Acute myeloid leukemia with t(11;19)(q23;p13) developing in an adult T-cell leukemia patient treated with combined chemotherapy including etoposide.
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Biomedical subjects
Publications and source records attributed to T Yamada.
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Recent studies suggest that cytotoxic T-lymphocytes expressing p38 mitogen-activated protein kinase (p38MAP kinase) contribute to allograft rejection in clinical heart transplantation. Interleukin-2 (IL-2), a potent T cell mitogen, activates the p38MAP kinase pathway, resulting in phosphorylation of target transcription factors. In this study we investigated the expression of activated p38MAP kinase in intragraft cell infiltrates following rat heterotopic small bowel transplantation and examined the effects of the immunosuppressant FK506 on intragraft expression of activated p38MAP kinase and allograft rejection. Allografts receiving FK506 (0.5 mg/kg per day i. m.) for 7 days as primary anti-rejection therapy had a significant reduction in histopathological evidence of allograft rejection on Day 7, compared to allograft controls. In addition, Western blotting analysis of intragraft cell infiltrates showed a reduction in the expression of activated p38MAP kinase in allografts treated with FK506. We conclude that intragraft cell infiltrate expression of activated p38MAP kinase is an important marker of acute rejection in this animal model of small bowel transplantation, and that FK506 is an effective immunosuppressant, in this situation, that may act in part by preventing the activation of p38MAP kinase.
We report on a case of CD20-positive peripheral T cell lymphoma. The lymphoma cell was positive for CD20 and T cell lineage markers such as cytoplasmic CD3, CD4, and CD5 and had a monoclonal rearrangement of the T cell receptor (TCR) gamma chain gene. The clinical characteristics resembled angioimmunoblastic lymphadenopathy: spontaneous regression of lymphadenopathy and immunological abnormalities such as polyclonal hypergammaglobulinemia, positive results of direct and indirect antiglobulin tests, and a high antinuclear antibody titer. We reviewed seven cases of CD20-positive T cell malignancies including the present case. Three were immature T cell malignancies (acute lymphoblastic leukemia) and four were peripheral T cell malignancies (non-Hodgkin's lymphoma and chronic lymphocytic leukemia). Hepatomegaly and/or splenomegaly were common features. Further cases must be evaluated to understand the clinical significance of the CD20 expression on the surface of T cell malignancies.
Lysosome-associated membrane proteins (LAMPs) are structural glycoproteins located on the lysosomal membrane and are thought to have an important role in protein degradation. Increased lysosomal activity is associated with the formation of rimmed vacuoles, which are observed in various muscle disorders such as inclusion body myositis (IBM) and distal myopathy with rimmed vacuole (DMRV). In the present study, we examined LAMP-1 and LAMP-2 in biopsied muscle specimens from four cases of sporadic IBM and two of DMRV, as well as six of myopathies without rimmed vacuoles. In all cases of IBM and DMRV, immunohistochemistry showed accumulation of LAMPs in the rimmed vacuoles and the subsarcolemmal portion of the vacuolated fibers. Immunoreactivities of LAMPs in the vacuolated fibers were often associated with those of cathepsin D; however, cathepsin D was not expressed on some LAMP-positive fibers. Further, atrophic muscle fibers were sometimes positive for LAMPs expression. These findings were more prominent in LAMP-2 than in LAMP-1. Thus, LAMP-2 may play an important role in the increased protein degradation in diseased muscle fibers. The increased expression of LAMPs in the vacuolated muscle fibers may be associated with the formation of rimmed vacuoles in IBM and DMRV.
A 32-year-old nulligravida was hospitalized because of preterm labor and treated with intravenous ritodrine hydrochloride. After 33 days of therapy, the patient developed a fine maculopapular rash.
UNLABELLED: An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. CONCLUSION: These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.
To enhance bacterial wilt resistance in tobacco expressing a foreign protein, we isolated the bacteriolytic gene from a bacteriophage that infects Ralstonia solanacearum. The bacteriolytic protein of phage P4282 isolated in Tochigi Prefecture was purified from a lysate of R. solanacearum M4S cells infected with the phage, and its bacteriolytic activity was assayed by following the decrease in the turbidity of suspensions of R. solancacearum M4S cells. The molecular weight of the bacteriolytic protein was approximately 71 kDa, and the sequence of the N-terminal 13 amino acids was determined. We used oligonucleotide probes based on this amino acid sequence to isolate the bacteriolytic gene from phage P4282 DNA. This gene of 2061 bp encodes a product of 687 amino acids, whose calaculated molecular weight was 70.12 kDa. The bacteriolytic gene was placed under the control of an inducible promoter. and the plasmid was transformed into Escherichia coli NM522. The soluble proteins extracted from E.coli NM522 cells harboring the plasmid with the bacteriolytic gene showed obvious bacteriolytic activities against several strains of R. solanacearum isolated in various districts in Japan. DNA fragments from five phages, isolated in Niigata, Aomori, Okinawa, Fukushima and Yamaguchi Prefectures, hybridized to the bacteriolytic gene of phage P4282. These observations indicate that the bacteriolytic protein shows nonspecific activity against R. solanacearum strains, and a sequence similar to that of the bacteriolytic gene is conserved in the DNA of other bacteriophages. These results indicate that the generation of transgenic (tobacco) plants expressing the bacteriolytic gene of phage P4282 might result in enhanced resistance to bacterial wilt in tobacco.
