Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with human immunodeficiency virus infection are predisposed to fungal, parasitic, and viral infections. Bacterial infection can also be seen, although ocular bacterial infections have not been reported in patients with acquired immunodeficiency syndrome until recently. We present two cases of Pseudomonas corneoscleritis and one case of Pseudomonas keratitis in patients with human immunodeficiency virus infection that failed to respond to antibiotic treatment. Predisposing factors included extended-wear soft contact lens use in one patient and exposure secondary to Bell's palsy in another patient. All three patients had neutropenia that may have contributed to their poor response to treatment. Enucleation was required to treat two patients with overwhelming infection. Enucleation has been rarely required for treatment of corneoscleritis in immunocompetent patients treated at our institution. Pseudomonas keratitis in human immunodeficiency virus-infected patients represents a serious ocular infection requiring early diagnosis and aggressive treatment.
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PMID:Fulminant pseudomonal keratitis and scleritis in human immunodeficiency virus-infected patients. 201 49

CD4(178)-PE40 is a recombinant protein consisting of the HIV envelope glycoprotein-binding region of human CD4 linked to active domains of Pseudomonas aeruginosa exotoxin A. The hybrid toxin selectively kills HIV-infected human T-cell lines and protects against HIV spread in mixtures of uninfected and infected cells. We now report that CD4(178)-PE40 also selectively kills chronically HIV-1-infected cells of monocyte/macrophage lineage. The results provide further support for therapeutic use of this hybrid toxin in the treatment of HIV-infected individuals.
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PMID:Anti-HIV effects of CD4-Pseudomonas exotoxin on human lymphocyte and monocyte/macrophage cell lines. 207 15

The specificity of HIV-1 (human immunodeficiency virus-1) protease has been evaluated relative to its ability to cleave the three-domain Pseudomonas exotoxin (PE66) and related proteins in which the first domain has been deleted or replaced by a segment of CD4. Native PE66 is not hydrolyzed by the HIV-1 protease. However, removal of its first domain produces a molecule which is an excellent substrate for the enzyme. The major site of cleavage in this truncated exotoxin, called LysPE40, occurs in a segment that connects its two major domains, the translocation domain (II), and the ADP-ribosyltransferase (III). This interdomain region contains the sequence ...Asn-Tyr-Pro-Thr... which is similar to that surrounding the scissile Tyr-Pro bond in the gag precursor polyprotein, a natural substrate of the HIV-1 protease. Nevertheless, it is not this sequence that is recognized and cleaved by the enzyme, but one 6 residues away, ...Ala-Leu-Leu-Glu... in which the Leu-Leu peptide bond is hydrolyzed. A second, slower cleavage takes place at the Leu-Ala bond 3 residues in from the NH2 terminus of LysPE40. When domain I of PE66 is replaced by a segment comprising the first two domains of CD4, the resulting chimeric protein is hydrolyzed at the same Leu-Leu bond by HIV-1 protease. Enzyme activities toward synthetic peptides modeled after the sequences defined above in LysPE40 are in complete accord, relative to specificity, kinetics, and pH optimum, with results obtained in the hydrolysis of the parent protein. These findings demonstrate that ideas concerning the specificity of the HIV-1 protease that are based solely upon its processing of natural viral polyproteins can be expanded by evaluation of other multidomain proteins as substrates. Moreover, it would appear that it is not a particular conformation, but sequence and accessibility that play the dominant role in defining sites in a protein substrate that are susceptible to hydrolysis by the enzyme.
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PMID:Interdomain hydrolysis of a truncated Pseudomonas exotoxin by the human immunodeficiency virus-1 protease. 210 21

