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)

Among 27 cases of Pseudomonas septicaemia in the Department of Paediatrics of Queen Mary Hospital from 1981 to 1988, we have identified 10 children without known predisposing causes before presentation and report their clinical features. Six were infants, of whom 4 developed shock on admission and died. Ecthyma gangrenosum was present in 4 patients. Pseudomonas aeruginosa was isolated in 8 patients. All isolates, except Ps. cepacia, were sensitive to gentamicin. One patient had cyclical neutropenia. Another had an appendicular abscess. Salmonella was cultured from the stool in one patient. Although Pseudomonas septicaemia is normally considered to be associated with underlying immunodeficiency, in 22% it occurred in previously healthy children. Mortality is high especially in infants who develop septicaemic shock. It is advisable to cover for Pseudomonas septicaemia with aminoglycosides or ceftazidime in sick septic infants.
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PMID:Pseudomonas septicaemia in apparently healthy children. 187 74

The earliest preparations of immunoglobulins (Ig) decreased the susceptibility of agammaglobulinemic patients to infections caused by pneumococci, Haemophilus influenzae, meningococci, streptococci, and Pseudomonas aeruginosa. Intramuscular administration of such preparations was painful and traumatic, especially for children. Ethanol-fractionated Ig could not be administered intravenously (IV) because the IgG molecules tended to aggregate and thus were more likely to produce anaphylactoid reactions. New Ig preparations, isolated at low pH (e.g., pH 4) in the presence of traces of pepsin to inhibit reaggregation, were well tolerated when administered IV. Thus a new era of treatment and prophylaxis of disease using IV Ig (IVIG) was launched. The IVIG preparations revolutionized the management of virtually all immunodeficiency syndromes characterized by failure of antibody responses. Amelioration of antibody deficiency secondary to certain chronic diseases or surgical trauma can be achieved with these preparations. Newer uses of IVIG include treatment of some autoimmune diseases; in some conditions, the beneficial influences may be attributable to antiidiotype antibodies present in the IVIG. Another likely explanation is that IVIG inhibits damage to cells and tissues by antibody-mediated cellular cytotoxicity or blocks phagocytosis that is facilitated by Fc receptor mechanisms. The value of IVIG in preventing infection in patients undergoing bone marrow or organ transplantation and in the treatment and prophylaxis of life-threatening infections in neonates and premature infants also is reviewed.
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PMID:Historic aspects of intravenous immunoglobulin therapy. 187 38

The case of a 9-month-old baby girl who failed to develop normally due to nutritional neglect and secondary immunodeficiency characterized by marked thymic involution is reported. The child died of systemic Pseudomonas aeruginosa (P. aeruginosa) infection manifested in pneumonia, lung abscesses, bacterial endocarditis and ecthyma gangrenosum. At autopsy the child was 64 cm in height (normal for a 4- to 5-month-old child) and 5.1 kg in weight (normal for a 2- to 3-month-old child). Multiple gangrenous ecthymas, consisting of deep ulcers, induration and inflammation, were observed in the skin over the entire body. The lungs showed hemorrhagic pneumonia, multiple lung abscesses, and necrotizing arteritis in the abscesses and surrounding areas. The thymus weighed 2.3 g and showed marked involution. Histological examination showed so-called nutritional thymectomy characterized by severe cortical atrophy and clustering, cystic dilation and amorphous changes of the Hassall's corpuscles. In the heart, dark brown verrucae were present at the attachment sites of the tendinous cords of the papillary muscle in the anterior and posterior cusps of the mitral valve, suggesting infectious endocarditis. Bacteriological examination demonstrated P. aeruginosa in the ecthymas, lung abscesses and blood. As primary immunodeficiency was considered unlikely, immunodeficiency secondary to thymic involution following malnutrition seemed to have led to a fatal systemic infection with P. aeruginosa, whose virulence is generally weak. This suggests a close association of the development of such infection and immunodeficiency with child neglect.
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PMID:Child neglect followed by marked thymic involution and fatal systemic pseudomonas infection. 191 16