We examined mutations in the forkhead transcription factor gene, FOXL2, in three members a Japanese family with autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and in 100 healthy controls. The FOXL2 was analyzed by direct genomic sequencing. A novel 17-bp deletion at nucleotides 1092-1108 in FOXL2 was found in the three affected patients. No mutation was found in any of the 100 healthy controls. The 17-bp deletion in FOXL2 may be involved in the pathogenesis of BPES in Japanese patients.
Hepatocyte growth factor (HGF) plays important roles in tumor development and progression. It is currently thought that the main action of HGF is of a paracrine nature: HGF produced by mesenchymal cells acts on epithelial cells that express its receptor c-MET. In this investigation, we explored the significance of c-MET expression in myofibroblasts, both in culture and in patients with lung adenocarcinoma. We first showed that human myofibroblasts derived from primary lung cancer expressed c-MET mRNA and protein by reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of myofibroblasts was stimulated in a dose-dependent manner by exogenously added recombinant human HGF whereas it was inhibited in a dose-dependent manner by neutralizing antibody to HGF. The addition of HGF in the culture medium stimulated tyrosine phosphorylation of c-MET. The c-MET protein was immunohistochemically detected in myofibroblasts in the invasive area of lung adenocarcinoma. Finally, the prognostic significance of c-MET expression in stromal myofibroblasts was explored in patients with small-sized lung adenocarcinomas. c-MET-positive myofibroblasts were observed in 69 of 131 cases (53%). A significant relationship between myofibroblast c-MET expression and shortened patient survival was observed in a whole cohort of patients including all pathological stages (two-sided P: = 0.0089 by log-rank test) and in patients with stage IA disease (two-sided P: = 0.0019 by log-rank test). These data suggest that the HGF/c-MET system constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This autocrine system may play a role in invasion and metastasis of lung adenocarcinoma.
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From the bark of Pinus strobus infected with pinewood nematode, Bursaphelenchus xylophilus, a stilbenoid 3-O-methyldihydropinosylvin and a flavanone (2S)-pinocembrin were isolated as active principles of inducibly produced antifungal compounds. The structures of the compounds were determined on the basis of spectroscopic analyses. Close investigations of spectroscopic analyses led to the complete assignment of 13C NMR and 1H NMR chemical shifts for the former compound and to the determination of the stereochemistry of the latter compound from P. strobus to be 2S. Furthermore, the distribution and time course accumulation of the identified compounds were investigated. The former compound was demonstrated to be nematocidal and the concentrations of the compound in the inoculated branches were sufficient enough to inactivate the pinewood nematode within one week after inoculation.
Two proteinaceous alpha-amylase inhibitors termed alphaAI-Pa1 and alphaAI-Pa2 were purified from seeds of a cultivated tepary bean (Phaseolus acutifolius A. Gray, cv. PI311897). The two inhibitors differed in their specificity towards alpha-amylases of insect pests such as bruchids, although neither showed any inhibitory activity against alpha-amylases of mammalian, bacterial or fungal origin. AlphaAI-Pa2 resembles two common bean inhibitors, alphaAI-1 and alphaAI-2, in several characteristics such as N-terminal amino acid sequences and oligomeric structure being composed of alpha and beta subunits. In contrast alphaAI-Pa1 is composed of a single glycopolypeptide with a molecular mass of 35 kDa, and its N-terminal amino acid sequence resembled that of seed lectins in tepary bean and common bean. The information on the two tepary bean alpha-amylase inhibitors may be useful not only for providing insight into critical structure for the specificity towards different alpha-amylase enzymes but also for enhancing insect resistance in crops.
BACKGROUND: Primary solitary amyloidoma of the spine is a rare disease characterized by localized deposition of amyloid. To the best of our knowledge, there have been only 14 cases previously reported in the literature. Patients with focal spinal amyloidoma usually have relatively long symptomatic periods preoperatively, ranging from 3 weeks to 6 years (mean: 12 months). Only two reported patients had acute paraplegia. We add a third case of a thoracic spine amyloidoma presenting with acute paraplegia. CASE DESCRIPTION: A 65-year-old man presented with a three-day history of progressive paraplegia and urinary retention. He was found to have severe cord compression at T2 on magnetic resonance imaging. He underwent emergent decompressive laminectomy with instrumentation for spinal stabilization. Histopathology revealed abundant amyloid deposits. A systemic work-up was negative for amyloidosis. The patient showed marked neurological improvement with residual mild spastic gait after 1 year. CONCLUSIONS: Primary spinal amyloidoma with acute paraplegia is rare. One-stage surgery combining prompt decompression and stabilization of the spinal column is mandatory in cases of spinal amyloidoma with acute myelopathy, because primary solitary amyloidoma carries a good prognosis.
