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)

Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour in mice and their in vivo anti-HIV-1 efficacy in an HIV-1 infection model in mice. In contrast to the saturation kinetics found in rats, intravenous injections of 10-300 mg/kg for both NCAs showed a linear correlation between the area under the curve (AUC) and the dose. The elimination t1/2 was 25 and 30 min for Suc-HSA and Aco-HSA, respectively. Preinjections of an excess of formaldehyde-treated albumin (Form-HSA) resulted in plasma levels that were 3- and 4-fold higher for Aco-HSA and Suc-HSA, respectively. These data indicate that elimination is at least partly (scavenger) receptor-mediated. Organ distribution studies 10 min after injection showed an accumulation in liver (Suc-HSA 17.3 +/- 6.6% of the dose; Aco-HSA 20.9 +/- 2.3%) and lungs (Suc-HSA 12.7 +/- 10.5%; Aco-HSA 16.0 +/- 13.6). Intraperitoneal injection of 300 mg/kg Suc-HSA resulted in a final bioavailability of about 0.45. Suc-HSA was also evaluated for its in vivo neutralizing capacity in a human-to-mouse chimeric model for HIV-1 infection. Intraperitoneal injections of 300 and 3 mg/kg Suc-HSA, given 15-30 min before the mice were challenged with the virus, sufficed to protect these mice against infection with the HIV-1 IIIB strain.
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PMID:Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice. 902 Oct 51

Detailed analyses of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocyte (CTL) responses in vaccinated and infected macaques may help to clarify the role of CTL immunity in protection against lentiviruses. Here, the optimal conditions for the measurement of SIV Gag-specific CTL were investigated by bulk and limiting dilution assays of peripheral blood mononuclear cells (PBMC) from naive and vaccinated cynomolgus macaques (Macaca fascicularis) infected with SIVmac32H(J5). In vitro restimulation was generally required for CTL detection. Selective activation of CD8+ and MHC-restricted SIV Gag-specific CTL was induced by stimulation with autologous para-formaldehyde-fixed B-lymphoblastoid cell lines infected with a recombinant vaccinia virus expressing SIV Gag. Applied to limiting dilution assays, antigenic stimulation reproducibly demonstrated SIV Gag-specific CTL precursors (CTLp) in PBMC of all animals studied, including those lacking significant responses in standard bulk CTL assays.
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PMID:Simian immunodeficiency virus (SIV)-specific CD8+ cytotoxic T lymphocyte responses of naive and vaccinated cynomolgus macaques infected with SIVmac32H(J5): quantitative analysis by in vitro antigenic stimulation. 928 55

The susceptibility of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare to the disinfections used for spillage and heat sensitive instruments has received much attention in recent years. The use of clinical isolates of M. tuberculosis and M. avium-intracellulare as test organisms is considered unsuitable for standard tests due to their hazardous nature (category 3 pathogens and slow growth rates). This has led to much debate in standards committees on the selection and use of a possible surrogate which would be safer and more practical to use and yet mimic the susceptibility of clinical isolates. This study compared the susceptibility of one possible surrogate Mycobacterium terrae NCTC 10856, with that of clinical isolates of M. tuberculosis H37 Rv and M. avium-intracellulare using a quantitative suspension test. The instrument and environmental disinfectants tested were a chlorine-releasing agent, sodium dichloroisocyanyurate (NaDCC) at 1000 ppm and 10,000 ppm av. Cl, chlorine dioxide at 1100 ppm av. ClO2 (Tristel, HayMan MediChem), 0.35% peracetic acid (NuCidex, Johnson & Johnson), 70% industrial methylated spirit (IMS), 2% alkaline glutaraldehyde (Asep, Galen), 10% succine dialdehyde and formaldehyde mixture (Gigasept, Schulke and Mayr). Results showed that the clinical isolate of M. avium-intracellulare was the most resistant of the three test organisms. M. terrae, which is not a category 3 pathogen, was slightly more resistant than M. tuberculosis and this would appear to be a suitable surrogate for establishing tuberculocidal activity. However, with an increase in the clinical significance of M. avium-intracellulare, particularly in human immunodeficiency virus (HIV) and immunocompromised patients, a more resistant surrogate is required. In the absence of such a surrogate, testing with M. avium-intracellulare in a clinical laboratory equipped for handling category 3 pathogens is still advised to establish mycobactericidal activity.
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PMID:Mycobacterium terrae: a potential surrogate for Mycobacterium tuberculosis in a standard disinfectant test. 956 69

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.
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PMID:Fusion-competent vaccines: broad neutralization of primary isolates of HIV. 1200 1

