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PubMed1975

Biochemical properties of wild mouse oncornaviruses with lymphomagenic and neurotropic activities.

The close immunologic relation between the group-specific and polymerase proteins of the wild mouse derived and the established strains of mouse type C oncornaviruses, and the lack of any unusual structural polypeptide or RNA components in the wild mouse virions, eliminate the possibility of detectable contamination by a class of virus different from the mouse oncornavirus class in the wild mouse virus preparations. Liquid hybridization studies with a wild mouse viral 70S 3H-RNA and cellular DNA under conditions of DNA excess, suggest that a significant fraction but not all of the virus-specific nucleotide sequences is present in all normal and tumored wild mouse tissues tested. These virus related sequences may possibly be attributed to a hypothetical endogenous inherited type C virus genome(s) carried by all wild mice or to an infection by one or more but not all of the different exogenous strains of wild mouse type C viruses which could possibly be present in the virus preparation used. The findings are consistent with wild mouse derived type C viruses being either entirely exogenous or a mixture of endogenous and exogenous viruses. This interpretation is also consistent with the earlier observation that certain wild mouse type C viruses are exogenously transmitted, transplacentally, and via milk. The possible relation of the virus heterogeneity or the distinct characteristics of the virus surface molecules to the diverse pathogenicity of the wild mouse oncornaviruses is discussed.

DNA Nucleotidyltransferases↗

PubMed2006

Analysis of bacteria-challenged wild silkmoth, Antheraea mylitta (lepidoptera) transcriptome reveals potential immune genes.

BACKGROUND: In the recent years a strong resemblance has been observed between the insect immune system and the mammalian innate immune mechanisms suggesting their common origin. Among the insects, only the dipterans (Drosophila and various mosquito species) have been widely investigated for their immune responses towards diverse pathogens. In the present study we constructed and analysed the immune transcriptome of the lepidopteran Antheraea mylitta, an economically important Indian tasar silkmoth with a view to unravel the potential immune-related genes and pathways. RESULTS: An expressed sequence tag (EST) library was constructed from mRNA obtained from fat bodies of A. mylitta larvae that had been challenged by infection with Escherichia coli cells. We identified 719 unique ESTs from a total of 1412 sequences so generated. A third of the transcriptome showed similarity with previously characterized immune-related genes that included both the known and putative immune genes. Of the four putative novel defence proteins (DFPs) annotated by PSI-BLAST three showed similarity to extracellular matrix proteins from vertebrates implicated in innate immunity, while the fourth was similar to, yet distinct from, the anti-microbial protein cecropin. Finally, we analysed the expression profiles of 15 potential immune-related genes, and the majority of them were induced more prominently with E. coli compared to Micrococcus luteus. We also identified several unknown proteins, some of which could have probable immune-related functions based on the results of the ProDom analysis. CONCLUSION: The present study has identified many potential immune-related genes in A. mylitta some of which are vertebrate homologues and others are hitherto unreported putative defence proteins. Several genes were present as members of gene families, as has also been observed in other insect species.

Amino Acid Sequence↗

PubMed1999

Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

STUDY OBJECTIVES: To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. DESIGN: Multicenter, cross-sectional, epidemiologic study. SETTING: Pneumology units in six secondary or tertiary hospitals in Spain. PATIENTS: Ninety-one patients with acute exacerbation of COPD were included. INTERVENTIONS: A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with < 10 epithelial cells and > 25 leukocytes per low magnification field (x 100). RESULTS: Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 < 50% than among those with FEV1 > 50% (p < 0.05). All patients with P. aeruginosa in sputum had FEV1 < 1,700 mL. FEV1 < 50% was associated with a very high risk of P. aeruginosa or H. influenzae isolation: the odds ratios (ORs) are 6.62 (95% confidence interval [CI], 1.2 to 123.6) and 6.85 (95% CI, 1.6 to 52.6), respectively. Furthermore, active tobacco smoking was associated with a high risk of H. influenzae isolation (OR, 8.1; 95% CI, 1.9 to 43.0). CONCLUSIONS: Patients with the greatest degree of functional impairment, as measured by their FEV1, presented a higher probability of having an isolation of P. aeruginosa or H. influenzae in significant concentrations in sputum during an exacerbation. The diagnostic yield of sputum in patients with an FEV1 > 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.

