Fumiaki Motoyoshi

Lymphocyte responses to food antigens in patients with atopic dermatitis who are sensitive to foods

The proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin or bovine serum albumin in children with atopic dermatitis (AD) who are sensitive to hens egg or cows milk were significantly higher than responses of PBMCs of healthy children and hens egg- or cows milk-sensitive children with immediate symptoms. However, the percentages of positive RAST for hens egg or cows milk in the patients with AD were lower than percentages in the patients with immediate symptoms. In the patients with AD, there were no significant correlations between the proliferative responses of PBMCs and the RAST values. There were no significant differences of RAST scores among groups of patients having different degrees of severity of AD. The proliferative responses of PBMCs to ovalbumin or bovine serum albumin in patients with severe AD or moderate AD who were sensitive to hens egg or cows milk tended to be higher than responses of patients with mild AD, respectively, but there were no significant differences in those results. Taken together, the combination of RAST and the detection of proliferative responses of PBMCs to each food antigen is very useful in the diagnosis of hypersensitivity in children with AD who are sensitive to food allergens.

The role of T lymphocytes in patients with food-sensitive atopic dermatitis

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hens egg or cows milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hens egg or cows milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hens egg were significantly higher than those of healthy children and patients sensitive to hens egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.

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 γ-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 antihuman 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.

Reduced secreted μ mRNA synthesis in selective IgM deficiency of Bloom's syndrome

Serum IgM concentrations were low although serum IgG and IgA concentrations were normal in both our patients with Blooms syndrome. Although the percentages of surface Ig‐earing cells were not reduced, the numbers of Ig‐ecreting cells were markedly reduced. The membran‐ound μ(μm) and secreted μ (μs) mRN As arc produced from transcripts of a single immunoglobulin μ gene by alternative RNA processing pathways. The control of μs mRNA synthesis depends on the addition of poly(A) to μs ‐erminal segment. In both patients, μ mRNA was well detected but μs ‐erminal mRNA was scarcely detected, suggesting that μ mRNA was well transcribed but μs mRNA was not. There was, at least, no mutation or deletion in the μs ‐erminal coding sequence, the RNA splice site (GG/TAAAC) at the 5’ end of μs ‐erminal segment and the AATAAA poly(A) signal sequence in both patients. Our results suggest that selective IgM deficiency in Blooms syndrome is due to an abnormality in the maturation of surface Ig‐earing B cells into Ig‐ecreting cells and a failure of μs mRNA synthesis. Moreover, reduced μs mRNA synthesis may be due to the defect on developmental regulation of the site at which poly(A) is added to transcripts of the μ gene.

Long‐term study of the immunodeficiency of Bloom's syndrome

The immune state was evaluated over a 10‐year period in two individuals with Blooms 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.

The effect of photosensitive dye Platonin on juvenile rheumatoid arthritis

Two children with juvenile rheumatoid arthritis (JRA) were given photosensitive dye Platonin in combination with prednisolone. Analysis of clinical and laboratory data showed that Platonin was efficacious in the improvement of the clinical symptoms and the severity of inflammation, or in the maintenance of the remission state. There were no adverse side effects during long-term administration of medication.

Diabetes mellitus in a young man with bloom's syndrome

Blooms syndrome (BS) is a rare autosomal recessive genetic disorder in which diabetes mellitus unusually frequently develops as a complication. We report on a 21‐year‐old Japanese male patient with BS who exhibited impaired glucose tolerance (IGT) in the initial oral glucose tolerance test (OGTT) and had developed patterns of diabetes mellitus by the second OGTT at the 2‐years‐and‐2‐months follow‐up. German and Passarge reported that the onset of diabetes in patients with BS was in late adolescence or early adulthood. Our results support the findings of German and Passarge. Therefore, when a person with BS reaches late adolescence or early adulthood, an OGTT is necessary to ascertain whether the patient has IGT or diabetes mellitus as a complication, regardless of whether or not diabetic signs such as glucosuria are present.

Severe heart failure due to ductal constriction caused by maternal indomethacin

Indomethacin is a prostaglandin synthesis inhibitor and has been used in the treatment of premature labor since the mid1970s. Experimental data indicates that maternal ingestion of indomethacin and other cyclo-oxygenase inhibitors can cause constriction of the fetal ductus arteriosus and persistent pulmonary hypertension of the newborn (PPHN). 1,2 Although an association between prostaglandin synthesis inhibitors and PPHN 3 or cardiac failure 4 has been described in case reports, studies of large series of neonates exposed in the antenatal period to indomethacin have failed to reveal severe cardiopulmonary effects. 5,6 It has been shown that ductal constriction induced by administration of indomethacin can cause right ventricular concentric hypertrophy and left ventricular dilatation in fetal rats. 7 Ductal constriction is assumed to cause pulmonary and right ventricular hypertension, decreased right ventricular output, rise in right atrial pressure, increased blood flow through the foramen ovale and increased volume load to the left ventricle. A patient, whose mother had been treated with indomethacin for premature labor from 26 to 34 weeks’ gestation, had severe congestive heart failure at birth. We consider that maternal administration of indomethacin caused ductal constriction and subsequently congestive failure occurred in the patient.

Chediak‐Higashi syndrome: report of a case with an ovarian tumor

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DNA MUTATION INDUCED IN THE SEQUENCE UPSTREAM OF THE SECRETED MYU C‐TERMINAL CODING SEQUENCE BY ULTRAVIOLET IRRADIATION IN THE CELL LINE OF BLOOM'S SYNDROME

Selective IgM deficiency is commonly found in Blooms syndrome (BS). We reported that membrane‐bound μ (μ m) mRNA was well transcribed but secreted μ (μ s) mRNA was not, although there was no mutation or deletion in the sequence including the (is C‐terminal coding sequence in the patients with BS. Furthermore, we have shown previously, preferential damage to IgM production by ultraviolet (UV) irradiation of the cells of the patient. In the study described here, mutation in the sequence which is upstream of the 5’ end of the μ s C‐terminal coding sequence was induced by UV irradiation in the lymphoblastoid cell line (LCL) of BS patient. These results suggest that abnormal repair of DNA damage is present in this LCL, and that preferential damage to IgM production by UV irradiation in this LCL may be due to the abnormal repair of DNA damage.