Disease relevance of GIF

• Congenital intrinsic factor (IF) deficiency is a disorder characterized by megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142) and GIF antibodies, with probable autosomal recessive inheritance [1].
• INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA [2].
• In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes [2].
• CONCLUSIONS: In children with chronic hepatitis B, INF-alpha promotes loss of viral replication markers and surface antigen and improves aminotransferases and histology [3].
• Intrinsic factor within parietal cells of patients with juvenile pernicious anemia. A retrospective immunohistochemical study [4].

Psychiatry related information on GIF

• GIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits neuron outgrowth in Alzheimer's disease [5].
• No signs of psychotic or depressive symptoms appeared during INF-alpha therapy [6].
• In the INF and INF/T groups, a localized pneumonic infiltrate containing P. haemolytica organisms was present [7].

High impact information on GIF

• Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion [8].
• Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis [2].
• The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production [2].
• INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes [9].
• We analyzed the effect of recombinant (r) tumor necrosis factor (TNF), lymphotoxin (LT), and gamma, alpha, and beta 1 interferons (INF-gamma, -alpha and -beta 1), alone and in combination, on GAG production by normal human lung fibroblasts. rTNF, rLT, and rINF-gamma each stimulated fibroblast GAG production [10].

Chemical compound and disease context of GIF

• A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (INF-alpha) in human immunodeficiency virus (HIV)-infected patients [11].
• After adding ribavirin to the therapy, the liver enzymes dropped again, and the PCR carried out 9 months after initiation and 6 months after the end of the 12 months INF-alpha treatment did not detect any virus RNA [6].
• Human tumor-necrosis factor (INF-alpha), induced by Sendai virus in peripheral blood mononuclear leukocytes (PBMC), was isolated using a monoclonal antibody to the protein and radioiodinated by the chloramine-T method [12].
• OBJECTIVES: To investigate the influence of interferon-beta-1b (INF-beta-1b) therapy on blood antioxidants (alpha-tocopherol and NADPH) in multiple sclerosis (MS) [13].
• We report here on a patient whose brain metastases responded to DTIC + INF-gamma [14].

Biological context of GIF

• The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families [15].
• A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency [1].
• Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at base pair g.68 (A>G) and expressed in COS-7 cells [1].
• Comparison of the genomic structure to gastric intrinsic factor (GIF), another vitamin B12 binding protein, revealed a strikingly similar intron/exon structure, with several positionally conserved splice sites [16].
• Our results indicate that INF-gamma can reprogram the myeloid progenitor cells to express a partially corrected phenotype [17].

Anatomical context of GIF

• Intrinsic factor was found on the perinuclear membrane, on rough endoplasmic reticulum, Golgi apparatus, tubulovesicles, and membranes of the multivesicular body in parietal cells [18].
• Intrinsic factor was absent from nuclei, mitochondria, basolateral surface membranes, blunt microvilli, and the cytosol [18].
• Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF-gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population [19].
• Previously we have shown that a single in vivo treatment of selected X-CGD patients with interferon-gamma (INF-gamma) resulted 14 days later in near-normal levels of superoxide generation by phagocytes [17].
• Thus, the enhanced attachment by primitive CML progenitor cells to INF-alpha-treated stromal cells might be due to changes in the neuraminic acid composition in the stromal cell layer [20].

Associations of GIF with chemical compounds

• Intrinsic factor (IF(50)) is a cobalamin (Cbl)-transporting protein of 50 kDa, which can be cleaved into two fragments: the 30 kDa N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20) [21].
• Letter: Intrinsic-factor antibody and vitamin B [22].
• Intrinsic factor deficiency in adults with normal hydrochloric acid production [23].
• By contrast, colonies derived 7 days after a single INF-gamma injection were able to generate superoxide as shown by increased NBT reduction [17].
• 5-FU cytotoxicity can be modulated by folinic acid (FA) or interferon-alpha (INF-alpha) [24].

Other interactions of GIF

• In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice [15].
• Biological recognition of Cbl-peptides was studied in the physiological order: binding by Intrinsic Factor (IF), recognition and transport of the IF-complexes by IF-Cbl receptors (IFCR) on Caco-2 monolayers and oral absorption of the Cbl-conjugates in the rat [25].
• The effect of a small dose of somatostatin (0.05 mg/h) on the gastric secretion of acid, pepsin and Intrinsic Factor (IF) after stepwise increases in the dose of pentagastrin was examined in six healthy volunteers [26].
• Intrinsic factor (IF) secretion in healthy male subjects was studied in response to pentagastrin stimulation with and without cimetidine, and to impromidine, a histamine H2 receptor agonist [27].
• The final preparation was greater than 99% 57Co SO3-Cb1 with an overall yield of greater than 70%, stable for up to four weeks at 20 degrees C in the dark, and capable of binding to the human Cb1 binding proteins Transcobalamin II (TC II), Intrinsic factor (IF) and Salivary R [28].

Analytical, diagnostic and therapeutic context of GIF

• In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients [29].
• Finally, gel filtration analyses of nuclear extracts from INF-gamma-treated cells demonstrate that there is a MCM5/3 subcomplex coeluting with Stat1 [30].
• A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia [19].
• Immunotherapy with INF-alpha/interleukin 2 can induce tumor regression in a proportion of patients with metastatic melanoma [31].
• Tumor-infiltrating macrophages are involved in suppressing growth and metastasis of human prostate cancer cells by INF-beta gene therapy in nude mice [32].

References