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Disseminated aspergillosis treated with amphotericin B and surgery in a boy with chronic granulomatous disease.

A case of systemic infection caused by Aspergillus fumigatus in a seven-year-old boy suffering from chronic granulomatous disease is described. The fungus had infiltrated his lungs, his left foot and the popliteal and inguinal lymph nodes. Amphotericin B, 1 mg/kg daily, was given for three months via a central venous catheter, Progressive anaemia made amputation of his left leg necessary. The bone tissue was heavily infiltrated with fungal elements. The regional lymph nodes were also resected because of fungal growth. After six months no fungi were found in liver aspirates taken on account of liver abscesses due to Staphylococcus aureus. The combined medical and surgical approach resulted in complete eradication of the Aspergillus infection, as verified by the disappearance of Aspergillus precipitins.

Amphotericin B↗

[Effect of cyclophosphamide in experimental histoplasmosis in the rat].

Histoplasmosis is a fungal disease caused by the dimorphous fungus Histoplasma capsulatum (Hc). Cyclophosphamide (Cy) was used as an immunomodulator capable of modifying the course of the disease, as well as of regulating the mechanisms involved in T-lymphocyte mediated immune response. Rats were subjected to intracardiac inoculation of Hc followed by a fractionated treatment with a 100 mg/kg body weight dose of Cy on days +4, +5, +6, +7 and +11 pi. Until day 26 pi, treatment with Cy caused 85% mortality whereas no mortality was observed among animals only inoculated with Hc. On day 14 pi, the group of Hc animals showed a delayed hypersensitivity test (DH) of 26.60 + 13.96 as determined by the swelling of the leg. Conversely, DH was significantly depressed in rats inoculated with Hc and treated with Cy: 3.88 +/- 1.00 (p < 0.01). Colony forming units count in this group was 2020 CFU/g of spleen, and 24 CFU/g of spleen (p < 0.01) in controls. A macroscopic study of the organs revealed that the animals in the Hc+Cy group had spleenomegaly and lungs with granuloma and hemorrhagic spots. The controls only presented small lung abscesses. These findings lead to the conclusion that Cy causes a deterioration of cell mediated immune response which results in the manifestation of an acute, fatal experimental mycosis.

Animals↗

Pulmonary aspergillosis: a spectrum of disease.

Although many species of the fungus Aspergillus have been identified, the most common human pathogen is A. fumigatus, which has a worldwide distribution. Although any organ may become infected, pulmonary aspergillosis is the most common manifestation. The spectrum of pulmonary aspergillosis includes saprophytic aspergillomas, allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis, and invasive aspergillosis. Immune status of the host, and the presence of underlying lung disease are important in determining the type of pulmonary involvement. Thus, the radiographic findings are variable. This article reviews the various manifestations of pulmonary aspergillosis, including the immune status of the patient, the presence of underlying lung disease, and the radiographic appearance of the different entities.

Aspergillosis↗

Iritis presumed as secondary to disseminated coccidioidomycosis.

BACKGROUND: Coccidioidomycosis is a systemic disease caused by a fungus found in soil and transmitted through inhalation. It is prevalent in western and southwestern United States, Mexico, and South and Central America. Results of skin testing, serologic testing, and tissue cultures confirm the diagnosis. Coccidioidomycosis can manifest in various ways: the infected individual may present asymptomatically, with an acute respiratory infection, or, in more severe or chronic cases, with a multiorgan presentation. Ocular involvement may include anterior segment, posterior segment, or extraorbital involvement. CASE REPORT: A case concerning a patient with iritis presumed as secondary to disseminated coccidioidomycosis is discussed. The patient initially presented to our clinic with signs and symptoms of acute, unilateral iritis and a recent history of iritis in the contralateral eye. The active inflammation was treated topically with Pred Forte and cyclopentolate and resolved without sequelae. Because the presentation was bilateral with an asymmetric timecourse, laboratory tests were ordered to rule out systemic association. Because all tests yielded negative results, the known history of disseminated coccidioidomycosis was presumed to be the etiology of this iritis. CONCLUSION: Although eye findings are rare, disseminated coccidioidomycosis is an important differential to consider when a patient presents with uveitis. For this reason, awareness and recognition of ocular signs and symptoms of this disease is significant in proper patient care and management.

