Terminal transverse limb defects and early chorionic villus sampling: Evaluation of 4,300 cases with completed follow-up

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = (1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9–10 weeks, 80.7% of TA-CVS procedures were carried out at 12–15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 Women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,645 TA) continuing pregnancies. The overall fetal loss rare <28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group. © 1993 Wiley-Liss, Inc.     

Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma

The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma.     

HER-2/neu and bcl-2 in ovarian carcinoma: clinicopathologic, immunohistochemical, and molecular study in patients with shorter and longer survival.

The bcl-2 protein is a membrane protein involved in prolonging cell survival by inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl-2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who had no evident disease 5 years after primary treatment compared with ovarian carcinomas obtained from patients, matched for stage, grade of differentiation, and treatment, who had died of progression of disease no later than 2 years after primary treatment. bcl-2 overexpression was statistically correlated with progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu status was found not to correlate with progression of disease during first-line chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically associated with the clinical outcome of ovarian cancer patients. Gene amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+ score, positive-staining ovarian carcinomas. None of the analyzed samples revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of additional prognostic or even predictive factors, such as bcl-2 expression, in patients with advanced ovarian carcinoma before the primary chemotherapeutic treatment may help in the management of patients who require a more tailored treatment. In addition, the gene amplification of the HER-2/neu suggests that HER-2 is a potential target for treatment in ovarian cancer.     

Protective Molecules–C-Reactive Protein (CRP), Serum Amyloid P (SAP), Pentraxin3 (PTX3), Mannose-Binding Lectin (MBL), and Apolipoprotein A1 (Apo A1), and Their Autoantibodies: Prevalence and Clinical Significance in Autoimmunity

Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity, as they can contribute to autoantigen overload, and may initiate an autoimmune response. The pentraxins are a group of highly conserved proteins including the short pentraxins, C-reactive protein (CRP) and serum amyloid-P (SAP), and the long pentraxin-3 (PTX3), which are all involved in innate immunity and in acute-phase responses. Mannan-binding lectin (MBL) is an activator of the complement system, and Apolipoprotein A-1 (Apo A-1) is pivotal in the cholesterol homeostasis and has anti-inflammatory properties. In addition to their role in innate immunity and inflammation, each of these five proteins participates in the removal of damaged and apoptotic cells. In this review, we discuss the clinical significance of different levels of these proteins, their role in the induction or protection from autoimmunity, and the presence of specific autoantibodies against them in the different autoimmune diseases.     

Interferon Gamma Alters the Phenotype of Rat Thymic Epithelial Cells in Culture and Increases Interleukin-6 Production

Rat thymic epithelial cells (TEC) in long-term culture were characterized by anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic analysis performed by a large panel of mAbs showed that the highest percentage of these cells was of the subcapsular/medullary type. Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC expression by TEC in culture as confirmed by immunohistochemistry and flow cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma- treated cultures showed higher interleukin-6 (IL-6) activity, compared to the control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6 activity was probably not a consequence of increased TEC number in IFN-gammatreated cultures because IFN did not significantly stimulate TEC proliferation in vitro. In contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is not only a regulatory molecule for T-cell proliferation, but could also be an autocrine growth factor for thymic epithelium.