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)

Fifty-eight patients with human immunodeficiency virus infection were analyzed for clinical manifestations and potential risk factors for Pseudomonas aeruginosa infection by use of case-control methodology. Most had AIDS. Of 73 episodes of P. aeruginosa infection, 45 (62%) were bacteremias primarily associated with central venous catheters (16), pneumonia (12), soft tissue (4), or urinary tract infections (4). Twenty-eight episodes (38%) were nonbacteremic, with pneumonia (13), soft tissue infections (6), and sinusitis (4) accounting for the majority of infections. Fifty episodes (68%) were community-acquired. The recurrence rate was 23%. The overall mortality attributable to P. aeruginosa infection was 22%. Central venous and urinary catheter use and steroid therapy were significantly more frequent in cases than controls (P < .05). Thus, P. aeruginosa infection in patients with advanced human immunodeficiency virus disease is often community-acquired and associated with substantial mortality and, in some cases, specific risk factors.
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PMID:Clinical manifestations and risk factors of Pseudomonas aeruginosa infection in patients with AIDS. 770 21

Host antibody response to toxin molecules is a major obstacle to the use of immunotoxins as efficacious agents in the treatment of human cancer and other diseases. In this study, a genetic form of immunotoxin has been designed which should eliminate toxin immunogenicity by replacing the toxin protein moiety with weakly immunogenic or nonimmunogenic plasmid DNA. A recombinant bifunctional fusion protein, which consists of a human antibody Fab targeting moiety [directed against gp120, the envelope glycoprotein of human immunodeficiency virus (HIV)-1] and a human DNA binding moiety (protamine), is used as a gene carrier. Toxin plasmid DNAs expressing the catalytic fragment of Pseudomonas exotoxin A (PEA) statically interact with the fusion proteins to form soluble protein-DNA complexes. The complexes are specifically transferred into HIV-1-infected cells by receptor-mediated endocytosis, resulting in selective killing of the target cells. These 'genetic immunotoxins' may have significant advantages over protein immunotoxins for the treatment of a variety of human diseases.
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PMID:Design of a genetic immunotoxin to eliminate toxin immunogenicity. 771 28

To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (HIV-1), a principal neutralizing domain (PND) peptide (KRIHIGPGRAFYT) (HIV-1MN) was covalently coupled to Pseudomonas aeruginosa toxin A (TA). Immunization of guinea-pigs with this conjugate vaccine, in the absence of an adjuvant, engendered a high-affinity antibody response to the homologous HIV-1MN PND peptide and to analogous peptides from variant strains of HIV-1. A substantial proportion of such antibodies was directed to the conserved GPGRAF motif. Anti-PND peptide antibodies were capable of neutralizing the homologous strain, HIV-1MN, in addition to two heterologous (RF, IIIB) variants, as determined either by inhibition of syncytia formation or by suppression of p24 antigen production in cultured cells. Therefore, the method of conjugation used preserved critical neutralizing epitopes expressed by the PND peptide. Monovalent or polyvalent PND-TA conjugates, which meet all safety criteria for human use, are a promising approach towards the development of an acquired immunodeficiency syndrome (AIDS) vaccine.
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PMID:Human immunodeficiency virus-1 principal neutralizing domain peptide-toxin A conjugate vaccine. 776 81

We conducted a case-control study to determine the incidence and clinical features of and risk factors for Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus (HIV). Twenty-five patients who had 37 episodes of P. aeruginosa infection from 1990 through 1992 were identified. Most of the patients (92%) were homosexual men with low CD4+ lymphocyte counts and a history of AIDS. The annual incidence rates of P. aeruginosa infection were 3.5% (1990), 6.3% (1991), and 8.7% (1992). Most infections were community-acquired (68%) and involved the respiratory tract (73%). Patients were more likely than HIV-infected controls to have AIDS and had more AIDS-defining opportunistic illnesses. The overall mortality was 36%. Recurrent episodes were common (39%). We conclude that P. aeruginosa infections may be an increasing problem in patients with extremely advanced HIV infection. Clinicians should consider including antibiotics with activity against P. aeruginosa in the empirical treatment for suspected bacterial infection in patients with advanced HIV infection.
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PMID:Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study. 781 59

