A previous study revealed that reduced expression (modulation) of the CD3 antigen is a common characteristic of alveolar T-cells in health and disease. As CD3 molecules are noncovalently bound to T-cell antigen receptors (TCR), it was hypothesized that modulation of TCR was also a feature of alveolar T-cells. To demonstrate this, lymphocytes from bronchoalveolar lavage fluid were stained with an anti-alphabeta TCR antibody and analysed by flow cytometry. The expression of alphabeta TCR by alveolar T-cells was evaluated by calculating mean fluorescence intensity (MFI) and was compared with alphabeta TCR expression by autologous blood T-cells. As anticipated from a previous study, modulation of TCR was observed not only in healthy volunteers but also in patients with pulmonary sarcoidosis, other pulmonary diseases, and nonpulmonary diseases. There were no significant differences in MFI of alveolar T-cells among the study groups. The degree of modulation assessed by the difference of MFI between blood and alveolar T-cells was greater for CD4+ cells than for CD8+ cells owing to the higher MFI of CD4+ blood T-cells. Coculture of alveolar macrophages with blood T-cells in vitro induced partial modulation of TCR. These results demonstrate the ubiquity of modulation of T-cell receptors on alveolar T-cells and suggest, in contrast to a previous report by other investigators that it is caused by some nonantigenic mechanism possibly inherent in the alveolar milieu. The implications of this phenomenon in in vivo immune responses of the lung need to be examined.

AllergyVolume 53, Issue 4 p. 452-454 Anaphylaxis to curry powder N. Ohnuma, N. Ohnuma First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this authorE. Yamaguchi, E. Yamaguchi First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this authorY. Kawakami, Y. Kawakami First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this author N. Ohnuma, N. Ohnuma First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this authorE. Yamaguchi, E. Yamaguchi First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this authorY. Kawakami, Y. Kawakami First Department of Medicine, School of Medicine Hokkaido University N-15, W-7, Kita-ku Sapporo 060 Japan Tel. +81-1-716-1161 (ext.) 5911 Fax: +81-11-727-6724 E-mail: Etsuro@med.hokudai.ac.jpSearch for more papers by this author First published: 29 April 2007 https://doi.org/10.1111/j.1398-9995.1998.tb03924.xCitations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume53, Issue4April 1998Pages 452-454 RelatedInformation

The mechanism of hyposensitization in bronchial asthma has not been fully elucidated, We established a hyposensitization model of bronchial asthma in rats and examined airway responses and immunological parameters. Brown Norway rats were sensitized by a subcutaneous injection of ovalbumin (OA) at day 1 and by the inhalation of 2% OA aerosol at day 15. Animals were hyposensitized by intraperitoneal injections of OA from day 17 to day 22, They were challenged with OA or acethylcholine (Ach) aerosol at day 23 and changes in intratracheal pressure were recorded, Lungs were lavaged and OA-induced proliferative: responses by blood lymphocytes were examined for animals without aerosol challenge at day 23. OA-specific serum IgE levels were measured by enzyme-linked immunosorbent assay. Hyposensitization significantly reduced the OA-induced immediate airway response, accumulation of CD4+ lymphocytes and eosinophils recovered by bronchoalveolar lavage, and the OA-induced proliferative response by blood lymphocytes. The airway responses to Ach and serum OA-specific IgE levels in hyposensitized group were not significantly different from those in the sensitized group. These results indicate that amelioration of airway inflammation and hyporesponsiveness of lymphocytes against OA are involved in the attenuated immediate antigen-induced airway response following hyposensitization.

An induction motor driving controller which can improve the performance of elevators is studied. The controller has three features. Firstly, it has an energy-saving control by which the induction motor stably generates motor torque at the maximum efficiency, regardless of the number of passengers boarding the car, even if both acceleration from a standstill and deceleration from steady-state are done for any elevator. Secondly, it can suppress vertical vibrations of elevators while performing energy-saving control. Thirdly, it ensures good performance of elevators even when the source voltage is reduced due to an overload on the source sides. The controller is judged suitable for the drive system of elevators on the basis of simulations and experiments.

BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.

