胰岛素样生长因子-Ⅰ对软骨细胞凋亡的抑制

目的:探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)对软骨细胞增殖及白细胞介素-1(IL-1)诱导软骨细胞凋亡的影响,揭示其抗损伤作用机制,为关节软骨损伤治疗提供理论依据。方法:分离培养人胚胎关节软骨细胞,采用四氮甲基唑蓝(MTT)法测定不同含量软骨细胞增殖活性的变化,利用光镜、电镜、DNA电泳及流式细胞仪测定作为凋亡检测指标。结果:IGF-Ⅰ呈剂量依赖式促软骨细胞增殖,当IGF-Ⅰ含量达50μg/L时,促软骨细胞增殖作用达最大值。IL-1组光镜、电镜下可见典型的细胞凋亡形态学改变,琼脂糖凝胶电泳示特征性的DNA梯状条带,IGF-Ⅰ处理组未见明显凋亡征象。流式细胞仪检测发现,IGF-Ⅰ处理后软骨细胞凋亡率显著降低。结论:IGF-Ⅰ能促进软骨细胞增殖,对IL-1诱导的软骨细胞凋亡具有保护作用。     

Basal B-cell receptor signaling in B lymphocytes: mechanisms of regulation and role in positive selection, differentiation, and peripheral survival

Summary:  B-cell development is a highly ordered multistep process dependent upon signals generated by the pre-B and B-cell antigen receptor (BCR). BCR signals drive maturation of the B cell by integrating a number of parallel and sequential biological processes that result in generation of fully immunocompetent B cells. Among these biological processes are positive selection through several developmental checkpoints, negative selection of potentially self-reactive B cells, and activation of the mature B cell. In addition, recent studies have shown that developing and mature B cells rely on the constant activity of the BCR for their continued survival. Ligand (antigen)-dependent and -independent mechanisms of BCR signaling have been proposed, but their specific contributions to B-cell maturation and differentiation in the bone marrow and periphery are not completely clear. We discuss here a model, whereby ligand-independent basal BCR activity would be sufficient to trigger B-cell development through to the mature stage. However, long-term survival and formation of specific mature B-cell populations may be dependent on ligand–receptor interactions.     

Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)?

Background  

Human monocytic ehrlichiosis (HME) and Rocky Mountain spotted fever (RMSF) are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Should punch biopsies be used when high-grade disease is suspected at initial colposcopic assessment? A prospective study

The reliability and applicability of colposcopically directed cervical punch biopsy was assessed in a sample of 170 paired punch and large loop excision of cervical transformation zone (LLETZ) specimens obtained from previously untreated women who had been selected for treatment on the basis of cytology and/or colposcopic findings and in whom the entire cervical transformation zone was visible. A single punch biopsy was taken immediately before the LLETZ, and all the specimens were reviewed by a single pathologist. Nine (5.3%) punch biopsies were inadequate. In terms of whether or not there was cervical intraepithelial neoplasia (CIN), the chance-corrected kappa analysis rated overall agreement as poor (kappa = 0.21, 95% confidence limits 0.02-0.39), whereas in terms of histologic grade, it was fair to moderate (kappa = 0.32, 95% confidence limits 0.23-0.42). Punch biopsy tended to underestimate the disease. The sensitivity and specificity of colposcopically directed punch biopsy for the detection of high-grade CIN was 74% and 91%, respectively, with positive- and negative predictive values of 97% and 48%, respectively. Two microinvasive and two intraepithelial glandular lesions were missed on punch biopsy. Punch biopsy should be avoided when high-grade disease is suspected.     

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.     

Colonic pseudolipomatosis, microscopically classified into two groups

Background: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. Methods: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Results: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal‐looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal‐looking surface or non‐elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable‐sized vacuoles, and were related to lymph follicles. Conclusion: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.