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PubMed1993

A basic-type PR-1 promoter directs ethylene responsiveness, vascular and abscission zone-specific expression.

Pathogenesis-related (PR) proteins form a heterogeneous group of host-encoded, low-molecular-mass proteins that are secreted through the exocytic pathway. They are synthesized by the plant in response to various stimuli, including pathogen attack or exposure to certain chemicals. The PRB-1b gene of Nicotiana tabacum codes for a basic-type PR-1 protein whose transcription is regulated by ethylene. A minimal ethylene-responsive promoter element was defined by deletion analysis in transgenic tobacco plants. Promoter sequences containing 213 bp or more were sufficient to enhance a 20-fold increase of beta-glucuronidase reporter gene expression in transgenic tobacco leaves exposed to 20 microliters l-1 of ethylene, while 67 bp were not sufficient to trigger ethylene responsiveness. All the constructs that retained ethylene inducibility exhibited phloem-specific activity, which was constitutive in petiole and pedicel abscission zones. This functional study was correlated to an in vitro screening of the major nuclear proteins' binding sites present on the promoter. Gel-shift analysis using nuclear extracts from ethylene-treated and non-treated plants revealed five sequence-specific protein-DNA complexes on promoter sequences spanning -863 to -142 bp. Constitutive expression of the basic-type PR-1 genes at the leaf and petiole or flower and pedicel interfaces may represent pre-emption of plant defenses against potential pathogens, suggesting a functional similarity to pathogen-induced expression in the leaf.

Base Sequence↗
PubMed2005

Arcanobacterium pyogenes: molecular pathogenesis of an animal opportunist.

Arcanobacterium pyogenes is a commensal and an opportunistic pathogen of economically important livestock, causing diseases as diverse as mastitis, liver abscessation and pneumonia. This organism possesses a number of virulence factors that contribute to its pathogenic potential. A. pyogenes expresses a cholesterol-dependent cytolysin, pyolysin, which is a haemolysin and is cytolytic for immune cells, including macrophages. Expression of pyolysin is required for virulence and this molecule is the most promising vaccine candidate identified to date. A. pyogenes also possesses a number of adherence mechanisms, including two neuraminidases, the action of which are required for full adhesion to epithelial cells, and several extracellular matrix-binding proteins, including a collagen-binding protein, which may be required for adhesion to collagen-rich tissue. A. pyogenes also expresses fimbriae, which are similar to the type 2 fimbriae of Actinomyces naeslundii, and forms biofilms. However, the role of these factors in the pathogenesis of A. pyogenes infections remains to be elucidated. A. pyogenes also invades and survives within epithelial cells and can survive within J774A.1 macrophages for up to 72 h, suggesting an important role for A. pyogenes interaction with host cells during pathogenesis. The two component regulatory system, PloSR, up-regulates pyolysin expression and biofilm formation but down-regulates expression of proteases, suggesting that it may act as a global regulator of A. pyogenes virulence. A. pyogenes is a versatile pathogen, with an arsenal of virulence determinants. However, most aspects of the pathogenesis of infection caused by this important opportunistic pathogen remain poorly characterized.

Actinomycetaceae↗
PubMed2004

DNA array analysis of altered gene expression in human leukocytes stimulated with soluble and particulate forms of Candida cell wall beta-glucan.

We previously reported that 1,3-beta-d-glucan derived from Candida albicans, a pathogenic fungus was obtained by oxidation of the cell wall with sodium hypochlorite (NaClO). It could be solubilized by treatment with dimethylsulfoxide (DMSO). We found that OX-CA and CSBG showed significantly different levels of activity toward leukocytes. Here, we have used cDNA microarrays to analyze the mRNA expression of 1176 genes in PBMCs stimulated with Candida cell wall glucan and considered the difference in the activation mechanism of OX-CA and CSBG. Total mRNA showed a significant change for 147 out of 1176 arrayed genes on stimulation with OX-CA and CSBG for 4 h. Among those genes, 62 were common, 26 were OX-CA-specific and 59 were CSBG-specific. Many of these up-regulated genes encode effectors with well-characterized proinflammatory properties. The expression of genes related with signal transduction differed in the particulate and soluble glucans derived from C. albicans having exactly the same primary structure. This fact suggested that each glucan induced specific biological activity through a different activation mechanism. This study using cDNA microarrays to analyze a broad spectrum of mRNA expression provides information on the biological activity of Candida cell wall glucan as a potential pathogenic factor.

Candida albicans↗
PubMed1998

The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia.

