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PubMed1989

[The immunology of rheumatoid arthritis. Influence of basic treatment].

Rheumatoid arthritis is a disease determined and influenced by many factors genetic, environmental, endocrine, psychological and immunological. Immunological mechanisms (hyperexpression of class II HLA antigens, cytokinin anomalies, functional deficiencies of certain lymphocyte categories, polyclonal activation of B lymphocytes with production of antibodies) suffice to maintain between them the immune response, synovial inflammation, and lesions of bone and cartilage. Progress in understanding these diverse pathogenic factors in RA will eventually lead more selectively targeted treatments to supercede the present empirical use of basic treatments.

Arthritis, Rheumatoid↗
PubMed1995

Thymic immunopathology and progression of SIVsm infection in cynomolgus monkeys.

Thymuses from 22 cynomolgus monkeys infected with simian immunodeficiency virus (SIVsm) developed characteristic cortical and medullary changes including formation of B-cell follicles (8/21) and accumulation of virus immune complexes. Advanced thymic histopathology was correlated with more pronounced immunodeficiency. SIVsm provirus was detected by polymerase chain reaction (PCR) in most (16/18) thymuses and spliced viral env mRNA in 3 (3/7) thymuses with advanced histopathologic changes indicative of thymic SIVsm replication. By combined in situ hybridization (ISH) and immunohistochemistry, viral RNA was localized mainly to the follicular dendritic network, macrophages, multinucleated giant cells, and lymphocytes of the medullary regions. Latent infection by an Epstein-Barr-related herpesvirus (HVMF1) was also found by PCR and by ISH in medullary regions of three (3 of 8) thymuses with B-cell follicles, suggestive of an inductive role for B-cell proliferation in these thymuses. In a control group of HIV-2-infected nonimmunosuppressed monkeys, no comparable thymic changes were observed. Our results indicate that SIV, and probably by analogy HIV, can have direct and diverse pathogenic effects on the thymus that are important in the development of simian (human) AIDS.

Animals↗
PubMed1998

Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells.

The initiation of an adaptive immune response requires Ag presentation in combination with the appropriate activation signals. Classically, Ag presentation and immune activation occur in the lymph node and spleen, where a favorable organ architecture and rich cellular help can enhance the process. Recently, several investigators have reported the use of DNA expression cassettes to elicit cellular and humoral immunity against diverse pathogens. Although the immune mechanisms involved are still poorly understood, plasmid inoculation represents a model system for studying immune function in response to invading pathogens. In this report, we demonstrate the presence of activated macrophages or dendritic cells in the blood lymphocyte pool and peripheral tissues of animals inoculated with DNA expression cassettes. These cells are directly transfected in vivo, present Ag, and display the surface proteins CD80 and CD86. Our studies indicate that these cells function as APC and can activate naive T lymphocytes. They may represent an important first step APC in genetic immunization and natural infection.

Animals↗
PubMed2002

Effects of agronomical measures on the microbial diversity of soils as related to the suppression of soil-borne plant pathogens.

The diversity of soil microbial communities can be key to the capacity of soils to suppress soil-borne plant diseases. As agricultural practice, as well as directed agronomical measures, are known to be able to affect soil microbial diversity, it is plausible that the soil microflora can be geared towards a greater suppressivity of soil-borne diseases as a result of the selection of suitable soil management regimes. In the context of a programme aimed at investigating the microbial diversity of soils under different agricultural regimes, including permanent grassland versus arable land under agricultural rotation, we assessed how soil microbial diversity is affected in relation to the suppression of the soil-borne potato pathogen Rhizoctonia solani AG3. The diversity in the microbial communities over about a growing season was described by using cultivation-based--plating on different media--and cultivation-independent--soil DNA-based PCR followed by denaturing gradient gel electrophoresis (DGGE) community fingerprinting--methods. The results showed great diversity in the soil microbiota at both the culturable and cultivation-independent detection levels. Using cultivation methods, various differences between treatments with respect to sizes of bacterial and fungal populations were detected, with highest population sizes generally found in rhizospheres. In addition, the evenness of eco-physiologically differing bacterial types was higher in grassland than in arable land under rotation. At the cultivation-independent level, clear differences in the diversities of several microbial groups between permanent grassland and arable land under rotation were apparent. Bio-assays that assessed the growth of R. solani AG3 hyphae through soil indicated a greater growth suppression in grassland than in arable land soils. Similarly, an experiment performed in the glasshouse showed clear differences in both microbial diversities and suppressiveness of R. solani growth in soil, depending on the presence of either maize or oats as the crop. The significance of these findings for designing soil management strategies is discussed.

Agriculture↗
PubMed1992

PCR-based RFLP analysis of DNA sequence diversity in the gastric pathogen Helicobacter pylori.

