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)

Cell lines secreting IgG1 human monoclonal antibodies (mAb) to the envelope glycoprotein, gp120, of human immunodeficiency virus (HIV) have been produced by transformation of peripheral blood cells from HIV-infected individuals and by fusion of transformed cells to a human-mouse heteromyeloma cell line (SHM-D33). Two human mAbs were site-selected by means of a 23-mer synthetic peptide spanning a portion of the third variable domain of gp120 from the MN strain of HIV. The two heterohybridomas produce three times more IgG than do their parent lymphoblastoid cell lines. The specificities of these mAbs have been mapped to sequences near the tip of the disulfide loop of the gp120 third variable domain, Lys-Arg-Ile-His-Ile and His-Ile-Gly-Pro-Gly-Arg, respectively. The mAbs have dissociation constants of 3.7 x 10(-6) M and 8.3 x 10(-7) M, neutralize HIVMN in vitro at nanogram levels, and bear the characteristics of antibodies associated with protective immunity in vivo.
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PMID:Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. 201 46

The nucleocapsid (NC) protein (p15) of the human immunodeficiency virus (HIV) has been cloned and overproduced (under the control of a phage T7 promoter) in soluble form in an Escherichia coli host. The soluble NC protein is a fusion protein containing 15 amino acids from the T7 gene 10 and 7 amino acids from the HIV p24 protein at the N-terminus to make a protein of 171 amino acids. The plasmid containing the fusion gene is designated p15DF. A homogeneous product has been isolated from the induced cells and, when isolated under aerobic conditions, contains 0.3-0.5 mol of Zn/mol of protein and has only 2 titratable SH groups. Reduction and refolding in the presence of Zn(II) yields a protein containing 2.0 mol of Zn/mol of protein and 6 titratable SH groups. On the other hand, if the cells are sonicated in 2 mM CdCl2 and purified at pH 5.0, an unoxidized protein containing 2 mol of Cd/mol of protein is obtained. The Cd(II) ions can be exchanged with Zn(II), Co(II), or 113Cd(II). The Co(II)2 NC protein shows d-d electronic transitions at 695 nm [epsilon = 675 M-1 cm-1 per Co(II)] and 640 nm [epsilon = 825 M-1 cm-1 per Co(II)] compatible with regular tetrahedral geometry around both Co(II) ions. The Co(II)2 and Cd(II)2 NC proteins show intense charge-transfer bands in the near-UV, at 355 nm (epsilon = approximately 4000 M-1 cm-1) and 310 nm (epsilon = approximately 8000 M-1 cm-1) for the Co(II) protein and 255 nm (epsilon = approximately 10(4) M-1 cm-1) for the Cd(II)2 NC protein, compatible with -S- coordination. 113Cd NMR of the 113Cd(II)2 NC protein shows two 113Cd NMR signals at 659 and 640 ppm, respectively, each integrating to approximately 1 Cd(II) ion. The downfield chemical shifts suggest coordination of each 113Cd(II) ion to 3 sulfur donor atoms. The spectroscopic data fully support the prediction that the NC protein binds metal ions to each of the tandem repeats of the -Cys-X2-Cys-X4-His-X4-Cys- sequence contained in the N-terminal half of the molecule. 113Cd NMR shows, however, that the sites are not identical. Isolation of the NC protein under standard aerobic conditions results in oxidation of the sulfhydryl groups and loss of the coordinated Zn(II) ions, while preparation of the NC protein as the Cd(II) derivative at low pH protects the sulfhydryl groups from oxidation.
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PMID:Physicochemical properties of cloned nucleocapsid protein from HIV. Interactions with metal ions. 203 85

The tat trans-activator proteins of the primate immunodeficiency viruses contain a highly conserved cysteine-rich domain. In human immunodeficiency virus type 1 tat there are seven cysteines located between residues 22 and 37 that are thought to form a metal-nucleic acid-binding structure. Most of the previous mutagenesis studies had demonstrated that these residues are essential for tat activity and virus expression. Here we show that potentially conserved cysteine-histidine substitutions within the proposed tetrahedral structure still eliminate tat activity and virus expression. Consistent with previous studies, one cysteine-to-histidine mutation (amino acid 31) had little effect on trans-activation. We have studied the functional properties, stability and subcellular localization of several tat protein mutants. Most of the mutants are stable and properly localized to the nucleus and/or nucleolus. However, cysteine-to-glycine at position 34 affected tat stability. Our studies with the histidine mutants suggest that tat does not assume the prototype "zinc finger" structure for metal binding.
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PMID:Conservative mutations in the putative metal-binding region of human immunodeficiency virus tat disrupt virus replication. 207 7

Two cases of cryptosporidiosis in adults were described. A 38 years old men presented with temporally reduced immunodeficiency and typical syndromes of 3 weeks duration. His wife had asymptomatic infection.
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PMID:[2 cases of cryptosporidiosis in adults]. 208 8

All retroviruses contain, in the nucleocapsid domain of the Gag protein, one or two copies of the sequence Cys-X2-Cys-X4-His-X4-Cys. We have generated a series of mutants in the two copies of this motif present in human immunodeficiency virus type 1. These mutants encoded virus particles that were apparently composed of the normal complement of viral proteins but contained only 2 to 20% of the normal level of genomic RNA. No infectivity could be detected in the mutant particles, while 10(5) infectious U were present in an equivalent amount of wild-type particles. Thus, the mutants have another defect in addition to the inefficiency with which they encapsidate genomic RNA. Our results show that both copies of the motif are required for normal RNA packaging and for infectivity. Mutants of this type may have important applications, including nonhazardous materials for research, immunogens in vaccine and immunotherapy studies, and diagnostic reagents.
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PMID:Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. 219 Nov 47

