RESUMO
After a minor blow to the neck from the handlebars of a bike, a 5-year-old boy developed a massive subcutaneous emphysema with respiratory distress. Orotracheal intubation was performed. A computed tomography (CT) scan of the neck and thorax showed a pneumomediastinum and a bilateral pneumothorax. No injury to the large airways was identified. The patient was stabilized by insertion of chest tubes and controlled ventilation. The endoscopic examination of the trachea revealed a tear of the pars membranacea, which was successfully treated conservatively. The specific features of the injury and the airway management are discussed based on a review of the current literature.
Assuntos
Lesões do Pescoço/diagnóstico por imagem , Enfisema Subcutâneo/terapia , Manuseio das Vias Aéreas , Pré-Escolar , Endoscopia , Humanos , Intubação Intratraqueal , Masculino , Lesões do Pescoço/terapiaRESUMO
BACKGROUND: Neopterin is produced by activated macrophages upon stimulation with interferon-γ (IFN-γ) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves. PATIENTS AND METHODS: In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed. RESULTS: Elevated levels (cut-off 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004). CONCLUSION: In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer-associated inflammatory reaction.
Assuntos
Biomarcadores Tumorais/urina , Imunidade Inata/efeitos dos fármacos , Neopterina/urina , Neoplasias Ovarianas/urina , Adulto , Idoso , Áustria , Intervalo Livre de Doença , Feminino , Humanos , Interferon gama/administração & dosagem , Interferon gama/urina , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Neoplasia Residual/urina , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologiaRESUMO
The control of Johne's disease requires the identification of Mycobacterium avium ssp. paratuberculosis (MAP)-positive herds. Boot swabs and liquid manure samples have been suggested as an easy-to-use alternative to sampling individual animals in order to diagnose subclinical Johne's disease at the herd level, but there is a need to evaluate performance of this approach in the field. Using a logistic regression model, this study aimed to calculate the threshold level of the apparent within-herd prevalence as determined by individual faecal culture, thus allowing the detection of whether a herd is MAP positive. A total of 77 boot swabs and 75 liquid manure samples were taken from 19 certified negative and 58 positive dairy herds. Faecal culture, three different polymerase chain reaction (PCR) methods and the combination of faecal culture with PCR were applied in order to detect MAP. For 50% probability of detection, a within-herd prevalence threshold of 1·5% was calculated for testing both matrices simultaneously by faecal culture and PCR, with the threshold increased to 4·0% for 90% probability of detection. The results encourage the use of boot swabs or liquid manure samples, or a combination both, for identifying MAP-positive herds and, to a certain extent, for monitoring certified Johne's disease-negative cattle herds.
Assuntos
Doenças dos Bovinos/epidemiologia , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Paratuberculose/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Feminino , Alemanha/epidemiologia , Modelos Logísticos , Esterco/microbiologia , Paratuberculose/microbiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterináriaRESUMO
BACKGROUND: In recent years interactions between surgical treatment of oral carcinoma and incidence of anxiety or depression have become a subject of discussions. This prospective study is a comparison between the extent of loss of speech intelligibility and presence of depressive symptoms or anxiety as a result of oral carcinoma. MATERIAL AND METHODS: One year after surgical therapy for oral carcinoma, 90 patients of an average age of 60±12 years were examined. Their speech intelligibility degree was measured using standardized automatic speech recognition (word recognition rate, WR). Symptoms of anxiety and depression were detected by use of HAD-Scales (HADS). Next to the relationship between WR and HADS other influential variables related to WR and HADS were statistically evaluated. RESULTS: The WR average was 53.2±17.2. Female WR was better than male. The difference between tumor classifications T1 and T4 compared to the WR reached statistical significance. Significant differences were detected between WR and "tumor localization", "graft donor site", "graft morphology", "tongue motility", and "tracheostoma" groups. There was a relationship between tongue motility and graft morphology, graft donor site and tumor localization. HAD-Scores in the mean were elevated: HADS-Total=43.3%, HADS-A=43.3% und HADS-D= 51.1%. WR correlates with HADS-D-Subscale, but not with HADS-A-Subscale. CONCLUSION: Communication disorders as a result of neoplasmic orofacial surgery may be related to extent of the treatment and to affective impairments. This should receive attention in the concept of rehabilitation.
