Journal of Laboratory and Clinical Medicine最新文献

{"title":"Characterization and gene transfer in mesenchymal stem cells derived from human umbilical-cord blood","authors":"Fei-Zhou Lu ,&nbsp;Masayuki Fujino ,&nbsp;Yusuke Kitazawa ,&nbsp;Taro Uyama ,&nbsp;Yuko Hara ,&nbsp;Naoko Funeshima ,&nbsp;Jian-Yuan Jiang ,&nbsp;Akihiro Umezawa ,&nbsp;Xiao-Kang Li","doi":"10.1016/j.lab.2005.07.003","DOIUrl":"10.1016/j.lab.2005.07.003","url":null,"abstract":"<div><p>It has been shown that the stromal-cell population found in bone marrow can be expanded and differentiated into cells with the phenotypes of bone, cartilage, muscle, neural, and fat cells. However, whether mesenchymal stem cells (MSCs) are present in human umbilical-cord blood (UCB) has been the subject of ongoing debate. In this study, we report on a population of fibroblastlike cells derived from the mononuclear fraction of human UCB with osteogenic and adipogenic potential, as well as the presence of a subset of cells that have been maintained in continuous culture for more than 6 months. These cells were found to express CD29, CD44, CD90, CD95, CD105, CD166, and MHC class, but not CD14, CD34, CD40, CD45, CD80, CD86, CD117, CD152, or MHC class II. We also compared gene expression after gene transfer using lenti- and adenoviral vectors carrying the green fluorescence protein to the MSCs derived from UCB because a reliable gene-delivery system is required to transfer target genes into MSCs, which have attracted attention as potential platforms for the systemic delivery of therapeutic genes. The lentiviral vectors can transduce these cells more efficiently than can adenoviral vectors, and we maintained transgene expression for at least 5 weeks. This is the first report showing that UCB-derived MSCs can express exogenous genes by way of a lentivirus vector. These results demonstrate that human UCB is a source of mesenchymal progenitors and may be used in cell transplantation and a wide range of gene-therapy treatments.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 271-278"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25663737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrathiomolybdate protects against cardiac damage by doxorubicin in mice","authors":"Guoqing Hou ,&nbsp;Robert Dick ,&nbsp;Gerald D. Abrams ,&nbsp;George J. Brewer","doi":"10.1016/j.lab.2005.07.004","DOIUrl":"10.1016/j.lab.2005.07.004","url":null,"abstract":"<div><p>Cardiac toxicity is the limiting factor in therapy with doxorubicin, an otherwise useful cancer drug. In this article we detail our study of a mouse model of doxorubicin-induced cardiac toxicity in which, after 4 days’ treatment, doxorubicin caused marked increases in plasma concentrations of creatine kinase, lactic dehydrogenase, and troponin I, indicators of cardiac injury; marked increases in the plasma concentrations of tumor necrosis factor-α and interleukin-1_β, both inflammatory cytokines; and a marked increase in the plasma concentration of interleukin-2, an indicator of cytotoxic T-cell activation. Therapy with tetrathiomolybdate, designed to limit copper availability, eliminated almost all of the increases of these six parameters in plasma. The marked protection against cardiac injury by doxorubicin in tetrathiomolybdate-treated animals suggests that tetrathiomolybdate would be of use clinically in helping prevent doxorubicin toxicity in patients. In other preclinical work, it has been shown that tetrathiomolybdate potentiates the chemotherapeutic effect of doxorubicin in cancer, so a double benefit might accrue clinically from the combined use of tetrathiomolybdate and doxorubicin. The mechanism by which tetrathiomolybdate protects against doxorubicin toxicity is of considerable interest. Our working hypothesis, based on the inhibition of interleukin-2 by tetrathiomolybdate as shown here, is that tetrathiomolybdate interrupts the inflammatory cascade at the activated–T-lymphocyte stage.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 299-303"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25650611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levosimendan improves postresuscitation outcomes in a rat model of CPR","authors":"Lei Huang ,&nbsp;Max Harry Weil ,&nbsp;Shijie Sun ,&nbsp;Gianluca Cammarata ,&nbsp;Lan Cao ,&nbsp;Wanchun Tang","doi":"10.1016/j.lab.2005.07.005","DOIUrl":"10.1016/j.lab.2005.07.005","url":null,"abstract":"<div><p>In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than β-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 μg kg⁻¹ over a 10-minute period, followed by infusion of 0.3 μg kg⁻¹ min⁻¹ over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 μg kg⁻¹ min⁻¹. Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16±2 hours), intermediate with dobutamine (11±2 hours) and least with saline-solution placebo (8±1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 256-261"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25663735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of cag genotypes and clinical outcome of Helicobacter pylori infection","authors":"Michele Sozzi ,&nbsp;Maria Luisa Tomasini ,&nbsp;Carla Vindigni ,&nbsp;Stefania Zanussi ,&nbsp;Rosamaria Tedeschi ,&nbsp;Giancarlo Basaglia ,&nbsp;Natale Figura ,&nbsp;Paolo De Paoli","doi":"10.1016/j.lab.2005.06.010","DOIUrl":"10.1016/j.lab.2005.06.010","url":null,"abstract":"<div><p><em>Helicobacter pylori</em> infecting strains may include colony subtypes with different cytotoxin-associated gene (<em>cag</em>) genotypes. We sought to determine whether the <em>cag</em> heterogeneity of infecting strains is related to the clinical outcome of infection. Gastric biopsies for culture and histologic study were taken from 19 patients infected with <em>cagA</em>-positive strains (6 with duodenal ulcer, 8 with atrophic gastritis, and 5 with nonatrophic gastritis). For each biopsy, DNA was extracted from 10 single colonies and from a sweep of colonies. Polymerase chain reaction (PCR) for <em>cagA</em> and <em>cagE</em> (both located in the right half of <em>cag</em>) and <em>virB11</em> (located in the left half of <em>cag</em>) was performed. Random amplified polymorphic DNA PCR (RAPD-PCR) and sequencing of <em>glmM</em> PCR product were performed to verify strain identity of colonies with different <em>cag</em> genotypes. In all patients, PCR from sweeps were positive for <em>cagA</em>, showing that all specimens contained <em>cagA</em>-positive <em>H. pylori</em> subtypes. In 11 patients, PCR products from all colonies were positive for <em>cagA</em>, <em>cagE</em>, and <em>virB11</em>, but in 8 patients, PCR products from varying numbers of colonies were negative for 1 or more <em>cag</em> genes. RAPD-PCR and sequencing of <em>glmM</em> PCR product confirmed the strain identities of colonies with different <em>cag</em> genotypes. We detected <em>cag</em> deletions in 6 of 8, 2 of 5, and 0 of 6 patients with atrophic gastritis, nonatrophic gastritis, and duodenal ulcer, respectively (<em>P</em> = .02). In conclusion, changes in <em>cag</em> genotype in single colony isolates from subjects infected with <em>cagA</em>-positive <em>H. pylori</em> strains are more common in atrophic than in nonatrophic gastritis or duodenal ulcer. These findings are consistent with host-induced (acid secretion?) adaptive changes in <em>cag</em> genotype during infection.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 262-270"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.06.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25663736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Information for readers","authors":"","doi":"10.1016/S0022-2143(05)00338-0","DOIUrl":"https://doi.org/10.1016/S0022-2143(05)00338-0","url":null,"abstract":"","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Page CO3"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0022-2143(05)00338-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136908081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"This month in J Lab Clin Med","authors":"Dale E. Hammerschmidt MD (Editor-in-Chief)","doi":"10.1016/j.lab.2005.09.002","DOIUrl":"https://doi.org/10.1016/j.lab.2005.09.002","url":null,"abstract":"","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 253-255"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136908075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"About the cover illustration","authors":"Dale E. Hammerschmidt MD (Editor-in-Chief)","doi":"10.1016/j.lab.2005.09.003","DOIUrl":"10.1016/j.lab.2005.09.003","url":null,"abstract":"","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 306-307"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.09.