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

Over recent years there has been a great deal of interest in the immunology, molecular biology and pathology of psoriasis and PsA. The pathogenetic mechanisms in PsA are less well understood than those described for psoriasis. There are almost certainly genetic and immune components. What is not clear is whether there is a primary immune defect or whether unknown stimuli lead to the recruitment of the immune system and establishment of the disease; nor is it absolutely clear whether PsA is an extension of psoriasis in certain prone individuals. Vascular abnormalities are the earliest histopathological changes to occur in the psoriatic plaque and are also prominent in the psoriatic synovium. Espinoza et al (1982) have suggested there may be a primary vascular defect in PsA. The fact that vascular changes occur before infiltration of immunocompetent cells and are the first changes to resolve with treatment of psoriasis is likely to be significant. Abnormalities in the cellular kinetics and growth factor sensitivity of keratinocytes, fibroblasts and synoviocytes have been highlighted previously. The ability of these cells to produce growth factors and express HLA class II antigens demonstrates the potential for them to initiate and maintain inflammation. The development and possible increased incidence of PsA in patients with such profound immunodeficiency as acquired immune deficiency syndrome suggests that T helper cells do not play a significant role in the establishment of the disease (Arnett et al, 1991). Previously, many immune changes were described. Unfortunately they are non-specific and do not indicate a fundamental defect or marker of PsA. Vasey (1985) has suggested that insidious exposure to Gram-positive bacteria from the gut, tonsils and psoriatic plaques results in chronically stimulated monocytes, macrophages and dendritic cells. These cells are able to migrate throughout the body. Repeated microtrauma may result in the homing of these cells to sites of injury in the skin, synovium and tendons. Interaction with genetically hyperactive synoviocytes and keratinocytes with concomitant release of growth factors may precipitate early lesions of psoriasis and PsA. This hypothesis needs to be substantiated, but it ties together some of the varying observations seen. Many abnormal laboratory findings have been described. Unfortunately, none of the serological changes is sufficiently specific to be of great help in diagnosis. CRP levels and the ESR remain the best promise as markers of the inflammatory component of the arthritis, while other indicators correlate with certain facets of the disease pathology, but as yet have not found a true niche in the management of PsA.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Laboratory findings and pathology of psoriatic arthritis. 807 97

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.
 ...
PMID:Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients. 809 21

Zidovudine treatment of individuals infected with human immunodeficiency virus type 1 (HIV-1) results in HIV-1 isolates with a reduced zidovudine sensitivity in vitro. This reduction is due to mutations causing amino acid substitutions at five codons (41, 67, 70, 215, and 219) on the reverse transcriptase enzyme of HIV. HIV-1 isolates were obtained 8 to 69 weeks after therapy discontinuation from 10 patients at different stages of disease. Zidovudine sensitivity was determined by the HeLa CD4+ plaque assay. The presence of the resistance-conferring mutations was determined by using a selective polymerase chain reaction. Sensitivity could be determined for six isolate pairs: one showed a decline in the 50% inhibitory zidovudine concentration after therapy discontinuation; four pairs did not show a change. The majority of changes in the five codons in isolates from all 10 patients were the result of a relative increase in the wild-type sequence. Complete changes from mutant to the wild type were seen for only two codons in isolates from two patients. This study of isolates from a small group of individuals at different stages of disease, who had been taking zidovudine for 1 to 2 years, shows that a period of 1 year without zidovudine may be required to achieve a change from a mutant or mixed virus population to a wild-type virus population.
 ...
PMID:Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates. 810 17

