Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice

The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4(+) and/or CD8(+) cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans. (C) 2003 Elsevier Science Ltd. All rights reserved.

Differential expression of the NMDA NR2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis

We have compared the expression pattern of NMDA receptor subunits (NR1 and NR2A-D)and NRI splice variants (NR1-1a/1b,-2a/2b,-3a/3b,4a/4b) in motor neuron populations from adult Wistar rats that are vulnerable (hypoglossal, XII) or resistant (oculomotor, III) to death in amyotrophic lateral sclerosis (ALS). The major finding was higher levels of expression of the NR2B subunit in the hypoglossal nucleus. Quantitative real-time PCR showed that NR1 was expressed at a greater level than any of the NR2 subunits (> 15 fold greater, P

Cytokines in the oral mucosa of mice infected with Candida albicans

Oropharyngeal candidiasis is associated with defects in cell-mediated immunity, and is commonly seen in immunocompromised patients. We have previously shown that T-cell-deficient BALB/c nude (nu/nu) mice are extremely susceptible to oropharyngeal candidiasis, and that recovery from a chronic infection is dependent on CD4 T lymphocytes. In this study we describe the local tissue cytokine profile in lymphocyte-reconstituted immunodeficient mice and their euthymic counterparts. Mice were infected orally with 10(8) cells of the yeast Candida albicans , and oral tissues sampled on days 0, 4, 8, and 14. Nude mice were reconstituted with 3 x 10(7) naive lymphocytes following oral inoculation. Interleukin (IL)-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were identified in the oral tissues of infected euthymic mice recovering from oral infection, as well as naive controls. TNF-alpha was identified in nude oral tissue on days 4 and 8, but only after lymphocyte reconstitution. No IL-2, IL-4 or IL-10 was detected in either euthymic or athymic mice at any time-point throughout the experiment. This study confirms the functional activity of T lymphocytes in reconstituted nude mice, and suggests that TNF-alpha may be an important mediator in the recovery from oropharyngeal candidiasis.

In vivo effects of chicken interferon-gamma during infection with Eimeria

Newly hatched chickens are highly susceptible to infection by opportunistic pathogens during the first 1 or 2 weeks of life, The use of cytokines as therapeutic agents has been studied in animal models as well as in immunosuppressed patients, This approach has become more feasible in livestock animals, in particular poultry, with the recent cloning of cytokine genes and the development of new technologies, such as live delivery vectors, We have recently cloned the gene for chicken interferon-gamma (Ch-IFN-gamma), Poly-HIS-tagged recombinant Ch-IFN-gamma was expressed in Escherichia coil, was purified by Ni chromatography, and was found to be stable at 4 degrees C and an ambient temperature for at least several months and Several weeks, respectively, Ch-IFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis, induced nitrite secretion from chicken macrophages in vitro, and enhanced MHC class II expression on macrophages, Administration of recombinant Ch-IFN-gamma to chickens resulted in enhanced weight gain over a 12-day period, Furthermore, the therapeutic potential of Ch-IFN-gamma was assessed using a coccidial challenge model, Birds were treated with Ch-IFN-gamma or a diluent control and then infected with Eimeria acervulina. Infected birds treated with Ch-IFN-gamma showed improved weight gain relative to noninfected birds, The ability of Ch-IFN-gamma to enhance weight gain in the face of coccidial infection makes it an excellent candidate as a therapeutic agent.

Patch dynamics and metapopulation theory: the case of successional species

We present a mathematical framework that combines extinction-colonization dynamics with the dynamics of patch succession. We draw an analogy between the epidemiological categorization of individuals (infected, susceptible, latent and resistant) and the patch structure of a spatially heterogeneous landscape (occupied-suitable, empty-suitable, occupied-unsuitable and empty-unsuitable). This approach allows one to consider life-history attributes that influence persistence in patchy environments (e.g., longevity, colonization ability) in concert with extrinsic processes (e.g., disturbances, succession) that lead to spatial heterogeneity in patch suitability. It also allows the incorporation of seed banks and other dormant life forms, thus broadening patch occupancy dynamics to include sink habitats. We use the model to investigate how equilibrium patch occupancy is influenced by four critical parameters: colonization rate? extinction rate, disturbance frequency and the rate of habitat succession. This analysis leads to general predictions about how the temporal scaling of patch succession and extinction-colonization dynamics influences long-term persistence. We apply the model to herbaceous, early-successional species that inhabit open patches created by periodic disturbances. We predict the minimum disturbance frequency required far viable management of such species in the Florida scrub ecosystem. (C) 2001 Academic Press.

Outcomes of cephalosporin treatment for serious infection due to apparently susceptible organisms producing extended-spectrum b-Lactamases: Implications for the clinical microbiology laboratory

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs, We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range, Thus, it is clinically important to detect ESBL production by klebsiellae or E, coli even when cephalosporin MICs are in the susceptible range (less than or equal to 8 mug/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).

Disease, habitat fragmentation and conservation

Habitat loss and the resultant fragmentation of remaining habitat is the primary cause of loss of biological diversity. How do these processes affect the dynamics of parasites and pathogens? Hess has provided some important insights into this problem using metapopulation models for pathogens that exhibit 'S-I' dynamics; for example, pathogens such as rabies in which the host population may be divided into susceptible and infected individuals. A major assumption of Hess's models is that infected patches become extinct, rather than recovering and becoming resistant to future infections. In this paper, we build upon this framework in two different ways: first, we examine the consequences of including patches that are resistant to infection; second, we examine the consequences of including a second species of host that can act as a reservoir for the pathogen. Both of these effects are likely to be important from a conservation perspective. The results of both sets of analysis indicate that the benefits of corridors and other connections that allow species to disperse through the landscape far outweigh the possible risks of increased pathogen transmission. Even in the commonest case, where harmful pathogens are maintained by a common reservoir host, increased landscape connectance still allows greater coexistence and persistence of a threatened or endangered host.

