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M Ott

Publications and source records attributed to M Ott.

At least 91 records · Page 5Linked to original sources

Analysis of virulence factors of Legionella pneumophila.

Legionella pneumophila, the causative agent of Legionnaires' disease is a facultative intracellular bacterium, which in the course of human infection multiplies in lung macrophages predominantly manifesting as pneumonia. The natural habitat of Legionella is found in sweet water reservoirs and man-made water systems. Virulent L. pneumophila spontaneously convert to an avirulent status at a high frequency. Genetic approaches have led to the identification of various L. pneumophila genes. The mip (macrophage infectivity potentiator) determinant remains at present the sole established virulence factor. The Mip protein exhibits activity of a peptidyl prolyl cis trans isomerase (PPIase), an enzyme which is able to bind the immunosuppressant FK506 and is involved in protein folding. The recently cloned major outer membrane protein (MOMP) could play a role in the uptake of legionellae by macrophages. Cellular models are useful in studying the intracellular replication of legionellae in eukaryotic cells. Human cell lines and protozoan models are appropriate for this purpose. By using U 937 macrophage-like cells and Acanthamoeba castellanii as hosts, we could discriminate virulent and avirulent L. pneumophila variants since only the virulent strain was capable of intracellular growth at 37 degrees C. By using these systems we further demonstrated that a hemolytic factor cloned and characterized in our laboratory, legiolysin (lly), had no influence on the intracellular growth of L. pneumophila.

Bacterial Outer Membrane Proteins↗

Dissection of pathogenetic determinants and their genomic positions for the evaluation of epidemic strains and infection routes.

The epidemiology of infectious diseases intends to disclose the infection routes and sources of the respective diseases in order to provide preventive measures. The success of such a task is directly dependent on the knowledge about the special biological quality and the environmental distribution of the causative agents. This will imply extensive laboratory analysis rather than statistical surveys. The laboratory analysis for epidemiological purposes comprises a set of sophisticated methods for the subdifferentiation of the isolates (e.g. serofermentative and electrotyping, genomic fingerprinting). These methods provide circumstantial evidence of genetic and thus, epidemiological relatedness. Also the dissection of the pathogenic personality of the respective infectious agents was shown to have epidemiologic implications. However, the virulence pattern and the pattern of the genomic position of the respective determinants were found to be well conserved. For this reason, the dissection of virulence factors in comparison to other clonal properties must be regarded only as an additional marker for epidemiological discrimination. Moreover, any form of epidemic virulence remains to be detected by future analysis.

Bacteria↗

Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition.

Total body water, body fat, body cell mass (BCM), extracellular mass (ECM), and the ECM-BCM ratio by impedance analysis were determined in 193 human immunodeficiency virus (HIV)-infected patients and 340 control subjects. Walter Reed (WR) classification was WR 2 in 26, WR 3-5 in 85, and WR 6 in 82 patients. Whereas resistance was increased, reactance and the phase angle were significantly reduced in all patient groups. Neither body weight nor body mass index (BMI) was affected in WR 2 patients, but BCM was reduced (31.9 +/- 4.3 vs 35.8 +/- 7.3 kg, P < 0.007) and ECM (31.2 +/- 4.4 vs 28.8 +/- 3.8 kg) as well as ECM-BCM ratio increased (0.99 +/- 0.14 vs 0.83 +/- 0.16, P < 0.001). In contrast to WR classification, diarrhea did not correspond with malnutrition. A loss of BCM (malnutrition) occurred already in otherwise symptomless HIV-infected patients (WR 2). This effect can be measured by tetrapolar impedence analysis but not by body weight or BMI.

Adult↗

Mite allergen content in mattress dust of Dermatophagoides-allergic asthmatics/rhinitics and matched controls.

