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PubMed2003

Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis.

One hundred and fifty-eight porcine strains of Pasteurella multocida, recovered primarily from cases of pneumonic pasteurellosis or progressive atrophic rhinitis (PAR) in England and Wales, were characterized by determination of their capsular types, presence or absence of the toxA gene and molecular mass heterogeneity of the heat-modifiable (OmpA) and porin (OmpH) proteins. Eighteen groups (clones) of strains were identified on the basis of specific combinations of capsular type, toxA status and outer-membrane protein (OMP)-type. The data provided evidence that different subpopulations of P. multocida are responsible for pneumonia and PAR in pigs. The majority (88 %) of cases of pneumonia were associated exclusively with non-toxigenic capsular type A strains of OMP-types 1.1, 2.1, 3.1 and 5.1 and capsular type D isolates of OMP-type 6.1. These strains were recovered from widespread geographical locations within England and Wales over a 12-year period and represented mostly single sporadic cases. The association of a small number of P. multocida variants with the majority of cases of porcine pneumonia suggests that these strains are not opportunistic pathogens of low virulence but represent primary pathogens with a relatively high degree of virulence. In contrast, the majority (76 %) of cases of PAR were associated with toxA-containing capsular type D strains of OMP-type 4.1 and capsular type A and D strains of OMP-type 6.1. Toxigenic capsular type A strains associated with PAR and non-toxigenic capsular type A strains associated with pneumonia represent distinct subpopulations of P. multocida that can be differentiated by their OMP-types. The association of capsular types A and D with strains of the same OMP-types, and the absence and presence of the toxA gene in strains of the same OMP-types, suggest that horizontal transfer of capsular biosynthesis and toxA genes has occurred between strains representing certain subpopulations of P. multocida.

Animals↗
PubMed2000

Endocardiac infectivity and binding to extracellular matrix proteins of oral Abiotrophia species.

Microorganisms of the genus Abiotrophia, formerly known as nutritionally variant streptococci, are members of the oral flora and often isolated from patients with endocarditis, but pathogenicity of oral Abiotrophia species has not been examined yet. In this study, 17 strains isolated from healthy human oral cavities and 7 reference strains (all derived from patients with endocarditis) of Abiotrophia spp. were tested for their abilities to cause infections in damaged heart tissues in catheterized rats and to adhere to extracellular matrix proteins in vitro. The reference strains of A. defectiva and A. adiacens showed high infectivities in the rats. Four oral isolates of these two species showed similarly high infectivities and three had moderate infectivities. Most of 10 oral strains of A. para-adiacens and A. elegans were found to be generally less infective. The highly infective A. adiacens strains showed markedly high fibronectin-binding capacity, suggesting a possible relationship between the fibronectin-binding capacity and damaged heart tissue infectivity of the Abiotrophia species. A. defectiva strains which were also highly infective had moderate levels of binding to fibronectin and other extracellular matrix proteins. Most of A. para-adiacens and A. elegans strains showed low or negligible binding capacities to any extracellular matrix proteins tested.

Animals↗
PubMed1999

Infectious coryza: overview of the disease and new diagnostic options.

Infectious coryza is a well-recognized and commonly encountered upper respiratory tract disease of chickens that is caused by the bacterium Haemophilus paragallinarum. The occurrence of recent outbreaks in North America has emphasized that the disease can be significant in meat chickens as well as layer chickens. In developing countries, coryza is commonly complicated by the presence of a range of other infections, resulting in severe disease and significant economic losses. Unusual forms of the disease, involving arthritis and septicemia, again associated with the presence of other pathogens, have been found in South America. Newly recognized bacteria such as Ornithobacterium rhinotracheale and phenotypic variant forms of both H. paragallinarum and close relatives (variant in that they no longer require V-factor for growth in vitro) have increased the difficulty associated with diagnosing the disease. There have been suggestions in both South America and South Africa that new serovars or serovar variants, associated with unusual clinical manifestations and causing vaccine failures, are emerging. Definitive evidence to confirm or deny the role of these "variants" in vaccine failures is currently not available. A new DNA-based diagnostic technique, involving PCR, has been recently described and will greatly assist in the diagnosis of infectious coryza.

