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)

Described here is a 59 year old man with dermatomyositis and hypogammaglobulinemia. His muscle power improved after corticosteroid therapy, but extensive amyloidosis and repeated infections appeared. Bone marrow morphology suggested multiple myeloma, but treatment with cytotoxic drugs had no beneficial effect on the amyloidosis. Because of rapid progression of the amyloidosis and further infections, cytotoxic drug therapy was stopped, corticosteroid dosage was decreased, and supplementary immunoglobulin therapy was instituted. The infections occurred less frequently and the amyloidosis appeared to regress. This case suggests that immunosuppressive therapy may exacerbate amyloidosis. The literature is reviewed, and the possible role of humoral immunodeficiency in the pathogenesis of amyloidosis is discussed. It is suggested that supplementary immunoglobulin may be beneficial in amyloidosis.
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PMID:Amyloidosis associated with dermatomyositis and features of multiple myeloma. The progression of amyloidosis associated with corticosteroid and cytotoxic drug therapy. 5 87

The eldest brother in a sibship of five children died of acute myelogenous leukemia at 10 years of age. The second and third eldest brothers died of hypoplastic anemia at ages five and nine years, respectively. A surviving 6 year old brother, the proband of the study, has abnormalities that suggest a preleukemic state: mild pancytopenia, platelet dysfunction, immunodeficiency, and bone marrow hypoplasia with approximately 18 per cent blast forms. His 17 year old sister has a mild normochromic normocytic anemia. Cytogenetic studies revealed C-group monosomy in the bone marrows of the proband and the third brother (45, XY, -C); band studies demonstrated that a No. 8 chromosome was missing in the proband (45, XY, -8). At least four of the siblings and their father had cerebellar ataxia, and evidence of a small cerebellum at autopsy examination or by computerized axial tomography. The disorder in this family has major features of two autosomal recessive preleukemic diseases, ataxia-telangiectasia and Fanconi's anemia. However, these and other inherited conditions were excluded by clinical or laboratory criteria, and no environmental causes of the familial disorder were found. The constellation of abnormalities in the family may constitute a new genetic syndrome.
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PMID:A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy. 28 89

A 28-year-old man with immunodeficiency with hyper IgM was studied. His serum immunoglobulins were characterized by the absence of IgA and low level of IgG associated with high level of IgM. The in vitro pokeweed mitogen (PWM)-induced immunoglobulin synthesis by his peripheral blood lymphocytes was depressed completely for IgA and moderately for IgG although normal numbers and proportions of IgA- and IgG-bearing lymphocytes (on the surface) were demonstrated in the peripheral blood. His T cells could not help IgA production by either normal or his own B cells, whereas they were more efficient helpers for IgM production by his own B cells than were normal T cells. In addition, his B cells produced no IgA and less IgG than normal B cells when co-cultured with normal T cells. This suggests that the failure of IgA specific T helper activity and the maturation arrest of B cells at the stage of the switchover from IgM- to IgG- and/or IgA-producing cells may be the major cause for the hypogammaglobulinaemia in this patient. It is uncertain whether the maturation arrest of B cells is secondary to the T cell defect in helper function for IgA production.
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PMID:Evidence for the failure of IgA specific T helper activity in a patient with immunodeficiency with hyper IgM. 31 10

The structure of a crystal complex of recombinant human immunodeficiency virus type 1 (HIV-1) protease with a peptide-mimetic inhibitor containing a dihydroxyethylene isostere insert replacing the scissile bond has been determined. The inhibitor is Noa-His-Hch psi [CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its Ki for inhibition of the HIV-1 protease is < 1.0 nM (Noa = 1-naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified form of valine, Amp = 2-pyridylmethylamine). The structure of the complex has been refined to a crystallographic R factor of 0.169 at 2.0 A resolution by using restrained least-squares procedures. Root mean square deviations from ideality are 0.02 A and 2.4 degrees, for bond lengths and angles, respectively. The bound inhibitor diastereomer has the R configurations at both of the hydroxyl chiral carbon atoms. One of the diol hydroxyl groups is positioned such that it forms hydrogen bonds with both the active site aspartates, whereas the other interacts with only one of them. Comparison of this X-ray structure with a model-built structure of the inhibitor, published earlier, reveals similar positioning of the backbone atoms and of the side-chain atoms in the P2-P2' region, where the interaction with the protein is strongest. However, the X-ray structure and the model differ considerably in the location of the P3 and P3' end groups, and also in the positioning of the second of the two central hydroxyl groups. Reconstruction of the central portion of the model revealed the source of the hydroxyl discrepancy, which, when corrected, provided a P1-P1' geometry very close to that seen in the X-ray structure.
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PMID:Crystal structure of a complex of HIV-1 protease with a dihydroxyethylene-containing inhibitor: comparisons with molecular modeling. 130 83

A 20-month-old Indian boy presented with recurrent pyogenic infections and failure to thrive. His IgG and IgA levels were low, but his IgM was elevated. He also had undetectable isohaemagglutinin titre and neutropenia, both parameters being poor prognostic indicators in this very rare primary immunodeficiency state--antibody deficiency with hyper IgM. Our patient subsequently succumbed to Pseudomonas aeruginosa septicaemia and meningitis inspite of aggressive antibiotic and intravenous gammaglobulin therapy. To the best of our knowledge, this is the first such case to be documented in Malaysia.
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PMID:Antibody deficiency with hyper IgM--a case report. 130 25