CD4(178)-PE40 is a recombinant protein consisting of a portion of human CD4 linked to active domains of Pseudomonas aeruginosa exotoxin A. In previous experiments with human T cell lines, the hybrid toxin was found to selectively kill cells infected with human immunodeficiency virus type 1 (HIV-1), and to inhibit HIV-1 spread in mixtures of infected and uninfected cells. CD4(178)-PE40 inhibits HIV-1 spread in cultured primary human lymphocytes. Moreover, the hybrid toxin selectively kills HIV-1 chronically infected monocyte/macrophage cell lines and inhibits HIV-1 spread in primary macrophage cultures. Control experiments indicate that the protective effects of CD4(178)-PE40 against HIV-1 spread are due to selective killing of the infected cells rather than simply to neutralization by the CD4 moiety. Thus, for the major cell types susceptible to HIV infection in vivo, surface envelope glycoprotein is expressed at sufficient levels to enable binding and internalization of CD4(178)-PE40 and consequent selective cell killing.
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PMID:Anti-HIV activity of CD4-Pseudomonas exotoxin on infected primary human lymphocytes and monocyte/macrophages. 201 Jun 26

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

We have explored the acyl-CoA substrate specificity of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (NMT) by synthesizing 81 fatty acid analogs and surveying their activity in a coupled in vitro assay containing Pseudomonas acyl-CoA synthetase and Escherichia coli-derived yeast NMT. Single oxygen or sulfur substitution for C-3 through C-13 is well tolerated by both enzymes. Detailed kinetic analyses suggest that the acyl-CoA and peptide-binding sites of NMT are relatively insensitive to placement of single group 6B heteroatoms. By contrast, di-oxygen-substituted analogs were very poor substrates, producing dramatic reductions in the affinity of NMTs peptide-binding site for a synthetic octapeptide substrate derived from the NH2-terminal sequence of a known N-myristoylprotein, the gag poly-protein precursor of human immunodeficiency virus 1 (HIV-1). This observation provides an example of binding site cooperativity in NMT. Replacement of one oxygen with sulfur at either the 6, 9, or 12 position of dioxatetradecanoic acids results in a general increase in peptide catalytic efficiency (Vmax/Km). An analysis of five fatty acids from octanoic to dodecanoic having terminal phenyl groups indicated that the best substrate was 10-phenyldecanoic acid even though Corey-Pauling-Koltun molecular models indicate that it has a length equivalent to that of tridecanoic acid. Six analogs having an equivalent length of 13 carbon atoms were subsequently prepared in which the phenyl group was systematically moved one methylene group closer to carboxyl. Movement of the phenyl just one carbon closer to carboxyl (producing 9-(p-methylphenyl) nonanoic acid) decreases peptide catalytic efficiency (Vmax/Km) severalfold compared to 10-phenyldecanoic acid. 10-(4-Tolyl)decanoic acid has the same relative positions of phenyl and carboxyl as 10-phenyldecanoic acid even though a methyl group is present on the phenyl ring. It produces peptide Km and Vmax values that are the same as 10-phenyldecanoic acid. Substitution of either oxygen or sulfur for a methylene group fails to override the effects noted when the phenyl group position is altered in the C-14 equivalent fatty acid series. Several fatty acids of differing chain lengths with cyclohexyl-, 2-furyl, and 2-thienyl groups at their omega termnius had activity profiles that paralleled those of the comparable phenyl-substituted compounds. Myristic acid analogs with triple bonds (beginning at positions 2 through 13), cis-double bonds (positions 3 through 13) and trans-double bond isomers (E5, E6, and E7) were also tested.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The substrate specificity of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase. Analysis of myristic acid analogs containing oxygen, sulfur, double bonds, triple bonds, and/or an aromatic residue. 202 98

