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Biomedical subjects

E Ikeda

Publications and source records attributed to E Ikeda.

At least 73 records · Page 4Linked to original sources
PubMed1996

HTLV-I uveitis.

Human T-cell lymphotropic virus type I (HTLV-I) is known to cause adult T-cell leukemia/T-cell lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recent seroepidemiologic, clinical, and virologic studies indicate that the virus is also related to a certain type of uveitis, which has been classified as uveitis without defined etiologies or idiopathic uveitis. According to the seroepidemiologic survey, the seroprevalence of HTLV-I in patients with idiopathic uveitis was significantly higher than that of two control groups, that is, patients with uveitis with defined etiologies and patients with nonuveitic ocular diseases. Clinically, the uveitis seen in HTLV-I carriers is characterized by moderate to severe cellular infiltration in the eye and by moderate retinal vasculitis, and the intraocular inflammation responds well to corticosteroid therapy. Interestingly, 25% of female patients with the disease had a previous history of Graves disease with hyperthyroidisms. The following virologic, molecular biologic findings suggest that cytokines produced by HTLV-I-infected T cells in the eye play the central role in the pathogenic mechanisms of the uveitis: (a) the virus load in the peripheral blood monocytes analyzed by the quantitative polymerase chain reaction methods was significantly greater in patients with the uveitis than in asymptomatic carriers, (b) the proviral DNA of HTLV-I and the gene expression of the virus at the mRNA level was detected in the infiltrating cells from the eyes of the patients, (c) the virus particles were detected by electron-microscopic examination in the T-cell clones established from the intraocular fluid of the patients, and (d) the HTLV-I-infected T cells produced a variety of cytokines without any stimuli, such as interleukin (IL)-1 alpha, IL-2, IL-3, IL-6, IL-8, IL-10, tumor necrosis factor alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Based on the seroepidemiologic, clinical, and virologic data, the uveitis seen in HTLV-I carriers is considered to be a distinct clinical entity related to HTLV-I infection, and the disease is designated as HTLV-I uveitis.

Adolescent↗
PubMed1996

Loss or somatic mutations of hMSH2 occur in hereditary nonpolyposis colorectal cancers with hMSH2 germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2. To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2-related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.

Alleles↗
PubMed1996

[Optimal dosage of UFT + MMC combination chemotherapy for advanced colorectal cancer--phase I/II study of combination chemotherapy of MMC with 2-week intervals and intermittent UFT administration--Study Group of UFTM Therapy for Advanced Colorectal Cancer].

A combined phase I/II study (UFTM) of tegafururacil (UFT) and mitomycin C (MMC) was performed to find the optimal dosage for advanced colorectal cancer. The study consisted of two parts. The first part confirmed the safety of UFTM and determined the administered doses. The second part evaluated the clinical response of UFTM. Based on the first part, the dosage regimen in the second part was established as follows; the treatment course consisted of 4 weeks and a bolus dose of MMC 6 mg/m2 was given every 2 weeks with daily oral UFT 400 mg/m2 for 5 consecutive days followed by 2 drug-free days; MMC was not given in the third course, and the treatment cycle of the above-mentioned 3 courses was repeated thereafter. In the second part, 26 of 28 patients could be evaluated for toxicity. Grade 3 or 4 toxicities were: anorexia 2, nausea and vomiting 1, leukopenia 1, and 2 cases of thrombocytopenia. The clinical responses of UFTM showed 1 CR and 4 PR in the 21 patients who could be evaluated for response (23.8%). The response rate was 38.5% (5/13) in patients naive to chemotherapy. UFTM can be performed effectively at outpatient clinics as long-term chemotherapy.

Adolescent↗
PubMed1995

Monosomy of chromosome 18 detected by fluorescence in situ hybridization in colorectal tumors.

