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Measurement of cellular immunity in human coccidioidomycosis.

Measurement of cellular immune response in human coccidioidomycosis, a disease of the Western Hemisphere caused by the soil-dwelling fungus Coccidioides, began more than 75 years ago. Numerous studies have shown that measurement of coccidioidal cellular immunity is a useful epidemiologic and clinical tool. The first widely used coccidioidal skin-test reagent, coccidioidin, was derived from a filtrate of cultured mycelia of Coccidioides by Smith and colleagues in the 1940's. It remained the standard until the 1970's, when spherulin, obtained from the spherule form of the fungus, was found to be more sensitive. Both reagents are specific indicators of coccidioidal cellular immunity. Since then, other coccidioidal antigens have been identified and in vitro tests of cellular immunity have been shown to yield comparable results to skin testing. In vitro assays have also begun to open a window on the specific immunologic events of coccidioidal cellular immunity. Persistent expression of coccidioidal cellular immune response appears to augur an improved clinical outcome. Despite this, a study of a coccidioidal vaccine failed to demonstrate efficacy. Current and future studies are focused on modulating the coccidioidal immune response in vitro and in vivo and on developing an improved vaccine.

Coccidioides↗

Treatment of histoplasmosis.

Histoplasmosis is an endemic mycosis, which is most prevalent in the Ohio and Mississippi valleys of North America. The causative organism is a dimorphic fungus, Histoplasma capsulatum. Histoplasmosis can present as a self-limited disease or cause life-threatening diseases resulting in considerable morbidity and mortality. Treatment is appropriate in patients with diffuse acute pulmonary infection, chronic pulmonary infection, mediastinal granuloma causing obstruction of important structures, or disseminated infection. Other chronic forms of disease such as fibrosing mediastinitis and broncholithiasis are unresponsive to pharmacologic treatment. Options for therapy include amphotericin B or one of its lipid formulations, and ketoconazole, itraconazole, or fluconazole. Recently, newer antifungal agents have been evaluated in animals models of histoplasmosis. Of these, a new triazole, posaconazole (SCH56592) appears most promising. Generally, amphotericin B or one of the lipid formulations is recommended as initial treatment in patients with more extensive diseases, felt to be ill enough to require hospitalization, and itraconazole for those who have milder illness, or to complete treatment after patients respond to amphotericin B. The role of intravenous formulation of itraconazole for severe histoplasmosis is unknown because studies comparing it with amphotericin B have not been conducted.

Amphotericin B↗

A Magnaporthe grisea cyclophilin acts as a virulence determinant during plant infection.

Cyclophilins are peptidyl prolyl cis-trans isomerases that are highly conserved throughout eukaryotes and that are best known for being the cellular target of the immunosuppressive drug cyclosporin A (CsA). The activity of CsA is caused by the drug forming a complex with cyclophilin A and inhibiting the calmodulin-dependent phosphoprotein phosphatase calcineurin. We have investigated the role of CYP1, a cyclophilin-encoding gene in the phytopathogenic fungus Magnaporthe grisea, which is the causal agent of rice blast disease. CYP1 putatively encodes a mitochondrial and cytosolic form of cyclophilin, and targeted gene replacement has shown that CYP1 acts as a virulence determinant in rice blast. Cyp1 mutants show reduced virulence and are impaired in associated functions, such as penetration peg formation and appressorium turgor generation. CYP1 cyclophilin also is the cellular target for CsA in Magnaporthe, and CsA was found to inhibit appressorium development and hyphal growth in a CYP1-dependent manner. These data implicate cyclophilins as virulence factors in phytopathogenic fungi and also provide evidence that calcineurin signaling is required for infection structure formation by Magnaporthe.

Amino Acid Sequence↗

Microarray analysis of Fusarium graminearum-induced wheat genes: identification of organ-specific and differentially expressed genes.

