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At least 1,621 records · Page 90Linked to original sources
PubMed2006

Characterization of a new Puumala virus genotype associated with hemorrhagic fever with renal syndrome.

Hantavirus serotype Puumala (PUUV) is the etiologic agent of Nephropathia epidemica (NE), a mild variant of Hemorrhagic Fever with Renal Syndrome (HFRS) in Europe, with lethality rates up to 1% among human patients. The serotype PUUV is composed of numerous geographically restricted strains forming a great number of phylogeographic lineages, sublineages, variants, and clusters. We describe a new, geographically and phylogenetically well-defined pathogenic PUUV sublineage in Southwest Germany (strain Heidelberg/hu) originated from an HFRS patient. The genetic analysis of PUUV strain Heidelberg/hu may contribute in future to better diagnostics, the development of vaccines, and the understanding of the factors that determine hantavirus pathogenesis.

Adult↗
PubMed1985

Pseudomonas aeruginosa in the oral cavity and sputum of patients with cystic fibrosis.

Patients with cystic fibrosis (CF) are often hosts to colonies of both mucoid and nonmucoid strains of Pseudomonas aeruginosa. The major pathogens for chronic and recurrent pulmonary infection in these patients are the mucoid variants of P. aeruginosa. Of the 31 CF patients studied, 14 patients yielded both mucoid and nonmucoid strains of P. aeruginosa from the various oral ecologic sites and saliva. Of the sites tested, the dorsum of the tongue gave the highest yield of P. aeruginosa (27 strains), followed by the buccal mucosa (17 strains), saliva (15 strains), and dental plaques (6 strains). Eleven patients had P. aeruginosa in the oral cavity and sputum simultaneously. Antibiotic susceptibility tests on these multiple isolates suggest that CF patients may be cocolonized or coinfected by two or more strains of P. aeruginosa. Therefore, it may be important to identify multiple isolates of P. aeruginosa, not only from sputum cultures but also from oral cultures, for antibiotic-susceptibility testing. Oral colonization by the mucoid variants of P. aeruginosa may lead to further colonization in the lower respiratory tract and subsequent pulmonary infection in CF patients.

Adolescent↗
PubMed1996

Inhibition of syncytia-inducing (SI) virus by autologous serum from HIV-1-infected individuals.

BACKGROUND: Progression from HIV infection to AIDS is often accompanied or even predicted by a switch of the virus to a more pathogenic or syncytia-inducing (SI) phenotype concomitant with the development of HIV variants escaping neutralizing antibodies. OBJECTIVE: Here we studied the capacity of sera to neutralize autologous SI-HIV or the laboratory strain III(B) and compared these data to the viral load in HIV-1-infected patients. METHODS: The SI phenotype of HIV was detected by co-cultivation of peripheral blood mononuclear cells (PBMCs) with MT2 cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1 : 15 and 1 : 75 were added to MT2 co-cultures with autologous PBMCs as well as with HIV-1/IIIB-infected H9 cells to study the inhibitory capacity. The p24 antigenemia was detected by enzyme-linked immunosorbent assay (ELISA) and the circulating HIV RNA was determined using the polymerase chain reaction (PCR). RESULTS: The SI virus was detected in PBMCs from 31/65 patients with < or = 200 CD4+ cells, 8/28 patients with 201-499 CD4+ cells, and 1/19 patients with > or = 500 CD4+ cells. Sera from 16/40 patients inhibited the autologous SI-HIV. In sera from patients with < or = 200 CD4+ cells, p24 antigen could be detected in 17/34 (50%) patients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%) patients carrying SI-HIV without serum inhibition. In contrast, all 12 sera with inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A similar tendency was seen in patients with higher CD4+ T-cell counts. The mean load of circulating HIV RNA did not differ among groups of patients. Independently of their neutralizing activity to the autologous SI virus, the majority of sera were able to neutralize the laboratory HIV-1/III(B). CONCLUSIONS: While most of the patients' sera neutralized the laboratory HIV-1/III(B) strain, only some sera were able to inhibit the autologous SI-HIV. In these cases, the detectable SI-HIV may still be controlled by the immune system in vivo, which is consistent with a low p24 antigenemia.

