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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 433 records · Page 24Linked to original sources

Long-term study of the immunodeficiency of Bloom's syndrome.

The immune state was evaluated over a 10-year period in two individuals with Bloom's syndrome. In both patients, serum concentrations of IgM were markedly low. Mildly decreased serum concentrations of IgG and IgA increased significantly with age, whereas the IgM levels remained low. From assessments of B-cell and T-cell functions in pokeweed mitogen-induced immunoglobulin production, the IgM deficiencies were thought to result from B-cell dysfunction. T-cell function appeared intact. Moreover, although the percentages of surface IgM-bearing cells were not reduced, the numbers of IgM-secreting cells were reduced. These findings suggest that the IgM deficiency is due to an abnormality in the maturation of surface IgM-bearing B cells into IgM-secreting cells.

Adolescent↗

Proliferative responses of CD4+ T-cell population to ovalbumin in patients with atopic dermatitis who are sensitive to hen eggs.

Proliferative responses of peripheral blood mononuclear cells and T cells with monocytes to ovalbumin were significantly higher than those of B cells with monocytes to ovalbumin in patients with atopic dermatitis (AD) who were sensitive to hen eggs. The CD4+ T-cell/CD8+ T-cell ratios (the values obtained by dividing the maximum stimulation index of CD4+ T cells with monocytes to ovalbumin by the maximum stimulation index of CD8+ T cells with monocytes to ovalbumin) were significantly higher in AD patients sensitive to hen eggs than in non-atopic healthy controls. The proliferative responses of CD4+ T cells with monocytes to ovalbumin were more intensive than those of CD8+ T cells with monocytes in patients with AD sensitive to hen eggs compared with non-atopic healthy controls. These results suggest that the cells responding to ovalbumin are predominantly CD4+ T cells. However, there was no relationship between the stimulation index of proliferative responses of peripheral blood mononuclear cells to ovalbumin and RAST scores for hen eggs. Thus it is possible that the majority of the CD4+ T cells which respond to ovalbumin are not CD4+ helper T cells for IgE production.

Adolescent↗

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.

Antibody Formation↗

Interleukin-2 production of lymphocytes in food sensitive atopic dermatitis.

The proliferative responses of peripheral blood mononuclear cells (PBMC) to food antigens in 22 patients with food sensitive atopic dermatitis were significantly higher than the responses of healthy children and food sensitive children with immediate symptoms. Moreover, the activity of interleukin-2 (IL-2) in supernatants of food antigen stimulated PBMC cultures from patients with atopic dermatitis was significantly higher than that in healthy children and food sensitive children with immediate symptoms. The activity of IL-2 in culture supernatants of separated cell populations stimulated with food antigens from patients with atopic dermatitis and healthy children was investigated. The activity of IL-2 in supernatants of food antigen stimulated T cell cultures could be detected in patients with atopic dermatitis but not in healthy children. These results suggest that the increased IL-2 production after food antigen stimulation is due to increased T cell activity in food sensitive atopic dermatitis.

B-Lymphocytes↗

Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders.

Proliferative responses of cord blood lymphocytes (CBLs) to food antigens and cord blood IgE concentrations were measured in 37 full term newborn infants for the prediction of allergic disorders. In these 37 infants who were followed up for two years, allergic history of the family was found in four (sensitivity 57.1%) and cord blood IgE concentrations were greater than 0.5 IU/ml in three (sensitivity 42.9%) of seven infants who developed allergic disorders. When CBLs were stimulated twice by ovalbumin or bovine serum albumin, the value of the stimulation index in proliferative responses of CBLs to ovalbumin or bovine serum albumin was greater than 1.5 in six (sensitivity 85.7%) of seven infants who developed allergic disorders. The specificity of the responses of CBLs in the prediction of the development of allergic disorders was 93.3%. The proliferative responses of CBLs to food antigens were useful in the prediction of not only development of allergic disorders but also offending allergens. These observations provide further evidence that sensitisation is occurring in utero. This would appear to be increasingly important in the genesis of early atopic problems. As our follow up is only two years, in utero sensitisation is a prediction for the early development of atopic disease but only longer follow up will show whether this holds good for allergic disorders at any age.

Allergens↗

Suppression by cyclosporin A of anti-GBM nephritis in rats.