Aged↗

PubMed2006

Emerging infectious determinants of chronic diseases.

Evidence now confirms that noncommunicable chronic diseases can stem from infectious agents. Furthermore, at least 13 of 39 recently described infectious agents induce chronic syndromes. Identifying the relationships can affect health across populations, creating opportunities to reduce the impact of chronic disease by preventing or treating infection. As the concept is progressively accepted, advances in laboratory technology and epidemiology facilitate the detection of noncultivable, novel, and even recognized microbial origins. A spectrum of diverse pathogens and chronic syndromes emerges, with a range of pathways from exposure to chronic illness or disability. Complex systems of changing human behavioral traits superimposed on human, microbial, and environmental factors often determine risk for exposure and chronic outcome. Yet the strength of causal evidence varies widely, and detecting a microbe does not prove causality. Nevertheless, infectious agents likely determine more cancers, immune-mediated syndromes, neurodevelopmental disorders, and other chronic conditions than currently appreciated.

Bacterial Infections↗

PubMed2002

Cutting edge: inflammatory signals drive organ-specific autoimmunity to normally cross-tolerizing endogenous antigen.

Links have been observed between infections and the development of autoimmunity. Proposed explanations include activation of self-Ag-bearing APC. Using a model system in which transgenic OVA is expressed in enterocytes, we showed that CD8 T cell recognition of cross-presented Ag in gut-associated lymph nodes was tolerogenic. However, concomitant infection with vesicular stomatitis virus encoding OVA abrogated tolerance and induced disease. We now show that following transfer of naive OT-I T cells, the addition of wild-type vesicular stomatitis virus, oral cholera toxin, or CD40 triggering can induce intestinal disease in transgenic mice. Tissue damage accompanied dramatic increases in cytokine release by activated OT-I cells in the intestine. The data indicated that products of antigenically unrelated infections can combine with cross-presented self-Ags on APC to prime autoaggressiveness, independent of additional Ag release. These results help explain how diverse pathogens, lacking any homology to self-proteins, could be causative agents in induction of organ-specific autoimmunity.

Adoptive Transfer↗

PubMed2004

TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses.

TLR signaling leads to dendritic cell (DC) maturation and immunity to diverse pathogens. The stimulation of TLRs by conserved viral structures is the only described mechanism leading to DC maturation after a virus infection. In this report, we demonstrate that mouse myeloid DCs mature normally after in vivo and in vitro infection with Sendai virus (SeV) in the absence of TLR3, 7, 8, or 9 signaling. DC maturation by SeV requires virus replication not necessary for TLR-mediated triggering. Moreover, DCs deficient in TLR signaling efficiently prime for Th1 immunity after infection with influenza or SeV, generating IFN-gamma-producing T cells, CTLs and antiviral Abs. We have previously demonstrated that SeV induces DC maturation independently of the presence of type I IFN, which has been reported to mature DCs in a TLR-independent manner. The data presented here provide evidence for the existence of a novel intracellular pathway independent of TLR-mediated signaling responsible for live virus triggering of DC maturation and demonstrate its critical role in the onset of antiviral immunity. The revelation of this pathway should stimulate invigorating research into the mechanism for virus-induced DC maturation and immunity.

Adaptor Proteins, Signal Transducing↗

PubMed2006

The application of molecular techniques to the study of hospital infection.

