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Biomedical subjects

A Shirai

Publications and source records attributed to A Shirai.

At least 55 records · Page 3Linked to original sources
PubMed1994

Lack of correlation between the number of circulating B cells and the concentration of serum antibodies reactive with the HIV-1 envelope glycoprotein.

Cells obtained from the peripheral blood of HIV-infected patients and volunteers immunized with HIV-1 vaccines are commonly used to study anti-viral responses, since lymphocytes from the central lymphoid organs are difficult to obtain. Analyses involving PBMC implicitly assume that circulating B cells provide an accurate reflection of the systemic humoral response induced by the HIV antigens. We examined this assumption by comparing the number of B cells secreting IgG anti-gp160/120 antibodies in the peripheral circulation with serum antibody titers. Results indicate that neither the magnitude nor duration of the serologic response detected in HIV-infected patients or gp160/gp120-immunized volunteers reproducibly correlates with the number of B cells secreting anti-envelope antibodies in the blood.

AIDS Vaccines↗
PubMed1993

Detection and quantitation of cells secreting IL-6 under physiologic conditions in BALB/c mice.

IL-6 is a pleiotropic cytokine involved in the regulation of hematopoiesis and lymphocyte activation. An extremely sensitive ELIspot assay was developed to detect and enumerate individual cells secreting IL-6 in normal BALB/c mice. Under physiologic conditions, the frequency of cells producing IL-6 in the bone marrow, spleen, and mesenteric lymph nodes of normal adult animals was approximately 0.5, 0.1, and 0.01%, respectively. FACS analysis revealed that macrophages and Mac1- B220- cells accounted for the vast majority of IL-6 production in the bone marrow, whereas T and B lymphocytes accounted for 4% and 38% of IL-6 production in the spleen. Simultaneous studies comparing cell number with IL-6 levels indicated that the average activated cell produced approximately 85 molecules of IL-6/s.

Animals↗
PubMed1993

Polyclonal B cell activation and antigen-specific stimulation in mice with chronic graft-versus-host reaction.

Primary chronic graft-versus-host reaction (GVHR) was induced in (C57BL/10 x DBA/2)F1 (BDF1) mice via the transfer of parental DBA/2 derived lymphocytes. A significant increase in the absolute number of IgM- and IgG-secreting cells was found in recipient BDF1 mice at 3 weeks post-transfer. The increase included B cells reactive with both self- and non-self-antigens, without being skewed toward the production of autoantibodies. Later in the disease process (approximately 6-8 weeks post-transfer), we detected an increased number of B cells that secreted antibodies reactive with a select subset of autoantigens in about 30% of BDF1 recipients (3 of 9 mice). These findings suggest that not only antigen-specific stimulation, which was detected in a late stage, but also initial polyclonal activation may account for chronic GVHR.

Animals↗
PubMed1993

Immunization with recombinant gp160 prolongs the survival of HIV-1 transgenic mice.

A strain of mouse transgenic for the env gene of the HIV-1 virus was used to study the immunogenicity of a gp160-derived vaccine (the protein encoded by the HIV env gene) and its effect on disease progression. Untreated transgenic mice frequently developed a rapidly progressive renal disease similar to that affecting approximately 10% of HIV-infected humans. When transgenic mice were immunized with recombinant purified gp160, their edema, proteinuria, and serum BUN levels were substantially reduced and their survival prolonged (p < 0.01). The increased longevity of immunized transgenic mice correlated with the production of IgG antibodies reactive with gp160.

AIDS Vaccines↗
PubMed1992

Inhibition of different steps of the ubiquitin system by cisplatin and aclarubicin.

Ubiquitin is involved in such fundamental cellular processes as cell cycle control, DNA repair, protein degradation and stress responses. We previously reported that cisplatin could inhibit the ubiquitin-ATP-dependent proteolysis and ubiquitination. We further investigated the effect of various antitumor agents on the ubiquitin system and found that aclarubicin (ACR) inhibits the ubiquitin-ATP-dependent proteolysis but not the ubiquitination process. We found that ACR as well as cisplatin inhibited the ubiquitin-ATP-dependent proteolytic activity of rabbit reticulocytes. The IC50 values of these agents were 52 and 90 microM, respectively. Although cisplatin inhibits the conjugation of ubiquitin to proteins through the inhibition of a ubiquitin-activating enzyme, ACR, at 120 microM, does not. Thus, the antitumor agents affecting the ubiquitin system could be classified into two groups; one is represented by cisplatin, which inhibits the ubiquitination of the proteins, and the other is ACR, which does not inhibit the ubiquitination but does inhibit the ubiquitin-ATP-dependent proteolysis. Mitomycin C belongs to the latter group.

