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 our study we examined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activity of a novel HIV-1 protease inhibitor, PNU-140690 (tipranavir), against patient-derived isolates resistant to multiple other protease inhibitors (PIs). The aim of our experiments was to investigate the genotypes and the in vitro phenotypes of drug resistance of PNU-140690. We carried out drug susceptibility tests with peripheral blood mononuclear cells and a fixed amount of infectious virus (1,000 50% tissue culture infective doses) to determine the 50% inhibitory concentration (IC(50)) and IC(90), PCR assays for the detection of drug resistance mutations in RNA in plasma, and direct sequencing of PCR products. Phenotypic resistance to PIs was invariably related to genotypic mutations. The substitutions among the amino acid residues of the protease included L10I, K20R, L24I, M36I, N37D, G48V, I54V, L63P, I64V, A71V, V77I, V82A, I84V, and L90M. Isolates from all of the patients had developed a maximal degree of resistance to indinavir, ritonavir, and nelfinavir (IC(50)s, >0.1 microM). We also compared these mutations with the amino acid changes previously described in association with in vivo tipranavir administration. The mutations included the following: I15V, E35D, N37D, R41K, D60E, and A71T. Infections with IIIB, 14aPre, and N70 were inhibited by an average drug IC(90) of 0.18 +/- 0.02 microM in multiple experiments. The average mean +/- standard error of mean IC(90) for the entire group of multidrug-resistant isolates derived from the mean values for two culture wells with p24 antigen supernatant appeared to be 0.619 +/- 0.055 microM (range, 0.31 to 0.86 microM). Tipranavir retained a sustained antiviral activity against PI-MDR clinical isolates and might be useful in combination regimens with other antiretroviral agents for patients who have already failed other PI-containing therapies.
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PMID:Susceptibility to PNU-140690 (Tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. 1077 Jul 70

Infection of the brain by lentiviruses, including human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV), causes inflammation and results in neurodegeneration. Molecular diversity within the lentivirus envelope gene has been implicated in the regulation of cell tropism and the host response to infection. Here, we examine the hypothesis that envelope sequence diversity modulates the expression of host molecules implicated in lentivirus-induced brain disease, including matrix metalloproteinases (MMP) and related transcription factors. Infection of primary macrophages by chimeric HIV clones containing brain-derived envelope fragments from patients with HIV-associated dementia (HAD) or nondemented AIDS patients (HIV-ND) showed that MMP-2 and -9 levels in conditioned media were significantly higher for the HAD clones. Similarly, STAT-1 and JAK-1 levels were higher in macrophages infected by HAD clones. Infections of primary feline macrophages by the neurovirulent FIV strain (V(1)CSF), the less neurovirulent strain (Petaluma), and a chimera containing the V(1)CSF envelope in a Petaluma background (FIV-Ch) revealed that MMP-2 and -9 levels were significantly higher in conditioned media from V(1)CSF- and FIV-Ch-infected macrophages, which was associated with increased intracellular STAT-1 and JAK-1 levels. The STAT-1 inhibitor fludarabine significantly reduced MMP-2 expression, but not MMP-9 expression, in FIV-infected macrophages. Analysis of MMP mRNA and protein levels in brain samples from HIV-infected persons or FIV-infected cats showed that MMP-2 and -9 levels were significantly increased in lentivirus-infected brains compared to those of uninfected controls. Elevated MMP expression was accompanied by significant increases in STAT-1 and JAK-1 mRNA and protein levels in the same brain samples. The present findings indicate that two lentiviruses, HIV and FIV, have common mechanisms of MMP-2 and -9 induction, which is modulated in part by envelope sequence diversity and the STAT-1/JAK-1 signaling pathway.
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PMID:Lentivirus infection in the brain induces matrix metalloproteinase expression: role of envelope diversity. 1090 75

