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PubMed2002

Identifying protein kinase inhibitors using an assay based on inhibition of aerial hyphae formation in Streptomyces.

We have identified a strain of Streptomyces in which aerial hyphae formation appears to be especially sensitive to inhibition by protein kinase inhibitors. Using this assay, a number of bacterial cultures have been screened and novel inhibitors of eukaryotic protein kinases have been identified. Since M. tuberculosis possesses multiple eukaryotic-like protein kinase genes, we tested the active kinase inhibitors for the inhibition of mycobacterial growth and obtained several potent compounds. This identifies a new biochemical class of antimycobacterial agents.

Bacillus↗
PubMed2000

[Development of arterial thrombus of Mucorales hyphae during deferoxamine therapy in a patient with aplastic anemia in transformation to myelodysplastic syndrome].

A 58-year-old woman with a diagnosis of aplastic anemia had been treated with anabolic steroid for mild anemia in 1984. In May 1995, pancytopenia progressed and the patient became dependent on red blood cell transfusions. Chromosome analysis of bone marrow cells revealed trisomy 8 and the patient was thought to have aplastic anemia in transformation to myelodysplastic syndrome. In July 1996, deferoxamine was administered for iron overload. The patient was admitted because of pneumonia on July 31, 1998. Chest computed tomograms showed arteriothrombus of the right pulmonary artery and pulmonary mycosis. Although an antifungal agent was administered, the patient experienced respiratory failure and eventually died of hypovolemic shock due to gastric bleeding from a Dieulafoy ulcer. Autopsy revealed arteriothrombus of hyphae of Mucorales in the right pulmonary artery and right renal artery branch. Cases of mucormycosis occurring in dialysis patients receiving deferoxamine have recently appeared in the literature. Deferoxamine may be a risk factor for mucormycosis. Deferoxamine has been also used in the treatment of iron overload patients with aplastic anemia. Four cases of mucormycosis developing in such patients have been reported in Japan including this case. There may be a relationship between mucormycosis and deferoxamine in patients with aplastic anemia.

Anemia, Aplastic↗
PubMed2000

[Lung cancer obscured by aspergillus hyphae].

A 66-year-old man was referred to our hospital because of cough. Chest X-ray films showed complete atelectasis of the left lung. Serum CYFRA was elevated. Bronchoscopic examination disclosed a white polypoid lesion occluding the left main bronchus. A biopsy specimen from the lesion revealed numerous aspergillus hyphae. Oral itraconazole (100 mg) and weekly endobronchial instillation of fluconazole were administered. Three months later, on the 12th bronchoscopic examination, the tumor occluding the left main bronchus was detected after the removal of aspergillus, and the biopsy findings yielded a diagnosis of squamous cell carcinoma. Aspergillosis complicated by lung cancer without cavity formation is very rare, and compounded the difficulty of diagnosing lung cancer in this case.

Aged↗
PubMed2001

Aliquandostipitaceae, a new family for two new tropical ascomycetes with unusually wide hyphae and dimorphic ascomata.

In two short surveys of lignicolous, fruitbody-forming ascomycetes in Thailand and southern China, six species were found, of which five were new to science. Two fungi with affinity to the Dothideomycetes, one from Thailand and one from China, are described here in the new genus ALIQUANDOSTIPITE: and included in the new family Aliquandostipitaceae. Aliquandostipite khaoyaiensis was found in a tropical rain forest in Thailand and A. sunyatsenii in a small stream in southern China. Both new species are closely related based on morphological and molecular characteristics and with uncertain affinity to other taxa of the Euascomycetes based on phylogenetic analyses of SSU rDNA sequences. The distinguishing features of the new species are the presence of both sessile and stalked ascomata side by side on the substratum and the widest hyphae known from ascomycetes.

Journal Article↗
PubMed2003

Comparative effect of osmium tetroxide and ruthenium tetroxide on Penicillium sp. hyphae and Saccharomyces cerevisiae fungal cell wall ultrastructure.

The fungal cell wall viewed through the electron microscope appears transparent when fixed by the conventional osmium tetroxide method. However, ruthenium tetroxide post-fixing has revealed new details in the ultrastructure of Penicillium sp. hyphae and Saccharomyces cerevisiae yeast. Most significant was the demonstration of two or three opaque diverse electron dense layers on the cell wall of each species. Two additional features were detected. Penicillium septa presented a three-layered appearance and budding S. cerevisiae yeast cell walls showed inner filiform cell wall protrusions into the cytoplasm. The combined use of osmium tetroxide and ruthenium tetroxide is recommended for post-fixing in electron microscopy studies of fungi.