CONTEXT: Nosocomial infections represent an important cause of morbidity and mortality in hospital settings, resulting in high health care costs. The roles of an epidemic investigation are to recognize that a problem exists, to compare characteristics of affected persons with those of similar but unaffected persons (case-control study), and to identify risk factors. Integrating typing methods as part of conventional epidemiologic surveillance is cost-effective and results in a reduction in rates of nosocomial infections. During the past 10 years, there has been unprecedented progress in molecular biology and in the application of nucleic acid technology to the study of the epidemiology of human infections. OBJECTIVES: To summarize the available molecular tests for determination of the relatedness of microorganisms causing nosocomial infections, emphasizing the most useful applications of the tests to the study of the epidemiology of hospital-acquired infection; and to discuss the appropriate use of these tests in the prevention and control of hospital-associated infection. DATA SOURCE: Published English-language literature from 1980 to the present. CONCLUSIONS: Pulsed-field gel electrophoresis is the method of choice for strain delineation. The newest techniques include polymerase chain reaction and multilocus sequence typing, in which various housekeeping genes that are stable markers of strain identity are sequenced. Molecular techniques are broadly applicable to the study of diverse pathogens. Typing data obtained by DNA analysis should always be considered together with epidemiologic information, because only this combination will enable the most accurate epidemiologic evaluation.

Cost-Benefit Analysis↗

PubMed1998

Overview of viral hepatitis.

Viral hepatitis is a general term that is reserved for infections of the liver caused by one of at least six distinct hepatitis viruses, designated hepatitis virus A, B, C, D, E, and G/GB. The human hepatitis viruses are a group of diverse pathogens that share an ability to cause inflammation and necrosis of the liver. The most notable sign of this disease is jaundice, an orange-yellow discoloration of the scleroproteins of the skin and conjunctivae caused by the deposition of bilirubin in the blood resulting from faulty excretion of bile pigment by damaged hepatocytes.

Acute Disease↗

PubMed1991

Bacterial adhesion to mucosal surfaces.

Bacteria utilize one or more of several mechanisms to adhere to mucosal surfaces. Members of the enterobacteriaceae and related bacteria typically elaborate adhesive filamentous appendages from their surfaces termed fimbriae (or pili). Vibrio cholerae expresses at least three types of these structures that are likely involved in various stages of colonizing the intestine. So far one of these, termed TCP for toxin coregulated pilus, has been shown to be essential for colonization and virulence in humans and in an infant mouse model. The major pilin subunit, TcpA, is a member of the type 4 pilin class, common to a number of diverse pathogenic bacteria. To understand how these pili function at the molecular level, a transposon mutagenesis was undertaken which identified at least a dozen genes involved in TCP biogenesis, function, and regulation. Despite this complexity, passive immunization of infant mice using polyclonal and monoclonal antibodies directed against TCP suggests that the adhesive moiety lies within the major pilin subunit itself, rather than as a minor pilus adhesin protein as in the case of the PAP and type 1 fimbriae of Escherichia coli. Pilin or peptides corresponding to the epitopes recognized by the monoclonal antibodies represent possible immunogens for improved cholera vaccines.

Animals↗

PubMed2001

Biochemical analysis of total collagen content and collagen types I, III, IV, V and VI in gingiva of various periodontitis categories.

Collagen is one of the chief components of the extracellular matrix of gingival connective tissue, where five different types have been identified to date. The molecular mechanism of collagen loss in periodontitis still needs to be explored. In the present study total collagen content was investigated in gingival connective tissue of adult periodontitis (AP) as well as early onset periodontitis patients (EOP) and clinically healthy subjects. Furthermore, collagen type I, III, IV, V andVI content was evaluated in gingival biopsies obtained from periodontitis patients. There was a statistically significant difference between AP (25.1 +/- 8.1 microg/mg) and EOP (15.6 +/- 4.0microg/mg) groups with regard to the total collagen content (P < 0.05). In the clinically healthy control group the total collagen content was 20.7 +/- 4.6microg/mg. Moreover, the distribution of collagen types exhibited variations in pooled homogenates of each periodontitis group. The total collagen loss seemed to be greater in the EOP patients than in the AP patients. When the ratio of fibril forming collagens to nonfibrillar collagens was evaluated, it seems to be decreased in AP patients in comparison to EOP patients. The findings of the present study suggest that different collagen types present in various periodontitis categories may be related with diverse pathogenic mechanisms acting in these diseases.

