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Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses nonpathogenic for fowl: nonexculsive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus.

A number of antigenic hybrids of influenza A viruses were produced possessing either the hemagglutinin or the neuraminidase of fowl plague virus and the corresponding antigen derived from another influenza A virus. Other recombinants were obtained carrying both surface antigens of fowl plague virus but differing from the parent in certain biological properties. None of the recombinants isolated were pathogenic for adult chickens. Most recombinants obtained after crosses between reciprocal recombinants carrying both fowl plague virus surface antigens were also apathogenic for chickens. Using the same parent recombinants for double infection some of the progeny "back-recombinants" were pathogenic, whereas others were not. From these results it is concluded that the surface components do not by themselves determine the pathogenicity of influenza A viruses.

Animals

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

[Pneumonia in AIDS: pathogen spectrum and diagnostic value of various fiberoptic bronchoscopy methods for the detection of pathogens].

39 fibre-bronchoscopic examinations were performed prospectively in 29 AIDS-patients with pneumonia. Specimens were obtained from the central bronchial system with a protected brush and by suction, from the infiltrated peripheral area by catheter suction, protected brush, bronchoalveolar lavage (BAL) and transbronchial biopsy in randomized order. In patients with non-bacterial pneumonia, pneumocystis carinii (n = 20) was the most frequent pathogen. In this group BAL had a significantly higher rate of pathogen detection than other techniques. In patients with bacterial pneumonia (n = 10) the pathogens were found in all cases by suction from the central bronchial system. Fibre-bronchoscopy in patients with AIDS and pneumonia should include specimens from the central bronchial system and a bronchoalveolar lavage.

Acquired Immunodeficiency Syndrome

Superiority of the chimpanzee animal model to study the pathogenicity of known Mycoplasma pneumoniae and reputed mycoplasma pathogens.

As far as we know, humans are the only known natural hosts for M. pneumoniae disease. Whereas volunteer studies have provided useful data on the pathogenesis of disease and efficacy of vaccines, experimentally inducing disease in humans raises serious ethical questions and has become increasingly difficult to defend. Thus, there is a genuine need for a satisfactory animal model to study M. pneumoniae disease. Using the cotton rat and developing chick embryo models, Eaton and co-workers (9-13) have clearly shown that the infectious "Eaton agent" was the cause of primary atypical pneumonia. After the causative agent was identified as M. pneumoniae (14), more definite and quantitative studies were possible. The hamster animal model has provided most of our information on the pathogenicity of strains, the pathogenesis of disease and the potency of inactivated vaccines. However, protective data obtained in hamsters immunized with the TS mutant vaccines did not correlate with data obtained in humans, raising concern regarding the use of the hamster animal model to evaluate the potency of live TS vaccines. The chimpanzee animal model has a number of advantages. Chimpanzees become clinically ill, show positive X-ray findings, and develop cold agglutinin titers. In fact, the experimentally induced disease in chimpanzees is remarkably similar to naturally occurring primary atypical pneumonia in patients. Because of the close genomic relationship, immunologic reagents prepared and used for human studies can also be used successfully in chimpanzee studies. The chimpanzee model also has some serious disadvantages. They are expensive to house and maintain and are generally not available to the scientific community. Nonetheless, chimpanzees are probably the best, most meaningful animal models established thus far to examine the infectious process, the immune response and the pathogenesis of this disease and to determine approaches to effective therapy and immunization of diseases produced by known pathogens, like M. pneumoniae, as well as reputed mycoplasma pathogens, such as M. genitalium and M. hominis.

Animals

The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals.

The sequencing of the genome of equine herpesvirus-1 (EHV-1) is reported in Elizabeth A. R. Telford, Moira S. Watson, Kathryn McBride, and Andrew J. Davison, 1992, Virology, 189, 304-316. The sequence was derived using a plaque-purified clone of EHV-1 strain Ab4 (designated Ab4p). To ensure that Ab4p shares the pathogenic characteristics of parental Ab4 (hereafter Ab4), both were inoculated intranasally into foals, specifically free from EHV-1 and EHV-4. Clinical signs, including rectal temperature, were similar for both viruses. In addition, nasal shedding of virus was observed over a 1- to 2-week period postinfection, and viremia was established with both Ab4 and Ab4p. Isolation of virus from one foal following intravenous administration of steroids indicates that Ab4p can establish latency and undergo reactivation. Finally, retinal lesions were observed and these were similar to those seen with Ab4. In conclusion, several pathogenic characteristics of Ab4 are retained in the plaque-purified clone, Ab4p.