Aclarubicin↗
PubMed1992

In vivo measurement of spatial dose distribution with thermoluminescent sheet around high dose-rate intracavitary source: application to rectal cancer.

For intracavitary high dose-rate radiation therapy, a thermoluminescent [TL] sheet for in vivo measurement of spatial dose distribution around source has been recently developed. The TL sheet was found to have a linear response with a very wide dynamic range from at least 0.002 cGy to 5000 cGy for 60Co gamma-rays. This TL sheet (40 cm x 50 cm x 200 microns), which is composed of Teflon mixed with BaSO4:Eu doped powder, is very flexible and can be cut to the desired size. In addition, this sheet is easy to handle because of its insensitivity to room light. The spatial dose distribution is displayed in a color mode by using a newly developed TL sheet readout system. For a clinical application, the TL sheet was wrapped on an applicator for intracavitary radiation therapy of a rectal cancer and was inserted into the rectum. The location of the TL sheet could be confirmed with diagnostic X ray film. After irradiation with high dose-rate 60Co source, the in vivo relative dose distribution on the surface of the rectum was determined. This TL sheet provided a convenient means of measuring the relative dose distributions around 60Co sources of various patterns in intracavitary radiation therapy.

Brachytherapy↗
PubMed1992

Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation.

Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number of IgM-, IgG-, and IgA-producing lymphocytes per 10(6) PBL was increased 2.8-, 3.4-, and 1.9-fold, respectively, compared with normal controls. 2-17% of IgG-secreting patient cells reacted with the gp160 envelope glycoprotein of HIV-1 (a 737-fold increase over background), while 1-9% reacted with p24 (140-fold over background). In addition to this HIV-specific B cell activation, the number of lymphocytes reactive with nonviral antigens such as DNA, myosin, actin, trinitrophenylated keyhole limpet hemocyanin, and ovalbumin was increased by a mean of 17.9-fold. Evidence suggests that the latter changes reflect an HIV-induced polyclonal B cell activation unrelated to the production of anti-HIV antibodies. For example, the proportion of IgG anti-gp160- and anti-p24-secreting lymphocytes declined in patients with advanced disease, whereas the number of B cells producing antibodies to non-HIV antigens rose. Moreover, CD4 cell count and T4/T8 ratio showed a significant inverse correlation with the degree of polyclonal activation but not with anti-HIV responsiveness. These observations demonstrate that both quantitative and qualitative changes in B cell activation accompany (and may be predictive of) disease progression in HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Increase in intracellular calcium induced by stimulating histamine H1 receptors in macrophage-like P388D1 cells.

The addition of histamine to macrophage-like P388D1 cells resulted in a dose-dependent increase in intracellular calcium [Ca2+]i measured by fura-2 in single cells. The maximum level of [Ca2+]i was obtained by addition of 1 x 10(-4) M histamine. The increase was primarily due to release from the intracellular store. The addition of an H1 specific antagonist pyrilamine before histamine treatment inhibited the increase reversibly, while an H2 specific antagonist cimetidine had no inhibitory effect. Histamine also resulted in a dose-dependent increase in cGMP but not in cAMP. These data suggest the existence of histamine H1 receptors in these cells and histamine may have some biological effect on the function of macrophages via [Ca2+]i and cGMP as the second messengers.

Animals↗
PubMed1991

Quantitation of IgM- and IgG-secreting B cells in the peripheral blood of patients with systemic lupus erythematosus.

An enzyme-linked immunospot assay was used to quantitate the number of autoantibody-secreting B cells in the peripheral blood of 67 patients with systemic lupus erythematosus. These patients had 1.5-4-fold more lymphocytes secreting IgG and IgM per million peripheral blood lymphocytes than did normal controls. There was a concomitant increase in the number of B cells secreting antibodies reactive with a diverse panel of foreign and self antigens (including actin, myosin, tri-nitrophenylated keyhole limpet hemocyanin, ovalbumin, and retroviral gp160). By comparison, the number of B cells producing anti-DNA antibodies was increased disproportionately. The magnitude of this anti-DNA response correlated significantly with disease activity. Thus, B cell activation in human systemic lupus erythematosus had characteristics of both generalized (polyclonal) B cell activation and (auto)antigen-specific immune stimulation.