The suppressive effect of cyclosporin A (CyA) on the development of glomerulonephritis was evaluated in rats with either original- or crescentic-type anti-glomerular basement membrane (GBM) nephritis. CyA (2.5, 10 or 20 mg/kg) was given p.o. daily to original-type anti-GBM nephritic rats for 10 days from the day after the injection of anti-GBM serum. The development of the nephritis was dose-dependently suppressed by CyA before the production of specific antibody against rabbit gamma-globulin (the heterologous phase). In addition, CyA suppressed glomerular infiltration of leukocyte subsets (leukocyte with common antigen, T cell, helper T cell, suppressor/cytotoxic T cell, macrophage/monocyte). CyA was given p.o. daily to crescentic-type anti-GBM nephritic rats for 10 days from the 10th day after the injection of anti-GBM serum. CyA-administration caused a distinct suppression of the deterioration of nephritis during the autologous phase. In addition, CyA markedly suppressed the antibody production. The above data indicate that CyA has a beneficial effect on anti-GBM nephritis, and the antinephritic action of this agent may be due to the inhibition of glomerular infiltration of leukocyte subsets as well as the suppression of the antibody production.

Acetylglucosaminidase↗

[Development of a new method for calibration of pneumotachograph according to flow rate--evaluation of a computer-controlled-system for assessing respiratory gas exchange using this method].

1) We evaluated the method for calibrating the pneumotachograph according to flow rate by the software on personal computer. Flow volume was detected using the approximated equation (y = 1.294x2 + 0.989x + 35.824, r = 0.976, p less than 0.01) from various mean flow rate and integration of output voltage. The error between syringe volume (21) and the estimated value on the equation was 10 +/- 8 ml (0.48 +/- 0.42%). 2) Using the method described in 1), we developed computer-controlled-system for assessing respiratory gas exchange by mixing chamber method. To evaluate the accuracy of the system as compared with the Douglas Bag method, we measured the gas parameters of the both methods for two male subjects at rest(3 and 5min) and steady state exercise (3 min., 60-240watt). The error between the both methods were within +/- 5% in ventilation(VE), mixed expired O2 (FEO2) and CO2 (FECO2) concentration, and were within +/- 8% in O2 uptake(VO2) and CO2 production (VCO2). There were high positive correlation (r greater than 0.99, p less than 0.01) between the both methods in the all parameters. These results indicate that the system in this study would be practical use, that VE can be measured in only one pneumotachograph, even if the range of flow rate was wide(e.g. from rest to heavy exercise).

Adult↗

Failure of c-myc gene expression in B cells of some patients with common variable immunodeficiencies.

Many reports have shown that expression of the c-myc protooncogene represents an early event of lymphocyte activation. Calcium influx and activation of protein kinase C synergistically bypass the early signal transduction of lymphocyte activation. In this study, the c-myc message of B cells or B cell lines stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), A23187, Staphylococcus aureus Cowan I (SAC), or anti-mu was not expressed or was poorly expressed in common variable immunodeficiency (CVID) patients whose B cells did not differentiate or only poorly differentiated to SAC plus recombinant interleukin 2, whereas the c-myc message of 1 CVID patient's B cells that differentiated well in IgM secretion to SAC plus recombinant interleukin 2 was well expressed when stimulated by TPA, A23187, SAC, or anti-mu. These results suggest that an abnormality exists in the early signal transduction process on some CVID patients' B cells and that it may be in the bypass by calcium influx and direct activation of protein kinase C.

Adult↗

Various responses of lymphocytes to Epstein-Barr virus in patients with common variable immunodeficiency.

The responses of lymphocytes to Epstein-Barr virus (EBV) were investigated in five patients with common variable immunodeficiency (CVID). In three patients with CVID in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were markedly reduced, PBMCs and/or B cells did not respond (or scarcely) to EBV. This may be due to reduction of B cell numbers or reduction of EBV receptor bearing cells. In one patient with CVID in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were mildly reduced, PBMCs and/or B cells responded well to EBV and secreted immunoglobulin (Ig). This result shows that the patient's B cells with EBV receptors are sufficient to transduct EBV-signals into the nucleus and to respond to EBV. In another patient in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were not reduced, PBMCs mildly responded to EBV and scarcely secreted Ig. This result shows that the patient's B cells with EBV receptors may not be sufficient to transduct EBV-signals into the nucleus and to respond to EBV.

Antibody-Producing Cells↗

[Late potentials in dilated cardiomyopathy in relation to ventricular tachycardia and cardiac function: their significance].