Assuntos
Transtornos de Ansiedade , Neoplasias Bucais/cirurgia , Inteligibilidade da Fala , Idoso , Ansiedade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
AIMS: Improvement of clinical diagnostics of idiopathic giant cell myocarditis (IGCM) and cardiac sarcoidosis (CS), two frequently fatal human myocardial diseases. Currently, IGCM and CS are diagnosed based on differential patterns of inflammatory cell infiltration and non-caseating granulomas in histological sections of endomyocardial biopsies (EMBs), after heart explantation or postmortem. We report on a method for improved differential diagnosis by myocardial gene expression profiling in EMBs. METHODS AND RESULTS: We examined gene expression profiles in EMBs from 10 patients with histopathologically proven IGCM, 10 with CS, 18 with active myocarditis (MCA), and 80 inflammation-free control subjects by quantitative RT-QPCR. We identified distinct differential profiles that allowed a clear discrimination of tissues harbouring giant cells (IGCS, CS) from those with MCA or inflammation-free controls. The expression levels of genes coding for cytokines or chemokines (CCL20, IFNB1, IL6, IL17D; P < 0.05), cellular receptors (ADIPOR2, CCR5, CCR6, TLR4, TLR8; P < 0.05), and proteins involved in the mitochondrial energy metabolism (CPT1, CYB, DHODH; P < 0.05) were deregulated in 2- to 300-fold, respectively. Bioinformatic analyses and correlation of the gene expression data with immunohistochemical findings provided novel information regarding the differential cellular and molecular pathomechanisms in IGCM, CS, and MCA. CONCLUSION: Myocardial gene expression profiling is a reliable method to predict the presence of multinuclear giant cells in the myocardium, even without a direct histological proof, in single small EMB sections, and thus to reduce the risk of sampling errors. This profiling also facilitates the discrimination between IGCM and CS, as two different clinical entities that require immediate and tailored differential therapy.
Assuntos
Cardiomiopatias/diagnóstico , Perfilação da Expressão Gênica/métodos , Sarcoidose/diagnóstico , DNA Complementar/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Estudos RetrospectivosRESUMO
Bacteria of many species are able to invade and colonize solid tumours in mice. We have focused on Salmonella enterica serovar Typhimurium. Detailed analysis revealed that such tumour-invading Salmonella form biofilms, thus providing a versatile in vivo test system for studying bacterial phenotypes and host-pathogen interactions. It appears that biofilm formation by S. typhimurium is induced as a defence against the immune system of the host, and in particular against neutrophils. Further, we extended our work to the clinically more relevant biofilm infection by Pseudomonas aeruginosa. The induction of P. aeruginosa biofilms in neoplastic tissue appears to be elicited as a reaction against the immune system. Reconstitution experiments reveal that T cells are responsible for biofilm induction. Isogenic mutants that are no longer able to form biofilms can be used for comparison studies to determine antimicrobial resistance, especially therapeutic efficacy against P. aeruginosa located in biofilms.
Assuntos
Biofilmes/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Neoplasias Experimentais/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Salmonella typhimurium/crescimento & desenvolvimento , Animais , Antibiose , Camundongos , Neutrófilos/microbiologia , Fagocitose , Pseudomonas aeruginosa/imunologia , Salmonelose Animal/microbiologia , Salmonella typhimurium/imunologia , Linfócitos T/microbiologiaRESUMO
BACKGROUND: Patient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA). METHODS: We retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0-10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors. RESULTS: The study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14-0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5-0.6, p < 0.001), reduced physical (CI 2.3-2.7, p ≤ 0.001) and psychological well-being (CI 2.1-2.5, p < 0.001), and higher BMI (CI 1.3-2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (ß = 0.04, CI 0.0-0.08, p 0.028). CONCLUSIONS: These findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient's perspective.
Assuntos
Arterite de Células Gigantes , Arterite de Takayasu , Humanos , Estudos Retrospectivos , Arterite de Células Gigantes/diagnóstico , Arterite de Takayasu/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Instituições de Assistência AmbulatorialRESUMO
Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.
