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PubMed1998

Small intestine pathogens in AIDS: conventional and opportunistic.

The small intestine, coming in direct contact with ingested potential pathogens, depends on active mucosal immunity to withstand invasion and damage. In patients with AIDS and severe impairment of immunoregulatory lymphocytes, proliferation of protozoal, viral, bacterial, and fungal pathogens produces diarrhea and malabsorption. When noninvasive tests of stool and blood fail to identify responsible organisms, endoscopy can reveal mucosal lesions which are suggestive if not diagnostic. Cryptosporidium, cf2E. intestinalis, cf1CMV, MAC, and other infections can be identified by intestinal biopsy quicker and often at lower overall cost than they can be by culture.

AIDS-Related Opportunistic Infections↗

PubMed2003

Oral microbial heat-shock proteins and their potential contributions to infections.

The oral cavity is a complex ecosystem in which several hundred microbial species normally cohabit harmoniously. However, under certain special conditions, the growth of some micro-organisms with a pathogenic potential is promoted, leading to infections such as dental caries, periodontal disease, and stomatitis. The physiology and pathogenic properties of micro-organisms are influenced by modifications in environmental conditions that lead to the synthesis of specific proteins known as the heat-shock proteins (HSPs). HSPs are families of highly conserved proteins whose main role is to allow micro-organisms to survive under stress conditions. HSPs act as molecular chaperones in the assembly and folding of proteins, and as proteases when damaged or toxic proteins have to be degraded. Several pathological functions have been associated with these proteins. Many HSPs of oral micro-organisms, particularly periodontopathogens, have been identified, and some of their properties-including location, cytotoxicity, and amino acid sequence homology with other HSPs-have been reported. Since these proteins are immunodominant antigens in many human pathogens, studies have recently focused on the potential contributions of HSPs to oral diseases. The cytotoxicity of some bacterial HSPs may contribute to tissue destruction, whereas the presence of common epitopes in host proteins and microbial HSPs may lead to autoimmune responses. Here, we review the current knowledge regarding HSPs produced by oral micro-organisms and discuss their possible contributions to the pathogenesis of oral infections.

Adaptation, Physiological↗

PubMed1992

Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex.

Utilizing a recombinant vaccinia expression system, we investigated the biological properties and CD4 receptor interactions of the envelope glycoproteins of a noncytopathic human immunodeficiency virus type 2 strain, termed HIV-2/ST, and a highly cytopathic variant derived from it. The efficiency and host cell range of syncytium formation by the recombinant glycoproteins of both viruses were highly restricted compared to those of prototypic strains of HIV (HIV-2/ROD or HIV-1/IIIB). However, the glycoprotein of cytopathic but not wild-type ST generated numerous large syncytia in the human T-cell line Sup T1 from which it was derived. A single cell line (Molt 4 clone 8) was permissive to fusion by both wild-type and cytopathic ST envelopes, but only the glycoprotein of cytopathic ST could be inhibited with a soluble form of the viral receptor CD4 (sCD4). While these results indicated major differences in the envelope glycoprotein-CD4 receptor interactions of wild-type versus cytopathic ST, direct and competition binding assays utilizing soluble external glycoprotein (SU) and sCD4 surprisingly revealed equivalent low binding affinity for both viruses. From these experiments we conclude that relevant biological properties (e.g., CD4 binding, cytopathic potential, and sCD4 neutralization) of HIV viruses which differ in their pathogenic potential are reflected in the sCD4 interactions of the assembled native envelope complex (as on cell or virion surfaces) but not the soluble SU glycoprotein.

CD4 Antigens↗

PubMed2001

Ecological effects on the oro- and nasopharyngeal microflora in children after treatment of acute otitis media with cefuroxime axetil or amoxycillin-clavulanate as suspensions.