We assessed the usefulness of ventricular late potentials (VLP) for detecting ventricular tachycardia (VT), and of the relationship between VLP and left ventricular dysfunction. The subjects consisted of 21 patients with dilated cardiomyopathy (DCM) not accompanied with ventricular conduction disturbances. Signal-averaged electrocardiograms were recorded by using VCM-3000. The signals of 200 or more beats were averaged through the 40-300 Hz band-pass filter until the noise level was reduced to less than one microvolt (microV). The duration (fQRSd) and the root mean square voltage (LP40) for the last 40 msec of the filtered QRS complex were calculated. The left ventricular diastolic dimension (LVDd), systolic dimension (LVDs) and the ejection fraction (EF) were obtained by echocardiography. Five of 21 patients had VT. fQRSd was significantly longer in patients with VT than in those without VT (158.8 +/- 8.6 vs 126.5 +/- 10.4 msec, p < 0.01). LP40 was significantly less in patients with VT than in those without VT (8.7 +/- 2.7 vs 24.1 +/- 12.3 microV, p < 0.01). If the presence of "fQRSd > or = 120 msec" or "LP40 < or = 20 microV" was defined as VLP positive, as in patients with old myocardial infarction, the criteria sensitivity was 100% and their specificity was 25% for detecting VT. If the presence of both "fQRSd > or = 135 msec" and "LP40 < or = 20 microV" was defined as VLP positive, the criteria sensitivity was 100%, and their specificity, 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Evidence for abnormally regulated alternative RNA processing of mu chain gene in B-lymphoblastoid cells from Bloom's syndrome.

Selective IgM deficiency is commonly found in patients with Bloom's syndrome. In this study, mu mRNA synthesis was investigated in B-lymphoblastoid cells transformed by Epstein-Barr virus (LCL) from a patient with Bloom's syndrome who showed selective IgM deficiency. LCL established from the patient with Bloom's syndrome well expressed IgM molecules in their surface, but scarcely produced secreted IgM, compared with healthy controls. The JH hybridization patterns of digested DNA of LCL from the patient with Bloom's syndrome showed the rearrangement of VDJ as well as those of control LCLs. The mu mRNA was well detected, but mu s C-terminal mRNA was poorly detected compared with control LCLs, indicating that secreted mu mRNA was poorly transcribed though membrane-bound mu mRNA was well transcribed. These results suggest that alternative RNA processing of mu chain gene is abnormally regulated in LCL from patients with Bloom's syndrome.

Adult↗

Serum IgG subclass concentrations before and after administration of intravenous immunoglobulin in common variable immunodeficiency.

IgG subclass levels were measured before and after administration of intravenous immunoglobulins (IVIGs) in patients with common variable immunodeficiency (CVI). Six patients were treated with IVIG at the dose of 100-150mg/kg to maintain a trough level of 200mg/dl every 4 or 5 weeks, except for patient 5 who was given IVIG only 3 or 4 times per year. Three kinds of IVIGs, polyethylene-glycol (PEG)-treated IVIG, alkylated IVIG and sulfonated IVIG were used for replacement therapy. Although serum IgGl levels were low before administration of IVIGs, they increased to the normal levels after each administration of IVIGs in four patients. IgG2 preserved normal levels before and after administration of IVIGs in all patients. IgG3 was present at low normal concentration in patient 1, low concentration in patients 2, 3 and 6, and undetectable in patients 4 and 5 before infusion. Although increases in IgG3 levels were shown after infusion of PEG-treated IVIG, there were no increases after infusion of sulfonated or alkylated IVIG. However, there have been several reports that IgG3 is detected in sulfonated or alkylated IVIG preparations by another method. IgG4 levels were somewhat low before administration, but four patients achieved normal serum levels with treatment. In light of the above results of replacement therapy with IVIGs, we should consider the IgG subclass levels for patients such as CVI or selective IgG subclass deficiency.

Adolescent↗

[Traditional religion and terminal care in the Ryukyus, southern Japan].

