Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00216 (ABC)
 8,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo presence of cytokines in human skin was examined by ABC- and IF-techniques, and by using antisera to human rIL-6, rIL-1-alpha, rIL-1-beta, rTNF-alpha and an antiserum to crude supernatants of Staph. albus activated human blood monocytes (anti-MK-antiserum) before and after absorption with rIL-6. The following normal and immunoinflammatory human skin states were examined: Normal skin. Examination of biopsies from 9 healthy individuals and single cell preparations from 3 healthy individuals revealed a granular intercellular/membrane associated staining for IL-6 and TNF-alpha in the upper epidermal layers. A cytoplasmic staining was also detected, most pronounced using the anti-rIL-6 antiserum. Membrane associated IL-6 and TNF-alpha were detected in epidermal single cell preparations, but CD1 positive LC failed to express any of the cytokines examined. Psoriasis skin. Biopsies from lesional and unaffected skin of 11 patients with chronic, nummular/plaque type psoriasis were investigated for IL-6, and in addition 5 of these, moreover, for TNF-alpha. Biopsies from lesional psoriatic skin continually revealed increased staining for IL-6 compared with non-lesional skin, where the staining was similar to that observed in healthy individuals. Epidermal TNF-alpha expression did not differ from that observed in normal skin. AIDS related Kaposi's sarcom. Epidermal staining patterns were similarly increased for IL-6 and TNF-alpha in biopsies obtained from nodular KS tumours compared with unaffected skin of 6 homosexual male AIDS patients, whereas the endotheloid cell of the tumour did not stain for any of the cytokines. Staining of unaffected skin was similar to that observed in healthy individuals. The allergic and irritant patch test reaction. Investigation of biopsies from 5 patients with positive APR and 5 healthy individuals with IPR disclosed increased epidermal staining for IL-6, but not for TNF-alpha, in both reactions, while staining from petrolatum tested and non-tested skin was similar to that observed in normal individuals. CD1 positive LC remained negative in all biopsies when stained for IL-6 and TNF-alpha. In vivo UV-irradiated skin. Using anti-MK and anti TNF-alpha antisera skin biopsies from 5 healthy subjects 24 h after UVB irradiation revealed markedly increased epidermal staining for both cytokines compared with non-irradiated skin. Furthermore, a gradual decrease in epidermal staining for IL-6 was observed in specimens from lesional skin of 6 patients with psoriasis taken before and during PUVA therapy, while staining of non-lesional skin remained unchanged.
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PMID:Epidermal expression of interleukin-6 and tumour necrosis factor-alpha in normal and immunoinflammatory skin states in humans. 156 57

As a diagnostic technique, in situ hybridization requires a long processing time, a degree of expertise and may be difficult to handle routinely in some laboratories. To simplify the in situ hybridization method, we have modified a microwave in situ hybridization technique and applied it to oral hairy leukoplakia (OHL) biopsies obtained from 10 HIV-seropositive patients (definitively diagnosed by a conventional in situ hybridization technique) with appropriate controls. It was necessary to design a novel chamber to avoid drying of sections during the hybridization step. This modified microwave in situ hybridization technique was equispecific and equisensitive to the conventional technique and it shortens the hybridization time from overnight incubation to 14 minutes. To determine the sensitivity of our microwave in situ hybridization method we applied it to previously documented tongue tissue obtained from an AIDS autopsy without clinical evidence of OHL, but found to contain Epstein-Barr virus (EBV) by conventional in situ hybridization. This tissue specimen acted as a low EBV copy number, positive control. The sensitivity of immunohistochemistry using three different commercial detection kits was compared to that of in situ hybridization on the same tissues, following optimisation steps. This included the use of 2 cycles of primary and biotinylated secondary antibodies (antibody double cycling). Clearly positive signals for EBV were detected in all OHL biopsies with the Vectastain Elite ABC and the Histostain-SP kits. The sensitivity of the three commercial detection kits was evaluated at immunohistochemistry level by their application to the low-EBV copy number positive control specimen. Signals for EBV antigen in the low copy number positive control specimen were obtained only with the Vectastain Elite ABC kit. This indicates that, in this application, use of the Vectastain Elite ABC kit gives comparable sensitivity for immunohistochemistry to that found by in situ hybridiation.
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PMID:A rapid microwave-in situ hybridization method for the definitive diagnosis of oral hairy leukoplakia: comparison with immunohistochemistry. 880 85

