Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
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Query: UMLS:C0001175 (
AIDS
)
120,706
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The significance of the following blood tests are examined: complete blood count; liver function tests; blood urea
nitrogen
and creatinine; blood glucose, electrolytes, and minerals; and amylase. Several questions are answered regarding test results, what blood cultures are, whether a blood transfusion is required for low hematocrit, and the potential of becoming anemic due to repeated blood testing.
AIDS
Clin Care 1995 Jul
PMID:Blood tests and what they mean. 1136 53
The nutritional abnormalities resulting from HIV/
AIDS
are discussed, including the consequences of wasting and its profound effects on patient quality of life. Deficits of vitamins A, E, B6 and B12, and riboflavin, zinc, and copper have been found in asymptomatic HIV-positive persons. The nutrient abnormalities may be linked to HIV disease progression. The cyclic process of contracting infections, requiring increased nutrients, is discussed. How the body suffering from HIV/
AIDS
-related wasting reacts to daily protein loss is examined, focusing on
nitrogen
depletion and increased lipogenesis.
...
PMID:Nutritional abnormalities in HIV/AIDS. 1136 62
Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new
AIDS
therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive
nitrogen
and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta-mercaptoethanol (beta-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase,
nitrogen
or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.
...
PMID:Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase. 1142 64
Cryptococcus neoformans is an important fungal pathogen in immunocompromised hosts. Capsulation, urease and melanin synthesis activity of the fungus are well known virulence factors. Although artificial melanin-deficient mutants of Cr. neoformans have been investigated, the clinical mutant is rare. We found a Cr. neoformans isolate in the cerebrospinal fluid of an
AIDS
patient which produced a light tan colony on a caffeic acid cornmeal agar (CACA) plate. The mycological feature of the isolate was as follows; normal capsulation, defective inositol assimilation ability, serotype A; urease-positive; mating type alfa; haploid; extremely slow growth in RPMI 1640 medium, Sabouraud dextrose broth, brain heart infusion broth and yeast
nitrogen
base; lower production of melanin with L-DOPA substrate; and low virulence to ddY mice. We also investigated the partial DNA sequence of CNLAC1 gene between the 3085th to 3623rd base. There were many substitutions, 3 insertions and 3 deletions in the isolate compared with GenBank accession number L22866. The result indicated some functional disorder in the gene. Although the CACA plate is an excellent selective medium for Cr. neoformans, other identification methods should also be used.
...
PMID:Atypical Cryptococcus neoformans isolate from an HIV-infected patient in Brazil. 1147 33
HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation. This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus. In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO). Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased. This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients. In parallel with the drop in lactoferrin, a marked increase in circulating
nitrogen
derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients. These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection. This overproduction of NO could play an important role in the development of
AIDS
symptoms and signs.
AIDS
Res Hum Retroviruses 2001 Jul 20
PMID:Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections. 1148 21
Type B lactic acidosis is a rare and often fatal complication seen in patients receiving the nucleotide analogues zidovudine, stavudine, didanosine, and lamivudine. We describe a case of a 51-year-old human immunodeficiency virus (HIV)-positive woman receiving three nucleotide analogues. She presented with nausea, vomiting, abdominal pain, and hepatic steatosis. Signs of mitochondrial toxicity were demonstrated by diffuse myopathy and pancreatitis. Serum riboflavin levels documented a deficiency that was treated with 50 mg of riboflavin daily. Immediately after treatment, serum blood urea
nitrogen
level, lactic acid levels, and arterial blood pH all returned to normal values. Her signs of mitochondrial toxicity also improved after treatment with riboflavin. Successful reversal of the patient's type B lactic acidosis after riboflavin therapy suggested that riboflavin deficiency plays a direct role in the development of nucleotide analogue-induced lactic acidosis. It is impossible to predict which patients are predisposed to the development of this syndrome. For this reason, it may be important to screen and treat riboflavin deficiency in patients on nucleoside analogues.