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BACKGROUND/AIMS: 8-Hydroxydeoxyguanosine (8-OHdG) is a promutagenic DNA lesion produced by oxygen radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. METHODS: Hepatic expression of 8-OHdG was immunohistochemically investigated in control and diseased human livers. RESULTS: While no positive immunolabeling for 8-OHdG was observed in control livers, 8-OHdG was widely evident in diseased livers. Nuclear expression of 8-OHdG in the hepatocytes and bile duct cells were found in various forms of chronic hepatitis. 8-OHdG-positive hepatocytes were especially abundant in the periportal area with piecemeal necrosis and prominent cell infiltration. The number of positive hepatocytes significantly increased with the progression of severity of chronic hepatitis activity (r(s)=0.68, P<0.05). In alcoholic liver disease, nuclear expression of 8-OHdG was detected in the hepatocytes in the area of alcoholic hepatitis. Regarding primary biliary cirrhosis, 8-OHdG was preferentially detected in the nuclei of injured bile ducts (11 of 12 cases, 91.7%) and occasionally (2 of 12 cases, 16.7%) in the nuclei of hepatocytes around the bile duct lesions. CONCLUSIONS: These results indicate that oxidative DNA damage is common in various forms of chronic liver disease suggesting a possible link between chronic inflammation and hepatocarcinogenesis.
Clone E86 was isolated as cDNA for elicitor-inducible gene from pea epicotyls by differential screening. The deduced amino acid sequence of E86 showed high homology to hypersensitivity-related protein hsr203J in tobacco and also showed significant homologies to the Ser-active hydrolases, such as mammalian hormone-sensitive lipases, bacterial lipases and esterases. E86 polypeptide possesses consensus amino acid sequence motifs (His-Gly) and (Gly-X-Ser-X-Gly) conserved in lipases and esterases and showed esterase degradation of p-nitrophenyl butyrate. Northern blot analysis revealed that the E86-transcript is abundant in roots and stems and was induced by fungal elicitor in pea epicotyls. However, elicitor-induced accumulation of E86 mRNA was significantly inhibited by the fungal suppressor. Furthermore the expression of the genes encoding E86 and phenylalanine ammonia-lyase was induced within 1 h after the inoculation of a nonpathogen, but it was delayed for 5 h by the inoculation of a compatible pathogen. These results suggest that the elicitor-induced Ser-active hydrolase derived from E86 gene might be related to the plant defense responses.
Recently, several substances from among the huge numbers of chemicals used by mankind have been implicated as instigators of disrupted endocrine function and related human health problems. Polystyrene (PS) is one of the most frequently used resins in the world, and the styrene oligomer dissolved out from PS has been designated as a potential trigger of estrogen-like activity in the Wingspread Declaration and the Japan Environment Agency's SPEED98 [JEA (Japan Environment Agency) Strategic Problem on Environmental Endocrine Disruptors '98 (SPEED) '98), http://www.env.go.jp/en/pol/speed98/sp98.html]. In order to assess the endocrine disrupting effect of styrene oligomers, we tested one styrene monomer (SM), three styrene dimers (SDs) and seven styrene trimers (STs), newly isolated from optical isomers, known to dissolve in small amounts from cup noodle containers made of polystyrene by the estrogen receptor binding assay, luciferase reporter gene assay, and human breast cancer cell MCF-7 proliferation assay. In all three tests, none of the SM, SDs and STs showed any significant activity. Accordingly, we concluded that these substances have no estrogenic activity.
OBJECTIVE: Megakaryocytopoiesis was dramatically augmented in human granulocyte colony-stimulating factor transgenic mice (G-Tg) compared to littermates. We examined the characteristics of megakaryocytes and megakaryocyte progenitor cells in these mice. MATERIALS AND METHODS: The numbers of colony-forming unit megakaryocytes (CFU-MK) and megakaryocytes in hematopoietic organs were counted. The megakaryocytes of G-Tg were examined ultrastructurally, and bone marrow transplantation studies using congenic G-Tg (Ly5.2) and C57BL/6 (Ly5.1) were performed. The number of day-14 colony-forming unit spleen (CFU-S) that contained megakaryocytes in [Ly5.1 > G-Tg] and [G-Tg > Ly5.1] mice also was counted. RESULTS: The number of CFU-MK increased markedly in the spleen, bone marrow, and peripheral blood. The number of megakaryocytes in the spleen and bone marrow also were increased in G-Tg mice. Ultrastructural analyses revealed that megakaryocytes in G-Tg mice were immature. Bone marrow transplantation studies of [Ly5.1 > G-Tg] mice resulted in a significantly increased number of megakaryocytes compared to [G-Tg > Ly5.1] mice. The number of day-14 CFU-S that contained megakaryocytes was increased markedly in [Ly5.1 > G-Tg] mice compared to [G-Tg > Ly5.1] mice. In vitro differentiation of megakaryocytes in [Ly5.1 > G-Tg] mice was induced by interleukin-11 and thrombopoietin. CONCLUSION: The results showed that the hematopoietic marrow microenvironment of G-Tg is important in augmenting megakaryocytopoiesis. [Ly5.1 > G-Tg] mice are potentially useful as a source of murine megakaryocytes and their progenitors.