4种支架构建复合式口腔黏膜的组织学特点

目的利用4种不同支架材料构建复合式口腔黏膜,并比较其组织结构特点。方法体外培养人口腔黏膜的成纤维细胞和角质形成细胞,在4种支架材料中加入成纤维细胞,培养7d后,在支架表面加入角质形成细胞,培养4d后,移至气-液界面继续培养7d。苏木精-伊红染色镜下观察构建的复合式口腔黏膜的组织形态学特点。结果 4种支架均可构建形成复层上皮。其中,上皮层与脱细胞真皮基质材料(de-epidermised dermis,DED)结合紧密,形成的人工黏膜有明显的上皮钉突。不同于以往报道,上皮层与Alloderm结合并不十分紧密。以胶原凝胶为基质形成的人工口腔黏膜最厚,有明显分层。以胶原海绵-胶原凝胶为基质形成的复层上皮在部分区域长入至胶原海绵的空隙中。结论以DED和胶原凝胶为支架构建的口腔黏膜更接近于天然结构,而后者脆性较大,限制了其临床应用的可能。     

The 14q+ chromosome in pre-B-ALL

A child who had acute lymphoblastic leukemia (ALL) associated with an 8;14 chromosome translocation and with a pre-B phenotype is described. The leukemic cells were determined to be pre-B-cells on the basis of intracytoplasmic mu-chain immunoglobulin (cIgM+) and the common-ALL antigen, lack of receptors for sheep erythrocytes, and lack of surface immunoglobulin. The 8;14 translocation is frequently found in patients with Burkitt's lymphoma and in most patients with B-cell ALL and is known to carry a poor prognosis. Thus far, no karyotypes have been reported for patients with pre-B-ALL. The present case indicates that a 14q+ chromosome may provide a proliferative advantage not only to cells with a B-cell phenotype, but also to pre-B-cells. The short survival of our patient also suggests that the 14q+ abnormality and the pre-B phenotype may signal a poor prognosis.     

The use of a recombinant immunoblot assay in the interpretation of anti- hepatitis C virus reactivity among prospectively followed patients, implicated donors, and random donors

Samples from prospectively followed recipients, their respective donors, and a cohort of random donors were used to evaluate the specificity and efficacy of a recombinant immunoblot assay (RIBA) as an adjunct to anti-hepatitis C virus (HCV) testing by enzyme immunoassay (EIA). RIBA reacted (RIBA+) in 100 percent of patients who developed hepatitis associated with anti-HCV seroconversion documented by EIA and in 100 percent of the EIA-positive (EIA+) donors implicated in these cases. In contrast, RIBA reacted in none of 10 recipients who were EIA+ but did not develop hepatitis, in none of 7 EIA+ patients with hepatitis B or cytomegalovirus infection, in 33 percent of EIA+ donors who were not implicated in hepatitis transmission, and in 37 percent of EIA+ random donors. Hence, the vast majority of EIA+ individuals who have ancillary evidence of HCV infection react on RIBA, whereas the majority of EIA+ individuals in low-risk settings do not react (RIBA-negative, or RIBA-). There was a strong association between RIBA reactivity and the presence of a surrogate marker (elevated alanine aminotransferase [ALT] and/or antibody to hepatitis B core antigen); 43 percent of RIBA+ implicated donors had a surrogate marker as compared to none of 14 EIA+, RIBA- donors. Among EIA+ random donors, 77 percent of those with a surrogate marker were RIBA+, as compared with 29 percent of those without a surrogate marker. In addition, in EIA+ donors, RIBA reactivity correlated with the extent of ALT elevation; 86 percent of those with an ALT greater than 135 IU per L were RIBA+ compared with 18 percent of those with an ALT less than 30 IU per L.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diphenylhydantoin-induced pure red cell aplasia

The pathogenesis of diphenylhydantoin-induced pure red cell aplasia was investigated in the case of a 32-year-old man who developed pure red cell aplasia while he was under treatment with diphenylhydantoin. The patient's serum IgG purified from serum drawn at the time of diagnosis suppressed normal allogeneic marrow colony-forming (CFU-E) and burst- forming (BFU-E) and autologous blood BFU-E growth in vitro only in the presence of diphenylhydantoin. This IgG-diphenylhydantoin complex had no effect on CFU-GM growth in vitro. Normal IgG or patient's IgG purified from serum drawn after the remission of red cell aplasia had no effect on erythroid colony formation in vitro in the presence of diphenylhydantoin. The IgG-diphenylhydantoin complex exerted no direct cytotoxic effect on normal marrow erythroblasts, CFU-E, and BFU-E, nor did it interfere with the action of erythropoietin on marrow erythroblasts. These studies suggest that diphenylhydantoin-induced red cell aplasia is immunologically mediated through an IgG inhibitor, which requires the presence of the drug to suppress erythroid colony formation in vitro. This inhibitor seems to exert its effect on erythroid progenitors at or beyond the stage of differentiation of CFU- E, but not on erythroblasts.     