Assuntos
Cardiomiopatias/genética , Cardiomiopatias/virologia , Infecções por Parvoviridae/virologia , Transcriptoma , Cardiomiopatias/complicações , DNA Viral/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/genética , Parvovirus B19 Humano/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A novel Gram-positive, aerobic, actinobacterial strain, CF5/5, was isolated from soil in the Sahara desert, Chad. It grew best at 20-35 °C and at pH 6.0-8.0 and with 0-4 % (w/v) NaCl, forming black-colored colonies. Chemotaxonomic and molecular characteristics of the isolate matched those described for members of the genus Geodermatophilus. The DNA G + C content was 75.9 mol%. The peptidoglycan contained meso-diaminopimelic acid; galactose and xylose were detected as diagnostic sugars. The main phospholipids were diphosphatidylglycerol, phosphatidylcholine, and phosphatidylinositol; MK-9(H(4)) was the dominant menaquinone. The major cellular fatty acids were: iso-C(16:0) and iso-C(15:0). The 16S rRNA gene showed 95.6-98.3 % sequence similarity with the other named members of the genus Geodermatophilus. Based on the polyphasic taxonomy data, the isolate is proposed to represent a novel species, Geodermatophilus saharensis with the type strain CF5/5(T) = DSM 45423 = CCUG 62813 = MTCC 11416.
Assuntos
Actinomycetales/classificação , Filogenia , Dióxido de Silício , Microbiologia do Solo , Actinomycetales/química , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Actinomycetales/ultraestrutura , Parede Celular/química , Chade , DNA Bacteriano/química , DNA Bacteriano/genética , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Especificidade da EspécieRESUMO
We performed long-haul WDM transmission experiments to compare 10 Gbit/s MSK and QPSK modulation with a channel grid of 12.5 GHz. A standard link setup with inline dispersion compensation was applied in combination with coherent detection and following offline signal processing. Both modulation formats showed nearly equal performance bridging about 4000 km at a BER of 10(-3).
RESUMO
A novel Gram-positive, aerobic, actinobacterial strain, CF5/4(T), was isolated in 2007 during an environmental screening of arid desert soil in Ouré Cassoni, Chad. The isolate grew best in a temperature range of 28-40 °C and at pH 6.0-8.5, with 0-1 % (w/v) NaCl, forming brown-coloured and nearly circular colonies on GYM agar. Chemotaxonomic and molecular characteristics of the isolate matched those described for members of the genus Geodermatophilus. The DNA G + C content of the novel strain was 75.9 mol %. The peptidoglycan contained meso-diaminopimelic acid as diagnostic diaminoacid. The main phospholipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, diphosphatidylglycerol and a small amount of phosphatidylglycerol; MK-9(H(4)) was identified as the dominant menaquinone and galactose as diagnostic sugar. The major cellular fatty acids were branched-chain saturated acids: iso-C(15:0) and iso-C(16:0). The 16S rRNA gene showed 96.2-98.3 % sequence identity with the three members of the genus Geodermatophilus: G. obscurus (96.2 %), G. ruber (96.5 %), and G. nigrescens (98.3 %). Based on the chemotaxonomic results, 16S rRNA gene sequence analysis and DNA-DNA hybridization with the type strain of G. nigrescens, the isolate is proposed to represent a novel species, Geodermatophilus arenarius (type strain CF5/4(T) = DSM 45418(T) = MTCC 11413(T) = CCUG 62763(T)).
Assuntos
Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Sedimentos Geológicos/microbiologia , Actinomycetales/citologia , Actinomycetales/genética , África do Norte , Técnicas de Tipagem Bacteriana , Composição de Bases , Chade , Clima Desértico , Sedimentos Geológicos/química , Filogenia , RNA Ribossômico 16S/genética , Dióxido de SilícioRESUMO
AIMS: The purpose of this study was to isolate new and potentially better polyhydroxyalkanoate (PHA)-producing bacteria, with a view to obtaining high yields from inexpensive substrates like glycerol, a major by-product of the biodiesel process. METHODS AND RESULTS: Eleven new plant original isolates of the genus Massilia, a poorly studied lineage within the Betaproteobacteria, were isolated and characterized. Two isolates, 2C4 and 4D3c, could not be assigned to a validated Massilia species and probably represent new species. Six isolates were found to produce poly-3-hydroxybutyrate (P3HB) when cultured with glucose or glycerol as carbon source. Isolate 4D6 accumulated up to 50 wt% of cell mass as polyhydroxybutyrate (PHB) when grown on glycerol. CONCLUSIONS: The phyllosphere may be a good source of bacteria unrelated or weakly related to human/animal pathogens for screening for new PHA producers for industrial application. Isolate 4D6 was capable of accumulating particularly high levels of PHB from glycerol. SIGNIFICANCE AND IMPACT OF THE STUDY: With the increase in biodiesel production, which generates increasing amounts of glycerol as a by-product, there is a major interest in exploiting this compound as feedstock for the synthesis of interesting products, like biopolymers, such as PHA. The new Massilia sp. 4D6 isolate described in this study may be a useful candidate as a cell factory for the industrial production of PHA from glycerol.