Coccidioidomycosis↗

Prevalence of rhinosporidiosis of the eye and its adnexa in Nepal.

This study describes the clinical features, diagnosis, and treatment of rhinosporidiosis of the eye and its adnexa in a series of 76 cases in Nepal and six originating in India. The disease caused by the fungus Rhinosporidium seeberi was seen most frequently in young children between eight and 10 years of age. Males were infected more than females (2.5:1). The conjunctiva was the most common site of infection in 76 (92.68%) of the cases. The lacrimal sac was affected only in six (7.32%) cases. Simple total excision of the conjunctival polyps gave highly satisfactory results in cases of conjunctival sac infections. Except for one patient, there were no recurrences in the 76 cases. Meticulous excision of polyps provided a satisfactory result in the treatment of six cases with lacrimal sac infection. Recurrence was noted in one of these six cases followed up to two and a half years after surgery. The conditions diagnosed clinically were confirmed by histopathology. This review of 82 cases is the first such report of rhinosporidiosis from Nepal.

Adolescent↗

[Clinical features of inflammatory bowel disease (author's transl)].

Inflammatory bowel disease may be caused by virus, bacteria, fungus, parasites or mechanical conditions. Among the inflammatory bowel diseases caused by bacteria salmonellosis and cholera are most important. Their treatment has been revolutionized within the last decade. Instead of the administration of antibiotics the usage of fluids, glucose and electrolytes represents the method of choice. Using the so called "traveller's disease" as an example the pathophysiological aspects of the treatment may be best explained. Etiology and pathogenesis of Crohn's disease, the incidence of which seems to be increasing lately, are still unknown. Before onset of treatment it is essential to establish an exact diagnosis, further to determine distribution and inflammatory activity, as those control the therapy. Salazosulphapyridine and steroids have proved effective drugs. Azathioprine should only be used combined with steroids. Recent investigations suggest that certain formula diets, such as e. g. Survimed, may be useful in the management of the disease as well.

Azathioprine↗

Negative regulation of defense responses in plants by a conserved MAPKK kinase.

The enhanced disease resistance 1 (edr1) mutation of Arabidopsis confers resistance to powdery mildew disease caused by the fungus Erysiphe cichoracearum. Resistance mediated by the edr1 mutation is correlated with induction of several defense responses, including host cell death. Double mutant analysis revealed that all edr1-associated phenotypes are suppressed by mutations that block salicylic acid (SA) perception (nim1) or reduce SA production (pad4 and eds1). The NahG transgene, which lowers endogenous SA levels, also suppressed edr1. In contrast, the ein2 mutation did not suppress edr1-mediated resistance and associated phenotypes, indicating that ethylene and jasmonic acid-induced responses are not required for edr1 resistance. The EDR1 gene was isolated by positional cloning and was found to encode a putative MAP kinase kinase kinase similar to CTR1, a negative regulator of ethylene responses in Arabidopsis. Taken together, these data suggest that EDR1 functions at the top of a MAP kinase cascade that negatively regulates SA-inducible defense responses. Putative orthologs of EDR1 are present in monocots such as rice and barley, indicating that EDR1 may regulate defense responses in a wide range of crop species.

Amino Acid Sequence↗

From interferon induction to fungal viruses.

Viruses of fungi (mycoviruses) were first discovered in diseased mushrooms. However the finding that the antiviral and interferon-inducing activities of extracts of apparently healthy isolates of a number of Penicillium species were due to the presence of double-stranded (ds) RNA arising from mycovirus infections sparked off an explosion of interest in what has now become a distinct area of virology. Two families of dsRNA mycoviruses are now established: the Totiviridae and the Partitiviridae which comprise isometric viruses with genomes of one or two dsRNA segments respectively. Virus isolates in both families often contain additional satellite dsRNAs, which may in some fungi (e.g. Saccharomyces cerevisiae, Ustilago maydis) code for "killer" proteins which are toxic to other sensitive strains of the same or closely related species. In Endothia parasitica, which causes chestnut blight disease, dsRNA is associated with hypovirulence and is enclosed in lipid-rich vesicles. In Ophiostoma (Ceratocystis) ulmi, which causes Dutch elm disease, dsRNA is associated with the mitochondria and, in some diseased isolates of the fungus, specific dsRNA segments are associated with reduction of cytochrome oxidase and respiratory deficiency, resulting in slow growth and abnormal morphology.

