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)

Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+ cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.
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PMID:Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. 154 90

Intravenous immunoglobulin (IVIG) therapy has been used not only as replacement treatment for immunodeficiency, but also as treatment of autoimmune diseases, specifically Kawasaki disease, systemic juvenile arthritis and juvenile dermatomyositis. In Kawasaki disease, IVIG reduces the incidence of coronary artery abnormalities, as well as rapidly improving clinical and laboratory variables such as fever and rash, platelet count, white blood cell count and serum albumin. Furthermore, a single high dose of 2 g/kg is as effective as 400 mg/kg x 4 days. In systemic juvenile arthritis, followup of at least one year demonstrated that monthly treatment with IVIG resulted in improvement of systemic disease in 10/11 patients, allowed for cessation of prednisone treatment in 7/8 patients and significant improvement of arthritis in 8 patients. In juvenile dermatomyositis, we report 2 uncontrolled trials of IVIG treatment that resulted in significant clinical improvement and steroid-sparing. In contrast, IVIG treatment of systemic lupus erythematosus (SLE) resulted in improvement in 3 patients, but exacerbation or new onset of renal disease in 3 patients. Overall, our report demonstrates that IVIG has been effective both in a controlled trial in Kawasaki disease and in uncontrolled trials in systemic juvenile arthritis and juvenile dermatomyositis. We suggest that IVIG should be used cautiously in SLE.
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PMID:Intravenous immunoglobulin therapy: magic or black magic. 801 61

Monocytes express cell surface receptors for extracellular matrix (ECM) proteins of basement membranes. These receptors are engaged during extravasation of cells through capillary endothelium into tissue. The number of human immunodeficiency virus (HIV)-infected monocytes that adhered to ECM over 2 h was threefold higher than that of uninfected control cells. This difference was ECM specific and was not observed with a bovine serum albumin substrate. Enhanced adhesion to ECM was evident in monocytes by 4 days after HIV infection and increased through 10 days. Monocytes exposed to a T cell-tropic HIV strain that binds to but does not replicate in monocytes showed no changes in adherence to ECM. Thus, productive infection of monocytes by HIV induces a significant increase in the capacity of these cells to interact with ECM. Enhanced adhesion of HIV-infected monocytes to ECM was associated with increased spreading: at 12 h, sixfold more HIV-infected monocytes were spread on ECM than were uninfected control cells. Cell processes of HIV-infected monocytes formed a complex network on ECM: many of these cells expressed HIV proteins as detected by indirect immunofluorescence. HIV-associated cytopathic effects and levels of virion-associated reverse transcriptase activity depended on the substrate to which monocytes were attached. Virus replication and cytopathic effects in monocytes adhered to ECM, fibronectin, or plastic alone were comparable. In contrast, HIV-infected monocytes attached to laminin showed a significant increase in virus replication and in extent of cytopathic effects through 2 weeks after infection. The lowest levels of HIV replication and cytopathic effects were in monocytes attached to collagen IV. Interactions between monocytes and ECM profoundly affect the manner in which these cells control HIV infection: HIV infection changes the capacity of infected monocytes to attach and spread on ECM; attachment to ECM alters the extent of virus replication in infected cells.
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PMID:Interactions between HIV-infected monocytes and the extracellular matrix: increased capacity of HIV-infected monocytes to adhere to and spread on extracellular matrix associated with changes in extent of virus replication and cytopathic effects in infected cells. 164 Jan 76

Oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease. During a 15-month period, we observed four cases of acute respiratory failure from Pneumocystis carinii pneumonia (PCP) in patients treated with oral cyclophosphamide and prednisone. One patient each had polyarteritis nodosa, Wegener's granulomatosis, bronchiolitis obliterans with organizing pneumonia, and chronic lymphocytic leukemia with red blood cell aplasia. Hypoalbuminemia (serum albumin level less than 3.0 g/dl) and daily therapy were associated with increased risk for development of PCP (p less than 0.05). None of the patients had leukopenia (less than 3,500/cu mm) or neutropenia (less than 1,000/cumm) at diagnosis. All were negative for the human immunodeficiency virus. Patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for PCP. A high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients; consideration for trimethoprim-sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed.
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PMID:Pulmonary complications of combination therapy with cyclophosphamide and prednisone. 167 Jun 29

A whole blood method requiring less than 4 ml of heparinized blood was developed to assess the practicality of preparing whole blood samples that could be easily stored, transported and readily used to determine the lymphocyte phenotypes and proliferation responses of individuals from remote areas who are infected with the human immunodeficiency virus. Minor modifications in standard whole blood procedure for lymphocyte phenotyping have significantly increased the stability of light scatter and fluorescence intensity of the cells for subsequent flow cytometry (FC) analysis. These changes include removal of lysis solution prior to fixation, fixation of monoclonal antibody-stained cells in 1% paraformaldehyde for 30 minutes and storage of fixed samples in medium containing 1% bovine serum albumin. Lymphocyte subsets and their functional subsets could reliably be determined on samples stored for up to 4 weeks. Further, blood samples could be kept at room temperature for up to 96 hours or at ambient temperature during transportation from Africa before staining for FC without affecting their quantitation. While samples could be processed for FC analysis under field-laboratory conditions, proliferation assays could only be performed on samples that were transported within 48 hours of their collection. The whole blood method saves time and expense and decreases the volumes of blood required to perform phenotypic analysis and functional assays on specimens collected in remote areas.
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PMID:Long-term preservation of whole blood samples for flow cytometry analysis in normal and HIV-infected individuals from Africa. 171 4

