Characterization of T cell epitopes in αs1-casein in cow''s milk allergic, atopic and non-atopic children

BACKGROUND: One to two percent of infants suffer from IgE-mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance. OBJECTIVE: To identify T cell epitopes in alphas1-casein, the most abundant milk protein, and to investigate T cell responses toward these epitopes in allergic, atopic and non-atopic children. METHODS: Allergen-specific T cell lines (TCLs) were derived from peripheral blood mononuclear cells of 11 cow's milk allergic, nine atopic and nine non-atopic children. T cell responses were measured to alphas1-casein and to overlapping peptides (18-mers), spanning the alphas1-casein molecule. Proliferation was determined by incorporation of (3)H-thymidine, and cytokine production (IL-10, IL-13 and IFN-gamma) was measured by ELISA. RESULTS: Four main regions (amino acid (AA) residues 43-66, 73-96, 91-114 and 127-180) in the alphas1-casein molecule were immunogenic to T cells, among which the AA residues 133-156 spanned the immunodominant part. Only subtle differences were found in peptide recognition between the subject groups. Some of the peptides induced slightly Th1- or Th2-skewed cytokine responses. The increased levels of IL-10 in response to alphas1-casein observed in TCLs from atopic children appeared not to be linked to recognition of specific IL-10-inducing epitopes. CONCLUSIONS: The immunodominant sequence in alphas1-casein is spanned by AA residues 133-156. Tolerance towards alphas1-casein in atopic children may be mediated by an overall induction of IL-10 and not by recognition of certain T cell epitopes. The identified T cell epitopes in children with cow's milk allergy may be useful targets in developing peptide immunotherapy.     

Transforming growth factor-β1 and interleukin-10 in breast milk and development of atopic diseases in infants

BACKGROUND: Precise relationship between breastfeeding and infant allergy is poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in colostrum and mature milk from allergic and non-allergic mothers and to verify relationship with allergic disease development. METHODS: Mothers (13 allergics, nine controls) of 22 newborns participated to prospective study on development of children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10 by ELISA. Children underwent paediatrician evaluation at 6 months of life. RESULTS: Data are presented as median values and range. A significant difference in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL) (P=0.015). IL-10 was weakly expressed without significant differences between allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0-42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but none from controls, presented atopic dermatitis. CONCLUSION: TGF-beta(1) was significantly less secreted in mature milk of allergic mothers, while no difference in IL-10 was found. Particular cytokine patterns in milk could influence development of atopic diseases. Further immunological studies in this field are necessary.     

Cloning and expression of SLC1OA4,a putative organic anion transport protein

AIM:To determine if novel bile acid transporters may be expressed in human tissues.METHODS:SLC10A1 (NTCP) was used as a probe to search the NCBI database for homology to previously uncharacterized ESTs. The homology search identified an EST (termed SLC10A4) that shares sequence identity with SLC10A1 and SLC10A2 (ASBT). We performed Northern blot analysis and RT-PCR to determine the tissue distribution of SLC10A4. SLC10A4 was cloned in frame with an epitope tag and overexpressed in CHO cells to determine cellular localization and functional analysis of bile acid uptake.RESULTS:Northern analysis revealed that SLC 10A4 mRNA is ubiquitously expressed fn human tissues with the highest levels of mRNA expression in brain,placenta, and liver. In SLC10A4-transfected CHO cells,immunoblotting analysis and immunofluorescence staining demonstrated a 49-kDa protein that is expressed at the plasma membrane and intracellular compartments.Functional analysis of SLC10A4 showed no significant taurocholate uptake in the presence of sodium when compared to untransfected CHO cells.CONCLUSION:To date, we have shown that this protein has no capacity to transport taurocholate relative to SLC1041; however, given its ubiquitous tissue distribution, it may play a more active role in transporting other endogenous organic anions.     

A Brief Mental Health Outcomes Measure: Translation and Validation of the Czech Version of the Schwartz Outcomes Scale-10

The Schwartz Outcomes Scale-10 (SOS-10) is a 10-item scale developed to measure the effectiveness of psychiatric treatments. Using standard methodology, we translated the scale into Czech and examined the psychometric properties of the Czech version. 207 in-patients admitted to Prague Psychiatric Center were included in the study. All patients completed the SOS at admission and discharge. The SOS-10 scale was also administered to 170 persons from the general population. Reliability, validity and sensitivity to treatment change of the Czech SOS-10 were analyzed. The Cronbach’s α coefficient was 0.92. The item-total correlation coefficients varied from 0.56 to 0.82. The SOS-10 correlated well with condition-specific measures including depression (BDI) and anxiety (BAI) and a global self-rated symptom severity scale (CGI). The SOS-10 also had significant correlations with the Health, Basic needs, Relationship, and Leisure time domains of the Czech version of the Subjective Quality of Life Analysis (SQUALA-CZ). The scale discriminated well between patients and controls, with patients scoring significantly lower on all SOS items. The patient sample’s admission and discharge scores were significantly different, indicating that the scale is sensitive to treatment changes. We concluded that the Czech SOS-10 is valid with reliability and factor structure similar to the American language version.     

