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Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 109 records · Page 6Linked to original sources
PubMed1999

Utilization of intestinal triglyceride-rich lipoproteins in mammary gland of cows.

Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating cows showed significantly (p < 0.05) larger A-V differences in both plasma TG and apoB-48 concentration of TRL than those in late- and non-lactating cows. These results suggested that TG in exogenous (intestinal) TRL was utilized for milk fat synthesis in lactating mammary gland of cows by the receptor-mediated uptake.

Animals↗
PubMed1999

Synergistic enhancement by 12-O-tetradecanoylphorbol-13-acetate and dibutyryl cAMP of 1alpha,25-dihydroxyvitamin D3 action in human promyelocytic leukemic HL-60 cells.

We have reported that dibutyryl cAMP (dbcAMP), an activator of cAMP-dependent protein kinase (PKA), potentiated the effects of 1alpha,25-dihydroxyvitamin D3(1,25-(OH)2D3)-induced 24-hydroxylation activity in HL-60 cells by increasing 1,25-(OH)2D3 receptor (VDR). The present study demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent phorbol ester, also potentiated the effect of 1,25-(OH)2D3 on HL-60 cells and that TPA and dbcAMP acted in a synergistic manner to enhance the effect of 1,25-(OH)2D3. It is interesting that TPA induced 24-hydroxylation activity far more efficiently than dbcAMP, in addition to their effects in increasing VDR. TPA increased basal levels of c-fos mRNA to the maximum by 1 h after the treatment, whereas dbcAMP failed to affect c-fos gene expression. Together with the previous data indicating the presence of AP-1-like sequence in the promoter of 24-hydroxylase gene, it was suggested that TPA potentiated the effect of 1,25-(OH)2D3 through an activation of c-fos gene expression. This notion was further supported by the data showing that TPA and dbcAMP also acted in a synergistic manner to activate c-fos gene expression. Neither TPA nor dbcAMP affected c-jun early response gene in the HL-60 clone used in the present study. The present study suggested that the activation of early c-fos response gene by TPA might be another mechanism to enhance the effect of 1,25-(OH)2D3, besides up-regulation of VDR.

Bucladesine↗
PubMed1999

Remission of insulin autoimmune syndrome in a patient with Grave's disease by treatment with methimazole.

The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacerbated IAS in the present case, although his HLA combination is identical to that of the previous cases.

Adult↗
PubMed1999

Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells.

Dendritic cells (DCs), which are the most effective professional antigen-presenting cells (APCs), initiate and regulate immune responses. In this report, we examine the role of DCs in the induction of autoimmune thyroiditis. Experimental autoimmune thyroiditis (EAT) induced by immunization with thyroglobulin (Tg) plus adjuvant is considered to be an animal model of autoimmune thyroiditis, and is categorized as a T cell-mediated autoimmune disease. To examine the contribution of DCs to EAT, naive DCs were purified from high responder B10BR mice and pulsed with various concentrations of porcine Tg (pTg). These pTg-pulsed DCs were transferred without adjuvant to syngenic BIOBR mice to induce EAT. Mice that had received pTg-pulsed DCs showed thyroiditis, and the degree of thyroiditis induced was positively correlated to the amounts of pTg used for the incubation (pulsing) of DCs. The severity of thyroiditis was also correlated to the amounts of anti-pTg IgG2a antibodies and IFN-gamma in the recipient sera, but not to IL-4 or IL-10, indicating that Th1 cells are mainly activated by pTg-pulsed DCs and attributable to the pathogenesis of EAT.

Animals↗
PubMed1999

[Recanalization of cerebral cortical venous thrombosis: a case report].

Several clinical cases of sinus thrombosis have been reported, but localized cerebral cortical venous thrombosis is a fairly rare clinical entity. We report a case of a 51-year-old woman who presented with right hemiparesis on admission. CT scan revealed subcortical hemorrhage with perifocal edema in the left front-parietal lobe. A T2W image revealed a large area of hyperintensity indicating edema, and coronal Gd enhanced T1 weighted image showed a reverse-triangle-shaped enhanced lesion. Left carotid angiogram showed cerebral cortical venous thrombosis in the left frontal lobe, but the superior sagittal sinus was not occluded. A month after admission, right hemiparesis had suddenly improved and the patient could walk without any support. Left carotid angiogram showed recanalization of thrombosed cortical veins and CT scan showed disappearance of any low density lesion indicative of edema. It is an important fact that neurological deficit improved quickly a month after onset, and it was suspected that, even without resorting to fibrinolytic therapy, recanalization of thrombosed cerebral veins would still eventually occur. We found the reverse-triangle-shaped enhanced lesion on MRI and we suspected that it was typical finding for cerebral cortical venous thrombosis.