The N-terminal region of the human immunodeficiency virus type 1 (HIV-1) gp41 appears to be involved in virus-cell membrane fusion. To study the influence of fusion domain structure on gp41 interaction with artificial lipid membranes, two families of peptides were synthesized. The peptides of the first family starting from the C-terminal Gly-532 of gp160 (BRU isolate) were assembled in a stepwise manner to N-terminus of gp41(Ala-517). These hydrophobic peptides, containing 10-16 amino acid residues (a.a.), were able to form channel-like current fluctuation through planar lipid membranes, and the longest 15-16 a.a. peptides lysed the liposomes. Peptides of the second family beginning from the C-terminal Arg-538 and continuing to Val-510 contained several hydrophilic amino acid residues. These 15-22 a.a. peptides also increased the conductance of planar lipid bilayers and lysed liposomes. The degree of liposome lysis depended upon peptide length and concentration. The attachment of gp120 C-terminal amino acid or peptides to N-terminus of 517-538 peptide resulted in complete loss of activity. The effects of the second family of peptides on membranes were reduced to a great extent at acidic pH. The conjugation of 22 a.a. Lys peptide with bovine serum albumin decreased its lytic activity. The circular dichroism study of these peptides revealed alpha-helix configuration in hydrophobic and aqueous media only for deca- and longer peptides. The electron microscopy of 22 a.a. peptide performed in the aqueous medium showed large spherical aggregates about 0.5-0.7 micron in diameter consisting of long filaments approximately 5 nm in diameter. Other tested peptides could generate only short strings. Thus, the effects of fusion peptides on lipid membranes depends on their sequence and length, secondary and tertiary structures, and freedom of their N-terminus.
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PMID:Investigation of human immunodeficiency virus fusion peptides. Analysis of interrelations between their structure and function. 173 43

We have shown that suramin can directly inhibit the binding of the human immunodeficiency virus type 1 gp120 envelope protein to immobilized CD4, thus helping to explain the previously described antiviral properties of suramin. However, physiological concentrations of serum albumin significantly attenuated suramin's antiviral effects, suggesting that only free suramin has antiviral properties. Reported discrepancies between in vitro and clinical activities of suramin may be due to differences between free suramin levels in experimental assays and those achievable clinically.
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PMID:The ability of suramin to block CD4-gp120 binding is reversed in the presence of albumin. 181 Jan 99

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.
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PMID:Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. 182 18

In order to assess the status of their immunologic system, a study was carried out in 38 adults with sickle-cell anaemia. Fifty healthy blood donors were used as control group. Significant decrease of serum albumin (p less than 0.02) and increase of alpha-globulins (p less than 0.01) and gamma-globulins (p less than 0.001) were present in the patients. They showed also significantly decreased percentage of spontaneous rosette-forming lymphocytes (p less than 0.01) and of lymphocytes responding to anti-CD3 monoclonal antibody (p less than 0.05) with respect to the control group. Such relative T-cell decrease in peripheral blood seemingly took place by means of decreasing CD4-positive subpopulations, whose percentage was significantly lower (p less than 0.001) in the patients than in the control subjects. Functional studies showed a significant decrease (p less than 0.001) of the activity of natural cytotoxic cells. None of the patients had antibodies against human immunodeficiency viruses type 1 and type 2, and 60% of them were positive to cytomegalovirus test. No statistical correlation was found between the immunological findings and the presence of antibodies against such virus, neither such alterations correlated with the number of blood units received by the patients.
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PMID:[Immunologic changes in sickle-cell anemia]. 185 69

In rural Haiti we measured and compared the muscle protein and calorie reserves (anthropometrics) as well as the visceral protein reserves (serum albumin, tuberculin sensitivity) in 56 HIV (human immunodeficiency virus type-1) seropositive and 108 HIV seronegative pulmonary tuberculosis patients. Results in patients were also compared to the results of the same measurements made in 160 age, sex and residence matched HIV seronegative controls without tuberculosis. Tuberculosis patients, regardless of HIV status, had significantly reduced muscle protein and calorie reserves compared to controls. The serum albumin was significantly lower in HIV seropositive tuberculosis patients (21.0 g/l) compared to HIV seronegative tuberculosis patients (26.9 g/l) and the serum albumin in both tuberculosis groups was significantly lower than in controls (41.3 g/l). The lower the serum albumin in the tuberculosis patients the greater the likelihood of a negative tuberculin test. HIV seropositive tuberculosis patients were significantly more likely to be tuberculin negative than HIV seronegative tuberculosis patients. Tuberculosis is associated with significant malnutrition. Worse malnutrition in tuberculosis patients co-infected with HIV suggests that the effect of the two pathogens on nutrition is additive or, alternatively, that tuberculosis patients who are particularly malnourished are at increased risk for HIV.
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PMID:Pulmonary tuberculosis, human immunodeficiency virus type-1 and malnutrition. 190 8


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