肠息肉发生的细胞和分子生物学研究进展

肠息肉是一类从黏膜表面突出到肠腔内的隆起状病变的临床诊断．在最近的研究中陆续证实,其发生和发展的原因和机制,是由于Bmprla,APC,SMAD4,PTEN,STK11等基强突变而使各种细胞信号分子通过影响BMP信号通路,PTEN信号通路及Wnt信号通路所组成的生长信号调控网络,造成β-catenin在肠干细胞中的过度积聚,使得肠干细胞功能紊乱,导致其自我更新、克隆增殖、分化和凋亡失去平衡的结果．     

Urothelial carcinoma of the upper urinary tract: inverted growth pattern is predictive of microsatellite instability

Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of hereditary nonpolyposis colorectal cancer syndrome (HNPCC), a disorder characterized by mutation or inactivation of a number of DNA mismatch repair genes and detectable as microsatellite instability (MSI). Some urothelial carcinomas display areas of endophytic, or inverted, growth. In this study, urothelial cancers of the upper urinary tract (n = 132) from patients treated at 2 tertiary care centers were studied to identify an association between growth pattern and MSI. Thirty-five neoplasms were microsatellite unstable (26.5%), and MSI was more frequent in papillary lesions than in sessile urothelial cancers (P = .033). The amount of inverted growth was estimated as a percentage of the total tumor. The interobserver and intraobserver concordance in recognizing inverted growth was good, and 65.7% of microsatellite-unstable tumors exhibited at least 20% of an inverted growth component, compared with only 17.5% of microsatellite-stable tumors (P < .0001). In this series, inverted growth predicted MSI with a sensitivity and specificity of .82. Inverted growth in urothelial carcinomas of the upper urinary tract may serve as a marker lesion for MSI and may help identify patients who should be offered testing for HNPCC.     

Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory

Primary Autosomal Recessive Microcephaly (MCPH) is characterized by congenital microcephaly usually without additional clinical findings. The most common gene implicated in MCPH is ASPM and a large percentage of mutations described have been homozygous and in consanguineous families primarily of East Asian and Middle Eastern origin. ASPM sequencing was performed on 400 patients between the years 2009 and 2012. Seventy of the patient samples were also analyzed for copy number changes in the ASPM gene. Forty protein truncating mutations, including 29 novel mutations, were identified in 39 patients with MCPH. Approximately one third of patients were compound heterozygotes, indicative of non‐consanguinity in these patients. In addition, 46 non‐synonymous variants were identified and interpreted as variants of uncertain significance. No deletion/duplication in ASPM was identified in the patients analyzed. A wide ethnic distribution was observed, including the first reported patients with ASPM‐related MCPH of Hispanic descent. Clinical information was collected for 26 of the ASPM‐positive patients and 41 of the ASPM‐negative patients. As more individuals are identified with MCPH, we anticipate that we will continue to identify ASPM mutation‐positive patients from all ethnic origins supporting the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations.     

Invasion pattern and histologic features of tumor aggressiveness correlate with MMR protein expression,but are independent of activating KRAS and BRAF mutations in CRC

KRAS/BRAF mutation testing and mismatch repair (MMR) protein immunohistochemistry have an established role in routine diagnostic evaluation of colorectal carcinoma (CRC). However, since the exact impact of these molecular characteristics on tumor morphology and behavior is still subject to research, the aim of our study was to examine associations between molecular and morphologic features that had not been analyzed in this combination before. KRAS (codons 12, 13, and 61) and BRAF (codon 600) mutation status and MMR protein expression were analyzed in a consecutive series of 117 CRC samples using DNA pyrosequencing and immunohistochemistry. Tumor cell budding, infiltration pattern, and peritumoral lymphocytic (PTL) reaction was assessed applying established criteria. Molecular and morphological findings were correlated applying chi-square and Fisher’s exact test. We found KRAS or BRAF mutations in 40 and 8 % of samples, while loss of MMR protein expression was observed in 11 %. Tumor budding was significantly associated with infiltrative growth, absence of PTLs, and blood and lymph vessel infiltration. Neither KRAS nor BRAF mutations were associated with a certain growth pattern or budding intensity of CRC, but loss of MMR protein expression was found in context with BRAF mutation, expanding growth, and presence of PTLs. Our results confirm an association between loss of MMR protein expression, presence of activating BRAF mutation, expanding growth, and PTL reaction as well as between tumor budding, infiltrative growth pattern, and tumor aggressiveness; however, there was no such association between the presence of an activating KRAS or BRAF mutation and a distinct invasion pattern or tumor aggressiveness in CRC.