The genetic linkage of atopy to chromosome 11q13 through maternally derived alleles has been previously reported. Linkage analysis in Japanese families did not confirm the existence of a major gene for atopy at this locus under the model of autosomal dominant inheritance. However, we observed a significant association between serum total IgE levels and genetic markers at this locus both in 14 Japanese atopic families and in 120 unrelated Japanese subjects. We detected eight alleles at the D11S97 locus and eight alleles in the CA/GT repeat region in the fifth intron of the Fc epsilon RI beta gene. A significantly increased frequency of the D11S97/PstI 0.96 kb allele was observed in the chromosomes of the subjects with high serum total IgE levels both in the family study (p < 0.001) and in the population study (p < 0.05). However, multipoint linkage analysis again did not show any evidence for the existence of a major gene regulating atopy on chromosome 11q13 with location scores to -35 under the model of maternal inheritance. Evidence against linkage was confirmed by the non-parametric linkage analysis, using the affected pedigree member method. Also, there was no substitution of isoleucine for leucine in the fourth transmembrane domain of Fc epsilon RI beta (Leu181), which was reported to be responsible for a subset of atopy in the British population. Therefore, the association of serum total IgE levels with chromosome 11q13 indicates that a gene or genes at this locus may contribute to the expression of high IgE levels in the Japanese population as well as in the British population, but the heterogeneity of the genetic regulation of serum total IgE levels is evident between the two populations.

To evaluate the role of gamma delta T cells in atopic asthma, we examined the relationship among atopy bronchial asthma, and genetic polymorphism of the gamma chain of T cell receptors (TCR) in families through atopic asthmatic probands. We recruited 5 families (69 subjects). Total serum IgE levels were estimated by a radioimmunosorbent test (IgE RIST). Skin prick tests were done with inhaled allergens consisting of house dust, grass and tree pollens, common molds, and animal danders. Antigen-specific IgE levels in response to these allergens were also measured by multiple antigen simultaneous test (IgE MAST). The atopic phenotype was determined by the presence of a positive skin test, an elevated antigen specific IgE value, an elevated total IgE level, or some combination of these. Although linkage of atopy or bronchial asthma to the gene encoding the gamma chain of TCR was excluded, the lod score between this gene and molds-specific IgE responses was 0.42 at the recombination fraction of 0.1. In an association study, a 19 kb allele of the gamma chain of the TCR gene was found more frequently in asthmatic subjects than in non-asthmatic subjects (p = 0.068). Also, molds-specific IgE responses were significantly associated with this allele (p = 0.018). These findings suggest that molds-specific IgE responses underlying atopic asthma are partly regulated by the gene encoding the gamma chain of the TCR.

BACKGROUND:Granulocyte-macrophage colony stimulating factor (GM-CSF) has several proinflammatory effects, some of which potentially favour granuloma formation. Its mRNA expression by the inflammatory cells recovered from lungs of patients with pulmonary sarcoidosis has been previously reported. In this study an association between GM-CSF expression and manifestations of the disease was explored.METHODS:GM-CSF mRNA was detected by reverse transcription polymerase chain reaction in the cells of bronchoalveolar lavage (BAL) fluid of 20 patients with pulmonary sarcoidosis.RESULTS:GM-CSF mRNA expression was positive in 15 of 20 patients with sarcoidosis. Fourteen of the 15 patients with positive mRNA expression had worsening or unchanged disease during the year preceding this study, on the basis of radiographic or physical findings, or both, whereas all five "negative" patients were judged to be improving. Similarly, serum levels of angiotensin converting enzyme, the proportion of lymphocytes in BAL fluid, and the CD4+/CD8+ ratio of lymphocytes in BAL fluid were significantly higher in the positive patients.CONCLUSIONS:There was an association between the presence of GM-CSF mRNA in the cells in BAL fluid and other indices of disease activity in sarcoidosis.

Atopy as defined in terms of IgE responsiveness was reported to be controlled by a single gene in British families, and this concept was further supported by a significant linkage between atopy and restriction fragment length polymorphism (RFLP) detected by a DNA probe specific to chromosome 11q13. To confirm this observation in a Japanese population, segregation and linkage analyses were done in four large families. Although segregation patterns of atopy were in agreement with the pattern of autosomal dominant inheritance, there was no significant linkage between atopy and locus 11q13. Alterations in the definitions of atopy did not affect the results. These findings suggested the presence of heterogeneity in genetic elements of atopy, even though atopy may be determined mainly by a single dominant gene.