Replacing the Pseudomonas exotoxin A (PE) cell binding domain with the human immunodeficiency virus (HIV) gp120 binding domain from CD4 yields a hybrid toxin (CD4-PE) with potential therapeutic use in treating acquired immunodeficiency syndrome (AIDS). To find the most therapeutically potent combination of CD4 and PE four different hybrid toxins composed of one [CD4(122)] or two [CD4(181)] Ig-like CD4 domains and sequences of PE where the binding domain was partially [PE(392)] or completely [PE(364)] removed were constructed and expressed in Escherichia coli. The number of CD4 domains determined the binding affinity to gp120 and in cell viability assays the window between specific and nonspecific cytotoxicity. The length of PE determined the potency of the drug. The optimal hybrid toxin was composed of two Ig-like domains of CD4 and PE(392). Investigation of the internalization mechanism of CD4-PE revealed that the hybrid toxin binds to target cells and is endocytosed within one hour. However, more than 6 hours are required for maximum translation inhibition. In contrast to PE which is inhibited by ammonium chloride treatment, cell toxicity of CD4-PE is not affected by ammonium chloride. Further investigations showed that the acid-induced hydrophobicity change which is required for membrane translocation is also observed with CD4-PE but at significantly higher pH than with PE.
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PMID:CD4-Pseudomonas exotoxin hybrid proteins: modulation of potency and therapeutic window through structural design and characterization of cell internalization. 206 20

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 virally encoded proteases from human immunodeficiency virus (HIV) and avian myeloblastosis virus (AMV) have been compared relative to their ability to hydrolyze a variant of the three-domain Pseudomonas exotoxin, PE66. This exotoxin derivative, missing domain I and referred to as LysPE40, is made up of a 13-kilodalton NH2-terminal translocation domain II connected by a segment of 40 amino acids to enzyme domain III of the toxin, a 23-kilodalton ADP-ribosyltransferase. HIV protease hydrolyzes two peptide bonds in LysPE40, a Leu-Leu bond in the interdomain region and a Leu-Ala bond in a nonstructured region three residues in from the NH2-terminus. Neither of these sites is cleaved by the AMV enzyme; hydrolysis occurs, instead, at an Asp-Val bond in another part of the interdomain segment and at a Leu-Thr bond in the NH2-terminal region of domain II. Synthetic peptides corresponding to these cleavage sites are hydrolyzed by the individual proteases with the same specificity displayed toward the protein substrate. Peptide substrates for one protease are neither substrates nor competitive inhibitors for the other. A potent inhibitor of HIV type 1 protease was more than 3 orders of magnitude less active toward the AMV enzyme. These results suggest that although the crystallographic models of Rous sarcoma virus protease (an enzyme nearly identical to the AMV enzyme) and HIV type 1 protease show a high degree of similarity, there exist structural differences between these retroviral proteases that are clearly reflected by their kinetic properties.
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PMID:Proteases from human immunodeficiency virus and avian myeloblastosis virus show distinct specificities in hydrolysis of multidomain protein substrates. 216 35

Contact lens (CL) fitting carries the risk of transmitting infectious agents, including adenovirus and Pseudomonas. Therefore, a number of precautions must be observed to ensure safety in the office. Paramount among these is hand washing, both immediately after contact with a patient's eyes and again between patients. Equally important is that all trial lenses and CLs removed from patients be disinfected before reuse. Low-water-content soft CLs can be heat disinfected; high-water-content CLs require chemical treatment. A combination of surfactant cleaning with a chlorhexidine-containing agent and hydrogen peroxide disinfection is preferred for rigid lenses to guarantee destruction of human immunodeficiency virus (HIV). The proper use of lens care solutions is also necessary to minimize the risk of their becoming contaminated with pathogenic organisms. Only commercially prepared solutions should be used, preferably in small-volume bottles that are frequently replaced. Preservative-free solutions should be discarded after 1 day's use, whereas preserved solutions may be used for up to 2 weeks. Sterile saline rather than tap water is recommended for rinsing rigid lenses. Finally, part of the clinician's responsibility in running a safe office is to educate patients about these hygienic practices.
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PMID:Is your office safe? Yes. 218 80


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