Journal Article↗
PubMed2004

Genetic analysis of DJ-1 in a cohort Parkinson's disease patients of different ethnicity.

Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease patients (ARPD) of European ancestry and young onset (YOPD) Ashkenazi Jewish and Afro-Caribbean patients. There is little information on the prevalence of DJ-1 mutations amongst Asian PD populations. In this study, we examined for DJ-1 mutations in consecutive YOPD and ARPD in a multi-ethnic cohort (Chinese, Malays, and Indians) of PD patients in a tertiary referral center. Sequence analysis of all the exons and the exon and intron boundaries of the DJ-1 gene were carried out. We did not find any DJ-1 mutations in these patients. A number of intronic variants with genotype frequency ranging from 15 to 90% were detected. Unlike Parkin, pathogenic DJ-1 mutations appear to be restricted to certain populations and are unlikely to be of clinical importance in our Asian cohort.

Adult↗
PubMed2006

Chinese Presenilin-1 V97L mutation enhanced Abeta42 levels in SH-SY5Y neuroblastoma cells.

Presenilin-1 gene mutations have been proven to be associated with the majority of early-onset familial Alzheimer's disease (FAD). There have been, however, no systematic studies of Presenilin-1 gene mutation in FAD in China so far. We found a novel Val-->Leu missense mutation at codon 97 (Val97Leu) of the Presenilin-1 gene in a Chinese FAD pedigree. To verify whether this mutation is pathologically functional, we established mutation type and wild type Presenilin-1 gene stably transfected cell lines (human neuroblastoma SH-SY5Y cells) to detect beta-amyloid (Abeta) concentrations using ELISA and radioimmunity methods. We also examined levels of beta-amyloid precursor protein cleaving enzyme (BACE) and amyloid precursor protein (APP) to explore their impact upon beta-amyloid production. Our results showed that Abeta42 concentration was significantly enhanced at 48h when compared to that at 24h in the mutant type cells. At 48h Abeta42 levels in the V97L mutants was also found to be elevated significantly, both intracellularly and extracellularly when compared to wild and mock transfected cells. The total Abeta in either group did not alter, consistent with unchanged BACE and APP expression levels. Our data reveal that the Presenilin-1 V97L variant can elevate Abeta42 levels both intracellularly and extracellularly, and was a potentially pathogenic mutation for this Chinese FAD pedigree. It also suggests that there are common mechanisms in the pathogenesis of FAD between Chinese and other ethnic populations, although their gene mutation sites are different.

Alzheimer Disease↗
PubMed1985

Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome.

A congenital hypokalemic tubular disorder is described with many features resembling Bartter syndrome. Additional features include prenatal onset with polyhydramnios and premature labor; failure to thrive; episodes of fever, vomiting, diarrhea, and renal electrolyte and water wastage; hypercalciuria; nephrocalcinosis; and osteopenia. Unlike Bartter syndrome, there is no defect in tubular reabsorption of chloride. Urinary levels of prostaglandin E2 and 7 alpha-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid are selectively elevated, indicating marked stimulation of renal and systemic PGE2 production. Chronic suppression of PGE2 activity by indomethacin corrects most of the abnormalities, and there is an immediate decompensation of the disease on indomethacin withdrawal. We conclude that these preterm infants have a distinct variety of hypokalemic tubular disorders rather than a variant of Bartter syndrome, because renal and systemic hyperprostaglandinism ranks high in the pathogenic chain of events, and the suppression of PGE2 hyperactivity is associated with significant improvement in the development (and probably in the prognosis) of the affected children.

Bartter Syndrome↗
PubMed1998

Phylogenetic analysis of Theileria and Babesia equi in relation to the establishment of parasite populations within novel host species and the development of diagnostic tests.