STUDY OBJECTIVE: To determine the influence of mini-BAL culture results on subsequent changes in antibiotic therapy and patient outcomes. DESIGN: Prospective, single-center, cohort study. SETTING: Medical ICU of Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: One hundred thirty mechanically ventilated patients undergoing mini-BAL for suspected ventilator-associated pneumonia (VAP). INTERVENTIONS: Mini-BAL, prospective patient surveillance, and data collection. MEASUREMENTS AND RESULTS: Sixty (46.2%) patients had mini-BAL cultures that yielded at least one pathogen potentially accounting for the clinically suspected episode of VAP (64 bacterial, 3 viral, 2 fungal). Among the 60 patients with microbiologically positive mini-BAL cultures, 44 (73.3%) were classified as receiving inadequate antibiotic therapy (ie, identification of a microorganism resistant to the prescribed antibiotic regimen). Prior antibiotic administration or its absence remained unchanged in 51 (39.2%) patients based on the mini-BAL culture results, while in another 51 (39.2%) patients, antibiotic therapy was either begun (n=7) or the existing antibiotic regimen was changed (n=44), and in the remaining 28 (21.6%) patients, antibiotic therapy was discontinued altogether. The hospital mortality rates of these three groups were statistically different: 33.3%, 60.8%, and 14.3%, respectively (p<0.001). The most common pattern of antibiotic resistance resulting in an antibiotic change following mini-BAL was the identification of a Gram-negative bacteria resistant to a prescribed third-generation cephalosporin in 23 of 44 (52.3%) patients. Twenty-one of these 23 patients (91.3%) received prior therapy with a cephalosporin class antibiotic during the same hospitalization. Having an immunocompromised state (adjusted odds ratio [OR]=2.45; 95% confidence interval, 1.56 to 3.85; p=0.047) and the presence of a pathogen in the mini-BAL culture resistant to the empirically prescribed antibiotic regimen (adjusted OR=3.28; 95% confidence interval, 2.12 to 5.06; p=0.006) were identified as risk factors independently associated with hospital mortality by logistic regression analysis. CONCLUSIONS: These data suggest that antibiotic selection prior to obtaining the results of lower airway cultures is an important determinant of outcome for patients with suspected VAP. A delay in initiating adequate antibiotic therapy was associated with a greater mortality. Therefore, the initial selection of antibiotics for the empiric treatment of VAP should be broad enough to cover all likely pathogens, including antibiotic-resistant bacteria. This appears to be especially important in patients having received prior antibiotics.

Adult↗
PubMed2002

Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens.

Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial. A case of cavitary pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated. B. bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter. Unlike previous work reporting the involvement of B. bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate. Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point. Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable. We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts.

AIDS-Related Opportunistic Infections↗
PubMed1984

Effects of overnight refrigeration on the microscopic evaluation of sputum.

Microscopic evaluation of sputum permits selection of specimens suitable for culture, assessment of likely pathogens, and the best interpretation of culture results. We prospectively evaluated 50 sputum specimens which were promptly submitted to our clinical laboratory; smears and cultures were performed both immediately and after 20 h of refrigeration. Specimens were grouped according to the numbers of squamous epithelial cells and neutrophils per low-power field present on coded Gram-stained smears. The numbers of bacteria in five oil immersion fields were used to characterize smears for predominant, mixed, or scanty forms. After refrigeration, only three specimens changed group from a definite loss of squamous epithelial cells, and only two changed group from a definite loss of neutrophils. Based on cellular composition, the majority of samples would have been processed identically both before and after refrigeration. In contrast, organism forms detected on smears and their relative quantities were dramatically altered after refrigeration. A predominant smear form was gained in 11 and lost in 8 refrigerated specimens. The frequent changes on smears observed overall resulted from both increases and decreases in numbers of bacteria and yeasts. The majority of sputum culture results were insignificantly affected by the refrigeration of specimens. We conclude that 20 h of refrigeration renders sputum useless for the microscopic evaluation of potential pathogens and the subsequent interpretation of culture results. However, overnight refrigeration does not affect the determination from smears of sputum suitability for culture based on cellular composition.

Bacteria↗
PubMed2006

Secreted neutral metalloproteases of Bacillus anthracis as candidate pathogenic factors.