An adeno-associated virus (AAV) genome with a Lys-to-His (K340H) mutation in the consensus nucleotide triphosphate binding site of the rep gene has a dominant-negative DNA replication phenotype in vivo. We expressed both wild-type (Rep78) and mutant (Rep78NTP) proteins in two helper-free expression systems consisting of either recombinant baculoviruses in insect cells or the human immunodeficiency virus type 1 long terminal repeat promoter in human 293 cell transient transfections. We analyzed nuclear extracts from both expression systems for the ability to complement uninfected HeLa cell cytoplasmic extracts in an in vitro terminal resolution assay in which a covalently closed AAV terminal hairpin structure is converted to an extended linear duplex. Although both Rep78 and Rep78NTP bound to AAV terminal hairpin DNA in vitro, Rep78 but not Rep78NTP complemented the terminal resolution assay. Furthermore, Rep78NTP was trans dominant for AAV terminal resolution in vitro. We propose that the dominant-negative replication phenotype of AAV genomes carrying the K340H mutation is mediated by mutant Rep proteins binding to the terminal repeat hairpin.
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PMID:In vitro resolution of adeno-associated virus DNA hairpin termini by wild-type Rep protein is inhibited by a dominant-negative mutant of rep. 130

Mutations designed by analysis of the Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV)-1 protease (PR) crystal structures were introduced into 1) the substrate binding pocket, 2) the substrate enclosing "flaps," and 3) surface loops of RSV PR. Each mutant PR was expressed in Escherichia coli. Changes in activity were detected by following cleavage of a truncated (NC-PR) precursor polypeptide in E. coli and cleavage of synthetic peptide substrates representing RSV and HIV-1 PR cleavage sites in vitro. Mutations in the substrate binding pocket exchanged amino acid residues located close to the substrate in the HIV-1 PR for structurally equivalent residues in the RSV PR. Changing histidine 65 to glycine (H65G) gave an inactive enzyme, while a double mutant R105P,G106V, as well as the triple mutant, H65G,R105P,G106V, produced enzymes which showed significant activity toward a substrate that represented a HIV-1 cleavage site. Mutating the catalytic aspartate (D37S) or an adjacent conserved alanine to threonine (A40T), produced inactive enzymes. In contrast, the substitution A40S was active, but showed a reduced rate of catalysis. Mutations in the flaps of conserved glycines (G69L, G70L) produced inactive PRs. Two extended RSV PR surface loops were shortened to the size found in HIV-1 PR and resulted in drastically reduced activity. These results have confirmed some of the basic predictions made from structural models but have also revealed unexpected roles and interactions in the protein.
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PMID:Mutations that alter the activity of the Rous sarcoma virus protease. 131 55

Respiratory infections occur commonly in patients with advanced human immunodeficiency virus (HIV) infection. Prompt accurate diagnosis is essential as many of the various available therapies have significant toxicities. We describe a patient previously diagnosed with the acquired immunodeficiency syndrome (AIDS) who was found to have cytomegalovirus (CMV) pneumonitis on bronchoscopy. His pneumonitis responded to treatment with the nucleoside analogue ganciclovir. Our patient is the first documented CMV pneumonitis in the Singapore HIV seropositive population.
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PMID:Cytomegalovirus pneumonitis in AIDS--a case report. 133 71

A unique case of a Chinese boy with Wiskott-Aldrich syndrome (WAS) associated with Takayasu's arteritis is reported. He had eczema, epistaxis and recurrent infections since early infancy and was found to have thrombocytopenia, negative delayed-type skin hypersensitivity, low T cell number and impaired lymphocyte proliferation to phytohaemagglutinin and concanavalin A. He had high normal serum immunoglobulin (Ig)G and IgA with low IgM and isohaemagglutinin. He presented with hypertensive encephalopathy at 5.5 years of age and an aortogram demonstrated abdominal aortic aneurysm with bilateral stenosis of renal arteries resulting in renovascular hypertension. His hypertension was difficult to control medically and autotransplant of his kidneys to the iliac arteries was performed, but he died in the immediate postoperative period. The relationship between immunodeficiency and collagen-vascular disease was discussed.
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PMID:Takayasu's arteritis associated with Wiskott-Aldrich syndrome. 135 86

The cDNAs for two DNA binding proteins of BTE, a GC box sequence in the promoter region of the P-450IA1(CYP1A1) gene, have been isolated from a rat liver cDNA library by using the BTE sequence as a binding probe. While one is for the rat equivalent to human Sp1, the other encodes a primary structure of 244 amino acids, a novel DNA binding protein designated BTEB. Both proteins contain a zinc finger domain of Cys-Cys/His-His motif that is repeated three times with sequence similarity of 72% to each other, otherwise they share little or no similarity. The function of BTEB was analysed by transfection of plasmids expressing BTEB and/or Sp1 with appropriate reporter plasmids into a monkey cell line CV-1 and compared with Sp1. BTEB and Sp1 activated the expression of genes with repeated GC box sequences in promoters such as the simian virus 40 early promoter and the human immunodeficiency virus-1 long terminal repeat promoter. In contrast, BTEB repressed the activity of a promoter containing BTE, a single GC box of the CYP1A1 gene that is stimulated by Sp1. When the BTE sequence was repeated five times, however, BTEB turned out to be an activator of the promoter. RNA blot analysis showed that mRNAs for BTEB and Sp1 were expressed in all tissues tested, but their concentrations varied independently in tissues. The former mRNA was rich in the brain, kidney, lung and testis, while the latter was relatively abundant in the thymus and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene. 135 62


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