Animals↗
PubMed1989

Whole, submandibular, and parotid saliva-mediated aggregation of Pseudomonas aeruginosa in cystic fibrosis.

The aggregation of mucoid and nonmucoid Pseudomonas aeruginosa by submandibular, parotid, and whole saliva from patients with cystic fibrosis (CF) and non-CF subjects was investigated. There were significant differences (P less than 0.01) in aggregation of mucoid and nonmucoid variants of P. aeruginosa by submandibular and whole saliva from CF patients and non-CF subjects. However, the differences in the parotid secretion were not as pronounced. Patients with CF who were colonized with P. aeruginosa demonstrated a significantly higher (P less than 0.05) percent aggregation of the mucoid variants by the submandibular secretion and of both mucoid and nonmucoid variants by whole saliva, compared with corresponding secretions from patients with CF not colonized with this pathogen. The parotid saliva aggregation activity was not markedly different for the two groups with CF. From patients with CF, whole saliva demonstrated a higher percent P. aeruginosa aggregation than did the submandibular saliva. In non-CF subjects, however, the percent aggregation of P. aeruginosa by submandibular saliva was higher than that by whole saliva. Our results indicate that the sero-mucous products of the submandibular gland have a more significant role in P. aeruginosa aggregation than the serous secreting parotid cells and that the submandibular secretion is possibly responsible for the differences in oral colonization by this pathogen in subjects with and without CF.

Adolescent↗
PubMed2000

Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1.

We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The prototypic gene in this cluster, set1, has been cloned and expressed. Recombinant SET1 stimulated the production of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. aureus but not in the other staphylococcal species examined. Sequence analysis of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency. The distribution of allelic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.

Amino Acid Sequence↗
PubMed1996

Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation.

Three naturally occurring variant human papillomavirus type 16 (HPV-16) E6 proteins, which contained amino acid substitutions predominantly near the N terminus, exhibited significant differences in their abilities to abrogate keratinocyte differentiation in response to serum and calcium and to induce the degradation of p53 in vitro. One variant surpassed the reference E6 protein in its ability to abrogate keratinocyte differentiation responses, whereas another showed a reduction in this activity. Interestingly, the biological activities of the HPV-16 E6 proteins and their abilities to induce p53 degradation in vitro were directly correlated. These results demonstrate that naturally occurring variants of HPV-16 differ in biological and biochemical properties which might result in differences in pathogenicity.

Base Sequence↗
PubMed2006

Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations.

PURPOSE: To determine the prevalence of FOXC1 and PITX2 mutations and to assess clinical phenotypes in a cohort of German patients with Axenfeld-Rieger malformations. METHODS: All coding exons of the FOXC1 and PITX2 genes were amplified by PCR from genomic DNA and subjected to direct DNA sequencing. Analysis of mutations in control subjects was performed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: Sequence variants were identified by DNA sequencing in 15 of 19 cases. Mutation screening identified four potentially pathogenic FOXC1 mutations causing amino acid substitutions (P79R, Y115S, G149D, and M161V) that were not present in 100 control subjects. In addition, two different 1-bp deletions causing a frameshift and subsequent premature stop codon were identified in two subjects. One patient harbored a FOXC1 nonsense mutation (S48X). Mutation screening also identified two potentially pathogenic PITX2 mutations (P64L and P64R) in two index patients that were excluded in 100 healthy control subjects. CONCLUSIONS: The findings in the present study clearly demonstrate that FOXC1 and PITX2 mutations are responsible for a significant proportion of Axenfeld-Rieger malformations in Germany.

Amino Acid Sequence↗
PubMed1999

Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 gaucher disease.

