Regional hypothermia reduces mucosal NF-kappaB and PMN priming via gut lymph during canine mesenteric ischemia/reperfusion

BACKGROUND: Mesenteric ischemia/reperfusion (I/R) activates pro-inflammatory mediators that exacerbate gut reperfusion injury and prime circulating neutrophils that cause remote organ injury. We have shown that regional intraischemic hypothermia protects the intestinal mucosa during I/R in rats. In this study, we examined the effects of regional hypothermia on I/R-induced transvascular protein clearance, NF-kappaB DNA binding activity, and polymorphonuclear neutrophil (PMN) priming via gut lymph in a canine mesenteric lymphatic fistula model. MATERIALS AND METHODS: Conditioned dogs underwent 60 min of mesenteric ischemia, with or without regional intraischemic hypothermia, and 3 h reperfusion. A mesenteric lymphatic fistula model was used to measure transvascular protein clearance and harvest lymph. Biopsies of distal ileum were obtained at baseline and 0, 180 min of reperfusion for NF-kappaB DNA binding activity using electrophoretic mobility shift assay (EMSA). A kinetic spectrophotometric assay was used to determine fMLP stimulated PMN superoxide production after priming by gut lymph obtained at baseline and 180 min reperfusion. RESULTS: Transvascular protein clearance increased during reperfusion compared to baseline, and hypothermia had no significant effect on this I/R-induced protein clearance. NF-kappaB activity increased three-fold at the end of ischemia and hypothermia prevented this early activation. PMN superoxide production increased 19-fold during I/R (0.06 +/- 0.04 versus 1.14 +/- 0.50 nmol O(2), P < 0.05), but only 2.5-fold during I/R + hypothermia (0.28 +/- 0.09 versus 0.70 +/- 0.32 nmol O(2), P = 0.2). CONCLUSIONS: Regional intraischemic hypothermia prevented early intestinal NF-kappaB activation, partially abrogated PMN priming via gut lymph, but had no significant effect on increased transvascular protein clearance during mesenteric I/R in dogs.     

Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA array technology, we wanted to document its phenotypical and molecular characteristics. We report herein 5 cases of UCNT that morphologically mimic HL and 3 classical UCNT cases. We compared the expression profiles of a thousand selected genes in HL-like UCNT and in classical UCNT cases. No difference in the profile of EBV infection was noted between the HL-like UCNT and control cases. Significant differences were detected in the expression of genes involved in the matrix modelling, angiogenesis, apoptosis and regulation of the Th-2 interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was expressed in both stromal and carcinoma cell populations of HL-like UCNT, this pattern being similar to the one observed in HL. These results show that UCNT morphologically resembling HL share also some specific phenotypical and molecular features with HL, and might deserve to be isolated as a particular UCNT subtype.     

What surgeons should know about viral hepatitis and hepatocellular carcinoma

Most patients with hepatocellular carcinoma (HCC) have viral hepatitis, either hepatitis C (HCV) or hepatitis B (HBV). HCV is an RNA virus that does not integrate into the host genome but likely induces HCC through viral protein: for example, host protein interactions or via the inflammatory response to the virus. Eradication of HCV with interferon plus riboviron therapy may help prevent cancer recurrence in selected patients. In contrast to HCV, HBV is an DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. HBV is usually classified as replicative (DNA-positive in the serum) or nonreplicative (DNA-negative in the serum). Treatment with nucleoside analogs is indicated in most patients with cirrhotic-stage replicating HBV. Nonreplicative stages of this virus do not merit therapy with these agents.     

