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Biomedical subjects

N Shimojo

Publications and source records attributed to N Shimojo.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparison of specificity between IgG, IgE and T cells to three casein components: implication for the role of circulating allergen-specific T cells in food allergy.

In order to investigate the role of food antigen-specific T cells circulating in the blood of patients with food allergy, we compared T cell response to three casein components (alpha s-, beta- and, kappa-casein) with specificities of IgG and IgE binding to the casein components in four milk-allergic patients (P1-4) with atopic dermatitis. In all patients the binding activities of IgG antibodies to alpha s-casein were most dominant, followed by those to beta- and to kappa-casein. The major component of casein bound by IgE antibodies was alpha s-casein in P1 and P3, kappa-casein in P2, and alpha s-casein as well as kappa-casein in P4; the order of casein components bound by IgE antibodies was different from that by IgG antibodies. Proliferative responses of peripheral blood mononuclear cells (PBMC) to casein components were so low that the dominance of casein recognition could not be clearly demonstrated. However, short-term T cell lines that specifically respond to casein were successfully established from PBMC of the four patients and the proliferative responses of the T cell lines to the three components of casein were in accord with the IgE antibody specificity to casein components but not with that of IgG antibody specificity. When taken together, these results indicate that casein-specific T cells circulating in the blood are involved in or reflect an allergic reaction against casein.

Caseins↗
PubMed1997

Characterization of monoclonal thyroid-stimulating and thyrotropin binding-inhibiting autoantibodies from a Hashimoto's patient whose children had intrauterine and neonatal thyroid disease.

A multiplicity of TSH receptor autoantibodies (TSHRAbs) have been characterized after subcloning heterohybridomas produced from the lymphocytes of a patient who has Hashimoto's thyroiditis and had three children with intrauterine or neonatal hyperthyroidism. Twelve clones produced stimulating TSHRAbs that increased cAMP levels and iodide uptake in rat FRTL-5 thyroid cells and increased cAMP levels in Chinese hamster ovary (CHO) cells transfected with the human TSHR; like 95% of Graves' stimulating TSHRAbs, all 12 have their functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity. All 12 bind to human thyroid membranes in the absence, but not the presence, of TSH, but are only weak inhibitors of TSH binding in assays measuring TSH binding-inhibiting Igs (TBIIs). In contrast, 8 different clones produced TSHRAbs that did not increase cAMP levels, but, instead, exhibited significant TBII activity. Four inhibited the ability of TSH or a stimulating TSHRAb to increase cAMP levels and had their functional epitope on the C-terminal portion of the TSHR external domain, residues 261-370, mimicking the properties of blocking TSHRAbs that cause hypothyroidism in patients with idiopathic myxedema. The 4 other TBIIs inhibited the ability of TSH, but not that of a stimulating TSHRAb, to increase cAMP levels, like TBIIs in Graves' patients. The functional epitope for 3 of these Graves'-like TBIIs was residues 90-165; the functional epitope for the fourth was residues 24-89. The fourth also increased arachidonic acid release and inositol phosphate levels in FRTL-5 thyroid cells and exhibited conversion activity, i.e. the ability to increase cAMP levels in the presence of an anti-human IgG. Thus, this TBII exhibited signal transduction activity, unlike the other 3 Graves'-like TBIIs. The patient, therefore, has stimulating TSHRAbs and 3 different types of TBIIs, each with different functional properties and different epitopes on the TSHR.

Adult↗
PubMed1997

[Eosinophils in stool smear in normal and milk-allergic infants].

Stool smears of newborn infants were investigated sequentially from birth through 6 months of life in order to study relation between appearance of eosinophils in stool and feeding of babies. In babies born to non-atopic parents, eosinophils appeared in stool smear soon after start of feeding, but disappeared in a short time. Eosinophils were found irrespective of types of feeding, i.e., breast feeding, powdered milk or amino acid formula. There was tendency of sustained presence of eosinophils in stool smears in babies born to severe atopic parents. These results suggest that appearance in stool of eosinophils does not necessarily mean allergic reaction to ingested foods and need attention in diagnosing milk allergy. Mechanisms of appearance and function of eosinophils in stool in normal babies may differ from those in pathological situations and need further detailed investigation.