Gaucher disease is an autosomal recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal hydrolase, acid beta-glucosidase. Three phenotypically distinct subtypes result from different acid beta-glucosidase mutations encoding enzymes with absent or low activity. A severe neonatal type 2 variant who presented with collodion skin, ichthyosis, and a rapid neurodegenerative course had two novel acid beta-glucosidase alleles: a complex, maternally derived allele, E326K+L444P, and a paternally inherited nonsense mutation, E233X. Because the only other non-pseudogene-derived complex allele, D140H+E326K, also had the E326K lesion and was reported in a mild type 1 patient with a D140H+E326K/K157Q genotype, these complex alleles and their individual mutations were expressed and characterized. Because the E233X mutation expressed no activity and the K157Q allele had approximately 1% normal specific activity based on cross-reacting immunologic material (CRIM SA) in the baculovirus system, the residual activity in both patients was primarily from their complex alleles. In the type 1 patient, the D140H+E326K allele was neuroprotective, encoding an enzyme with a catalytic efficiency similar to that of the N370S enzyme. In contrast, the E326K+L444P allele did not have sufficient activity to protect against the neurologic manifestations and, in combination with the inactive E233X lesion, resulted in the severe neonatal type 2 variant. Thus, characterization of these novel genotypes with non-pseudogene-derived complex mutations provided the pathogenic basis for their diverse phenotypes.

Alleles↗
PubMed2000

Analysis of the HIV-1 nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy.

Great variability in the course of human immunodeficiency virus type 1 (HIV-1) infection results from a complex interplay between host and virus factors. Some of the patients with prolonged nonprogressive infection have been reported to harbor virus variants with gross deletions in the accessory nef gene that has been implicated in in vivo pathogenicity in simian and mouse models. To investigate the role of nef-deleted HIV-1 in long-term nonprogressor (LTNP) drug addicts in Italy the nef sequence from proviral DNA was analyzed from five LTNPs and five rapid progressor controls. Only small (2-12 amino acids) in-frame deletions and insertions were detected in the N-terminal polymorphic and variable regions obtained from three LTNPs and one rapid progressor. There was no evidence of premature termination of the Nef protein and all of the identified functional motifs were well conserved in both groups. Phylogenetic analysis showed interdigitation of nef sequences obtained from LTNPs and rapid progressors. The nef sequence of one LTNP, however, diverged significantly from those of the other patients. Availability of two additional blood DNA samples obtained previously from this subject allowed to detect evolution of nef at 14-17 years of HIV-1 infection, including progressive deletions. Although alterations of nef may be relatively frequent and continue to evolve in LTNPs, this study of a small number of patients does not indicate that gross deletions or loss of functional motifs play a major role in delaying or halting disease progression in infected drug abusers in Italy.

Adolescent↗
PubMed2000

[Signal identification of potentially pathogenous Yersinia].

A four-tube method with diagnostic nutrient media is proposed for differentiating between pathogenic and apathogenic Yersinia. Yersinia cultures are detected by inoculating typical or suspected colonies from solid media to media with lactose, glucose, urea, and indicators. Subsequent culturing in three other media (with sucrose and sorbitol, with esculin, rhamnose, and salicin, and with pyrasinamide) and the use of appropriate indicators help detect potentially pathogenous pseudotuberculous and enteric Yersinia of 1B, 2, 3, and 5 biovars from apathogenic species and variants. The method is simple, rapid, economic, reliable, and is recommended for clinical laboratory diagnosis.

Bacterial Typing Techniques↗
PubMed2001

Lack of BCL10 mutations in multiple myeloma and plasma cell leukemia.

To determine whether the BCL10 mutation plays a role in the oncogenesis of plasma cell dyscrasias, we used polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis and examined the genomic BCL10 mutations in 57 patients with multiple myeloma or plasma cell leukemia and 52 normal bone marrow samples. We found three polymorphic sequence variants, either alone or in combination, at codons 5 and 8, and in intron 1 at base 58 of the BCL10 gene in 37 patients with plasma cell dyscrasia. Identical aberrant band shifts were also observed in 34 normal marrow samples. No polymorphic variants were identified in exon 2 or 3 in either patient or control samples, and no pathogenic mutations were detected. Patients with plasma cell dyscrasias in Taiwan appeared to have a higher frequency of polymorphisms at codon 5 and intron 1 at base 58, and a lower frequency at codons 8 and 213. Our results suggest that BCL10 is not involved in the oncogenesis of plasma cell dyscrasias.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Questions concerning plasma cell leukaemia.