DNA sequence diversity among 60 independent isolates of the gastric pathogen Helicobacter pylori was assessed by testing for restriction fragment length polymorphisms (RFLPs) in several PCR-amplified gene segments. 18 Mbol and 27 HaeIII RFLPs were found in the 2.4 kb ureA-ureB (urease) segment from the 60 strains; this identified 44 separate groups, with each group containing one to four isolates. With one exception, each isolate not distinguished from the others by RFLPs in ureA-ureB was distinguished by Mbol digestion of the neighboring 1.7 kb ureC-ureD segment. The 1.5 kb flaA (flagellin) gene, which is not close to ure gene cluster, was also highly polymorphic. In contrast, isolates from initial and followup biopsies yielded identical restriction patterns in each of the three cases tested. The potential of this method for detecting population heterogeneity was tested by mixing DNAs from different strains before amplification: the arrays of restriction fragments obtained indicated co-amplification from both genomes in each of the five pairwise combinations tested. These results show that H. pylori is a very diverse species, that indicate PCR-based RFLP tests are almost as sensitive as arbitrary primer PCR (RAPD) tests, and suggest that such RFLP tests will be useful for direct analysis of H. pylori in biopsy and gastric juice specimens.

Base Sequence↗
PubMed1997

Molecular population genetics of Drosophila immune system genes.

A striking aspect of many vertebrate immune system is the exceptionally high level of polymorphism they harbor. A convincing case can be made that this polymorphism is driven by the diversity of pathogens that face selective pressures to evade attack by the host immune system. Different organisms accomplish a defense against diverse pathogens through mechanisms that differ widely in their requirements for specific recognition. It has recently been shown that innate defense mechanisms, which use proteins with broad-spectrum bactericidal properties, are common to both primitive and advanced organisms. In this study we characterize DNA sequence variation in six pathogen defense genes of Drosophila melanogaster and D. mauritiana, including Andropin; cecropin genes CecA1, CecA2, CecB, and CecC; and Diptericin. The necessity for protection against diverse pathogens, which themselves may evolve resistance to insect defenses, motivates a population-level analysis. Estimates of variation levels show that the genes are not exceptionally polymorphic, but Andropin and Diptericin have patterns of variation that differ significantly from neutrality. Patterns of interpopulation and interspecific differentiation also reveal differences among the genes in evolutionary forces.

Animals↗
PubMed2005

Correlation between the genetic diversity of nosocomial pathogens and their survival time in intensive care units.

Bacteria differ in their ability to survive in the hospital environment outside the human host. Species remaining viable and infectious have a higher chance of being transmitted, giving them a fitness advantage in hospitals. This differential fitness could be expected to alter the genetic population structure of bacterial populations in hospitals, and should be reflected by the relative abundance of several successful clones. The objective of this study was to test for a potential correlation between tenacity, i.e. environmental survival, and clonal abundance determined by the genetic diversity in different bacterial species from prospectively collected isolates of intensive care patients. A literature review was performed to identify mean environmental survival times for the most important pathogens in intensive care units (ICUs): Staphylococcus aureus, enterococci, Acetinobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and Stenotrophomonas maltophilia. To determine the genetic diversity of the natural population of these species in ICUs, a prospective 18-month study was conducted in five units with median nosocomial infection rates. All clinical isolates were collected, and highly discriminatory DNA fingerprinting techniques were used to identify specific clones. A diversity index for each species was calculated as the number of distinguishable genotypes in the population divided by size. The correlation between survival times and the diversity indices for the individual pathogens was investigated using non-parametric methods. Although 21 studies were identified in the literature, only two were relevant. They showed median survival times between 1.5 days (P. aeruginosa) and 60.0 days (Enterococcus faecium). During the prospective ICU study, 1264 pathogens were investigated and simple diversity indices between 49.1 (Enterococcus faecalis) and 89.8 (E. coli) were found. A correlation between survival times and the diversity indices for the individual pathogens was found (correlation coefficient 0.821, P=0.024). Environmental survival may be an important factor contributing to the ecological fitness of some nosocomial pathogens in ICUs. Infection control measures should consider this finding.

Bacterial Infections↗
PubMed1995

RFLPs in mitochondrial and nuclear DNA indicate low levels of genetic diversity in the oak wilt pathogen Ceratocystis fagacearum.

Genetic diversity in the oak wilt pathogen Ceratocystis fagacearum was assessed using restriction fragment length polymorphisms (RFLPs) of the mitochondrial DNA (mtDNA) and anonymous RFLP loci in the nuclear DNA (nuDNA). No genetic variation was detected in the mtDNA among 27 isolates sampled from a broad geographical area. Southern hybridization to 100 anonymous, random, nuDNA probes detected a low level of variation among nine of the isolates. Only 35 out of 437 probe-enzyme combinations detected RFLPs. Most of the RFLPs appeared to result from insertions and deletions of less than 200 bp. A composite multilocus haplotype based on hybridization to six anonymous probes could differentiate each of the nine isolates tested, suggesting that these probes may be useful for further studies of the population biology and epidemiology of this pathogen. Hypotheses are presented to account for the low level of genetic variation.