To evaluate the pathogenic potential of Bacillus anthracis-secreted proteases distinct from lethal toxin, two neutral zinc metalloproteases were purified to apparent homogeneity from the culture supernatant of a non-virulent delta Ames strain (pXO1-, pXO2-). The first (designated Npr599) is a thermolysin-like enzyme highly homologous to bacillolysins from other Bacillus species. The second (designated InhA) is a homolog of the Bacillus thuringiensis immune inhibitor A. These proteases belong to the M4 and M6 families, respectively. Both enzymes digested various substrates, including extracellular matrix proteins, endogenous inhibitors, and coagulation proteins, with some differences in specificity. In addition, InhA accelerated urokinase-mediated plasminogen activation, suggesting that InhA acts as a modulator of plasmin in the host inflammatory system. Relevant to epithelial barrier function, Npr599 and InhA significantly enhanced syndecan-1 shedding from cultured normal murine mammary gland cells without affecting their viability through stimulation of the host cell ectodomain shedding mechanism. In addition, Npr599 and InhA directly cleaved recombinant syndecan-1 fused to glutathione S-transferase. Mass spectrometric analysis suggested that the cleavage sites of Npr599 and InhA are the Asp(39)-Asp(40) and Gly(48)-Thr(49) bonds, respectively. We propose that Npr599 and InhA from B. anthracis are multifunctional pathogenic factors that may contribute to anthrax pathology through direct degradation of host tissues, increases in barrier permeability, and/or modulation of host defenses.

Animals↗
PubMed2004

Detection and enumeration of Cryptosporidium sp. oocysts in sewage sludge samples from the city of Florianópolis (Brazil) by using immunomagnetic separation combined with indirect immunofluorescence assay.

In the last few decades, agricultural reclamation of sewage sludge has increased in many countries. However, this practice must be adopted under recommended conditions to limit the risks associated with the presence of potential pathogens, including protozoan parasites such as Cryptosporidium. In the present work, we evaluated immunomagnetic separation (IMS) combined with an indirect immunofluorescence assay (IFA) in order to detect Cryptosporidium oocysts in sewage sludge samples obtained from the Municipal Wastewater Treatment Plant (MWTP) operating in the city of Florianópolis, State of Santa Catarina, Brazil. Integrated application of spontaneous sludge sedimentation and centrifugation of the supernatant, purification and concentration of oocysts through immunomagnetic separation as well as detection and quantification by means of indirect immunofluorescence using highly specific monoclonal antibodies, proved to be an effective multiple-analysis tool for monitoring the presence of Cryptosporidium oocysts in urban sewage sludge samples. Among 27 samples collected from MWTP, 20 (74.07%) were positive for Cryptosporidium sp. The efficiency of recovery by using the internal control ColorSeed (Biotechnology Frontiers Inc., Sydney, NSW, Australia) was medially 39.96 +/- 11.20%. Actually, oocysts were recovered from 100% of the positive samples tested and the number of Cryptosporidium oocysts found in the samples ranged from one to four. These results demonstrated a high recovery rate of Cryptosporidium oocysts in sewage sludge samples by using IMS-IFA analysis. In conclusion, such an approach can be applied to monitor the presence of the parasite and to determine the potential contamination of sludge destined for soil application.

Agriculture↗
PubMed2002

Growth of Escherichia coli O157:H7 in raw ground beef stored at 10 degrees C and the influence of competitive bacterial flora, strain variation, and fat level.

Pure-culture broth-based models of the growth of Escherichia coli O157:H7 have been used to estimate its behavior in ground beef, even though these models have not been adequately validated for this food product. This situation limits accurate estimates of the behavior of E. coli O157:H7 in ground beef and introduces uncertainties in risk assessments. In the present study, the growth of single and multiple strains of E. coli O157:H7 were measured in retail ground beef stored at 10 degrees C for up to 12 days, and the results were compared with estimates generated by the U.S. Department of Agriculture's Pathogen Modeling Program (PMP; version 5.1). At pH 5.9, the PMP predicted a maximum population density (MPD) of 9.13 log10 CFU/g, an exponential growth rate (EGR) of 0.052 log10 CFU/h, and a lag time of 56.3 h. Similar parameter values were observed for sterilized ground beef; however, no lag phase was observed. In contrast, the mean MPD and EGR for retail ground beef were 5.09 log10 CFU/g and 0.019 log10 CFU/h, respectively, and no lag phase was observed. Both the EGR and the MPD increased with decreasing fat levels. There was low variation in the MPD and EGR parameters for the nine E. coli O157:H7 ground beef isolates. Two isolates of competitive native flora were separately added to sterilized ground beef, and the EGR and MPD decreased as the ratio of competitive flora to E. coli O157:H7 increased. For one strain, at ratios of 1:1, 10:1, and 100:1, the EGRs were 0.033, 0.025, and 0.018 log10 CFU/h, respectively, and the MPDs were 6.14, 5.08, and 4.84 log10 CFU/g, respectively. These results demonstrate that existing broth-based models for E coli O157:H7 must be validated for food and that models should consider the effects of the food matrix, the competitive microflora, and potential pathogen strain variation.