肝炎肝硬化患者血清IL-10、IL-18水平的变化及意义

目的探讨血清IL10、IL18在肝炎肝硬化的发病机制中的作用。方法62例肝炎肝硬化患者根据childpugh分级法分为3组:childpughA级组19例、childpughB级组23例和childpughC级组20例。采用ELISA法检测3组患者和20例健康献血员血清IL10、IL18的水平。结果childpughA、B、C级组血清IL18水平均明显高于对照组(P均<0.01),childpughA级组血清IL10水平略高于对照组,但无显著性差异(P>0.05);childpughB、C级组明显低于对照组(P<0.05);有腹水组、无腹水组血清IL18水平均明显高于对照组(P均<0.01),有腹水组血清IL10水平明显低于无腹水组、对照组(P<0.05,P<0.01);血清IL10水平与血清IL8水平呈负相关(r=-0.51,P<0.01);血清白蛋白水平与血清IL10水平呈正相关(r=0.566,P<0.01),与血清IL8水平呈负相关(r=-0.315,P<0.01);血清凝血酶原活动度与血清IL10水平呈正相关(r=0.506,P<0.01),与血清IL18水平呈负相关(r=-0.463,P<0.01);血清总胆红素水平与血清IL8水平呈正相关(r=0.677,P<0.01),与血清IL10水平呈负相关(r=-0.339,P<0.01)。结论IL10、IL18在肝炎肝硬化的发病机制中起一定的作用,其水平与肝损害程度密切相关。     

Scales of depression,ill-being and the quality of life—is there any difference? An assay in taxonomy

The application of a model based on the three time dimensions of past, present and future can be used to generate an alternative taxonomy for the classification of depression, ill-being and quality of life. In relation to time, depression can be defined as the passage from a healthy past to a painful present, ill-being as the painful present of the individual and the quality of life (QOL) as the degree to which the subject's present life is commensurate with his aspirations. Such an approach opens up conceptual and methodological areas of research which will allow the construction of a new type of scale. Depression scales should be constructed with two time dimensions: past and present; ill-being scales only refer to the present and QOL scales should have two time dimensions: present and future. It would be possible to combine these three scales into a single scale with three dimensions. Such a scale would enable depression and ill-being to be quantified, accurately diagnosed and monitored. The relative importance of principal symptoms could be assessed, facilitating the choice of therapy and follow-up methods.     

Interstitial deletion of 10q: Clinical features and literature review

We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley-Liss, Inc.     

Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323–339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance

BACKGROUND: Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance. OBJECTIVE: To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323-339 (OVAp). METHODS: BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis. RESULTS: Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4(+) T cells in BLN of OVA-treated mice only. CONCLUSION: INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4(+) T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.     

不明原因复发性流产患者子宫内膜/早孕蜕膜组织HOXA-1O基因的表达

目的探讨不明原因复发性流产（URSA）与子宫内膜／早孕蜕膜组织HOXA-10基因表达的关系。方法采用原位杂交技术，以HOXA-10反义核苷酸为探针检测51例URSA患者及38例正常生育（NF）组的分泌期子宫内膜／早孕蜕膜组织HOXA-10mRNA的表达水平，并以灰度阳性单位（PU值）表示。结果NF组子宫内膜分泌早期HOXA-10mRNA表达的PU值腺体为（6．66±0．11），间质为（6．76±0．15）；分泌中期分别为（10．95±0．90）及（11．46±1．08）；分泌晚期分别为（11．05±1．12）及（11．54±1．10）；蜕膜组织分别为（11．55±1．14）及（11．93±1．92）；分泌中晚期及蜕膜组织的Pu值显著高于分泌早期。URSA组不同时期子宫内膜及早孕蜕膜组织中HOXA-10mRNA的表达水平基本一致，无明显的分泌中晚期及早孕期峰，并且分泌中晚期及早孕蜕膜组织的PU值明显低于NF同期组。两组各期腺体和间质的PU值无显著差异。结论子宫内膜HOXA-10基因在分泌中晚期及早孕蜕膜组织中的高表达可能和孕卵着床及妊娠维持密切相关，其表达缺陷可能是导致URSA发生的重要原因之一。     

Conners教师评定量表的中国城市常模和信度研究

目的　建立Conners教师评定量表 (TRS)的中国城市常模 ,并对其进行信度检验。方法　在全国 14个城市对 35 76名儿童年进行Conners教师量表的评定 ,对其中 4 0名儿童间隔二周进行重测。结果　TRS各条目分与量表总评分之间的相关系数在 0 2 6 5～ 0 6 89;总问卷Cronbachα系数为 0 94 1,Spearman brown分半信度为 0 896 ,间隔二周量表总分的重测相关系数为 0 5 4 4 ,4个因子的重测相关系数在 0 391～ 0 6 71(P <0 0 1)。结论　Conners教师评定量表的中国城市常模符合我国国情 ,具有良好的信度 ,值得推广和应用。