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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 523 records · Page 29Linked to original sources
PubMed1997

HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines.

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.

Animals↗
PubMed1997

Human endogenous retroviruses: expression in various organs in vivo and its regulation in vitro.

To evaluate the role of human endogenous retroviruses in vivo, we examined their expressions in various organs from autopsy cases by Northern blot and RT-PCR. ERV3 (HERV-R) mRNA was expressed in many organs, and the level of expression in individuals and organs considerably differed. However, expression in the adrenal gland showed consistently high levels in every individual. lambda 4-1 (HERV-E) mRNA was expressed less compared with that of ERV3, and could not be detected in the adrenal gland by Northern blot, although the expression of lambda 4-1 generally correlated with that of ERV-3 in placentas. We also examined the effect of cytokines on the transcriptional regulation of ERV3 in vitro. Although the level of ERV3 expression in cultured synovial cells did not change after IL-1 beta treatment, the level in cultured proximal tubular epithelial cells was upregulated. The evidence suggests that distinct regulatory pathways may exist for the expression of human endogenous retroviruses in different cell types.

Adrenal Glands↗
PubMed1997

Cell-free transmission of Fv-4 resistance gene product controlling Friend leukemia virus-induced leukemogenesis in mice.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). The Fv-4' env antigen that binds to the cell surface of Fv-4'-bearing C3H cells was found in sera from normal Fv-4'-bearing C4W mice. The serum Fv-4' env antigen binds to ecotropic MuLV receptors, shown by specific binding to transfectant cells expressing ecotropic MuLV receptors but not to parental mink cells. To determine whether the binding of Fv-4' env antigen to the putative MuLV receptors would block FLV infection, C3H thymocytes or spleen cells that had been preincubated with C4W serum were mixed with FLV and the subsequent production of MuLV specific antigens was examined. C3H thymocytes or spleen cells treated with C4W serum became refractory to binding by FLV. These results provide evidence that the Fv-4' env antigen is released from C4W-derived cells in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with FLV. The implication of these findings for gene therapy of retrovirus-induced disease such as acquired immune deficiency syndrome (AIDS) is discussed.

Animals↗
PubMed1997

Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.

To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.

Animals↗
PubMed1997

HTLV-I induced myeloneuropathy in WKAH rats: apoptosis and local activation of the HTLV-I pX and TNF-alpha genes implicated in the pathogenesis.

To investigate the pathogenesis of HTLV-I associated diseases, we established a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in WKAH rats. In the spinal cords of WKAH rats carrying HTLV-I, chronological histopathology revealed the occurrence of apoptotic cell death starting at 9 months after the infection, followed by demyelination, macrophage infiltration, and the activation of astrocytes starting at 12, 15 and 20 months, respectively. Apoptosis of the Schwann cells was also observed in the peripheral nerves of these rats. By RT-PCR, pX mRNA of HTLV-I was selectively expressed in the diseased spinal cords and peripheral nerves, but not in the unaffected cerebra, cerebella, even though provirus DNAs were consistently identified in these tissues. Among several cytokines examined, mRNA expression and production of TNF-alpha were frequently detected in the spinal cord and the cerebrospinal fluid. The collective evidence suggests that the selective activation of HTLV-I, in particular Tax expression, and/or the production of TNF-alpha in target spinal cord and peripheral nerves are causally related to apoptotic death of the oligodendrocytes and Schwann cells, a major pathogenetic pathway of HTLV-I induced myeloneuropathy in the WKAH rat.

Animals↗
PubMed1997

HTLV-I env-pX transgenic rats: prototype animal model for collagen vascular diseases.

To evaluate the function of HTLV-I env-pX gene in vivo, we developed two lines of transgenic rats (env-pX rats) that expressed env-pX gene products, under control of own LTR promotor. In various tissues of the rats, env and pX mRNAs were constitutively expressed, irrespective of age. At age 5 weeks, swelling of the bilateral ankle joints histologically showing synovial lining hyperplasia, severe chronic inflammation, erosion of the joint cartilage, and bone destruction with pannus formation began to develop in these env-pX rats. These histologic features resemble those of rheumatoid arthritis (RA) in man. High titered rheumatoid factors and low anti-dsDNA antibodies and hyper-gamma globulinemia were detected. Necrotizing arteritis resembling polyarteritis nodosa, polymyositis, myocarditis and Sjögren syndrome-like sialoadenitis developed, together with RA-like arthritis even in one individual animal. Thymic atrophy with low body weight was also observed. The evidence indicates that env-pX rats appear to be suitable animal models for elucidating pathogenetic mechanisms involved in not only HTLV-I related diseases but also various collegen vascular and autoimmune diseases of unknown etiology in man.