BACKGROUND: At least two different evolutional pathways of colorectal cancer, namely the adenoma-carcinoma sequence and de novo carcinogenesis, have been indicated. However, whether there is a difference between them in affected chromosomes and genes has not yet been elucidated. Chromosomal examination is expected to provide a clue to an answer to this question. In this study, the relation of aberrations in chromosome 18 to type of colorectal cancer was examined. METHODS: Numeric aberrations in chromosome 18 were investigated in 71 colorectal tumors by means of fluorescence in situ hybridization, using an alphoid satellite DNA probe specific for the pericentromeric region on chromosome 18. RESULTS: The loss of one chromosome 18 was found in 33% (6 of 18) of patients with early cancer, excluding those with cancer in an adenoma. The loss was frequent in early colorectal carcinomas without foci of adenoma (four of six patients, 67%), whereas monosomy 18 was not significant in those with foci of adenoma except for patients with a hereditary background. Specimens exhibiting monosomy 18 were macroscopically classified as flat lesions, but the converse was not true. No adenoma showed monosomy 18. It was encountered in 44% of nine cancers with invasion to the muscularis propria. However, no significant subpopulation of monosomy 18 was present in cancers penetrating through the serosa or adventitia in which polysomic populations were often identified alternatively. Furthermore, tetrasomy for this chromosome was exclusive in these advanced cancers. CONCLUSIONS: The loss of chromosome 18 is closely related to colorectal cancers without foci of adenoma.

Adenoma↗
PubMed1995

Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells.

Vascular endothelial growth factor (VEGF) is an endothelial specific angiogenic mitogen secreted from various cell types including tumor cells. Increasing evidence suggests that VEGF is a major regulator of physiological and pathological angiogenesis, and the VEGF/VEGF receptor system has been shown to be necessary for glioma angiogenesis. Hypoxia seems to play a critical role in the induction of VEGF expression during glioma progression. C6 glioma cells provide an in vivo glioma model for the study of tumor angiogenesis, and the expression of VEGF in C6 cells has been shown to be up-regulated by hypoxia in vitro. However, little is known about the molecular mechanism of hypoxic induction of VEGF. Here, we demonstrate that hypoxic induction of VEGF in C6 cells is due to both transcriptional activation and increased stability of mRNA. Nuclear run-on assays revealed a fast and lasting transcriptional activation, whereas the determination of mRNA half-life showed a slower increase of mRNA stability during hypoxia. Reporter gene studies revealed that hypoxia responsive transcription-activating elements were present in the 5'-flanking region of the VEGF gene. These results suggested that several distinct molecular mechanisms were involved in hypoxia-induced gene expression and were activated in a biphasic manner.

Animals↗
PubMed1995

[A case of traumatic diaphragmatic hernia accompanied with rupture of pericardium].

We experienced a case of left traumatic diaphragamatic hernia accompanied with rupture of pericardium after blunt trauma by traffic accident. A 55-year-old man who had suffered blunt chest and upper abdominal trauma because of smash of two cars when he had been turning to right in the corner was admitted to our hospital. On arrival at the hospital, the patient complained severe dyspnea that reduced by lying on his right. Another position couldn't be taken because of deterioration of dyspnea. Chest X-ray showed disappeared left diaphragmatic line and abnormal transparent mass that suggest alimentary canal in the left intrapleural space. Cardiac ultrasonography showed abnormal tubular mass close to the left side of mediastinum that deviated to right. The patient was diagnosed as traumatic diaphragmatic hernia and emergency operation was performed. Left diaphragma was lacerated sagitally toward its top for about 12 cm in length. Left pleuropericardium was seen to be lacerated longitudinally for about 8 cm in length in front of the phrenic nerve intraoperatively. Both lacerations were closed by direct suture. The patient discharged on the 37th postoperative day without phrenic nerve palsy. At making diagnosis of patient with chest and abdominal trauma, injure of diaphragma and/or pericardium also must be considered. If it is possible, operation must be performed without hesitation in order to get good prognosis.

Accidents, Traffic↗
PubMed1994

Yge1p, a eukaryotic Grp-E homolog, is localized in the mitochondrial matrix and interacts with mitochondrial Hsp70.