Brain↗
PubMed1999

[The natural history of a dural arteriovenous fistula associated with sinus thrombosis: a case report].

The patient, a 52-year-old man, complained of vertigo. CT scan revealed right cerebellar infarction and he was admitted to our hospital. MRI revealed a fresh thrombus in the right transverse sinus and angiography revealed the occlusion of the right transverse-sigmoid sinus. He complained of vertigo again and he was re-admitted to our hospital 4 months after the first admission. Angiography revealed a dural arteriovenous fistula (DAVF) of the right transverse-sigmoid sinus fed by the right occipital artery and the right transverse-sigmoid sinus was found to be recanalized. The angiography which was carried out one year after the second admission, revealed also an enlarged DAVF fed by the left occipital artery and the right transverse sinus was occluded again. There are two theories about the pathogenesis of DAVF. One is that it is congenital and the other that it is acquired, but it is still controversial. Our case suggested that sinus thrombosis induced DAVF initially and the DAVF induced sinus thrombosis secondarily. The causal relations between DAVF and sinus thrombosis probably changed inversely over a long term and, when we discuss the pathogenesis of DAVF, we must understand the natural history of DAVF starting from the occurrence of sinus thrombosis.

Arteriovenous Fistula↗
PubMed1999

[Autoimmune polyglandular syndrome].

Among many etiologies for hypoparathyroidism, one of the inheritable forms of hypoparathyroidism, called as autoimmune polyglandular syndrome (APS), appears as a complex of hypofunction of several endocrine glands, candidiasis, pernicious anemia and vitiligo. Idiopathic hypoparathyroidism in APS typically presents by 20 years of age. Among the three most components of APS I, candidiasis is usually the first manifestation. Hypoparathyroidism almost invariably precedes the onset of Addison's disease. One should remember that Addison's disease can mask the presence of hypoparathyroidism and that glucocorticoid replacement therapy alone can cause hypocalcemic crisis.

Addison Disease↗
PubMed1999

Genetic polymorphism of CYP2D6 in the Japanese population.

The frequencies of CYP2D6 mutations in a Japanese population were investigated. Individuals were classified into three groups: control individuals, cancer patients and Parkinsonians. Genotyping for CYP2D6*3, CYP2D6*4 and CYP2D6*18 was carried out using the polymerase chain reaction, and that for CYP2D6*5 was also carried out using XbaI restriction fragment length polymorphism. The frequencies of the CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*18 mutant alleles were 0%, 0.77%, 4.10% and 0.53% in more than 256 Japanese control individuals, respectively. Based on these data, the population frequency of the CYP2D6 poor metabolizer phenotype was estimated to be 0.29%. The distribution of the four mutated alleles was not significantly different between control individuals and cancer patients or Parkinsonians.

Alleles↗
PubMed1998

Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells.

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-Ealpha. When immature DCs from I-Ab mice were cultured for 5-20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC-peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DRalpha includes the same peptide sequence as mouse I-Ealpha. Antigen transfer was preceded by uptake of B cell fragments into MHC class II-rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1-10 thousand times more efficient in generating MHC-peptide complexes than preprocessed I-E peptide. When we injected different I-E- bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

Animals↗
PubMed1998

Retroviral gene transfer: effects on endothelial cell phenotype.

BACKGROUND: Endothelial cells (EC) are an attractive target for somatic cell gene therapy, both for the treatment of cardiovascular disease and for the systemic delivery of recombinant gene products directly into the circulation. Recent evidence, however, suggests that viral transduction may induce unfavorable changes in EC phenotype. We examined the proliferative capacity and cell adhesion molecule (CAM) profile of EC after retroviral gene transfer (GT), employing a clinically relevant ex vivo GT protocol. METHODS: Human umbilical vein EC (HUVEC, N = 14 isolates) were exposed to supernatants containing the MFG.nlsLACZ vector, which codes for a nuclear localized beta-galactosidase. Control HUVEC were exposed to empty virus (CRIP) or no virus (NT). Efficiency of GT was quantitated by direct counting of beta-galactosidase-stained cells on a grid. Proliferation was quantitated by a 1-week assay of viable cell counts. Expression of EC activation molecules (Class II major histocompatibility antigen [MHC II], E-selectin, intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) was examined using fluorescent cytometry (FACS) at rest and after cytokine stimulation. RESULTS: GT was reproducibly efficient (mean 57%, range 40-77%) using sequential viral exposures without selection. NT, CRIP, and LACZ-transduced HUVEC exhibited identical FACS profiles for E-selectin, ICAM-1, VCAM-1, and MHC II at rest, consistent with a nonactivated state. Upregulation of expression by cytokine was quantitatively similar for all groups. Growth rates were likewise not different between groups. CONCLUSIONS: Retroviral vectors may be employed to achieve high percentages of transduced EC for ex vivo GT without the use of selection. Transduced EC generated in this fashion are not activated, demonstrate an unaltered pattern of inducible CAM expression, and exhibit normal cell growth. The effects of GT on target cell phenotype are likely to be both vector and protocol specific and should be carefully assessed in each case prior to in vivo applications.