OBJECTIVE: To evaluate if the extent of normal microflora disturbances differed between treatment with amoxycillin-clavulanate administered in an active form and cefuroxime axetil administered as an inactive prodrug. METHODS: Twenty-eight children, 0.5-5 years old, diagnosed with acute otitis media (AOM), were treated with either amoxycillin-clavulanate (13.3 mg/kg 3 times daily) or cefuroxime axetil (15 mg/kg twice daily) for 7 days. Saliva samples and nasopharyngeal swabs were collected before, directly after and 2 weeks after treatment. The saliva samples were quantitatively and qualitatively analyzed and the nasopharyngeal swabs were qualitatively analyzed. All isolated strains were tested for beta-lactamase production. RESULTS: Both treatment regimens gave rise to similar alterations of the normal oropharyngeal microflora. In both groups, the amount of Streptococcus salivarius was significantly reduced (P < 0.05). The most common causative pathogens of acute otitis were S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. On the day of enrollment, approximately half of the patients, in both groups, were infected with more than one pathogen. The rate of infection or colonization with more than one potential pathogen was low on day 7 but recurred 2 weeks after treatment to similar levels as on day 0. The total number of patients with reinfection, recolonization or recurrence of pathogens on day 21 was 11/12 in the amoxycillin-clavulanate group and 4/7 in the cefuroxime axetil group. The most common beta-lactamase producer was M. catarrhalis. CONCLUSION: The local high concentration of antibiotics in the oropharynx immediately after intake of antibiotic suspensions seem to have little or no impact on the extent of disturbance of the microflora in this region. Children of this age group seem prone to either reinfection, recolonization or persistence of pathogens within 2 weeks after treatment. Furthermore, co-infection with more than one pathogen seems common in children with AOM and infection with beta-lactamase producing microorganisms occurs frequently.

Acute Disease↗

PubMed1992

Antibacterial therapy for lower respiratory tract infections in adults: a review.

Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for acute community-acquired lower respiratory tract infections remains to be established. Suggested regimens, in the absence of persuasive findings from gram-stained preparations of sputum, are best guesses made on the basis of clinical and epidemiological data. Results from randomized controlled trials are only partially helpful since most trials require the isolation of a potential pathogen, a condition that excludes as many as half of all potential study participants. Nonetheless, initial therapy for patients producing phlegm with abundant polymorphonuclear leukocytes should be chosen on the basis of the predominant organisms seen on a stained sputum smear. Patients who are admitted to the hospital from home, greater than 50 years of age, and not producing phlegm can be safely treated with amoxicillin or a second-generation cephalosporin. Atypical pneumonia in younger patients is best treated with erythromycin or tetracycline. Patients admitted from nursing homes, who frequently fail to respond to an initial treatment course in the absence of a diagnostic sputum sample, should receive empirical therapy with an agent that is also active against aerobic gram-negative rods.

Anti-Infective Agents↗

PubMed1991

[Vibrio alginolyticus and swimmer's otitis externa. 2 cases and review of the literature].

We describe two patients with acute diffuse external otitis (swimmer's otitis) acquired in the Mediterranean shore, with Vibrio alginolyticus recovered from ear fluid. We describe the biochemical profile and sensitivity pattern (MIC) of both strains, comparing it to previously published data. A literature review was also performed, in which we found evidence for increasing concern of V. alginolyticus as an human pathogen. Also there is a need for considering halophilic vibrio as potential pathogens, specially if there is also epidemiologic support.

Adult↗

PubMed1995

[Balanitis and infectious agents. A prospective study of 100 cases].

INTRODUCTION: The aim of this study was: 1) to evaluate the rate of micro-organism isolation in 100 patients consulting for balanitis at the Centre of sexually transmitted diseases at the St. Louis Hospital in Paris in comparison with that of micro-organisms isolated in 60 men without balanitis; 2) to search for a possible correlation between the clinical aspect of the disease and the nature of the infectious agent identified. METHODS: One hundred consecutive patients were included in the study. All underwent a clinical examination and samples were taken for bacteriology, mycology and virology examinations. Sixty healthy volunteers served as controls. Two samples were taken from the balanopreputial groove in search for fungi and bacteria. RESULTS: Candida albicans (CA) was isolated in 33 p. 100 of the patients. A pathogenic bacteria (beta-haemolytic streptococci, Staphylococcus aureus, Klebsiella), or a potentially pathogenic germ (Haemophilus parainfluenzae, anaerobic bacteria, Gardnerella vaginalis, Streptococcus milleri, group HB5) was found without CA in 28 p. 100 of the cases, a commensal flora (enterobacteria, group D streptococci) was found without CA in 8 p. 100 and in 31 p. 100 of the cases non causal agent could be identified. DISCUSSION: This series confirms the non-pathogenic nature of commensal bacteria: the number of isolations was similar in the subjects with and without balanitis (p < 0.9). The role played by the other bacteria in the development of balanitis is discussed: saprophytic association or direct pathogenesis? The significant difference in the rate of bacteria isolations in patients with balanitis compared with controls (p < 0.001) is in favour of a pathogenic role. The clinical presentation was not predictive of the presence of any particular micro-organism excepting the presence of pustules which were highly suggestive of candidiasis.

