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PubMed2004

Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice.

Amino acid residues 111-129 represent an immunodominant epitope of myelin basic protein (MBP) in humans with human leukocyte antigen (HLA)-DRB1*0401 allele(s). The MBP 111-129-specific T cell clone MS2-3C8 was repeatedly isolated from a patient with multiple sclerosis (MS), suggesting an involvement of MS2-3C8 T cells in the pathogenesis. To address the pathogenic potential of the MS2-3C8 T cell clone, we generated transgenic (Tg) mice expressing its T cell receptor and restriction element, HLA-DRB1*0401, to examine the pathogenic characteristics of MS2-3C8 Tg T cells by adoptive transfer into HLA-DRB1*0401 Tg mice. In addition to the ascending paralysis typical of experimental autoimmune encephalomyelitis, mice displayed dysphagia due to restriction in jaw and tongue movements and abnormal gait. In accordance with the clinical phenotype, infiltrates of MS2-3C8 Tg T cells and inflammatory lesions were predominantly located in the brainstem and the cranial nerve roots in addition to the spinal cord and spinal nerve roots. Together, these data suggest a pathogenic role of MBP-specific T cells in inflammatory demyelination within the brainstem and cranial nerve roots during the progression of MS. This notion may help to explain the clinical and pathological heterogeneity of MS.

Amino Acid Sequence↗
PubMed2005

Microbiology and antimicrobial management of sinusitis.

Sinusitis generally develops as a complication of viral or allergic inflammation of the upper respiratory tract. The bacterial pathogens in acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, while anaerobic bacteria and Staphylococcus aureus are predominant in chronic sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in immunocompromised patients and in those who have nasal tubes or catheters, or are intubated. Many of these organisms recovered from sinusitis became resistant to penicillins either through the production of beta-lactamase (H. influenzae, M. catarrhalis, S. aureus, Fusobacterium spp., and Prevotella spp) or through changes in the penicillin-binding protein (S. pneumoniae). The pathogenicity of beta-lactamase-producing bacteria is expressed directly through their ability to cause infections, and indirectly through the production of betalactamase. The indirect pathogenicity is conveyed not only by surviving penicillin therapy, but also by 'shielding' penicillin-susceptible pathogens from the drug. The direct and indirect virulent characteristics of these bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. The antimicrobials that are the most effective in management of acute sinusitis are amoxycillin-clavulanate (given in a high dose), the newer quinolones (gatifloxacin, moxifloxacin) and the second generation cephalosporins (cefuroxime, cefpodoxime, cefprozil or cefdinir). The antimicrobials that are the most effective in management of chronic sinusitis are amoxycillinclavulanate, clindamycin and the combination of metronidazole and a penicillin.

Acute Disease↗
PubMed1999

Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances.

STUDY OBJECTIVE: To compare the time above the minimum inhibitory concentration (T>MIC) for five parenteral beta-lactam antibiotics against common nosocomial bacterial pathogens at different creatinine clearances (Clcr). INTERVENTIONS: Serum concentration-time profiles were simulated for cefepime, ceftazidime, piperacillin, piperacillin-tazobactam, and imipenem at Clcr ranging from 120-30 ml/minute. The MIC data for 90% of organisms (MIC90) were collected for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus, and a weighted geometric mean MIC90 was calculated. The T>MIC was calculated as percentage of the dosing interval in which free concentrations exceeded the weighted geometric mean MIC90. A T>MIC of 70% or greater was considered desirable for all organisms except S. aureus (> or = 50%). MEASUREMENTS AND MAIN RESULTS: Cefepime 2 g every 12 hours (Clcr > or = 70 ml/min) and every 24 hours (Clcr < or = 60 ml/min) achieved desirable T>MIC for all Enterobacteriaceae and S. aureus at every Clcr. Imipenem 0.5 g achieved desirable T>MIC for E. coli, K. pneumoniae, C. freundii, and S. aureus at every Clcr. However, imipenem T>MIC was less than 70% for the following regimens and organisms: S. marcescens 0.5 g every 6 hours (Clcr > or = 90 ml/min), E. aerogenes 0.5 g every 6 hours (Clcr > or = 80 ml/min), E. cloacae 0.5 g every 6 hours (Clcr > or = 100 ml/min), S. marcescens 0.5 g every 8 hours (Clcr 60-70 ml/min), E. cloacae 0.5 g every 8 hours (Clcr 60-70 ml/min), and E. aerogenes 0.5 g every 8 hours (Clcr 50-70 ml/min). Ceftazidime 2 g every 8 hours (Clcr 60-100 ml/min) and every 12 hours (Clcr 40-50 ml/min) achieved desirable T>MIC for E. coli, K. pneumoniae, S. marcescens, and S. aureus only. At every dose and Clcr, piperacillintazobactam achieved desirable T>MIC for S. aureus but not for any Enterobacteriaceae at Clcr > 50 ml/minute. Piperacillin did not achieve desirable T>MIC for any organism, and none of the beta-lactams attained a T>MIC of 70% or above for P. aeruginosa at any Clcr. CONCLUSION: At every Clcr, cefepime achieved a desirable T>MIC for more nosocomial pathogens than any other beta-lactam evaluated. Based on pharmacodynamic data, cefepime is an appropriate empiric choice for treatment of nosocomial infections. However, when P. aeruginosa is a potential pathogen, empiric combination therapy should be considered.