The classical concept of plasma cell leukaemia (PCL) is reviewed. This disease invariably concerns myeloma, either in its terminal phase (secondary PCL) or particularly rapid and aggressive (primary PCL). A more precise definition of primary PCL would be given by the term leukaemic myelomatosis. Characterization of the membrane antigen CD 56, responsible for the cytoadhesion of malignant plasmocytes in the bone marrow, today offers a convincing pathogenic hypothesis to elucidate this affection which would now appear to be no more than a variant form of myeloma. Acute immunoblastic-plasmoblastic leukaemia and mature cell leukaemic lymphoma would seem to be pathologically related to PCL. Finally, the problems posed by the "enigmatic" plasmacytoid monocyte are discussed.

Antigens, CD↗
PubMed2004

[C4d: a pathogenetically relevant marker in kidney transplantation].

Antibody-mediated allograft rejection should be discriminated from cell-mediated rejection processes since these two distinct pathogenic mechanisms are likely to require different therapeutic approaches. The complement split product C4 d (although biologically inactive by itself) turned out to be a reliable diagnostic marker of antibody-induced complement activation in kidney allografts. In contrast to other organs like heart and bowel, there is no indication that ischemia/reperfusion injury might induce the classical pathway of complement activation in the kidney. Endothelial C4 d deposits in peritubular capillaries of transplanted kidneys are therefore robust indicators of antibody-mediated alloreactivity with potentially unfavourable outcome. The high efficiency of therapeutic strategies aimed at removing alloantibodies from the recipient's circulation (i.e. immunoadsorption and plasmapheresis) in cases of C4d positive rejection further underscores the important pathogenic role of antibodies in renal allograft rejection and the diagnostic relevance of endothelial C4 d deposits. C4 d deposits can also occur de novo in late allograft biopsies. Their association with basement membrane injury in peritubular capillaries and glomeruli, which are the hallmarks of chronic rejection, indicates a contribution of humoral immune reactions to chronic rejection. Due to the clinical relevance of humoral rejection and due to the fact that the latest update of the Banff classification introduced the pathogenically based subdivision of acute rejection into a cell-mediated and an antibody-mediated variant every renal allograft biopsy should be stained for C4 d. It is important to be aware that humoral and cellular rejection often occur simultaneously and that C4d deposits alone are not an unequivocal proof of humoral rejection that immediately requires treatment.

Basement Membrane↗
PubMed1984

Mycoplasma mycoides infections in ruminants: the current situation.

Recent reports of naturally occurring infections with the large colony variant of Mycoplasma mycoides subsp. mycoides are collated and considered together with the results of experimental pathogenicity studies. The information is assessed to indicate where further investigation would add to knowledge of M. mycoides subsp. mycoides as a ruminant pathogen.

Animals↗
PubMed1999

Lymphokines modulate the growth and survival of thymic tumor cells containing a novel feline leukemia virus/Notch2 variant.