Cell Wall↗
PubMed1992

[Modulating effects of extractum semen Persicae and cultivated Cordyceps hyphae on immuno-dysfunction of inpatients with posthepatitic cirrhosis].

The treatment of 65 cases (with 20 cases in the control group) of patients with post-hepatic cirrhosis by Extractum Semen Persicae (ESP) and cultivated Cordyceps Hyphae (CH) was reported, and the adjustment of the disorders of both cellular and humoral immune functions was investigated. The results indicated apparently that the restrained cellular immune function, among which the rate of lymphocyte transformation, the NK cell's function, CD8+ and CD4+ cells in the patients' group were lower than those in the healthy group. The CD8+ cell count was positively correlated with lymphocyte transformation rate and the humoral immune hyperfunction revealing that the levels of IgG, IgA, ssIgA and CIC of the patients were abnormally higher than those of healthy subjects, while level of C3 was negatively correlated with that of CIC. After the treatment, rate of transformation, function of NK cell, CD8+, CD4+ cells and the ratio of CD4+/CD8+ improved; levels of IgG, IgA, ssIgA and CIC reduced, while those of C4 and C3 rose. These results revealed the ESP and cultivated CH could modulate the cellular immune function, inhibit the humoral immune hyperfunction and increase serum complement level in patients with post-hepatitic cirrhosis, which were correlated to the improvement of hepatic function. Disorder of immune function was one of the important causes of liver cell necrosis, inflammatory cell infiltration and fibroplastic proliferation. The results showed that the drugs are of some value in the treatment of patients with post-hepatitic cirrhosis.

Adult↗
PubMed1988

A novel natural inhibitor from Candida albicans hyphae causing dissociation of the neutrophil respiratory burst response to chemotactic peptides from other post-activation events.

Previous work established that Candida albicans hyphae release several inhibitors of human neutrophil function. We now report that the crude hyphal inhibitory product (CHIP) inhibits superoxide anion (O2-) production stimulated by FMLP in a dose-related manner with an EC50 of approximately 2 micrograms/ml. CHIP also inhibited O2- production stimulated by A23187 and by opsonized zymosan, although this effect could be overcome by increasing the concentration of agonist. No inhibition of the PMA-stimulated burst was seen at any concentration of PMA tested, indicating that CHIP neither affected polymorphonuclear neutrophil viability nor quenched superoxide anion detection. A saturating dose of inhibitor had no effect on chemotaxis stimulated either by 0.1 to 100 nM FMLP or by zymosan-activated serum. Peak inositol trisphosphate levels stimulated by FMLP were not inhibited by a dose of CHIP producing maximum inhibition of FMLP-induced superoxide production. Peak changes in cytosolic free calcium levels (as measured by indo-1 fluorescence) stimulated by 50 nM or greater FMLP were unaffected by CHIP, although for subsaturating doses of FMLP a more rapid decline from peak calcium levels was seen in CHIP-exposed cells. Taken together, these data suggest that the common fungal pathogen C. albicans releases a substance that selectively impairs the neutrophil respiratory burst. It appears to do so without inhibiting the fully assembled NADPH oxidase and with minimal or no effect on events tightly coupled to FMLP-R/G protein activation, suggesting that these events may be uncoupled from activation of the burst. In addition, the absence of effect of CHIP on chemotaxis despite profound inhibition of the respiratory burst suggests these neutrophil functions may be mediated by divergent transduction pathways.

Calcium↗
PubMed1985

Electrobiology of fungal hyphae.

Hyphae of many fungi drive electric currents through themselves. In Achlya bisexualis the current is carried by protons which enter the apical region by symport with amino acids and are expelled distally. The proton current may play a role in the spatial localization of apical growth.

Electric Conductivity↗
PubMed1988

[The effect of cytochalasin A on the composition of subcellular fractions of hyphae in the growth of Mucor mucedo L. I. Composition of the plasmalemma].

The plasma membrane of young hyphae of Mucor mucedo L. growing in presence or absence of cytochalasine A was isolated by continuous density gradient centrifugation using Percoll at 10% or on discontinuous sucrose density gradient. Isolated membranes were characterized by enzymatic markers and cytochemical reactions, using electron microscopy. Lipid composition and protein content were determined. From the enzymatic point of view, the cytochalasine A induced a decrease (60%) in ATPase activity and with regard to the chemical composition of the membrane, a decrease in sterol content and in the sterol-phospholipid ratio as well as a decrease in protein content and an increase in the proportion of cysteine relative to other amino acids.

