Biomedical subjects

Y Moroi

Publications and source records attributed to Y Moroi.

At least 19 recordsLinked to original sources

PubMed2001

[A multicenter cross-sectional study on the Health Related Quality of Life of patients with rheumatoid arthritis using a revised Japanese version of the Arthritis Impact Measurement Scales Version 2 (AIMS 2), focusing on physical disability and its associative factors].

OBJECTIVE: A multicenter cross-sectional survey was conducted to study the current status of Health Related Quality of Life (HRQL) of Japanese patients with rheumatoid arthritis using a revised Japanese version of the AIMS 2, to investigate the association among the self-report physical disability scores and demographic, socioeconomic, and clinical variables in these patients. METHODS: A Japanese version of the AIMS 2 was administered to the randomly chosen 1614 patients with classical and definite rheumatoid arthritis attending arthritis clinics at eleven hospitals across the country. Self-report functional disability scores (FDSs) were calculated, by which patients were classified into five groups with graded levels of disability. Univariate correlations were examined between FDSs and the scores of the other four components of AIMS-HRQL, disease duration, age, medical costs, and physical and laboratory measures. Analysis of variance was performed to test for among level differences of these variables in each group of patients. Mean values and standard deviations of FDSs were calculated and analysis of variance was used to test for among level differences of the following factors: demographic, socio-economic, clinical measures, and treatment status. RESULTS: Among four scales composing the AIMS 2-HRQL, work disability scores were most strongly correlated with FDSs, followed by the scores of pain, affection and social interaction. The more severely disabled group proved to have weaker grip strength, higher joint count, longer disease duration, higher ESR and blood level of CRP, and lower level of Hb. Patients with more disabilities proved to be older, pay more medical costs, have longer duration of morning stiffness, and higher level of RF. Patients with more advanced Steinbrocker's functional class, doctor's global assessment, Steinbrocker's anatomical stage, higher daily dose of prednisolone intake, lower level of annual income and formal education, and patients taking more kinds of NSAIDs proved to be more severely disabled. Separate, single (never married, widowed), and divorced patients proved to be more severely disabled compared with married ones. Overall, females were more disabled than males. CONCLUSION: Physical disability is associated with the other important aspects of QOL, clinical signs and symptoms, and socio-economic conditions in RA patients. Prevention and management of physical disability should be seriously planned in consideration of the changes in these conditions in RA patients.

Arthritis, Rheumatoid↗

PubMed2000

Solubilization of Polycyclic Aromatic Compounds into n-Decyltrimethylammonium Perfluorocarboxylate Micelles.

Solubilization of polycyclic aromatic compounds in aqueous dilute solutions of three cationic amphiphiles was studied. The maximum additive concentrations (MACs) of the aromatic compounds were constant below their critical micelle concentrations (cmcs) and monotonically increased above the cmcs. The first stepwise association constants (K(1)) between a solubilizate monomer and a vacant micelle were evaluated from the MACs for the solubilizates using the mass action model for solubilization into micelles in the dilute solution. The standard Gibbs energy changes of solubilization (DeltaG degrees ) were calculated from K(1), and the enthalpy and entropy changes of solubilization were estimated from the temperature dependence. MACs of each surfactant at the same surfactant concentration above the cmc were different depending on the cmc, but there was little difference in the DeltaG degrees values. Some differences appeared in the enthalpy and entropy values in accordance with their micellar size or degrees of counterion binding to micelles. DeltaG degrees for solubilization decreased linearly with carbon number of aromatic solubilizate for each micellar solution. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70.

Heat shock proteins 70 (hsp70) derived from tissues and cells can elicit cytotoxic T lymphocyte (CTL) responses against peptides bound to hsp70. However, peptides can markedly differ in their affinity for hsp, and this potentially limits the repertoire of peptides available to induce CTL by the hsp immunization. Hybrid peptides consisting of a high-affinity ligand for the peptide-binding site of hsp70 joined to T cell epitopes by a glycine-serine-glycine linker were constructed. Immunization with hybrid peptides complexed to mouse hsp70 effectively primed specific CTL responses in mice and were more potent than T cell peptide epitopes alone with hsp70. In vivo immunization with hsp70 and hybrid peptides led to rejection of tumors expressing antigen with greater efficacy than immunization with peptide epitope plus hsp70. Induction of CTL responses occurred independently of CD4(+) T cells, suggesting that immunization directly primed antigen-presenting cells to elicit CD8(+) cytotoxic T cell responses without T cell help. Both peptide/hsp70 complexes and mouse hsp70 alone were able to induce cultures of mouse bone marrow-derived dendritic cells (DC) to release cytokines, including DC from endotoxin-resistant C57BL/10Sc mice. Thus, hsp70/hybrid peptide complexes can activate DC for cytokine release, providing a potential adjuvant effect that could bypass T cell help.