Infections by human and simian immunodeficiency viruses (HIV and SIV) are independent of host cell division since the preintegration complex (PIC), containing the viral DNA, is able to undergo active nuclear import after viral entry. In order to clarify the mechanisms responsible for nuclear import of the PIC, we have analyzed the subcellular distribution and the karyophilic properties of its viral components, matrix protein (MA), integrase (IN), Vpr, and Vpx. Although MA has been reported to contain a nuclear localization signal, the MA/GFP fusions are excluded from the nucleus and associated with cellular membranes. In contrast, both HIV-1 and SIV IN and Vpr localize in the nucleus of transfected cells. Interestingly, only Vpx from SIVsm virus accumulate in the nucleus while SIVsm Vpr is uniformly distributed throughout nucleus and cytoplasm. Coexpression of MA, Vpr, and IN does not induce any change in their respective intracellular localizations. Finally, we confirm the karyophilic properties of HIV-1 IN and Vpr using an in vitro nuclear import assay. These results indicate that the viral proteins IN and Vpr, which are strongly associated with the viral DNA within PIC, may participate in the nuclear import of the HIV PIC.
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PMID:Cellular distribution and karyophilic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses. 1103 35

A cross-sectional survey was conducted of sexually transmitted diseases (STDs) and risky behaviors among 407 drug abusers in treatment facilities in 1998. Infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus type 2 (HSV-2), and syphilis were detected by testing serum antibody levels; chlamydia and gonorrhea were detected by testing nucleic acid levels in urine. Logistic regression analysis was performed to measure associations. Prevalences of antibodies were as follows: to HSV-2, 44.4%; to HCV, 35.1%; to HBV, 29.5%; to HIV, 2.7%. The prevalence of syphilis was 3.4%; of chlamydia, 3.7%; and of gonorrhea, 1.7%. Of the 407 subjects, approximately 62% had markers for 1 of the STDs. HIV infection was associated with African American race, use of smokable freebase (crack) cocaine, and STD history. HBV infection was associated with age >30 years, injecting drugs, needle sharing, a history of treatment for drug abuse, and African American race. HCV infection was associated with an age >30 years, injecting drugs, and needle sharing, and HSV-2 infection with an age >30 years, female sex, and African American race. Syphilis was associated with a history of STDs. High prevalences of STDs among drug abusers indicate the need for integration of STD screening and treatment into drug treatment programs.
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PMID:Prevalence of sexually transmitted infections and associated risk factors among populations of drug abusers. 1104 71

Unlike hepatitis B virus and human immunodeficiency virus, there currently are no immunization or chemoprophylactic interventions available to prevent infection after an occupational exposure to hepatitis C virus (HCV). A "Reality Check" session was held at the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections to gather information on current practices related to management of occupational exposures to HCV, generate discussion on controversial issues, and identify areas for future research. Infection control professionals in attendance were knowledgeable in most issues addressed regarding the management of occupational exposures to HCV. Areas of controversy included the use of antiviral therapy early in the course of HCV infection and the appropriate administrative management of an HCV-infected healthcare worker.
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PMID:Management of occupational exposures to hepatitis C virus: current practice and controversies. 1119 26

Despite advances in diagnosis and treatment, the epidemiological status of the human immunodeficiency virus (HIV) infection is far from under control in most of the developing world. Sub-Saharan Africa, Southeast Asia and India show increased rates of new infections. In Latin America and the Caribbean there were 1.6 million estimated cases of HIV-infected patients at the end of 1997. Fungal diseases have been one of the most relevant diagnoses in relation to the acquired immunodeficiency syndrome (AIDS). Infections due to Candida species and Cryptococcus neoformans var. neoformans are common worldwide. Histoplasma capsulatum, Coccidioides immitis and Penicillium marneffei are important causes of disease in endemic areas. Infection due to Sporothrix schenckii, Blastomyces dermatitidis and Paracoccidioides brasiliensis are uncommon even where they are endemic. Phaeohyphomycetes, hyalohyphomycetes and zygomycetes are still rare as a cause of disease among AIDS patients. However, agents pertaining to these groups, such as Aspergillus spp., have an increasing incidence. Superficial mycoses due to dermatophytes have special features from epidemiological, clinical and therapeutic points of view.
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PMID:Mycoses associated with AIDS in the Third World. 1120 55

