Modified C-Reactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro

Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.     

Surgical site infections at the National Cancer Institute in Mexico: a case-control study

OBJECTIVES: To quantify the surgical infection rate and to identify risk factors associated with surgical site infection. METHODS: We conducted a case-control study of all surgical patients between January 1, 1993, and June 30, 1994. The frequency of surgical site infection per 100 surgeries was calculated. The odds ratio (OR) was estimated by using logistic regression analysis. SETTING: A 130-bed tertiary-care teaching hospital for adult patients with cancer. RESULTS: The study followed 3372 surgeries. Three hundred thirteen patients had a surgical site infection (rate per 100 surgeries: 9. 30). The risk factors associated with surgical site infection were diabetes mellitus (OR = 2.5, 95% confidence interval [CI] = 1.27-4. 91), obesity (OR = 1.76, 95% CI = 1.14-2.7), presence of surgical drains for >5 and <16 days (OR = 1.84, 95% CI = 1.02-3.31), and presence of surgical drains for >/=16 days (OR = 2.14, 95% CI = 1. 0-4.6). The bacteria most frequently isolated were Escherichia coli 38 (21.8% of the total of microorganisms found), Pseudomonas sp 22 (12.6%), Staphylococcus aureus 16 (9.2%), and coagulase-negative Staphylococcus 25 (13.6%). The coexistence of other nosocomial infections was greater among the cases (OR = 1.8, 95% CI = 1.1-3.1) than in the control group. CONCLUSIONS: The surgical site infection rate in our hospital is slightly higher than the rates reported for general hospitals. The risk factors associated with surgical site infection are similar to those previously reported. Diabetes mellitus, obesity, and prolonged presence of a surgical drain increased the risk of infection.     

Expression of protectin (CD59) in human melanoma and its functional role in cell- and complement-mediated cytotoxicity

Immunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra- and intertumor heterogeneity. SDS-PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5 U/ml of phosphatidylinositol-specific phospholipase C completely abolished cell-surface expression of CD59. Interferon-γ and/or tumor necrosis factor-α or phorbol 12-myristate 13-acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59-specific mRNA. F(ab')₂ fragments of anti-CD59 MAb YTH53.1 did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine-activated killer (LAK) cells. In contrast, the whole lg molecule of MAb H19 or YTH53. I significantly (p < 0.05) enhanced NK-cell-mediated lysis of melanoma cells, suggesting the induction of antibody-dependent cell-mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53. I or its F(ab')₂ fragments significantly (p < 0.05) enhanced, in a dose-dependent fashion, the lysis of anti-GD3-sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host-tumor interaction by protecting neoplastic cells from complement-mediated lysis. © 1995 Wiley-Liss, Inc.     

An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico

The p53 tumor suppressor gene is commonly mutated in human hepatocellularcarcinoma (HCC). The most frequent mutation in HCC in populationsexposed to a high dietary intake of aflatoxin Bl (AFB1) is anAGG^arg     

Origin of a central nervous system lymphoid neoplasm in an immunocompromised host with acute lymphoblastic leukemia

We describe a case of relapsed pediatric pre-B acute lymphoblastic leukemia (ALL) with a simultaneous presentation of an intracerebral lymphoid mass. Cytogenetic, immunophenotypic and molecular analysis (immunoglobulin heavy chain and T-cell receptor gene rearrangements) revealed that the brain neoplasm was distinct from the relapsed leukemia. We discuss the etiology of this extremely rare event, and raise issues about the clonality of lymphoid neoplasms and the behavior of hematopoietic cells within the central nervous system (CNS).     

Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation of p16(INK4a), p14(ARF), and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.     

Seroreactivities against Saccharomyces cerevisiae and Mycobacterium avium subsp. paratuberculosis p35 and p36 antigens in Crohn's disease patients

Crohn's disease (CD) is an idiopathic chronic inflammatory bowel disease (IBD). Accurate diagnosis of the disease is of great clinical importance to assess its prognosis and success of therapy. Recent studies have validated and confirmed the potential utility of anti-Saccharomyces cerevisiae (baker's yeast; ASCA) IgG/IgA antibodies and anti-M. avium ss. paratuberculosis p35/p36 antibodies, separately, as serological markers to identify patients with CD. The efficacy of these markers was evaluated in the same patients with Crohn's disease. The anti-ASCA IgA/IgG and the anti-M. avium ss. paratuberculosis p35/p36 antibodies were positive in 60% (36/60) and 86.7% (52/60) of CD patients, respectively. When all the serologic markers were considered, the sensitivity in detecting CD was increased to 95.0% (57/60); 21 of 24 ASCA-negative patients were p35/p36-positive and five of eight of p35/p36-negative patients were ASCA-positive. This investigation further establishes the utility of p35 and p36 recombinant clones for the diagnosis of CD, and reveals the complimentary role of ASCA and p35 and p36 for effective detection of CD. Larger studies are needed to investigate the combined use of these serologic markers for the diagnosis of CD.