Some Candida albicans isolates from AIDS patients with oropharyngeal candidiasis are becoming resistant to the azole antifungal agent fluconazole after prolonged treatment with this compound. Most of the C. albicans isolates resistant to fluconazole fail to accumulate this antifungal agent, and this has been considered a cause of resistance. This phenomenon was shown to be linked to an increase in the amounts of mRNA of a C. albicans ABC (ATP-binding cassette) transporter gene called CDR1 and of a gene conferring benomyl resistance (BENr), the product of which belongs to the class of major facilitator multidrug efflux transporters (D. Sanglard, K. Kuchler, F. Ischer, J. L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother. 39:2378-2386, 1995). To analyze the roles of these multidrug transporters in the efflux of azole antifungal agents, we constructed C. albicans mutants with single and double deletion mutations of the corresponding genes. The mutants were tested for their susceptibilities to these antifungal agents. Our results indicated that the delta cdr1 C. albicans mutant was hypersusceptible to the azole derivatives fluconazole, itraconazole, and ketoconazole, thus showing that the ABC transporter Cdr1 can use these compounds as substrates. The delta cdr1 mutant was also hypersusceptible to other antifungal agents (terbinafine and amorolfine) and to different metabolic inhibitors (cycloheximide, brefeldin A, and fluphenazine). The same mutant was slightly more susceptible than the wild type to nocodazole, cerulenin, and crystal violet but not to amphotericin B, nikkomycin Z, flucytosine, or pradimicin. In contrast, the delta ben mutant was rendered more susceptible only to the mutagen 4-nitroquinoline-N-oxide. However, this mutation increased the susceptibilities of the cells to cycloheximide and cerulenin when the mutation was constructed in a delta cdr1 background. The assay used in the present study could be implemented with new antifungal agents and is a powerful tool for assigning these substances as putative substrates of multidrug transporters.
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PMID:Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. 889 Nov 34

The wall-less mycoplasmas have revealed unusual microbial strategies for adaptive variation of antigenic membrane proteins exposed during their surface colonization of host cells. In particular, high-frequency mutations affecting the expression of selected surface lipoproteins have been increasingly documented for this group of organisms. A novel manifestation of mutational phase variation is shown here to occur in Mycoplasma fermentans, a chronic human infectious agent and possible AIDS-associated pathogen. A putative ABC type transport operon encoding four gene products is identified. The 3' distal gene encoding P78, a known surface-exposed antigen and the proposed substrate-binding lipoprotein of the transporter, is subject to localized hypermutation in a short homopolymeric tract of adenine residues located in the N-terminal coding region of the mature product. High-frequency, reversible insertion/deletion frameshift mutations lead to selective phase variation in P78 expression, whereas the putative nucleotide-binding protein, P63, encoded by the most 5' gene of the operon, is continually expressed. Mutation-based phase variation in specific surface-exposed microbial transporter components may provide an adaptive advantage for immune evasion, while continued expression of other elements of the same transporter may preserve essential metabolic functions and confer alternative substrate specificity. These features could be critical in mycoplasmas, where limitations in both transcriptional regulators and transport systems may prevail. This study also documents that P63 contains an uncharacteristic hydrophobic sequence between predicted nucleotide binding motifs and displays an amphiphilic character in detergent fractionation. Both features are consistent with an evolutionary adaptation favoring integral association of this putative energy-transducing component with the single mycoplasma membrane.
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PMID:Localized frameshift mutation generates selective, high-frequency phase variation of a surface lipoprotein encoded by a mycoplasma ABC transporter operon. 919 Aug 19

Increased activation of CD8+ T cells, particularly increased expression of CD38 antigen, has been shown to strongly correlate with progression of human immunodeficiency virus-positive (HIV+) individuals to acquired immunodeficiency syndrome (AIDS) and death. As part of a study evaluating responses to a recombinant gp160 vaccine, we have used quantitative three-color flow cytometry (QFCM) to further investigate the relationships among several measures of lymphocyte activation/immunological status. Parameters evaluated included 1) absolute circulating counts for the major lymphocyte phenotypes (T, B, NK) and selected activated/regulatory subsets believed to have clinical value in the monitoring of patients with HIV infection; 2) level of CD38 expression (antibody-binding capacity [ABC]) on the lymphocyte subsets defined by CD8, CD38, and HLA-DR; and 3) serum levels of soluble CD8. CD8+DR+CD38+ counts were found to be markedly increased (approximately 10-fold) in HIV+ individuals, whereas CD4+CD45RA+ counts were markedly decreased (approximately 5-fold). We confirmed previous reports that CD38 expression on CD8 T cells (here reported as CD38 ABC) are increased in asymptomatic HIV+ individuals as compared with healthy controls, and further found that CD38 ABC was elevated approximately 2-fold on CD8+DR+ cells as compared with CD8+DR- cells in healthy controls, and almost 2-fold further elevated on CD8+DR+ cells in HIV+ individuals compared with CD8+DR+ cells in healthy controls. In agreement with previous studies, we found increased serum CD8 levels (sCD8) and increased CD8+DR+ counts in asymptomatic HIV+ individuals. However, when sCD8 was expressed relative to CD8+DR+ cell counts (RsCD8), this index was found to be significantly decreased in HIV+ individuals. Although CD38 ABC on CD8+DR+ cells showed no correlation with sCD8, it was significantly correlated with RsCD8 in both HIV+ and HIV- individuals. Absolute lymphocyte counts were strongly correlated with both CD38 ABC and RsCD8 in HIV+ individuals. However, CD4 counts were correlated with CD38 ABC (but not RsCD8) in HIV+ patients and with RsCD8 (but not CD38 ABC) in HIV-controls. Our results suggest that QFCM is significant in understanding the role of CD8+DR+CD38+ cells in processes such as lymphocyte homeostasis and HIV-induced CD4-cell depletion.
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PMID:Indicators of T-cell activation: correlation between quantitative CD38 expression and soluble CD8 levels in asymptomatic HIV+ individuals and healthy controls. 977 71