Animals

Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals.

Both intranasal (i.n.) and intracerebral (i.c.) inoculation of mice with wild-type equine herpesvirus type 1 (wt EHV-1) caused clinical signs and mortality. Virus could be recovered from target organs (turbinates, lungs and blood) for several days. By contrast, the thymidine kinase (TK)-deficient deletion mutant PR1 produced markedly less clinical disease following both i.n. and i.c. inoculation, and, in particular, no mortality occurred. PR1 did, however, establish productive infections following either route of inoculation. High titres of virus were recovered from target organs although virus did not persist for as long as wt EHV-1 and no viraemia was detected. Primary i.n. infection of mice with either wt EHV-1 or PR1 protected against subsequent challenge with wt EHV-1 5 weeks later. I.n. inoculation of specific pathogen-free (EHV-free) foals with PR1 produced results similar to those observed after infection of mice. Clinical signs were milder than for wt EHV-1 and pyrexia was short-lived or absent. PR1 could be recovered from nasal mucus at high titres but it persisted for only 5 days post-infection compared to 11 days in the case of wt EHV-1. No viraemia was detected in foals infected with PR1. On challenge with wt EHV-1, foals given a primary infection with the mutant were partially protected; but a viraemia with a TK+ EHV-1 was observed. These results demonstrate that our TK- mutant PR1 is markedly less pathogenic than wt EHV-1, despite being able to replicate in the host. The use of TK-deficient mutants of EHV-1 as potential vaccines in the horse is discussed.

Animals

Occurrence of acute infectious bursal disease with high mortality in Japan and pathogenicity of field isolates in specific-pathogen-free chickens.

Highly virulent infectious bursal disease virus (IBDV) was isolated from field cases, and the pathogenicity of the isolates was examined in specific-pathogen-free chickens. Chickens inoculated with the isolates developed severe clinical disease with a high mortality rate. Histopathologically, infectious bursal disease was characterized by bursal and thymic necrosis, aplastic anemia, acute hepatitis with fatty change, and systemic inflammatory response. In addition to functional abnormalities in the liver, a hypoxic state was induced by aplastic anemia and severe inflammation in the pulmonary air capillary walls. These pathological changes appeared to be closely related to the cause of death.

Animals

Pathogenicity of recent isolates of infectious bursal disease virus in specific-pathogen-free chickens: protection conferred by an intermediate vaccine strain.

The pathogenicity of recent isolates of infectious bursal disease virus and the protection conferred against them by a commercial vaccine strain of intermediate virulence were examined in specific-pathogen-free chickens. Based on clinical signs, mortality, and macroscopic lesions in susceptible chickens, the isolates designated as A-Delmarva and U-28 were distinct from a previously known serotype I virulent isolate (Edgar). Histopathological analysis of the bursa of Fabricius did not establish differences between the field isolates. Although the vaccine strain produced some degree of bursal damage in antibody-free chickens, it was significantly less severe than the damage caused by the field isolates. The active immune response induced by vaccination was cross-protective against the pathological effects produced by the different isolates used in this study.

Animals

Comparative study of the temperature profiles of growth and death of the pathogenic yeast Cryptococcus neoformans and the non-pathogenic Cryptococcus albidus.

The temperature profiles of two species of Cryptococcus were compared. The pathogenic Cr. neoformans had a maximum temperature for growth of 39.8 degrees C and the non-pathogenic Cr. albidus, of 30.2 degrees C. The specific growth rates measured in the former were of an order of magnitude higher than in the latter, whereas the Arrhenius plots of the specific thermal death rates did not show a significant difference.

Cryptococcus

Adherence of pathogenic and non-pathogenic Entamoeba histolytica strains to neutrophils.