Antibodies, Antinuclear↗
PubMed1991

Preferential proliferation of anti-DNA producing cells of NZB mice in NZB.xid recipients.

B cells from autoimmune NZB mice were transferred into unmanipulated non-autoimmune NZB.xid mice. The number of antibody-producing cells against various antigens in recipient mice was monitored at varying time after cell transfer using ELISPOT assay. NZB B cells producing antibody against all antigens we examined were able to proliferate in NZB.xid mice, which supports the idea of polyclonal B cell activation. However, anti-DNA producing cells proliferated most rapidly, and anti-BrMRBC producing cells proliferated more rapidly than B cells of other antigenic specificities. The percentage of anti-DNA producing cells in total immunoglobulin-producing cells increased over time whereas the percentage of anti-ovalbumin producing cells kept the same level. This indicates directly the preferential proliferation of NZB anti-DNA producing cells in NZB.xid mice. The result shows the responsibility of antigen-specific stimulation or activation on autoimmunity in the context of polyclonal B cell activation.

Actins↗
PubMed1990

[Serum type III procollagen N-terminal peptide in patients with collagen diseases].

The serum concentration of type III procollagen N-terminal peptide (P III P) level is known to reflect the activity of collagen biosynthesis. To analyze the correlation between the disease activity and serum P III P levels in collagen diseases, serum P III P levels in patients with rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), and other collagen diseases were measured. In some patients serum levels of prolyl++-hydroxylase, which is an intra-cellular enzyme of collagen biosynthesis, were measured. Serum P III P levels were elevated in patients with PSS and MCTD/overlap syndrome, suggesting a high rate of collagen biosynthesis by fibroblasts. Patients with RA showed no significant elevation of serum P III P compared with normal control group. But the group of RA patients with elevated ESR and/or serum CRP values showed high levels of serum P III P. The correlation between the disease activity and serum P III P levels was observed in RA patients with positive rheumatoid factor (RF), but not patients without RF. In addition we measured P III P levels in synovial fluid of RA and osteoarthritis patients. The levels were one to three hundred times higher than serum levels, and they showed the positive correlation with serum levels, suggesting that serum P III P might be originated from synovial P III P.

Adult↗
PubMed1990

[Their titers and recognized molecules of IgG class anti-BCG antibody in sera from patients with tuberculosis].

Hypergammaglobulinemia is a frequent complication of tuberculosis. Serum levels of each class of immunoglobulin were analyzed among tuberculosis patients. Adult patients had high levels of IgG and IgA, but IgM levels were not elevated. These data suggested that antibody responses to mycobacterial antigens might be influenced by individual immune responses. In order to analyze the specific antibody responses to mycobacterial antigens, IgG class antibodies reactive with BCG proteins were enumerated by an enzyme-linked immunosorbent assay (ELISA). Patients were shown to have significantly higher a mount of IgG antibodies than healthy controls. Sera from patients with active tuberculosis had high consistently titers of antibodies. Antibody titers returned to a normal range after effective treatment, suggesting that the measurement of IgG anti-BCG antibodies would be useful for the diagnosis and follow-up of tuberculosis. In addition, serum antibody profiles were analyzed by immunoblotting. Sonicated whole BCG proteins were electrophorased and transferred to nylon sheets by Western blotting. Then the sheets were developed with sera from patients or controls. Mycobacterial cell wall contains a vast array of proteins so that comparison of the antibody profiles from different sera revealed striking individual variations. However two kinds of proteins, whose molecular sizes were 65KDa and 16KDa, were considered to be significant. The 65 KDa protein was recognized in most sera from both patients and controls. The protein may be related to a "common antigen" present in a wide variety of bacteria. These observations may shed a new light on the role of 65KDa protein in the regulation of the immune systems, for example a individual highly primed to 65KDa protein may amount an exaggerated and potentially harmful response to cross-reactive antigens from other essentially non-pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Quantitation of autoantibody-secreting B cells in systemic lupus erythematosus.