Anti-Bacterial Agents↗
PubMedDate not supplied

Kawasaki disease: update on diagnosis, treatment, and a still controversial etiology.

Diagnosis of Kawasaki syndrome still relies solely on clinical criteria because the etiology is unknown. However, the function and structure of different bacterial superantigens as potential pathogens are discussed. In this regard, the recent determination of the crystal structure of the toxic shock syndrome toxin-1 superantigen complexed with major histocompatibility complex class II suggests potential implications for the controversial findings concerning a role of those superantigens in Kawasaki disease. Although a specific therapy is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin therapy combined with oral aspirin.

Child↗
PubMed1978

Coxsackievirus B cardiopathy and angiopathy in the hypercholesterolemic host.

Studies on the pathogenic potential of the human cardiotropic enterovirus, coxsackievirus B5, show that this agent localizes and replicates in the aorta of mice. Nutritionally-induced hypercholesterolemia leads to an increased replication and persistence of virus in tissues, specifically the aorta. Coxsackievirus B cardiopathy is markedly augmented in the hypercholesterolemic host, resulting in a persistent cardiomyolysis which is not evident in virus-infected animals with normal cholesterol levels. Pathological changes in the aorta become evident only months after the acute infection, and only in hypercholesterolemic animals previously infected with coxsackievirus B5. Our findings of coxsackievirus B-induced angiopathy and cardiopathy in the hypercholesterolemic host extend the known pathogenic range of these human viruses, and further emphasizes their potential as etiological agents of cardiovascular disease.

Animals↗
PubMed1990

Challenge studies in volunteers using Escherichia coli strains with diffuse adherence to HEp-2 cells.

Diffusely adherent (DA) Escherichia coli, a newly described category, has been associated with diarrhea in children in some but not all epidemiologic studies. To investigate its diarrheagenic potential, two strains of DA E. coli were fed to adult volunteers in doses of 10(5)-10(10) colony-forming units. None of 22 volunteers who received strain 57-1 or of 21 who received strain C1845 developed symptoms of diarrhea as defined for this study. All volunteers shed the challenge DA E. coli in their stools. Duodenal string cultures were positive in some volunteers only at the highest doses. Only 6 developed IgG or IgA antibodies to whole DA E. coli. Thus, the pathogenic potential of DA E. coli could not be shown in this model. Further studies are needed to characterize potential virulence factors of DA E. coli that might distinguish a pathogenic subset.

Adult↗
PubMed1995

Antibiotic susceptibility of the sputum pathogens and throat swab pathogens isolated from the patients undergoing treatment in twenty-one private clinics in Japan.

Bacteriology of the respiratory isolates from 2,539 patients with respiratory infections in 21 primary care clinics was documented. Of a total of 1,887 strains of potential pathogens recovered from 1,507 patients, 996 were gram-positive and 891 were gram-negative. Major pathogens were Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. The MIC's against microbial isolates of six antimicrobial agents were determined. Ciprofloxacin and ofloxacin were more active against S. aureus, Moraxella catarrhalis and Pseudomonas aeruginosa, and ampicillin and cefteram were more active against S. pnuemoniae and S. pyogenes than four other antimicrobials tested, respectively, in this experiment. New quinolones and new generation cephems were active against H. influenzae and Enterobacteriaceae. Only one strain of S. aureus was methicillin-resistant. As regards other pathogens, 6.5% of S. pneumoniae and 14.9% of H. influenzae were resistant to ampicillin, and 26.7% of H. influenzae were beta-lactamase-positive. MRSA was found infrequently. But ampicillin-resistant S. pneumoniae and H. influenzae were found in primary care clinics almost as frequently as in intensive-medication-oriented clinics.

Adolescent↗
PubMed1988

Pathogenic bacteria and fungi associated with external ocular diseases in dogs: 131 cases (1981-1986).