Deficient in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) occurs in patients infected with the human immunodeficiency virus (HIV), with the most deficient responses associated with opportunistic infections (OI). The peripheral blood mononuclear cells (PBMC) which produce IFN-alpha in response to HSV are light density, HLA-DR+ cells lacking any unique surface markers and have been termed "natural interferon-producing cells" (NIPC). In this study, IFN-alpha responses were measured and the ELISpot assay was utilized to determine the frequency of NIPC in response to HSV. As expected, HIV-infected patients had depressed IFN-alpha production. In the ELISpot assay, healthy controls had a mean frequency of 1:703 NIPC among PBMC; each NIPC made approximately 2 international units (IU) of IFN-alpha. HIV-infected patients on average had fourfold less NIPC than controls and produced 1 IU IFN-alpha/NIPC; the plaque size for patient samples was often smaller than that for controls. NIPC frequency and IFN-alpha production were lowest in patients with a history of OI. In conclusion, deficient IFN-alpha production by AIDS patients results from reductions in both the frequency and the activity of NIPC, probably reflecting a gradual turning off of IFN-alpha production.
 ...
PMID:Decreased frequency of functional natural interferon-producing cells in peripheral blood of patients with the acquired immune deficiency syndrome. 818 Nov 90

Expression of human immunodeficiency virus-1 integrase in Escherichia coli, at levels that had no effect on bacterial cell growth, blocked plaque formation by bacteriophages having single-stranded genomic DNA (M13) or RNA (R17, Q beta, PRR1). Plaque formation by phages having double-stranded genomic DNA (T4, PR4) was unaffected. Integrase also inhibited infection by the phagemid M13KO7, but it had no effect on production of phage once infection by M13KO7 was established. This result indicated that integrase affects an early stage in infection. Integrase also inhibited phage production following transfection by either single-stranded or double-stranded (replicative form) M13 DNA, it blocked M13 DNA replication, as assayed by incorporation of radioactive nucleotides into DNA, and it failed to affect bacterial pilus function. These data suggest that integrase interacts in vivo with phage nucleic acid, a conclusion supported by studies in which integrase was shown to have a DNA-binding activity in its C-terminal portion. This portion of integrase was both necessary and sufficient for interference of plaque formation by M13 in the present study. Expression of the N-terminal portion of integrase at the same level as intact integrase had little effect on phage growth, indicating that expression of foreign protein in general was not responsible for the inhibitory effect. The simple bacteriophage assay described is potentially useful for identifying integrase mutants that lack single-stranded DNA binding activity.
 ...
PMID:HIV-1 integrase blocks infection of bacteria by single-stranded DNA and RNA bacteriophages. 820 87

Prostaglandin E2 (PGE2) appears to have an immunosuppressive role in human immunodeficiency virus (HIV) infection. Therefore, the effect was studied of PGE2 pretreatment of T lymphocytes from patients with lymphadenopathy associated syndrome (LAS) on the expression of CD25 and CD71 as well as plaque forming cell (PFC) generation in pokeweed mitogen (PWM)-driven cultures. The PGE2-treated or untreated T lymphocytes were cultured with B cells and monocytes in the presence of PWM. Both CD25 and CD71 expression were assessed with an immunofluorescence technique; PFC generation was tested by hemolysis. Before exposure to PWM, LAS lymphocytes showed activation as evidenced by high CD25 and CD71 expression and PFC generation. Pretreatment by PGE2 did not inhibit expression of activation markers and PFC generation in LAS cultures, in contrast to what happened in control cultures. Thus, LAS lymphocytes are activated in vivo and are less sensitive to PGE2 inhibition than normal lymphocytes.
 ...
PMID:Impairment of lymphocyte sensitivity to prostaglandin E2 in cultures from patients with lymphoadenopathy associated syndrome. 823 82

