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)

Highly purified, recombinant preparations of the virally encoded proteases from human immunodeficiency viruses (HIV) 1 and 2 have been compared relative to 1) their specificities toward non-viral protein and synthetic peptide substrates, and 2) their inhibition by several P1-P1' pseudodipeptidyl-modified substrate analogs. Hydrolysis of the Leu-Leu and Leu-Ala bonds in the Pseudomonas exotoxin derivative, Lys-PE40, is qualitatively the same for HIV-2 protease as published earlier for the HIV-1 enzyme (Tomasselli, A. G., Hui, J. O., Sawyer, T. K., Staples, D. J., FitzGerald, D. J., Chaudhary, V. K., Pastan, I., and Heinrikson, R. L. (1990) J. Biol. Chem. 265, 408-413). However, the rates of cleavage at these two sites are reversed for the HIV-2 protease which prefers the Leu-Ala bond. The kinetics of hydrolysis of this protein substrate by both enzymes are mirrored by those obtained from cleavage of model peptides. Hydrolysis by the two proteases of other synthetic peptides modeled after processing sites in HIV-1 and HIV-2 gag polyproteins and selected analogs thereof demonstrated differences, as well as similarities, in selectivity. For example, while the two proteases were nearly identical in their rates of cleavage of the Tyr-Pro bond in the HIV-1 gag fragment, Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val, the HIV-1 protease showed a 64-fold enhancement over the HIV-2 enzyme in hydrolysis of a Tyr-Val bond in the same template. Accordingly, the HIV-2 protease appears to have a different specificity than the HIV-1 enzyme; it is better able to hydrolyze substrates with small amino acids in P1 and P1', but is variable in its rate of hydrolysis of peptides with bulky substituents in these positions. In addition to these comparisons of the two proteases with respect to substrate specificity, we present inhibitor structure-activity data for the HIV-2 protease. Relative to P1-P1' statine or Phe psi [CH2N]Pro-modified pseudopeptidyl inhibitors, compounds having Xaa psi[CH(OH)CH2]Yaa inserts were found to show significantly higher affinities to both enzymes, generally binding from 10 to 100 times stronger to HIV-1 protease than to the HIV-2 enzyme. Molecular modeling comparisons based upon the sequence homology of the two enzymes and x-ray crystal structures of HIV-1 protease suggest that most of the nonconservative amino acid replacements occur in regions well outside the catalytic cleft, while only subtle structural differences exist within the active site.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Specificity and inhibition of proteases from human immunodeficiency viruses 1 and 2. 220 91

The CD4 molecule is a high affinity receptor for the human immunodeficiency virus (HIV) envelope glycoprotein (gp160 or gp120). This glycoprotein is expressed on the surface membrane of cells infected with HIV. It has, therefore, been suggested that a soluble form of CD4 might be used as a targeting agent to deliver toxins selectively to cells infected with HIV. We demonstrate that CD4-Pseudomonas exotoxin A (PE) conjugates inhibit the proliferation of gp160-transfected Chinese hamster ovary cells and block HIV replication in virus-infected H9 cells. However, this inhibition of HIV replication appears to be incomplete since virus replication occurs following removal of the toxin conjugates from these cultures. Moreover, CD4-PE conjugates delay but do not inhibit HIV replication in human peripheral blood lymphocytes. These studies suggest that such conjugates should be assessed only as potential adjunctive therapies in the acquired immunodeficiency syndrome.
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PMID:CD4-Pseudomonas exotoxin conjugates delay but do not fully inhibit human immunodeficiency virus replication in lymphocytes in vitro. 224 39

Either ricin A chain (RAC) or Pseudomonas exotoxin (PE) was conjugated with a murine monoclonal antibody (0.5 beta) directed against an external envelope glycoprotein (gp120) of human immunodeficiency virus (HIV). Effects of the immunotoxins produced against infected cells were evaluated. Selective inhibition of the proliferation and killing of chronically HIV infected cells were observed in the presence of the immunotoxins. To determine the feasibility of the immunotoxins against the infected cells in seropositive subjects, we attempted to detect gp120-bearing cells in peripheral blood mononuclear cells (PBM) by cytofluorography. Cells in the monocyte/macrophage region of 2 of 10 PBM samples from HIV-infected individuals were found to react with 0.5 beta (18.1% and 12.8%). Furthermore, the cell population which was reactive with 0.5 beta was also susceptible to RAC conjugated with 0.5 beta. These results suggest that the strategy of using anti-gp120 immunotoxin to eliminate HIV-infected cells may be feasible in infected individuals.
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PMID:Selective killing of HIV-infected cells by anti-gp120 immunotoxins. 232 57