Medical records of 131 dogs with external ocular diseases were reviewed. Bacteriologic culture of swab specimens from 151 eyes revealed 100 eyes (66.2%) were considered positive for potentially pathogenic microorganisms. Of 127 species of microorganisms (bacterial and fungal) isolated, 50 (39.3%) were Staphylococcus spp (S intermedius, 17.3%). Streptococcus spp were the next most frequently isolated organism at 32 (25.2%), (Str canis, 16.5%). beta-Hemolytic streptococci (17%) were isolated more frequently than were alpha-hemolytic streptococci (9%), and coagulase-positive staphylococcal species (29%) were isolated almost 3 times as often as were coagulase-negative species (11%). Fungal and yeast organisms were isolated from 4.6% of the eyes. In vitro, most Staphylococcus spp were susceptible to cephalothin, bacitracin, and gentamicin, whereas most Streptococcus spp were susceptible to chloramphenicol, erythromycin, carbenicillin, and cephalothin. Pseudomonas spp were sensitive to tobramycin, gentamicin, and amikacin.

Animals↗
PubMed2002

Hereditary non-polyposis colorectal cancer (HNPCC): phenotype-genotype correlation between patients with and without identified mutation.

Affected members of hereditary non-polyposis colorectal cancer (HNPCC) families develop colorectal cancer at an early age (mean 45 yr) and frequently get extracolonic cancers particularly in the uterus, urinary tract, and small intestine. They have a high risk of developing more than one primary colorectal cancer if not treated with subtotal colectomy at first operation and have more frequent right-sided colon cancers and less frequent rectum cancers, compared to patients with sporadic colorectal cancer. We have screened 31 families fulfilling the Amsterdam criteria and 54 families with a colorectal cancer clustering but not fulfilling the Amsterdam criteria for mutations in MLH1 and MSH2 by direct sequencing, and detected a mutation in 61% of the Amsterdam positive families but only in 15% of the Amsterdam negative families. Genotype-phenotype correlation was compared between 141 affected individuals with an identified mutation and 78 affected individuals from Amsterdam positive families in which a mutation was not identifiable in MLH1 or MSH2. In the affected persons with identified mutations, all expected phenotypic traits were represented, whereas affected persons in whom no mutation was detected fell into two clearly distinguishable subgroups. The minor subgroup, in which no mutation was identified, generally had the same characteristics as found in affected persons with identified mutations. The major subgroup differed significantly in clinical features and exhibited phenotypic traits similar to those found in late-onset families, including abundance of rectal cancer, few HNPCC-related cancers, lower frequency of multiple colorectal cancers, and later age at onset. Finally, for six missense mutations and one single codon deletion, the pathogenic potential was evaluated by domain localization, lod score calculation or segregation analysis when possible, and mutation-induced biochemical change. The results indicate that the majority of missense mutations are pathogenic, although further characterization by functional assays is necessary before implementation in predictive testing programs.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Differential effects of cyclosporins A and G on functional activation of a T-helper-lymphocyte line mediating experimental autoimmune uveoretinitis.

The effect and relative efficiency of cyclosporin A (CsA) and cyclosporin G (CsG) on suppressing the activation of primed autoimmune rat T-helper lymphocytes were assayed. The autoimmune T-helper cells (ThS) are a long-term line specific to the retinal soluble antigen (SAg) and can adoptively transfer experimental autoimmune uveoretinitis (EAU), after in vitro reactivation with antigen or mitogen, to naive syngeneic hosts. Antigen-driven production of interleukin-2 (IL-2) and antigen-driven proliferation were inhibited in a dose-dependent manner and to a similar extent at each of the respective cyclosporin concentrations. CsA was 8-10 times more potent than CsG, with ID50-CsA occurring at 0.5 to 2 ng/ml, and ID50-CsG at 5 to 20 ng/ml, depending on the experiment and the cyclosporin batch. Addition of exogenous lymphokines in the form of rat spleen concanavalin A (Con A)-conditioned medium (SCM) or recombinant IL-2 (but not recombinant IL-1) was able to reverse only about half of the inhibition, as measured along the linear part of the dose-response curve. Inhibition of IL-2 production was lost if a maximally inhibitory dose of cyclosporin was added to the cultures later than 8 hr after antigen stimulation, while proliferation was still suppressed to 50% by cyclosporin added as late as 12 hr and could not be restored by addition of SCM. Both cyclosporins at concentrations that blocked proliferation and IL-2 production significantly suppressed the generation of high-affinity and low-affinity IL-2 receptors by ThS in response to antigen (as assayed by direct binding of 125I-IL-2). These results suggest that CsA and CsG inhibit antigen-induced expansion of ThS by interfering with more than one activation step. In contrast, the in vitro activation of the uveitogenic potential of ThS cells, incubated with antigen in the presence of CsA or CsG and adoptively transferred into untreated recipients, was not affected by the cyclosporins. Thus, triggering of the pathogenic potential of primed autoimmune T-helper lymphocytes can take place in the presence of cyclosporin and in the absence of cellular proliferation.