Ascomycota↗
PubMed2004

Distinct diversity of the cag pathogenicity island among Helicobacter pylori strains in Japan.

The severity of Helicobacter pylori-related disease is correlated with the presence of a cag pathogenicity island (PAI). Genetic diversity within the cag PAI may have a modifying effect on the pathogenic potential of the infecting strain. We analyzed the complete cag PAI sequences of 11 representative Japanese strains according to their vacA genotypes and clinical effects and examined the relationship between the diversity of the cag PAI and clinical features. The cag PAI genes were divided into two major groups, a Western and a Japanese group, by phylogenetic analysis based on the entire cag PAI sequences. The predominant Japanese strains formed a Japanese cluster which was different from the cluster formed by Western strains. The diversity of the cag PAI was associated with the vacA and cagA genotypes. All strains with the s1c vacA genotype were in the Japanese cluster. In addition, all strains with the East Asian-type cagA genotype were also in the Japanese cluster. Patients infected with the Japanese-cluster strain had high-grade gastric mucosal atrophy. These results suggest that a distinct diversity of the cag PAI of H. pylori is present among Japanese strains and that this diversity may be involved in the development of atrophic gastritis and may increase the risk for gastric cancer.

Antigens, Bacterial↗
PubMed2006

Effect of microbial pathogens on the diversity of aquatic populations, notably in Europe.

The expansion of aquaculture and the demand for ornamental fish have resulted in the large-scale movements of aquatic animals and their pathogens. Here we review the most important non-native fish and shellfish pathogens in European waters and their global impacts on wild fish host populations. The role of theoretical models in the study of the impact of microbial pathogens is discussed, including its integration into risk assessments.

Animals↗
PubMed2003

[Genetic diversity analysis of Chinese stylo anthracnose pathogens using random amplified polymorphic DNA].

Genetic diversity of 43 Colletotrichum gloeosporioides isolates from stylo in China were analyzed using random amplified polymorphic DNA (RAPD) with eight arbitrary 10-base oligonucleotide primers compared with 276 isolates from other countries including two of Colletotrichum cutaturn based on a wide survey and disease sample collection. The results showed a good DNA polymorphism between isolates. The amplified fragments were between 0.3-2.8 kb. Chinese isolates were grouped in clusters II, III and VI with the majority in cluster VI based on six clusters of isolates from South America, the centre of origin of Stylosanthes genus. The genetic variation in the Chinese pathogen population was very limited compared with that in South America, the centre of host-pathogen diversity. The results also showed that a genetic variation in Chinese population of Colletotrichum gloeosporioides existed, though this variation was less significant. Isolates grouped by geographic origin and host species or genotypes indicated isolates from different host species or genotypes had their own parasitic specialization on genetic basis and pathogens from different countries evolved in their own way relatively.

China↗
PubMed2004

Genetic diversity of human pathogenic members of the Fusarium oxysporum complex inferred from multilocus DNA sequence data and amplified fragment length polymorphism analyses: evidence for the recent dispersion of a geographically widespread clonal lineage and nosocomial origin.

Fusarium oxysporum is a phylogenetically diverse monophyletic complex of filamentous ascomycetous fungi that are responsible for localized and disseminated life-threatening opportunistic infections in immunocompetent and severely neutropenic patients, respectively. Although members of this complex were isolated from patients during a pseudoepidemic in San Antonio, Tex., and from patients and the water system in a Houston, Tex., hospital during the 1990s, little is known about their genetic relatedness and population structure. This study was conducted to investigate the global genetic diversity and population biology of a comprehensive set of clinically important members of the F. oxysporum complex, focusing on the 33 isolates from patients at the San Antonio hospital and on strains isolated in the United States from the water systems of geographically distant hospitals in Texas, Maryland, and Washington, which were suspected as reservoirs of nosocomial fusariosis. In all, 18 environmental isolates and 88 isolates from patients spanning four continents were genotyped. The major finding of this study, based on concordant results from phylogenetic analyses of multilocus DNA sequence data and amplified fragment length polymorphisms, is that a recently dispersed, geographically widespread clonal lineage is responsible for over 70% of all clinical isolates investigated, including all of those associated with the pseudoepidemic in San Antonio. Moreover, strains of the clonal lineage recovered from patients were conclusively shown to genetically match those isolated from the hospital water systems of three U.S. hospitals, providing support for the hypothesis that hospitals may serve as a reservoir for nosocomial fusarial infections.

Animals↗
PubMed1996

Virulence and pathogenicity associated with diversity of Trypanosoma cruzi stocks and clones derived from Chagas' disease patients.