AIDS
Patient Care STDS 2001 Dec
PMID:Emerging role of riboflavin in the treatment of nucleoside analogue-induced type B lactic acidosis. 1178 75
The human cyclophilin hCyp-18, an abundant peptidyl-prolyl cis-trans isomerase (PPIase) implicated in protein folding, controls the infection of CD4(+) T-cells by HIV-1, the pathologic agent of
AIDS
. Therefore, hCyp-18 is an interesting target for the development of novel anti-HIV-1 therapeutics. We focused on the design of transition-state analogue inhibitors of the PPIase activity of cyclophilin. Most experimental results reported in the literature suggest that hCyp-18 catalyzes the pyramidalization of the
nitrogen
of pyrrolidine via an H-bond network which results in the deconjugation of the amino acyl-prolyl peptide bond. We proposed the Glypsi(PO(2)R(1)-N)Pro motif (R = alkyl or H) as a selective transition-state analogue inhibitor of cyclophilin. This motif was inserted in Suc-Ala-Ala-Pro-Phe-pNA, a peptide substrate of hCyp-18. The pseudopeptide Suc-Ala-Glypsi(PO(2)Et-N)Pro-Phe-pNA 1b bound to hCyp-18 (K(d) = 20 +/- 5 microM) and was able to selectively inhibit its PPIase activity (IC(50) = 15 +/- 1 microM) but not hFKBP-12, another important PPIase. Deprotection of the phosphonamidate moiety resulted in a complete lack of inhibition. We previously demonstrated that reduction of the Phe-pNA moiety caused a quantitative reduction of the affinity; however, Suc-Ala-Glypsi(PO(2)Et-N)Pro-Phepsi(CH(2)-NH)pNA 7b still bound and inhibited hCyp-18, suggesting that the Glypsi(PO(2)Et-N)Pro motif plays the major role in the binding to cyclophilin. Consequently, we propose compound 1b as being a novel transition-state mimic inhibitor of hCyp-18.
...
PMID:Synthesis and evaluation of Glypsi(PO(2)R-N)Pro-containing pseudopeptides as novel inhibitors of the human cyclophilin hCyp-18. 1219 Mar 14
Plasma cell neoplasia occurs much less frequently than high-grade B-cell non-Hodgkins lymphoma in HIV-infected patients, but is nevertheless an
AIDS
-associated malignancy. In this report, we describe the fine-needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41-yr-old HIV-infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 x 10(9)/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea
nitrogen
(2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched-out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte-common antigen (LCA), but strongly positive for CD38 and kappa light chain. Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched-out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation.
...
PMID:Fine-needle aspiration cytology of a case of HIV-associated anaplastic myeloma. 1235 99
Body composition has become the main outcome of many nutritional intervention studies including osteoporosis, malnutrition, obesity,
AIDS
, and aging. Traditional indirect body composition methods developed with healthy young adults do not apply to the elderly or diseased. Fast neutron activation (for N and P) and neutron inelastic scattering (for C and O) are used to assess in vivo elements characteristic of specific body compartments. Non-bone phosphorus for muscle is measured by the (31)P(n, alpha)(28)Al reaction, and
nitrogen
for protein via the (14)N(n,2n)(13)N fast neutron reaction. Inelastic neutron scattering is used to measure total body carbon and oxygen. Body fat is derived from carbon after correcting for contributions from protein, bone, and glycogen. Carbon-to-oxygen ratio (C/O) is used to measure the distribution of fat and lean tissue in the body and to monitor small changes of lean mass. A sealed, D-T neutron generator is used for the production of fast neutrons. Carbon and oxygen mass and their ratio are measured in vivo at a radiation exposure of less than 0.06 mSv. Gamma-ray spectra are collected using large BGO detectors and analyzed for the 4.43 MeV state of carbon and 6.13 MeV state of oxygen, simultaneously with the irradiation. P and N analysis by delayed fast neutron activation is performed by transferring the patient to a shielded room equipped with an array of NaI(Tl) detectors. A combination of measurements makes possible the assessment of the "quality" of fat-free mass. The neutron generator system is used to evaluate the efficacy of new treatments, to study mechanisms of lean tissue depletion with aging, and to investigate methods for preserving function and quality of life in the elderly. It is also used as a reference method for the validation of portable instruments of nutritional assessment.
...
PMID:Use of D-T-produced fast neutrons for in vivo body composition analysis: a reference method for nutritional assessment in the elderly. 1474 91
Nitric oxide (
nitrogen
monoxide; NO) is a simple molecule with diverse biological functions. NO and related reactive
nitrogen
oxide species (RNOS) mediate intricate physiological and pathophysiological effects in the central nervous system. Depending on environmental conditions, NO and RNOS can initiate and mediate neuroprotection or neurotoxicity either exclusively or synergistically with other effectors. The focus of this review is limited to the neuroprotectant/neurotoxic role of NO in
Acquired Immune Deficiency Syndrome
(
AIDS
) Dementia Complex (aka HIV--Associated Dementia; HAD) Amyotrophic Lateral Sclerosis (aka Lou Gehrig's Disease), Alzheimer's Disease, Huntington's Disease, Multiple Sclerosis and Parkinson's Disease. This review will shed light on the question: "How important is NO in neurodegenerative diseases?"
...
PMID:Nitric oxide neurotoxicity in neurodegenerative diseases. 1476 6
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