Two hundred and sixty-two patients (actual number 162) of hematological malignancies were admitted to our department from November 1977 to December 1986. Fourty-three of them (16.4%) were demonstrated to be accompanied with sepsis by blood culture. In acute non-lymphocytic leukemias (AML, APL, AMoL) the rate of sepsis was 33.8% (27 patients), while in lymphocytic malignancies (ML, HD, ATL) it was 11.7% (16 patients), particularly being 3.0% in ATL. Among the detected pathogenic microorganisms, gram-negative bacilli were 86.2% in the former and 50.0% in the latter. Especially, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli occupied 58.6% of the total in the former. Laboratory examination, when sepsis occurred, revealed peripheral neutropenia in acute non-lymphocytic leukemias (mean 831/cmm) but not in lymphocytic malignancy (mean 4,420/cmm). And 20 of the 27 cases showed remarkable neutropenia of below 500/cmm in the former. On the other hand in the latter, out of 16 only one with ATL was the case. Hypogammaglobulinemia was one of the characteristic features in lymphocytic malignancies but not in acute non-lymphocytic leukemias. Hypogammaglobulinemia in lymphocytic malignancies might be affected by long-term immunodepressant therapy. Immunologic skin reaction was demonstrated to be decreased in lymphocytic malignancies on admission. From the findings mentioned above, affecting factors to infections may be mainly neutropenia in acute non-lymphocytic leukemias and immunodeficiency in lymphocytic malignancies. And sepsis can occur frequently under neutropenic condition. In ATL both of humoral- and cellular-immunologic disturbance were detected before therapy. But peripheral neutrophil count was maintained to be normal and this could be the reason for the low septic incidence in ATL despite of total immunodepression.
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PMID:[Infections in hematological malignancies--clinical analysis of septic patients admitted to the Second Department of Miyazaki Medical College Hospital in the past ten years]. 240 13

Effect of gamma globulin preparations on opsonic activity in whole blood from non-immunodeficiency was studied using chemiluminescence as the parameter of phagocytic function of granulocytes. Poly (ethylene) glycol treated, Fc-intact preparation clearly enhanced chemiluminescence (luminol-dependent) of blood cells phagocytosing zymosan, Escherichia coli (E. coli), or Pseudomonas aeruginosa (P. aeruginosa), but pepsin-treated preparation showed no effect. Whole blood added with intact preparation at the final concentration of 4 mg/ml showed enhanced CL induced by E. coli and P. aeruginosa in many individuals, especially in infancy, although in adult age suppressive effect was often observed. In six patients with pediatric malignancy and three newborns with suspected septicemia, CL induced by E. coli or P. aeruginosa was measured after the administration of 150 mg/kg of intact preparations, and 4/6 of malignancy showed increased CL by E. coli, and all infants showed increased CL by E. coli and P. aeruginosa. These results suggest that intact gamma globulin preparation can increase phagocytic ability of whole blood in non-immunodeficiency via its opsonins, and may justify the administration of intact gamma globulins in non-immunodeficiency for the purpose of treating bacterial infections in some selected cases.
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PMID:Effect of gamma-globulin preparations on phagocytic function of whole blood. 242 98

We previously described an unusual recombinant protein, designated CD4(178)-PE40, containing the gp120 binding region of human CD4 linked to active regions of Pseudomonas exotoxin A. The ability of this molecule to selectively inhibit protein synthesis in cells expressing the surface envelope glycoprotein of human immunodeficiency virus (HIV) suggested this molecule may be useful in treating infected individuals. To further evaluate its therapeutic potential, several in vitro properties of this hybrid toxin were examined. CD4(178)-PE40 was found to be an extremely potent cytotoxic agent, selectively killing HIV-infected cells with IC50 values around 100 pM. In a coculture system employing mixtures of HIV-infected and -uninfected cells, the hybrid toxin inhibited spread of the infection, as judged by a delay in HIV-induced cell killing and a dramatic suppression of free virus production. Experiments with control recombinant proteins indicated that this protective effect was primarily due to selective killing of the HIV-infected cells, rather than to a simple blocking effect of the CD4 moiety of the hybrid toxin. Using recombinant vaccinia viruses as expression vectors, we found the hybrid toxin to be active against cells expressing the envelope glycoproteins of divergent isolates of HIV-1, as well as HIV-2 and simian immunodeficiency virus. These results provide further support for the therapeutic potential of CD4(178)-PE40 in the treatment of HIV-infected individuals.
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PMID:CD4-Pseudomonas exotoxin hybrid protein blocks the spread of human immunodeficiency virus infection in vitro and is active against cells expressing the envelope glycoproteins from diverse primate immunodeficiency retroviruses. 248 Jun 5