Animals↗

PubMed1999

A role for a melanosome transport signal in accessing the MHC class II presentation pathway and in eliciting CD4+ T cell responses.

Melanosomal membrane proteins are frequently recognized by the immune system of patients with melanoma and vitiligo. Melanosomal glycoproteins are transported to melanosomes by a dileucine-based melanosomal transport signal (MTS). To investigate whether this sorting signal could be involved in presentation of melanosome membrane proteins to the immune system, we devised a fusion construct containing the MTS from the mouse brown locus product gp75/tyrosinase-related protein-1 and full-length OVA as a reporter Ag. The fusion protein was expressed as an intracellular membrane protein, sorted to the endocytic pathway, processed, and presented by class II MHC molecules. DNA immunization with this construct elicited CD4+ T cell proliferative responses in vivo. Ag presentation and T cell responses in vitro and in vivo required a functional MTS. Mutations of either the upstream leucine in MTS or elimination of the entire MTS negated in vitro Ag presentation and in vivo T cell responses. In a mouse melanoma model, DNA immunization with MTS constructs protected mice from tumor challenge in a CD4+ T cell-dependent manner, but complete deletion of MTS decreased tumor rejection. Therefore, MTS can target epitopes to the endocytic pathway leading to presentation by class II MHC molecules to helper T cells.

Amino Acid Sequence↗

PubMed1999

Micelle Formation of Anionic Surfactant with Divalent Counterion of Separate Electric Charge.

The critical micelle concentration (CMC) of the anionic surfactant, 1,1'-(1,omega-decanediyl) bispyridinium hexadecane-1-sulfonate (C10BP(C16)2) was determined by electrical conductivity measurements at various temperatures. The degree of counterion binding to micelles was evaluated from the change in CMC with total counterion concentration. The molecular weight of the micelles was determined by static light scattering. The mass action model was applied to micelle formation in order to calculate the three micellization parameters, the micellization constant, the micelle aggregation number, and the number of counterions per micelle. Thermodynamic parameters (DeltaG0, DeltaH0, -TDeltaS0) for the micellization were evaluated by their temperature dependence. The findings were: (1) Micelle formation was entropy-driven over the whole temperature range examined. (2) C10BP(C16)2 had a higher degree of counterion binding to micelles compared with those of monovalent counterion. (3) The plots of log CMC against the carbon number of the homologous surfactant ions gave a straight line, indicating that free energy change per methylene group for micelle formation was -1.18RT for surfactant ions. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects.

An important issue for effective vaccines is the development of potent adjuvants that can facilitate induction or augmentation of immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for myeloid progenitors of monocytes and dendritic cells (DC), which upon maturation are antigen-presenting cells (APC). The adjuvant effects of inoculation of DNA encoding GM-CSF into skin were studied. Initial experiments examined whether the GM-CSF gene injected into the skin of mice could affect the density of epidermal DC (Langerhans cells). DNA encoding GM-CSF delivered by particle bombardment into skin resulted in a significant increase of epidermal DC at the inoculation site. Kinetic analysis of epidermal recruitment after GM-CSF inoculation showed an increase in DC that peaked at seven days. This increase was accompanied by recruitment of DC into draining lymph nodes. The adjuvant effects of DNA encoding GM-CSF inoculated into skin were measured by the ability to augment antibody and T-cell responses against poorly immunogenic tumor antigens. Peptide immunization at skin sites containing epidermal DC newly recruited by GM-CSF DNA elicited T-cell responses against mutant p53, whereas peptide immunization of control skin sites did not elicit any detectable T-cell responses. Likewise, generation of antibodies following immunization with DNA encoding human gp75TRP1, a tyrosinase family member expressed by melanomas, was accelerated and protection from tumor challenge augmented by GM-CSF DNA.

Adjuvants, Immunologic↗

PubMed1998

Heteroclitic immunization induces tumor immunity.