Breast Feeding↗
PubMed1997

[Flow cytometric analysis for the activation of peripheral immunoregulatory cells from patients with bronchial asthma].

By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.

Adolescent↗
PubMed1996

Induction of Graves-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule.

Graves disease is an autoimmune thyroid disease characterized by the presence of antibodies against the thyrotropin receptor (TSHR), which stimulate the thyroid to cause hyperthyroidism and/or goiter. By immunizing mice with fibroblasts transfected with both the human TSHR and a major histocompatibility complex class II molecule, but not by either alone, we have induced immune hyperthyroidism that has the major humoral and histological features of Graves disease: stimulating TSHR antibodies, thyrotropin binding inhibiting immunoglobulins, which are different from the stimulating TSHR antibodies, increased thyroid hormone levels, thyroid enlargement, thyrocyte hypercellularity, and thyrocyte intrusion into the follicular lumen. The results suggest that the aberrant expression of major histocompatibility complex class II molecules on cells that express a native form of the TSHR can result in the induction of functional anti-TSHR antibodies that stimulate the thyroid. They additionally suggest that the acquisition of antigen-presenting ability on a target cell containing the TSHR can activate T and B cells normally present in an animal and induce a disease with the major features of autoimmune Graves.

Animals↗
PubMed1996

Lactate in cord blood and its relationship to pH and catecholamines in spontaneous vaginal deliveries.

The interrelationships between lactate and pH, nonadrenaline (NA), adrenaline (A) and dopamine (DA) were investigated in cord artery (CA) and vein (GV) blood at delivery. Sixty consecutive, spontaneous, vaginal deliveries with fetuses in cephalic presentation were assessed. Median gestational age at delivery was 40 weeks (range, 35-43). There were significant correlations between lactate and pH (P < 0.01), NA (P < 0.01), A (P < 0.05) and arterio-venous NA (P < 0.05) and DA differences (P < 0.01) in CA blood, while no variable correlated significantly to lactate in CV blood. The higher levels both of lactate and of catecholamines in CA blood are probably fetally derived. Dividing the material into high and low lactate subgroups (cut-off level, 75th percentile) showed a high lactate level to be associated with lower pH and higher catecholamine levels in CA blood, though the relationship was only statistically significant for pH. The levels both of catecholamines and of lactate were lower than those reported for cases of fetal distress, and reflect the lower level of fetal stress in the present series of normal deliveries. The low level of fetal stress and the differences in turnover rates between catecholamines and lactate might obscure their causal relationships, vis-a-vis fetal adaptation to extrauterine life during the course of parturition.

Delivery, Obstetric↗
PubMed1996

Establishment and characterization of alpha s1-casein-specific T-cell lines from patients allergic to cow's milk: unexpected higher frequency of CD8+ T-cell lines.

To study cow's milk allergy at the cellular level, we assessed the reactivity of peripheral blood mononuclear cells from patients allergic to cow's milk to alpha s1-casein, which is one of the major allergens in cow's milk. Proliferation of the cells to alpha s1-casein activation showed a rather weak response. Therefore to understand T-cell reactivity to alpha s1-casein in more detail, we prepared alpha s1-casein-specific T-cell lines from patients allergic to cow's milk and established 26 T-cell lines. These T-cell lines could be classified into three groups by analyzing their surface marker expression: those containing predominantly CD4+ CD8- T cells, those containing both CD4+CD8- and CD4-CD8+ T cells, and those containing predominantly CD4- CD8+ T cells. The CD8+ T cells were obtained at an unexpectedly higher frequency from the patients. These T-cell lines produced interferon-gamma and IL-4. These results suggest that CD8+ T cells specific for alpha s1-casein and CD4+ T cells were primed by the stimulation with alpha s1-casein in patients allergic to milk and that both T cells may play a key role in the onset, progression of, or recovery from cow's milk allergy.

