Biomedical subjects

A Yachie

Publications and source records attributed to A Yachie.

At least 55 records · Page 3Linked to original sources

PubMed1997

Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils.

Apoptosis is well known to be mediated by oxidative stress. To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-Fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-Fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway.

Apoptosis↗

PubMed1997

Induction of autocytotoxic T cells with cyclosporine and interferon-gamma for patients with non-Hodgkin's lymphoma after transplantation of peripheral blood stem cells.

BACKGROUND: Autologous graft-versus-host disease is inducible after autologous bone marrow transplantation by means of administration of cyclosporine. OBJECTIVE: This study was performed to investigate the inducibility of autologous graft-versus-host disease after transplantation of peripheral blood stem cells (PBSCs). METHODS: Two patients with non-Hodgkin's lymphoma in remission underwent PBSC transplantation followed by administration of cyclosporine and low-dose interferon-gamma. RESULTS: Although autologous graft-versus-host disease did not develop in either patient, T lymphocytes with cytotoxic activity against autologous lymphocytes appeared transiently in the early posttransplant period. Such autocytotoxic lymphocytes were not detectable in another patient who underwent PBSC transplantation who did not receive cyclosporine and interferon-gamma. When CD4+ and CD8+ cells were sorted from the peripheral blood mononuclear cells of one of the two patients and tested for cytotoxicity against autologous lymphocytes, only CD8+ cells exhibited cytotoxic activity. CONCLUSIONS: The results indicate that administration of cyclosporine and interferon-gamma after PBSC transplantation can induce autocytotoxic CD8+ T cells, even though it may not produce autologous graft-versus-host disease. It is unclear whether induction of such autocytotoxic T cells among patients with non-Hodgkin's lymphoma who undergo PBSC transplantation has any antilymphoma effect.

Adult↗

PubMed1997

Decreased expression of 20-kD homologous restriction factor (HRF20, CD59) on T lymphocytes in Epstein-Barr virus (EBV)-induced infectious mononucleosis.

HRF20 (CD59) is one of the membrane-associated complement regulatory proteins. The characteristic function of CD59 is to prevent membrane attack complex (MAC) formation on the cell surface and to protect the cell from complement-mediated cell lysis. We examined the expression of CD59 antigen on T cell subpopulations in patients with acute infectious mononucleosis (IM) and analysed the relationship between the amount of CD59 expression and activation-induced cell death of mature T cells with apoptosis. Decreased expression of CD59 on CD8+ T cells, especially on CD45RO+ and HLA-DR+ activated T cells, was marked in acute IM patients. In contrast, activated CD4+ T cells from IM patients expressed as much CD59 antigen as CD4+ T cells from healthy volunteers. After incubation-induced cell death, viable CD8+ T cells showed normal amounts of CD59 antigen on their surface. CD59dim CD8+ T cells were more susceptible to apoptosis than CD59bright CD8+ T cells. These findings suggest that decreased expression of CD59 on CD8+ T cells may discriminate the susceptibility of activated CD8+ T cells to activation-induced cell death in IM.

Acute Disease↗

PubMed1997

Infectious mononucleosis as a disease of early childhood in Japan caused by primary Epstein-Barr virus infection.

The present study investigated 54 pediatric patients with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) in Japan. Most of the acute cases clustered within the first 5 years of life, and the peak incidence was observed at around 4 years of age. These patients were arbitrarily separated into three age groups (less than 3 years, 3-5 years, and 6-14 years). Fever, pharyngitis, lymphadenopathy and hepatomegaly were detected in more than 80% of all cases. Tonsillitis and splenomegaly were present in about 60% of cases. Skin manifestations and eyelids edema were less often detected in the older age group than in the young age groups. In addition to an increase of total white blood cell and lymphocyte counts in the peripheral blood, a significant increase in the percentage of CD3+ CD8+ HLA-DR+ T cells was always observed. Epstein-Barr virus seropositivity increased soon after birth and reached approximately 70% around 3 years of age. Close to 100% of the adult controls were EBV seropositive. The results suggest that EBV-induced acute IM is a disease of early childhood in Japan.

Adolescent↗

PubMed1997

[Identification of impaired cholesterol biosynthesis in a Japanese patient of Smith-Lemli-Opitz syndrome].

We reported the decreased level of cholesterol as well as the elevated levels of 7- and 8-dehydrocholesterol in the serum and erythrocytes of a Japanese patient with Smith-Lemli-Opitz syndrome. These findings suggested that the detection of these precursors of cholesterol synthesis should become an important biochemical parameter for this syndrome in which clinical features are not always obvious.

Adult↗

PubMed1996

Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan.