Two new vitamin D metabolites were isolated in pure form from separate incubations of homogenates of chick small intestinal mucosa or rat kidney employing either 1 alpha,25-dihydroxyvitamin D3 (28 microM) or 1 alpha,24R,25-trihydroxyvitamin D3 as substrate (0.17-1.3 microM). The newly characterized compounds and the amounts isolated in pure form from separate isolations are, respectively: 1 alpha,25-dihydroxy-24-oxo-vitamin D3 (1,25(OH)2-24-oxo-D3), 147 micrograms from kidney and 4.2 and 40 micrograms from intestine; 1 alpha,23,25-trihydroxy-24-oxo-vitamin D3 (1,23,25(OH)3-24-oxo-D3), 155 micrograms from kidney and 5.9 and 34 micrograms from intestine. Their structures were identified after extensive high pressure liquid chromatography by means of ultraviolet absorption spectrometry, mass spectrometry of the free compounds and their trimethylsilylated derivatives, proton nuclear magnetic resonance spectrometry, specific chemical reduction of the 24-oxo functionality with sodium borohydride, as well as direct comparison with synthetic 1,25(OH)2-24-oxo-D3. These structural assignments for both compounds correct previous determinations which had been proposed (Ohnuma, N., Kruse, J. R., Popjak, G., and Norman, A. W. (1982) J. Biol. Chem. 257, 5097-5102). The activity of the C-24 oxidation pathway used for the production of the 1,25(OH)2-24-oxo-D3 and 1,23,25(OH)3-24-oxo-D3 can be enhanced 10-fold by prior priming of the chicks or rats with a single intravenous dose of 1,25(OH)2D3 (1-12 nmol/100 g body weight); the induction of the enzyme activity is maximal by 3-6 h and returns to basal levels within 12 h. Further, 1,25(OH)2D3, 1,24,25(OH)3D3, and 1,25(OH)2-24-oxo-D3 all were found to be capable of serving as a precursor with chick intestine and rat kidney homogenates of 1,23,25(OH)3-24-oxo-D3. Collectively these results suggest the existence of a C-24 oxidation pathway for metabolism of 1,25(OH)2D3 by the target intestinal mucosa and kidney to 1,23,25(OH)3-24-oxo-D3. The pathway may play an important role in controlling the tissue levels of this hormonally active form of vitamin D3.

Two new metabolites of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], namely 1,25(OH)2-24-oxo-vitamin D3 and 1,23,25(OH)3-24-oxo-vitamin D3, have been prepared in vitro using chick intestinal mucosal homogenates. To investigate the binding of 1,25(OH)2-[23-3H]-24-oxo-D3 and 1,23,25(OH)3-[23-3H]-24-oxo-D3 to the chick intestinal receptor we have isolated both metabolites in radioactive form using an incubation system containing 1,25(OH)2-[23,24-3H))-D3 with a specific radioactivity of 5.6 Ci/mmol. Both metabolites were highly purified by using Sephadex LH-20 chromatography followed by high-pressure liquid chromatography (HPLC). Sucrose density gradient sedimentation analysis showed specific binding of both tritium-labeled metabolites to the chick intestinal cytosol receptor. Experiments were carried out to determine the relative effectiveness of binding to the chick intestinal mucosa receptor for 1,25(OH)2D3. The results are expressed as relative competitive index (RCI), where the RCI is defined as 100 for 1,25(OH)2D3. Whereas the RCI obtained for 1,25(OH)2-24-oxo-D3 was 98 +/- 2 (SE), the RCI for 1,23,25(OH)3-24-oxo-D3 was only 28 +/- 6 (SE). Also, the biological activity of both new metabolites was assessed in vivo in the chick. In our assay for intestinal calcium absorption, 1,25(OH)2-24-oxo-D3 was active at a dose level of 1.63 and 4.88 nmol/bird (at 14 h), whereas 1,23,25(OH)3-24-oxo-D3 showed only weak biological activity in this system. In our assay for bone calcium mobilization, administration of both new metabolites showed modest activity at the 4.88-nmol dose level, which was reduced at the 1.63-nmol dose level. The results indicate that biological activity declines as 1,25(OH)2D3 is metabolized to 1,24R,25(OH)3D3, 1,25(OH)2-24-oxo-D3, and then 1,23,25(OH)3-24-oxo-D3.

Two new vitamin D metabolites were isolated in pure form from incubations of 53 nM 1,25-dihydroxyvitamin D3 with homogenates of small intestinal mucosa of vitamin D-replete chicks. The birds were injected intravenously with 8 to 9 nmol of 1,25-dihydroxyvitamin D3/100 g body weight 5 to 8 h before death. The isolation involved methanol-chloroform extraction and four successive chromatographic procedures (Sephadex LH-20 and high performance liquid chromatography). Chemical structures of the metabolites are proposed on the basis of (a) their chromatographic behavior, (b) their mass spectra, and (c) ultraviolet absorption spectra. They are identified as 1 alpha,25-dihydroxy-23-oxo-vitamin D3 and 1 alpha,25,26-trihydroxy-23-oxo-vitamin D3. Neither of the two new metabolites is produced by the intestinal mucosa when 1,25S,26-trihydroxyvitamin D3 is used as a substrate.