Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Discoid lupus erythematosus (DLE)-like lesions and recurrent aphthous-like stomatitis have often been described in carriers of X-linked chronic granulomatous disease (CGD). The capacity of the polymorphonuclear leucocytes to reduce nitroblue tetrazolium (NBT) after stimulation with phorbol myristate acetate (NBT test), a function of normal oxidative metabolism, was determined in 34 patients with DLE of whom 17 also suffered from recurrent stomatitis. The NBT test turned out to be normal in all 34 patients, indicating that none of them were carriers of X-linked CGD. In spite of the negative results of this study it is recommended that all female patients suffering from DLE in combination with recurrent aphthous-like stomatitis are screened by means of the NBT test, because this examination is simple and inexpensive, and because of the importance of identifying carriers of CGD with a view to genetic guidance.
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PMID:Discoid lupus erythematosus and carrier status of X-linked chronic granulomatous disease. 665 47

Out of fifteen carriers of X-linked chronic granulomatous disease five had discoid lupus erythematosus-like skin lesions together with recurrent aphthous-like stomatitis, another five had only recurrent aphthous-like stomatitis, and the remainder were symptom-free. In individual carriers monocytes and neutrophils were equally reduced in their capacity for superoxide production, [1-14C]glucose oxidation and antibody-dependent cytotoxicity; but within he group of carriers a broad spectrum of depression was found. The degree of depression was closely related to the manifestations of clinical disease. It is suggested that the defective oxygen-dependent metabolism might play an aetiological role in the development of inflammatory diseases in carriers of chronic granulomatous disease. Two out of 10 unselected females with discoid lupus erythematosus were shown to be carriers of X-linked chronic granulomatous disease. Screening for this carrier state might therefore be of importance in these patients.
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PMID:Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease. 727 85

X-linked agammaglobulinemia in humans and X-linked immunodeficiency (xid) in mice are both caused by mutations in Bruton's tyrosine kinase (Btk). Xid mice lack the early T cell-independent type 2 (TI-2) antibody response to polio virus and to a recombinant vaccinia virus (Vacc-IND-G) expressing the neutralizing determinant of vesicular stomatitis virus (VSV). This response could be restored by introduction of one or two copies of a murine Btk cDNA transgene driven by the Ig heavy chain promoter plus enhancer and depended crucially on a sufficient Btk expression level. Introduction of the same transgene into wild-type mice had little to no negative effect. The TI-1 antibody response to VSV and the T cell-dependent response to lymphocytic choriomeningitis virus were comparable in all mice tested. All mice analyzed eventually reached similar primary and memory antibody titers against all viruses independent of the mouse Btk genotype. These studies show that the xid mutation in mice has no dominant negative effect and that a transgene - even when not provided in the natural genetic context - may be able to restore functional defects resulting from genetic mutation.
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PMID:A Btk transgene restores the antiviral TI-2 antibody responses of xid mice in a dose-dependent fashion. 1050 72

Hemophilia A is an inheritable X-linked bleeding disorder most frequently occurring as a consequence of genetic alterations within the factor VIII (FVIII) gene. In the present study, pseudotyped human immunodeficiency virus type 1 (HIV-1)-derived lentivectors expressing hFVIII were assessed for the ability to correct the hemophilia A phenotype in FVIII knockout mice. Therapeutic levels of plasma hFVIII (1-7 ng/mL) were detected in C57B1/6 mice (4-5 weeks old) after portal vein administration of hFVIII-expressing lentivectors pseudotyped with the rhabdoviral vesicular stomatitis viral G protein (VSV-G). More importantly, transduction of hemophilia A mice with FVIII expressing lentivectors resulted in transient correction of the bleeding diathesis phenotype. Moreover, the use of alternate viral pseudotypes based on the lymphocytic choriomeningitis virus (LCMV) resulted in similar circulating levels of FVIII. Interestingly, similar doses of LCMV-pseudotyped lentiviral vectors resulted in minimal systemic or hepatic injury as measured by plasma alanine transferase (ALT), aspartate transferase (AST), and tumor necrosis factor (TNF)-alpha compared to the more commonly used envelope, VSV-G. In summary, these studies demonstrated both the potential merit of lentivectors in terms of correcting monogenic inherited disorders, and also the importance of using alternate pseudotypes, such as LCMV, to safely transfer therapeutic genes in vivo without producing adverse effects.
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PMID:Correction of bleeding diathesis without liver toxicity using arenaviral-pseudotyped HIV-1-based vectors in hemophilia A mice. 1457 28