Deficiencies of Bruton's tyrosine kinase (Btk) have been implicated in the pathogenesis of human X-linked agammaglobulinemia (XLA). The distinctive phenotype observed in B-cell deficiency indicates the crucial role of Btk in B-cell development. This report describes a nationwide study of Btk deficiency in Japan, covering 51 XLA patients (35 independent families). Along with the identification of mutations, the resulting protein products were characterized by an in vitro kinase assay and a Western blot analysis. Thirty-one of the families were found to have mutations in the coding region of Btk. Although mutations were not found in the cDNA of 4 families, the Btk transcripts of these patients were greatly reduced. The identification of several novel missense mutations, in combination with the result of other studies, clarified the presence of two (missense) mutation hot spots, one in the SH1 and the other in the PH domain. The absence of kinase activity seen in 32 of the families underscored the importance of Btk protein analysis as a diagnostic indicator of XLA. The protein analysis also clarified the different effects of missense mutations on kinase activity and protein stability.

Adolescent↗

PubMed1996

Absence of CD69 expression on peripheral eosinophils in episodic angioedema and eosinophilia.

A 45-year-old woman with episodic angioedema and eosinophilia is presented. CD69, which is one of the surface antigens of activated eosinophils, was not expressed on the peripheral eosinophils in this patient, in contrast to hypereosinophilic syndrome. This suggests that CD69, which is not dependent on eosinophil density, may be another useful activation marker of eosinophils to distinguish episodic angioedema and eosinophilia from hypereosinophilic syndrome.

Angioedema↗

PubMed1996

Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells.

Human memory (CD45RO+) CD4+ T cells can be distinguished into two subpopulations on the basis of expression of the lymph node homing receptor, L-selectin (CD62L). In a prior study we showed that human L-selectin-positive memory T-helper (Th) cells promote the maturation of IgG- and IgA-producing cells by naive B cells. To further elucidate the contribution of memory CD4+ T cells to B-cell differentiation, human memory CD4+ T cells with or without L-selectin expression were evaluated for production of cytokines that participate in regulation of immunoglobulin production. It was found that L-selectin-positive human memory CD4+ T cells produce mainly interleukin (IL)-4 and IL-5, whereas L-selectin-negative CD4+ T cells produce mainly interferon-gamma (IFN-gamma). This profile of cytokine expression coincides with the profile that distinguishes Th1 and Th2 subsets. In contrast to the murine system, IL-10 production was similarly contributed by human L-selectin-positive and -negative memory CD4+ T-cell subpopulations. These results suggest that the human L-selectin-negative and -positive subpopulations of human memory CD4+ T cells contain Th1-like and Th2-like cytokine-producing cells, respectively.

Adult↗

PubMed1996

Inhibitory action of sulfatide, a putative ligand for L-selectin, on B cell proliferation and Ig production.

The interaction of L-selectin and its ligand is widely accepted to mediate leukocyte rolling and adhesion on the endothelial surface. Although L-selectin is ubiqultously expressed on lymphoid cells, its role in execution of lymphocyte functions is unknown. By flow cytometric analysis using mAb specific for sulfatide, a putative ligand for L-selectin, we found that sulfatide was selectively expressed on B cells, but not on T cells. To elucidate the involvement of L-selectin and its ligand in B cell activation, the present study was undertaken to investigate effects of sulfatide on T cell-dependent and -independent Ig production by B cells. In pokeweed mitogen-stimulated cultures, addition of sulfatide resulted in almost complete inhibition of Ig production by B cells in the presence of memory CD4+ T cells, whether L-selectin-positive or -negative. A similar inhibition of Ig production by sulfatide was found when B cells were stimulated with Staphylococcus aureus Cowan I and IL-2. Unlike sulfatide, a desulfated form of sulfatide, galactosylaceramide, did not show any effects on Ig production by B cells. Maximal inhibition of Ig production was observed when sulfatide was added at the early period of culture. Sulfatide suppressed effectively proliferation of B cells, but not of T cells. Sulfatide competed the binding of anti-L-selectin mAb to B cells, suggesting it could interfere B cell activation by blocking L-selectin function. The results suggest a novel role of the L-selectin/its ligand system in the initiation of B cell activation.

Adult↗

PubMed1996

Degos' disease: radiological and immunological aspects.

We present an 18-year-old patient with Degos' disease who manifested the sudden onset of paraplegia. Neurological examination revealed a rt-hemianopsia, paraparesis (with a sensory level at Th12), and a neurogenic bladder. Brain MRI showed multiple cerebral infarctions accompanied by small hemorrhagic areas and GdDTPA enhancement of the dura. A cerebral angiogram displayed stenosis, ectasia, and aneurysms involving the peripheral branch of arteries. Stenoses also were observed in the celiac artery and small arteries in the 1t-kidney. Skin biopsy exhibited hyperkeratosis, atrophy of the epidermis, and necrobiosis of the collagen layer. Laboratory examinations disclosed persistent elevations of the thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), and cytotoxic T cell subset (CD8+CD11-), illustrating the coagulative, fibrinolytic, and immunological implications of this disease.