Assuntos
Glicerol/metabolismo , Hidroxibutiratos/metabolismo , Oxalobacteraceae/isolamento & purificação , Poliésteres/metabolismo , Poli-Hidroxialcanoatos/biossíntese , Glucose/metabolismo , Microbiologia Industrial , Oxalobacteraceae/classificação , Oxalobacteraceae/metabolismo , Plantas/microbiologia , ProibitinasRESUMO
Parvovirus B19 is a frequent virus detected in endomyocardial biopsies of patients with clinically suspected myocarditis or dilated cardiomyopathy (DCM). Viruses often cause a more symptomatic disease with increased tissue injury if they become reactivated. A disease-specific differential expression of microRNAs (miRNAs) has been described in the regulation of replicating viruses. Analyzing patients with latent and reactivated B19V infection, we found 29 differentially regulated miRNAs and, in order to test whether predicted genes are differentially expressed, selected mRNAs were tested by TaqMan-QPCR.
Assuntos
Cardiomiopatias/genética , Cardiomiopatias/virologia , Marcadores Genéticos/genética , MicroRNAs/genética , Infecções por Parvoviridae/genética , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Cardiomiopatias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/diagnósticoRESUMO
Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10ΔccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10ΔccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis.
Assuntos
Cápsulas Bacterianas/biossíntese , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Glucose/metabolismo , Proteínas Repressoras/metabolismo , Streptococcus suis/patogenicidade , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/genética , DNA Complementar/genética , DNA Complementar/metabolismo , Perfilação da Expressão Gênica , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras/genética , Streptococcus suis/genética , Streptococcus suis/crescimento & desenvolvimento , Streptococcus suis/metabolismo , Suínos , Virulência , Fatores de Virulência/genéticaRESUMO
Abnormal accumulation of the amyloid-beta peptide (Abeta) in the brain appears crucial to pathogenesis in all forms of Alzheimer disease (AD), but the underlying mechanisms in the sporadic forms of AD remain unknown. Transforming growth factor beta1 (TGF-beta1), a key regulator of the brain's responses to injury and inflammation, has been implicated in Abeta deposition in vivo. Here we demonstrate that a modest increase in astroglial TGF-beta1 production in aged transgenic mice expressing the human beta-amyloid precursor protein (hAPP) results in a three-fold reduction in the number of parenchymal amyloid plaques, a 50% reduction in the overall Abeta load in the hippocampus and neocortex, and a decrease in the number of dystrophic neurites. In mice expressing hAPP and TGF-beta1, Abeta accumulated substantially in cerebral blood vessels, but not in parenchymal plaques. In human cases of AD, Abeta immunoreactivity associated with parenchymal plaques was inversely correlated with Abeta in blood vessels and cortical TGF-beta1 mRNA levels. The reduction of parenchymal plaques in hAPP/TGF-beta1 mice was associated with a strong activation of microglia and an increase in inflammatory mediators. Recombinant TGF-beta1 stimulated Abeta clearance in microglial cell cultures. These results demonstrate that TGF-beta1 is an important modifier of amyloid deposition in vivo and indicate that TGF-beta1 might promote microglial processes that inhibit the accumulation of Abeta in the brain parenchyma.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Microglia/metabolismo , Fator de Crescimento Transformador beta/fisiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Vasos Sanguíneos/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1RESUMO
Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man.
Assuntos
Interferon gama/farmacologia , Lipase Lipoproteica/sangue , Neoplasias/metabolismo , Proteínas Recombinantes/farmacologia , Triglicerídeos/sangue , Adulto , Idoso , Feminino , Glicoproteínas/sangue , Humanos , Interferon gama/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Fator de Necrose Tumoral alfaRESUMO
With the aid of monoclonal antibody (mAb) 2625, raised against the lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we isolated mutant 811 from the virulent wild-type strain RC1. This mutant was not reactive with mAb 2625 and exhibited an unstable phenotype, since we observed an in vitro and in vivo switch of mutant 811 to the mAb 2625-positive phenotype, thus restoring the wild-type LPS. Bactericidal assays revealed that mutant 811 was lysed by serum complement components, whereas the parental strain RC1 was almost serum resistant. Moreover, mutant 811 was not able to replicate intracellularly in macrophage-like cell line HL-60. In the guinea pig animal model, mutant 811 exhibited significantly reduced ability to replicate. Among recovered bacteria, mAb 2625-positive revertants were increased by fourfold. The relevance of LPS phase switch for pathogenesis of Legionella infection was further corroborated by the observation that 5% of the bacteria recovered from the lungs of guinea pigs infected with the wild-type strain RC1 were negative for mAb 2625 binding. These findings strongly indicate that under in vivo conditions switching between two LPS phenotypes occurs and may promote adaptation and replication of L. pneumophila. This is the first description of phase-variable expression of Legionella LPS.
