小儿哮喘病人外周血单核细胞表型的变化

目的: 探讨小儿哮喘病人外周血中单核细胞表型特征, 以了解它与气管中巨噬细胞之间的相互关系和作用。方法: 采用全血单克隆抗体(CD14、CD16、HLA-DR、CD44、CD69)三色或双色荧光标记方法, 利用流式细胞仪检测细胞的阳性百分比和平均荧光强度。结果: 哮喘病人CD14和CD14⁺/CD16⁺中的CD16细胞的平均荧光强度、CD14⁺/CD16⁺和CD16^-粒细胞的百分率都明显高于健康对照组。结论: 哮喘病人外周血中的单核细胞具有组织中巨噬细胞的特征。     

Partial deletion of 14q and partial duplication of 14q in sibs: Testicular mosaicism for t(14q;14q) as a common mechanism

The propositus and a subsequently born sister presented with multiple congenital anomalies. Chromosome analyses were performed initially on peripheral blood lymphocytes from the propositus and his parents: the propositus was found to have a deletion of chromosome 14 (q32.11->qter); the parents' chromosomes were normal. When the sister of the propositus was born, she was determined to have a duplication of an equivalent segment of 14qter. Chromosome studies on the parents' fibroblasts demonstrated no structural abnormality or mosaicism. The parents have an older, phenotypically normal, healthy daughter, which supports mosaicism for intragonadal t(14;14)(q32.11;q32.33) in one parent. Chromosome polymorphism comparisons show that the normal number 14 chromosome in the propositus and his sister was inherited from the mother, thus indicating paternal testicular mosaicism. Clinical findings are compared to those of other reported cases of deletion 14q and duplication 14q.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts

BACKGROUND: In bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts. OBJECTIVE: This study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts. METHODS: Using primary bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14). RESULTS: Transfected cells showed enhanced expression of the appropriate mRNA species by RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels in epithelial supernatants were increased most by cotransfection with pro-MMP-2 and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation, supernatants from transfected cells were found to enhance DNA synthesis of primary airway fibroblast cultures compared with controls. There was a strong correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell conditioned media and fibroblast proliferation as indicated by DNA synthesis. The MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while the addition of exogenous purified MMP-2 alone also increased fibroblast proliferation. CONCLUSIONS: Our results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.     

CD14lowCD16high: A cytokine-producing monocyte subset which expands during human immunodeficiency virus infection

Infection with the human immunodeficiency virus HIV-1 is associated with the expansion of a CD14^lowCD16^high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14^lowCD16^high circulating monocytes co-express MAX.1, p150,95 and HLADR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)-1α and tumor necrosis factor (TNF)-α than the CD14^highCD16^low monocyte population from the same patients. The CD14^lowCD16^high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14^lowCD16^high monocyte subset, which produce high amounts of TNF-α and IL-1α, may participate in the immune dysfunction observed during HIV infection.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Requirement for IFN-gamma in IL-12 production induced by collaboration between v(alpha)14(+) NKT cells and antigen-presenting cells

Two cytokines IL-4 and IL-12 are known to determine the balance between T(h)1 and T(h)2 development. In addition to IL-4 production of V(alpha)14(+) NKT cells, they have recently been demonstrated to have the capacity to stimulate IL-12 production by antigen-presenting cells (APC). This study demonstrates that IFN-gamma is absolutely required for the NKT cell-stimulated IL-12 production. Culture of B cell-depleted spleen cells from C57BL/6 mice with alpha-galactosylceramide (alpha-GalCer) capable of selectively stimulating V(alpha)14/J(alpha)281(+) NKT cells resulted in the production of IL-12 together with IL-4. Whereas IL-4 production occurred in culture of IFN-gamma(-/-) C57BL/6 splenocytes, the same culture failed to generate IL-12 production. While IL-12 production induced during culture of V(alpha)14(+) NKT cells and APC depended on the interaction between CD40 ligand on NKT cells and CD40 on APC, the expression levels of these key molecules were comparable in cells from wild-type and IFN-gamma(-/-) mice. Addition of rIFN-gamma to alpha-GalCer stimulated IFN-gamma(-/-) splenocyte culture, and administration of rIFN-gamma to alpha-GalCer-injected IFN-gamma(-/-) mice resulted in the restoration of IL-12 production in vitro and in vivo. These results illustrate a mandatory role for IFN-gamma in V(alpha)14(+) NKT cell-stimulated IL-12 production by APC.     

The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma

AIMS: Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population. METHODS AND RESULTS: Sixty-two cases of follicular lymphoma were retrieved for immunohistochemistry, and t(14;18) translocation analysis by polymerase chain reaction and fluorescent in-situ hybridization techniques. Bcl-2 expression was present in 74% of the cases. CD10 expression was also relatively low (61%), with decreasing frequency of expression in high-grade tumours. Bcl-6 protein was expressed in most of the tumours (88%) regardless of the tumour grade. The t(14;18) translocation was detected in 46 cases (74%) with an extremely high rate of t(14;18) translocation in ethnic Indian cases (100%). CONCLUSION: The frequency of t(14;18) translocation in this series of follicular lymphomas was higher when compared with previous Asian reports, but in accordance with European and North American findings. CD10 expression is strongly associated with a t(14;18) translocation event, but the overall CD10 expression was relatively low, possibly due to the high proportion of high-grade tumours in the series. t(14;18) translocation was not associated with Bcl-2 or Bcl-6 expression.     

Anti-TWEAK monoclonal antibodies reduce immune cell infiltration in the central nervous system and severity of experimental autoimmune encephalomyelitis

TWEAK is a member of the TNF family, constitutively expressed in the central nervous system (CNS), with pro-inflammatory, proliferative or apoptotic effects depending upon cell types. Its receptor, Fn14, is expressed in CNS by endothelial cells, reactive astrocytes and neurons. We showed that TWEAK and Fn14 mRNA expression increased in spinal cord during experimental autoimmune encephalomyelitis (EAE). We investigated the role of TWEAK during EAE using neutralizing anti-TWEAK antibody in myelin oligodendrocyte glycoprotein (MOG) induced EAE in C57BL/6 mice. We observed a reduction of disease severity and leukocyte infiltration when mice were treated after the priming phase.     

Emergence and wide dissemination of CTX-M-type ESBLs, and CMY-2- and DHA-1-type AmpC beta-lactamases in Korean respiratory isolates of Klebsiella pneumoniae

Respiratory isolates of Klebsiella pneumoniae in Korea during 2002-2003 were studied to determine the prevalence and types of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated AmpC beta-lactamases (PABLs). ESBL-production was tested by double-disk synergy, and genotypes of beta-lactamases were determined by PCR and sequencing. ESBLs were detected in 28.4% of 373 isolates, and the most prevalent types were SHV-12 (63 isolates) and CTX-M-14 (9 isolates). Forty of 75 ESBL-producers (53.5%) also had PABLs: 21 isolates with CMY-2-like, 17 with DHA-1-like. Pulsed-field gel electrophoresis showed 19 types and 25 of 74 isolates had an identical pattern, indicating nosocomial spread. Dissemination of ESBL- and PABL-producing K. pneumoniae strains in Korea is a particular concern, as it limits the choice of antimicrobial agents for treatment of infections.