Abdominal Abscess↗

PubMed1996

The relationship between serum levels of interleukin-6 and thyroid hormone during the follow-up study in children with nonthyroidal illness: marked inverse correlation in Kawasaki and infectious disease.

Our previous study demonstrated that the serum IL-6 correlated inversely with serum T3 and the T3/T4 ratio in children with acute respiratory infection during the acute phase of illness. To investigate whether serum IL-6 inversely correlates with serum thyroid hormone during not only the active stage of the disease but also in the follow-up period in nonthyroidal illness, we measured serum levels of IL-6, T3 and T4 in 31 children from the acute to the convalescent phase. They were divided into 3 groups; 7 patients with Kawasaki disease, 16 patients with infectious disease and 8 patients with non-inflammatory disease. In the follow-up of patients with Kawasaki disease, a marked inverse relationship was observed between serum IL-6 and T3 (r = -0.844, P < 0.001) or the T3/T4 ratio (r = -0.863, P < 0.001). Serum T4 showed a weak but significant negative correlation with serum IL-6 (r = -0.474, P = 0.035) only in this situation. There was also a significant negative correlation between serum IL-6 and T3 (r = -0.582, P < 0.001) or the T3/T4 ratio (r = -0.660, P < 0.001) during the follow-up of children with infectious disease. In the follow-up study of patients with non-inflammatory disease, however, no significant relationships were observed between serum thyroid hormones and IL-6. IL-6 may be one important factor involved in the decrease in the serum T3 level and the T3/T4 ratio in patients with nonthyroidal illness particularly characterized by strong inflammation and activation of the immune system as observed in Kawasaki and infectious disease.

Adolescent↗

PubMed1996

[Assessment by flow cytometric method of IgE-binding state of basophils in allergic disorders].

Basophils, as well as mast cells, express Fc epsilon RI on the surface. It is known that activation of basophils and mast cells leads to induction of chronic allergic inflammation. In this study, levels of IgE bound to the surface of peripheral blood basophils were measured using a flowcytometry, and their clinical relevance was evaluated. Peripheral whole blood samples were stained with FITC-conjugated anti-IgE. The fluorescence intensity of the FITC-positive cells within mononuclear cell region was determined. Basophil-bound IgE levels increased along with age and reached invariably high levels of adults. The levels of basophil-bound IgE were higher among allergics than normal controls, in early infancy. In addition, many of the infants with repeated wheezing episodes also exhibited high levels of it. These findings suggest that early exposure of predisposed infants to antigens leads to early sensitization of circulating basophils. Basophil-bound IgE levels correlated well with serum IgE concentration, but they remained constant when IgE concentrations exceeded 300 ng/ml, suggesting that IgE-binding capacity of basophils become saturated at this IgE level. In conclusion, it is shown that flowcytometric measurement of basophil-bound IgE provides a useful method of analyzing this rare cell population within the peripheral circulation, and it serves as a critical parameter to evaluate the allergic inflammation in vivo.

Adolescent↗

PubMed1996

The role of vacuolar H(+)-ATPase in the control of intragranular pH and exocytosis in eosinophils.

The presence of vacuolar H(+)-ATPase (V-ATPase) on exocytotic granules in eosinophils and the role of this enzyme in exocytosis were explored in this study. Antibody against 116-kd subunit of V-ATPase positively stained eosinophil granules in immunofluorescence analysis. When eosinophil lysate was extracted immunomagnetically with the same antibody, the extracted fraction contained a considerable amount of eosinophil peroxidase, a marker of eosinophil-specific granules, which indicates that V-ATPase was present on the membranes of eosinophil exsosomal granules. The pH of the eosinophil granules, measured fluorometrically with acridine orange as a delta pH-sensitive dye, was estimated to be 5.1. The acidity of the eosinophil granules was perturbed by bafilomycin A1, a potent selective inhibitor of V-ATPase, which indicates that the low pH of these granules is maintained by V-ATPase activity. BafilomycinA1 and NH4Cl, both of which raise the intragranular pH to neutral, inhibited the eosinophil peroxidase exocytosis induced by platelet-activating factor. These agents did not, however, affect the changes in cytosolic free calcium concentration [Ca2+]i induced by platelet-activating factor. These observations suggest that bafilomycin A1 inhibited a delta pH-requiring step in eosinophil exocytosis that was preceded by the [Ca2+]i transient in the signal transduction pathway, and, hence, the findings suggest the pivotal role of V-ATPase in maintaining intragranular pH and its function of eosinophil exosomal granules.

Ammonium Chloride↗

PubMed1995

Differential protective action of cytokines on radiation-induced apoptosis of peripheral lymphocyte subpopulations.