Monoclonal antibodies prepared against recombinant Vif derived from the 34TF10 strain of feline immunodeficiency virus (FIV) were used to assess the expression and localization of Vif in virus-infected cells. Analyses by Western blotting and by immunoprecipitation from cells infected with FIV-34TF10 revealed the presence of a single 29-kDa species specific for virus-infected cells. Confirmation of antibody specificity was also performed by specific immunoprecipitation of in vitro-transcribed and -translated recombinant Vif. Localization experiments were also performed on virus-infected cells, using different fixation procedures. Results for methanol fixation protocols similar to those reported for localization of human immunodeficiency virus (HIV) Vif showed a predominant cytoplasmic localization for FIV Vif, very similar to localization of HIV type 1 Vif and virtually identical to the localization observed for the Gag antigens of the virus. However, with milder fixation procedures that used 2% formaldehyde at 4 degrees C, FIV Vif was strongly evident in the nucleus. The localization was distinct from the nuclear localization noted with Rev and did not involve the nucleolus. Attempts to show colocalization or coprecipitation of Vif with Gag antigens were unsuccessful. In addition, Vif was not detected in purified FIV virions. The results are consistent with the notion that the primary role of Vif in virus infection initiates in the nucleus.
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PMID:Feline immunodeficiency virus Vif localizes to the nucleus. 1068 67

Cells infected in vitro with immunodeficiency viruses have been examined by electron microscopy in situ hybridization (EM ISH) methods for localization of viral RNA. Techniques used for preparation of specimens and probes are described. Unambiguous positive results were obtained using a mixture of two or three single negative strand DNA oligonucleotides complementary to regions of the gag, env and nef genes, each 200-300 bases and labelled with dig-11-UTP. Positive strand probes were used as a negative control. Cells were fixed with a mixture of formaldehyde and glutaraldehyde, dehydrated in ethanol with progressive lowering of temperature and embedded in Lowicryl K4M or HM20 at -35 degrees C. Permeabilization or pre-treatment of sections with proteinase K was not essential. The hybridization mixture was applied for 3-4h at 37 degrees C and probe was visualized by direct immuno-staining with sheep anti-digoxigenin antibodies conjugated to 10nm gold. This method would be suitable for future studies of the pathogenesis of retroviral infections and as a basis for further development of the EM ISH technique. EM ISH of in vitro infections of immunodeficiency viruses has shown the location of viral RNA in immature and mature viruses and its relationship to multimerized Gag protein during viral budding. The label for RNA has also been found in the cytoplasm of infected cells; it was mainly located adjacent to the plasma membrane and unassociated with visible Gag proteins. This may indicate that viral RNA migrates to the plasma membrane independently of the Gag protein and may, in some instances, arrive at the plasma membrane prior to the Gag protein. Viral RNA has also been found in the nucleus of peripheral blood mononuclear cells (PBMC) that were showing no morphological evidence of infection. The RNA was typically located in the nucleolus and in peripheral dense chromatin. These cells, which displayed morphological features of macrophage lineage, may have been the initial cell type to be infected in the PBMC.
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PMID:Ultrastructural localization of the RNA of immunodeficiency viruses using electron microscopy in situ hybridization and in vitroinfected lymphocytes. 1116 78

During a study of intestinal parasitic infections in human immunodeficiency virus-positive patients, a parasite belonging to the phylum Myxozoa, recently described from human samples, was identified in one sample. When this parasite was stained by the modified Ziehl-Neelsen staining method, the features of the spores were identified: they were pyriform in shape, had thick walls, and had one suture and two polar capsules, with each one having four or five coils. The suture and two polar capsules were observed with the chromotrope-modified stain. The number of stools passed was more than 30 per day, but oocysts of Isospora belli were also found. Upon reexamination of some formalin- or merthiolate-iodine-formaldehyde-preserved samples an identical parasite was found in another sample from a patient presenting with diarrhea. Strongyloides stercoralis larvae and eggs of Hymenolepis nana and Ascaris lumbricoides were also found in this sample. Given that both patients were also infected with other pathogens that cause diarrhea, the possible pathogenic role of this parasite could not be established. The probable route of infection also could not be established.
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PMID:Myxobolus sp., another opportunistic parasite in immunosuppressed patients? 1132 17