Fungi↗

Production of a novel compound, 7,10,12-trihydroxy-8(E)-octadecenoic acid from ricinoleic acid by Pseudomonas aeruginosa PR3.

The production and its potential use of a novel trihydroxy unsaturated fatty acid, 7,10,12-trihydroxy-8(E)-octadecenoic acid (TOD), were investigated. TOD was formed by Pseudomonas aeruginosa PR3 (NRRL B-18602) in a culture supplied with exogenous ricinoleic acid. The yield of TOD production was always higher in a rich culture medium than in minimal screening medium. Extending the conversion time from 48 to 72 h prior to lipid extraction led to a 65% reduction in yield, indicating that TOD was further metabolized by strain PR3 and that control of reaction time is important to achieving a maximum yield. The optimum culture density, reaction time, pH, temperature, and substrate concentration for the production of TOD were: 20-24 h culture growth, 48 h, 7.0, 25 degrees C, and 1% (vol/vol), respectively. Under optimum conditions, the yield of TOD production was greater than 45%. TOD was found to be an antifungal agent most active against the fungus that causes blast disease in rice plants, the most important fungal disease affecting rice production worldwide.

Culture Media↗

Characterisation of a cyanide hydratase gene in the phytopathogenic fungus Leptosphaeria maculans.

A gene encoding a cyanide hydratase was cloned from an aggressive isolate of Leptosphaeria maculans, the fungus which causes blackleg disease of oilseed Brassica spp. This enzyme catalyses the breakdown of hydrogen cyanide to a less toxic compound, formamide. The predicted amino acid sequence of cyanide hydratase in L. maculans is 77% and 82% identical to cyanide hydratases from two other ascomycetes, Gloeocercospora sorghi and Fusarium lateritium, respectively. The gene is present as a single copy in the L. maculans genome, in both aggressive and non-aggressive isolates, although there is a restriction fragment length polymorphism between these two isolate groups for this gene. The cyanide hydratase promoter contains four putative target sites for GATA transcription factors, proteins that regulate nitrogen metabolism and other processes. Transcription of cyanide hydratase in an aggressive L. maculans isolate is induced strongly by potassium cyanide. Transcription of the gene is detectable in cotyledons of Brassica juncea and B. napus during infection. L. maculans can utilise the reaction product, formamide, as a sole source of nitrogen.

Amino Acid Sequence↗

Malabsorption syndrome occurring in the course of disseminated histoplasmosis: case report and review of gastrointestinal histoplasmosis.

Histoplasmosis is caused by the dimorphic fungus, Histoplasma capsulatum. The disease spectrum varies from a mild respiratory infection to a lethal, disseminated form. Involvement of any part of the gastrointestinal tract may occur with the disseminated form, and symptoms reflect that portion involved. A case of malabsorption syndrome occurring during the course of disseminated histoplasmosis is reported, and the literature of gastrointestinal histoplasmosis is reviewed.

Biopsy↗

[Histoplasmosis, caused by Histoplasma capsulatum, and AIDS].

Histoplasma capsulatum histoplasmosis occurs frequently in endemic areas and with the AIDS outbreak, it appears as an opportunistic fungus involved in disseminated disease. We report the clinical, biological and treatment features of seven cases diagnosed in the CISIH of the Eastern part of Paris. Clinically, four patients were suffering from pulmonary symptoms, in three cases digestive disorders and in three cutaneous lesions. In all cases, the mycologic diagnosis was necessary. Amphotericin B and itraconazole were used as treatment for five patients (two died before the diagnosis was completed). Among these five subjects, four died (death was attributed to histoplasmosis in only one case). These observations emphasize the importance of this infection in HIV-infected patients coming from endemic areas.

AIDS-Related Opportunistic Infections↗

GhHb1: a nonsymbiotic hemoglobin gene of cotton responsive to infection by Verticillium dahliae.