The majority of patients with human immunodeficiency virus (HIV) infection will develop acute sinusitis. This may be a single episode, or may be the beginning of a long course of recurrent sinusitis, of which the etiology is not yet well understood. A retrospective study of cultures from antral washings was conducted to determine the organisms that were more commonly isolated in patients with HIV infection and sinusitis. Forty-seven organisms were isolated from the sinus cultures of 41 HIV-positive patients. The most common organisms isolated were Streptococcus pneumoniae (19%), Streptococcus viridans (19%), and Pseudomonas aeruginosa (17%). Pseudomonas aeruginosa is an atypical cause of acute sinusitis in the general population but was found to be an important pathogen in our HIV-infected patients. Other atypical organisms were also isolated, including Listeria monocytogenes and Candida albicans. It is important to recognize that atypical organisms must be considered if an HIV-infected patient with sinusitis does not respond to initial antibiotic therapy. A discussion follows emphasizing the need for prompt diagnosis and treatment of sinusitis in HIV infection.
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PMID:Sinusitis in human immunodeficiency virus infection: typical and atypical organisms. 789 79

The safety, immunologic, and antiviral effects of a recombinant biologic product that combines the second and third domains of the CD4 molecule and Pseudomonas exotoxin A (PE40) were evaluated in 21 human immunodeficiency virus (HIV)-infected subjects in a phase III open-label dose-ranging study. Subjects with CD4+ lymphocyte counts of 100-500/mm3 received CD4-PE40 at 40, 80, or 160 micrograms/m2 by infusion three to seven times over 10 days. At the maximum tolerated dose (80 micrograms/m2), peak CD4-PE40 levels were 65-130 ng/mL with a serum half-life of 3.6 +/- 1.5 h. Toxicity, primarily increased hepatic transaminases, was dose-related and reversible. HIV DNA proviral levels in peripheral blood mononuclear cells and plasma HIV RNA remained stable during and after CD4-PE40 infusions. The relative resistance of clinical isolates of HIV, limits of the tolerated dose, and the immunogenicity and short half-life of the protein may explain the lack of in vivo antiviral effect of CD4-PE40.
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PMID:Failure of short-term CD4-PE40 infusions to reduce virus load in human immunodeficiency virus-infected persons. 793 Jun 96

Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 micrograms/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 micrograms/kg. The major toxicity was a transient dose-dependent elevation in hepatic aminotransferases peaking 48 h after infusion. Anti-Pseudomonas exotoxin antibody developed in 58% of recipients, and sera from 13 of 17 showed neutralizing activity against sCD4-PE40. No consistent changes in immunologic or virologic markers were observed. Weekly infusions of < or = 10 micrograms/kg of sCD4-PE40 are generally well tolerated, but additional studies correlating optimal dosing and frequency of administration with efficacy will be needed to define the role of this novel agent in the management of HIV-1-infected patients.
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PMID:Use of recombinant soluble CD4 Pseudomonas exotoxin, a novel immunotoxin, for treatment of persons infected with human immunodeficiency virus. 796 11

To study the variability of human immunodeficiency virus type 1 (HIV-1), we used immunotoxins to select for variants within a population of H9 cells persistently infected with a molecular clone of HIV-1 designated NL4-3. Chimeric immunotoxin CD4-PE40 (a chimeric fusion protein consisting of the amino-terminal two domains of CD4 and the carboxy-terminal domains of Pseudomonas exotoxin A) was used to select for cells lacking cell surface expression of HIV Env (envelope proteins gp160, gp120, and gp41). The cells described here (A1, A7, C9, and E9) fail to express HIV proteins because they have markedly diminished transcription of the integrated provirus (A1, A7, and E9) or no HIV provirus (C9). Analysis demonstrated that two different cloned variants, A1 and E9, contain the complementary sequence of tRNA(3Lys) (45 bp) inserted 3' to the primer-binding site, following by a 169-bp deletion through the start of the gag gene. No HIV mRNA was detected by Northern (RNA) blotting, but PCR demonstrated the presence of the viral message. These variants were found very infrequently in the unselected H9/NL4-3 cell population, and they contained proviruses distinct from that found in the dominant population. In addition, all of these variants had similar patterns of CD4 surface expression that allowed them to escape reinfection within the tissue culture. The data are discussed with regard to mechanisms and errors of HIV reverse transcription, as well as the evolution of mutants within a population of persistently infected cells.
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PMID:Unique insertion sequence and pattern of CD4 expression in variants selected with immunotoxins from human immunodeficiency virus type 1-infected T cells. 798 70

Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) is a monomeric enzyme that is essential for vegetative growth. Nmt1p catalyzes the co-translational transfer of myristate from CoA to the amino-terminal Gly of cellular proteins in an ordered Bi Bi reaction mechanism that initially involves binding of myristoyl-CoA to the apoenzyme. Forty one fatty acid analogs were synthesized to define features in the acyl chain of myristoyl-CoA which are important determinants of its recognition by Nmt1p's acyl-CoA binding site as well as to help us deduce the structure of the binding site itself. These analogs included dicarboxylic acids, omega-nitrocarboxylic acids, analogs equivalent in length to C13:0-C15:0 which contain electronegative halogens at their omega-termini, hydroxytetradecanoic acids with hydrogen replaced by OH from C3 to C13, and azidophenyl-containing fatty acids with the linear azide unit attached either meta or para to phenyl and with variations in the length of their methylene chains. These compounds were converted to their CoA derivatives using Pseudomonas acyl-CoA synthetase and then surveyed as substrates for purified Nmt1p in an in vitro assay system that included an octapeptide derived from residues 1-8 of the human immunodeficiency virus Pr55gag polyprotein precursor. The results suggest that the myristoyl-CoA binding site contains a conical-shaped "receptor" that interacts with the omega-terminus of the bound acyl chain of acyl-CoAs. The acuteness of this cone determines the enzyme's capacity to accommodate steric bulk at the omega-terminus as well as Nmt1p's sensitivity to the distance between the eclipsed C5-C6 bond of a bound acyl chain and its omega-terminus. The activity profile of the various analog-CoAs also indicates that the enzyme's myristoyl-CoA binding site can accommodate fatty acid analogs with marked increases in polarity at their omega-terminus (compared to C14:0) as long as their chain length is equivalent to that of myristate.
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PMID:The substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Polar probes of the enzyme's myristoyl-CoA recognition site. 810 19

Haemophilus ducreyi, a cause of genital ulcer disease in developing countries, appears to facilitate the heterosexual transmission of the human immunodeficiency virus in Africa. Despite an increase in studies of this gram-negative human pathogen, little is known about the pathogenesis of chancroid. Our studies have shown that the lipooligosaccharides (LOS) of H. ducreyi may play an important role in ulcer formation. Monoclonal antibody and mass spectrometric analyses identified a terminal trisaccharide present on H. ducreyi LOS that is immunochemically similar to human paragloboside. This epitope is present on the LOS of Neisseria gonorrhoeae, and it may be the site of attachment for pyocin lysis. We have used pyocin, produced by Pseudomonas aeruginosa, to select LOS variants with sequential saccharide deletions from N. gonorrhoeae. On the basis of the similarities between N. gonorrhoeae and H. ducreyi LOS, we employed the same technique to determine if H. ducreyi strains were susceptible to pyocin lysis. In this study, we report the generation of a pyocin N-resistant H. ducreyi strain which synthesizes a truncated version of the parental LOS. Further studies have shown that this H. ducreyi variant has lost the terminal LOS epitope defined by monoclonal antibody 3F11. This report demonstrates that H. ducreyi is sensitive to pyocins and that this technique can be used to generate H. ducreyi LOS variants. Such variants could be used in comparative studies to relate LOS structure to biologic function in the pathogenesis of chancroid.
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PMID:Use of pyocin to select a Haemophilus ducreyi variant defective in lipooligosaccharide biosynthesis. 818 62


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