The divergence of parasites is important for maintenance within an established host and spread to novel host species. In this paper we have carried out phylogenetic analyses of Theileria parasites isolated from different host species. This was performed with small subunit ribosomal RNA sequences available in the data bases and a novel sequence amplified from Theileria lestoquardi DNA. Similar phylogenetic studies were carried out with sequences representing the major merozoite/piroplasm surface antigen (mMPSA) from the data base, and novel sequences representing 2 mMPSA alleles from T. lestoquardi, a full length sequence of a Theileria taurotragi mMPSA gene and partial sequences of two new allelic variants of the Babesia equi mMPSA gene homologue. The analysis indicated that the pathogenic sheep parasite T. lestoquardi has most probably evolved from a common ancestor of T. annulata. Interestingly, the level of mMPSA sequence diversity found for T. lestoquardi was surprisingly low, while diversity between the B. equi sequences was higher than that found within any of the classical Theileria species. The possible implications of these results for the establishment of Theileria parasites within novel species are discussed. Extensive cross-reactivity of a range of antisera was found when tested against recombinant mMPSA polypeptides from different Theileria (including B. equi) species. The cross-reactivity between mMPSA polypeptides and sequence diversity are relevant for the development of species specific diagnostic tests.

Amino Acid Sequence↗
PubMed1998

Mucosal immunoadjuvant activity of recombinant Escherichia coli heat-labile enterotoxin and its B subunit: induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with influenza virus surface antigen.

The Escherichia coli heat-labile enterotoxin (LT) is a very potent mucosal immunogen. LT also has strong adjuvant activity towards coadministered unrelated antigens and is therefore of potential interest for development of mucosal vaccines. However, despite the great demand for such mucosal vaccines, the use of LT holotoxin as an adjuvant is essentially precluded by its toxicity. LT is composed of an A subunit, carrying the toxic ADP-ribosylation activity, and a pentamer of identical B subunits, which mediates binding to ganglioside GM1, the cellular receptor for the toxin. In this paper, we demonstrate that recombinant enzymatically inactive variants of LT, including the LTB pentamer by itself, retain the immunoadjuvant activity of LT holotoxin in a murine influenza model. Mice were immunized intranasally (i.n.) with influenza virus subunit antigen, consisting mostly of the isolated surface glycoprotein hemagglutinin (HA), supplemented with either recombinant LTB (rLTB), a nontoxic LT mutant (E112K, with a Glu112-->Lys substitution in the A subunit), or LT holotoxin, and the induction of systemic IgG and local S-IgA responses was evaluated by direct enzyme-linked immunosorbent assay (ELISA). Immunization with subunit antigen alone resulted in a poor systemic IgG response and no detectable S-IgA. However, supplementation of the antigen with E112K or rLTB resulted in a substantial stimulation of the serum IgG level and in induction of a strong S-IgA response in the nasal cavity. The adjuvant activity of E112K or rLTB under these conditions was essentially the same as that of the LT holotoxin. The present results demonstrate that nontoxic variants of LT, rLTB in particular, represent promising immunoadjuvants for potential application in an i.n. influenza virus subunit vaccine. Nontoxic LT variants may also be used in i.n. vaccine formulations directed against other mucosal pathogens. In this respect, it is of interest that LT(B)-stimulated antibody responses after i.n. immunization were also observed at distant mucosal sites, including the urogenital system. This, in principle, opens the possibility to develop i.n. vaccines against sexually transmitted infectious diseases.

Administration, Intranasal↗
PubMed2003

The pathogenicity of strains of Salmonella paratyphi B and Salmonella java.