In order to replace antiknock leaded derivatives in gasoline, legislations were enacted in the United States and other countries to find safer additives and to reduce CO, O3, and volatile organic compounds (VOCs) in non-attainment areas. Oxygenates commonly used include various alcohols and aliphatic ethers. Methyl tert-butyl ether (MTBE) is the most widely used and studied ether oxygenate and is added to gasoline at concentrations up to 15% by volume. Inhalation of fumes while fueling automobiles is the main source of human exposure to MTBE. Humans are also exposed when drinking water contaminated with MTBE. Epidemiological, clinical, animal, metabolic and kinetic studies have been carried out to address human health risks resulting from exposure to MTBE. MTBE is an animal carcinogen, but its human carcinogenic potential remains unclear. Because MTBE functions as a non-traditional genotoxicant, several mechanisms were suggested to explain its mode of action, such as, functioning as a cytotoxic as opposed to a mitogenic agent; involvement of hormonal mechanisms; or operating as a promoter instead of being a complete carcinogen. Some studies suggested that carcinogenicity of MTBE might be due to its two main metabolites, formaldehyde or tributanol. A role for DNA repair in MTBE carcinogenesis was recently unveiled, which explains some, but not all effects. The totality of the evidence shows that, for the majority of the non-occupationally exposed human population, MTBE is unlikely to produce lasting adverse health effects, and may in some cases improve health by reducing the composition of emitted harmful VOCs and other substances. A small segment of the population (e.g. asthmatic children, the elderly, and those with immunodeficiency) may be at increased risk for toxicity. However, no studies have been conducted to investigate this hypothesis. Concern over ground and surface water contamination caused by persistent MTBE has lead the Environmental Protection Agency (EPA) to proposed reducing or eliminating its use as a gasoline additive. The major potential alternatives to MTBE are other forms of ethers such as ethyl tert-butyl ether (ETBE) or tert-amyl methyl ether (TAME), and alcohols such as ethanol. More definitive studies are needed to understand the mechanism(s) by which aliphatic ethers may pose health and environmental impacts. The switch from MTBE to ethanol is not without problems. Ethanol costs more to produce, poses challenges to the gasoline distribution system, extends the spread of hydrocarbons through ground water in gasoline plumes, and in the short-term is unlikely to be available in sufficient quantity. Moreover, its metabolite acetaldehyde is a possible carcinogen that undergoes a photochemical reaction in the atmosphere to produce the respiratory irritant peroxylacetate nitrate (PAN). Congress is addressing whether the Clean Air Act Amendments (CAA) provisions concerning reformulated gasoline (RFG) should be modified to allow refineries to discontinue or lessen the use of oxygenates.
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PMID:Toxicology and human health effects following exposure to oxygenated or reformulated gasoline. 1164 Oct 38

In situ hybridization detection of viral RNAs in formaldehyde-fixed tissue specimens is used frequently to characterize the extent of viral replication within host tissues. The ability to determine the level of expression of viral RNAs in situ is dependent upon many factors including the extent of cross-linking during fixation, the pretreatment regimen utilized to relieve the effects of cross-linking, and the hybridization and wash protocols. In efforts to improve our ability to detect cells infected productively by simian immunodeficiency virus (SIV) in rhesus macaque tissues, the effects of unconventionally high (40 degrees C) and more standard low (4 degrees C) temperature fixation in 4% paraformaldehyde/phosphate buffered saline were tested empirically on in situ hybridization signals. In addition, hybridization temperatures ranging between 37 and 75 degrees C were utilized to determine the optimal hybridization conditions for detection of SIV productively infected cells. Fixation conditions of 40 degrees C and hybridization conditions of 50-55 degrees C were identified as providing the greatest sensitivity for detecting RNA(+) cells and for quantitating the signal per cell, while still allowing antigenic epitopes to be detected by immunohistochemical staining. These data indicate that the signal intensity following in situ hybridization for viral RNAs is dependent upon the combined effects of tissue fixation and in situ hybridization temperatures.
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PMID:Improved detection of simian immunodeficiency virus RNA by in situ hybridization in fixed tissue sections: combined effects of temperatures for tissue fixation and probe hybridization. 1168

A coproprotozoal study was carried out on 63 patients suffering from malignancy. The majority had cancer of haemopoietic system. All patients were under chemotherapy and included: Group A (33 children) and Group B (30 adults) of whom 20 immunocompetent diarrhoeic patients of matched age and sex were considered as controls. Stool samples were examined by merthiolate iodine-formaldehyde concentration technique (MIF). Modified Zeihl-Neelsen (ZN) stain was performed for Cryptosporidium oocysts. Detection of Cryptosporidium coproantigen by enzyme-linked immunoassay test (Ridascreen test), was used. Immunoglobulins (IgG, IgM, IgE & IgA), C3, C4 and CD4:CD8 ratio, were measured. According to their levels 25 out of 63 patients had both humoral and cellular immunodeficiency. The incidence of Cryptosporidium in cancer patients was 23.8%, while it was 37.7% and 91% in children and adults immunodeficient patients, respectively. ZN stain was able in diagnosed Cryptosporidium in 13 out of 35 immunodeficient cases while ELISA detected only 11 cases. Cryptosporidium infection in immunodeficient cancer patients had significantly more frequent and prolonged duration of diarrhoea than in negative ones.
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PMID:Incidence of cryptosporidiosis in immunodeficient cancer patients in Egypt. 1204 67


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