The present study describes several in vitro activities of CD4(178)-PE40, a recombinant protein containing a portion of human CD4 linked to active regions of Pseudomonas aeruginosa exotoxin A. Using assays for cell viability, we demonstrate that the hybrid toxin displays highly selective cytotoxicity for HIV-infected T lymphocytes. In a latently infected human T-cell line which is inducible for HIV expression, toxin sensitivity is observed only upon virus induction. At concentrations which readily kill HIV-infected T cells, CD4(178)-PE40 has no observable cytotoxic effects on uninfected human cell lines expressing surface major histocompatibility complex (MHC) Class II molecules, and does not interfere with cellular responses known to be dependent on functional association between CD4 and MHC Class II molecules.
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PMID:Recombinant CD4-Pseudomonas exotoxin hybrid protein displays HIV-specific cytotoxicity without affecting MHC class II-dependent functions. 211 47

In parenteral drug abuse, cutaneous manifestations are very common. A variety of skin lesions are indicators of a possible drug addiction: obliteration of peripheral veins and hyperpigmentation of the overlying skin, punched-out scars due to subcutaneous injection, persistent edema following thrombophlebitis, and excoriations due to heroin pruritus. Infectious and non-infectious complications may be accompanied by typical skin alterations, such as ecthyma in sepsis caused by Pseudomonas aeruginosa, multiple ulcers due to embolic infarct, or hypersensitivity reactions mediated by an immunological process. A variety of serious complications may develop at the injection sites: abscesses, gangrene, necrosis, or necrotizing fasciitis. These examples show that the dermatologist is in many ways involved in the care for addicted patients. In addition, these patients frequently suffer from sexually transmitted diseases or blood-borne infections; HIV-infection is rapidly spreading in this group. We now face new problems of differential diagnosis, especially since constitutional symptoms of HIV-infection may mimic symptoms of drug abuse and vice versa. Moreover, immunological alterations similar to those in HIV patients may even occur in drug addicts who are not infected with the virus.
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PMID:[Skin changes in drug-dependent patients]. 219 89

During a 5 year period at St Stephen's hospital, London, septicaemia was detected in 66 patients with the acquired immune deficiency syndrome (AIDS) and in 13 other patients with non-AIDS-associated HIV infections. The most frequent pathogens in patients with AIDS were Mycobacterium avium-intracellulare, Streptococcus pneumoniae, Pseudomonas aeruginosa, Cryptococcus neoformans and staphylococci. A series of HIV-associated septicaemias reported from other centres in different countries has shown great variation in the pattern of aetiological agents observed, which may partly reflect differences in the local socio-economic condition, ethnic backgrounds, other predisposing factors, and blood culture techniques. Salmonella species were a prominent cause of septicaemia in several reports. Most centres have also reported an increasing problem with septicaemias associated with intravenous lines in patients receiving antiviral or other parenteral drug therapy.
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PMID:Septicaemia in patients with AIDS. 220 Nov 8

The microflora of 297 psoriasis patients was extensively examined. Throat, urine, and skin surfaces from scalp, ears, chest, face, axillary, submammary, umbilical, upper back, inguinal crease, gluteal-fold, perirectal, vaginal, pubis, penis, scrotal, leg, hands, feet, finger, and toenail areas were cultured for aerobic bacteria, yeast, and dermatophytes. Antibody levels to streptococcal enzymes were performed (streptolysin-O, DNAse-B, hyaluronidase, STREPTOZYME). Giemsa smears and KOH preparations were also used to determine yeast and dermatophyte presence. Associated organisms thought to provoke a psoriatic attack were as follows: streptococcal groups A, B, C, D, F, G, S viridans, S pneumoniae; Klebsiella pneumoniae, oxytoca; Escherichia coli; Enterobacter cloacae, E aerogenes, E agglomerans; Proteus mirabilis, P vulgaris; Citrobacter freundii, C diversus; Morganella morganii; Pseudomonas aeruginosa, P maltiphilia, P putida; Serratia marcescens; Acinetobacter calbio aceticus, A luoffi; Flavobacterium specie; CDC groups Ve-1, Ve-2, E-o2; Bacillus subtilis, cereus; Staphylococcus aureus; Candida albicans, C parapsilosis; Torulopsis, glabrata; Rhodotorula and dermatophytes. One or more antistreptococal enzyme tests was positive in 50% of patients. Titers to hepatitis E were elevated in one patient and to HIV in two patients.
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PMID:The role of microorganisms in psoriasis. 228 71