Serial Candida albicans isolates from recurrent episodes of oropharyngeal candidosis (OPC) in four AIDS patients which became fluconazole-resistant during therapy were analysed by molecular methods. The CARE-2 fingerprint patterns of the isolates demonstrated that in all four patients fluconazole resistance developed in a previously more susceptible strain. In two cases resistance correlated with enhanced expression of genes encoding multiple drug resistance proteins that mediate active drug efflux. Enhanced mRNA levels of the CDR1/CDR2 genes encoding ABC transporters were observed in fluconazole-resistant isolates from one patient compared with the corresponding susceptible isolates. The fluconazole-resistant isolates from another patient exhibited high mRNA levels of the MDR1 gene encoding a membrane transport protein of the major facilitator superfamily that was not detectably expressed in any of the fluconazole-susceptible isolates. These results demonstrate that in AIDS patients with recurrent OPC the development of fluconazole resistance is usually caused by molecular changes in a previously susceptible C. albicans strain from the same patient.
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PMID:Molecular aspects of fluconazole resistance development in Candida albicans. 1054 86

The First International Conference on Therapies for Viral Hepatitis, held in December 1995, brought together researchers, clinicians, and pharmaceutical manufacturers devoted to finding more effective ways to treat several varieties of hepatitis. Hepatitis B (HBV) affects an estimated 300 to 350 million people; up to 25 percent of that number will die of liver cirrhosis or hepatocellular carcinoma. The only currently available treatment is interferon, which is effective in only forty percent of the cases and has dose-limiting side effects. Nucleoside analog drugs have gained increasing attention because of their use in treating opportunistic infections in HIV-positive patients. Hepatitis C (HCV) affects only 75 to 100 million but is potentially more dangerous, since 85 percent of those with the disease will develop persistent and chronic liver infections and 70 percent will develop chronic liver disease. Hepatitis D (HDV) requires HBV for its replication cycle, and appears to respond to treatment for HBV. However, interferon is not effective in cases where the patient has both HBV and HDV. Hepatitis G (HGV) causes transfusion-associated non-ABC hepatitis with mild symptoms, and it is unclear if HGV causes chronic liver disease. Regimens for chronic viral hepatitis are desperately needed.
J Int Assoc Physicians AIDS Care 1996 Feb
PMID:First International Conference on Therapies for Viral Hepatitis. 1136 35

An ABC television news poll, released February 1, 1996, indicates that Americans' concerns that they might personally contract HIV are at an all-time low. Coincidentally, the number of people reporting that they personally know of someone with AIDS or who has died from AIDS has grown to 39 percent. The survey followed Los [name removed]'s return to professional basketball. Seventy-four percent of those polled were in favor of [name removed]'s return.
AIDS Policy Law 1996 Mar 08
PMID:Concern about catching HIV is at an all-time low, poll says. 1136 20

A poll released on April 21, 1997 by Louis Harris and Associates indicates that Americans' concern about AIDS continues to lessen and the majority believe that a vaccine will be found within the next five years. Fifty-one percent of those surveyed said that it was likely AIDS would become an epidemic for the public at large; in 1992, 65 percent of those surveyed expected a general epidemic. Concern about infection is greatest among African Americans, people with low household incomes, those aged 18-24, and Hispanics. These figures are consistent with an ABC News poll conducted in 1996.
AIDS Policy Law 1997 May 02
PMID:Public, less worried about AIDS, sees a vaccine on horizon. 1136 10

Glaxo Wellcome has expanded its access program for its experimental drug abacavir (Ziagen, formerly known as 1592). The program already includes 1900 patients since its start last summer and the newly expanded program is less restrictive. Patients over 13 years of age who have already failed standard treatments are eligible. These patients must take Ziagen as part of a combination antiretroviral treatment including at least one other antiretroviral the patient has never taken before. Pregnant or nursing women, and patients with medical conditions who cannot use the drug safely are excluded. Children under 13 years old may participate in a pediatric program. Presently it is not clear who would benefit from taking abacavir. An estimated three percent of patients taking Ziagen experienced hypersensitivity reaction, characterized by a fever in conjunction with nausea, malaise and possibly a rash. If hypersensitivity occurs, the patient must discontinue use indefinitely; symptoms will disappear within one to two days of termination. More information is available from the Abacavir Coordinating Center.
AIDS Treat News 1998 Mar 20
PMID:1592 (abacavir, or new name Ziagen) more widely available March 23. 1136 46


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