It has been suggested that the mites Dermatophagoides pteronyssinus and D. farinae are important indoor environmental factors facilitating both the sensitization of atopic subjects and asthmatic attacks of house dust-sensitive patients. Contradictory results have been reported about the current exposure to mites or their allergens among patients and control groups of atopic or non-atopic subjects. In order to determine whether there is a difference in mite exposure levels between D. pteronyssinus-sensitized asthmatics and/or rhinitis and control subjects we considered a case-control study of 70 patients with asthma and/or rhinitis and positive skin test reactions to D. pteronyssinus and twice as many control subjects who were matched as to age and sex. The first control subject for each patient was an immediate neighbour of the patient and the second was patient arbitrarily chosen among hospitalized patients. Mite allergen exposure was measured in mattress dust collected under standardized conditions, by measuring Der p I+Der fI content and by performing a semiquantitative guanine determination (Acarex-test). The content of Der p I and Der fI was very high both in the homes of patients and those of healthy individuals: 69% of the total samples contained more than 10 micrograms Der pI+Der fI/g of dust. There was no significant difference between cases and controls with respect to Der p I, Der fI, Der p I+Der fI content and Acare class distributions. The calculated odds-ratios associated with the Acarex test and the mite allergens did not differ significantly from the level 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Genetic analysis of the gene cluster encoding nonfimbrial adhesin I from an Escherichia coli uropathogen.

The chromosomally encoded nonfimbrial adhesion I (NFA-I) from Escherichia coli urinary tract isolate 827 (O83:K1:H4) mediates agglutination of human erythrocytes. Subclones were constructed from an NFA-I-expressing recombinant E. coli K-12 clone, derived from a genomic library of E. coli 827. Minicell analysis and nucleotide sequencing revealed that proteins of 30.5, 9, 80, 15, and 19 kDa encoded on a stretch of approximately 6 kb are involved in the expression of NFA-I. NFA-I exhibits a polymeric structure, which disintegrates with elevated temperature into a 19-kDa monomer but with some relatively stable dimers. By using gold-conjugated monoclonal antibodies directed against NFA-I in electron microscopy, the adhesin could be localized on the outer surface of the recombinant E. coli K-12 bacteria. The nucleotide sequence of the nfaA gene encoding the monomeric structural subunit of the adhesin was determined. An open reading frame of 184 amino acids encoding the NfaA precursor, which is processed to the mature protein, was found; it consisted of 156 amino acids with a calculated molecular weight of 16,000. Peptide sequencing of the NFA-I subunit protein confirmed that this open reading frame corresponds to the NfaA coding locus. Furthermore, the nucleotide sequence of the open reading frame termed NfaE, located at the proximal part of the DNA stretch responsible for NFA-I expression, was elaborated. NfaE consists of 247 amino acids, including a presumptive 29-amino-acid signal peptide, leading to a molecular weight of 24,000 for the mature protein. The nfaE sequence shares homology with the 27-kDa CS3 protein, which is involved in the assembly of CS3 fibrillae, and might encode the 30.5-kDa protein, detected in minicells.

Adhesins, Escherichia coli↗

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.

The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) usage, HLA class II restriction elements, and epitope specificity using a total of 215 long-term MBP-specific T cell lines (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly heterogeneous. Using a panel of overlapping synthetic peptides spanning the entire length of human MBP, at least 26 epitopes recognized by human TCL could be distinguished. The MBP domain most commonly recognized was sequence 80-105 (31% of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301, DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene-transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP. These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this restricted epitope profile remained stable for > 2 yr. The TCR beta chain sequences of TCL specific for the immunodominant region of HK are consistent with an oligoclonal response against the epitopes of this region (80-105). Further, two pairs of identical sequences were established from TCL generated from this patient at different times (June 1990 and June 1991), suggesting that some TCL specific for the immunodominant region persisted in the peripheral repertoire. The possible role of persistent immunodominant epitope clusters in the pathogenesis of MS remains to be established.

Adult↗

Duration of the multifetal gestation, birth weight and infant prognosis.