Adult↗

PubMed2003

Pathogens: raft hijackers.

Throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. At the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. Pathogens have evolved many strategies to ensure their own survival and to evade the host immune system, in some cases by hijacking rafts. However, understanding the means by which pathogens exploit rafts might lead to new therapeutic strategies to prevent or alleviate certain infectious diseases, such as those caused by HIV-1 or Ebola virus.

Animals↗

PubMed1979

Evaluation of industrial yeasts for pathogenicity.

Eleven yeasts representative of species of industrial interest were compared with Candida albicans for their potential pathogenicity for untreated and cortisone-treated mice. Only C. tropicalis produced a progressive infection similar to that produced by C. albicans. Candida lipolytica, Torulopsis spp., and Hansenula polymorpha were not recovered from mice 6 days after inoculation. Kluyveromyces fragilis, C. pseudotropicalis, C. utilis, C. guilliermondii and C. maltosa were recovered from mice but did not produce evidence of infection.

Animals↗

PubMed2003

DNA vaccination against specific pathogenic TCRs reduces proteinuria in active Heymann nephritis by inducing specific autoantibodies.

We have previously identified potential pathogenic T cells within glomeruli that use TCR encoding Vbeta5, Vbeta7, and Vbeta13 in combination with Jbeta2.6 in Heymann nephritis (HN), a rat autoimmune disease model of human membranous nephritis. Vaccination of Lewis rats with naked DNA encoding these pathogenic TCRs significantly protected against HN. Proteinuria was reduced at 6, 8, 10, and 12 wk after immunization with Fx1A (p < 0.001). Glomerular infiltrates of macrophages and CD8(+) T cells (p < 0.005) and glomerular IFN-gamma mRNA expression (p < 0.01) were also significantly decreased. DNA vaccination (DV) causes a loss of clonality of T cells in the HN glomeruli. T lymphocytes with surface binding of Abs were found in DNA vaccinated rats. These CD3(+)/IgG(+) T cells expressed Vbeta5 and Vbeta13 that the DV encoded. Furthermore, FACS shows that these CD3(+)/IgG(+) cells were CD8(+) T cells. Analysis of cytokine mRNA expression showed that IL-10 and IFN-gamma mRNA were not detected in these CD3(+)/IgG(+) T cells. These results suggest that TCR DNA vaccination produces specific autoantibodies bound to the TCRs encoded by the vaccine, resulting in blocking activation of the specific T cells. In this study, we have shown that treatment with TCR-based DV, targeting previously identified pathogenic Vbeta families, protects against HN, and that the mechanism may involve the production of specific anti-TCR Abs.

Animals↗

PubMed2004

Pathogenicity of Helicobacter rodentium in A/JCr and SCID mice.

Helicobacter rodentium was first recognized as a potential pathogen when it was isolated, along with Helicobacter bilis, from a colony of scid/Trp53 knockout mice with diarrhea. Clinical disease in these mice was more severe than that previously reported in mice infected with H. bilis alone, thus suggesting that H. rodentium contributed to the pathogenesis of enteritis. The purpose of the study reported here was to address two questions: is H. rodentium pathogenic in mice, and when co-infection with a pathogenic helicobacter occurs, does H. rodentium augment disease? To this end, A/JCr and C.B-17/IcrCrl-scidBr mice were inoculated with H. rodentium and/or H. hepaticus. Twelve weeks after inoculation, mice were euthanized. The cecum and liver were evaluated microscopically for evidence of disease. Cecal interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), interleukin 10 (IL-10), and interferon gamma (IFN-gamma) mRNA values were measured as an indicator of mucosal immune response. Hepatic lesions were not identified in mice mono-infected with H. rodentium; likewise, cecal lesion scores were not significantly different from those of uninfected controls. With the exception of an increased IL-10 mRNA value in SCID mice, mean immune-related gene expression in H. rodentium mono-infected and uninfected control mice was not significantly different. In contrast, all mice infected with H. hepaticus developed moderate to severe hepatitis, significant increase in cecal lesion scores, and increased immune-related gene expression. The C.B-17/IcrCrl-scidBr mice co-infected with H. hepaticus and H. rodentium had liquid cecal contents and low terminal body weight. Further, compared with mice infected with H. hepaticus alone, co-infection was associated with significant increases of IL-10, MIP-1alpha, and IP-10 mRNA values in C.B-17/IcrCrl-scidBr and IFN-gamma and MIP-1alpha mRNA values in A/JCr mice. These results suggested that H. rodentium alone does not cause hepatitis or enteritis in A/JCr or C.B-17/IcrCrl-scidBr mice; however, co-infection with H. hepaticus and H. rodentium was associated with augmented cecal gene expression and clinical manifestation of disease in immunodeficient mice.