Animals↗
PubMed2001

Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification.

OBJECTIVE: Elevated cartilage inorganic pyrophosphate (PPi) production and PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity are strongly linked with aging-related cartilage calcification in meniscal and articular cartilages. We hypothesized that there were divergent relationships of 3 NTPPPH isozymes with cartilage matrix calcification and sought to identify them. METHODS: We studied knee medial meniscal expression in situ of 3 NTPPPH isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family: plasma cell membrane glycoprotein 1 (PC-1, or PDNP1), autotaxin (ATX, or PDNP2), and B10/PDNP3. We also used complementary DNA transfection to assess differential functions in matrix calcification of each NTPPPH isozyme in vitro in meniscal cells. RESULTS: We observed diffuse cell-associated ATX and B10/PDNP3 expression in central (chondrocytic) and, to a lesser degree, peripheral (fibroblastic) regions of normal, degenerative uncalcified, and degenerative calcified menisci. In contrast, PC-1 expression was only robust at sites of apoptotic cells and calcification in central regions of degenerative menisci. Only PC-1 was abundant at the perimeter of meniscal cells and in association with meniscal cell-derived matrix vesicles (MVs). Because each PDNP-family isozyme was expressed by cells near calcifications, we transfected the isozymes in nonadherent knee meniscal cells cultured with ascorbic acid, beta-glycerophosphate, and dexamethasone supplementation to stimulate them to calcify the matrix. PC-1, but not ATX or B10/PDNP3, consistently promoted increased MV NTPPPH, MV-associated PPi, and extracellular PPi. PC-1 also increased matrix calcification (with hydroxyapatite crystals) by meniscal cells. ATX uniquely induced alkaline phosphatase activity, but promoted only moderately increased matrix calcification. CONCLUSION: We identified divergent effects of 3 PDNP-family NTPPPH isozymes on meniscal cell matrix calcification. Increased expression of PC-1 is both a marker and a potential pathogenic factor for knee meniscal cartilage matrix calcification.

Aging↗
PubMed2004

Cu/Zn-superoxide dismutase (GLY93-->ALA) mutation alters AMPA receptor subunit expression and function and potentiates kainate-mediated toxicity in motor neurons in culture.

The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains a mystery. One potential pathogenic mechanism is excitotoxicity due to disturbances of glutamatergic neurotransmission, particularly via AMPA-sensitive glutamate receptors. We report here that motor neurons from a familial ALS-linked superoxide dismutase (SOD1) mutant G93A mouse show an higher susceptibility to kainate-induced excitotoxicity. Moreover, they expressed GluR(3) and GluR(4) mRNA at detectable levels more frequently, with a modified electrophysiology when compared with control and wild-type SOD1 motor neurons. Thus, the SOD1 G93A mutation causes changes in the AMPA-receptor expression and function, as well as a susceptibility to kainate-mediated excitotoxicity, which may promote the motor neuron degeneration seen in ALS.

Alanine↗
PubMed2005

Tannerella forsythia-induced alveolar bone loss in mice involves leucine-rich-repeat BspA protein.

Tannerella forsythia (formerly Bacteroides forsythus) is one of the periodontal pathogens recently implicated in the development of periodontal disease. The cell-surface-associated, as well as the secreted, leucine-rich-repeat protein (BspA) of this bacterium have been suggested to play roles in bacterial adherence, and also in inflammation, by triggering release of pro-inflammatory cytokines from monocytes and chemokines from osteoblasts, leading to inflammation and bone resorption. In this study, we sought to determine the pathogenic potential of T. forsythia and the in vivo role of the BspA protein in pathogenesis in the mouse model of infection-induced alveolar bone loss. The results showed alveolar bone loss in mice infected with the T. forsythia wild-type strain, whereas the BspA mutant was impaired. In conclusion, evidence is presented in support of T. forsythia as an important organism involved in inducing alveolar bone loss, and the BspA protein is an important virulence factor of this bacterium.

Alveolar Bone Loss↗
PubMed1979

In vitro survival of human pathogenic fungi in seawater.