Cell Division↗
PubMed1998

A new strategy for treatment of autoimmune diseases in chimeric resistant MRL/lpr mice.

A new strategy for the treatment of autoimmune diseases in chimeric resistant MRL/lpr mice is established. The strategy includes injection of cyclophosphamide (CY), fractionated irradiation (5 Gy x 2), bone grafts (to recruit stromal cells), and two transplantations of whole bone marrow cells (WBMCs) from allogeneic normal C57BL/6 mice (CY/2X/Bone/2BMT). MRL/lpr mice, thus treated, survived more than 40 weeks (1 mouse survived for >40 weeks, 7 for >50 weeks, and 4 for >60 weeks after these treatments). Immunohistological studies showed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as systemic lupus erythematosis and rheumatoid arthritis. The levels of autoantibodies (IgM/IgG rheumatoid factors and IgM/IgG anti-ssDNA antibodies [Abs]) in the treated mice decreased to those in the normal mice. In addition, successful cooperation among T cells, B cells, and antigen-presenting cells (APCs) was observed. Abnormal T cells with immunophenotypes of B220+/Thy-1+/CD3+/CD4-/CD8- present in untreated MRL/lpr mice disappeared, and the hematolymphoid cells of the treated mice were of donor origin. However, the mice that had been irradiated with 8.5 Gy and then reconstituted with T-cell-depleted BMCs plus bone grafts died within 2 weeks due to the side effect of irradiation. The depletion of CD8+ cells (not CD4+ cells) from WBMCs resulted in graft failure; 60% of the recipient mice, thus treated, died within 2 weeks, and all recipients died by 15 weeks. Furthermore, limiting dilution assays showed that approximately more than 0.5% of T cells contained in the BMCs are necessary not only for engraftment of BMCs but also for long-term disease-free survival of the recipients. In contrast, recipients that had received CD4-depleted BMCs with CY plus fractionated irradiation (5Gy x 2) survived for more than 40 weeks without showing graft-versus-host reaction (GVHR). This indicates that CD8(+)cells in the BMCs are essential for the successful engraftment of the donor-type hematolymphoid cells.

Animals↗
PubMed1998

A strategy for organ allografts without using immunosuppressants or irradiation.

A strategy to achieve regular and long lasting organ and tissue allografts without using immunosuppressants and/or irradiation has been established for mice. One hundred percent of skin allografts can be induced to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be described as follows: (i) donor T cells from the spleen of the donor facilitate the acceptance of the allogeneic engraftment, (ii) donor-specific anergy is induced in the cytotoxic T-lymphocytes of the recipients, (iii) T helper type 2 cells become the dominant T cells in the recipients that are accepting the skin transplants, and (iv) a lasting chimerism (microchimerism) is established in these recipients. This strategy, perhaps with minor modifications, might permit one also to overcome major barriers to organ allografting in humans. If this were the case, it could represent production of long lasting immunologic tolerance without need for irradiation or cytotoxic chemo-preparative regimen and as such could greatly facilitate allotransplantation free of episodes of chronic or acute rejection or toxic and damaging preparatory regimens.

Adoptive Transfer↗
PubMed1998

Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy.