For the higher numbered multifetal gestation, duration of gestational age decreases in spite of different medical activities. On the other hand increasing gestational age often strongly suggests the need for delivery by caesarean section for maternal indications. After the 32nd week of gestation in general no serious respiratory problems should be expected, and there may be no essential increase in fetal weight, but the risk of intrauterine death increases due to placental insufficiency. Therefore, for logistic reasons we propose liberal indications for caesarean section after the 32nd week of the multifetal gestation.

Birth Weight↗

123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism.

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used in a prospective study to investigate 83 patients with parkinsonism (Hoehn and Yahr stages I to III) who had not been previously treated with dopamimetic drugs. All patients had clinical signs that were compatible with Parkinson's disease. An additional 13 patients had clinical signs of another basal ganglia disorder, such as progressive supranuclear palsy or multisystem atrophy. 123I-IBZM-SPECT results were compared with clinical responses to subcutaneous injections of the D1/D2-receptor agonist apomorphine (83 patients) and to long-term oral dopamimetic therapy (62 patients). Results from 123I-IBZM-SPECT predicted a positive or negative response to apomorphine in 69 of 76 patients (apomorphine responses were equivocal in 7 patients) and a response to dopamimetic therapy in 54 of 62 patients. All patients with a clinical diagnosis of progressive supranuclear palsy or multisystem atrophy had reduced 123I-IBZM binding. In six of these patients, the response to apomorphine was negative, and none clearly benefited from long-term oral levodopa therapy. Imaging of dopamine D2 receptors with 123I-IBZM-SPECT appears to distinguish between patients with de novo parkinsonism that is levodopa-responsive (probably Parkinson's disease of Lewy body type) and that which does not respond to levodopa therapy.

Adult↗

Intestinal absorption and malnutrition in patients with the acquired immunodeficiency syndrome (AIDS).

The relation of small intestinal dysfunction and malnutrition (body composition and serum index parameters of nutrition) was investigated in 36 male patients with AIDS. Mucosal absorptive capacity was assessed by the 25 g D-xylose test. D-xylose absorption (2 h - serum profile and 5 h - urine) classified 17 patients as having impaired and 19 patients as having normal absorption. In both groups body weight, body mass index as well as body composition analysis indicated malnutrition when compared to healthy male controls (n = 340) or asymptomatic HIV-infected patients (n = 26). Patients with abnormal D-xylose test had more severe malnutrition indicated by a lower body cell mass (17.7 +/- 5.4 vs. 22.5 +/- 4.5 kg; p < 0.01) and an increased ratio of extracellular mass to body cell mass (1.99 +/- 0.82 vs. 1.45 +/- 0.46 p < 0.01). Total serum protein, albumin, cholinesterase activity, cholesterol and LDL were significantly diminished in AIDS-patients with abnormal D-xylose test compared to those with normal D-xylose absorption. Intestinal dysfunction indicated by decreased D-xylose Intestinal dysfunction indicated by decreased D-xylose absorption thus represents an important feature of malnutrition and wasting, and patients with abnormal D-xylose absorption have more profound impairment of body composition, visceral proteins and lipids reflecting malnutrition than patients with unaffected intestinal absorption.

AIDS-Related Opportunistic Infections↗

Distribution of legionellae in a hospital water system: prevalence of immunologically and genetically related Legionella pneumophila serogroup 6 isolates.

A hospital warm water system was monitored for the presence and distribution of legionellae. Subtyping of ten selected Legionella pneumophila isolates, originating from four different sites in the system by using serogroup specific antisera in an indirect immunofluorescence test, revealed that nine of the ten isolates belong to serogroup 6, while the remaining one was serogroup 10. Two monoclonal antibodies (mAbs) specific for a subgroup of serogroup 6 strains were further used for characterization. None of the strains reacted with these mAbs. Genome analysis by elaborating NotI profiles using the pulsed field gel electrophoresis (PFGE) technique revealed that nearly all serogroup 6 isolates derived from different sites, including a new building connected by a ring pipe, were identical according to restriction fragment patterns. The patterns were distinguishable from those of the two L. pneumophila serogroup 6 reference strains, and from that of the L. pneumophila serogroup 10 isolate. These data argue for a relatively homogeneous L. pneumophila serogroup 6 population in the entire water system.