Animals↗
PubMed1991

Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital.

Seventy-four children ages 1 to 9 years hospitalized because of severe pneumonia were investigated using blood cultures, lung aspirates, nasopharyngeal aspirates, serology and antigen detection procedures. A bacterial infection was identified in 57 (77%), a viral infection was seen in 25 (34%) and 18 (24%) had mixed viral-bacterial infections. The bacterial pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae found in 61 and 15% of patients, respectively. The viral pathogen most frequently recovered was respiratory syncytial virus (12%). Evidence of Chlamydia pneumoniae strain TWAR and Mycoplasma pneumoniae infection was found in 12 and 4% of cases, respectively. Overall a potential pathogen was identified in 60 (81%) children, with evidence of polymicrobial infection in 30 cases (40.5%). The study provides information on the relative role of different infectious agents in the etiology of severe pneumonia in children in a developing country.

Acute Disease↗
PubMed2001

Impact of Helicobacter pylori virulence on the outcome of gastroduodenal diseases: lessons from the microbiologist.

Two main pathogenic factors have been described in Helicobacter pylori strains: the cag pathogenicity island (cag PAI) and the vacuolating cytotoxin VacA. The cag PAI is comprised of approximately 40 open reading frames probably originating from another species. It encodes a type IV secretion system, i.e., an apparatus derived from pili which may contribute to the transfer of bacterial molecules to epithelial cells. One of the most well known is the CagA protein which is involved in cell actin rearrangement. Another important property is the induction of interleukin 8, a proinflammatory mediator, which is the consequence of other cag PAI genes. VacA has also been the subject of numerous studies. In vitro, it leads to vacuoles in epithelial cells from the late endosome compartment. However, its main impact could be to induce apoptosis by acting on mitochondria, as was shown in a recent study. The presence of cag PAI as well as VacA has been associated with a higher pathogenic potential of H. pylori strains. Indeed, both are often found simultaneously, but it may well be that the combination of the two, with specific adherence properties, increases even more the pathogenicity of the strains.

Antigens, Bacterial↗
PubMed1980

Epidemiology of infection by nontuberculous mycobacteria. I. Geographic distribution in the eastern United States.

The nontuberculous mycobacterial group Mycobacterium avium-M. intracellular-M. scrofulaceum (MAIS) was isolated from 33% of the water samples collected from various aquatic environments in the southeastern United States. By contrast, only 20% of the water samples collected in the northeastern United States (New Jersey northward) yielded MAIS organisms. The most frequent recovery of MAIS organisms (37%) was from water samples with salinities from 0.1 to 1.9 g% (grams of NaCl/100 ml of sample). Other saprophytic slow- and rapid-growing nontuberculous mycobacteria were also isolated. The fewer MAIS organisms recovered from marine waters (20%) relative to those from freshwaters (37%) suggested that ocean water may not be a primary origin of these pathogens, although it still may be a source of infection. Our data implied a positive correlation between the frequency of persons reacting to MAIS antigens and the presence of these potential pathogens in the coastal region of the eastern United States.

Humans↗
PubMedDate not supplied

Extracellular proteases of Staphylococcus spp.

Bacterial proteases secreted into an infected host may exhibit a wide range of pathogenic potentials. Staphylococci, in particular Staphylococcus aureus, are known to produce several extracellular proteases, including serine-, cysteine- and metalloenzymes. Their insensitivity to most human plasma protease inhibitors and, even more, the ability to inactivate some of these make the proteases potentially harmful. Indeed, several recent studies have shown that staphylococcal proteases are able to interact with the host defense mechanisms and tissue components as well as to modify other pathogen-derived virulence factors. A tight, cell density-dependent control of proteolytic activity expression, similar to that of the well-defined virulence determinants, further suggests the role of staphylococcal proteases in the infection process. Consistently, alterations in coordinated expression of extracellular proteins markedly diminished the virulence. However, despite these data and the fact that a strain deficient in sspABC operon coding for serine (sspA) and cysteine (sspB) proteases was highly attenuated in virulence in the animal infection model, it was impossible to unambiguously demonstrate the importance of any particular protease as a virulence factor. Therefore, it can be assumed that the orchestrated expression and interaction of a variety of extracellular and cell surface proteins rather than any particular one is responsible for the staphylococcal pathogenicity and that the proteases apparently play an important role in this complex process. Such redundant mechanism is very well suited for promoting the survival of staphylococci under diverse environmental conditions encountered in the infected host.

