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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 361 records · Page 20Linked to original sources

HUB1 is an autoantigen frequently eliciting humoral immune response in patients with adult T cell leukemia.

The immunological screening of a cDNA phage expression library prepared from an adult T cell leukemia (ATL) cell line, ST1, was performed with IgG class antibodies in the serum of an ATL patient by the SEREX method to analyze the repertoire of antigen molecules in ATL. Ten different cDNAs, 7 previously reported and 3 newly identified, were isolated. One of the identified cDNAs was homologous to the recently reported gene, HTLV-I U5RE binding protein 1 (HUB1) encoding a protein binding to a possible repressor element of the long terminal repeat of the human T lymphotropic virus type I (HTLV-I). The obtained cDNA was expressed as a fusion protein with glutathione S-transferase. HUB1 protein was prepared by subsequent treatment of the fusion protein with thrombin. Reactivity of IgG serum samples from ATL patients, asymptomatic HTLV-I carriers and normal donors against the purified protein was examined by Western blot analysis. Twenty-one out of 30 samples (70.0%) from ATL patients, 10/24 samples (41.7%) from HTLV-I carriers and 9/24 samples (37.5%) from healthy donors showed positive reactivity, indicating the autoantigenicity of HUB1. The development of ATL may be related to higher production of antibodies against HUB1.

Adult↗

Inhibition of growth of Escherichia coli O157:H7 in fresh radish (Raphanus sativus L.) sprout production by calcinated calcium.

The inhibitory effect of calcinated calcium on the growth of Escherichia coli O157:H7 during fresh radish (Raphanus sativus L.) sprout production was studied. It was revealed that the addition of 0.4% (wt/vol) calcinated calcium into radish sprouting medium which was artificially contaminated with E. coli O157:H7 (3.0 to 3.2 log CFU/ml) completely inhibited the growth or inactivated the microorganism. When radish seed extract was used instead of radish sprout production, the same extent of growth inhibition or inactivation was observed with much lower amounts (0.07%) of calcinated calcium under similar experimental conditions. The findings suggested that calcinated calcium may be useful to control E. coli O157:H7 contamination during the production of radish sprouts.

Brassicaceae↗

[Two cases in which the presence of ciliospinal response led to indecisiveness in the evaluation of brain death].

The ciliospinal reflex was first described by Budge in 1852. This reflex is used as an indicator of brain stem and autonomic nervous system functioning. In the Japanese guideline for determining brain death, the absence of this reflex is considered essential. We reported two cases in which the ciliospinal responses judged to be present resulted in the authors' indecision in determining brain death. They were the cases of a 74-year-old woman who suffered a right putaminal hemorrhage and that of a 28 year-old male with severe head and cervical cord injury. Although brain death was suspected in both cases from its clinical courses, the fact that the ciliospinal reflex was present in each case kept us from declaring that these patients were in the state of brain death. The center of the ciliospinal reflex lies in the first three segments of the thoracic spinal segments and two pathways are involved in this reflex. A noxious stimulation to the face will be registered through the brain stem, but if stimulation is in the neck or upper trunk, it may go directly to the spinal center. Because of the latter pathway to the spinal center, this reflex might remain in patients in whom the brain stem is completely nonfunctioning. Therefore, the presence of this reflex dose not always preclude a state of brain death.

Adult↗

[Detection of activated platelets by flow cytometry].

While bleeding time and platelet aggregometry are the two standard clinical tests of platelet function, an increasing number of flow cytometric studies using activation-dependent monoclonal antibodies have been reported recently. Those include an IgM antibody, PAC-1, which binds to the fibrinogen binding site exposed by a conformational change in the GPIIb-IIIa complex of activated platelets. In our study, platelets in whole blood bound to PAC-1 when activated by a wide range of ADP concentrations. ADP-induced PAC-1 binding to platelets was suppressed in individuals who had taken an oral antiplatelet drug, ticlopidine. Whole blood flow cytometry have advantages such as minimal artifact and smaller sample volume. Platelet activation and its suppression by antiplatelet therapy may be evaluated by using ADP-induced PAC-1 binding in many clinical settings where platelet hyperreactivity and/or circulating activated platelets play a role.