Risks of infection associated with endoscopy, sources of infection, relevant microorganisms (P. aeruginosa, Serratia, HIV, HB, Cryptosporidiosis), disinfection procedures and the steps of disinfection procedures and reasons for failing of disinfection procedures are discussed. Channel systems and rinsing solutions are relevant but until today underestimated sources of infection. In detail the contamination of the channel system in endoscopes, problems of good disinfection and the significance of mechanical cleaning are described. In cases of Pseudomonas aeruginosa infections after endoscopy an immediate investigation of the contamination of the endoscope and of rinsing solutions is necessary. Automatic disinfection systems are requested, because with such systems a higher security for patient and personal is achievable. A regular control of the efficacy of the disinfection process by a competent Hygiene-Institute is recommended.
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PMID:[Hygienic measures in endoscopy]. 228 43

An autopsy case of a 37-year-old Japanese man, confirmed as an AIDS patient infected by an undetermined route of transmission, is presented. The initial symptoms of full-blown AIDS in this case were neurological, and the patient died of severe pneumonia 9 months after onset. The main histo- and immunopathological features were a marked depletion of helper-inducer T cells and dendritic reticulum cells in the lymphoid tissues, opportunistic infections, and some neuropathologic changes. Very few cells, possibly macrophages, immunoreactive with a monoclonal antibody (VAK-5) against HIV-gag protein P24 were found in the mediastinal lymph nodes. Numerous pathogens had induced opportunistic infections in many organs: severe and generalized cytomegalovirus infection, Pneumocystis carinii pneumonia, bronchopneumonia (possibly due to Pseudomonas aeruginosa), candidiasis in the tongue and oral cavity, and atypical mycobacteriosis in the pulmonic hilar lymph nodes. Vascular proliferation was found in the perinodal regions of some lymph nodes, but this was not neoplastic vascular proliferation compatible with that of localized Kaposi's sarcoma.
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PMID:Histo- and immunopathological features of terminal AIDS. An autopsy case of a Japanese man with neurological signs as initial symptoms. 321 10

The thermal denaturation of the chimeric protein toxin known as sCD4(178)-PE40 (sCD4-PE40) was studied using differential scanning calorimetry (DSC). sCD4-PE40 consists of HIV-binding domains of the T-cell membrane protein known as CD4 and the cytotoxic domains of Pseudomonas exotoxin A (PE40). sCD4-PE40 undergoes two DSC transitions. An endothermic transition associated with unfolding of the CD4 and PE40 components occurs at approximately 46 degrees C in buffered saline at pH 6.5. An exothermic transition associated with precipitation of unfolded protein occurs at higher temperatures. Both transitions are irreversible. DSC studies of solutions of pH 5.0 to 9.5 indicate that sCD4-PE40 shows maximal thermal stability at around pH 6.5. Variable pH experiments are also presented on solutions of sCD4(183) and PE40 revealing how these components denature as independent structural entities. sCD4(183) denaturation occurs at significantly higher temperatures than does the CD4 component of sCD4-PE40. PE40 denaturation occurs at the same temperatures as sCD4-PE40. These results suggest that the native CD4 and PE40 components are independent and non-interacting entities in the chimeric sCD4-PE40 molecule and that unfolding of the less-stable PE40 component induces unfolding of the CD4 component. These destabilizing interdomain interactions of sCD4-PE40 are in contrast to the stabilizing interactions which apparently exist in wild-type Pseudomonas exotoxin A between its PE40 domains and the cell binding domain of the native toxin (analogous to the CD4 component in sCD4-PE40). Reasons are discussed why the type of interdomain interactions observed for sCD4-PE40 might be the norm for chimeric proteins.
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PMID:Interdomain interactions in the chimeric protein toxin sCD4(178)-PE40: a differential scanning calorimetry (DSC) study. 747 46


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