Pancreatic sarcoidosis

The authors report the case of a 30 year-old man with previous history of sarcoidosis, who presented with a painful infiltration of the pancreas. A review of the literature showed that symptomatic pancreatic sarcoidosis was uncommon, since only 8 other cases have been reported. Pancreatic involvement is frequently associated with hepatic infiltration (5/6 cases). Exocrine or endocrine dysfunction are possible. Diagnosis is made only at exploratory laparotomy. Prognosis is good. Steroid therapy is indicated in this peculiar type of pancreatitis, because of its long-range effectiveness on the outcome of the disease.     

Demonstration of clonal heterogeneity in adenocarcinomas on Barrett's esophagus by flow cytometric study of cellular DNA content]

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.     

A trial use of lenses of human placental collagen in epikeratoplasty procedures

Epikeratoplasty is a refractive surgery procedure described by Werblin and Kaufman which is simple, effective and reversible. However its development is hampered by the need of human corneas. We evaluated this procedure in rabbits and monkeys using lenticules of human collagen. The collagen is obtained from frozen human placentas, washed and subjected to pepsin digestion; it is contained in the supernatant of centrifugation and can be isolated by a physico-chemical treatment. 15 days after surgery the lenses of 14 rabbits were completely covered with a layer of epithelial cells. 6 months after surgery, the eyes of 14 monkeys were quiet and the lenses were covered with an epithelium made up of 2 to 5 layers of cells. The lens exhibited no inflammatory infiltration and there was no inflammatory reaction around the lens. These studies are still preliminary and longer term tests are necessary. These initial results are very encouraging, prompting us to develop the use of this type of material in refractive surgery.     

Bacteriocin from epidemic Listeria strains alters the host intestinal microbiota to favor infection

Listeria monocytogenes is responsible for gastroenteritis in healthy individuals and for a severe invasive disease in immunocompromised patients. Among the three identified L. monocytogenes evolutionary lineages, lineage I strains are overrepresented in epidemic listeriosis outbreaks, but the mechanisms underlying the higher virulence potential of strains of this lineage remain elusive. Here, we demonstrate that Listeriolysin S (LLS), a virulence factor only present in a subset of lineage I strains, is a bacteriocin highly expressed in the intestine of orally infected mice that alters the host intestinal microbiota and promotes intestinal colonization by L. monocytogenes, as well as deeper organ infection. To our knowledge, these results therefore identify LLS as the first bacteriocin described in L. monocytogenes and associate modulation of host microbiota by L. monocytogenes epidemic strains to increased virulence.The gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen that causes foodborne infections in humans and animals. Upon consumption of contaminated food, L. monocytogenes reaches the intestinal lumen, crosses the intestinal barrier, and disseminates within the host. The clinical manifestations of listeriosis vary from a mild, self-limiting gastroenteritis to severe intestinal and systemic infections, with a fatality rate estimated to 20–30% of infected individuals (1). Host gut microbiota plays a critical role in resistance against colonization by invading pathogens within the intestine (2). The mechanisms of L. monocytogenes to compete with the host microbiota to survive in the intestine remain unknown.During the last decades, the majority of Listeria studies in bacterial pathophysiology, cell biology, and immunology compared three pathogenic strains from lineage II: EGD, EGD-e, and 10403S (3). Interestingly, major listeriosis epidemics have been preferentially associated to L. monocytogenes clonal groups belonging to the evolutionary lineage I and, more specifically, to serotype 4b (4, 5), but the molecular mechanisms that contribute to the higher virulence potential of these bacterial strains have not been identified yet.Bacteriocins are bacterially synthesized proteinaceous substances that target and inhibit the growth of closely related bacteria, allowing competition in diverse ecological niches, including the digestive tract (6, 7). Production of these antimicrobial peptides is widespread among bacterial species, and such production is made possible by biosynthetic machineries present in the genome, plasmids, or conjugative transposons (7). A conserved biosynthetic gene cluster for the production of bacteriocins displaying thiazole and oxazole heterocycles was discovered in 2008 in six microbial phyla (8). These gene clusters encode a toxin precursor and all indispensable proteins for toxin maturation in a mode similar to that associated with the bacteriocin microcin B17 (8). This gene cluster in L .monocytogenes was only present in a subset of lineage I strains responsible for the majority of Listeria epidemics (9). This L. monocytogenes toxin was designated Listeriolysin S (LLS) and was shown to produce a hemolytic and cytotoxic factor necessary for virulence in a murine intraperitoneal (i.p.) infection model (9).The aim of the present work was to understand where LLS is produced in a murine oral infection model, as well as to investigate the function of this virulence factor. Interestingly, to our knowledge, we show that LLS is the first bacteriocin described in L. monocytogenes. This toxin that is specifically expressed in the intestine augments host colonization.     

Positive VEGF Immunostaining Independently Predicts Poor Prognosis in Curatively Resected Gastric Cancer Patients: Results of a Study Assessing a Panel of Angiogenic Markers

Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) contribute to gastric cancer aggressiveness by up-regulating the expression of proteases. We evaluated the expression and the prognostic significance of angiogenic factors and proteases in 148 patients with R0-resected gastric cancer. Expression of VEGF, Ang-2, cyclooxygenase-2 (COX-2), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, matrix metalloproteinases (MMP)-1 and -9 were assayed by immunohistochemistry. After a mean of 63 ± 4 months, 81 out of 148 patients had died due to disease. The probability of being free of recurrence was 62, 48, and 42% at 2, 5, and 10 years, respectively. Single bivariate analysis identified VEGF, Ang-2, COX-2, PAI-1, and MMP-9 expression, along with several clinicopathological parameters (grade of curability, lymph node ratio, pTNM, pT, pN), as variables associated with both decreased disease-specific survival and recurrence. On multivariate analysis, after adjusting for significant clinical covariables, positive VEGF immunostaining was the primary prognostic factor, and no other tumor marker variable could add any significant improvement for the prediction, for both disease-specific survival (p = 0.001; HR, 3.27; 95% CI, 1.76 to 6.10) and tumor recurrence (p = 0.002; HR, 2.81; 95% CI, 1.48 to 5.35). Our study suggests that VEGF alone may be clinically useful for establishing therapeutic decisions in gastric cancer patients. Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, Fl, May 13–17, 2005 (poster presentation). óscar Vidal, Antonio Soriano-Izquierdo, contributed equally to this work.     

Photorefractive keratectomy following undercorrected myopic epikeratoplasties]

Five eyes had a delayed refractive regression following myopic epikeratoplasty; the undercorrection ranged between -8.00 and -10.00 diopters. Four of the 5 eyes had a loss of best spectacle visual acuity of two Snellen lines or more. Excimer laser photorefractive keratectomy was performed to achieve a full refractive correction. A dense subepithelial haze was observed in the 5 eyes. The 3 months postoperative refraction ranged between -1.00 D and +2.50 D but the spectacle corrected visual acuity reached only 0.1 to 0.2. Because of the poor visual acuity results, the five epikeratoplasty lenticles were removed, resulting in restoration of best preoperative spectacle visual acuity in 4 of the 5 eyes. Excimer laser photorefractive keratectomy was not a helpful means of correcting residual high myopia after myopic epikeratoplasty. The poor results may be explained by the preexisting stromal abnormalities.