Yeast Yge1p, the gene product of YGE1, is a eukaryotic GrpE homolog found recently (Ikeda et al., 1994). We have revealed here that Yge1p is a soluble protein in the mitochondrial matrix. Depletion of Yge1p in yeast cells resulted in accumulation of the precursor of F1-ATPase beta subunit in vivo, suggesting that Yge1p is involved in protein import into mitochondria. Overexpression of Yge1p in the temperature-sensitive mutant strains of mitochondrial hsp70, Ssc1p, caused hypersensitivity to temperature for cell growth, suggesting a genetic interaction between the YGE1 and SSC1 genes. A physical interaction between Yge1p and Ssc1p was directly demonstrated by co-immunoprecipitation of Ssc1p by the anti-Yge1p antibodies. We propose that Yge1p functions in cooperation with Ssc1p in a similar manner as bacterial GrpE with DnaK.

Bacterial Proteins↗
PubMed1994

YGE1 is a yeast homologue of Escherichia coli grpE and is required for maintenance of mitochondrial functions.

The grpE gene is a heat shock gene of Escherichia coli whose product functions as a chaperone to (re)fold proteins. We found a yeast homologue of grpE and designated it YGE1. YGE1 can replace grpE in E. coli, indicating that YGE1 is a functional homologue of grpE. Deletion of YGE1 is lethal. During depletion of the Yge1 product, mitochondria are sequestered in mother cells thereby accumulating cells without mitochondria, suggesting that Yge1 protein plays a pivotal role in maintaining mitochondrial functions.

Amino Acid Sequence↗
PubMed1993

Expression of thrombomodulin in patients with spontaneous occlusion of the circle of Willis.

BACKGROUND AND PURPOSE: We examined the expression of thrombomodulin, a recently isolated anticoagulant protein, in endothelial cells from patients with spontaneous occlusion of the circle of Willis (cerebrovascular moyamoya disease) to determine whether lack of the expression of thrombomodulin might lead to the thrombogenicity in patients with this disease. METHODS: The intracranial internal carotid arteries, the external carotid arteries, and the vertebral or basilar arteries from 12 autopsied patients who had this disease and eight control autopsied patients were examined immunohistochemically by using the antiserum against human thrombomodulin. RESULTS: All of the endothelial cells from the patients with this disease and from the control patients were positive for thrombomodulin. Immunoelectron microscopy also disclosed normal localization of thrombomodulin on the luminal plasma membrane. Immunohistochemically, we could find no significant differences in the expression of thrombomodulin among the arteries examined in this study. CONCLUSIONS: We conclude that as far as we investigated immunohistochemically, the thrombogenicity in this disease is almost unlikely to depend on the abnormal expression of thrombomodulin.

Adolescent↗
PubMed1992

Characterization of a staurosporine- and temperature-sensitive mutant, stt1, of Saccharomyces cerevisiae: STT1 is allelic to PKC1.

Staurosporine is an antibiotic that specifically inhibits protein kinase C. Fourteen staurosporine- and temperature-sensitive (stt) mutants of Saccharomyces cerevisiae were isolated and characterized. These mutants were divided into ten complementation groups, and characterized for their cross-sensitivity to K-252a, neomycin, or CaCl2. The STT1 gene was cloned and sequenced. The nucleotide sequence of the STT1 gene revealed that STT1 is the same gene as PKC1. The STT1 gene conferred resistance to staurosporine on wild-type cells, when present on a high copy number plasmid. STT1/stt1::HIS3 diploid cells were more sensitive to staurosporine than STT1/STT1 diploid cells. Analysis of temperature-sensitive stt1 mutants showed that the STT1 gene product functioned in S or G2/M phase. These results suggest that a protein kinase (the STT1 gene product) is one of the essential targets of staurosporine in yeast cells.

Alkaloids↗
PubMed1992

Preclinical and clinical study of FK506 in uveitis.

Efficacy of a new immunosuppressive agent, FK506, in refractory uveitis was studied in 8 patients: 5 with Behcet's disease and 3 with idiopathic retinal vasculitis. The agent was given by oral administration every 12 hours. The previous therapy with systemic corticosteroids or immunosuppressive agents including cyclosporine failed to subside uveitis in these cases. During the observation period of 21.6 +/- 7.8 weeks (mean +/- SD) under FK506 at doses with 0.05, 0.1, 0.15 or 0.2 mg/kg/day, the visual acuity was increased in 44% of treated eyes, unchanged in 44% and decreased in 12%. The inflammatory activity in the ocular fundus was improved in 69% and unchanged in 6% of treated eyes. The effects of FK506 on uveitis by the criteria of improvement of visual acuity and uveitis activity was dose-dependent: 0.05 and 0.1 mg/kg/day were ineffective but 0.15 and 0.2 mg/kg/day were effective in most cases. One patient with Behcet's disease converted from cyclosporine developed moderate renal impairment in 4 weeks under FK506 and the therapy was discontinued in 8 weeks, though the uveitis activity as well as visual acuity was markedly improved. Other 7 cases had no side effect of FK506. Although the number of cases was small and observation period was short, the present clinical data indicate that FK506 is effective to treat refractory uveitis.