CD8-Positive T-Lymphocytes↗
PubMed1996

Diminished interferon-gamma (IFN-gamma) production by bacterial antigen-specific T cells in atopic patients.

In this study, we established and studied cytokine production of T cell lines (TCL) specific to either a purified protein derivative of Mycobacterium tuberculosis (PPD) or Dermatophagoides farinae (Df) from atopic patients and non-atopic healthy subjects. IFN-gamma was detected in the culture supernatants of all of 36 PPD-specific TCL established from healthy controls, whereas only 24 of 38 PPD-specific TCL from patients produced IFN-gamma. Furthermore, the amounts of IFN-gamma produced by PPD-specific TCL from patients were significantly lower than those from healthy controls. No IL-4 was detected in any PPD-specific TCL from either healthy controls or atopic patients. The amounts of IL-4 production from Df-specific TCL from atopic patients were much higher than from healthy controls, while few TCL produced IFN-gamma. These results suggest that the skewing to the Th2-type T cell response in atopic patients is a response not only to allergens, but also to bacterial antigens, compared with non-atopic subjects. Activation of PPD-specific TCL from patients with calcium ionophore A23187 plus phorbol myristate acetate resulted in much higher IFN-gamma production than in TCL established from healthy controls, indicating that the low production of IFN-gamma by PPD-specific T cells from atopic patients is not due to an intrinsic T cell defect but to some regulatory mechanisms.

Animals↗
PubMed1996

Allergenic epitopes of ovalbumin (OVA) in patients with hen's egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide.

We studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347-385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. these results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVA-B1). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.

Allergens↗
PubMed1996

Establishment and characterization of ovalbumin-specific T cell lines from patients with egg allergy.

In order to investigate T cell recognition of allergens in hen egg allergy, we have established 30 ovalbumin (OVA)-specific T cell lines (TCLs) from peripheral blood mononuclear cells of 6 patients with atopic dermatitis, who are positive for IgE antibodies to OVA and clinically allergic to hen egg, and characterized them for their cytokine production pattern. All TCLs we could study were mainly composed of CD4+ T cells. Most TCLs produced significant amounts of interleukin 4 (IL-4) and IL-5 but no or very little interferon gamma on antigen stimulation, suggesting that these TCLs belong to TH2-type T cells. Restriction elements and epitope specificities were further studied on some TCLs. Antibody blocking of the proliferative responses of the TCLs to OVA indicated that HLA-DR are acting as the dominant restriction elements for these TCLs with minor contribution of HLA-DQ. By use of 187 overlapping synthetic peptides covering the whole sequence of OVA, at least 3 different T cell epitopes were identified.

Allergens↗
PubMed1996

Skeletal muscle kallikrein. Potential role in metabolic regulation.

Skeletal muscle glucose metabolism appears to be regulated by locally derived factors as well as by systemically circulating hormones. Local factors may be particularly important during exercise, when substrate demand can increase rapidly. Numerous studies in perfused limbs suggest that the kallikrein-kinin system may participate in the regulation of substrate delivery and utilization by skeletal muscle. Evidence also suggests that kinins mediate the increase in insulin sensitivity after administration of converting enzyme inhibitors. Tissue kallikrein has been isolated and purified from rat skeletal muscles, and its level is highest in muscle with high oxidative activity. In other tissues, kallikrein synthesis is under the influence of insulin. It has not been possible to demonstrate effects of kallikrein or kinins on glucose metabolism in isolated skeletal muscle or cardiocytes. Therefore modulation of glucose metabolism by kallikrein or kinins may only be observed in intact perfused tissues or organs.

Animals↗
PubMed1995

Routine measurements of umbilical artery lactate levels in the prediction of perinatal outcome.