The survival of propagules from 4 pathogenic fungi, Trichophyton mentagrophytes, Trichosporon cutaneum, Candida albicans, and Microsporum gypseum was studied in seawater subjected to different temperature (20--35 degrees C) and salinity (6--50%) levels in diurnal rhythm of 12 h cycles. Survival was measured by viability of propagules over a period of 52 weeks. All fungi, except T. cutaneum at 35 degrees C survived the experimental conditions for 52 weeks. Temperature was the most influential factor. When temperature increased, M. gypseum responded with enhanced viability whereas survival for C. albicans and T. cutaneum was inhibited. At 35 degrees C, T. cutaneum was not viable after 6--7 weeks even though it survived the initial 5 weeks with less loss of viability than the other test organisms. No correlation was seen between salinity level and loss of viability. Diurnal light had an inhibitory effect on T. cutaneum and C. albicans survival under in vitro conditions approximating those of seawater in Hawaii. M. gypseum had the highest level of survival over 52 weeks under usual in situ conditions simulated in vitro, followed by T. mentagrophytes, T. cutaneum, and C. albicans. Survival for 52 weeks even when salinity and temperature levels exceed those of the natural habitat indicates that seawater which washes sand beaches can be an environmental niche for potentially pathogenic fungi.

Candida albicans↗
PubMed2005

Pathogenesis of unexplained drowning: new insights from a molecular autopsy.

OBJECTIVE: To perform a molecular autopsy involving the RyR2-encoded cardiac ryanodine receptor/calcium release channel to determine whether mutations responsible for catecholaminergic polymorphic ventricular tachycardia (CPVT) represent a novel pathogenic basis for unexplained drownings. METHODS: A cardiac channel molecular autopsy was performed on 2 individuals who died of unexplained drowning and whose cases were referred to the Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn. Comprehensive mutational analysis of all 60 protein-encoded exons of the 5 long QT syndrome-causing cardiac channel genes and a targeted analysis of 18 RyR2 exons known to host RyR2-mediated CPVT-causing mutations (CPVT1) was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. RESULTS: Both individuals harbored novel mutations in RyR2. Postmortem mutational analysis revealed a familial missense mutation in exon 14, R414C, in a 16-year-old girl. A 9-year-old boy possessed a sporadic missense mutation in exon 49, V2475F. Both amino acid positions involve highly conserved residues that localize to critical functional domains in the calcium release channel. Neither substitution was present in 1000 reference alleles. CONCLUSIONS: This molecular autopsy study provides proof of principle that RyR2 mutations can underlie some unexplained drownings. A population-based genetic epidemiology study that involves molecular autopsies of individuals who die of unexplained drowning is needed to determine the prevalence and spectrum of KCNQ1 and now RyR2 mutations as potential pathogenic mechanisms for drowning.

Adolescent↗
PubMed1993

Human herpesvirus 6 is present in lesions of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a disease characterized by Langerhans cell infiltration of skin and bone, with its most severe form manifested by multifocal infiltration of many organs. The etiology is unknown, although viral infection has been proposed as a potential pathogenic factor. Human herpesvirus 6 (HHV-6), a recently described member of the human herpesvirus family, has been associated with atypical or malignant lymphocytic processes, and immune disorders. Based on these observations, we suspected that HHV-6 may play a role in the pathogenesis of LCH. Lesional tissue of 30 patients with LCH was retrospectively examined for the presence of HHV-6 by using the polymerase chain reaction. Tissue specimens from 63 patients with other benign and malignant histiocytic and lymphocytic diseases served as controls. In addition, all specimens were examined with control primers specific for herpes simplex virus (HSV). HHV-6 DNA was detected in lesions of 14 of 30 patients with LCH (47%). On clinical subgroup analysis, HHV-6 DNA was found in 10 of 16 patients with extraosseous disease (63%) and in four of 14 patients with disease limited to bone (29%). In each case, the prevalence of HHV-6 in LCH lesions was statistically significant, when compared to the control population. HSV DNA was not found in any of the LCH or control specimens. Although the presence of a virus alone does not establish a causal role in the disease, it supports the possibility of an etiologic relationship. From this study, we emphasize the need for further investigation of the potential HHV-6-mediated pathogenesis of LCH.

Adolescent↗
PubMed2005

Characterization of a binary tandem domain F-type lectin from striped bass (Morone saxatilis).