AIMS: To relate the diseases caused by strains of Salmonella paratyphi B and S. java to pathogenic mechanisms expressed by these bacteria for the purpose of organism discrimination. METHODS AND RESULTS: Epidemiological data relating to cases of disease caused by strains of S. paratyphi B and S. java, isolated over a 10-year period, were analysed with respect to patients' symptoms, particularly those involving enteric fever. Strains of S. paratyphi B and S. java were also examined for a range of known pathogenic mechanisms. Infection with S. paratyphi B involved pyrexia in 12.5% of patients compared with 2.2% of patients infected with S. java. These organisms could not be differentiated based on the pathogenic properties examined. CONCLUSIONS: Strains of S. paratyphi B appear not to be a major cause of enteric fever but primarily a cause of gastroenteritis, in common with S. java. Both organisms express similar pathogenic mechanisms, and strains of S. java are probably d-tartrate utilizing variants of S. paratyphi B. SIGNIFICANCE AND IMPACT OF THE STUDY: Strains of S. paratyphi B are very closely related organisms, primarily causing gastroenteritis. From this study it would appear that strains of S. paratyphi B are not a major cause of enteric fever.

Adolescent↗
PubMed2006

Tigecycline and the need for a new broad-spectrum antibiotic class.

BACKGROUND: Lack of progress in developing new antimicrobials, particularly new classes, as opposed to variants of existing agents, has contributed to the emergence of antibiotic-resistant pathogens. METHODS: Data synthesis after review of pertinent English-language literature. RESULTS: The development of new classes of antimicrobial agents is crucial, considering the increasing prevalence of nosocomial pathogens resistant to empiric as well as second- and third-line antibiotic choices. Tigecycline has recently been approved for the treatment of complicated skin and skin structure as well as intra-abdominal infections. Published data on the in vitro and in vivo properties of tigecycline, the first-in-class glycylcycline, are reviewed. CONCLUSION: It is plausible that tigecycline could to some extent replace available broadspectrum agents for approved indications and thereby reduce the selective pressure for some currently prevalent multi-resistant pathogens in the hospital setting.

Anti-Bacterial Agents↗
PubMed2025

CREMSA: compressed indexing of (ultra) large multiple sequence alignments.

MOTIVATION: Recent viral outbreaks motivate the systematic collection of pathogenic genomes in order to accelerate their study and monitor the apparition/spread of variants. Due to their limited length and temporal proximity of their sequencing, viral genomes are usually organized, and analyzed as oversized Multiple Sequence Alignments (MSAs). Such MSAs are largely ungapped, and mostly homogeneous on a column-wise level but not at a sequential level due to local variations, hindering the performances of sequential compression algorithms. RESULTS: In order to enable an efficient handling of MSAs, including subsequent statistical analyses, we introduce CREMSA (Column-wise Run-length Encoding for MSAs), a new index that builds on sparse bitvector representations to compress an existing or streamed MSA, all the while allowing for an expressive set of accelerated requests to query the alignment without prior decompression. Using CREMSA, a 65 GB MSA consisting of 1.9M SARS-CoV 2 genomes could be compressed into 22 MB using less than half a gigabyte of main memory, while executing access requests in the order of 100&#x2009;ns. Such a speed up enables a comprehensive analysis of covariation over this very large MSA. We further assess the impact of the sequence ordering on the compressibility of MSAs and propose a resorting strategy that, despite the proven NP-hardness of an optimal sort, induces greatly increased compression ratios at a marginal computational cost. AVAILABILITY AND IMPLEMENTATION: CREMSA is freely accessible at https://gitlab.univ-lille.fr/cremsa/cremsa. The Snakemake workflow for the benchmarks is available at: https://gitlab.univ-lille.fr/cremsa/bench. The data used in the paper is on Zenodo at https://zenodo.org/records/14698859 and https://zenodo.org/records/15100011.

SARS-CoV-2↗
PubMed1988

Isolation of colonial variants of Bacteroides gingivalis W50 with a reduced virulence.

