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Biomedical subjects

A Sonoda

Publications and source records attributed to A Sonoda.

At least 19 recordsLinked to original sources

Polymorphism in the promoter of lipopolysaccharide receptor CD14 and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: A growing amount of evidence suggests that infectious and inflammatory processes may be involved in the initiation of arteriosclerosis, but the mechanisms are conceivably multifactorial and complex. Two European groups have recently demonstrated that a C(-260)-->T polymorphism in the promoter of the CD14 lipopolysaccharide receptor may be a risk factor for coronary artery disease (CAD). The T allele of this polymorphism reportedly increases the expression of CD14 and may be involved in atherogenesis. In the present study we investigated a possible association between the C(-260)-->T polymorphism in the CD14 promoter and the occurrence of symptomatic ischemic cerebrovascular disease (CVD). METHODS: Genotype frequencies of the C(-260)-->T polymorphism in the CD14 promoter were determined in 235 patients with CVD, as confirmed by brain CT and/or MRI, and 309 age- and sex-matched control subjects. RESULTS: The distribution of genotypes was as follows: CVD patients, T:/T: 24.3%, C:/T: 53.2%, and C:/C: 22. 6%; controls, T:/T: 26.9%, C:/T: 50.2%, and C:/C: 23.0%. There was no significant difference between the CD14 promoter genotypes of the CVD patients and the controls (chi(2)=0.601, P:=0.741). We also measured the concentration of serum soluble CD14 and the density of membranous CD14 on monocytes in the CVD patients, but the polymorphism was not associated with either the concentration of soluble CD14 or the density of membranous CD14 (P:=0.358, P:=0.238, respectively). CONCLUSIONS: Our results indicate that the C(-260)-->T polymorphism in the CD14 promoter is not associated with an increased risk for CVD.

Cerebrovascular Disorders↗

Association between platelet glycoprotein Ibalpha genotype and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Platelets play pivotal roles in the development of ischemic cerebrovascular disease (CVD). The platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor, which plays a major role in the initial phase of platelet activation under high shear stress conditions. This study was designed to investigate the association between a genetic variation of this receptor and the prevalence of CVD. METHODS: Two hundred patients with ischemic CVD, as confirmed by brain CT and/or MRI, and 317 age- and sex-matched control subjects without clinical evidence of CVD or cardiovascular disease were analyzed for their genotype frequencies of the (145)Thr/Met dimorphism of the alpha-chain of GPIb (GPIbalpha). RESULTS: Genotypes with (145)Met (T/M and M/M) were more frequently found in the CVD patients (26.5%) than in control subjects (14.2%, P=0.0005). The genotype effect was more obvious in those <60 years of age or without acquired cardiovascular risk factors. The odds ratio for nonsmoking women <60 years of age was 10. 6 (95% confidence intervals, 2.2 to 51.7). Although the number of patients studied was small (n=24), transient ischemic attack showed the highest odds ratio (4.3, P=0.0004), followed by lacunar infarction (OR=2.2, P=0.0024) and atherothrombotic infarction (OR=1. 5, P=0.3143). Logistic regression analysis revealed that the presence of Met-allele was independently associated with CVD. CONCLUSIONS: Our study suggests that the platelet GPIbalpha genotype is a genetic risk factor for ischemic CVD.

Alleles↗

ACAID induced by allogeneic corneal tissue promotes subsequent survival of orthotopic corneal grafts.

PURPOSE: To determine whether immune deviation is induced by allogeneic corneal tissue implanted in the anterior chamber and whether survival of subsequent orthotopic corneal allografts is thereby enhanced. METHODS: Corneal tissue from C57BL/6 mice was implanted in the anterior chamber of eyes of BALB/c mice. The fate of these implants was assessed histologically, and the donor-specific immune response of recipient mice was tested for donor-specific delayed hypersensitivity and the capacity to accept or reject C57BL/6 corneas grafted orthotopically into the fellow eye. RESULTS: C57BL/6 cornea implants in the anterior chamber failed to induce donor-specific delayed hypersensitivity but impaired donor-specific delayed hypersensitivity in a proportion of recipients with implants in place for 2 weeks. Mice with donor-specific delayed hypersensitivity rejected the intraocular implants. Mice bearing C57BL/6 cornea implants in the anterior chamber for 2 (but not 4) weeks accepted the C57BL/6 corneas grafted orthotopically into the fellow eye at a high rate and with few rejection reactions. CONCLUSIONS: Implantation of allogeneic corneal tissue in the anterior chamber of the eye has the transient capacity to alter the recipient alloimmune response in a manner that promotes survival of subsequent orthotopic corneal allografts.