Among other functions, lectins play an important role in the innate immune response of vertebrates and invertebrates by recognizing exposed glycans on the surface of potential pathogens. Despite the typically weak interaction of lectin domains with their carbohydrate ligands, they usually achieve high avidity through oligomeric structures or by the presence of tandem carbohydrate-binding domains along the polypeptide. The recently described structure of the fucose-binding European eel agglutinin revealed a novel lectin fold (the "F-type" fold), which is shared with other carbohydrate-binding proteins and apparently unrelated proteins from prokaryotes to vertebrates, and a unique fucose-binding sequence motif. Here we described the biochemical and molecular characterization of a unique fucose-binding lectin (MsaFBP32) isolated from serum of the striped bass (Morone saxatilis), composed of two tandem domains that exhibit the eel carbohydrate recognition sequence motif, which we designate F-type. We also described a novel lectin family ("F-type") constituted by a large number of proteins exhibiting greater multiples of the F-type motif, either tandemly arrayed or in mosaic combinations with other domains, including a putative transmembrane receptor, that suggests an extensive functional diversification of this lectin family. Among the tandem lectins, MsaFBP32 and other tandem binary homologues appear unique in that although their N-terminal domain shows close similarity to the fucose recognition domain of the eel agglutinin, their C-terminal domain exhibits changes that potentially could confer a distinct specificity for fucosylated ligands. In contrast with the amniotes, in which the F-type lectins appear conspicuously absent, the widespread gene duplication in the teleost fish suggests these F-type lectins acquired increasing evolutionary value within this taxon.

Amino Acid Sequence↗
PubMed2002

Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure.

OBJECTIVE: Inflammation may play a pathogenic role in chronic heart failure (CHF). The objective of the study was to characterise the imbalance in the cytokine network in CHF. METHODS: cDNA expression arrays were used to analyse the gene expression of cytokines and related mediators in peripheral blood mononuclear cells (PBMC) from CHF patients (n=8) and healthy controls (n=8). Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of individual genes in additional 12 patients and eight controls. RESULTS: From 375 genes, 34 were upregulated and two downregulated in CHF patients in the cDNA expression array experiments. Regulated genes included chemokines/-receptors, members of the transforming growth factor beta superfamily, orphan receptors and in particular several members of the tumor necrosis factor (TNF) superfamily. Thus, 4-1BB ligand (L), APRIL, CD27L, CD40L, FasL, LIGHT, TRAIL-receptor 4 were upregulated, while TRAIL-receptor 3 was downregulated. Real-time quantitative RT-PCR confirmed significantly upregulated gene expression of APRIL, LIGHT, FasL and CD27L in CHF patients and showed in addition significantly enhanced gene expression of TNFalpha and TRAIL. CONCLUSION: The present study demonstrates differential gene expression in PBMC of several members of the cytokine network in CHF. In particular, the enhanced expression of several ligands in the TNF superfamily may reflect a potential pathogenic role of these cytokines in CHF.

4-1BB Ligand↗
PubMed1999

Endemic burkholderia cepacia bacteraemia: clinical features and antimicrobial susceptibilities of isolates.

Burkholderia cepacia has emerged as a nosocomial pathogen, causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. Reports of clinical features of endemic B. cepacia bacteraemia in non-CF patients are rare. Twenty-five patients with B. cepacia bacteraemia were matched with 25 controls with nosocomial Escherichia coli bacteraemia at China Medical College Hospital, Taichung, Taiwan, over a period of 3 y. Case-patients included 16 men and 9 women, from 13 to 75 y. All had severe underlying diseases, most commonly malignancy (44%). Twenty-four patients (96%) had nosocomial infections. Five patients (20%) had polymicrobial bacteraemia. Our controls included 11 men and 14 women, age range 18-80 y. The most common underlying disease was malignancy (44%). Multivariate analysis revealed that indwelling central venous catheter was the significant risk factor predisposing to B. cepacia bacteraemia (p= 0.025). Eleven case-patients met the definition of catheter-related bloodstream infection. Fifteen patients (60%) received appropriate antimicrobial therapy after notification of positive blood cultures and susceptibility patterns. The overall case-fatality rate was 12% (3/25), only 1 of whom died of B. cepacia bacteraemia. There was no statistically significant difference in overall mortality rate between case-patients and controls. All isolates were susceptible to ceftazidime, piperacillin and minocycline and 84% of the isolates were susceptible to imipenem. B. cepacia should be considered a potential pathogen in hospitalized patients with severe underlying diseases, particularly those with indwelling central venous catheters.

Adolescent↗