Photochemical decontamination (PCD) of platelet concentrates, with adequate preservation of platelet function, has been shown using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA). To further evaluate this technique, models for the inactivation of pathogenic human cell-associated viruses and integrated proviral sequences are required. We have assessed the ability of the PCD technique to inactivate cell-associated human immunodeficiency virus 1 (HIV-1) in platelet concentrates. We correlated PCD inhibition of HIV-1 infectivity with 8-MOP-DNA adduct formation in contaminating nucleated cells, and measured the inhibition of polymerase chain reaction (PCR)-mediated amplification of cellular DNA sequences as a surrogate for inactivation of integrated proviral nucleic acid sequences. After PCD treatment (8-MOP 300 micrograms/mL, UVA 17 mW/cm2) for 60 minutes, 0.5 x 10(6) plaque-forming units (PFU)/mL of cell-associated HIV-1 were inactivated and no virus was detectable by infectivity assay. After 60 minutes of PCD, 15 8-MOP-DNA adducts per 1,000 bp were formed, while in the absence of UVA, no adducts were formed. PCR-mediated amplification of a 242-bp cellular DNA sequence (HLA-DQ-alpha) was inhibited when greater than eight psoralen-DNA adducts per 1,000 bp were present. These studies indicate that high titers of cell-associated HIV-1 in platelet concentrates were inactivated by PCD, and the numbers of 8-MOP-DNA adducts in nucleated cells were sufficient to inhibit amplification of DNA segments that encode for as few as 80 amino acids. Based on the frequency of 8-MOP-DNA adducts, for the 10-kb HIV-1 genome, the probability of an integrated genome without at least one 8-MOP adduct after 60 minutes of PCD was 10(-33).
 ...
PMID:Photochemical inactivation of cell-associated human immunodeficiency virus in platelet concentrates. 832 30

Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.
 ...
PMID:In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease. 835 53

Human immunodeficiency virus (HIV-1) is generally transmitted by parenteral contact with infected body secretions. Although extensive epidemiological data and familial studies have failed to provide any conclusive data that saliva may act as a vehicle for transmission of AIDS, both professional and public anxieties remain. The present study, as well as others, suggests that salivary secretions may act as inhibitors of HIV-1 replication in vitro. In our study, the inhibitory activity was determined to be associated mainly with secretions obtained from the human submandibular-sublingual glands. Human submandibular-sublingual (HSMSL) and parotid (HPS) salivas were collected and tested for their ability to modulate the replication of HIV-1, using a plaque assay on HeLa/CD4+ cell monolayers. Initial results examining freshly collected salivary samples from ten individuals confirmed the results previously obtained by Fox et al. (1988, 1989). An average plaque reduction of approximately 66% was obtained with HSMSL, in contrast to 34% reduction obtained with HPS. Titration of the inhibitory activity in HSMSL showed detectable levels at a 1:500 dilution. Comparison of inhibitory activity of dialyzed and lyophilized saliva to fresh saliva indicated little difference between the two samples when filtration occurred after the addition of HIV-1. However, the effect of filtration was significantly diminished in the lyophilized samples. Electron microscopic examination of the saliva-HIV incubates revealed the aggregation/entrapment of virus particles by salivary components. These results suggest that human salivary secretions (with HSMSL > HPS) may have a role in modulating the infectivity of HIV-1.
 ...
PMID:Aggregation of human immunodeficiency virus type 1 by human salivary secretions. 837 99

Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polyproteins in cultures of human immunodeficiency virus type 1 (HIV-1)-infected T lymphocytes and, as a result, inhibit the infectivity of HIV-1 for such cultures. The ability of HIV-1 protease inhibitors to suppress replication of the C-type retrovirus Rauscher murine leukemia virus (R-MuLV) and the HIV-related lentivirus simian immunodeficiency virus (SIV) was examined in plaque reduction assays and syncytium reduction assays, respectively. Three of seven compounds examined blocked production of infectious R-MuLV, with 50% inhibitory concentrations of < or = 1 microM. Little or no cellular cytotoxicity was detectable at concentrations up to 100 microM. The same compounds which inhibited the infectivity of HIV-1 also produced activity against SIV and R-MuLV. Electron microscopic examination revealed the presence of many virions with atypical morphologies in cultures treated with the active compounds. Morphometric analysis demonstrated that the active compounds reduced the number of membrane-associated virus particles. These results demonstrate that synthetic peptide analog inhibitors of retroviral proteases significantly inhibit proteolytic processing of the gag polyproteins of R-MuLV and SIV and inhibit the replication of these retroviruses. These results are similar to those for inhibition of HIV-1 infectivity by these compounds, and thus, R-MuLV and SIV might be suitable models for the in vivo evaluation of the antiretroviral activities of these protease inhibitors.
 ...
PMID:Antiretroviral activities of protease inhibitors against murine leukemia virus and simian immunodeficiency virus in tissue culture. 838 40


<< Previous 1 2 3 4 5 6 7 8 9 10