In tumor transplantation models in mice, cytotoxic T lymphocytes (CTLs) are typically the primary effector cells. CTLs recognize major histocompatibility complex (MHC) class I-associated peptides expressed by tumors, leading to tumor rejection. Peptides presented by cancer cells can originate from viral proteins, normal self-proteins regulated during differentiation, or altered proteins derived from genetic alterations. However, many tumor peptides recognized by CTLs are poor immunogens, unable to induce activation and differentiation of effector CTLs. We used MHC binding motifs and the knowledge of class I:peptide:TCR structure to design heteroclitic CTL vaccines that exploit the expression of poorly immunogenic tumor peptides. The in vivo potency of this approach was demonstrated using viral and self-(differentiation) antigens as models. First, a synthetic variant of a viral antigen was expressed as a tumor antigen, and heteroclitic immunization with peptides and DNA was used to protect against tumor challenge and elicit regression of 3-d tumors. Second, a peptide from a relevant self-antigen of the tyrosinase family expressed by melanoma cells was used to design a heteroclitic peptide vaccine that successfully induced tumor protection. These results establish the in vivo applicability of heteroclitic immunization against tumors, including immunity to poorly immunogenic self-proteins.

Amino Acid Sequence↗

PubMed1998

Micelle formation of sodium cholate and solubilization into the micelle.

The micellization of sodium cholate (NaC) was studied at 298.2 K by aqueous solubility at different pH values. Using a stepwise association model of cholate anions without the sodium counterion, the aggregation number (n) of the cholate micelle was evaluated and found to increase with the total concentration, indicating that the mass action model worked quite well. The n value at 60 mM was found equal to 16. The membrane potential measurement of sodium ion with a cation exchange membrane was made in order to confirm the low counterion binding to micelle. The solubilization of alkylbenzenes (benzene, toluene, ethylbenzene, n-propylbenzene, n-butylbenzene, n-pentylbenzene, n-hexylbenzene) and polycyclic aromatic compounds (naphthalene, anthracene, pyrene) into the aqueous micellar solution of sodium cholate was carried out. Solubilizate concentrations at equilibrium were determined spectrophotometrically at 298.2 K. The first stepwise association constants (K1) between solubilizate monomer and vacant micelle were evaluated from the equilibrium concentrations and found to increase with increasing hydrophobicity of the solubilizate molecules. From the Gibbs energy change for solubilization at the different mean aggregation numbers and from molecular structure of the solubilizates, the function of sodium cholate micelle for solubilization was discussed and was compared with data from conventional aliphatic micelles.

Micelles↗

PubMed1998

Tumor immunity and autoimmunity induced by immunization with homologous DNA.

The immune system can recognize self antigens expressed by cancer cells. Differentiation antigens are prototypes of these self antigens, being expressed by cancer cells and their normal cell counterparts. The tyrosinase family proteins are well characterized differentiation antigens recognized by antibodies and T cells of patients with melanoma. However, immune tolerance may prevent immunity directed against these antigens. Immunity to the brown locus protein, gp75/ tyrosinase-related protein-1, was investigated in a syngeneic mouse model. C57BL/6 mice, which are tolerant to gp75, generated autoantibodies against gp75 after immunization with DNA encoding human gp75 but not syngeneic mouse gp75. Priming with human gp75 DNA broke tolerance to mouse gp75. Immunity against mouse gp75 provided significant tumor protection. Manifestations of autoimmunity were observed, characterized by coat depigmentation. Rejection of tumor challenge required CD4(+) and NK1.1(+) cells and Fc receptor gamma-chain, but depigmentation did not require these components. Thus, immunization with homologous DNA broke tolerance against mouse gp75, possibly by providing help from CD4(+) T cells. Mechanisms required for tumor protection were not necessary for autoimmunity, demonstrating that tumor immunity can be uncoupled from autoimmune manifestations.

Animals↗

PubMed1998

Fc receptors are required in passive and active immunity to melanoma.

Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) gamma-/- mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective tumor immunity in models of passive and active immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization with mAb against gp75 or active immunization against gp75 prevented the development of lung metastases. This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact in gamma-/- mice because IgG titers against gp75 develop normally in gamma-/- mice immunized with gp75. However, uncoupling of the Fc gamma R effector pathway from antibody recognition of tumor antigens resulted in a loss of protection against tumor challenge. These data demonstrate an unexpected and critical role for FcRs in mediating tumor cytotoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.

