Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a variety of fungal species, mating between haploid cells is initiated by the action of peptide pheromones. The identification and characterization of several fungal pheromones has revealed that they have common structural features classifying them as lipopeptides. In the course of biosynthesis, these pheromones undergo a series of posttranslational processing events prior to export. One common modification is the attachment of an isoprenoid group to the C terminus of the pheromone precursor. Genetic and biochemical investigations of this biosynthetic pathway have led to the elucidation of genes and enzymes which are responsible for isoprenylation of other polypeptides including the nuclear lamins, several vesicular transport proteins, and the oncogene product Ras. The alpha-factor of Saccharomyces cerevisiae serves as a model for studying the biosynthesis, export, and bioactivity of lipopeptide pheromones. In addition to being isoprenylated with a farnesyl group, the alpha-factor is secreted by a novel peptide export pathway utilizing a yeast homolog of the mammalian multidrug resistance P-glycoprotein. The identification of putative lipopeptide-encoding loci within other fungi, including the human immunodeficiency virus-associated opportunistic pathogen Cryptococcus neoformans and the plant pathogen Ustilago maydis, has stimulated much interest in understanding possible roles for pheromones in fungal proliferation and pathogenicity. Knowledge of variations within the processing, export, and receptor-mediated signal transduction pathways associated with different fungal lipopeptide pheromones will continue to provide insights into similar mechanisms which exist in higher eukaryotes.
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PMID:Fungal lipopeptide mating pheromones: a model system for the study of protein prenylation. 756 12

Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a filamentous mold aerobically on the surface of broth cultures but at the bottom of the flask where the environment was anaerobic it reproduced as budding yeast cells. Several infectious fungal pathogens of humans, namely Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenkii, and Coccidioides immitis change from a multicellular filamentous form to an unicellular morphology when they invade tissues. The ability of pathogenic fungi to assume a different shape is referred to as dimorphism. This phenomenon has intrigued clinicians, and medical mycologists since its discovery at the turn of the century. The ability of pathogens to initiate infection, invade host tissues and survive in mammalian hosts is critically linked to the induction of specific gene products. In dimorphic fungi, developmentally regulated gene expression is particularly important, since they may exist in phylogenetically distinct hosts with different body temperatures. Using Histoplasma capsulatum as a model to study parasite-host interactions at the biochemical and molecular level, my laboratory has attempted to relate the clinical spectrum of disease to natural variations in the characteristics of this organism and to adaptations it must make as a saprobe and a parasite. Histoplasma capsulatum is the etiologic agent of histoplasmosis, a respiratory infection that is world-wide in distribution. As a saprobe in soil it is mycelial, but it becomes a budding yeast as a parasite in susceptible hosts. These morphological phases can be reversibly reproduced in vitro by shifting the temperature from 25 degrees C, at which it is mycelial, to 37 degrees C, when it becomes a budding yeast. The process of mycelial-to-yeast conversion is of particular interest since it is triggered by an increase in temperature and conversion to virulence. Viable mycelial fragments and conidia become airborne and enter the pulmonary tract by inhalation after which the fungus rapidly disseminates to other organs. Progressive disseminated histoplasmosis along with candidiasis, cryptococcosis, and invasive aspergillosis are opportunistic fungal infections in patients who are immunosuppressed or otherwise debilitated. Importantly, they are diagnostic hallmarks of acquired immunodeficiency disease syndrome (AIDS). The clinical features of these infections and the genetic characteristics of the etiologic agents present unique parasite-host interactions that make them valuable research models to study. In the infected host, Histoplasma capsulatum encounters various environmental stresses to which it adapts by regulating the expression of specific genes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Unraveling the secrets of Histoplasma capsulatum. A model to study morphogenic adaptation during parasite host/host interaction. 757 55

