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Biomedical subjects

T Endo

Publications and source records attributed to T Endo.

At least 37 records · Page 2Linked to original sources

Distribution and toxicity of mercury in rats after oral administration of mercury-contaminated whale red meat marketed for human consumption.

Toothed-whales and dolphins have been hunted for human consumption in Japan, and their muscles (red meats) are highly contaminated with mercury (Hg). We investigated the distribution and toxicity of Hg in rats after oral administration of Hg-contaminated whale red meat marketed for human consumption in Japan. Rats were orally administered the red meat homogenate for seven consecutive days (0.5 g red meat/kg-bw/day). The red meat administered to rats contained 81microg/g of total mercury (T-Hg) and 13.4 microg/g of methyl mercury (M-Hg). This dose corresponds to the human consumption of 210 g red meat/60 kg-bw/week, exceeding by about 29 times the provisional tolerable weekly intake of M-Hg at 1.6 microg/kg-bw/week set by JECFA [JECFA, 2003. Joint FAO/WHO expert committee on food additives. 61st meeting, Rome]. Twenty-four hours after the last administration, the distribution of T-Hg in rat organs and biochemical parameters in serum were analyzed. The administration of red meat significantly elevated T-Hg concentrations in the liver, kidney, erythrocytes, cerebral cortex and medulla oblongata from the control levels but did not elevate the T-Hg concentration in serum, showing the typical distribution pattern of M-Hg, not of inorganic Hg. The administration slightly but significantly increased GTP activity and P concentration and decreased BUN concentration in serum, although no abnormalities were observed in rat body weight gain and movement during the 7 days. The occasional consumption of red meat from small cetaceans, therefore, could pose a health problem for not only pregnant women but also for the general population.

Administration, Oral↗

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma.

Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5(+) and CD20(+) atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5(+) primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.

Antibodies, Monoclonal↗

Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts.

BACKGROUND AND AIMS: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-Ir on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. METHODS: We assessed the effect of IGF-Ir ligands on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. RESULTS: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed tumorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-1 activation induced by IGF-I, IGF-II, and des(1-3)IGF-I, but not by insulin. IGF-Ir/dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-Ir/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. CONCLUSIONS: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer.

Adenoviridae↗

Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers.

BACKGROUND AND AIMS: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. METHODS: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. RESULTS: cDNA array revealed that matrilysin was maximally upregulated in the metastasis signature identified. Tumour matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between matrilysin and nodal metastasis. CONCLUSIONS: We have provided evidence that tumour matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.

Adenocarcinoma↗

[Pulmonary large cell carcinoma contiguous to bullae with massive bullous hematoma and hemoptysis; with special reference to 20 cases of Japanese reports].

A 50-year-old man with continuous hemosputa and large hematoma of left upper lobe contiguous to bilateral emphysematous bullous disease was admitted for surgery to stop hemorrhage and to resect left lung hematoma and multiple bullae. Bullectomy and neodymium yttrium aluminum garnet (Nd-YAG) laser irradiation to bullae of left upper lobe performed successfully with maximum preserved pulmonary function of it. Pathological examination, however, revealed anaplastic carcinoma inside bulla of S(1+2)c with minimal invasion into adhered parietal pleura (p 3). Left upper lobectomy was carried out with complete mediastinal lymph node dissection (ND 2 b). The final pathological diagnosis was large cell carcinoma of left S(1+2)c with the staging pT3N0M0 and stage II. The patient lives actively in daily life more than 7 years without any recurrence. Clinical analysis of Japanese 20 cases of lung carcinoma with initial signs of hemosputa and/or hemoptysis contiguous to emphysematous bullae elucidate following important facts. Hemosputa and hemoptysis play important role for early finding and diagnosis of lung cancer contiguous to bullous disease, especially in patients of early clinical stage with or without computed tomography (CT) exams and promise to better surgical prognosis and survivals as compared with non hemosputa ones.

Blister↗

Fukutin and alpha-dystroglycanopathies.

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose beta1, 2-N-acetylglucosaminyltransferase (POMGnT1), respectively. Recent studies have revealed that posttranslational modification of alpha-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. All are characterized by hypoglycosylated alpha-dystroglycan. Fukutin's function and the relation with other alpha-dystroglycanopathies are discussed.