Animals↗

PubMed1998

Micelle Formation of Lithium 1-Perfluoroundecanoate

Solution properties of lithium 1-perfluoroundecanoate have been studied by electroconductivity and membrane potential measurements. The degree of counterion binding to micelles was not precisely determined by the Corrin-Harkins plots. The aggregation numbers and the degrees of counterion binding over the temperature range from 288.2 to 313.2 K have been evaluated by a new method that combined the above two measurements and the mass-action model. The thermodynamic parameters of micellization were determined from the temperature dependence of the parameters obtained. The surfactant with a long perfluoroalkyl chain showed micellization properties much different from the corresponding hydrocarbon surfactant in that the temperature dependence of the aggregation number, the degree of counterion binding, the enthalpy change of micellization, and the entropy change of micellization are much greater. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

PubMed1998

Solubilization of n-Alkylbenzenes into Lithium 1-Perfluoroundecanoate Micelles

The solubilization of benzene, toluene, ethylbenzene, n-propylbenzene, n-butylbenzene, n-pentylbenzene, n-hexylbenzene, and some arenes into lithium 1-perfluoroundecanoate micelles was measured with increasing the surfactant concentration. Concentrations of all the solubilizates in equilibrium were determined spectrophotometrically at 293.2, 298.2, 303.2, and 308.2 K. The concentration of benzene, toluene, naphthalene, anthracene, and pyrene was not found to increase under the same condition. The first stepwise association constants (K1) between solubilizate monomer and vacant micelle were evaluated from the equilibrium concentration of solubilizate and were found to increase with increasing hydrophobicity of the solubilizate molecules for the alkylbenzenes. The thermodynamic parameters in this system were compared with those for solubilization into 1-dodecanesulfonic acid micelles. These solubilizates were all solubilized on the surface region of the fluorocarbon micelles, which is different from the previous result that the solubilizates with longer alkyl chains were in the inner part of the above-mentioned hydrocarbon micelles. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

PubMed1997

Micelle Formation of n-Decyltrimethylammonium Perfluorocarboxylates

Critical micelle concentrations (CMCs) of three ionic surfactants that contain n-decyltrimethylammonium ion as a surfactant cation and bromide, perfluoroacetate, and perfluoropropionate anions as a counterion, respectively, were determined by electrical conductivity at several temperatures. The degrees of counterion binding to micelle were obtained at the same temperatures as the change in CMC with total counterion concentration. Molecular weights of micelles were determined by static light scattering. The change in monomeric surfactant ion concentration with total surfactant concentration was determined by membrane potential measurement. The mass-action model was applied to micelle formation to calculate the three micellization parameters: micellization constant, micelle aggregation number, and number of counterions per micelle. Thermodynamic parameters (DeltaG0, DeltaH0, DeltaS0) of the micelle formations were calculated from the temperature dependence of these parameters. At lower temperatures micellization has been found to be entropy driven, whereas it is enthalpy driven at higher temperatures. For n-decyltrimethylammonium perfluoropropionate, however, the tendency is quite different from those of other surfactants. The micellization parameters also made it possible to evaluate the concentration change of monomeric surfactant ion with total surfactant concentration. The evaluated concentration explains the results from the membrane potential measurement.

Journal Article↗

PubMed1996

Monolayer Properties of Long-Chain Alkylammonium Perfluorohexanoates on the Concentrated Sodium Chloride Solution

Surface pressure (pi)- and surface potential (DeltaV)-area (A) isotherms were obtained for monolayers of alkylammonium perfluorohexanoates of four different alkyl chains (m) on water and 4.4 M NaCl solutions as a function of molecular area of various temperatures by the Langmuir and the ionizing electrode methods. As for octadecylammonium perfluorohexanoate (C18F11), the pi-A curves of these long-hydro-short-fluoro chain salt showed three phase transition points. Judging from the surface potential and the apparent molar quantity together with our previous data on the transitions, the first was assigned to the transition from the expanded (E) phase to the condensed (C-I) phase, the second from the C-I phase to another condensed (C-I') phase, and the third from the (C-I') phase to another condensed (C-II) phase. From the surface potential, the apparent molar entropy change, and the phase diagram, the orientation of long-hydro-short-fluoro chain salts in the monolayer state was discussed.

Journal Article↗

PubMed1995

[Quality of life, subjective health status and health and life satisfaction in rheumatoid arthritis].