Assuntos
Legionella pneumophila/patogenicidade , Lipopolissacarídeos/imunologia , Virulência/genética , Animais , Anticorpos Monoclonais/farmacologia , Antígenos de Superfície/imunologia , Divisão Celular/genética , Mapeamento de Epitopos , Feminino , Cobaias , Células HL-60 , Humanos , Memória Imunológica/imunologia , Legionella pneumophila/genética , Doença dos Legionários/microbiologia , Lipopolissacarídeos/química , Pulmão/microbiologia , Masculino , Microscopia Imunoeletrônica , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , SorologiaRESUMO
OBJECTIVE: The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker, Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting. METHOD: A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping. RESULTS: Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11 deletion (Prader-Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf-Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality. CONCLUSION: The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT).
Assuntos
Anormalidades Múltiplas/diagnóstico , Deleção Cromossômica , Cariotipagem , Técnicas de Amplificação de Ácido Nucleico/métodos , Diagnóstico Pré-Natal , Telômero/genética , Anormalidades Múltiplas/genética , Adulto , Bandeamento Cromossômico/métodos , Análise Mutacional de DNA , Feminino , Idade Gestacional , Humanos , Cariotipagem/métodos , Metáfase , Gravidez , Kit de Reagentes para Diagnóstico , Estudos RetrospectivosRESUMO
The microbiome of freshwater sponges is rarely studied, and not a single novel bacterial species has been isolated and subsequently characterized from a freshwater sponge to date. A previous study showed that 14.4% of the microbiome from Ephydatia fluviatilis belong to the phylum Planctomycetes. Therefore, we sampled an Ephydatia sponge from a freshwater lake and employed enrichment techniques targeting bacteria from the phylum Planctomycetes. The obtained strain spb1T was subject to genomic and phenomic characterization and found to represent a novel planctomycetal species proposed as Planctopirus ephydatiae sp. nov. (DSM 106606â¯=â¯CECT 9866). In the process of differentiating spb1T from its next relative Planctopirus limnophila DSM 3776T, we identified and characterized the first phage - Planctopirus phage vB_PlimS_J1 - infecting planctomycetes that was only mentioned anecdotally before. Interestingly, classical chemotaxonomic methods would have failed to distinguish Planctopirus ephydatiae strain spb1T from Planctopirus limnophila DSM 3776T. Our findings demonstrate and underpin the need for whole genome-based taxonomy to detect and differentiate planctomycetal species.
Assuntos
Filogenia , Planctomycetales/classificação , Poríferos/microbiologia , Animais , Água Doce , Microbiota , Planctomycetales/isolamento & purificaçãoRESUMO
In the last few years, the Biophysics Working Group of the Institute of Aerospace Medicine of the German Aerospace Center (DLR) started the development of a small low power consumption radiation detector system for the measurement of the absorbed dose to be applied in various environments, such as onboard aircraft, in space, and also as a demonstration tool for students. These so called DLR M-42 detectors are based on an electronics design, which can easily be adjusted to the user- and mission-requirements. M-42 systems were already applied for measurements in airplanes, during two MAPHEUS (Materialphysikalische Experimente unter Schwerelosigkeit) rocket missions, and are currently prepared for long term balloon experiments. In addition, they will be part of the dosimetry suite of the upcoming Matroshka AstroRad Radiation Experiment on the NASA Artemis I mission. This paper gives an overview of the design and the testing of the DLR M-42 systems and provides highlighted results from the MAPHEUS campaigns where the detectors were tested for the first time under space flight conditions. Results clearly show that the system design enables independent measurements starting upon rocket launch due to the built-in accelerometer sensors and provides data for the relevant 6 min of µ-gravity as given for the MAPHEUS missions. These 6 min of the µ-gravity environment at altitudes between 100 and 240 km lead to a total absorbed dose of 1.21 ± 0.15 µGy being equivalent to half a day of radiation background measured with the M-42 in the laboratory at DLR, Cologne, Germany.