Animals↗

[Multi-parametric analysis for leukemic immunophenotyping].

We have investigated whether immunophenotyping measured by laser flow cytometry could be corresponding to FAB classification of acute leukemias, using multi-parametric analysis. Sixty-one patients with acute leukemias have been evaluated, including 23 patients with acute lymphocytic leukemias (ALL) and 38 patients with acute myelogenous leukemias. In principal component analysis, positive cell surface antigens could be classified into groups along to the cell lineage and differentiation. In discriminant analysis, the sensitivity by immunophenotypic method to FAB subtypes was 75%, whereas the specificity was over 90%. In cluster analysis, patients have been classified into 4 groups, which essentially corresponded to ALL, M1/M2, M3 and M4/M5. Based on those multi-parametric analysis, a new flow chart has been established, resulting that the sensitivity and the specificity was improved to over 90% and 95% respectively. These results suggest that the classification of acute leukemia using the flow chart could be useful tools for diagnosis of subtypes of acute leukemias.

Antigens, Surface↗

All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells.

Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (D3) are well known for inducing differentiation in many leukemic cell lines. The nuclear signalling pathways of RA and D3 are mediated through their cognate receptors, the retinoic acid receptor (RAR) and vitamin D3 receptor (VDR), respectively. Retinoid X receptor (RXR) is an auxiliary factor that forms a heterodimer with RAR and VDR, enabling their efficient transcriptional activation. 9-cis RA, a high-affinity ligand for RXR, greatly enhanced D3-induced CD14 expression in U937 cells, while RA alone did not induce CD14 expression. 9-cis RA also resulted in morphological changes of U937 cells to macrophage-like cells when combined with D3, while RA alone resulted in granulocyte-like cells. RA and D3 together enhanced c-fms expression, phagocytic activity, and acted synergistically to promote nitroblue tetrazolium reduction activity and inhibit proliferation. Northern analysis showed that U937 cells constitutively expressed RAR-alpha, VDR and RXR-alpha mRNAs. RA or D3 alone or in combination did not affect RAR-alpha and VDR expression, while 9-cis RA and 9-cis RA plus all-trans RA significantly reduced RXR-alpha expression. Interestingly, D3 could restore the down-regulation of RXR-alpha mRNA by 9-cis RA. These findings suggest that there is crossover of the nuclear signalling pathways of RA and D3. This may have clinical implications in that RA and D3 may be used in combination for differentiation-inducing therapy in acute myelogenous leukemia and myelodysplastic syndrome.

Antineoplastic Agents↗

A novel monoclonal antibody mNI-58A against the alpha-chain of leukocyte function-associated antigen-1 (LFA-1) blocks the homotypic cell aggregation and actively regulates morphological changes in the phorbol myristate acetate (PMA)-activated human monocyte-like cell line, U937.

A monoclonal antibody (mAb), designated mNI-58A, was produced by immunizing mice with the lipopolysaccharide (LPS)-stimulated monocyte-like cell line, U937. The antigen defined by mNI-58A was widely expressed on various lymphoid cells and all cell lines examined except the erythroid cell line, K562. When the reactive patterns between mNI-58A and the mAbs to various human differentiation antigens (CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, HLA-class I and-class II antigen) were compared, that of mNI-58A was found to be similar to those of the leukocyte function-associated antigen-1 (LFA-1) mAbs. Using a competitive immunofluorescence binding assay it was found that the preincubation with one of the CD11a mAbs, 2F12 completely blocked the subsequent binding of mNI-58A. mNI-58A prevented the homotypic cell aggregation of the phorbol myristate acetate (PMA)-activated U937 cells (referred to as PMA-U937) and PMA-activated Epstein-Barr virus (EBV)-transformed B cell lines, B-85 and Mann. mNI-58A markedly induced the spread formation of the PMA-U937 cells following this blocking of the homotypic cell aggregation, whereas 2F12 did not under the same condition. The spread formation induced by mNI-58A was completely blocked by cytochalasin B (CyB), cytochalasin D (CyD), cycloheximide (CHX) or protein kinase C inhibitors, sphingosine and H-7. The U937 cells markedly adhered to the tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs) and also to the extracellular matrix protein, fibronectin, but mNI-58A did not enhance or block these adhesion process. mNI-58A precipitated two glycoproteins with molecular weight 180 kDa and 95 kDa as determined by SDS-PAGE analysis, which were identical to the LFA-alpha (CD11a) and beta (CD18) chains of leukocyte integrin precipitated by the CD11a mAbs, respectively. Sequential immunoprecipitation studies using the CD11a mAb (2F12) also indicate that mNI-58A recognizes an epitope on the alpha-chain of the LFA-1 molecule. The ability of mNI-58A to block the PMA-U937 cells and to induce the spread formation of these cells suggests that mNI-58A is a novel mAb reacting with an epitope on the alpha-chain of LFA-1 different from those recognized with the existing CD11a mAbs.