A Japanese version of Arthritis Impact Measurement Scales (AIMS) was developed after the original AIMS Version 2 and utilized for Quality of Life (QOL) measurement in 691 patients with Rheumatoid Arthritis (RA). Various medical (physical and laboratory) examinations, which are widely used in the clinical settings for the assessment of RA activity and severity, were also performed by physicians. Interrelationships between QOL, patient subjective health status, and health and life satisfaction were analyzed with the following results: 1: The effect of QOL impairment by RA upon patients' subjective health rating and health satisfaction were not constant over the range of severity of disease status. Pain was found to lower overall subjective health and health satisfaction regardless of RA class. On the other hand, while the deterioration of mobility aspects of QOL had negative effects upon patients' subjective health status and satisfaction among less-disabled RA patients, any of physical aspects of QOL, including the degree of mobility impairment, showed no significant association with patients' subjective health status and satisfaction in the more disabled. 2: Psychological aspects of QOL (mood and tension) had significant associations with patients' subjective health status and satisfaction. In the less severe group, mood impairment had a significant effect on subjective health and satisfaction, while in the more severe group tension showed a significant association. It was indicated that management of psychological aspects of QOL is important in RA patients to improve and advance their subjective health status and satisfaction. 3: Although social aspects of QOL, i.e. social support, social life and job status, showed no significant relationship to subjective health rating and health satisfaction, those with less disease severity who lacked social support and who had a jobless state were likely to have lower disease acceptance and life satisfaction, while those with more severe disease who had less social interaction manifested lower life satisfaction. These results suggested that social aspects of QOL, while not directly associated with subjective health rating, could be important factors affecting disease acceptance and life satisfaction.

Adult↗

PubMed1994

Ultraviolet-B irradiation alters cytokine production by immune lymphocytes in herpes simplex virus-infected mice.

Previous studies from our laboratories have shown that UV-B irradiation at the site of an intradermal infection of herpes simplex virus (HSV) resulted in a higher incidence of zosteriform lesions and suppressed cellular immune responses to HSV in mice. In order to determine whether the production of T-cell-derived cytokine (IFN-gamma, IL-2 and IL-4) by immune cells from irradiated mice is also suppressed, we examined the production of cytokines by lymph node cells and spleen cells taken from UV-B irradiated, HSV type 1 (HSV-1)-infected mice. UV-B irradiation (120 mJ/cm2) prior to HSV-1 infection was found to markedly suppress IFN-gamma production compared to that of the non-irradiated control. IL-4 production was enhanced compared to IL-2 in the UV-B irradiated mice. These results suggest that alteration(s) in the cytokine production profile may therefore be involved in the development of severe skin lesions caused by HSV infection in UV-B irradiated mice.

Animals↗

PubMed1993

Chromosome abnormalities in peripheral lymphocytes from patients with progressive systemic sclerosis.

Chromosomal abnormalities in cultured peripheral lymphocytes from 14 progressive systemic sclerosis (PSS) patients and 15 normal subjects were examined. No increase was observed in the frequency of chromosome aberrations in PSS patients who had not received any medical treatment. Those who had received medication showed an increased frequency of dicentrics (0.3%) although the frequency was not significantly higher than that for normal subjects. It is not clear, however, whether the increase was due to the hypersensitivity of PSS patients to agents used for therapeutic purposes.

Adult↗

PubMed1993

Augmentation of in vitro cytolytic activity of LAK cells with heated ATL-derived cell lines.

Three adult T-cell leukemia/lymphoma-derived cell lines, MT-2, MJ, and HUT102, were investigated to determine how they responded to hyperthermia, lymphokine-activated killer (LAK) cells, or a combination of both in vitro. All three cell lines showed a similar sensitivity to LAK cells, but revealed varying degrees of sensitivity to hyperthermia (MT-2 < MJ < HUT102) by 51Cr release assay. Hyperthermia did not cause immediate cell death as determined by the trypan blue exclusion test, but did cause substantial decreases in the numbers of heated cells within 2 days. The density of the cells began to increase thereafter, which was consistent with the results of the experiments labeling the cells with 3H-TdR after hyperthermia. When the cells were heated at 39-43 degrees C for 1-3 hr and then interacted with various LAK cell/ATL cell (E/T) ratios at 37 degrees C for 4 hr, total cytolysis of the cells increased in a synergistic and/or additive manner over that of the cells without hyperthermia. Prolonged incubation of the cells at high temperature did not necessarily cause a large increase in the interaction of LAK cells after hyperthermia. This augmentation of cytolysis by LAK cells after hyperthermia was not seen in normal peripheral lymphocytes. These results suggest that the combination therapy of hyperthermia and LAK cells may be more specific, useful, and effective for treating malignant lymphoma.

Cytotoxicity, Immunologic↗