An ELISA spot assay was used to quantitate the number of autoantibody-secreting B cells in the peripheral blood of patients with systemic lupus erythematosus. Patients with active disease had 20 fold more anti-DNA, 4 fold more anti-actin and 3 fold more anti-myosin secreting lymphocytes than controls but normal numbers of anti-cardiolipin and anti-transferrin secreting B cells. 60% of SLE patients had increased numbers of B cells reactive with multiple autoantigens. These data suggest that B cell activation in SLE may be influenced by both antigen-specific and antigen-independent factors.

Actins↗
PubMed1989

[A case report of macroamylasemia with rheumatoid arthritis].

A patient of rheumatoid arthritis complicated with macroamylasemia. Serum amylase level was persistently elevated without any apparent cause. Amylase creatine clearance ratio was reduced inspite of normal renal function. These findings suggested the presence of macroamylasemia. The abnormal molecular size of amylase isozyme was electrophoresed. Thin layer chromatography and electroimmunosyneresis revealed that the amylase binding molecule was immunoglobulin (IgA kappa type). The etiology and the clinical significance of the macroamylasemia remain unclear. Amylase binding immunoglobulin is thought to be autoantibody to amylase. Thus, the association with autoimmune diseases is suggested. However, only few cases have been reported of autoimmune diseases complicated with macroamylasemia. In this case, macroamylase appeared about 10 months after the onset of RA. Serum amylase level was inconsistent during the clinical course. Further follow-up study is considered to be important.

Amylases↗
PubMed1984

Lack of transplacental infection with scrub typhus organisms in laboratory mice.

Female mice were inoculated with either a virulent or avirulent strain of Rickettsia tsutsugamushi before (1 month and 1 week) or after (approximately 10 days) impregnation. From each group, two pregnant mothers were killed on day 20 post-impregnation, and fetuses and placentas were examined for rickettsiae. Organisms were isolated from 80% of placentas but not from the fetuses. Immediately following parturition, litters from 50% of the infected mothers were exchanged with litters from uninfected mothers. In all cases, no scrub typhus rickettsiae were found in the litters examined on days 1, 7, and 30 postpartum, and no antibody was found in sera collected 1 and 2 months postpartum.

Animals↗
PubMed1984

Febrile illness in Malaysia--an analysis of 1,629 hospitalized patients.

We studied 1,629 febrile patients from a rural area of Malaysia, and made a laboratory diagnosis in 1,025 (62.9%) cases. Scrub typhus was the most frequent diagnosis (19.3% of all illnesses) followed by typhoid and paratyphoid (7.4%); flavivirus infection (7.0%); leptospirosis (6.8%); and malaria (6.2%). The hospital mortality was very low (0.5% of all febrile patients). The high prevalence of scrub typhus in oil palm laborers (46.8% of all febrile illnesses in that group) was confirmed. In rural Malaysia, therapy with chloramphenicol or a tetracycline would be appropriate for undiagnosed patients in whom malaria has been excluded. Failure to respond to tetracycline within 48 hours would usually suggest a diagnosis of typhoid, and indicate the need for a change in therapy.

Adolescent↗
PubMed1983

Development of antibody to Rickettsia tsutsugamushi in soldiers in Malaysia.

Malaysian, British and New Zealand soldiers were tested for evidence of infection with Rickettsia tsutsugamushi after several weeks' exposure to the infection during field exercises in Malaysia. 39 (5.0%) of 787 British and New Zealand soldiers developed immunofluorescent antibody (IFA) to R. tsutsugamushi to a titre of 1:50 and two (0.3%) to a titre of 1:100. 11 (1.5%) of 751 Malaysian soldiers also developed low titres less than or equal to 1:100. These low antibody levels were not correlated with clinical disease, and their significance is unknown. Seven (0.9%) of the Malaysians showed an IFA rise to greater than or equal to 1:200, and three of these experienced febrile illnesses, one lasting two weeks. An additional eight Malaysian soldiers had an IFA titre of greater than or equal to 1:400 when first tested and six of these also had a Proteus OXK agglutinin titre of greater than or equal to 1:160, indicating infection shortly before the study.

Antibodies, Bacterial↗