Adenosine Triphosphatases↗
PubMed1988

[Localization and dynamics of lipase accumulation in Penicillium solitum hyphae].

Lipase localization in the mycelium of Penicillium solitum was studied with cytochemical and immunofluorescent methods. The use of these methods provided detection of the enzyme on the cell walls of the fungus at all periods of its cultivation. The enzyme was not detected in the cell cytoplasm. Measuring of lipase concentrations on the cell walls in relation to the cultivation period suggested that excretion of the exoenzyme into the medium followed its accumulation on the cell walls of the hyphae.

Cell Wall↗
PubMed1988

[The effect of cytochalasin A on the composition of subcellular fractions of hyphae in the growth of Mucor mucedo. II. Composition of the cell wall].

Walls of young hyphae of Mucor mucedo L. growing in the presence or absence of cytochalasin A were isolated and their chemical content determined. Cytochalasin A induced modified proportions of various monomers resulting in a reduction of the (neutral sugars + glucuronic acid)/glucosamine ratio. The walls contained less proteins but more chitin-chitosan and phosphate. These modifications are discussed in relation to ultrastructural changes described previously.

Amino Acids↗
PubMed1980

[Physiological studies on thermophilic hydrocarbon-utilizing hyphae fungi (author's transl)].

Out of different substrates, thermophilic n-alkane-assimilating hyphae fungi were isolated and the strains of Aspergillus fumigatus and Mucor lusitanicus selected for physiological investigations. The growth curves, obtained in hydrocarbon and glucose at different temperatures, showed three phases: 1) initial growth phase, 2) linear growth phase, and 3) lysis phase. Maximum dry matter and maximum protein content occurred within a range of 35-40 degrees C. During the entire time of growth the DNA content per mg dry matter was almost the same, i.e., 0.1-0.2 per cent. The ascertained specific protease activity of Aspergillus fumigatus correlated with protein synthesis and protein decomposition of the biomass. The results of our investigations are being discussed.

Aspergillus fumigatus↗
PubMed1994

[Pharmacological actions of hyphae body of Auricularia auricula (L. ex Hook) Underw and its alcoholic extract].

The percent peripheral blood T lymphocytes were elevated and HC50 reduction induced by cyclophosphamide was recovered after the hyphae body of Auricularia auricula had been ip administered in mice. The action of blood platelet agglutination in rats induced by ADP was inhibited and the time of erythrocytic electrophoresis in mice was shortened after the alcoholic extract had been ig administered.

Animals↗
PubMed1975

Ribosomal proteins from vegetative hyphae and from spores of Streptomyces griseus.

Ribosomes from vegetative cells and spores of Streptomyces griseus have been used to prepare ribosomal proteins for polyacrylamide gel electrophoresis. Differences in the gel electrophoretic profile of proteins from vegetative cells and spore ribosomes can be detected. Spore ribosomes were stable during the isolation process, but in the case of vegetative cell ribosomes it was necessary to use protease inhibitor to obtain reproducible results. Suspensions of washed ribosomes of vegetative hyphae have higher proteolytic activity than ribosomes from spores.

Ribosomal Proteins↗
PubMedDate not supplied

Production of cytokines by alveolar and peritoneal macrophages stimulated by Aspergillus fumigatus conidia or hyphae.

Aspergillus fumigatus is an opportunistic pathogen responsible for severe, invasive infections in neutropenic hosts. Lung clearance of A. fumigatus conidia seems to be mediated by phagocytic cells and oxygen radicals. It is not known if cytokines or nitrogen radicals are also involved. We tested for the production of TNF alpha, IL-1 and nitric oxide (NO) after stimulation of mouse macrophages with the fungus. We found that both cytokines, but not NO, were produced in a dose-dependent manner during the first 24 h of culture. Except for a faster kinetic, no appreciable differences were seen between alveolar and peritoneal macrophages. Furthermore, both hyphae and conidia, either alive or killed, were capable of inducing cytokines production. However, among different Aspergillus spp. only A. fumigatus and A. flavus seemed to induce significant amount of TNF alpha and IL-1, whereas A. terreus and A. niger were less effective. In no case could we detect production of NO. Finally, macrophages from dexamethasone-treated mice failed to produce cytokines in response to A. fumigatus conidia. These results indicate that in normal hosts inflammatory cytokines contribute to the natural response against Aspergillus infections and suggest that the impairment of cytokine production, in immunodepressed patients, may favour the growth and spread of the fungus.

Animals↗
PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae.

Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O2-) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml-1) for 48 h suppressed O2- release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml-1) and IFN-gamma (1.2 ng ml-1) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O2- release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis.

Adult↗