Fungal infections figures large in HIV-infected patients. Candida infections of the mucous membranes belong to the main manifestations of immunodeficiency in HIV infection. For therapy and prophylaxis of oropharyngeal candidosis mainly systemically acting azoles as ketoconazole, fluconazole and itraconazole are applied; antimycotics to be administered topically regularly fail to act in patients with progressing disease. Ketoconazole tablets were used with good success in previous years of the AIDS epidemics. Application of ketoconazole in liquid formulation led to a significant increase in efficacy. Subsequently fluconazole proved to be a triazole with evidently better pharmacological properties leading to good clinical efficacy. Presently it represents the drug of first choice in acute and maintenance therapy of recurrent oropharyngeal and oesopharyngeal candidosis. In the case of therapy failure with fluconazole the administration of itraconazole in liquid cyclodextrine formulation can replace or at least delay the administration of amphotericin B plus flucytosine, a therapy rich in toxic side effects. The standard therapy of disseminated cryptococcosis--particularly of cerebral manifestation--is still the administration of amphotericin B combined with flucytosine. Alternative drugs are represented by fluconazole and itraconazole. However, an azole monotherapy seems to be legitimate only in primary cryptococcosis of the lungs or in early stages of secondary extrapulmonary infection. Cryptococcal meningitis requires an intense initial therapy. New therapy strategies were developed combining azoles with standard antimycotic drugs. The value of amphotericin B in liposomal or lipid complex formulations is still undetermined due to the up to now low number of AIDS patients treated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapy of candidiasis and cryptococcosis in AIDS]. 760 45

Surgical consultation is regularly requested for diagnosis and treatment of pulmonary complications of the endemic mycosis, Histoplasma capsulatum, Blastomyces dermatitidis and Coccidioidomycosis immitis, and the yeast Cryptococcus neoformans. All resemble pulmonary malignancies. Histoplasmosis causes pericarditis, mediastinal fibrosis and mediastinal granuloma, which can cause entrapment of vascular structures, the esophagus, and the trachea. Coccidioidomycosis can cause spontaneous pneumothorax and thin wall cavities that can be superinfected with tuberculosis and Aspergillosis. The pathogenesis, diagnosis, and treatment of these organisms are discussed with emphasis on the new oral therapies and complications encountered in persons with human immunodeficiency virus (HIV) infection.
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PMID:The endemic mycoses: surgical considerations. 761 61

A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans. He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed. We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS. Only three other cases of empyema, one of them in an HIV-infected patient, have been reported. A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients.
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PMID:Cryptococcal empyema: case report and review. 762 32

The Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) has been conjugated to tetanus toxoid (GXM-TT) as an investigational vaccine. GXM-TT elicits antibodies that are protective in C. neoformans-infected mice. In an effort to characterize the fine specificity and molecular structure of human GXM-TT-elicited antibodies, we generated two GXM monoclonal antibodies (MAbs) from peripheral blood lymphocytes of a volunteer GXM-TT recipient and studied serum GXM antibody idiotype expression in 10 additional vaccinees. The MAbs, 2E9 and 3B6, are the immunoglobulin M(lambda) isotype and bind capsular polysaccharides of C. neoformans serotypes other than the serotype A that was used for immunization. Neither antibody competes with murine GXM MAbs for antigen binding, suggesting that the human MAbs recognize a different epitope. The B-cell superantigen staphylococcal protein A binds both MAbs, and human immunodeficiency virus gp120 binds 2E9. MAb nucleic acid sequence analysis revealed that both antibodies use an identical V lambda 1a-J lambda genetic element with different, somatically mutated, members of the VH3 gene family and different DH and JH gene elements. The gene elements used by both MAbs occur in fetal B-lymphocyte repertoires, autoantibodies, and other polysaccharide antibodies. Post-GXM-TT vaccination GXM antibodies from 10 additional vaccinees expressed a shared idiotype defined by rabbit antiserum raised against MAb 2E9. Our data suggest that the human GXM antibody response is restricted and raise questions regarding the importance of specific variable-region elements and superantigens in the generation of human antibody responses to encapsulated pathogens.
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PMID:Analysis of human monoclonal antibodies elicited by vaccination with a Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide vaccine. 762 23

A chest x-ray showing a large tumor-like opacity in the left lower lobe and endoscopy visualizing a budding mass suggested a diagnosis of bronchial carcinoma in a 55-year old, tobacco-smoking Cambodian who consulted for hemoptysis and altered general status. Histological study of bronchial biopsies allowed differential diagnosis of cryptococcosis. Serologic tests for human immunodeficiency virus were negative and there was no other cause of immunodepression. Left lower lobectomy was performed at the German hospital of the APRONUC in Phnom Penh. Examination of the surgical specimen confirmed massive bronchopulmonary cryptococcosis. Two months after the procedure the patient was readmitted for neuromeningial cryptococcosis that responded well to fluconazole. Another relapse occurred 5 months later and was treated using the same drug. The patient is currently in remission. An increasingly common deep mycosis that is serious but curable with proper treatment, cryptococcosis deserves the full attention of physicians working in Cambodia where, as in other tropical zones, it is likely that this infection will progress with the incidence of AIDS. Symptoms can be misleading, suggesting neuromeningial or pulmonary tuberculosis. The value of India ink smear which should be performed in all patients presenting lymphocytic meningitis with hypoglycorrhachia must be emphasized. In the present case bronchoscopy was useful to distinguish from bronchopulmonary cancer.
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PMID:[Severe pulmonary and meningeal cryptococcosis in an immunocompetent Cambodian]. 763 12

