Home About us Contact
|
Home About us Contact | ||
|
|
||
Infection Leads (infection + lead)
Selected AbstractsGenetic Admixture in Brazilians Exposed to Infection with Leishmania chagasiANNALS OF HUMAN GENETICS, Issue 3 2009Nicholas A. Ettinger Summary Visceral leishmaniasis (VL) in northeast Brazil is a disease caused by infection with the protozoan Leishmania chagasi. Infection leads to variable clinical outcomes ranging from asymptomatic infection to potentially fatal disease. Prior studies suggest the genetic background of the host contributes to the development of different outcomes after infection, although it is not known if ancestral background itself influences outcomes. VL is endemic in peri-urban areas around the city of Natal in northeast Brazil. The population of northeast Brazil is a mixture of distinct racial and ethnic groups. We hypothesized that some sub-populations may be more susceptible than others to develop different clinical outcomes after L. chagasi infection. Using microsatellite markers, we examined whether admixture of the population as a whole, or markers likely inherited from a distinct ethnic background, differed between individuals with VL, individuals with an asymptomatic infection, or individuals with no infection. There was no apparent significant difference in overall population admixture proportions among the three clinical phenotype groups. However, one marker on Chr. 22 displayed evidence of excess ancestry from putative ancestral populations among different clinical phenotypes, suggesting this region may contain genes determining the course of L. chagasi infection. [source] The Effect of the cag Pathogenicity Island on Binding of Helicobacter pylori to Gastric Epithelial Cells and the Subsequent Induction of ApoptosisHELICOBACTER, Issue 6 2007Yutaka Minohara Abstract Background:,Helicobacter pylori infection leads to gastritis, peptic ulcer, and gastric cancer, in part due to epithelial damage following bacteria binding to the epithelium. Infection with cag pathogenicity island (PAI) bearing strains of H. pylori is associated with increased gastric inflammation and a higher incidence of gastroduodenal diseases. It is now known that various effector molecules are injected into host epithelial cells via a type IV secretion apparatus, resulting in cytoskeletal changes and chemokine secretion. Whether binding of bacteria and subsequent apoptosis of gastric epithelial cells are altered by cag PAI status was examined in this study. Methods:, AGS, Kato III, and N87 human gastric epithelial cell lines were incubated with cag PAI-positive or cag PAI-negative strains of H. pylori in the presence or absence of clarithromycin. Binding was evaluated by flow cytometry and scanning electron microscopy. Apoptosis was assessed by detection of DNA degradation and ELISA detection of exposed histone residues. Results:,cag PAI-negative strains bound to gastric epithelial cells to the same extent as cag PAI-positive strains. Both cag PAI-positive and cag PAI-negative strains induced apoptosis. However, cag PAI-positive strains induced higher levels of DNA degradation. Incubation with clarithromycin inactivated H. pylori but did not affect binding. However, pretreatment with clarithromycin decreased infection-induced apoptosis. Conclusions:,cag PAI status did not affect binding of bacteria to gastric epithelial cells but cag PAI-positive H. pylori induced apoptosis more rapidly than cag PAI-negative mutant strains, suggesting that H. pylori binding and subsequent apoptosis are differentially regulated with regard to bacterial properties. [source] The Effect of Helicobacter pylori Infection on Levels of DNA Damage in Gastric Epithelial CellsHELICOBACTER, Issue 5 2002S. M. Everett Abstract Background.Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells. Methods. Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage. Results. DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5,75.8), n = 18 and 21% (11.9,29.8), n = 65, respectively, p < .001]. Intermediate levels were found in reactive gastritis [55.5% (41.3,71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3,60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3,51.0), p = .007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = ,.92 and ,.88 for normal mucosa and H. pylori gastritis, respectively). Conclusions. Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis. [source] Effect of Helicobacter pylori infection on cyclooxygenase-2 expression in gastric antral mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Hong LU OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX-2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX-2 may contribute to gastrointestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX-2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori- infected patients, who also had chronic gastritis, both before and after anti- H. pylori treatment. The COX-2 protein was stained by using immunohistochemical methods and COX-2 expression was quantified as the percentage of epithelial cells expressing COX-2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase-2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase-2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX-2 expression in H. pylori -infected mucosa was compared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX-2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX-2 protein, suggesting that the enzyme is involved in H. pylori -related gastric pathology in humans. [source] Substance P receptor antagonist reverses intestinal pathophysiological alterations occurring in a novel ex-vivo model of Cryptosporidium parvum infection of intestinal tissues derived from SIV-infected macaquesJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2008A. Garza Abstract Background,Cryptosporidium infection leads to life-threatening diarrhea in AIDS patients. Pathogenesis of cryptosporidiosis is due to intestinal physiological alterations. We devised an ex-vivo model using ex-vivo Cryptosporidium parvum infection of jejunal tissues derived from SIV-infected macaques and studied the role of substance P (SP) in the pathogenesis of cryptosporidiosis. Methods, We measured jejunal SP protein levels using ELISA, and electrophysiological alterations using the Ussing chamber technique in an ex vivo model of Cryptosporidium infection. Paraformaldehyde-fixed jejunum from SIV-infected macaques with and without naturally occurring cryptosporidiosis was studied for SP protein expression by immunohistochemistry and fluorescence deconvolution microscopy. Results,Ex-vivo Cryptosporidium -infected tissues and tissues from SIV-infected macaques with naturally occurring cryptosporidiosis demonstrated elevated SP protein levels compared with tissues from SIV-infected animals without ex-vivo C. parvum infection or tissues from SIV-infected animals that have no evidence of cryptosporidiosis. In our ex-vivo model of Cryptosporidium infection, we demonstrated pathophysiological alterations that were blocked by SP-receptor antagonist treatment. Conclusions, These studies suggest that SP-receptor antagonists could prove useful for treatment of AIDS-related cryptosporidiosis. [source] Serum and salivary antibodies to a mycobacterial 65-kDa stress protein are elevated in HIV-positive patients and modified by oral candidiasisMOLECULAR ORAL MICROBIOLOGY, Issue 5 2000M. M. Coogan Serum immunoglobulin G (IgG) and IgA, and salivary IgA antibodies to a mycobacterial stress protein (mSP65) were determined in human immunodeficiency virus (HIV),positive patients, acquired immunodeficiency syndrome (AIDS) patients and HIV-negative controls with or without oral candidiasis. Serum IgG antibodies were elevated in patients with HIV infection and AIDS and especially in subjects with candidiasis compared with controls (P<0.02, P<0.005). This was not apparent with serum IgA. In the absence of candidiasis, salivary IgA antibodies were elevated in HIV-positive patients compared with AIDS (P<0.005) patients and healthy controls (P=0.001). The relative avidity of serum IgG antibodies to mSP65 in controls with candidiasis was lower than healthy controls (P<0.0001). In saliva there was a decrease in the relative avidity of IgA antibodies in AIDS patients with candidiasis compared with HIV patients (P< 0.03). In patients without candidiasis, the relative avidity was higher in HIV patients than healthy controls (P=0.02). The results suggest that HIV infection leads to raised serum and salivary antibodies to heat shock proteins. Concurrent Candida infection may modify both the titer and relative avidity differently for serum and saliva. [source] Secondary bacterial infection in plasma endotoxin levels and the acute-phase response of mice infected with Trypanosoma brucei bruceiPARASITE IMMUNOLOGY, Issue 7 2009R. NGURE Summary Murine Trypanosoma brucei brucei infection leads to elevated plasma endotoxin-like activity levels not related to parasitaemia levels accompanied by the development of acute-phase response and increased plasma levels of serum amyloid P (SAP) and haptoglobin (Hp). To determine the source of the endotoxin-like activity and role of secondary bacterial infection in the pathogenesis of trypanosomosis, infected mice were treated with the antibiotic ciprofloxacin. Plasma endotoxin-like activity levels, irrespective of treatment, were elevated three- to fourfold, beginning 7 days after infection. Plasma protein concentrations increased markedly following infection from 7 days after infection (DAI). Peak Hp and SAP concentrations in ciprofloxacin-treated and -untreated infected mice were attained 7 and 14 DAI, respectively. Thereafter, both protein levels gradually declined until the end of the experiment, but Hp levels for non-treated mice declined up to 21 DAI and thereafter significantly increased on 28 and 35 DAI. Whole-trypanosome lysate and the membrane-enriched fraction demonstrated endotoxin-like activity, with the former having higher levels. The results suggest that the endotoxin-like activity in trypanosome fractions and plasma