Candida albicans was found to repeatedly colonise and invade the duodenal ulcer base in a 45 years old otherwise healthy patient receiving H2 receptor antagonists for a prolonged period. He had no delayed hypersensitivity to Candida skin test, and had T cell deficiency, abnormality in T cell blast transformation, defective macrophage migration inhibition factor (MIF) and IgA hypogammaglobulinemia. When treated with ketoconazole alone his ulcer healed completely. Ulcer scar biopsy and aspirates revealed no Candida and anti candidal antibodies disappeared from his serum. His T cell blastoid transformation, MIF and skin DTH to Candida were restored to normal levels, but IgA levels remained unchanged. Thus H2 receptor antagonists probably caused abnormalities in T helper cells leading to lymphokine unresponsiveness and subsequently loss of cellular immunity to candidal antigen. This combined with prior IgA immunodeficiency resulted into severe invasive candidiasis.
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PMID:Severe duodenal candidiasis in a patient with IgA deficiency and T cell defects. 230 8

In an effort to improve the clinical signs of Parkinson's disease, we have implanted mesencephalic dopamine cells from a 7-week human embryo into the caudate and putamen of a 52-year-old man with Parkinson's disease. Fetal tissue was obtained from elective abortion. The woman and the patient with Parkinson's disease were unknown to each other. The woman gave specific consent and was not paid. The patient had a 20-year history of parkinsonism treated with multiple drug therapies including levodopa/carbidopa (Sinemet) every 2 1/2 hours. His symptoms were worse on the left side. For 5 months prior to transplantation, the patient underwent clinical evaluations by both a neurologist and a computer system installed in his home for daily measurement of walking and hand movements. Preoperative positron emission tomographic scanning with 6-L[18F]fluorodopa (fluorodopa) demonstrated severe dopamine depletion bilaterally. Fetal tissue was matched to the patient for ABO blood antigens, and maternal serum was screened for hepatitis B and human immunodeficiency virus type 1 prior to surgery. Fetal tissue was implanted stereotactically throughout the caudate and putamen on the right side of the brain via 10 needle tracks. The patient was not immunosuppressed. Results 12 months after surgery showed 42% improvement in left-hand speed before the first morning dose of drug and 40% greater response to drug therapy. Right-hand speed increased 15% before drug therapy and 23% after drug therapy. Reaction time was unaffected. Walking speed increased 33% after drug administration, although walking speed before the first morning dose of drugs declined 40%. Walking speed on an all-day basis improved 17%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transplantation of human fetal dopamine cells for Parkinson's disease. Results at 1 year. 233 98

We present the case of a 26-year-old human immunodeficiency virus-seropositive man who developed progressive multifocal leukoencephalopathy as the initial manifestation of AIDS. He appears to have responded dramatically to therapy with 3'-azido-3'-deoxythymidine (AZT). His neurologic status deteriorated shortly after an AZT dose reduction. He has stabilized since resuming his previous AZT dose. Although it remains unclear whether AZT is useful in the treatment of JC virus infection, we think that all AIDS patients with progressive multifocal leukoencephalopathy should be offered treatment with AZT, especially in light of recent reports describing a possible potentiation of human immunodeficiency virus infection of the central nervous system in this setting.
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PMID:Human immunodeficiency virus-associated progressive multifocal leukoencephalopathy: apparent response to 3'-azido-3'-deoxythymidine. 235 8

Expression of the human immunodeficiency virus tat-encoded protein (Tat) is required for virus replication. A genetic approach was used to facilitate the purification of biologically active Tat. A recombinant Tat protein containing a stretch of six histidine residues and a protease cleavage site was engineered and purified to greater than 95% homogeneity in a single step by immobilized metal-ion chromatography with a special affinity resin that has selectivity for proteins with neighboring histidine residues. A modified scrape loading method for introduction of protein into cell monolayers was used to demonstrate that the purified Tat retained biological activity. Tat function was completely blocked in the presence of transcription inhibitors, which demonstrates the requirement of ongoing mRNA synthesis for trans-activation. These studies indicate that the mechanism of trans-activation is unlikely to involve a direct action of Tat on mRNA stability, transport, or translation and provides the basis for a rapid assay that can be used to identify inhibitors of trans-activation. The methods described herein should be useful for the functional analysis of other proteins that do not confer activity through a receptor-mediated pathway.
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PMID:Bioassay for trans-activation using purified human immunodeficiency virus tat-encoded protein: trans-activation requires mRNA synthesis. 253 34

The tat protein of human immunodeficiency virus (HIV) has a characteristic cysteine-rich region containing 7 cysteines within 16 residues. The role of this region was investigated by creation of several tat gene mutants. The activities of the novel tat gene translational products were assayed by measuring the co-transfected chloramphenicol acetyl-transferase (CAT) gene expression controlled by HIV long-terminal repeat (LTR) in the COS 7 cells. Substitution of either Cys22 with Gly, or Cys34-Gln-Val-Cys with His-Gln-Val-His, and deletion behind Lys50 of the tat protein caused a drastic loss in its activity.
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PMID:Role of the cysteine-rich region of HIV tat protein on its trans-activational ability. 254 58


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