The public health significance of traditional religions in terminal care was studied in the Ryukyu Archipelago. The traditional religious view of life, in which death at home is ideal, is still maintained: while inhabitants seek modern medical care in facilities outside of the island, they are transported back to die in their homes when their condition becomes critical. Most of the general hospitals, special nursing homes for the aged, and psychiatric hospitals of Okinawa allow bereaved families to perform "Nujifa", a traditional religious ritual for transferring soul of the dead from the death to their own home, that functions as a significant factor in relieving grief. In many of the special nursing homes for aged, not a few aged women practiced activities uniquely associated with traditional religion on strongly reflecting the fact that endemic religion is deeply embedded in their thinking. Although acculturation is in rapid progress in the Ryukyu Archipelago, such endemic religion still has a significant effect on the people. Therefore these religious factors should be considered in the terminal medical care of these people.

Aged↗

Abnormal responses of the autonomic nervous system in food-dependent exercise-induced anaphylaxis.

We investigated abnormal responses of the autonomic nervous system and measured plasma histamine levels before and after exercise challenge following food ingestion in four patients with food-dependent exercise-induced anaphylaxis. The patients' histories and the radioallergosorbent tests showed that food-dependent exercise-induced anaphylaxis resulted from preexercise-ingestion of shrimp, hen's egg, and any food in two patients, one patient and one patient, respectively. The plasma histamine level increased in only one of four patients when the exercise challenge followed the ingestion of nonoffending foods. Our investigation of changes in the autonomic nervous system before and after food-exercise challenge in all patients included comparing results obtained after the food-exercise challenge in controls and comparing results obtained before food-exercise challenge in the patients. After food-exercise challenge, systolic blood pressure significantly decreased and the heart rate increased during the postural test, heart rate tended to decrease in the Aschner test, and the increase of systolic blood pressure was reduced in the cold pressor test. After food-exercise challenge, the parasympathetic nervous activity increased and responsiveness of the sympathetic nervous system was reduced. Food-dependent exercise-induced anaphylaxis may therefore occur in relation to allergic reactions and abnormality of the autonomic nervous system.

Adolescent↗

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.

Adult↗

Expression of immunoglobulin genes in common variable immunodeficiency.

Five common variable immunodeficiency (CVI) patients were analyzed for expression of immunoglobulin (Ig) genes. In the pokeweed mitogen (PWM)-induced Ig-production assay, the combination of T and B cells showed that all patients' T cells had normal helper functions and all patients' B cells had profound defects. The defective B-cell maturation stages based on their Ig gene expression patterns were variable. One of five patients showed normal mu-chain gene expression and nearly normal IgM production, but neither IgG nor IgA production, which suggested that this patient's B-cell defects might lie on a mu- to gamma or mu- to alpha class-switch stage. B cells in another patient showed low mu-chain gene expression and low IgM production, but an Ig enhancer region, which is an important region for expression of Ig genes, was intact. Thus, this patient might have a transacting factor defect which interacts with the Ig enhancer region. The other three patients showed no mu-chain gene expression and no IgM production. Thus, their B-cell defects lay on the B-cell maturation stage, similar to X-linked agammaglobulinemia. These results showed that primary B-cell defects in CVI occurred at several B-cell differentiation stages, which could be recognized by expression of Ig genes.

Adult↗

Suppression of immunoglobulin production of lymphocytes by intravenous immunoglobulin.

The proliferative responses and the immunoglobulin production of peripheral blood mononuclear cells to pokeweed mitogen were dose-dependently suppressed by sulfonated intravenous immunoglobulin (IVIG), polyethylene glycol-treated IVIG, pH 4-treated IVIG, or human gamma-globulin, but they were not or only slightly suppressed by human serum albumin or pepsin-treated IVIG. Moreover, the suppression of immunoglobulin production by sulfonated IVIG, polyethylene glycol-treated IVIG, or pH 4-treated IVIG was seen in the cases in which B cells preincubated with IVIGs were cocultured with T cells and monocytes preincubated with or without IVIGs and in the cases in which monocytes preincubated with IVIGs were cocultured with T cells and B cells preincubated with or without IVIGs. However, in the cases in which only T cells were preincubated with IVIGs, immunoglobulin production was not suppressed. The suppression of the monocyte function by IVIGs tended to be less than the suppression of the B-cell function by IVIGs. Moreover, the suppression by IVIGs was blocked by anti-human IgG Fc. Our results suggest that IVIGs suppress the immunoglobulin production of lymphocytes through suppression of the B-cell function and the antigen presenting-cell function by attachment of IVIGs to Fc receptors of B-cell membranes and antigen presenting-cell membranes.

Antigen-Presenting Cells↗