The case findings in a 22-year-old male patient of keratosis follicularis spinulosa decalvans are described. In addition to the characteristic cutaneous, occular and histological features, he had striking angular stomatitis and fissuring of the tongue simulating vitamin B-complex deficiency. This is an unreported feature to our knowledge. The mode of inheritance suggested X-linked trait.
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PMID:Keratosis follicularis spinulosa decalvans. 2095 6

Gene therapy for hematological disorders relies on the genetic modification of CD34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. Here, we show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem cells (HSCs) as entry receptor, transfers genes preferentially into cells with high engraftment capability. Transduction of unstimulated CD34(+) cells with CD133-LV resulted in gene marking of cells with competitive proliferative advantage in vitro and in immunodeficient mice. The CD133-LV-transduced population contained significantly more cells with repopulating capacity than cells transduced with vesicular stomatitis virus (VSV)-LV, a lentiviral vector pseudotyped with the vesicular stomatitis virus G protein. Upon transfer of a barcode library, CD133-LV-transduced cells sustained gene marking in vivo for a prolonged period of time with a 6.7-fold higher recovery of barcodes compared to transduced control cells. Moreover, CD133-LV-transduced cells were capable of repopulating secondary recipients. Lastly, we show that this targeting strategy can be used for transfer of a therapeutic gene into CD34(+) cells obtained from patients suffering of X-linked chronic granulomatous disease. In conclusion, direct gene transfer into CD133(+) cells allows for sustained long-term engraftment of gene corrected cells.
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PMID:CD133-targeted gene transfer into long-term repopulating hematopoietic stem cells. 2584 27

The goal of this study was to assess the efficacy of concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) after neoadjuvant chemotherapy (NACT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 120 patients with stage III-IVB NPC treated with NACT followed by IMRT alone (39 patients, arm 1) or CCRT (81 patients, arm 2) between May 2009 and June 2012 were eligible for study inclusion. NACT consisted of docetaxe (DOC, 60 mg/m(2), day 1) and cisplatin (DDP, 100 mg/m(2), days 1-5, every 3 weeks). Concurrent chemotherapy was nedaplatin (NDP, 25 mg/m(2), days 1-3, every 3 weeks). The median follow-up period was 41 (range 5-52) months, and the 3-year overall survival, distant metastases-free survival, locoregional relapse-free survival, and progression-free survival rates of arm 1 and arm 2 were 83.3 and 87.4% (P = 0.516), 81.7 and 79.6% (P = 0.596), 86 and 92.3% (P = 0.920), 76.4 and 76.4% (P = 0.709), respectively. During radiotherapy, the most commonly recorded grade 3/4 adverse events were anemia (7.7 vs. 4.9%), leucopenia (10.2 vs. 3.7%), thrombocytopenia (12.8 vs. 3.7%), neutropenia (15.4 vs. 6.2%), nausea/vomiting (7.7 vs. 12.3%), stomatitis/mucositis (38.5 vs. 46.9%), xerostomia (35.9 vs. 30.8%), dermatitis (7.7 vs. 7.4%), and fatigue(15.4 vs. 17.2%) for arm 1 and arm 2. The results of this study indicated that added concurrent chemotherapy to IMRT after neoadjuvant DOC and DDP treatment for locoregionally advanced NPC was probably not be necessary.
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PMID:The role of concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) after neoadjuvant docetaxel and cisplatin treatment in locoregionally advanced nasopharyngeal carcinoma. 2563 34

We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7). SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype. The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues. Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles. In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG. This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function. Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected. Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation. These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
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PMID:A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation. 3033 41