A wheat cDNA microarray consisting of 5739 expressed sequence tags (ESTs) was used to investigate the transcriptome patterns of the glume, lemma, palea, anther, ovary and rachis dissected from infected wheat spikes after inoculation with the fungus Fusarium graminearum, the causal agent of fusarium head blight (FHB) disease. Stringent conditions were employed to reduce the false discovery rate. The significance analysis of microarrays (SAM) was used to identify transcripts that showed a differential response between fungal-challenged vs. control plants. To verify the microarray data, Northern blot analysis was carried out on randomly selected up-regulated clones. We observed 185 (3.2%) up-regulated and 16 (0.28%) down-regulated ESTs in the six organs constituting the wheat spike. Many up-regulated ESTs (46.67%) showed no homology with sequences of known functions, whereas others showed homology with genes involved in defence and stress responses, the oxidative burst of H(2)O(2), regulatory functions, protein synthesis and the phenylpropanoid pathway. The monitoring of genes in specific organs avoided the averaging of expression values over multiple organs that occurs when using data from the whole spike. Our data allowed us to uncover new up-regulated genes expressed in specific organs. The study revealed that each organ had a defined and distinctive transcriptome pattern in response to F. graminearum infection.

DNA, Complementary↗

RNA-mediated gene silencing in the phytopathogenic fungus Bipolaris oryzae.

The Ascomycetous fungus Bipolaris oryzae is the causal agent of brown leaf spot disease in rice and is a model for studying photomorphogenetic responses by near-UV radiation. Targeted gene disruption (knockout) for functional analysis of photomorphogenesis-related genes in B. oryzae can be achieved by homologous recombination with low efficiency. Here, the applicability of RNA silencing (knockdown) as a tool for targeting endogenous genes in B. oryzae is reported. A polyketide synthase gene (PKS1), involved in fungal DHN melanin biosynthesis pathways, was targeted by gene silencing as a marker. The silencing vector encoding hairpin RNA of the PKS1 fragment was constructed in a two-step PCR-based cloning, and introduced into the B. oryzae genomic DNA. Silencing of the PKS1 gene resulted in albino phenotypes and reduction of PKS1 mRNA expression. These results demonstrate the applicability of targeted gene silencing as a useful reverse-genetics approach in B. oryzae.

Ascomycota↗

Disseminated paracoccidioidomycosis with peripleuritis in an AIDS patient.

Paracoccidioidomycosis is one of the most frequent systemic and endemic mycoses of Latin America caused by a dimorphic fungus. In AIDS patients, paracoccidioidomycosis appears as a severe and disseminated disease with a wide spectrum of clinical findings. The CD4 counts are usually less than 200 cell/mu L. We present a case of disseminated paracoccidioidomycosis with peripleuritis and subcutaneous abscesses on the chest wall as initial manifestation of AIDS. In endemic countries, paracoccidioidomycosis should be included as an opportunistic infection in AIDS.

AIDS-Related Opportunistic Infections↗

Record of Evlachovaea sp. (Hyphomycetes) on Triatoma sordida in the state of Goiás, Brazil, and its activity against Triatoma infestans (Reduviidae, Triatominae).

A fungal isolate was detected on a dead Triatoma sordida (Stål) collected in a peridomestic area in central Brazil. The fungus belongs to Evlachovaea Borisov and Tarasov, a new genus that was recently described in Russia. The isolate seems to be a third species and the second new and undescribed species from Brazil. The fungus was shown to be active against Triatoma infestans (Klug) third-instar nymphs at a humidity close to saturation. However, activity was reduced at a lower humidity (75%). Values of LC50 varied between 1.1 x 10(5) and 1.5 x 10(4) conidia/cm2 treated surface, 15 and 20 d after fungal application and incubation at humidity close to saturation. This new fungus may have a potential for biological control of peridomestic Chagas' disease vectors during the rainy season.

Animals↗

Immunotherapy of allergic bronchopulmonary aspergillosis: a clinical and experimental approach.

Allergic bronchopulmonary aspergillosis (ABPA) is a severe allergic pulmonary complication caused by the saprophytic fungus Aspergillus fumigatus. The present review examines the pathogenesis of this disease describing in detail the role of innate and acquired immunity in the induction of sensitivity to A.fumigatus. Different approaches in developing specific immunotherapeutic treatments such as induction of anergy, regulatory cells, a switch from Th2 to Th1 type of immune response, CpG and genetic immunization and the usage of altered peptides or modified allergens are critically examined.

Animals↗

Fusarium brain abscess. Case report.

The common soil fungus, Fusarium, is rarely pathogenic in man but occasionally causes serious disease, particularly in immunocompromised hosts. A case is reported of Fusarium brain abscess and meningitis occurring in a patient with chronic infectious mononucleosis syndrome and immunodeficiency. The patient died despite aspiration of the abscess and treatment with amphotericin B. This case demonstrates the importance of identifying the offending pathological organism through abscess aspiration in immunocompromised patients.

