gene has been investigated intensively as a new candidate tumor suppressor gene in many malignant tumors. Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy associated with human T-cell lymphotrophic virus type 1 (HTLV-1). As the development to ATL is believed to require not only HTLV-1 infection but also accumulation of genetic alterations, we investigated the relationship between alterations in the CDKN2 gene and ATL. Alterations in the CDKN2 gene were detected in approximately 15 to 20% of ATL patients. Interestingly, most of the patients with CDKN2 gene alterations had the aggressive form of ATL. The CDKN2 gene appears to be the major tumor suppressor gene on chromosome 9p21, and alteration in this gene may play an important role during late stages in the transformation process induced by HTLV-1.

Cyclin-Dependent Kinase Inhibitor p16↗

PubMed1998

Production and effects of interleukin-6 and other cytokines in patients with non-Hodgkin's lymphoma.

Cytokines are regulatory molecules that are produced by a variety of cell types and are characterized by numerous biologic functions involved in the regulation of the immune system and hematopoiesis. This review summarizes the functions and regulation of cytokines in lymphomas and discusses the effect of a specific cytokine, interleukin-6 (IL-6), in B-cell lymphomas. IL-6 is a multipotent cytokine that can mediate the differentiation of B-cells into immunoglobulin-secreting cells, stimulate the autocrine or paracrine growth of myeloma cells, induce acute-phase proteins in liver cells, and may influence the pathogenesis of several diseases by autocrine or paracrine mechanisms. Patients with non-Hodgkin's lymphoma (NHL) have increased serum concentrations of IL-6; increased IL-6 levels can be associated with the presence of B-symptoms. Data presented in this review indicate that neoplastic cells from patients with NHL contained high concentrations of IL-6. Thus, elevated serum levels of IL-6 appear to originate from the lymphoma cells in patients with B-cell NHL, suggesting that the neoplastic cells may modulate the general status of patients with B-cell NHL. The inhibition or modification of the production of IL-6 in lymphoma cells may lead to a more effective control of the general status of patients with B-cell NHL.

Acute-Phase Reaction↗

PubMed1998

High-risk myelodysplastic syndromes and hypermethylation of the p15Ink4B gene.

Recent studies have elucidated that not only genetic alterations but also epigenetic changes may play an important role in carcinogenesis. In particular, de novo methylation of CpG islands within the promoter region associated with the inactivation of tumor suppressor genes (TSGs) has been demonstrated in various malignancies. Since de novo acute myelogenous leukemia shows frequent inactivation of the p15INK4B gene through the promoter methylation only, we investigated the methylation status of the p15INK4B gene in myelodysplastic syndrome (MDS). In MDS, the p15INK4B gene is also frequently hypermethylated at the promoter region located at the 5'-CpG island of exon 1. Association of frequent and strong methylation with high-risk MDS suggested that promoter methylation of the p15INK4B gene plays an important role as a late event during MDS progression. Since several TSGs and growth regulatory genes, including the p15INK4B gene, may be inactivated through promoter hypermethylation in hematological malignancies, modulation of the methylation status may be considered as a novel treatment modality in MDS.

Animals↗

PubMed1998

Analysis of bax protein in sphingosine-induced apoptosis in the human leukemic cell line TF1 and its bcl-2 transfectants.

Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily induced to undergo apoptotic cell death by a variety of stimuli, including depletion of granulocyte-macrophage colony-stimulating factor (GM-CSF) or exposure to methylmethane sulfonate (MMS) (100 microg/mL), ultraviolet light (15 J/m2), X-ray irradiation (20 Gy), or sphingosine, a sphingolipid breakdown product (5 microM). In contrast, bcl-2 transfectants of TF1 (TF1-bcl2), which we established, were resistant to most of these treatments but remained sensitive to sphingosine. Neither C2- nor C6-ceramide (short-chain ceramide) induced apoptosis in TF1-mock and TF1-bcl2 cells. Sphingosine-induced apoptosis could not be inhibited by fumonisin B1, which can prevent conversion of sphingosine to ceramide, suggesting that sphingosine itself, not ceramide, possesses apoptosis-inducing capability. Western blotting, which revealed a 21-kDa bax protein in untreated cells, revealed the presence of an additional 18-kDa protein in GM-CSF-depleted and MMS- or sphingosine-treated TF1-mock cells. In TF1-bcl2 cells, this protein was not detected after GM-CSF depletion or MMS treatment, but was observed after sphingosine treatment. Immunoprecipitation with anti-bcl2 antibody, followed by immunoblotting with anti-bax antibody, showed that both the 21-kDa bax protein and the 18-kDa protein heterodimerized with bcl-2 protein. These results suggest that sphingosine is a unique reagent for apoptosis and that it can overcome bcl-2 gene expression. Furthermore, induction of 18-kDa bax-related protein may play an important role in apoptosis. Sphingosine, but not ceramide, may prove applicable as a reagent for future cytotoxic drugs used to treat intractable tumors overexpressing bcl-2.

Apoptosis↗

PubMed1998

Continuous and simultaneous cultivation of benthic food diatom Nitzschia sp. and abalone Haliotis sieboldii by using deep seawater.

By using low-temperature, clean, and nutrient-rich properties of deep seawater (DSW; seawater below the euphotic layer), a continuous and simultaneous cultivation system for a benthic food diatom, Nitzschia sp., and juvenile abalone was established. Cell suspension of Nitzschia sp. was added to a bioreactor made of acrylic pipe (7 cm diameter x 50 cm long) containing short vinyl tubes (2 cm diameter x 2 cm long) as substrata. DSW collected from 320 m depth at Muroto City, in Kochi Prefecture, Japan, was supplied to the reactor and incubated under natural light (ca. 6000 lux) with a continuous DSW flow rate of 40 turnovers per hour. After growing enough benthic diatoms in the reactor, juveniles of abalone, Haliotis sieboldii (shell length ca. 10-20 mm) were put into a reactor, and cultivated simultaneously with food diatoms in the continuous flow system. During the four-month incubation, 7-month-old abalone juveniles with a shell length of 12.4 (average) +/-0.2 (SD) mm were grown to 19.4 (+/-1.7) mm in the reactor. Daily growth rates of abalones were 50-110 µm/day. These results indicate that the continuous cultivation system with DSW supports the growth of juvenile abalone without any supply of seaweed until it grows to release size.

Journal Article↗

PubMed1997

Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma.

BACKGROUND: Mutations of the p53 gene are associated with a poor prognosis in several types of cancer. We investigated the prognostic importance of p53 mutations in patients with aggressive B-cell lymphoma. METHODS: We examined the relation between the presence or absence of a detectable p53 mutation in lymphoma cells and the response to chemotherapy and overall survival in 102 previously untreated patients with aggressive B-cell lymphoma. Mutations of the p53 gene were identified by polymerase-chain-reaction-mediated analysis of single-strand conformation polymorphisms and by direct sequencing. RESULTS: Of 102 cases of aggressive B-cell lymphoma, 22 (22 percent) involved p53 mutations. The rate of complete remission was significantly lower in patients with a tumor carrying a p53 mutation (6 of 22 patients, 27 percent) than in those with the wild-type p53 gene (61 of 80 patients, 76 percent) (P<0.001). Overall survival was significantly lower among patients with p53 mutations than among those with the wild-type p53 gene; the Kaplan-Meier estimates of survival at five years were 16 percent and 64 percent, respectively (P<0.001). Multivariate analysis incorporating prognostic factors from the international prognostic index demonstrated that p53 mutations had independent effects on the rates of complete remission and survival. When we categorized patients according to the international prognostic index, we found no effect of p53 mutations in patients in the groups at high-intermediate and high risk. However, these mutations were significantly associated (P< 0.001) with low rates of complete remission (33 percent vs. 91 percent) and survival (27 percent vs. 81 percent at five years) in the groups at low and low-intermediate risk. CONCLUSIONS: Mutations of the p53 gene are associated with a poor prognosis in patients with aggressive B-cell lymphoma.