Aging↗
PubMed1997

[Peripheral carcinoid tumor of the lung presenting as a solitary mass shadow on a chest roentgenogram and diagnosed by CT-guided percutaneous needle biopsy].

A 59-year-old woman was referred to our clinic because a solitary mass shadow (2.5 cm in diameter was seen in the left lower lung field on a chest roentgenogram. Transbronchial biopsy via a fiberoptic bronchoscope did not yield a definitive diagnosis. Examination of a specimen obtained by CT-guided percutaneous needle biopsy revealed that the tumor consisted of small cells proliferating in a solid, tubular, pseudoglandular, and follicular pattern, which suggested the diagnosis of carcinoid. A left lower lobectomy was performed, and several hilar and mediastinal lymph nodes were also removed. The tumor cells did not show pleomorphism of nuclei, mitotic activity, or necrosis. Grimelius and immunohistochemical stains for chromogranin. A, neuron-specific-enorase, synaptophysin, and serotonin were positive. These findings confirmed the diagnosis of carcinoid CT-guided percutaneous needle biopsy can be useful for the diagnosis of peripheral carcinoid and other peripheral lung tumors.

Biopsy, Needle↗
PubMed1997

[Adenocarcinoma of the lung associated with acute promyelocytic leukemia and miliary tuberculosis].

A 44-year-old man was admitted to the hospital because of acute promyelocytic leukemia. A nodular shadow (2.5 cm in diameter) was seen in the right upper lung field on a chest roentgenogram. During the administration of combination chemotherapy for the leukemia, diffuse granular shadow appeared in all lung fields. Transbronchial lung biopsy findings indicated tuberculosis. The patient was given streptomycin, isoniazid, rifampicin and ethambutol, but the nodular show enlarged and a pleural effusion appeared on the right side. Cytologic examination of the pleural effusion revealed adenocarcinoma. Similar findings were obtained from a second transbronchial lung biopsy. The frequency of association of lung cancer and other malignancy is about 4%. The incidences of primary lung cancer found during the course of active tuberculosis, active pulmonary tuberculosis found during the course of primary lung cancer, and tuberculosis found during the course of acute leukemia are 0.9 to 1.4%, 0.4 to 4.3%, and 2.4 to 4.5%, respectively. To our knowledge, this is the first case in Japan in which adenocarcinoma of the lung was associated with acute promyelocytic leukemia and tuberculosis.

Adenocarcinoma↗
PubMed1997

An autopsy case of acute chloroform intoxication after intermittent inhalation for years.

A 39-year-old female died shortly after inhalation of chloroform by a saturated towel placed over her face by her lover, who also inhaled and became unconscious. They had inhaled chloroform once or twice a month for about seven years. Fatal level of chloroform was detected in the blood and tissues by gas chromatographic/mass spectrometric analysis. The fragmentation and waviness of cardiomyocytes that indicates hypercontraction, along with the edema and hemorrhage of the lung, shows the presence of acute heart failure possibly caused by arrhythmias or cardiac depression. The unusual numbers of lipofuscin pigments in the heart as well as in the liver may be generated by the chronic use of chloroform.

Acute Disease↗
PubMed1997

[The family function of patients on home oxygen therapy and their main caregivers].

We examined family APGAR scores in patients on home oxygen therapy (n = 101) and their main caregivers (n = 91), and compared them with those obtained from members of a seniors' club who were not on home oxygen therapy themselves, nor had any family members on home oxygen therapy. Furthermore, the relationship between the main caregivers recognition of the patients' mental state and the patients' CESD score was examined. Family APGAR scores for the main caregivers were significantly lower than those of the patients (p < 0.002), or the seniors' club members (p < 0.004). Since most the main caregivers were women, we compared family APGAR scores of the female main caregivers and the age-matched female members of the seniors' club, revealing that the satisfaction of the female main caregivers with the "adaptation" component of the APGAR score (the component dealing with support given when something troublesome happens), was significantly lower than that of the members of the seniors' club (p < 0.0001). The CESD of the patients whom the main caregivers recognized as depressed was significantly higher. Thus, we concluded that satisfaction of the main caregivers with family function who were family members was low, and that the role of the main caregivers is important in alleviating the depression of patients on home oxygen therapy.