Animals↗
PubMedDate not supplied

The relationship of absorption characteristics and gastrointestinal side effects of oral antimicrobial agents.

Normal bowel flora play an important role in preserving gastrointestinal (GI) function. They inhibit colonization by pathogenic bacteria, help in the metabolism of by-products of drugs and endogenous substances, aid in the synthesis of vitamins, and stimulate nonspecific host immune systems that protect against potential pathogens. Antimicrobial agents that are poorly absorbed from the GI tract can substantially alter the bowel flora. Narrow-spectrum antimicrobial agents are less likely to disrupt the bowel flora than broad-spectrum agents. Drugs that undergo extensive enterohepatic circulation can also disrupt normal flora. Knowledge of the extent of GI absorption, bile excretion, and spectrum of activity allows prediction of the likelihood of GI side effects. For example, clindamycin, which is relatively poorly absorbed and has significant bile secretion, is associated with a high incidence of diarrhea. The use of an antibiotic with a relatively narrow spectrum, excellent GI absorption, and minimal bile excretion should reduce the incidence of GI side effects.

Administration, Oral↗
PubMed1990

[Bronchopulmonary infection due to Branhamella catarrhalis in patients with obstructive lung disease].

During the period from February 1988 to April 1990, 214 sputum samples from COPD patients with bronchopulmonary infection were quantitatively cultured. 17 strains were identified as Branhamella catarrhalis, being present in 7.9% of all sputum cultures and 11.0% of those positive for a pathogen (Quantity = 10(10)/L of Isolated Organism). Half of B. catarrhalis infection was isolated in mixed with other pathogens. Haemophilus influenza was the most frequently associated pathogen. The second was H. influenza plus Streptococcus pneumoniae. Of 17 B. catarrhalis, 2 strains were positive for beta-lactamase. The incidence of B. catarrhalis infection varied with the seasons, being prevalent in late winter and early spring. Many factors contributed to the pathogenicity of B. catarrhalis, such as the rapid increase of positive beta-lactamase strains and the change of seasons. The result showed that B. catarrhalis was the fourth frequent pathogen in COPD patients accompanied with bronchopulmonary infection. Most of the strains were resistant to penicillin, and beta-lactamase strains were discovered. Therefore, B. catarrhalis should be as a potential pathogen to be identified in sputum. A suitable method was recommended to identified B. catarrhalis.

Aged↗
PubMed1995

[Viruses of parasitic protozoa].

The authors present the actual review on several publications concerning the molecular characterizations of the viruses found in parasitic protozoa such as Giardia, Trichomonas, Leishmania and Entamoeba histolytica. All of the RNA viruses observed in parasitic protozoa showed several similarities and did not considerably differ from the viruses found in simple eukaryotic cells; they closely correspond to dsRNA viruses of yeast. The supposition that the protozoan symbionts detected in laboratories transfer to their hosts in natural conditions seemed to be rational, though, there are no evidences that these symbionts are potential pathogens. However, the opinion reiterates that intestinal protozoa (e.g. Entamoeba histolytica) may serve as vectors for HIV or cofactors of HIV infection. The authors point out that irrespective of the potential role of viruses as vectors in the transfection system for parasitic protozoa, the observed viral system constitutes an unusual experimental system to solve the problems of gene expression.

Animals↗
PubMed2003

Functionality of enterococci in meat products.

The presence of enterococci in meat fermentation is a constant as reported in the literature. Despite the concern about pathogenicity of enterococci, recent studies point out that food and meat enterococci, especially Enterococcus faecium have a much lower pathogenicity potential than clinical strains. Enterococci possess a competitive advantage over other microbiota in meat fermentations, and many enterococci isolated from sausages have the ability to produce enterocins harbouring antimicrobial activity against pathogens and spoilage microorganisms of meat concern. The application of enterocins producing enterococci or their purified metabolites, as extra hurdles for preservation in sausage fermentation and in sliced-vacuum packed cooked meat products can be beneficial, preventing the outgrowth of Listeria monocytogenes and slime-producing lactic acid bacteria. Enterocins and bacteriocinogenic enterococci hold considerable promise as alternatives to traditional chemical preservatives and they could be exploited for the control of emergent pathogens in meat products. Their inhibitory effect can be increased when used in conjunction with particular physical and chemical processes, but current regulation is hampering the application of purified bacteriocins.

Bacteriocins↗