of infected mice is due to the trypanosome. Further elevation of haptoglobin during the late stages of infection in non-treated mice suggests the involvement of secondary bacterial infection. [source] Reconstituting retroviral (ReCon) vectors facilitating delivery of cytotoxic genes in cancer gene therapy approachesTHE JOURNAL OF GENE MEDICINE, Issue 2 2008Eva Maria Brandtner Abstract Background We have previously described the generation of reconstituting retroviral (ReCon) vectors designed for cancer gene therapy using cytotoxic gene products. The unique vector structure with a promoter physically separated from the transgene allows generation of stable virus producer cells irrespective of the toxic gene. The mechanism of synthesis of DNA from retroviral RNA dictates that infection leads to the reconstitution of functional expression cassettes in the target cell. Methods To improve vector titres, a cytomegalovirus enhancer was inserted upstream of the 5,-long-terminal repeat (LTR); the Woodchuck hepatitis virus post-transcriptional regulatory element and an elongated attachment site upstream of the 3,-LTR were included. In addition, a bacterial origin of replication was deleted and a functional internal polyadenylation signal mutated. Transcriptional targeting was attempted by introducing mammary tissue-specific promoters such as the U3 region of mouse mammary tumour virus or the promoter of the whey acidic protein encoding gene. All modifications were analysed in detail with respect to virus production and infectivity. Finally, the vector was armed with the ,-holin encoding gene and transduced cells were analysed for cytotoxic effects. Results Distinct modifications of the vector resulted in a titre improvement of more than 560-fold. Compatibility of the optimized vector with targeted cellular promoters was demonstrated. When equipped with the cytotoxic gene, stable producer cells could be successfully established and high titre virus infection resulted in rigorous target cell killing. Conclusions The ReCon vector in its optimized form is an attractive tool for cancer gene therapy approaches. Copyright © 2007 John Wiley & Sons, Ltd. [source] The possible role of bovine herpesvirus type-4 infection in cow infertilityANIMAL SCIENCE JOURNAL, Issue 3 2010Sibel GÜR ABSTRACT Experimental and field studies have proven that the bovine herpesvirus type-4 (BHV-4) infection leads to various reproductive system problems. In this study, the role of BHV-4 infection in repeat breeding was investigated serologically. Eighty-four samples were obtained from repeat-breeding diagnosed cows in two organized dairy herds; an equal number of healthy cows were sampled from the same farms. The rest of the samples (105) were obtained from reproductively normal cows that were breeding in 18 small enterprises as a control group. The seropositivity proportion in repeat-breeding diagnosed cows was found to be significantly higher (69% (58/84)) than other cows (44% (37/84)) on the same farms. The lowest antibody positivity value for BHV-4 was detected as 24.7% (26/105) in the samples from family-type small farms. The odds ratio (OR) value was calculated as 2.834 in repeat-breeding diagnosed and healthy cows on the same farms, while 6.778 was determined in cows with and without reproductive problems on organized farms compared to small farms. As a result, the BHV-4 infection can be considered one of the reasons for repeat breeding besides other reproductive disorders. [source] Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disordersANNALS OF NEUROLOGY, Issue 3 2010Yeon-Joo Kang PhD Objective Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) protects against HIV/gp120-mediated neuronal damage in culture and in vivo. Methods Initially, we tested the neuroprotective effects of various concentrations of EPO, IGF-I, or EPO+IGF-I from gp120-induced damage in vitro. To assess the chronic effects of EPO+IGF-I administration in vivo, we treated HIV/gp120-transgenic or wild-type mice transnasally once a week for 4 months and subsequently conducted immunohistochemical analyses. Results Low concentrations of EPO+IGF-I provided neuroprotection from gp120 in vitro in a synergistic fashion. In vivo, EPO+IGF-I treatment prevented gp120-mediated neuronal loss, but did not alter microgliosis or astrocytosis. Strikingly, in the brains of both humans with HAND and gp120-transgenic mice, we found evidence for hyperphosphorylated tau protein (paired helical filament-I tau), which has been associated with neuronal damage and loss. In the mouse brain following transnasal treatment with EPO+IGF-I, in addition to neuroprotection we observed increased phosphorylation/activation of Akt (protein kinase B) and increased phosphorylation/inhibition of glycogen synthase kinase (GSK)-3,, dramatically decreasing downstream hyperphosphorylation of tau. These results indicate that the peptides affected their cognate signaling pathways within the brain parenchyma. Interpretation Our findings suggest that chronic combination therapy with