Adolescent↗

PubMed2003

[Ectopic tooth in the nasal cavity].

The eruption of a canine tooth into the nasal cavity constitutes one topographic form of dental ectopy. We report a case and discuss the diagnostic aspects and diverse pathogenic theories proposed. This unusual situation should be suspected in patients with nasal obstruction and unilateral fetid purulent rhinorrhea.

Cuspid↗

PubMed1992

Regulatory role of heat shock protein-specific T cells in host defense.

During infection with L.monocytogenes, a facultative intracellular bacteria, TcR gamma/delta T cells specific for 65 kd hsp precede TcR alpha/beta T cells specific for the listerial antigens in appearance. The gamma/delta T cells provide a first line of defense against the infection by recognizing exogenous and endogenous 65 kd hsp on infected cells and producing cytokines such as gamma IFN. The hsp-specific T cells respond quickly to antigenically diverse pathogens before antigen-specific T cells expand clonally, and they play a role in covering the gap between the phagocytic system and highly evolved immune response. 65 kd hsp-specific T cells play important roles not only in host defense mechanism against infection with various pathogens but also in induction of auto-immune disease. Both 65 kd hsp-specific gamma delta T cells and 65 kd hsp-specific alpha beta T cells abrogate the unresponsiveness of the self-reactive alpha beta T cells and/or B cells by producing IL-2 and contribute to induction of autoimmune disease.

Animals↗

PubMed2004

[Epidural spinal cord stimulation for interstitial cystitis].

INTRODUCTION: Interstitial cystitis, a chronic inflammatory disorder of the bladder wall, is highly painful and incapacitating. Urinary frequency and urgency develop, as well as nocturia, dysuria, perineal pain and reduction of bladder capacity. The condition seems to arise from a variety of factors with multiple and diverse pathogenic mechanisms and is refractory to medical and surgical treatment. Because treatments are ineffective and recent studies have implicated an inflammatory neurogenic mechanism in the pathogenesis of interstitial cystitis, neuromodulation by epidural spinal cord stimulation has been suggested for treating patients in whom other measures have failed. CASE DESCRIPTION: A 66-year-old woman with a 9-year history of urinary incontinence, urinary urgency and suprapubic pain was diagnosed of interstitial cystitis. She was referred to our pain clinic with persistent symptoms after repeated attempts to treat the condition medically. After implantation of a cephalocaudal (retrograde) epidural spinal cord stimulator, pain decreased 80% and the improvement has been maintained with no complications. CONCLUSION: Results from this and previous reports allow us to state that retrograde epidural spinal cord stimulation seems to be a relatively non-invasive therapeutic approach for treating interstitial cystitis that is refractory to conventional treatments.

Aged↗

PubMedDate not supplied

[Spinal cord ischemia after thoracic and thoracoabdominal aortic aneurysm repair].

In this paper, the author reviews the problematic around the spinal cord ischemic disfunction that sometimes occurs following the surgical management of thoracic and thoracoabdominal aortic aneurysm. After an anatomical review of the spinal cord vascularization, the diverse pathogenic mechanisms involved are described together with its importance and clinical significance, as well as the multiple procedures, techniques and pharmacotherapy employed nowadays aimed at lowering the occurrence of this most dramatic complication of thoracic and thoracoabdominal aortic aneurysm repair.

Aortic Aneurysm, Abdominal↗

PubMed1992

Systemic lupus erythematosus with central nervous system involvement.

Real or suspected brain involvement occurs in the majority of patients with systemic lupus erythematosus. The clinical manifestations are myriad and are accounted for by diverse pathogenic mechanisms. Purely psychological disturbances and psychiatric syndromes with organic components account for the majority of cases. Metabolic disturbances, drug effects, and infections may masquerade for immune-related brain dysfunction. In the absence of reliable and specific indicators of lupus brain activity, successful management requires the combined skills and clinical judgment of the rheumatologist, neurologist, and psychiatrist.

Brain Diseases↗

PubMed2005

[Molecular analysis of telomere length in follicular lymphomas. Its participation in tumor progression].