The spontaneous appearance of unusual colony forms was observed during prolonged growth of Bacteroides gingivalis W50 in a chemostat. Two variants were selected for further study which could be distinguished from the parent strain by the rate and intensity of pigmentation of their colonies. For example, after anaerobic incubation for 14 days, variant W50/BR1 produced brown colonies whereas those of the parent strain were black; in contrast, variant W50/BE1 did not show signs of pigmentation until incubation had continued for 21 days. In subsequent studies in the chemostat, variant W50/BE1 bred true even after prolonged growth whereas other colony forms appeared after incubation of variant W50/BR1 for 14 days. The relatedness of W50/BR1 and W50/BE1 to the parent strain was confirmed by comparisons of the whole-cell fatty-acid profiles, the patterns of pre-formed enzymes and by the metabolic end products after growth. However, the variants did differ from the parent strain in their virulence in a mouse pathogenicity model. The parent strain killed all mice given infective doses greater than 5 x 10(8) cfu whereas W50/BR1 was much less virulent (2 out of 10 mice killed and higher infective doses needed for higher mortality rates) and W50/BE1 was avirulent at all infective doses tested.

Animals↗
PubMed2006

Heterochromatin-mediated control of virulence gene expression.

In recent years, the sequencing and annotation of complete genomes, together with the development of genetic and proteomic techniques to study previously intractable eukaryotic microbes, has revealed interesting new themes in the control of virulence gene expression. Families of variantly expressed genes are found adjacent to telomeres in the genomes of both pathogenic and non-pathogenic organisms. This subtelomeric DNA is normally heterochromatic and higher-order chromatin structure has now come to be recognized as an important factor controlling both the evolution and expression dynamics of these multigene families. In eukaryotic cells, higher-order chromatin structure plays a central role in many DNA processes including the control of chromosome integrity and recombination, DNA partitioning during cell division, and transcriptional control. DNA can be packaged in two distinct forms: euchromatin is relatively accessible to DNA binding proteins and generally contains active genes, while heterochromatin is densely packaged, relatively inaccessible and usually transcriptionally silent. These features of chromatin are epigenetically inherited from cell cycle to cell cycle. This review will focus on the epigenetic mechanisms used to control expression of virulence genes in medically important microbial pathogens. Examples of such control have now been reported in several evolutionarily distant species, revealing what may be a common strategy used to regulate many very different families of genes.

Animals↗
PubMed2001

Mutation analysis of the entire replicated portion of PKD1 using genomic DNA samples.

The replicated portion of PKD1, which comprises nearly 70% of the length of the gene, is predicted to harbor at least 85% of the mutations present in affected autosomal dominant polycystic kidney disease type 1 pedigrees. The relative paucity of reported mutations involving this segment is attributable to the significant technical challenges posed by the genomic structure of the gene. Previous genomic DNA-based strategies were unable to evaluate exons 1 and 22 and relied on the use of 10- to 13-kb PCR products. In this report, a set of six novel primer pair combinations, which can be used with previously reported reagents to analyze all of the exons in the replicated region (exons 1 to 34), are described. No product is greater than 5.8 kb in length, and various primer combinations can be used to reduce this length in half. Using this approach, two new pathogenic mutations, four novel disease-associated missense substitutions, and six new normal variants were identified. These new reagents should prove useful to investigators interested in performing DNA testing for this disorder.

Base Sequence↗
PubMed2005

Distribution of Porphyromonas gingivalis fimA genotypes in Japanese children and adolescents.

BACKGROUND: Porphyromonas gingivalis is considered to be one of the most important pathogens in periodontal disease and its fimA genes have been classified into six variants (types I through V and Ib). A majority of the P. gingivalis organisms isolated from periodontitis patients are type II, followed by type IV, while type I is prevalent in healthy adults. METHODS: A total of 650 saliva samples were taken from 464 children (3 to 18 years of age), who visited Osaka University Dental Hospital. Genomic DNA was extracted from each sample and analyzed using a polymerase chain reaction (PCR) method with P. gingivalis-specific primers, followed by an additional PCR assay to determine the fimA genotypes for P. gingivalis- positive subjects. RESULTS: Fifteen (3.23%) of the subjects were P. gingivalis-positive and none of those samples showed a positive reaction to the type II fimA-specific primers, while four, one, and two subjects were shown to be positive for the type I, Ib, and III genotypes, respectively. In addition, the type IV genotype was detected in three subjects in the older age group. CONCLUSIONS: Our findings suggest that a limited number of children harbor P. gingivalis, and that the distribution of type II and IV fimA genotypes is extremely low. Further, some adolescents were found to possess the type IV fimA genotype which has been shown to be possibly related to adult periodontitis, in contrast to types I, III, and V.