Administration, Oral↗
PubMed1991

Functional T cell subpopulations responsible for hyposecretion of IL-2 in patients with systemic lupus erythematosus.

The ability of T cells to secrete IL-2 in patients with systemic lupus erythematosus (SLE) was investigated. In patients with SLE, impaired IL-2 production by peripheral blood lymphocytes stimulated with mitogens is well known. In this paper, we report that purified T cells stimulated with mitogens, in the presence of Epstein-Barr virus transformed B cells (B-LCL) as an accessory cell, however, could secrete a large quantity of IL-2 as much as normal T cells. In order to study this potential capacity of T cells to secrete IL-2 in patients with SLE, IL-2 secreting T cells were examined. To obtain these cells, T cells were divided into cluster forming cells and noncluster forming cells after short culture of T cells with accessory cells in the presence of Con A. Then the ability of IL-2 production in two kinds of separated T cells was examined. We found that 1) after short culture with B-LCL, the cluster forming T cells could secrete IL-2 when cultured again, but non-cluster forming T cells could not, even in the presence of B-LCL, 2) after short culture with macrophages, in normal donors and SLE patients, noncluster forming T cells were able to secrete a greater amount of IL-2 than cluster forming and undivided T cells when cultured with B-LCL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Goblet cell carcinoid of the vermiform appendix with ovarian metastasis mimicking mucinous cystadenocarcinoma.

We describe a case of goblet cell carcinoid of the vermiform appendix, which metastasized to the bilateral ovaries, uterus, vagina and peritoneum three years and four months after appendectomy. The appendiceal tumor showed transmural infiltration of carcinoembryonic antigen-positive goblet cell-type tumor cells, intermingled with a small number of argyrophilic cells immunoreactive for serotonin and chromogranin A. The presence of neurosecretory-type granules was confirmed ultrastructurally in some mucin-negative tumor cells. The pattern of proliferation was typical of carcinoid tumor originating from the lower-most part of the mucosa, and showed lymphatic permeation. The metastatic lesions in the pelvic organs showed either diffuse infiltration of goblet cell-type tumor cells or mucinous cystadenocarcinoma-like features, the latter being evident in the right ovary. No neuroendocrine component was identified in the metastatic deposits. The kinship of appendiceal goblet cell carcinoid to adenocarcinoma is discussed.

Adult↗
PubMed1991

Systemic vascular changes in spontaneous occlusion of the circle of Willis.

BACKGROUND AND PURPOSE: We examined the presence of systemic etiologic factors causing vascular changes in so-called "spontaneous occlusion of the circle of Willis" (cerebrovascular moyamoya disease) to determine whether extracranial, as well as intracranial, vessels are involved in this disease. METHODS: Histopathologic examination and morphometric analysis of the extracranial vessels were performed in 13 patients with this disease. RESULTS: The histopathologic findings of the extracranial vessels were as follows: 1) advanced intimal fibrous thickening similar to that of the intracranial vessels; and 2) characteristic intimal fibrous nodular thickening, which may indicate organization of mural thrombi, at the proximal portions of the pulmonary arteries in three of 13 patients. Morphometric analysis revealed significant intimal thickening of the pulmonary arteries (p less than 0.05), renal arteries (p less than 0.05), and pancreatic arteries (p less than 0.01) in patients with this disease as compared with age- and sex-matched control patients. CONCLUSIONS: On the basis of these findings, it is highly likely that this disease has systemic etiologic factors, as well as focal etiologic factors, that work to create vascular change in both the intracranial and extracranial vessels.

Adolescent↗