Aged↗
PubMed1996

Long-term smoking impairs platelet-derived nitric oxide release.

BACKGROUND: Long-term smoking impairs endothelium-dependent vasodilation, which is mediated by nitric oxide (NO). However, it is unknown whether long-term smoking impairs the platelet-derived NO release, which regulates platelet aggregation. METHODS AND RESULTS: Platelet-derived electrical current induced by collagen was measured with an NO-selective electrode in 12 smokers and 11 nonsmokers. Collagen-induced intraplatelet cGMP and platelet aggregation was measured in smokers and nonsmokers. S-nitroso-N-acetyl-dl-penicillamine, a direct NO donor, dose dependently increased in electrical current (r = .99). Collagen induced platelet aggregation and dose dependently increased electrical current (r = .94). Collagen-induced electrical current and cGMP were significantly augmented by L-arginine, a precursor of NO, and attenuated by NG-monomethyl-L-arginine, an inhibitor of NO synthesis. Significant correlation was found between collagen-induced electrical current and cGMP (r = .73). These findings indicate that the change in electrical current reflects the NO release through the L-arginine-NO pathway in platelets. Collagen-induced electrical current (6.7 versus 13.8 pA; P < .001) and cGMP (1.2 versus 3.0 pmol/10(9) platelets; P < .005) were significantly lower in smokers than in nonsmokers. Although L-arginine increased cGMP levels in both smokers and nonsmokers, the level was still lower in smokers than in nonsmokers. The inhibitory effect of L-arginine on collagen-induced platelet aggregation was significantly lower in smokers than in nonsmokers (P < .05). CONCLUSIONS: These findings provide evidence that platelet-derived NO release is significantly impaired in long-term smokers, resulting in the augmentation of platelet aggregability.

Adult↗
PubMed1996

The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

Acute Disease↗
PubMed1996

Inhibitory effect of tranilast on activation and transforming growth factor beta 1 expression in cultured rat stellate cells.

Stellate cells, the primary extracellular matrix-producing cells in the liver, undergo activation characterized by fibrogenesis, proliferation and smooth muscle alpha-actin expression, in hepatic fibrosis or when cultured on plastic. TGF beta 1 is known to have a pivotal role in fibrogenesis. Tranilast, a drug used for allergic diseases with anti-inflammatory effects, is known to inhibit collagen synthesis by cultured fibroblasts. Thus, effects of tranilast on activation and TGF beta 1 expression in stellate cells was investigated in vitro. Tranilast reduced collagen synthesis in a dose-related manner up to 50.8% of the control. This effect was reversible after tranilast withdrawal. The mobility of procollagen on gel electrophoresis and the ratio of intracellular procollagen to extracellular collagen concentrations were not affected by tranilast. Tranilast decreased DNA synthesis and increased smooth muscle alpha-actin expression. mRNA expressions of procollagen and TGF beta 1 were reduced by tranilast. Tranilast with anti-fibrogenic and anti-inflammatory actions merits consideration as a candidate for therapeutic agent of hepatic fibrosis.

Animals↗
PubMed1996

Hydrolases acting on glycosidic bonds: chromatographic and electrophoretic separations.

We describe analyses of unusual human alpha-amylase, performed in our laboratory and review available methods for amylase study. Electrophoretic and chromatographic methods provide an effective means for the analysis of amylase isoenzymes and unusual amylase. The recent identification of a selective inhibitor and a monoclonal antibody to amylase isoenzyme contributes to rapid routine clinical assays of amylase isoenzymes. However unusual amylases such as variants, macroamylasemia and sialyl salivary-type amylasemia cannot be detected by those conventional methods. The unusual amylases can only be detected by electrophoresis and can be easily characterized by combination study with chromatographic methods. Electrophoretic and chromatographic methods are universal means to validate unusual amylases found in patient sera. Further basal studies are needed to define the roles of salivary amylase in exocrine fluids using those separation techniques.

Amylases↗
PubMed1996

Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and gametogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KIT(G559) or KIT(V814), KIT(G559) induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KIT(V814) induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KIT(G559) and KIT(V814)-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild-type KIT-infected cells. Furthermore, transgenic mice expressing KIT(V814) developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KIT(V814), in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies.

Animals↗