[A CASE OF ORAL MITE ANPHYLAXIS IN WHICH BASOPHIL ACTIVATION TEST WAS USEFUL FOR DIAGNOSIS].

We treated a 13-year-old girl who developed dyspnea after ingestion of okonomiyaki, a Japanese savory pancake prepared from takoyaki flour mix that was opened several months ago and had been stored at ambient temperature. She was found to be sensitized to mite antigen, and microscopic examination of the flour specimen revealed contamination with mites. Therefore, she was diagnosed with oral mite anaphylaxis (OMA). For a more definitive diagnosis, we performed the basophil activation test (BAT) not only in this patient but also in a healthy woman who was not sensitized to mite (control), using the mite-contaminated flour and unopened takoyaki flour mix as antigens. The objective was to rule out the possibility of non-specific basophil activation induced by takoyaki flour mix. A strong activation of the patient's basophils was observed on stimulation with mite-contaminated flour, whereas no reaction was observed on stimulation with flour from the unopened pack. In the healthy control, no reaction was observed on stimulation with either of the flour samples. We demonstrate that BAT may be a useful substitute to the oral food challenge test for the auxiliary diagnosis of OMA.

Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo.

We show here that a zinc finger transcriptional repressor, Slug, which is aberrantly upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in normal hematopoietic progenitor cells. Slug(-/-) mice were much more radiosensitive than wild-type mice, dying earlier and showing accentuated decreases in peripheral blood cell counts, as well as abundant microhemorrhages and widely disseminated bacterial microabscesses throughout the body. Slug expression was detected in diverse subsets of hematopoietic progenitors, but not in more differentiated B and T lymphoid cells, and there was a significant increase in apoptotic (TUNEL-positive) bone marrow progenitor cells in irradiated Slug(-/-) mice compared to wild-type controls. These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage.

Three familial cases of drug-resistant Mycoplasma pneumoniae infection.

UNLABELLED: Mycoplasma pneumoniae infection is believed to result from defective host immune response rather than from direct cell injury by the organism itself. In this context, emergence of drug-resistant M. pneumoniae may provide us with special opportunities to study the pathogenesis from a clinical point of view. In this report, three patients with intrafamilial M. pneumoniae infection are presented. M. pneumoniae was isolated with a Hayflick pleuropneumonia-like organism diphasic medium. Minimal inhibitory concentrations of antibiotics were determined by a broth microdilution method. Polymerase chain reaction and restriction fragment length polymorphism analysis were done to determine point mutation in domain V of the 23S rRNA gene. As a result, all three strains from the three intrafamilial cases had the same drug-resistant point mutation, specifically A-to-G transition at position 2063. However, their clinical courses were quite different; a 6-year-old girl suffered severe pneumonia, a 5-year-old girl had mild pneumonia, and a 3-year-old boy had only a fever of 1-day duration without pneumonia. CONCLUSIONS: Our clinical and laboratory observations strongly support the idea that the host immune maturity, rather than a virulence factor of the organism, is a major determinant factor of disease severity of M. pneumoniae infection and that drug resistance does not necessarily lead to a serious clinical outcome.

A polymorphism of the 5' flanking region of tumour necrosis factor α gene is associated with thyroid-associated ophthalmopathy in Japanese.

OBJECTIVE: We have studied the polymorphism of the 5' flanking region of the tumour necrosis factor (TNF)-α gene in order to better understand the genetic background of autoimmune thyroid disorders and thyroid-associated ophthalmopathy. PATIENTS AND METHODS: We studied the polymorphism of the 5' flanking region of the TNF-α gene at positions - 1031 (T to C change, termed as - 1031C), - 863 (C to A, - 863 A), - 857 (C to T, - 857T), - 308 (G to A, - 308 A) and - 238 (G to A, - 238 A) in Japanese patients with Graves' disease [n = 173, 62 of whom had associated ophthalmopathy (American Thyroid Association (ATA) class III or greater)] and healthy control subjects (n = 575), using a polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS: The allele frequency of - 857T in the Graves' disease patients (22.5% vs. 17.7%, OR = 1.35, P = 0.045, corrected P = 0.23) was slightly greater than in the Japanese healthy subjects, respectively. However, the difference was not statistically significant. In Graves' disease patients with evident ophthalmopathy (ATA class III or greater), the allele frequencies of - 1031C and - 863 A were significantly greater than those with no or mild ophthalmopathy (ATA class 0-II) (31.5% vs. 13.5%, OR =2.94, P < 0.0001, corrected P < 0.0005; 23.4% vs. 11.7%, OR =2.30, P = 0.0044, corrected P = 0.022, respectively) and in control subjects. The strength of the association of the polymorphism - 1031C increased with the severity of ophthalmopathy, with odds ratios of 2.36 for ATA class III, and 5.43 for ATA class IV-VI, respectively, compared with Graves' disease with no or mild ophthalmopathy (ATA class 0-II). Although the phenotype frequency of DRB1*0901 was not different among Graves' disease patients with or without ophthalmopathy and control subjects, the phenotype frequency of DRB1*0901(-)/-1031C(+) was significantly increased in Graves' disease patients with ophthalmopathy compared to those with no or mild ophthalmopathy (OR = 4.91, P = 0.0005) or control subjects (OR = 4.59, P < 0.0001). CONCLUSIONS: These results suggest that the - 1031C or - 863 A alleles, or a gene in linkage disequilibrium with the TNF-α gene, predispose to the development of ophthalmopathy in Japanese patients with Graves' disease.

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo.

Nuclear factor interleukin-3 (Nfil3; also known as E4-binding protein 4) is a basic region leucine zipper transcription factor that has antiapoptotic activity in vitro under conditions of growth factor withdrawal. To study the role of Nfil3 in vivo, we generated gene-targeted Nfil3-deficient (Nfil3(-/-)) mice. Nfil3(-/-) mice were born at normal Mendelian frequency and were grossly normal and fertile. Although numbers of T cells, B cells, and natural killer (NK) T cells were normal in Nfil3(-/-) mice, a specific disruption in NK cell development resulted in severely reduced numbers of mature NK cells in the periphery. This defect was NK cell intrinsic in nature, leading to a failure to reject MHC class I-deficient cells in vivo and reductions in both interferon gamma production and cytolytic activity in vitro. Our results confirm the specific and essential requirement of Nfil3 for the development of cells of the NK lineage.