Animals↗

Aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies.

Dystroglycan is encoded by a single gene and is cleaved into two proteins, alpha- and beta-dystroglycan, by posttranslational processing. In skeletal muscle, dystroglycan is a component of the dystrophin-glycoprotein complex. alpha-Dystroglycan is an extracellular peripheral membrane glycoprotein that binds to beta-dystroglycan, which is a transmembrane glycoprotein. alpha-Dystroglycan is heavily glycosylated and its sugars have a role in binding to laminin, neurexin and agrin. The main glycan of alpha-dystroglycan was found to be O-mannosylglycan which is a ligand of laminin. We identified and characterized two glycosyltransferases involved in the biosynthesis of O-mannosylglycans. These two enzymes are responsible for congenital muscular dystrophies, muscle-eye-brain disease and Walker-Warburg syndrome. These results indicate that O-mannosylation of alpha-dystroglycan is important in muscle and brain development. This review describes the relation between aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies.

Dystroglycans↗

Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection.

T cells mediating chronic rejection (CR) of human kidney allografts were characterized by comparing them with those mediating acute rejection (AR). Two lines of analysis were performed using biopsy specimens (23 CR and 8 AR). First, the extent of infiltration of CD4+ and CD8+ T cells into allografts was assessed from mRNA expression of CD4 and CD8. The group of CR specimens was not significantly different from the group of AR specimens in terms of the extent of CD4+ and CD8+ T cell infiltration, underlining the importance of the immunological contribution to the progress of CR. Second, Th1/Th2 polarization in infiltrating T cells was investigated by measuring mRNA expression of interferon gamma (IFN-gamma; a Th1 cytokine) and interleukin 4 (IL-4; a Th2 cytokine). IFN-gamma expression was detected in most CR specimens, and was not significantly different between the group of CR specimens and the group of AR specimens. On the other hand, IL-4 expression was detected in only two CR specimens and one AR specimen; from its pathological features, the AR in this last case was concomitant with CR. These results suggest that most cases of CR and of AR are mediated by Th1 mechanisms, although some cases of CR show features of both Th1 and Th2.

Acute Disease↗

Expression of IAP family proteins in colon cancers from patients with different age groups.

Members of the inhibitor of apoptosis protein (IAP) family including survivin, are expressed in many tumors. However, age-related changes in their expression in cancer have not been clarified. Thus, we investigated the expression of mRNA-coding for IAP family proteins in colon cancer samples from young (<70 years of age) and elderly (>70 years) patients by real-time quantitative RT-PCR. Samples were collected from cases with well-differentiated adenocarcinoma or moderately differentiated adenocarcinoma and their adjacent normal epithelial tissue. Well-differentiated adenocarcinoma tended to express higher levels of survivin than normal mucosa, and expression in moderately differentiated adenocarcinoma was significantly greater than in normal mucosa in samples from both groups of patients ( p<0.05, respectively). When samples were compared between the different age groups, the normal mucosa exhibited similar levels of survivin expression. However, samples from older patients showed a significantly higher level of expression than those from younger patients in well and moderately differentiated adenocarcinomas ( p<0.05, respectively). In contrast, the levels of expression of cIAP1, cIAP2, and NAIP in the cancerous tissues were lower than those found in normal mucosa regardless of age. As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group ( p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group ( p<0.05). XIAP expression was similar in normal and cancerous tissues in both the young and elderly groups. These results suggest that the expression of IAP family proteins, especially survivin, is associated with the age-related biological characteristics of colon cancer.

Adenocarcinoma↗

Light therapy for non-seasonal depression.