Antibodies, Blocking↗

In vivo function of homing receptors participating in lymphocyte recirculation: transfer analysis in SCID mice.

In order to examine the in vivo function of the adhesion molecules implicated in lymphocyte homing, blocking effects of antibodies against various adhesion molecules on lymphocyte migration were tested in SCID mice into which BALB/c donor splenocytes had been transferred. It was proved that the transferred donor splenocytes migrated to peripheral lymph nodes (LNs) of SCID mice. T and B lymphocytes were distributed in the specialized compartments as seen in the LNs of normal mice. Migration of lymphocytes to the local LNs was accelerated by stimulation with ovalbumin and complete Freund's adjuvant. This experimental system with accelerated migration was applied to analyze the in vivo function of adhesion molecules, and the following findings were obtained. Combined use of antibodies against lymphocyte-function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) strongly inhibited the migration of T lymphocytes to the peripheral LNs. Antibodies against very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) led to diminished B lymphocyte migration and disturbed compartmentalization of T lymphocytes in the paracortex. Migration of both T and B lymphocytes to the LNs was completely inhibited by the antibody against L-selectin. These results indicate that L-selectin plays an essential role in migration of both T and B lymphocytes into peripheral LNs but LFA-1/ ICAM-1 and VLA-4/VCAM-1 play different roles in compartmentalization of T and B lymphocytes in the peripheral LNs. In contrast, these adhesion molecules were not involved in lymphocyte migration to the splenic white pulp, indicating that the mechanisms for lymphocyte homing to the white pulp are quite different from those to the peripheral LNs.

Animals↗

[Immunophenotypic analysis of lymphocyte subpopulation and hematological malignancies].

Determination of the human lymphocyte subpopulation selected by immunofluorescence and the phenotypic analysis of hematological malignant cells by laser flow cytometry have become popular and useful tests in various laboratories. However, several lines of evidence have questioned the accuracy and reproducibility of these analysis. We examined the problems of laser flow cytometric analysis to measure the lymphocyte subpopulation and determine the phenotypic expression of hematological malignancies. In lymphocyte subset analysis, no survey has been applied to reveal the accuracy and reproducibility of these tests. We compared the accuracy of gating events and the ratio of lymphocytes using leuco GATE/simul SET analysis to those by manual gate method analysis. We found that there were some patients with SLE in which the accurate lymphocyte subpopulation was difficult to calculate due to the gating of lymphocytes by either method. Furthermore, apparent differences in the lymphocyte population were observed between these methods. In the phenotypic analysis of hematological malignancies, there have been several problems over 30% of the total cells had to be abnormal cells. Second, the malignant cells were difficult to gate unless the information of the size, shape and cellular density were obvious. Third, the phenotype of malignant cells were often different from that of the normal matured cells in the some lineage. However, flow cytometric analysis was useful to determine the cell lineage of peroxidase-negative cells and to diagnose the hybrid leukemia. In summary, the phenotypic analysis using flow cytometry and various monoclonal antibodies are clinically useful tests to diagnose the immunological disorders and hematological malignancies. However, there remain several problems to be solved in the near future.

Antibodies, Monoclonal↗

Retinoids (all-trans and 9-cis retinoic acid) stimulate production of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by human bone marrow stromal cells.

Retinoic acids (RAs) exert pleiotropic effects on cellular growth and differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell lines and cells from patients with acute myelogenous leukemia (AML) in vitro. Despite information on the effects of RAs on hematopoietic cells, little is known about how RAs act on the hematopoietic microenvironment, especially on bone marrow stromal cells. Based on recent observations that various cytokines produced mainly by bone marrow stromal cells regulate hematopoiesis, we analyzed the effects of RAs on cytokine production by these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell line KM101, which produces macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) constitutively, enhanced mRNA levels of both cytokines in a dose-dependent manner. Both RAs also stimulated M-CSF production from primary cultures of human bone marrow stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-alpha mRNA expression in a dose-dependent manner, but did not affect levels of RAR-alpha mRNA. These findings may have important biologic implications for both the role of RAs in hematopoiesis and the therapeutic effects of ATRA on the hematopoietic microenvironment in patients with acute promyelocytic leukemia (APL).

Bone Marrow Cells↗

[The effect of stressor experiences and optimism upon stress responses].