Adenosine Diphosphate↗

Platelet membrane protein CD36.

CD36 is one of the major glycoproteins of platelets and known as GPIV. Besides platelets, CD36 is distributed in megakaryocytes, monocytes, capillary endothelium and mammary epithelial cells. In vitro analyses, CD36 is reported to act as receptors to a variety of ligands including collagen, thrombospondin, malaria-infected erythrocytes and oxidized LDL. However, it remains unclear to which of these functions CD36 is critical in vivo. CD36-deficient individuals can be the key to answer this question. In calcium-deficient state, CD36-deficient platelets exhibited a delay and decline of irreversible aggregation on agonist stimulation. Irreversible aggregation of platelets depends on intake of arachidonic acid once-secreted from platelets and production of its metabolite Eps/TxA2. The calcium influx in response to U46619 (TxA2 analogue) of CD36-deficient platelets was not different from normal platelets in the presence of indomethacin and ETYA. Defective aggregation of CD36-deficient platelets in calcium-deficient state seemed to be derived from defective intake of arachidonic acid. This assumption was verified by our results that inhibitory effect of arachidonic acid in aggregation depended on the presence of platelet CD36. Intake of arachidonic acid through CD36 may have an effect in low concentration state of arachidonic acid. The CD36 deficiency is present in several % in Japanese and approximately 0.3% in Caucasians and is divided in type I (deficient in platelets and monocytes) and type II (deficient only in platelets). Analyses of CD36 cDNA revealed that codon 90 (proline/serine) was critical as to the surface expression of CD36 protein. By analyses of CD36 genomic DNA, the CD36 gene could be classified; 1) serine90 type that was not translated as CD36 protein, 2) proline90 type that was not transcribed to mRNA, 3) proline90 type that was transcribed only in monocytes and not in platelets, 4) proline90 type that was transcribed in platelets but in very small amounts and 5) wild type proline 90. The results of family studies were consistent with the assumption described above.

Arachidonic Acid↗

[Effective chemo-endocrine combination therapy for obstructive-jaundice caused by multiple liver metastasis of recurrent breast cancer--a case report].

A 68-year-old woman complained of obstructive jaundice 9 years after a radical mastectomy. CT scan demonstrated multiple metastasis of the liver and two coin lesions of the right lung. The biliary tract was completely obstructed at the portal fissure. Multiple liver and lung metastasis of breast cancer were diagnosed because of high CA 15/3 serum levels and normal gastrointestinal study. Following unsuccessful treatment with tamoxifen (TAM), we used toremifene (TORE) and 5'-deoxy-5-fluorouridine (5'-DFUR) followed by percutaneous transhepatic cholangiodrainage (PTCD). The biliary tract was reopening and jaundice disappeared with improvement of the general condition. Then endocrine therapy with medroxy progesterone acetate and UFT and chemotherapy with CAF (Cyclophosphamide, Adriamycin, 5-FU) were begun. A partial response (PR) was obtained with the disappearance of liver metastasis and two coin lesions of the lung 5 months after the first treatment. The effect of chemo-endocrine combination therapy continued for 5 months. Survival time from recurrence was 13 months. In our case, PR was obtained by using chemo-endocrine combination therapy, although a poor prognosis has been reported in patients with obstructive jaundice caused by multiple liver metastasis of recurrent breast cancer.

Aged↗

[Coronary thrombosis and cell adhesion molecules].