BACKGROUND: Efficacy of light therapy for non-seasonal depression has been studied without any consensus on its efficacy. OBJECTIVES: To evaluate clinical effects of bright light therapy in comparison to the inactive placebo treatment for non-seasonal depression. SEARCH STRATEGY: We searched the Depression Anxiety & Neurosis Controlled Trials register (CCDANCTR January 2003), comprising the results of searches of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 -), EMBASE (1980 -), CINAHL (1982 -), LILACS (1982 -), National Research Register, PsycINFO/PsycLIT (1974 -), PSYNDEX (1977 -), and SIGLE (1982 - ) using the group search strategy and the following terms: #30 = phototherapy or ("light therapy" or light-therapy). We also sought trials from conference proceedings and references of included papers, and contacted the first author of each study as well as leading researchers in the field. SELECTION CRITERIA: Randomized controlled trials comparing bright light with inactive placebo treatments for non-seasonal depression. DATA COLLECTION AND ANALYSIS: Data were extracted and quality assessment was made independently by two reviewers. The authors were contacted to obtain additional information. MAIN RESULTS: Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. In general, the quality of reporting was poor, and many reviews did not report adverse effects systematically. The treatment response in the bright light group was better than in the control treatment group, but did not reach statistical significance. The result was mainly based on studies of less than 8 days of treatment. The response to bright light was significantly better than to control treatment in high-quality studies (standardized mean difference (SMD) -0.90, 95% confidence interval (CI) -1.50 to -0.31), in studies applying morning light treatment (SMD -0.38, CI -0.62 to -0.14), and in sleep deprivation responders (SMD -1.02, CI -1.60 to -0.45). Hypomania was more common in the bright light group compared to the control treatment group (risk ratio 4.91, CI 1.66 to 14.46, number needed to harm 8, CI 5 to 20). Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. Treatment REVIEWERS' CONCLUSIONS: For patients suffering from non-seasonal depression, bright light therapy offers modest though promising antidepressive efficacy, especially when administered during the first week of treatment, in the morning, and as an adjunctive treatment to sleep deprivation responders. Hypomania as a potential adverse effect needs to be considered. Due to limited data and heterogeneity of studies these results need to be interpreted with caution.

Depression↗

Localized relapse in bone marrow of extremities after allogeneic stem cell transplantation for acute lymphoblastic leukemia.

We report a patient with a relapsed in bone marrow of extremities after allogeneic peripheral blood stem cell transplantation for acute lymphoblastic leukemia (ALL). The patient complained of pain in the right upper arm and left leg 15 months after transplantation. Magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal findings in bone marrow of upper and lower extremities. There were no findings of relapse in aspirates from the sternum and iliac bone marrow. Biopsy specimen from the iliac bone marrow showed normocellular marrow without leukemic cells. Biopsy specimen from the right humerus revealed marked leukemic cell infiltration in the bone marrow. This is apparently the first case of localized relapse of ALL in bone marrow of extremities. Physicians should be aware of unusual relapse sites of leukemia after allogeneic stem cell transplantation. MRI and FDG-PET may be of value in detecting this type of relapse.

Adult↗

Contamination by mercury and cadmium in the cetacean products from Japanese market.

Cetaceans hunted coastally in Japan include several species of odontocete (dolphins, porpoises and beaked whales), and fresh and frozen red meat and blubber, as well as boiled internal organs, such as liver, lung, kidney and small intestine, are still sold for human consumption. Furthermore, red meat and blubber products originating from mysticete minke whales caught in the Antarctic and Northern Pacific are also sold for human consumption. We surveyed mercury and cadmium contamination levels in boiled liver, lung, kidney and red meat products being marketed in Japanese retail outlets. We also analyzed the DNA of these products to obtain information concerning gender and species. Total mercury (T-Hg) and methyl mercury (M-Hg) contamination levels in all the cetacean products were markedly higher in odontocete species than in mysticete species, and slightly higher in females than in males. T-Hg contamination in the organs was seen in the following order: boiled liver>boiled kidney=boiled lung>red meat. In particular, T-Hg concentrations in the boiled liver were high enough to cause acute intoxication even from a single ingestion: the mean +/-SD (range) of T-Hg was 388+/-543 (0.12-1980) microg/wetg. In contrast, although M-Hg contamination in the liver was not markedly higher than that in other organs, M-Hg contamination was in the following order: boiled liver>odontocete red meat>boiled kidney>boiled lung. The contamination levels of T-Hg and M-Hg in odontocete red meat, the most popular whale product, were 8.94+/-13.3 and 5.44+/-5.72 microg/wetg, respectively. These averages exceeded the provisional permitted levels of T-Hg (0.4 microg/wetg) and M-Hg (0.3 microg/wetg) in marine foods set by the Japanese Ministry of Health, Labor and Welfare by 22 and 18 times, respectively, suggesting the possibility of chronic intoxication by T-Hg and M-Hg with frequent consumption of odontocete red meat. Cadmium contamination levels in boiled liver, kidney and lung were 8.59+/-12.0, 10.4+/-8.6 and 1.66+/-1.27 (microg/wetg), respectively.