The present studies investigated whether or not optimism/pessimism is a cognitive mediator of future depression for people who have experienced many negative life events. Subjects were administered optimism scales, stress response scales at Time 1. They then completed the stressor scale and stress response scales at Time 2, about six weeks later. The results showed the interaction of stressor experiences and optimistic diathesis: Subjects who have higher stressor experiences and higher stable and global explanatory style for negative events showed higher depressive responses. Other indices of optimistic diathesis--Life Orientation, Cognitive Style, and Internality dimension of Attributional Style--did not produce this interaction effect. Moreover, this interaction did not appear in the psychological stress response other than depression. These results were consistent with diathesis-stress model of depression.

Adult↗

[Analysis of DNA contents in hematological malignant cells using whole blood lysis method].

The experiments have been undertaken whether DNA contents could be measured using whole blood lysis method by FACScan. Cell population in the phases of G1, S and G2 + M were well analyzed, when we used 3 x 10(6) cells lysed with 0.1% Triton X-100 in 1 ml of phosphate buffered saline, staining with 30 micrograms/ml of propidium iodide (PI) within 30 min after staining with PI. We have further developed cell cycle analysis for cells bearing lineage specific antigens recognized with FITC-conjugated monoclonal antibodies using two color analysis. When we fixed cells with 50% ice-cold ethanol after staining cells with FITC-conjugated antibodies, positive population ratio in these cells have been unchanged before and after fixing for CD3, CD4, CD5, CD8. CD10, CD19, CD14, CD33, and HLA-DR, but CD7 positive cells were markedly decreased after fixing. Using this method, CD41 positive leukemia cells have 3.4% in S phase and 6.8% in G2 + M phase, while CD41 negative cells have 1.8% in S phase and 2.0% in G2 + M phase in a patient with AML: M7, resulting leukemia cells were rich in S phase and G2 + M phase. The similar results were obtained in patients with AML:M2 using CD33 antibodies. During the clinical course, the changes of the blast numbers were well-correlated with changes of S-phase proportion in the patient with AML:M2. Among 47 patients with hematological malignancies in our hospital tested here, only 2 cases with 4.3% of total patients showed to have aneuploidy in malignant cells. One is a patient with non-Hodgkin lymphoma, the other is myelodysplastic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

HLA class II antigens are associated with Japanese pemphigus patients.

We investigated the HLA class II antigens in 30 Japanese cases of pemphigus, 17 cases of pemphigus vulgaris (PV) and 13 cases of pemphigus foliaceus (PF), by both serologic and restriction fragment length polymorphism (RFLP) analyses. We detected two major haplotypes susceptible to PV, i.e., DRw12-DQw7 and DRw6-DQw5. In contrast, DR2 was absent in PV. RFLP analyses showed that DRw6 PV patients had a disease-associated restriction fragment representing DQw5, the same association as that found in DRw6 Jewish PV patients. However, DRw12 Japanese PV patients had DQw7, whereas DR4 Jewish PV patients had DQw8. On the other hand, all 13 PF patients were serologically typed for DQw1, which could not be further subdivided into DQw5 by RFLP analyses. These results suggest that Japanese and Jewish PV patients may be immunogenetically closely related to each other, but Japanese PV patients appear to be immunogenetically different from Japanese PF patients.

Autoantibodies↗

[HLA antigens in 11 cases of patients with recurrent erythema and anti-SS-B antibody].

HLA antigens were studied in 11 cases of patients with recurrent erythema and anti-SS-B antibody. Among DR antigens positive associations with DR5, DRw6 (including DRw13), and DRw52 were obtained. These data demonstrated that 11 cases of this report are immunogenetically closely related to each other and appear to be related to Sjögren's/lupus erythematosus overlap patients.

Antibodies, Antinuclear↗

Synthesis and antitumor activity of analogues of ifosfamide modified in the N-(2-chloroethyl) group.

A series of 3-(2-chloroethyl)-N-(2-X-ethyl)tetrahydro-2H-1,3,2-oxazaphosphorin -2-amine 2-oxides with various X substituents have been prepared by cyclization of racemic ifosfamide or its enantiomers with sodium hydride and subsequent treatment of intermediary products with hydrobromic acid, diethyl hydrogen phosphate, dibenzyl hydrogen phosphate, p-toluenesulfonic acid, and acetic acid. All of these compounds were tested in vivo against L 1210 lymphoid leukemia in mice. Only bromo analogue 13 and its enantiomers were effective, exceeding the activity of racemic ifosfamide and cyclophosphamide. The therapeutic index of the racemic 13 and its levorotatory enantiomer was about 1.7 times higher than that for ifosfamide and about 2.7 times higher than that for cyclophosphamide.

Animals↗