Aged↗

PubMed1997

Hypermethylation of the p15INK4B gene in myelodysplastic syndromes.

Previous studies have shown that the cyclin-dependent kinase inhibitor (CDKI) genes p15INK4B and p16INK4A are frequently inactivated by genetic alterations in many malignant tumors and that they are candidate tumor-suppressor genes. Although genetic alterations in these genes may be limited to lymphoid malignancies, it has been reported that their inactivation by aberrant methylation of 5' CpG islands may be involved in various hematologic malignancies. In this study, we investigated the p15INK4B and p16INK4A genes to clarify their roles in the pathogenesis of myelodysplastic syndrome (MDS). Southern blotting analysis showed no gross genetic alterations in either of these genes. However, hypermethylation of the 5' CpG island of the p15INK4B gene occurred frequently in patients with MDS (16/32 [50%]). Interestingly, the p15INK4B gene was frequently methylated in patients with high-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-t], and overt leukemia evolved from MDS; 14/18 [78%]) compared with patients with low-risk MDS (refractory anemia [RA] and refractory anemia with ring sideroblast [RARS]; 1/12 [8%]). Furthermore, methylation status of the p15INK4B gene was progressed with the development of MDS in most patients examined. In contrast, none of the MDS patients showed apparent hypermethylation of the p16INK4A gene. These results suggest that hypermethylation of the p15INK4B gene is involved in the pathogenesis of MDS and is one of the important late events during the development of MDS.

Carrier Proteins↗

PubMed1997

Analysis of intramedullary cell density by MRI using the multiple spin-echo technique.

Analysis of the intramedullary cell distribution by magnetic resonance imaging (MRI) using conventional techniques involves subjectively interpreting images and estimating the cell distribution on the basis of signal intensity characteristics. In recent years, attempts have been made to achieve more precise analysis by new techniques, including chemical shift imaging. The multiple spin-echo (MSE) technique offers some advantages over conventional MRI. Since it allows measurement of the transverse magnetization decay curve at 32 or more points, it is capable of separating several tissue components with different relaxation times. In addition, this technique can be used with MRI instruments having a static magnetic field as low as 1.0 Tesla. In the present study, the intramedullary cell density was assessed by MRI using the MSE technique in 4 patients with aplastic anemia (AA), 4 patients with myelodysplastic syndrome (MDS), and 5 normal subjects. The water component of the marrow (with a short relaxation time) and the fat component (with a long relaxation time) were separated from each other by analyzing MR images obtained using the MSE technique, and the signal intensity ratio of the 2 components was calculated. The ratio was significantly higher in the AA group than in the other groups (AA vs. MDS, P = 0.0209, AA vs. normal controls, P = 0.0143). The present technique appears promising for quantitative assessment of the intramedullary cell density.

Adolescent↗

PubMed1997

Enhancement of tumor cell susceptibility to tumor-infiltrating lymphocytes by cisplatin.

Some means of enhancing the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TIL) are required in adoptive immunotherapy. This study was designed to investigate whether or not tumor cell lysis by TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. Autologous tumor cells and established cancer cell lines, including KATO-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the production of TNF alpha from TIL were analyzed. Tumor cells treated with 2 micrograms/ml cisplatin for 12 h in vitro were more susceptible to bulk-cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor cells showed a higher binding ratio to TIL than did non-treated tumor cells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of tumor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhancement of cytotoxic activity by TIL in cisplatin-treated tumor cells was caused by a higher binding ratio to TIL and higher susceptibility to the TNF produced by TIL.

Antigens, Neoplasm↗

PubMed1997

Periosteal chondrosarcoma invading the medullary cavity.

We present a case of periosteal chondrosarcoma of the femur, in which a tumor invaded the medullary cavity and the lesion was clearly demonstrated only on MRI. To the best of our knowledge, there have been no previous reports of an intramedullary lesion caused by periosteal chondrosarcoma demonstrated on MRI.

Adult↗