Animals↗

PubMed1987

Growth of pathogenic Candida isolates anaerobically and under elevated concentrations of CO2 in air.

Individual isolates of seven potentially pathogenic yeast species in the genus Candida all grew to some extent in Eagle's minimal essential medium including serum under elevated concentrations of CO2 and in anaerobic gas jars. The C. glabrata and C. tropicalis isolates had the highest anaerobic growth rates and yields, the C. guilliermondii and C. parapsilosis isolates had the lowest, and the C. albicans, C. krusei and C. pseudotropicalis isolates gave intermediate growth rates and yields. The same relative abilities to grow anaerobically were seen when the seven isolates were cultured in liquid and on agar formulations of a peptone-glucose broth and two media containing Yeast Nitrogen Base.

Aerobiosis↗

PubMed1981

Detection of lysozyme production using modified technique as an aid for the identification of pathogenic staphylococci causing some animal and human diseases.

Lysozyme production is an essential character of the potentially pathogenic staphylococci. In the present work 88 strains of animal origin and 40 strains of human origin were tested. Of 103 strains isolated from pathogenic cases of human and animal origin 89 (86.4%) were lysozyme producers and 86 (83.5%) were coagulase positive. Out of 75 strains isolated from pathogenic cases of animal origin 75 (100%) were lysozyme producers and 71 (94.6%) were coagulase positive. On the other hand out of 28 strains isolated from pathogenic human cases 14 (50%) were lysozyme producers and 15 (53.6%) were coagulase positive. This indicates that lysozyme production could be a better index of pathogenic staphylococci than the coagulase measurement specially in cases of animal origin strains. The method used in this work for the determination of the lysozyme production seems to be a simple one if compared with other used methods.

Animals↗

PubMedDate not supplied

Simian retrovirus infections: potential confounding variables in primate toxicology studies.

Various species of nonhuman primates are natural hosts for 6 exogenous retroviruses, including gibbon-ape leukemia virus (GaLV), simian sarcoma virus, simian T-lymphotropic virus (STLV), simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), and simian foamy virus (SFV). These viruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from highly pathogenic to nonpathogenic, depending on various host, virus, and environmental factors. Latent or subclinical infections are common, and various procedures associated with experimental protocols may lead to virus reactivation and disease. Adverse effects on toxicologic research by undetected retroviral infections can occur in several ways, including loss of experimental subjects (and statistical power) due to increased morbidity and mortality. In addition, results may be confounded by virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and responses, and interference with in vitro assays and/or destruction of primary cell cultures. Key clinical and epidemiological features of several important retroviruses are reviewed, with emphasis on viruses infecting species of macaques most commonly used as research subjects in primate toxicology studies. Examples of actual and potential confounding of toxicologic studies by retroviruses are discussed, including altered cytokine profiles in healthy STLV carriers, and clinical and pathological abnormalities induced by SRV infection. Adequate prestudy viral screening is critical to exclude retrovirus-infected primates from toxicologic research protocols and prevent potential confounding of research results.

Animals↗

PubMed2000

Microbes in tree swallow semen.