Adolescent↗

[Genital histoplasmosis. Presentation of a clinical case].

OBJECTIVES: On December 1905 Darling, resident histopathologist on the Panama Channel area, observed a parasite in the large mononuclear cells of different organs. Negroni in 1914 described the first Argentinean case. Lung, oral, nasal, and laryngeal involvement are common. On the other hand, genital involvement is uncommon. The objective of this war is to communicate the case of a patient with genital histoplasmosis. METHODS/RESULTS: A 60-year-old Argentinian male started two years before with penile lesions and pruritus. Two partial penile resections had been performed in 1999, but pathology reports were not available. The lesions evolved towards ulceration and bleeding. Surgical toilette was carried out. A partial penectomy and glanuloplasty with an original technique were performed. Pathology revealed intracellular and extracellular spherical microorganisms. Morphologically it was histoplasma capsulatum. The histoplasmosis is an endemic mycosis. The infection takes place when inhaling the microconidiae of the fungus filamentous phase. Only a small number of people develop the disease after infection. Diagnosis is made by discovering of 2-3 micron yeasts with Giemsa stain. CONCLUSIONS: If a patient from the histoplasmosis endemic area has a granular lesion, a mycotic disease should be considered.

Antifungal Agents↗

Phaeohyphomycosis of the maxilloethmoid sinus caused by Drechslera spicifera: a new fungal pathogen.

"Phaeohyphomycosis" refers to soft tissue and systemic infections caused by dematiacious septate fungi. Drechslera spicifera, a dematiacious fungus, rarely pathogenic in humans was found to cause maxilloethmoid sinus disease in two immunocompetent children. The clinical presentation was similar to noninvasive aspergillosis. Intracavitary surgical excision without adjuvant chemotherapy resulted in apparent cure. The microbiologic and clinicopathologic aspects of this mycotic sinus disease are reviewed and discussed in relation to the entire spectrum of human disease reported which has been attributed to this organism.

Adult↗

Analysis of fumonisin B1 in rodent feed by CE with fluorescence detection of the FMOC derivative.

A fast, simple, and environmentally friendly method has been developed for the analysis of fumonisin B1 (FB1) in rodent feed using CE. FB1 is the major fumonisin metabolite produced by the fungus Fusarium moniliforme and has been implicated in human and animal diseases. FB1 was extracted from rodent feed with acetonitrile/water (50/50) (vol/vol) and cleaned up with a C18 Sep-Pak Vac cartridge (Waters Corp., Milford, MA, U.S.A.). FB1 was quantitated after elution from the column using capillary electrophoresis with a 25-mM sodium borate buffer (pH 9.0) containing 10% acetonitrile and fluorescence detection of the (9-fluorenylmethyl) chloroformate (FMOC) derivative. The minimum detectable amount in rodent feed was 0.5 pmm. Recovery values in spiked rodent feed averaged more than 87% over the 2-20 ppm range.

Animal Feed↗

Cutaneous sporotrichosis presenting as a keratoacanthoma.

Sporothrix schenckii is a ubiquitous dimorphic fungus with a variety of clinical presentations, including imitation of other diseases such as pyoderma, rosacea, and pyoderma gangrenosum. A case in which sporotrichosis appeared as a keratoacanthoma-like nodule on the lower lip of a young woman is presented, with treatment considerations and diagnostic pitfalls.

Adult↗

Rectal botryomycosis mimicking carcinoma.

Botryomycosis is a granulomatous disease that was first recognized in horses. The lesion is infective with fungus-like grains similar to the sulfur granules in actinomycosis. We report 54-year-old woman with a strong suspicion of rectal carcinoma that turned out to be rectal botryomycosis. She responded to erythromycin.

Actinomyces↗

Dominant-negative interference with defence signalling by truncation mutations of the tomato Cf-9 disease resistance gene.