Tumorigenesis occurs through a multistep process initiated by genetic lesions and facilitated by endogenous and external growth/survival signals. In many malignancies, specific oncogenic mutations correlate with phenotypic characteristics, inferring lineage-specific pathogenic mechanisms. To characterize these relationships in a unique feline tumor, we studied primary cells and two-cell lines independently-derived from a thymic lymphoma that contained and actively expressed a novel feline leukemia virus (FeLV) recombinant with transduced host Notch2 sequences. All three tumor cell populations contained similar FeLV/Notch2 proviral variants and phenotypically resembled mature thymocytes. Multiple Notch2 transcripts were expressed in the cell lines, including species that correspond to viral genomes and spliced subgenomic viral mRNA. Tumor cell line FeLV/Notch2 virus was packaged into virions; however, the variant was not efficiently transmitted to feline cells in vitro. Primary tumor cells constitutively expressed mRNA for interleukin-4 (IL-4), IL-6 and the p40 subunit of IL-12. Lymphokine mRNA was not detected in established tumor cell lines nor was T-cell growth-promoting activity found in culture supernatants. Exogenous IL-4 enhanced primary tumor cell survival, but inhibited proliferation of the cell lines. Interleukin-4 abrogated hydrocortisone-induced apoptosis in all three populations and had divergent effects on cell line clonogenic colony formation. Exogenous IL-7 and, to a lesser degree, IL-6 also had variable positive effects on the growth and viability of the tumor cell populations. Collectively, these data suggest that thymocytes are susceptible to the transforming potential of dysregulated Notch2 and that thymopoietic factors could, through overlapping and distinct mechanisms, promote the survival and outgrowth of FeLV/Notch2-containing neoplastic cells.

Animals↗
PubMed2001

Surfactant protein D-coated Klebsiella pneumoniae stimulates cytokine production in mononuclear phagocytes.

Encapsulated Klebsiella pneumoniae strains K21a, K10, and K50, all of which contain dimannose sequences in their capsular polysaccharides that are recognized by the mannose receptor of macrophages, stimulated interleukin secretion and cytokine mRNA expression by human monocyte-derived macrophages. By contrast, the corresponding unencapsulated phase variants and the K2 strain, which lack the dimannose sequence, did not. Coating of unencapsulated phase variants of Klebsiella strains with surfactant protein (SP)-D resulted in marked stimulation of cytokine mRNA accumulation. The induction of cytokine mRNA via the mannose receptor occurred only in monocyte-derived macrophages, whereas that caused by SP-D-coated Klebsiella strains occurred in both macrophages and peripheral-blood monocytes. The results suggested that innate immunity against pulmonary pathogens might be mediated by SP-D, which acts as an opsonin to enhance the interaction of macrophages with unencapsulated phase variants originating from the upper respiratory tract, and by macrophage mannose receptors, which recognize encapsulated variants expressing capsular dimannose residues.

Cytokines↗
PubMed1983

Multiflagellate variants of Vibrio anguillarum.

An ultrastructural examination of six strains of Vibrio anguillarum of varying virulence for eels revealed an apparent correlation between pathogenicity and the possession of more than one flagellum. The relationship between V. anguillarum surface appendages and virulence is discussed.

Animals↗
PubMed2003

Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection.

It is believed that replication capacity is an important determinant of human immunodeficiency virus type 1 (HIV-1) pathogenicity and transmissibility. To explore this, we conducted a comprehensive analysis of the replication properties of nine drug-resistant and nine drug-susceptible viral isolates derived from patients with primary HIV-1 infection. Viral isolates were tested for single-cycle infectivity in the GHOST cell line. The infectivity of isolates carrying resistance-associated mutations was significantly higher than that of drug-susceptible isolates. Additionally, the growth kinetics of these isolates were determined in CD4+ T lymphocytes. Drug-resistant isolates replicated as well as drug-susceptible viruses. Insertion of the resistance-conferring regions into an NL4-3-based molecular background resulted in chimeras that displayed a modest but significant reduction in replication capacity compared to the drug-susceptible chimeric viruses. Of note, two multidrug-resistant isolates and one protease inhibitor-resistant isolate displayed higher rates of infectivity and growth kinetics than the other drug-resistant or drug-susceptible isolates. These distinct replicative features, however, were not seen in the corresponding chimeras, indicating that changes within the C-terminal region of Gag as well as within the protease and reverse transcriptase genes contribute to but are not sufficient for the level of compensatory adaptation observed. These findings suggest that some drug-resistant viruses isolated during primary infection possess unique adaptive changes that allow for both high viral replication capacity and resistance to one or more classes of antiretroviral drugs. Further studies are needed to elucidate the precise regions that are essential for these characteristics.

Amino Acid Substitution↗