Chromosome 2q terminal deletion: report of 6 new patients and review of phenotype-breakpoint correlations in 66 individuals

We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic-like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling.     

Role of new population of peripheral CD11c(+)CD8(+) T cells and CD4(+)CD25(+) regulatory T cells during acute and remission stages in rheumatoid arthritis patients.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a CD4(+)-dependent chronic systemic inflammatory disease with autoimmune features. Autoreactive CD4(+) T-cell activation can result in autoimmune diseases. One of the key regulators is the CD4(+)CD25(high) regulatory T (Treg) cell. In an animal arthritis model, CD11c(+)CD8(+) T cells were found to be elevated, and could suppress pathogenic CD4(+) T cells after cross-linking with CD137. The purpose of this study was to compare the expression of CD137, CD4(+)CD25(high) Treg cells, and CD11c(+)CD8(+) in the peripheral blood T lymphocytes of RA patients during active and remissive states, and evaluate the correlation with disease activity. METHODS: Thirty nine RA patients treated at the rheumatology outpatient clinic at the Changhua Christian Hospital were assessed clinically for disease activity and classified as either highly active or remissive by the Disease Activity Score 28. Peripheral blood mononuclear cells were isolated from these patients and compared against normal controls. RESULTS: The presence of CD11c(+)CD8(+) T cells or the expression of CD137 molecules in peripheral blood cells was not related to disease activity. In contrast, CD4(+)CD25(high) Treg cell levels were increased significantly in patients with active RA compared with patients with remissive RA or controls (p<0.05). These lymphocytes were intact, without evidence of apoptosis. CONCLUSIONS: Our results indicate that CD4(+)CD25(high) Treg cells play an important role in modulating RA disease activity and can serve as a parameter of disease activity.     

上颌窦的胚胎发育

对46例(92侧)12～40周胎儿标本的上颌窦,行冠状切,HE染色,光镜观察:(1)原始上颌窦在胚胎第20～22周由原始筛漏斗底部扩展而成,上颌窦位于钩突和中鼻道外侧壁的外侧,窦腔与眼眶之间的骨板最薄,且骨化较晚.(2)窦口位于上颌窦的顶部(壁),随胎龄增长,”钩突角”变小.向外下的筛漏斗渐近水平位.(3)出生时,上颌窦大小约3.0×5.0×6.5mm.窦内粘膜上皮细胞呈立方形或矮柱状,其纤毛稀疏,,固有膜增厚、疏松,内含极少量血管和腺体.结果表明:出生时,上颌窦虽已出现,但粘膜厚,窦腔小,且与眼眶的毗邻关系密切,上颌窦粘膜的组织结构与鼻腔粘膜的结构有所不同.     

脑胶质瘤中血脑屏障的超微结构特点

８例胶质瘤病例，标本分别取自同一病例的瘤体，瘤周水肿区和邻近脑组织。瘤体和瘤周水肿区血脑屏障超微结构变化无明显差异，内皮肿胀，毛细血管腔狭小，腔面有稀疏的绒毛样突起，内皮为无孔型，胞质内胞饮泡较多，内皮紧密连接增长，细胞连接间隙增宽，基膜完整，基膜完整，胶质膜缺损。     

脑血流断层显像Bullseye显示

为了探讨用Bullseye显示脑血流灌注显像数据的可能性,对8例典型脑梗塞病例及15例脑血流断层显像常规分析可疑病例的脑血流断层显像的横断面数据进行Bullscye显示,结果8例典型病人病灶用普通Bullseye即显示良好;常规分析可疑病例病变用普通Bullseye 8例显示良好,变黑Bullseye 13例显示出病灶;结果提示利用Bullseye显示脑血流灌注显像数据的可能。     

人CD226分子胞膜外区D1和D2真核表达载体的构建、表达和鉴定

目的 构建含有人CD226分子胞膜外区结构域1(D1)和结构域2(D2)的真核表达载体,表达并纯化重组蛋白.方法用特异性引物分别扩增CD226 D1和D2的基因,定向插入真核表达载体pSecTag2B-Fc,进行酶切和DNA测序鉴定,重组质粒瞬时转染293T细胞,收集上清,纯化蛋白及SDS-PAGE和Western blot鉴定表达产物.结果利用PCR方法克隆出CD226胞膜外区D1和D2的基因,并正确插入pSecTag2B-Fc载体中,真核表达载体瞬时转染293T细胞,Western blot结果证实转染293T细胞的培养上清液中含有hCD226D1-Fc和hCD226D2-Fc融合蛋白,培养上清经亲和层析柱纯化,可获得较高纯度的重组蛋白.结论 成功的构建了分泌型融合蛋白hCD226D1-Fc和hCD226D2-Fc真核表达载体,获得纯度较高的融合蛋白,为进一步探讨其配受体的相互作用机制奠定了基础.     

Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells

Synthesis of the epidermal growth factor (EGF) receptor has been analyzed in a series of variant A431 human epidermoid carcinoma cell clones reported to contain different amounts of EGF binding sites. The amount of EGF receptor protein, quantitated by immunoaffinity chromatography, and EGF receptor mRNA, quantitated by cDNA hybridization, were closely correlated to the extent of EGF receptor gene amplification. This correlation existed in variants selected for reduced EGF receptors and in revertants from those variants with increased EGF receptors. There was also a correlation between the frequency of translocation of chromosome 7, containing the EGF receptor gene, and EGF receptor protein. These results support gene amplification as the mechanism enhancing A431 cell EGF receptor protein and determining growth responses.     

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.     

Humoral and cellular immune response after measles vaccination in Taiwan.

Measles immunoglobulin G (IgG) seroepidemiologic studies have been widely used to monitor the effectiveness of measles immunization programs in Taiwan. However, studies about cellular immunity against the measles virus have been lacking. This study surveyed cellular immunity after measles, mumps and rubella combined vaccine (MMR) immunization in Taiwan. Seventy six people between 1 and 80 years of age were enrolled. All patients lived in northern Taiwan, and none of them had immunodeficient disease. Every enrolled patient donated a tube of heparinized blood between January 2004 and June 2004 for cross-sectional studies of IgG seroepidemiologic and MMR-specific lymphoproliferative response. The results showed that the current 3-dose (measles x 1 + MMR x 2) measles immunization program induced slightly higher IgG seroprevalence (100% vs 85%, p=0.244) and a higher frequency of significant (stimulation indices > or = 3) MMR-specific lymphoproliferative response (50% vs 15%, p=0.044) than a 2-dose (measles x 1 + MMR x 1) immunization program, although there was no difference in IgG titers and stimulation indices. Furthermore, the population aged older than 36 years (pre-immunization era) had higher IgG titers and seroprevalence, and similar MMR-specific lymphoproliferative responses to that of the population aged younger than 36 years (post-immunization era). In summary, with the limited data, the current 3-dose (measles x 1 + MMR x 2) measles immunization policy probably more effectively induces humoral and cellular immunity than the 2-dose (measles x 1 + MMR x 1) policy. Measles IgG seroprevalence in populations of different age groups exceeds nearly 90%. Measles has been eliminated temporarily in Taiwan. For a better understanding of the durability of vaccine-induced immunity and in order to establish the most appropriate immunization schedule, long-term and large-scale prospective studies of measles-specific seroepidemiology and cellular immunity will be needed.     

Activation of transforming growth factor-beta1/p38/Smad3 signaling in stromal cells requires reactive oxygen species-mediated MMP-2 activity during bone marrow damage

Dose-escalated chemotherapy has proven utility in a variety of treatment settings, including preparative regimens before bone marrow or hematopoietic stem cell transplantation. However, the potential damage imposed by aggressive regimens on the marrow microenvironment warrants further investigation. In the present study, we tested the hypothesis that dose-escalated chemotherapy, with etoposide as a model chemotherapeutic agent, activates the transforming growth factor beta-1 (TGF-beta1) signaling pathway in bone marrow stromal cells. After high-dose etoposide exposure in vitro, Smad3 protein was phosphorylated in a time-and dose-dependent manner in marrow-derived stromal cells, coincident with the release of active and latent TGF-beta1 from the extracellular matrix. Phosphorylation was modulated by p38 kinase, with translocation of Smad3 from the cytoplasm to the nucleus subsequent to its phosphorylation. Etoposide induced activation of TGF-beta1 followed the generation of reactive oxygen species and required matrix metalloproteinase-2 (MMP-2) protein availability. Chemotherapy effects were diminished in MMP-2(-/-) knockout stromal cells and TGF-beta1 knockdown small interfering RNA-transfected stromal cells, in which phosphorylation of Smad3 was negligible after etoposide exposure. Stable transfection of a human MMP-2 cDNA into bone marrow stromal cells resulted in elevated phosphorylation of Smad3 during chemotherapy. These data suggest TGF-beta1/p38/Smad3 signaling cascades are activated in bone marrow stromal cells after dose-escalated chemotherapy and may contribute to chemotherapy-induced alterations of the marrow microenvironment.