It is established that soluble factors involved in cell growth can prevent apoptosis of hematolymphoid cell lines in factor-deprived situations. The present study investigates the possible protective effects of various cytokines on radiation-induced apoptosis of apparently quiescent lymphocyte subpopulations. The exposure to gamma-irradiation resulted in appreciable apoptotic changes in all of lymphocyte subpopulations. Natural killer (NK) cells were the most radiosensitive, whereas CD8+ T and B cells showed weaker susceptibility to radiation and CD4+ T cells were relatively radioresistant. The radiation-induced apoptosis in NK cells was significantly inhibited by IL-2. In addition to IL-2, IL-4 and IL-7 rescued both CD4+ and CD8+ T cells from radiation-induced cell death. The viability of B cells was maintained by the presence of IL-4 but not others in culture. Furthermore, we conclude that the protective effect by each cytokine on radiation-induced apoptosis might be partly attributed to enhancement of cellular expression of bcl-2 protein.

Adult↗

PubMed1995

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals.

Neonatal B cells with the naive (sIgD+) phenotype are able to generate IgG- and IgA-producing cells as well as IgM production in the presence of memory CD4+ T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO+) CD4+ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgG1 and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgG1 and IgG3, although memory (sIgD-) B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults' naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgA1, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgG1 and IgG3 may be controlled by their own age-dependent maturation process.

Adult↗

PubMed1995

Pulmonary vasculitis with hypereosinophilia and episodic pulmonary hypertension: report of three siblings.

Three siblings with eosinophilia who developed pulmonary hypertension are reported. They consisted of a 3 year old boy (case 1), a 9 year old boy (case 2) and a 13 year old girl (case 3), all of whom died within an 18 month period of severe episodic attacks of pulmonary hypertension and the resultant low cardiac output. Marked peripheral eosinophilia was found in cases 1 and 2, and mild eosinophilia in case 3. Open lung biopsy of case 1 revealed pulmonary arteritis with massive eosinophilic infiltration and intimal thickening of muscular arteries of 300-1500 microns in diameter. At autopsy, cases 2 and 3 showed almost similar findings, comprising widespread obliteration of the pulmonary arteries by concentric intimal thickening, medial hypertrophy and recanalized thrombi of arterioles. Rarely, there were foci of granulomas in the thickened intima surrounding birefringent foreign bodies. There were small areas of infarction in the lungs and heart due to arterial thrombi. Vascular lesions other than those in the lungs were mild and almost limited to the branches of the coronary arteries. Therefore, the present cases appear to be a single disease of pulmonary hypertension secondary to endothelial injury and the resultant intimal fibrosis probably evoked by toxic substances, although such agents were not confirmed.

Adolescent↗

PubMed1995

Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia.

In some patients with aplastic anemia (AA), hematopoietic function is dependent on continuous administration of cyclosporine A (CyA). These AA patients may have T lymphocytes whose myelosuppressive effect is mitigated by CyA. We established a total of 29 T cell clones from the bone marrow of a CyA-dependent AA patient in relapse. Some of the CD4+ T cell clones demonstrated a specific proliferative response to irradiated autologous bone marrow cells enriched for CD34+ cells (CD34(+)-rich cells) obtained from the patient in remission. One of the T cell clones showing the best proliferative response to CD34(+)-rich cells carried the T cell receptor V beta 17 and produced interferon-gamma (IFN-gamma) only when cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony formation by colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) by approximately 60% when it was cultured with autologous CD34(+)-rich cells in methylcellulose medium, although the clone did not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in vitro hematopoietic progenitor cell growth by the T cell clone was partially abrogated by the addition of CyA to the culture. These findings suggest that in some patients with CyA-dependent AA, CD4+ T cells autoreactive to hematopoietic progenitor cells exist and may play an important role in the pathogenesis of bone marrow failure.

Adult↗

PubMed1994

Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils.

The recently identified Fas antigen (Ag) is a cell surface molecule that can mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown to prolong the cellular survival by inhibiting apoptosis. To elucidate the physiologic significance of expression of both molecules, we examined the expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was expressed on a fraction of lymphocytes, both neutrophils and monocytes expressed Fas Ag constitutively. In contrast, there was marked difference among these leukocytes regarding bcl-2 expression. Lymphocytes expressed bcl-2 intensely, but monocytes showed weaker bcl-2 expression, and neutrophils were essentially absent for bcl-2 expression. Seemingly reflecting this lack of bcl-2-expression, neutrophils more easily underwent apoptotic cell death in vitro as compared with monocytes and lymphocytes. We showed that anti-Fas antibody affectively accelerated apoptotic cell death in neutrophils. However, the apoptosis-inducing effect of anti-Fas antibody was minimal on monocytes, and lymphocytes were resistant to this antibody. These results suggest that anti-Fas-mediated cell death may, in part, be determined by bcl-2 expression status in Fas+ lymphoid and hematopoietic cells.

Adult↗