Adolescent↗
PubMed2002

Feline host range of canine parvovirus: recent emergence of new antigenic types in cats.

Since the emergence of Canine parvovirus (CPV-2) in the late 1970s, CPV-2 has evolved consecutively new antigenic types, CPV-2a and 2b. Although CPV-2 did not have a feline host range, CPV-2a and 2b appear to have gained the ability to replicate in cats. Recent investigations demonstrate the prevalence of CPV-2a and 2b infection in a wide range of cat populations. We illustrate the pathogenic potential of CPV in cats and assess the risk caused by CPV variants.

Amino Acid Sequence↗
PubMed2003

The C264Y missense mutation in the extracellular domain of L1 impairs protein trafficking in vitro and in vivo.

The neural cell adhesion molecule L1, a member of the immunoglobulin superfamily, performs important functions in the developing and adult nervous system and is implicated in neuronal migration and survival, elongation, fasciculation and pathfinding of axons, and synaptic plasticity. This view is in line with the fact that mutations in the L1 gene result in severe neurological syndromes in humans. Patients with missense mutations in the extracellular domain of L1 often develop severe phenotypes. Here, we characterized in vitro and in vivo the missense mutation C264Y, which is located in the extracellular domain of L1 and causes a severe phenotype in humans. Transfection studies in vitro demonstrate that L1 carrying this missense mutation is not expressed at the cell surface but instead is located intracellularly, most likely within the endoplasmic reticulum. Lack of cell surface expression of L1 with a C264Y mutation was confirmed in a transgenic mouse line expressing the C264Y mutation under the control of the L1 promoter in an L1-deficient background. Analysis of these transgenic mice indicates that they represent functional null mutants, phenotypically indistinguishable from L1-deficient mice. These observations corroborate the view that impaired cell surface expression of mutated variants of L1 is a potential explanation for the high number of severe pathogenic mutations identified within the human L1 gene.

Animals↗
PubMed2003

Osteopetrosis.

Osteopetrosis is a rare skeletal condition characterized by skeletal sclerosis caused by aberrant osteoclast-mediated bone resorption. Three clinically distinct forms of osteopetrosis are recognized--the infantile malignant autosomal recessive form, the intermediate autosomal recessive form, and the adult benign autosomal dominant form. The disease represents a spectrum of clinical variants because of the heterogeneity of genetic defects resulting in osteoclast dysfunction. The pathogenic defects may be intrinsic to either the osteoclast-monocyte lineage or the mesenchymal cells that constitute the microenvironment that supports osteoclast ontogeny and activation. Implicated factors include specific proto-oncogenes, growth factors, and immune regulators. A subset of patients with the intermediate autosomal recessive form has been characterized with carbonic anhydrase II isoenzyme deficiency. Management of patients with osteopetrosis requires a comprehensive approach to characteristic clinical problems including hematologic and metabolic abnormalities, fractures, deformity, back pain, bone pain, osteomyelitis, and neurologic sequelae. Medical treatment of osteopetrosis is based on efforts to stimulate host osteoclasts or provide an alternative source of osteoclasts. Stimulation of host osteoclasts has been attempted with calcium restriction, calcitrol, steroids, parathyroid hormone, and interferon. Bone marrow transplant has been used with cure for infantile malignant osteopetrosis. As osteopetrosis likely represents a spectrum of underlying etiologies resulting in osteoclast dysfunction, effective therapies most likely need to be individualized.

Humans↗