A fundamental role of cell adhesion molecules are implicated for the disease process of acute coronary syndromes. Among adhesion molecules, platelet membrane glycoprotein Ib binds to the von Willebrand factor and thereby activates glycoprotein IIb/IIIa, resulting in platelet aggregation. P-selection is rapidly translocated onto the cell surface within minutes and adheres to a sialylated fucosylated carbohydrate structure, sialyl Lewis(x), on leukocytes. P-selectin mediates adhesion of leukocytes to the activated platelets. Thus, these platelet glycoproteins play a active role in cell-extracellular matrix interaction and cell-cell interaction at the first step of the thrombus formation at the culprit lesion of the coronary artery. The more comprehensive understandings of adhesion molecules and their functions may promote the more effective therapeutic strategies for the acute coronary syndromes.

Coronary Thrombosis↗

[Typical thymic carcinoid tumor with multiple metastases diagnosed by pleural effusion cytology].

A 57-year-old man was referred and admitted to our hospital because of anterior mediastinal tumors and pericardial effusion. Although his condition had been diagnosed as thymic cancer by another hospital, a cytologic examination of pleural effusion specimens obtained a positive stain for chromogranin A, and yielded a diagnosis of thymic carcinoid tumor with multiple metastases. Despite irradiation and relief therapy, the patient died 8 months later. A histopathologic examination of the thymic tumor at autopsy revealed typical carcinoid patterns. The cytologic examination proved capable of accurately diagnosing the carcinoid tumor. Although such tumors are usually considered to have a good prognosis, unfavorable outcomes are also a possibility, as was demonstrated in this case.

Carcinoid Tumor↗

[Pre-beta-migrating lipoprotein A-I concentration in normal full-term maternal blood].

Hyperlipidemia in pregnancy accompanying selectively-raised concentrations of serum apolipoprotein A-I (apoA-I) and high-density lipoprotein-2-cholesterol (HDL2-C) had been considered to be, at least in part, mediated by sex hormones. On the other hand, it is known that oral estrogen-replacement therapies in postmenopausal women raise serum concentrations of lipoprotein A-I without apoA-II (LpA-I) originated from the liver. This study was performed to clarify the relations among the concentrations of pre-beta-migrating LpA-I (pre-betaLpA-I) and of serum apoA-I and of HDL-C. And we discussed the origin of pre-beta LpA-I in normal full-term maternal blood. Pre-beta LpA-I concentrations in 12 maternal (mean +/- SD = 33.8 +/- 7.6 mg/dl) and umbilical cord blood (mean +/- SD = 3.1 +/- 1.9 mg/dl) pairs and those in 20 healthy non-pregnant adult female controls (mean +/- SD = 13.5 +/- 6.1 mg/dl) were determined using the crossed immunoelectrophoresis. (1) The higher concentration of maternal pre-beta LpA-I than that of control was contributed to the high concentration of maternal serum apoA-I but not to the high concentration of maternal HDL-C, so it would loosen the correlativity between serum apoA-I concentration and HDL-C concentration because pre-beta LpA-I was cholesterol-poor. (2) It did not correlate with the high concentration of chylomicron, which made us speculate that maternal pre-betaLpA-I might be possible to be originated from the liver by the action of endogenous estrogen. And, (3) no correlation between the concentrations of pre-beta LpA-I from maternal blood and those from cord blood respectively will support the idea that their lipoprotein metabolisms would be independent with each other.

Adult↗

A case of malignant lymphoma producing autoantibody against platelet glycoprotein Ib.

