Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bovine viral diarrhea virus (BVDV) infection continues to have a significant impact upon US cattle producers despite the availability of more than 140 federally licensed vaccines. Detection and control is hampered by viral heterogeneity that results in differences in neutralizing epitopes, cytopathology and virulence. Recently it was found that there are two different genotypes, BVDV1 and BVDV2, among BVDV. BVDV2 isolates make up a significant proportion of the BVDV isolated in North America. Serologically BVDV2 viruses can be distinguished from BVDV1 and border disease viruses. Mab binding also distinguishes between BVDV1, BVDV2 and BDV. Like the BVDV1 viruses, BVDV2 viruses may exist as one of two biotypes, cytopathic or noncytopathic, based on their activity in cultured cells. Cytopathogenic effects on cultured cells does not correlate with virulence in vivo, as BVDV2 associated with hemorrhagic syndrome (HS) are noncytopathic. Variation among BVDV1 and BVDV2 in the 5' UTR is similar. Phylogenetic analysis and differences in virulence suggest that BVDV2 are heterogeneous. Symptoms resulting from BVDV2 infections may range from clinically inapparent to clinically severe. Recently, disease outbreaks associated with acute uncomplicated BVDV infection have been reported in the US and Canada. These outbreaks of clinically severe disease, termed HS, were all associated with viruses from the BVDV2 genotype. Not all BVDV2 isolates cause clinically severe disease. Avirulent BVDV2 isolates do exist and may predominate over virulent BVDV2 in nature. When virulent BVDV2 viruses are inoculated into calves they induce a disease characterized by fever, diarrhea, leukopenia, lymphopenia, neutropenia, thrombocytopenia, and death. Infection with avirulent BVDV2 results in a reduction of luekocytes that may be accompanied by a low-grade fever. These viruses do not cause clinical disease or a clinical leukopenia.
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PMID:Phylogenetic, antigenic and clinical characterization of type 2 BVDV from North America. 1104 8

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo.
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PMID:Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. 2511 82

The main identified function of BCL2 protein is to prevent cell death by apoptosis. Mouse knock-out for Bcl2 demonstrates growth retardation, severe polycystic kidney disease (PKD), grey hair and lymphopenia, and die prematurely after birth. Here, we report a 40-year-old male referred to for abdominal and thoracic aortic dissection with associated aortic root aneurysm, PKD, lymphocytopenia with a history of T cell lymphoblastic lymphoma, white hair since the age of 20, and learning difficulties. PKD, which was also detected in the father and sister, was related to an inherited PKD1 mutation. The combination of PKD with grey hair and lymphocytopenia was also reminiscent of Bcl2-/- mouse phenotype. BCL2 gene transcript and protein level were observed to be dramatically decreased in patient peripheral blood T-cells and in his aorta vascular wall cells, which was not detected in parents and sister T-cells, suggesting an autosomal recessive inheritance. Accordingly, spontaneous apoptosis of patient T-cells was increased and could be rescued through stimulation with an anti-CD3 antibody. Direct sequencing of BCL2 gene exons, promoter and 3'UTR region as well as BCL2 mRNA sequencing failed in identifying any pathogenic variant. Array-CGH was also normal and whole exome sequencing of the patient, parents and sister DNA did not detect any significant variant in genes encoding BCL2-interacting proteins. miRNA array identified an up-regulation of miR-181a, which is a known regulator of BCL2 expression. Altogether, miR-181a-mediated decrease in BCL2 gene expression could be a modifying factor that aggravates the phenotype of a PKD1 constitutive variant.
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PMID:A constitutive BCL2 down-regulation aggravates the phenotype of PKD1-mutant-induced polycystic kidney disease. 2897 48