The tomato Cf-9 gene confers resistance to races of the leaf mould fungus Cladosporium fulvum that carry the Avr9 avirulence gene. Cf-9 was isolated by transposon tagging using a modified maize Dissociation (Ds) element. This generated an allelic series of Ds-induced mutations of Cf-9, of which two were found to confer novel phenotypes in a screen for mutants affecting wild-type Cf-9 function in trans. Genetic and molecular analysis of these mutants suggested semidominant, Avr9-dependent, negative-interfering mutations involving Ds insertions in a defined subregion of Cf-9. Interference was associated with expression of the 5'-end of Cf-9 upstream of the Ds insertions in these mutants, suggesting that truncated Cf-9 proteins were the likely cause of interference. Transgenic tomato lines harbouring Cf-9 constructs with premature stop codons in positions similar to the Ds insertions also showed interference, indicating that the presence of Ds was not required for interference to occur. Interestingly, interference in these transgenic lines was completely dominant and was associated with a pronounced developmental phenotype that was dependent on co-expression of Cf-9, Avr9 and a truncated Cf-9 transgene. However, interference with a weakly autoactive Hcr9 gene was Avr9-independent and did not cause a developmental phenotype, suggesting that localized restoration of Cf-9/Avr9-dependent cell death was responsible for the developmental phenotype. The restricted region in which truncation of Cf-9 results in dominant-negative interference suggests that leucine-rich repeats (LRR) 16-19 of Cf-9 may mediate dimerization of Cf-9 and LRRs 20-23 may mediate interactions with downstream partner proteins required for Cf-9 signalling, or vice versa.

Amino Acid Motifs↗

Aspergillosis of the urinary tract: ascending route of infection and evolving patterns of disease.

Aspergillosis limited to the urinary tract is a rare disease, seen most often in patients with altered immunity, especially diabetics. The disease has 3 patterns, 2 of which have been described previously. We report the first case documenting the ascending route of infection. Multiple urine cultures may be required for proper identification. Histopathology and culture of sloughed tissue and fungus balls shed per urethram are the essential means of reliable diagnosis. successful treatment of this disease localized to the urinary tract require a high index of suspicion in certain clinical settings, prompt diagnosis, a combination of systemic and local antifungal chemotherapy, and surgical drainage when necessary.

Amphotericin B↗

The development and endophytic nature of the fungus Heteroconium chaetospira.

The root endophytic fungus Heteroconium chaetospira was isolated from roots of Chinese cabbage grown in field soil in Japan. This fungus penetrates through the outer epidermal cells of its host, passes into the inner cortex, and grows throughout the cortical cells, including those of the root tip region, without causing apparent pathogenic symptoms. There are no ultrastructural signs of host resistance responses. H. chaetospira has been recovered from 19 plant species in which there was no disruption of host growth. H. chaetospira has a symbiotic association with Chinese cabbage. The fungus provides nitrogen in exchange for carbon. These associations are beneficial for the inoculated plants, as demonstrated by increased growth rate. When used as a preinoculum, H. chaetospira suppresses the incidence of clubroot and Verticillium yellows when the test plant is post-inoculated with the causal agents of these diseases. H. chaetospira is an effective biocontrol agent against clubroot in Chinese cabbage at a low to moderate soil moisture range and a pathogen resting spore density of 10(5) resting spores per gram of soil in situ. Disease caused by Pseudomonas syringae pv. macricola and Alternaria brassicae on leaves can be suppressed by treatment with H. chaetospira. The fungus persists in the roots and induces systemic resistance to the foliar disease.

Alternaria↗

Liberalization of donor criteria in lung and heart-lung transplantation.

Since March 1986, we have performed 26 heart-lung transplantations, 42 single-lung transplantations, 9 bilateral single-lung transplantations, and 1 double-lung transplantation. The original lung donor requirements were as follows: age less than 40 years, no smoking history; no gram-negative rods or fungus on sputum Gram stain; arterial oxygen tension greater than 140 mm Hg on an inspired oxygen fraction of 0.40; no infiltrate or pneumothorax on the chest radiograph; and donor height within 15 cm (6 inches) of recipient height. As the number of potential recipients increased, so did the waiting time. To counter this delay, during the past year we have liberalized our donor criteria. We now accept lung donors up to age 60 years. Any kind of smoking history is acceptable unless there is chronic obstructive pulmonary disease or pulmonary fibrosis on the chest radiograph. Sputum must be free from fungus, but gram-negative rods are treated with appropriate antibiotics. The arterial oxygen tension on an inspired oxygen fraction of 0.40 should be greater than 100 mm Hg, and a small pulmonary infiltrate is not worrisome. This liberalization of the donor pool for lung and heart-lung transplantation has not adversely affected early outcome.

Adult↗