A frequently hypothesized but poorly studied cost of multiple mating in birds is that exposure to pathogenic sexually transmitted microbes (STM's) can lower reproductive success. Conversely, female birds may benefit from high frequencies of copulation and multiple copulation partners if they receive cloacal inoculations of beneficial STM's that can either protect them against future encounters with pathogens and/or serve as therapy against present infection. We examined the semen of 30 male tree swallows (Tachycineta bicolor) in 1998 to determine the presence and prevalence of potential pathogenic and beneficial STM's. Semen was collected directly from males after applying gentle pressure to the cloaca and we used standard microbiological techniques to identify microbes. We found that 19 of 30 samples contained one or more types of microbes. In these 19 positive samples, we isolated both pathogenic and beneficial microbes from 11, only pathogenic microbes from seven, and only beneficial microbes from one. This variation among males suggests that females would benefit from considering a particular male's potential as a donor of either pathogenic or beneficial STM's as a criterion for mate choice. There were few significant differences between males with pathogen-infected semen and those without pathogens in their semen in measures of size, morphology, and ectoparasite score and feather damage. Likewise, there were few significant differences between males with beneficial Lactobacilli spp. in their semen and those without Lactobacilli spp. in their semen in measures of size, morphology, and ectoparasite score and feather damage. We were unable to determine if there was a relationship between microbe presence and prevalence on reproductive performance.

Animals↗

PubMed2002

Systematic analysis of sequences of anti-DNA antibodies--relevance to theories of origin and pathogenicity.

Sequence analysis of anti-DNA antibodies is important in determining the molecular features which distinguish potentially pathogenic antibodies from those which are less likely to be pathogenic. Previous analysis of murine anti-DNA antibody sequences suggested that particular murine immunoglobulin genes are used preferentially to encode such antibodies and that somatic mutations to arginine, asparagine and lysine may be important in the creation of DNA binding sites. In this paper, a systematic analysis of published human anti-DNA sequences shows no strong evidence for preferential usage of particular human V(H) or V(L) genes in anti-DNA antibodies. Somatic mutations in IgG and IgA antibodies are clustered in the complementarity determining regions (CDRs) due to the effect of antigen drive. This process contributes to an excess of arginine, asparagine and lysine residues in these CDRs, some of which are likely to play an important role in binding to DNA. Computer modeling and in-vitro expression experiments are likely to help define the roles played by these residues in antigen binding and pathogenicity more clearly.

Amino Acid Sequence↗

PubMed1991

[Pneumonia: identification of respiratory pathogens].

The etiological diagnosis of pneumonia is necessary because it will condition therapy. The broad spectrum of potential pathogens is reduced when the host's condition and the events around the pneumonia episode are taken in account. Community acquired pneumonia in an immunocompetent host most often is caused by bacteria (predominantly S. pneumoniae) or by mycoplasma or respiratory viruses. Microbiological diagnosis relies on direct sputum examination and culture (for bacterial agents) and on serology (for nonbacterial agents). In a compromised host, the spectrum of etiological agents is broader; sputum examination often is unrewarding and invasive investigations are necessary. Bronchoscopy with bronchoalveolar lavage is increasingly used, allowing an abundant material to be analyzed with a battery of tests directed against the pathogens most probable in view of the clinical setting. Direct examinations with special stains for bacteria, fungi, parasites, and viruses offer a rapid diagnosis in some cases. Various cultural procedures for bacteria, viruses and fungi, particularly in the absence of previous antimicrobial therapy, will establish the etiological diagnosis in the majority of pneumonia cases and help to select specific therapy.

Bronchoalveolar Lavage Fluid↗

PubMed1986

Studies in sporotrichosis: fungal morphogenesis and pathogenicity in differing environments.

Sporothrix schenckii exhibits different morphology and pathogenic properties according to the source and circumstances of its growth. The present study considers the morphology and experimental pathogenicity in relation to - the 'wild' strains; the possible circumstances enhancing pathogenicity in strains recovered from the soil; the rate and nature of the transformational steps in morphology, in human and experimental infections by established pathogenic strains; the elimination of pathogenic strains to the surface of clinical lesions, enabling a simplified diagnostic proof of infection; the rate and nature of the reversion of pathogenic forms to the 'wild' type when the constraints of the host are lessened; the plasticity of conidium-pigmentation as a sign of pathogenicity; the morphological conversions on moist wattle-wood as occur in the Gold Mines; and a note on the therapeutic value of itraconazole. Host resistance is seen to play a larger part in morphology of the pathogenic phase, and exhaustion of natural food resources as the generator of potentially pathogenic forms.

Animals↗