Antibodies, Bacterial↗

High concentrations of soluble tumor necrosis factor receptors in ascites.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ampicillin tolerance of Legionella pneumophila for counter-selection of transconjugants in heterospecific matings with Escherichia coli donors.

Legionella pneumophila, the causative agent of Legionnaires' disease is sensitive to ampicillin. However, the slowly growing bacteria are not killed even by high doses of this antibiotic. This natural tolerance was used for counter-selection of trans-conjugants in heterospecific matings with Escherichia coli as donor. This approach is useful for gentic manipulations in Legionella, as it avoids the use of antibiotic-resistant variants, which have to be tested for full virulence before use.

Ampicillin↗

Evidence for the production of high amounts of interleukin-6 in the peritoneal cavity of patients with ascites.

The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites.

Adult↗

Clonal analysis of Escherichia coli serotype O6 strains from urinary tract infections.

A total of 36 Escherichia coli urinary tract isolates (UTI) of serotype O6, with different combinations of capsule (K) and flagellin (H) antigens, were analysed according to the outer membrane pattern (OMP), serum resistance properties, mannose-resistant hemagglutination using various types of erythrocytes, and also for the genetic presence and the expression of P-fimbriae, S fimbriae/F1C fimbriae, Type 1 fimbriae, aerobactin and hemolysin. Twenty selected strains were further analysed by pulsed field gel electrophoresis (PFGE), elaborating genomic profiles by XbaI cleavage and subsequent Southern hybridization to virulence-associated DNA probes. It could be shown that O6 UTI isolates represent a highly heterogeneous group of strains according to the occurrence and combination of these traits. Relatedness on the genetic and the phenotypic level was found for some of the strains exhibiting the same O:K:H:F serotype. DNA long-range mapping further indicated some interesting features, according to the copy number and the genomic linkage of virulence genes.

Bacterial Adhesion↗

Genetics of Escherichia coli uropathogenicity: analysis of the O6:K15:H31 isolate 536.

E. coli strain 536 (O6:K15:H31) isolated from a case of acute pyelonephritis, expresses S-fimbrial adhesins, P-related fimbriae, common type I fimbriae, and hemolysins. The respective chromosomally encoded determinants were cloned by constructing a genomic library of this strain. Furthermore, the strain produces the iron uptake substance, enterocheline, damages HeLa cells, and behaves in a serum-resistant mode. Genetic analysis of spontaneously arising non-hemolytic variants revealed that some of the virulence genes were physically linked to large unstable DNA regions, termed "pathogenicity islands", which were mapped in the respective positions on the E. coli K-12 linkage map. By comparing the wild type strain and mutants in in vitro and in vivo assays, virulence features have been evaluated. In addition, a regulatory cross talk between adhesin determinants was found for the wild-type isolate. This particular mode of virulence regulation is missing in the mutant strain.

Chromosome Mapping↗

Restriction fragment length polymorphism and virulence pattern of the veterinary pathogen Escherichia coli O139:K82:H1.

Escherichia coli O139:K82:H1 strains originating from outbreaks and single cases of oedema disease in pigs were characterized by their genomic restriction fragment length polymorphism (RFLP), their virulence pattern, and by the occurrence as well as the genomic distribution of the determinants for hemolysin (hly) and verotoxins (shiga-like toxins; sltI, sltII). Whereas the RFLPs revealed considerable variation among the E. coli O139:K82:H1 isolates depending the origin and epidemic source of the strains, the virulence gene slt II was found to be present in nearly all strains in a particular chromosomal region. Similar to RFLPs, the plasmid profiles are useful for epidemiological analysis.

Animals↗