EPO+IGF-I provides neuroprotection in a mouse model of HAND, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3, signaling. This combination peptide therapy should therefore be tested in humans with HAND. ANN NEUROL 2010;68:342,352 [source] Interleukin-1 receptor phosphorylation activates Rho kinase to disrupt human gastric tight junctional claudin-4 during Helicobacter pylori infectionCELLULAR MICROBIOLOGY, Issue 5 2010Tamia K. Lapointe Summary Helicobacter pylori infects more than half of the human population worldwide. In the absence of treatment, this persistent infection leads to asymptomatic gastritis, which in some cases can progress into gastric ulcers and adenocarcinomas. The host,microbial interactions that govern the clinical outcome of infection remain incompletely understood. H. pylori is known to disrupt gastric epithelial tight junctions, which may represent a significant component of disease pathogenesis. The present study demonstrates that H. pylori disrupt epithelial tight junctional claudin-4 in a Rho kinase (ROCK)-dependent manner in human gastric epithelial (HGE-20) cell monolayers, independently of the virulence factors CagA and VacA, and without altering claudin-4 transcription. In the same epithelial cell model, interleukin (IL)-1,, mediated a similar ROCK-dependent pattern of tight junction disruption. Further experiments revealed that H. pylori infection induced IL-1 receptor type I (IL-1RI) phosphorylation, independently of epithelial secretion of its endogenous ligands IL-1,, IL-1, or IL-18. Finally, inhibition of IL-1RI activation prevented H. pylori -induced ROCK activation and claudin-4 disruption. Taken together, these findings identify a novel pathophysiological mechanism by which H. pylori disrupts gastric epithelial barrier structure via IL-1RI-dependent activation of ROCK, which in turn mediates tight junctional claudin-4 disruption. [source] Role of novel protein kinase C isoforms in Lyme arthritisCELLULAR MICROBIOLOGY, Issue 8 2007Ok S. Shin Summary Inflammation caused by Borrelia burgdorferi infection occurs as a result of induction of pro-inflammatory cytokines from activation of multiple signalling pathways. It has previously been shown that mitogen-activated protein kinase (MAPK) and Janus kinase/signal transducer and activator of transcription signalling pathways are activated by B. burgdorferi in cultured human chondrocytes. Protein kinase C (PKC) signalling pathways are potential candidates that may control these downstream signalling pathways. Here we show that B. burgdorferi infection leads to phosphorylation and activation of novel PKC isoforms (PKC ,, ,, , and ,) in a time-dependent manner. A specific inhibitor of novel PKC isoforms blocked the induction of pro-inflammatory molecules in response to B. burgdorferi infection as did transient transfection of novel PKC dominant-negative plasmids into chondrocytes. B. burgdorferi -induced p38 MAPK phosphorylation was also significantly inhibited by an inhibitor of novel PKC isoforms, suggesting that PKC activation occurs upstream of p38 activation. In vivo, administration of an inhibitor of classical and novel PKC isoforms to C3H/HeN mice infected with B. burgdorferi resulted in significantly reduced ankle inflammation and swelling. In conclusion, these data suggest that novel PKC isoforms are specifically activated by B. burgdorferi infection and this can contribute to the regulation of inflammation in vitro and in vivo. [source] Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colonCELLULAR MICROBIOLOGY, Issue 4 2006Jennifer R. O'Hara Summary We tested the hypothesis that Citrobacter rodentium infection leads to changes in the mucosal enteroendocrine signalling and the enteric nervous system and that the host's immune response contributes to these changes. Enteroendocrine cells, serotonin (5-HT) reuptake transporter (SERT), 5-HT release, and inducible nitric oxide synthase (iNOS) expression were assessed in the colon of infected wild-type or severe combined immunodeficient (SCID) mice. Immunoreactivity for iNOS and neuropeptides were examined in the submucosal and myenteric plexuses. Mice were orogastrically infected with C. rodentium and experiments were conducted during the injury phase (10 days) and the recovery phase (30 days). 5-HT and somatostatin enteroendocrine cells and SERT were significantly reduced 10 days after infection, with numbers returning to control values at 30 days. 5-HT release was increased at 10 days. Changes to the mucosal serotonin signalling system were not observed in SCID mice. iNOS immunoreactivity was increased in the submucosa and mucosa at 10 days and returned to baseline levels by 30 days. No differences were observed in neuropeptide or iNOS immunoreactivity in the enteric plexuses following infection. The host's immune response underlies changes to enteroendocrine cells, SERT expression and 5-HT release in C. rodentium infection. These changes could contribute to disturbances in gut function arising from enteric infection. [source] | |||||||||||||