The intraspecific variation that has been described in Trypanosoma cruzi was examined in recent isolates from Chagas' disease patients, using behavioral and molecular markers for characterization of the parasite stocks and derived clones. We used these parasite populations to determine virulence and pathogenicity in vivo. The T.cruzi stocks mSLU142 (megaesophagus) and hSLU239 (heart disease) and the clones h1 and h2 induced very low parasitemias in BALB/c mice, whereas high parasitemias were obtained with clones m1, m2, m3, and m4. Clones m1-m4 also produced heart lesions of higher intensity than those observed in mice infected with the h1 and h2 clones. Furthermore, the heart lesions produced by all of these clones were significantly more intense than those seen in mice infected with either of the T. cruzi parental stocks. In addition, neither the kinetics of growth, doubling time, differentiation in axenic culture, zymodemes, nor DNA restriction length polymorphisms showed correlations with parasitemias and pathogenicity in mice. This study suggests that multiple biochemical and physiological markers are required to enable an association of clinical and pathologic manifestations of the disease with intrinsic characters of the T. cruzi populations.

Animals↗
PubMed1991

Sparse diversity of potential pathogenic soil micro-fungi in the Ukraine.

Soil from steppe and garden reserves, and urban park and wharf regions in the Ukraine, U.S.S.R., were studied for keratinophilic as well as for other predominant micro-fungal species. Most of the fungi were nonpathogens, and potential skin infecting fungi were limited to Microsporum gypseum and Trichophyton ajelloi. Species diversity identified population variation between collection sites.

Fungi↗
PubMed2001

Detecting anomalous gene clusters and pathogenicity islands in diverse bacterial genomes.

A gene in a genome is defined as putative alien (pA) if its codon usage difference from the average gene exceeds a high threshold and codon usage differences from ribosomal protein genes, chaperone genes and protein-synthesis-processing factors are also high. pA gene clusters in bacterial genomes are relevant for detecting genomic islands (GIs), including pathogenicity islands (PAIs). Four other analyses appropriate to this task are G+C genome variation (the standard method); genomic signature divergences (dinucleotide bias); extremes of codon bias; and anomalies of amino acid usage. For example, the cagA domain of Helicobacter pylori is highly deviant in its genome signature and codon bias from the rest of the genome. Using these methods we can detect two potential PAIs in the Neisseria meningitidis genome, which contain hemagglutinin and/or hemolysin-related genes. Additionally, G+C variation and genome signature differences of the Mycobacterium tuberculosis genome indicate two pA gene clusters.

Bacteria↗
PubMed1985

Epidemiology of community-acquired respiratory tract infections in adults. Incidence, etiology, and impact.

Upper respiratory tract infections are the most common types of infectious diseases among adults. It is estimated that each adult in the United States experiences two to four respiratory infections annually. The morbidity of these infections is measured by an estimated 75 million physician visits per year, almost 150 million days lost from work, and more than $10 billion in costs for medical care. Serotypes of the rhinoviruses account for 20 to 30 percent of episodes of the common cold. However, the specific causes of most upper respiratory infections are undefined. Pneumonia remains an important cause of morbidity and mortality for nonhospitalized adults despite the widespread use of effective antimicrobial agents. There are no accurate figures on the number of episodes of pneumonia that occur each year in ambulatory patients. In younger adults, the atypical pneumonia syndrome is the most common clinical presentation; Mycoplasma pneumoniae is the most frequently identified causative agent. Other less common agents include Legionella pneumophila, influenza viruses, adenoviruses, and Chlamydia. More than half a million adults are hospitalized each year with pneumonia. Persons older than 65 years of age have the highest rate of pneumonia admissions, 11.5 per 1,000 population. Pneumonia ranks as the sixth leading cause of death in the United States. The pathogens responsible for community-acquired pneumonias are changing. Forty years ago, Streptococcus pneumoniae accounted for the majority of infections. Today, a broad array of community-acquired pathogens have been implicated as etiologic agents including Legionella species, gram-negative bacilli, Hemophilus influenzae, Staphylococcus aureus and nonbacterial pathogens. Given the diversity of pathogenic agents, it has become imperative for clinicians to establish a specific etiologic diagnosis before initiating therapy or to consider the diagnostic possibilities and treat with antimicrobial agents that are effective against the most likely pathogens.

Adolescent↗
PubMed2005

Statistics of infections with diversity in the pathogenicity.

The statistics of outbreaks in a model for the propagation of meningococcal disease is analyzed, taking into account the possibility that the population is fragmented into weakly connected patches. It is shown that, depending on the size of the sample studied, the ration between the variance and the average of infected cases can vary from unity (Poisson statistics) to epsilon(-1), where epsilon is the normalized infection rate.

Disease Outbreaks↗