Animals↗

Clonality analysis of T cells mediating acute and chronic rejection in kidney allografts.

The clonality of T-cell populations mediating acute and chronic rejection (AR and CR, respectively) of kidney allografts was ascertained by investigating the diversity of TCRBV genes expressed by allograft-infiltrating T cells. Both oligoclonality and polyclonality cases were found in biopsy specimens of AR as well as CR. These results indicated that the T-cell clonality in each specimen did not correlate directly with the mode of rejection. When AR and CR specimens were compared, however, the CR specimen group was significantly more polyclonal (or less oligoclonal) than the AR group. This result may reflect the higher chance of epitope spreading in the more slowly progressing CR than in AR.

Clone Cells↗

Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus.

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Animals↗

Peripheral blood stem cell mobilization following CHOP plus rituximab therapy combined with G-CSF in patients with B-cell non-Hodgkin's lymphoma.

We mobilized peripheral blood stem cells (PBSC) following CHOP plus rituximab (CHOP-R) therapy, and compared with the findings following CHOP therapy without rituximab. All patients were given G-CSF starting from day 11 after CHOP therapy. Patients in the CHOP-R group (n=8) were given rituximab on day 12. Target CD34(+) cells number was collected in a single leukapheresis on day 14, from all the eight patients in the CHOP-R group. PBSC mobilization kinetics, CD34(+) cells yield and colony-forming ability in the graft collection, toxicity during mobilization, and engraftment after transplantation of CHOP-R group were not significantly different from those in the CHOP group (n=8). In all patients given CHOP-R therapy, CD20(+) cells and immunoglobulin heavy chain (IgH) rearrangement in the graft collection were undetectable by flow-cytometric analysis and Southern blot analysis, respectively, but with PCR analysis two of eight grafts were positive for IgH rearrangement. While further studies are needed to evaluate the efficacy of purging and the outcome of patients undergoing autologous transplantation, CHOP-R therapy can be safely and effectively used in the mobilization phase of PBSC collection, without excess clinical toxicity or deleterious effect on PBSC mobilization kinetics or engraftment time.

Adult↗

A preliminary analysis of the balance between Th1 and Th2 cells after CD34+ cell-selected autologous PBSC transplantation.

BACKGROUND: CD34+ cell-selected autologous PBSC transplantation (CD34+ APBSCT) is a procedure used for the treatment of patients with malignant disease that is intended to eliminate residual tumor cells from autologous grafts. However, frequent infectious complications after CD34+ APBSCT can occur. A delay of recovery of the absolute number of CD4+ T cells after transplantation was reported to be one disadvantageous factor. As data on T-cell function after CD34+ APBSCT are scanty, we analyzed changes in T-helper cell 1 (Th1) and T-helper cell 2 (Th2) after CD34+ APBSCT to evaluate immune reconstitution. METHODS: Twelve patients underwent APBSCT (CD34+APBSCT group, n=4, and unselected APBSCT, n=8). Peripheral blood (PB) samples were obtained at 2, 4, 8, 12 and 16 weeks after the transplantation. The dynamics of the Th1 and Th2 were analyzed at a single-cell level, using flow cytometry. RESULTS: In the CD34+ APBSCT group, not only the absolute count of CD4+ T cells but also the proportion of Th1 cells in CD4+ T cells and the ratio of Th1 to Th2 after transplantation were significantly decreased at 2 and 4 weeks after transplantation compared with findings in the unselected APBSCT group. DISCUSSION: We suggest that higher rates of infectious complications after CD34+ APBSCT may be due to the inability of residual T cells from the CD34+ cell selection to generate mature T cells that function adequately against infection. Although further study would be required, our preliminary data provide some information on the immune reconstitution after CD34+ APBSCT and differentiation of T lymphocytes into Th1 and Th2 in vivo.

Adult↗