The adherence of polymorphonuclear leukocytes (PMNs) to eight pathogenic and nine nonpathogenic strains of Entamoeba histolytica was examined. No difference between pathogenic and nonpathogenic strains was found. The addition of different carbohydrates confirmed the importance of the 170-kDa lectin of E. histolytica in binding to PMNs, corroborated by the finding that treatment of PMNs with galactosidase inhibited adherence. Inhibition of the microfilament system of E. histolytica using cytochalasin B resulted in a loss of adherence to PMNs. Inhibition of the microtubule system using nocodazole did not affect adherence. Preincubation of the trophozoites with serum resulted in enhanced adherence, but the serum factor responsible for this effect could not be identified. Fibronectin, vitronectin, integrins (CD11/CD18 molecules), complement, and mannose-binding protein did not seem to mediate adherence between E. histolytica and PMNs. In summary, these results indicate that defective adherence mechanisms are not a common feature of nonpathogenic E. histolytica strains.

Acetylgalactosamine

Virulence of pathogenic and non-pathogenic zymodemes of Entamoeba histolytica (Indian strains) in guinea-pigs.

Guinea-pigs were inoculated with Entamoeba histolytica strains isolated from cases of amoebic liver abscess, amoebic dysentery and asymptomatic cyst passers and the strains were classified in zymodemes by isoenzyme electrophoresis. It was observed that certain non-pathogenic zymodemes were potentially pathogenic for the guinea-pigs. The relationship of zymodemes and virulence in laboratory animals is discussed.

Amebiasis

Protection against establishment of latent infections in mice immunized with a non-pathogenic herpes simplex virus mutant and reinfected with the pathogenic parental strain.

Immunization of hairless mice with a TK-, ACVr, non-pathogenic herpes simplex virus (HSV) type 1 mutant protected the mice against reinfection with lethal doses of the parental pathogenic HSV strain. The protection conferred by the mutant against the establishment of latency after reinfection with the parental strain was dependent on the site of reinfection; after reinfection at the same site, only 2% of mice became latently infected, compared to 32% after reinfection at a distant site. When inoculation with the mutant was done at two different sites, single reinfections at any site led to the establishment of latency in 4% of the mice. The mutant by itself was almost completely latency-negative: only 4.5% of the mice developed latency in trigeminal ganglia and 2.3% in the spinal ganglia. The rate of mutant-induced latent infections is partly related to the dose of the virus; however, lower doses of the mutant may not colonize the ganglia, and therefore fail to protect against challenge infections.

Animals

Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species.

The presence of highly conserved regions within previously determined porin gene sequences from Neisseria meningitidis and Neisseria gonorrhoeae permitted the construction of oligonucleotide primers for PCR amplification of other neisserial porin genes. Although two separate porin genes (porA and porB) are present in N. meningitidis only a single fragment, corresponding to porB, could be amplified from this species. The amplified porB genes from four different meningococcal serotypes, which express the class 3 outer membrane protein, were sequenced. Amplified fragments corresponding to porin genes from N. lactamica and N. sicca were also sequenced. In common with the known neisserial porins, models of the organisation of the predicted proteins indicated trans-membrane structures with eight surface exposed loops. In the meningococcal class 3 proteins the main regions of sequence variation, which must be responsible for serotype specificity, were located on loops 5 and 7. A phylogenetic analysis of the family of porins from the Neisseria confirmed the close relationship of the meningococcal class 3 protein with the gonococcal PIA protein, while the gonococcal PIB protein was shown to be closely related to the N. lactamica porin. The close relationship seen between porins of the pathogenic and non-pathogenic Neisseriae identified no obvious virulence-associated regions in the proteins, but did suggest that the current nomenclature for neisserial porin genes may need reviewing.

Alleles

Similarity between the Rhizobium meliloti fliP gene and pathogenicity-associated genes from animal and plant pathogens.

The nucleotide sequence of the Rhizobium meliloti (Rm) fliP gene was determined. Rm strains carrying insertions within this gene were non-motile, lacked flagella and formed normal N2-fixing root nodules on alfalfa. The FliP protein showed similarity to several bacterial gene products involved in pathogenicity in both plant and animal pathogens. It is likely that all of these proteins share a common functional role in the secretion of specific proteins from bacterial cells.

Amino Acid Sequence

Ribosomal DNA sequences in the differentiation of pathogenic and non-pathogenic isolates of Entamoeba histolytica.