Expression of a model gene in prostate cancer cells lentivirally transduced in vitro and in vivo

In a preclinical model for prostate cancer gene therapy, we have tested lentiviral vectors as a practical possibility for the transfer and long-term expression of the EGFP gene both in vitro and in vivo. The human prostate cancer cell lines DU145 and PC3 were transduced using experimental conditions which permitted analysis of the expression from a single proviral vector per cell. The transduced cells stably expressed the EGFP transgene for 4 months. After injection of the transduced cell populations into Nod-SCID mice a decrease in EGFP was only observed in a minority of cases, while the majority of tumors maintained transgene expression at in vitro levels. In vivo injection of viral vector preparations directly into pre-established subcutaneous or orthotopic tumor masses, obtained by implantation of untransduced PC3 and DU145 cells led to a high transduction efficiency. While the efficiency of direct intratumoral transduction was proportional to the dose of virus injected, the results indicated some technical limitations inherent in these approaches to prostate cancer gene therapy.     

Subcutaneous lymphoblastic lymphomas. Expression of cellular adhesion molecules: 2 cases

We report two cases of subcutaneous lymphomas with a study of cellular adhesion molecules compared to those expressed on blasts at a later blastic phase. The striking different profile of adhesive phenotype in the two conditions is the expression of the interactions of blasts with their microenvironments. It seems that 1 integrins-dependant pathway sustains mainly the development of hematopoietic precursors in extra-medullary niches, while their contact with bone-marrow stroma and their trans-endothelial migration implicates Selectins and Immunoglobulins molecules.     

灰毡毛忍冬化学成分研究V灰毡毛忍冬素F和G的结构测定

灰毡毛忍冬化学成分研究Ｖ灰毡毛忍冬素Ｆ和Ｇ的结构测定陈敏，吴威巍，沈国强，罗思齐，李惠庭（上海医药工业研究院２０００４０）灰毡毛忍冬（ＬｏｉｎｃｅｒａｍａｃｒａｎｔｈｏｉｄｅｓＨａｎｄ．－Ｍａｚｚ）系忍冬科忍冬属植物，别名大花忍冬，分布于贵州、广西、...     

槲寄生化学成分的研究——Ⅳ.槲寄生新甙Ⅳ的结构

前文曾报道从槲寄生中分离及确定五个新黄酮甙的结构。本文报道另一新黄酮化合物(Ⅳ)的分离和结构测定。槲寄生(Viscum coloratura(Kom)Nakai)生药的乙醇提取物,分别用石油醚、醋酸乙酯和正丁醇萃取,正丁醇萃取物经聚酰胺细粉和硅胶低压柱层析,分离得到Ⅳ。通过光谱分析和水解试验,确定Ⅳ的结构为鼠李秦素-3-0-β-D-(6″-β-羟基-β-甲基戊二酸半酯)-葡     

Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.     

Ghrelin expression in hyperplastic and neoplastic proliferations of the enterochromaffin-like (ECL) cells

Ghrelin, a recently discovered peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation of growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal and cardiac functions. Because a cell of origin for ghrelin has not been convincingly identified in the gastric mucosa thus far, we studied the immunohistochemical expression of ghrelin in proliferative lesions of the enterochromaffin-like (ECL) cells—a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as well. Formalin-fixed, paraffin embedded tissues from three cases of gastric ECL cell hyperplasia and five ECL carcinoids (three with coexisting foci of diffuse, linear, and micronodular hyperplasia) were immunohistochemically stained for ghrelin, using a commercially available antibody. The Sevier-Munger stain for ECL cells and immunohistochemical stains for chromogranin, gastrin, serotonin, somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation with the ghrelin staining results. All ECL cell carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains for chromogranin and VMAT-2. Immunoreactivity for ghrelin was seen in 4/5 ECL carcinoids, all cases of ECL cell hyperplasia, as well as in all areas with linear and micronodular hyperplasia adjacent to the ECL cell carcinoids. In each instance, such staining was confined to the Sevier-Munger, and VMAT-2 positive cells only. Our findings indicate that the ECL cells are either the ghrelin-producing cells of the gastric mucosa or acquire the capability to synthesize ghrelin during proliferative states encompassing the entire hyperplasia to neoplasia spectrum. In view of the orexigenic and other known actions of ghrelin, the functional and/or biologic significance of ghrelin production in such ECL cell proliferations needs to be investigated further.