A 61-year-old woman was referred to our hospital for refractory thrombocytopenia (3 x 10(3)/microliter) and massive melena. Bone marrow aspiration revealed normal cellularity and increased megakaryocytes (250/microliter). An abdominal computerized axial tomography scan showed isodensity masses on both adrenal glands. 67 Ga-scintigraphy exhibited strong uptake into the bilateral adrenal tumor and mediastinal region. IgM-type antibody against platelet glycoprotein Ib (GpIb) was detected in the patient's serum. A needle biopsy of the right adrenal tumor was performed, and histology was non-Hodgkin's lymphoma (NHL), diffuse large B-cell type. Following the diagnosis of autoimmune thrombocytopenia associated with lymphoma, administration of corticosteroid (predonisolone 60 mg/day) and high-dose intravenous globulin (15 g/day x 4 days) was carried out, but neither was effective in normalizing the thrombocytopenia. Immunosuppressive therapy (cyclophosphamide 500 mg and 1 mg of vincristine) markedly restored the platelet counts to 7.2 x 10(4)/microliter and ceased the melena; furthermore, the size of adrenal tumors decreased by more than 60% after therapy. We cultured the lymphoma cells drawn by needle biopsy with IL-6 in vitro and found that the lymphoma cells produced IgM-type antiplatelet antibodies against platelet GpIb in the culture supernatant. Thus this is a rare case of NHL in which the production of antiplatelet antibody from lymphoma cells was confirmed in vitro.

Autoantibodies↗

[Quality of life in patients with testicular cancer after high orchiectomy, radiation therapy or chemotherapy].

We evaluated the physical or psychosocial states of testicular cancer patients receiving orchiectomy, radiation therapy and chemotherapy to assess their quality of life during and after treatment. The subjects were 33 post-treatment patients with testicular cancer who responded to the questionnaire we mailed to them. The quality of life score during chemotherapy showed a decrease, which was accompanied by gastrointestinal symptoms induced by anti-cancer drugs. With regard to the difference in adjuvant treatment types, the surveillance group showed the highest score in the satisfaction of daily life. Moreover, married patients tended to be satisfied with daily life more than non-married patients. With regard to sexual or erectile function, scores of testicular cancer patients, especially in the retroperitoneal lymph node dissection group, were inferior to these of normal volunteers. In conclusion, the physical or psychosocial states after treatment for testicular cancer depend not only on treatment type but also marriage status.

Adult↗

Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I.

Human T-cell lymphotropic virus type I (HTLV-I) is associated with various clinical disorders including adult T cell leukemia, myelopathy, arthropathy. Hypercalcemia resulting from osteoclast activation and a variety of hematopoietic abnormalities have been also observed in HTLV-I infected patients, however, precise mechanism about initial trigger(s) prior to presenting symptoms is still unknown. In this study, to assess effects of HTLV-I on hematopoiesis, we analysed characteristics of early hematopoietic precursors in HTLV-I env-pX transgenic rats. Progenitor cells for osteoclasts were significantly increased even in the marrow of asymptomatic env-pX rats. Progenitors for B cells were also highly enriched, while colony forming cells (CFC) elicited by GM-CSF(CFU-GM) and M-CSF(CFU-M) were comparable to normal littermates. Following arthritis in env-pX transgenic rats, osteoclastogenesis was further augmented and the CFCs were increased. Bone marrow cells carrying adjuvant-induced arthritis retained a constant number of progenitors for osteoclast and B lymphocytes, whereas the number of CFU-GM and CFU-M increased. These results indicate that the env-pX transgene affect early stages of osteoclast and B-cell lineages prior to developing diseases, in contrast, an increase of the CFCs was caused indirectly by arthritis. This study provides a novel standpoint for the mechanisms of pathogenesis by HTLV-I.

Animals↗

Novel mutations of the glutaryl-CoA dehydrogenase gene in two Japanese patients with glutaric aciduria type I.

We identified three different point mutations in the glutaryl-CoA dehydrogenase (GCDH) gene in two unrelated Japanese patients with glutaric aciduria type I (GA-I). One patient was a homozygote for Arg355His and the other a compound heterozygote for Ser305Leu and Met339Val. Arg355His and Met339Val are mutations hitherto undescribed, and all three mutations are predicted to alter the secondary structure of GCDH. Molecular analysis is useful for definite diagnosis and/or prenatal diagnosis of GA-I.

Amino Acid Metabolism, Inborn Errors↗