BACKGROUND: Cell adhesion molecules are among the key factors in the development of the malignant potential of brain tumors. The aim of this study was to investigate the expression of the neural cell adhesion molecule (NCAM) in human astrocytic tumors and assess any relationship between NCAM expression and the degree of malignancy. METHODS: The expression of NCAM was examined in 52 astrocytic tumors by Western blot analysis. From them the authors selected 23 adult supratentorial ordinary astrocytic tumors and performed quantitative Western blot analysis for each isoform (NCAM 172-180, NCAM 145, NCAM 125-130) to investigate any correlation between the expression of each NCAM isoform and the histologic and biologic malignancy (histology, proliferating cell indices [PCIs] determined by MIB-1 immunohistochemistry, and manifestation on magnetic resonance images [MRIs]). Immunohistochemistry with antihuman NCAM monoclonal antibody was also performed on the tumors from which cryostat sections were available. RESULTS: Most of the astrocytomas and anaplastic astrocytomas revealed 3 bands at 180, 145, and 125-130kD, whereas in glioblastomas the bands tended to diminish. The expression of each NCAM isoform in astrocytic tumors decreased in proportion to the progression of the histologic malignancy, and the results were also corroborated by immunohistochemical evaluation. An inverse correlation was also observed between the amount of NCAM expression and MIB-1 PCIs. NCAM expression was hardly detectable in those tumors with highly invasive manifestation on MRIs. CONCLUSIONS: To the authors' knowledge, this study provides the first direct evidence that NCAM is down-regulated in the development of the malignancy of astrocytic tumors; and it is suggested that reduced NCAM expression might be involved in the development of biologic malignancy.

Adult↗
PubMed1998

Molecular basis of bovine red-cell protein 4.2 polymorphism in Japanese black cattle.

Cattle were divided into three groups according to the red cell-protein 4.2 (P4.2) phenotypes P4.2(76), P4.2(75) and P4. 2(76/75), whose red cells contained Mr 76000 (P4.2/76), 75000 (P4. 2/75) and both 76000 and 75000 isoforms respectively. To elucidate the molecular basis that underlies the diversity of P4.2, the gene structures of bovine P4.2/76 and P4.2/75 were investigated. Two P4.2 cDNA clones were isolated from bone-marrow cDNAs of the animal with the P4.2(76/75) phenotype. These were identical in size (2.2 kb), encoding major erythroid P4.2 with 687 amino acids, but were different in three nucleotides, resulting in changes of amino acids at the 599th, 601st and 627th residues. Analysis of genomic DNA from the three phenotypes demonstrated that these two clones were derived from gene transcripts by which P4.2/76 and/or P4.2/75 were produced. In vitro transcription and translation of P4.2/76 and P4.2/75 cDNAs indeed generated P4.2/76 and P4.2/75 identical in size to the red-cell proteins. These findings demonstrated that polymorphism of the P4.2 gene at codons 599, 601 and 627 of P4.2 cDNA was the cause of the molecular diversity of bovine red-cell P4.2. Although distinct electrophoretic mobilities suggested a structural difference in the two isoforms, this polymorphism appeared to have little effect at least on P4.2 association with band 3, since no significant difference was observed in the amount of P4.2 relative to total membrane proteins despite the phenotype difference for P4.2.

Amino Acid Sequence↗
PubMed1998

Stimulatory effects of hepatocyte growth factor on hemopoiesis of SCF/c-kit system-deficient mice.

In this study, we report that W/W mutant mice, which have severe macrocytic anemia caused by a deficit of extracellular domain in c-kit molecules and therefore die perinatally, have hemopoietic stem cells (HSCs) and mature hematolymphoid cells in the bone marrow (BM), thymus, and spleen, although there are significant decreases in cell counts. Moreover, the mitogen-induced proliferative response, mixed lymphocyte reaction, and anti-SRBC plaque formation of spleen cells in W/W mice are similar to those in age-matched +/? littermates and normal mice, suggesting that the SCF/c-kit system is necessary for cell proliferation but not essential for HSCs to differentiate. We next examine the stimulatory effects of hepatocyte growth factor (HGF) on hemopoiesis in W/W mice. HGF has a stimulatory effect on the colony formation (CFU-C) of W/W BM cells when cultured using either a methylcellulose assay (containing cytokines) or a long-term culture (LTC) assay. A similar stimulatory effect of HGF is observed in the other W or SI locus-mutant mice (W/Wv and SI/SId mice), which show less severe anemia than W/W. The numbers of nonadherent cells and cobblestone colonies significantly increase in the LTCs using their BM cells. In addition, in vivo administration of HGF shows a transient increase in the CFU-C counts in BM cells and peripheral blood cells. RBC, WBC, and platelet counts also increased. These results suggest that the SCF/c-kit system is not essential to hemopoiesis but that a compensatory system such as the HGF/c-met system functions in the SCF/c-kit system-deficient mice.

Anemia, Macrocytic↗