The effect of infection with human immunodeficiency virus (HIV) on the capacity of human lymphocytes and monocytes to inhibit and kill Cryptococcus neoformans in an 18-h assay was examined. In vitro infection of the Jurkat human T cell line with each of 3 HIV strains caused significant loss of anticryptococcal activity, which peaked 3-4 weeks after HIV infection. Lymphocytes from HIV-seropositive and -seronegative persons had similar activity, even if highly enriched for CD4 cells. The activity of lymphocytes from both seropositive and seronegative donors was increased by culture with interleukin-2 and phytohemagglutinin, but only activated lymphocytes from seronegative donors caused a reduction in C. neoformans colony-forming units. Both peripheral blood mononuclear cells and monocytes from HIV-positive persons had significantly reduced antifungal activity compared with cells from seronegative donors. Thus, under defined conditions, infection with HIV can impair the anticryptococcal activity of both lymphocytes and monocytes. Such qualitative defects may contribute, together with CD4 lymphocytopenia, to the particular susceptibility of HIV patients to cryptococcosis.
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PMID:The effect of infection with human immunodeficiency virus on the anticryptococcal activity of lymphocytes and monocytes. 765 57

We compared the abilities of random amplification of polymorphic DNA and DNA fingerprinting, with oligonucleotide probes, to type five pairs of Cryptococcus neoformans clinical isolates recovered from five separate human immunodeficiency virus-positive patients in London, England. The two techniques had comparable discriminatory abilities when applied to these isolates. A total of eight different isolate types were demonstrated in these patients. No isolate type was observed in more than one patient. Two of the isolate pairs recovered from single episodes of cryptococcosis within 1 day of each other were genotypically indistinguishable by both methods. The other three pairs of isolates were all distinguishable. One of these isolate pairs was obtained from a single episode of cryptococcosis, while the other two were obtained from recurrent infections. These results indicate that multiple strains of C. neoformans may be responsible for a single episode of cryptococcosis and that recurrent infection may occur as a result of reinfection with a novel strain.
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PMID:Involvement of multiple Cryptococcus neoformans strains in a single episode of cryptococcosis and reinfection with novel strains in recurrent infection demonstrated by random amplification of polymorphic DNA and DNA fingerprinting. 765 Feb 17

Autopsy or biopsy findings in 10 human immunodeficiency virus (HIV)-positive persons from Bangalore, India, revealed a wide spectrum of pathological changes. Patients' mean age was 33.4 years and the mean duration between symptom onset and death was 27.13 days. Nine patients had evidence of neuro-acquired immunodeficiency syndrome (AIDS) and 8 of them succumbed to various opportunistic infections. Histologic examination showed diffuse cryptococcal meningitis in 5 cases; 2 cases showed disseminated systemic cryptococcosis. Pulmonary tuberculosis was present in 3 patients. Despite no signs of associated neurotuberculosis in any patient, 4 autopsied and 1 biopsied case showed evidence of systemic tuberculosis. Toxoplasma encephalitis was present in 2 cases; observed in this series was the first case, in India, of co-existent toxoplasma and acanthamoeba. Other bacterial infections such as meningococcal meningitis and psudomonas septicemia were found in 3 cases; pneumocystis carinii pneumonia was present in 1 case. Evidence of early HIV leukoencephalopathy was observed in the only asymptomatic HIV-positive individual (who died in a traffic accident). AIDS-associated bacterial infections caused by organisms other than Mycobacterium tuberculosis are often underdiagnosed and should be considered in developing countries. In cases of cryptococcal and tuberculosis meningitis or multiple parasitic infections, patients should be screened for associated HIV infection.
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PMID:Pathological lesions in HIV positive patients. 775 Oct 41


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