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25650613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum complement factor I decreases Staphylococcus aureus phagocytosis","authors":"Kenji M. Cunnion,&nbsp;E. Stephen Buescher,&nbsp;Pamela S. Hair","doi":"10.1016/j.lab.2005.07.001","DOIUrl":"10.1016/j.lab.2005.07.001","url":null,"abstract":"<div><p>Complement-mediated opsonization of <em>Staphylococcus aureus</em> is a critical host defense in animal models. Specifically, C3b and CD35 play important roles in effective opsonophagocytosis of <em>S. aureus</em>. We have shown that complement control protein factor I mediates cleavage of the complement opsonin C3b bound to the <em>S. aureus</em> surface. In this study, we examined the physiologic relevance of this observation by determining whether factor I-mediated cleavage of <em>S. aureus</em>-bound C3b decreased phagocytosis of <em>S. aureus</em> by neutrophils. Compared with controls, anti-factor I antibody inhibited C3b-cleavage on the <em>S. aureus</em> surface by &gt;83% (as measured by iC3b generation) and increased phagocytosis of <em>S. aureus</em> by &gt;100%. Treatment of C3b-coated <em>S. aureus</em> with factor I increased generation of iC3b (75%), decreased the total amount of C3-fragments bound to the <em>S. aureus</em> surface (58%), and decreased the number of bacteria phagocytosed (40%). Testing specifically for C3-fragments shed from the <em>S. aureus</em> surface, we found that factor I increased shedding (43%). Notably, these factor I-mediated effects were of the same magnitude regardless of whether factor H, a known cofactor for factor I, was present. These findings indicate that <em>S. aureus</em> benefits from, and possibly manipulates, the normally host-protective activity of factor I cleavage of C3b, which results in bacterial escape from complement-mediated opsonophagocytosis. Because escaping opsonophagocytosis-mediated destruction is a necessary mechanism for bacterial survival resulting in human disease, preventing cleavage of C3b on the <em>S. aureus</em> surface, and thereby enhancing opsonophagocytosis, is a promising potential target for therapeutic intervention.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 279-286"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25663738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock","authors":"N.J.H. Raat","doi":"10.1016/j.lab.2005.07.011","DOIUrl":"10.1016/j.lab.2005.07.011","url":null,"abstract":"","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 304-305"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25650612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-reactive protein increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells","authors":"Gabriella Doronzo,&nbsp;Isabella Russo,&nbsp;Luigi Mattiello,&nbsp;Mariella Trovati,&nbsp;Giovanni Anfossi","doi":"10.1016/j.lab.2005.07.010","DOIUrl":"10.1016/j.lab.2005.07.010","url":null,"abstract":"<div><p>The C-reactive protein (CRP) is a strong predictor of cardiovascular events both in the general population and in patients with coronary artery disease. We aimed to evaluate whether in cultured human vascular smooth muscle cells (hVSMC) CRP modulates the synthesis and release of metalloproteinase-2 (MMP-2), which is deeply involved in plaque instabilization and vascular remodeling, and of the tissue inhibitor of metalloproteinase-2 (TIMP-2). Both in supernatants and in cell lysates of cultured hVSMC exposed to CRP (0–10 mg/L), we evaluated MMP-2 activity (gelatin zymography), MMP-2 and TIMP-2 protein synthesis (immunoblotting), MMP-2 and TIMP-2 mRNA expression (reverse transcription-polymerase chain reaction). CRP effects were also investigated after cell exposure to specific MEK inhibitor PD98059 (15–30 μmol/L) to evaluate the involvement of mitogen-activated protein kinase (MAPK). CRP upregulated MMP-2 mRNA expression. MMP-2 synthesis and activity were increased by 1–10 mg/L CRP starting from 8-hour incubation. The effect was prevented by exposure to PD98059. CRP did not modify TIMP-2 mRNA expression, protein synthesis, and secretion. CRP, at concentrations that predict cardiovascular events, upregulates MMP-2 mRNA expression and increases MMP-2 protein synthesis and release in hVSMC through mechanisms involving activation of MAPK pathway. These data indicate that CRP is not only a risk marker for vascular events, but it is also directly involved in the mechanisms leading to remodeling and instabilization of atherosclerotic plaque.</p></div>","PeriodicalId":16273,"journal":{"name":"Journal of Laboratory and Clinical Medicine","volume":"146 5","pages":"Pages 287-298"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.lab.2005.07.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25650610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}