Telomeres are essential for maintaining chromosomal integrity and stability. We studied here telomere length (TL) in bone marrow and/or lymph node from 36 patients: 29 with follicular lymphoma (FL) at diagnosis and 7 with diffuse large B cell lymphoma secondary to FL (S-DLBCL). TL was evaluated using terminal restriction fragments (TRF) assay. BCL-2 gene rearrangement was analyzed by nested and long distance PCR. Mean TRF values showed significant telomere shortening in FL (4.18 +/- 0.18 Kb) and S-DLBCL (3.31 +/- 0.25 Kb) respect to controls (8.50 +/- 0.50 Kb) (p<0.001). Differences between both histological subtypes (p=0.036) were also detected. Moreover, the samples positive for BCL-2 rearrangements showed longer TL (4.25 +/- 0.19 Kb) than the negative ones (3.39 +/- 0.30 Kb) (p=0.023). A trend to telomere shortening was observed when Major Breakpoint Region (MBR-JH), minor cluster region (mcr-JH) and BCL-2 negative patients were compared (4.35 +/- 0.21 Kb; 3.84 +/- 0.45 Kb and 3.39 +/- 0.30 Kb, respectively). Our results show a TL reduction in FL and S-DLBCL, with significant short TRFs in the last group, suggesting the participation of telomere shortening in tumor progression. Furthermore, the differences detected between BCL-2 positive and negative FL support the involvement of diverse pathogenic mechanisms.

Adult↗

PubMed2005

[Recombination within the human leucocyte antigen].

Understanding with greater clearness the characteristics of recombination within the human leucocyte antigen(HLA) is of deep significance to gaining an insight into the evolutionary process of shaping HLA allelic diversity and ultimately the human resistance against diverse pathogens. Family studies and statistical analysis of recombination have provided estimations of recombination fractions across the major histocompatibility complex and have identified the potential recombination hotspots. Other characteristics such as haplotype specificity and sequence motifs have been intensively studied. The recombination fractions, hotspots and other characters are reviewed in this paper.

Gene Frequency↗

PubMed2005

Phenotypic & genotypic conservation of ompL1 & lipL41 among leptospiral isolates of Andaman Islands.

BACKGROUND & OBJECTIVES: The leptospiral antigens that are conserved among the diverse pathogenic leptospires have potential importance in the development of new serodiagnostic and immunoprotective strategies. The present study was therefore carried out to find out the phenotypic conservation of the leptospiral proteins OmpL1 and LipL41, and the genetic conservation of ompL1 and lipL41 genes among the leptospiral isolates of Andaman Islands and among the reference strains. METHODS: In one dimensional SDS-PAGE the leptospiral samples prepared from strains of various leptospiral serovars were run and transferred on to nitrocellulose paper and probed with pooled convalescent phase human sera to find out the phenotypic conservation of the protein fragments at 31 and 41 kDa. Further, the proteins were indirectly confirmed as OmpL1 and LipL41 by using specific rabbit hyperimmune sera. Specific primers were utilized to amplify the fragments to study the genetic conservation of ompL1 and lipL41. Further, these two fragments were sequenced and BLAST analysis was done with the whole genome of Leptospira interrogans serovar Lai for comparison. RESULTS: Analysis of individual immunoblots using patient sera showed that the OmpL1 and LipL41 were conserved among all the isolates used in the study. Further, these two proteins were probed with specific rabbit hyperimmune sera of OmpL1 and LipL41 for confirming the fragments and it was found to be conserved among all the isolates. The PCR based amplification further showed that the genes ompL1 and lipL41 were conserved among the leptospiral isolates studied. Sequencing followed by BLAST analysis of these showed 97 per cent similarity with the whole genome sequence and low score values in comparison with other bacterial species. INTERPRETATION & CONCLUSION: The antigenic and genetic conservation of the two proteins, OmpL1 and LipL41, indicated that these could be potential candidates for development of diagnostic test systems for leptospirosis.

Animals↗