ABSTRACT
BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake. METHODS: Among 160 de-novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non-motor features were evaluated using questionnaires and laboratory tests. RESULTS: Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non-motor impairments. CONCLUSIONS: These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non-motor manifestations compared with PD with decreased MIBG.
Subject(s)
Heart/diagnostic imaging , Parkinson Disease/diagnostic imaging , 3-Iodobenzylguanidine/metabolism , Aged , Cognition Disorders/etiology , Cognition Disorders/psychology , Constipation/etiology , Cost of Illness , Female , Humans , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Olfaction Disorders/etiology , Olfaction Disorders/physiopathology , Parkinson Disease/complications , Positron-Emission Tomography , REM Sleep Behavior Disorder/etiology , Radiopharmaceuticals/metabolismABSTRACT
A*02:590 differs from A*02:01:01:01 by a nucleotide substitution at codon 152 (GTG â GCG) with amino change.
Subject(s)
Alleles , Exons , HLA-A2 Antigen/genetics , Point Mutation , Amino Acid Substitution , Asian People , Base Sequence , Codon/chemistry , Genotype , HLA-A2 Antigen/immunology , Histocompatibility Testing , Humans , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNAABSTRACT
Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-ß/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.
Subject(s)
Autophagy/physiology , Collagen Type I/metabolism , Hepatic Stellate Cells/cytology , Hepatic Stellate Cells/metabolism , Phospholipase D/metabolism , Cell Line , Gene Expression Regulation, Enzymologic/physiology , HumansABSTRACT
This communication describes three novel DRB3 alleles whose exon 2 sequences are identical to that of DRB3*010102 except for a single nucleotide substitutions. Comparing with DRB3*010102, the sequence of DRB3*010105, DRB3*0112, and DRB3*0113 differ at codon 31 (TTC -> TTT), codon 84 (GGG -> CGG; Gly -> Arg), and codon 37 (TTC -> CTC; Phe -> Leu), respectively.
Subject(s)
Amino Acid Substitution/genetics , HLA-DR Antigens/genetics , Alleles , Base Sequence , Exons/genetics , HLA-DRB3 Chains , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
The sequence of human leukocyte antigen (HLA)-Cw*0349 is identical to that of HLA-Cw*030301 except for a single nucleotide substitution at codon 156 (CTG-->CGG) resulting in an amino acid change from Leu to Arg.
Subject(s)
Alleles , HLA-C Antigens/genetics , Amino Acid Substitution , Asian People/genetics , Base Sequence , Humans , Korea , Molecular Sequence Data , Point Mutation , Sequence AlignmentABSTRACT
Genotype of the human leukocyte antigen (HLA)-DQA1 locus was analyzed in Koreans (n= 467) using the 14th International Workshop protocol established to characterize the sequences of exons 1-4 of the gene. Unexpectedly, it appeared that the DQA1 (19 alleles) was more diverse than DQB1 (15 alleles) in the study population. DQA1*010201, DQA1*0303, DQA1*0103, and DQA1*0302 appeared to be major alleles exhibiting more than 10%. Among six allele groups, DQA1*01-*06, DQA1*01 showed highest diversity exhibiting seven different alleles. Analysis using maximum likelihood method showed numerous multi-locus HLA haplotypes. High relative linkage disequilibrium values (RLD) of the two-locus haplotypes and exclusive association of a specific DQA1 allele with a specific DRB1 and/or DQB1 alleles suggested tight linkage of DQA1 to DRB1 and DQB1. In HLA-matching process for hematopoietic stem cell transplantation, however, DQA1 typing would be informative for individuals carrying specific DRB1 allele (DRB1*0802, DRB1*1201, or DRB1*1403) that could be associated with multiple DQA1 alleles in the study population. Information obtained in this study will be useful in medical and forensic areas as well as in anthropology.
Subject(s)
Genetic Variation , Genetics, Population , HLA-DQ Antigens/genetics , Histocompatibility Testing/methods , Sequence Analysis, DNA , Alleles , HLA-DQ alpha-Chains , Haplotypes/genetics , Humans , Korea , Polymerase Chain ReactionABSTRACT
Four novel human leukocyte antigen (HLA)-DQA1 alleles have been characterized by direct DNA sequencing of coding exons 1-4. All the novel alleles exhibited a single nucleotide substitution either in exon 3 or in exon 4 when compared with previously defined alleles. Thus, it is likely that alleles were generated by point mutation from pre-existing alleles in the population. Substitutions resulted in either a silent (DQA1*010203) or an amino acid change (DQA1*0506, DQA1*0507, and DQA1*0508). The substituted sites were both previously known polymorphic and conserved positions. Putative haplotypes associated with the novel alleles were deduced based on the HLA types shared by the individuals carrying a novel allele or from previously reported population data.