Analysis of the sequence and expression of a second putative acetylcholinesterase cDNA from organophosphate-susceptible and organophosphate-resistant cattle ticks

The cattle tick, Boophilus microplus, is a major pest of cattle in Australia, Central and South America, and parts of Africa and Asia. Control of ticks with organophosphates (OPs) and carbamates, which target acetylcholinesterases (AChE), led to evolution of resistance to these pesticides. Alleles at the locus studied here, AChE2, from OP-susceptible female ticks from Australia and Mexico differed at 46 of 1689 nucleotide positions (20 putative amino acid differences) whereas alleles from three strains of OP-resistant ticks from Australia differed with the allele from the Australian susceptible ticks at six to 13 nucleotide positions (three to six putative amino acid differences). However, the role, if any, of these polymorphisms in the OP-resistance phenotype is unknown. Certainly none of the polymorphisms correspond to sites in ACK that are involved in catalysis or binding of acetylcholine in other organisms. Both of the AChE loci of B. microplus, AChE1 and AChE2, are apparently expressed in synganglia; AChE1 is also expressed in salivary glands and ovaries, in OP-susceptible and OP-resistant ticks. This seems to contradict studies of enzyme kinetics, which indicated that only one form of AChE was present in the synganglia, the site of the action of OPs, in this species of tick. (C) 2002 Elsevier Science Ltd. All rights reserved.

Effect of organic amendments and solarisation on Fusarium wilt in susceptible banana plantlets, transplanted into naturally infested soil

Despite extensive research since pathogenicity was first established in 1919, no cultural or chemical control strategy has proven effective against Fusarium wilt of bananas. The efficacy of cultural control is attributed to the suppression of pathogen activity. Yet, amending naturally infested soil with aged chicken manure has been shown to enhance disease severity, without any change in the activity of the pathogen Fusarium oxysporum f. sp. cubense (Foc) in the soil. In this study, the effect of amending soil with composted sawdust, and of solarising soil, was compared with the effect of amending soil with chicken manure. Bioassays comparing the activity of Foc in the soil with the extent of invasion of banana pseudostem tissue by Foc were used to investigate why strategies targetting pathogen survival have not proven successful in controlling this disease. The enhancement of Foc invasion of the banana plantlets was reproduced with the addition of chicken manure to the naturally infested soil. However, changes in the activity of Foc in the soil were not associated with changes in the frequency of invasion of the plantlets. Invasion of banana pseudostems in the sawdust and solarisation treatments was not significantly different from invasion in the respective control treatments, despite a reduction in the activity of Foc in the sawdust-amended soil and an enhancement in the solarised soil. Moreover, the increase in Foc activity in the solarised soil recorded during the bioassays occurred despite the effectiveness of solarisation in reducing the survival of Foc in pre-colonised banana root tips buried in the soil. Changes in the frequency of invasion were associated with changes in the availability of mineral nitrogen, particularly ammonium N. These results suggest that the physiological response of banana cultivars to ammonium N may be associated with their susceptibility to Fusarium wilt. Accordingly, cultural strategies for controlling Panama disease will only be effective if they enhance the ability of the host to resist invasion.

A physiological product-release model for baculovirus infected insect cells

Existing models describe the product release from baculovirus infected insect cells as an unspecific protein leakage occurring in parallel with protein production. The model presented here shows that the observed product release of normally non-secreted proteins can be described through cell death alone. This model avoids the implicit non-physiological assumption of previous models that cells permeable to recombinant protein as well as trypan blue continue to produce protein. (c) 2005 Wiley Periodicals, Inc.

Active and passive immunization against oral Candida albicans infection in a murine model

Background/aims: Clinical and laboratory studies are consistent with a major role for cell-mediated immunity in recovery from oral infection with Candida albicans, but the role of humoral immunity remains controversial. The purpose of this study was to establish the relative contributions of cellular and humoral immunity to protection against oral candidiasis in a murine model, and to determine whether host responses could be enhanced by different immunization strategies. Results: Active oral immunization was protective in BALB/c and CBA/CaH mice, reducing both fungal burden and duration of infection after secondary challenge, whereas systemic immunization failed to protect against subsequent oral challenge. Candida-specific IgM was the predominant antibody detected in serum following both primary and secondary oral challenge; however, Candida-specific salivary IgA was not detectable. Immunization by passive transfer of either lymphocytes or immune serum did not confer any significant protection against oral infection in either susceptible or resistant mouse strain. Conclusion: The data demonstrate a possible role for mucosa-associated immunity following active immunization by the oral route, most likely exerted by local T lymphocytes resident in the oral mucosa, but there was no evidence to support a role for humoral immunity in protection against oral candidiasis.

Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou Province, China

Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. Clinical symptoms of arsenicosis may include changes of skin pigmentation, hyperkeratosis of hand and feet, skin cancers, liver damage, persistent cough and chronic bronchitis. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-bome arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those in the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age (< 20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation. (c) 2005 Elsevier Inc. All rights reserved.