OBJECTIVE: Our purpose was to compare lactate levels with acid-base balance in the umbilical artery with respect to the prediction of pregnancy outcome. STUDY DESIGN: A prospective study of 4045 cord samples was performed. Lactate was measured with a new method that requires 5 microliters of blood and provides the result within 1 minute. RESULTS: The umbilical artery lactate concentrations were significantly elevated in instrumental deliveries (2.65 +/- 1.2 mmol/L) and in emergency cesarean sections (2.44 +/- 1.7 mmol/L) compared with spontaneous vaginal delivery (1.87 +/- 0.94 mmol/L) (p < 0.001, p < 0.001). Lactate correlated significantly to fetal pH, hemoglobin, base deficit, PCO2, and HCO3-. Lactate was comparable to pH and base deficit in sensitivity, specificity, and positive and negative predictive values in relation to morbidity and mortality. CONCLUSION: Umbilical artery lactate concentration and acid-base balance predicted perinatal outcomes with similar efficacies; however, its simplicity makes lactate analysis an interesting alternative in obstetric care.

Bicarbonates↗
PubMed1995

Continuous maternal glucose infusion during labor: effects on maternal and fetal glucose and lactate levels.

Fetal and neonatal glucose and lactate levels and acid-base balance after continuous maternal infusion of 5% dextrose at 180 mL/h (9 g/h) was compared with 0.9% saline solution in a prospective, randomized study from selected monitored labors. An infusion of 5% dextrose produced significantly increased glucose levels in maternal (p < 0.01), cord artery (p < 0.01), and cord vein (p < 0.001) blood. An increased maternal insulin level was also present (p < 0.05), but no differences in cord insulin levels were observed. beta-Hydroxybutyrate was lower in maternal (p < 0.05) and cord vein (p < 0.01), but not in cord artery blood, after maternal dextrose infusion. No significant changes occurred in blood lactate levels between the two groups in either mother, fetus, cord, or neonate. Acid-base balance in cord blood did not differ between the two groups. Maternal infusion of 5% dextrose at 180 mL/h (9 g/h), compared with saline solution, produces higher glucose levels in both mother and fetus, but increased insulin concentrations only in the mother. Dextrose infusion also lowers beta-hydroxybutyrate in maternal and cord vein blood. No differences were seen in lactate levels or cord acid-base balance. Both regimens seem safe according to risks for lactacidosis and neonatal hypoglycemia in the normoxemic, normal size fetus.

3-Hydroxybutyric Acid↗
PubMed1995

Scalp blood lactate: a new test strip method for monitoring fetal wellbeing in labour.

OBJECTIVE: To determine fetal scalp blood lactate with a new test strip method in parturients with normal and abnormal cardiotocograms during labour and to describe the relation to maternal lactate, fetal scalp blood pH, cord artery lactate and acid-base balance. SETTING: Labour wards at the University Hospitals of Huddinge and Lund and at the County Hospital of Ostersund, Sweden. MATERIALS AND METHOD: Fetal scalp blood was sampled for lactate (n = 269) and pH (n = 285) determination in 177 parturients with abnormal intrapartum CTG. Lactate and pH were also analysed in a group of 64 women with normal pregnancies and with a reactive fetal heart rate tracing prior to sampling of fetal scalp blood. At fetal blood sampling lactate was also determined in maternal capillary blood, while at birth lactate and acid-base balance in cord artery blood was performed in almost all cases. MAIN OUTCOME MEASUREMENTS: Medians and percentiles (lactate and acid-base balance). Correlation between fetal scalp blood lactate (dependent) and scalp blood pH, cord artery blood lactate and acid-base parameters and labour time prior to fetal blood sampling. RESULTS: In the group with abnormal cardiotocograms, fetal scalp and umbilical artery blood lactate and acid-base parameters differed significantly from the same parameters in the normal group. The fetal-maternal lactate gradient changed from negative in the normal group to positive in the fetal distress group. Multiple regression analysis, with scalp lactate as the dependent parameter, revealed a significant correlation with fetal scalp blood pH (P < 0.001) and umbilical artery lactate (P < 0.01). CONCLUSIONS: Intrapartum scalp blood lactate was significantly correlated with pH and cord artery lactate. The results indicate that increased lactate levels in fetal blood sampling describes fetal lactacidosis. The new disposable test strip requiring only 5 microliters of blood for lactate determination may be better than traditional methods for monitoring fetal wellbeing in labour.

Acid-Base Equilibrium↗