Bloodstream infections are a frequent complication in human immunodeficiency virus (HIV)-infected adults in Africa and usually associated with a poor prognosis. We evaluated bloodstream infections across a decade in 3 prospective cross-sectional surveys of consecutive medical admissions to the Kenyatta National Hospital, Nairobi, Kenya. Participants received standard clinical care throughout. In 1988-1989, 29.5% (28 of 95) of HIV-positive patients had bloodstream infections, compared with 31.9% (46 of 144) in 1992 and 21.3% (43 of 197) in 1997. Bacteremia and mycobacteremia were significantly associated with HIV infection. Infections with Mycobacterium tuberculosis, non-typhi species of Salmonella (NTS), and Streptococcus pneumoniae predominated. Fungemia exclusively due to Cryptococcus neoformans was uncommon. Clinical features at presentation remained similar. Significant improvements in the survival rate were recorded among patients with NTS bacteremia (20%-83%; P<.01) and mycobacteremia (0%-73%; P<.01). Standard clinical management can improve outcomes in resource-poor settings.
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PMID:Trends in bloodstream infections among human immunodeficiency virus-infected adults admitted to a hospital in Nairobi, Kenya, during the last decade. 1141 86

The pathogenicity of the nondiphtheria corynebacteria, most commonly known as coryneform bacteria in humans has been recognized in the last two decades. Corynebacterium xerosis is part of the normal flora of the skin, nasopharynx, conjunctives and it has recently been isolated from vaginal swabs. During the last few years, there has been an increased number of case reports claiming an association of C. xerosis with diseases, like septicemia, endocarditis, pleuropneumonia, peritonitis, osteomyelitis, septic arthritis, mediastinitis, meningitis, ventriculitis specially in immunocompromised patients or surgical patients. Infections due to C. xerosis have been reported rarely in newborn. We report a case of sepsis due to C. xerosis in a newborn without evident immunodeficiency. Our case further support the recognition of C. xerosis as a human pathogen and reinforces the fact that it should not be routinely considered as a contaminant.
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PMID:[Sepsis caused by Corynebacterium xerosis in neonatology: report of a clinical case]. 1142 46

A patient with end-stage renal disease due to human immunodeficiency-associated nephropathy developed fever, cough and chest pain over a week's duration. He was diagnosed with lung abscess and started on antibiotic coverage. He underwent bronchoscopy because of progression of his illness and persistent fever and bronchoalveolar lavage culture isolated Legionella micdadei. In spite of appropriate antibiotic therapy, the patient remained febrile for 10 days, necessitating chest tube drainage. After a 6-week course of antibiotics and drainage, the patient made an uneventful recovery. Infections due to L. micdadei may be hard to diagnose because of difficulties in isolating this bacteria.
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PMID:Legionella micdadei lung abscess in a patient with HIV-associated nephropathy. 1144 94

The symposium on Virus Infections and Tumors of the Oral Mucosae was organized as a joint meeting of the Arbeitskreis Oralpathologie and Oralmedizin and the Arbeitsgemeinschaft Dermatologische Infektiologie (ADI) der Deutschen Dermatologischen Gesellschaft. The main topics of the meeting were herpes virus infections, human papillomavirus (HPV) infections and human immunodeficiency virus (HIV) infections of the oral mucosae. Clinically both diagnostic, differential diagnostic and therapeutic aspects of the virus-associated diseases were discussed in several presentations. Another important issue was the role of these viruses, particularly of HPVs, in the origin and development of oral cancer. Apparently besides smoking and alcohol other risk factors comprise high risk HPVs, immunodeficiency and possibly also genetic factors. Whether neonatal early infections may predispose children to a specific cancer risk in their future life is still at a level of discussion. Some arguments, however were shown that tonsillar carcinoma, which shows the highest prevalence of the high-risk HPV 16- DNA sequences between all oral cancer, is possibly an epidemiologically and etiologically distinct tumor. It is argued that this tumor is probably less dependent on classical carcinogens than other oral malignant tumors.
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PMID:Virus infections and tumors of the oral mucosae. Symposium of the "Arbeitskreis Oralpathologie und Oralmedizin" and the "Arbeitsgemeinschaft Dermatologische Infektiologie der Deutschen Dermatologischen Gesellschaft", Rostock, July 6-7, 2001. 1169 31


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