Recombinant ribosomal DNA sequences were amplified by PCR and used as probes to perform a fingerprint analysis of total DNA from different Entamoeba histolytica isolates. RFLPs obtained with one of the probes, R-1, support previous proposals that pathogenic and non-pathogenic E. histolytica are closely related, yet genotypically distinct. Another probe, R-2, while not distinguishing between the two forms of E. hystolytica, was able to differentiate between them and E. moshkovskii, which has morphologically identical cysts and trophozoites. A third probe, BR-1, identified strain-specific RFLPs.

Animals

Asymptomatic intestinal colonization by pathogenic Entamoeba histolytica in amebic liver abscess: prevalence, response to therapy, and pathogenic potential.

Since the application of isoenzyme electrophoresis to the study of Entamoeba histolytica, the prevalence and natural history of asymptomatic intestinal colonization in patients with amebic liver abscess (ALA) has not been addressed. We prospectively evaluated this enteric phase in 50 patients with ALA, using two dosage regimens of metronidazole. The overall prevalence of asymptomatic colonization was 72% (36/50). All these isolates, without exception, proved to express pathogenic zymodemes. Despite a 100% clinical response of the hepatic lesions, failure to eradicate the organism from the bowel occurred in 20 of these 36 subjects. During longitudinal posttreatment surveillance, three carriers returned with second bouts of invasive disease: one with dysentery and two with liver abscesses. Thus, in patients with ALA, there is a high prevalence of intestinal colonization with exclusively pathogenic strains, and treatment with metronidazole frequently results in a continued carrier state. These carriers have a propensity for developing recurrent invasive disease and constitute a public health hazard.

Adult

Candida krusei: biology, epidemiology, pathogenicity and clinical manifestations of an emerging pathogen.

Early reports of Candida krusei in man describe the organism as a transient, infrequent isolate of minor clinical significance inhabiting the mucosal surfaces. More recently it has emerged as a notable pathogen with a spectrum of clinical manifestations such as fungaemia, endophthalmitis, arthritis and endocarditis, most of which usually occur in compromised patient groups in a nosocomial setting. The advent of human immunodeficiency virus infection and the widespread use of the newer triazole fluconazole to suppress fungal infections in these patients have contributed to a significant increase in C. krusei infection, particularly because of the high incidence of resistance of the yeast to this drug. Experimental studies have generally shown C. krusei to be less virulent than C. albicans in terms of its adherence to both epithelial and prosthetic surfaces, proteolytic potential and production of phospholipases. Furthermore, it would seem that C. krusei is significantly different from other medically important Candida spp. in its structural and metabolic features, and exhibits different behaviour patterns towards host defences, adding credence to the belief that it should be re-assigned taxonomically. An increased awareness of the pathogenic potential of this yeast coupled with the newer molecular biological approaches to its study may facilitate the continued exploration of the epidemiology and pathogenesis of C. krusei infections.

Animals

Fate of pathogenic and non-pathogenic Escherichia coli strains in two fermented milk products.

The growth and survival of pathogenic and non-pathogenic strains of Escherichia coli was determined in traditionally fermented pasteurized and unpasteurized milk and in Lacto, an industrially fermented milk. Each milk treatment was incubated at 20 degrees C for 24 h and then stored at either 20 degrees C or 5 degrees C for 96 h. Lacto inhibited all the three E. coli strains. Two strains could not be recovered and the third survived only in very low numbers after 24 h storage of Lacto at both 20 degrees C and 5 degrees C. All three E. coli strains survived and multiplied to maximum cell numbers in the range 10(7)-10(9)/ml during traditional fermentation of unpasteurized milk. Cell numbers decreased to 10(3)-10(6) and 10(2)-10(5) during storage of the fermented product at 20 degrees C and 5 degrees C respectively. Higher maximum numbers, 10(9)-10(10), of the three strains of E. coli were attained during traditional fermentation of pasteurized milk. The numbers decreased to 10(5)-10(8) and 10(4)-10(7) during storage of the fermented product at 20 degrees C and 5 degrees C respectively. Generally, fewer E. coli survived when the fermented milk products were stored at refrigeration temperature.

Animals