We developed a particle concentration fluorescent immunoassay to quantify the binding in solution of the human immunodeficiency virus (HIV) external glycoprotein (gp120) to soluble CD4 (sCD4). The assay is rapid (1 hr), quantitative, and requires as little as 0.1 pmole of gp120 per evaluation. We find that gp120, purified from recombinant baculovirus infected insect cells, is suitable for the assay. Moreover, sCD4s obtained either from recombinant E. coli or mammalian cells, consisting of the N-terminal two domains (about 180 amino acids) as well as linked to the active regions of Pseudomonas exotoxin A, bind gp120 similarly.
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PMID:A rapid solution immunoassay to quantify binding of the human immunodeficiency virus envelope glycoprotein to soluble CD4. 254 87

Contamination of twenty endoscopes used in patients with AIDS was assessed. The suction-biopsy, air, and water channels and the insertion tube were sampled after use, after washing in detergent, and after disinfection for 2 min in 2% alkaline glutaraldehyde. The polymerase chain reaction with Southern blotting, cell cultures, and antigen immunoassay were used to detect human immunodeficiency virus (HIV). Samples were also examined for cytomegalovirus, adenoviruses, enteroviruses, herpes simplex virus, myxoviruses, hepatitis B surface antigen, fungi, and bacteria. Seven of twenty unwashed endoscopes were contaminated by HIV. Commensal bacteria were found in all endoscopes, Candida albicans in six, Staphylococcus aureus in five, and Pseudomonas aeruginosa in five. Washing alone removed all detectable organisms from 66 of 68 contaminated sites; Neisseria spp were recovered from two air channels after washing but not after disinfection. Washing achieved a mean reduction of 4.93 (95% confidence interval 3.69-6.17) colony forming units per ml.
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PMID:Contamination of endoscopes used in AIDS patients. 256 80

During the 11 month period up to 30 September 1987, 37 patients (26 male, 11 female, mean age 27 years) with respiratory symptoms who were human immunodeficiency virus (HIV) positive, were studied prospectively on 40 occasions to determine the cause of any pulmonary complications. HIV was heterosexually transmitted. Predominant symptoms were cough (89%), fever (89%), weight loss (83%), and dyspnoea (60%). Transnasal fibre-optic bronchoscopy (with bronchoalveolar lavage, bronchial brushings and transbronchial lung biopsies) was performed on 35 patients, twice on 3 patients. 'Tru-cut' lung biopsies were obtained from 2 patients who died before bronchoscopy. Pulmonary tuberculosis was the commonest disease, being found in one-third of the patients (12 of 37). Mycobacterium tuberculosis was cultured from 4; the remainder of the plates were contaminated. Pneumocystis carinii was present in 8 patients: as the sole pathogen in 3, with Streptococcus pneumoniae in 4, Staphylococcus aureus in 2, and one also had tuberculous lymphadenitis. Endobronchial Kaposi's sarcoma was seen in 6 of 7 patients with skin nodules. Bacterial pathogens isolated included Staph. aureus (5), S. pneumoniae (5), Klebsiella pneumoniae (2), Haemophilus influenzae (2), H. parainfluenzae (1) and Pseudomonas aeruginosa (1). Invading Aspergillus fumigatus was diagnosed by lung biopsy in one. No diagnosis was reached for 8 patients. It is concluded that in Central Africa pulmonary complications in AIDS patients are similar to those in Europe and North America but the incidence of different pathogens depends on the prevalence of pathogens in the community. M. tuberculosis is probably the commonest pathogen. This study has confirmed that P. carinii pneumonia does occur, but occurs less frequently.
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PMID:Pulmonary diseases in patients infected with the human immunodeficiency virus in Zimbabwe, Central Africa. 261 33

Certain types and causes of pneumonia are unique to the immunocompromised host. The most frequent causes are cytomegalovirus, Pneumocystis carinii, varicella zoster virus, Candida species and Aspergillus species. Lymphoid interstitial pneumonia has recently been recognized in children with the acquired immunodeficiency syndrome. With the exception of varicella-zoster pneumonitis, an invasive procedure, such as open lung biopsy, is required to establish a definitive diagnosis. Infrequent causes of pneumonitis in immunocompromised children include Toxoplasma gondii; Cryptosporidium; Herpes simplex; adenovirus, gram-negative bacillary infections (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Legionella pneumophilia); Nocardia spp; zygomycetes, and Cryptococcus neoformans. The discovery of any of the aforementioned pneumonias suggests the patient may have a serious underlying immunodeficiency.
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PMID:Pneumonia in the immunocompromised child. 282 16


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