Verticillium wilt of cotton is a widespread and destructive disease that is caused by the fungus pathogen Verticillium dahliae. Although no cotton cultivar is immune to the disease, some genotypes exhibit superior wilt tolerance. To gain an insight into the molecular mechanisms responsible for wilt tolerance, we employed the method of suppression subtractive hybridization (SSH) to isolate genes whose expression is up-regulated after inoculation of the pathogen in a wilt-tolerant cotton cultivar (Gossypium hirsutum cv. BD18). Among the identified candidate ESTs, a cDNA representing a nonsymbiotic hemoglobin gene (designated GhHb1) was further characterized in this study. Northern blot hybridization demonstrated that GhHb1 shares similar characteristics to some other nonsymbiotic hemoglobin genes including the hypoxic stress-induced expression. Sub-cellular localization analysis indicated that GhHb1 proteins were predominantly present in the nucleus with a minor amount appearing in the cytoplasm. Two novel features of GhHb1 were also identified, indicating that GhHb1 expression is activated in the cotton roots after inoculation with V. dahliae and that exogenous hydrogen peroxide induces GhHb1 expression. These results suggest that the GhHb1 may play a role in the defense response of G. hirsutum against V. dahliae invasion.

Amino Acid Sequence↗

An iterative type I polyketide synthase PKSN catalyzes synthesis of the decaketide alternapyrone with regio-specific octa-methylation.

A biosynthetic gene cluster containing five genes, alt1-5, was cloned from Alternaria solani, a causal fungus of early blight disease to tomato and potato. Homology searching indicated that the alt1, 2, and 3 genes code for cytochrome P450s and the alt4 gene for a FAD-dependent oxygenase/oxidase. The alt5 gene encodes a polyketide synthase (PKS), named PKSN, that was found to be an iterative type I complex reduced-type PKS with a C-methyltransferase domain. To identify the PKSN function, the alt5 gene was introduced into the fungal host Aspergillus oryzae under an alpha-amylase promoter. The transformant produced a polyketide compound, named alternapyrone, whose structure is shown to be 3,5-dimethyl-4-hydroxy-6-(1,3,5,7,11,13-hexamethyl-3,5,11-pentadecatrienyl)-pyran-2-one. Labeling experiments confirmed that alternapyrone is a decaketide with octa-methylation from methionine on every C(2) unit except the third unit.

Alternaria↗

Fusarium oxysporum G-protein beta subunit Fgb1 regulates hyphal growth, development, and virulence through multiple signalling pathways.

The vascular wilt fungus Fusarium oxysporum causes disease in a wide variety of crops. A signalling cascade controlled by the extracellular-regulated mitogen-activated protein kinase (MAPK) Fmk1 was previously found to be required for plant infection. To investigate the role of the heterotrimeric G-protein beta subunit Fgb1 as a putative upstream component of the Fmk1 signalling cascade, we generated F. oxysporum strains carrying either a Deltafgb1 loss-of-function allele or an fgb1(W115G) allele that mimicks the yeast STE4(W136G) mutation resulting in insensitivity to the cognate G-protein alpha subunit. Both types of mutants showed reduced virulence on tomato plants, similar to Deltafmk1 strains. However, in contrast to the latter, Deltafgb1 mutants displayed an abnormal hyphal growth phenotype with highly elongated cells, increased tip growth, a completely straight hyphal growth axis, and reduced subapical branching. Exogenous cAMP reversed part but not all of the Deltafgb1 growth phenotypes. Likewise, expression of the fgb1(W115G) allele only partly reversed growth phenotypes and failed to restore virulence on plants, whereas reintroduction of a functional fgb1 allele fully restored the wild type phenotype. Immunoblot analysis showed that levels of Fmk1 phosphorylation in fgb1 mutants were comparable to those in the wild type strain. Our results support a model in which Fgb1 controls hyphal growth, development and virulence in F. oxysporum both through cAMP-dependent and -independent pathways.

Calcium↗

Regulation of mating and pathogenic development in Ustilago maydis.

The plant pathogenic fungus Ustilago maydis induces disease only in its dikaryotic stage that is generated after mating. This process involves coordinated cAMP and mitogen-activated protein kinase signalling to regulate transcriptional as well as morphological responses. Among the induced products is the key regulator for pathogenic development. Recent advances identified crucial nodes that interconnect these pathways. The key regulator orchestrates a complex transcriptional cascade, the components of which have been uncovered by genomic strategies. This is complemented by insights into organization, dynamics and function of the cytoskeleton, which begin to establish the links between signalling, intracellular transport processes and morphology.

Fungal Proteins↗