Medium-chain fatty acids enhance expression and histone acetylation of genes related to lipid metabolism in insulin-resistant adipocytes.

BACKGROUND: The expressions of genes related to lipid metabolism are decreased in adipocytes with insulin resistance. In this study, we examined the effects of fatty acids on the reduced expressions and histone acetylation of lipid metabolism-related genes in 3T3-L1 adipocytes treated with insulin resistance induced by tumor necrosis factor (TNF)-α. METHODS: Short-, medium-, and long-chain fatty acid were co-administered with TNF-α in 3T3-L1 adipocytes. Then, mRNA expressions and histone acetylation of genes involved in lipid metabolism were determined using mRNA microarrays, qRT-PCR, and chromatin immunoprecipitation assays. RESULTS: We found in microarray and subsequent qRT-PCR analyses that the expression levels of several lipid metabolism-related genes, including Gpd1, Cidec, and Cyp4b1, were reduced by TNF-α treatment and restored by co-treatment with a short-chain fatty acid (C4: butyric acid) and medium-chain fatty acids (C8: caprylic acid and C10: capric acid). The pathway analysis of the microarray showed that capric acid enhanced mRNA levels of genes in the PPAR signaling pathway and adipogenesis genes in the TNF-α-treated adipocytes. Histone acetylation around Cidec and Gpd1 genes were also reduced by TNF-α treatment and recovered by co-administration with short- and medium-chain fatty acids. GENERAL SIGNIFICANCE: Medium- and short-chain fatty acids induce the expressions of Cidec and Gpd1, which are lipid metabolism-related genes in insulin-resistant adipocytes, by promoting histone acetylation around these genes.

A case of gastric granular cell tumor.

We herein describe an extremely rare case of gastric granular cell tumor (GCT). The gastric submucosal tumor showed a central tiny depression on the surface with a molar tooth-like appearance on esophagogastroduodenoscopy. Our case highlights that gastric GCT should be considered as differential diagnosis of gastric submucosal tumors.

Chronic Expanding Hematomas That Occurred 20 Years or More After Primary Total Hip Arthroplasty: A Report of 2 Cases.

CASE: We report 2 patients who developed chronic expanding hematomas (CEHs) more than 20 years after ceramic-on-polyethylene total hip arthroplasty (THA). One CEH occurred after a minor fall, and the other appeared with no obvious injury. Neither of the 2 was on anticoagulation. Each caused extensive osteolysis. CONCLUSION: The only 2 previously reported post-THA cases of CEH involved metal-on-metal THAs and occurred several years after the index THA. Our patients show that CEH also can occur after ceramic-on-polyethylene THA, even after an uneventful clinical course of more than 20 years. Complete removal of both hematoma stopped osteolytic progression, with no recurrence to date.

Desmoplastic myxoid tumor, SMARCB1-mutant: a new variant of SMARCB1-deficient tumor of the central nervous system preferentially arising in the pineal region.

Desmoplastic myxoid tumor (DMT), SMARCB1-mutant is a recently proposed brain tumor that occurs in the pineal region of adults. This tumor is characterized by desmoplastic stroma and various degrees of myxoid matrix. Tumor cells with low-grade morphology show polyphenotypic immunoreactivity, and rhabdoid cells are rare. We herein present a case with some uncommon features such as no myxoid stroma and slightly elevated proliferating activity. To date, knowledge on the variety of SMARCB1/INI1-deficient tumors of the central nervous system is gradually increasing, encompassing highly aggressive to slow-growing varieties. DMT, SMARCB1-mutant seems to be relatively benign, but careful attention is necessary because SMARCB1/INI1 deficiency is generally a genetic signature of concern.

Recurrent Epstein-Barr Virus-positive (EBV+) Primary Central Nervous System Lymphoma (PCNSL) in a Patient with Clinical Features of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS).

Primary central nervous system lymphoma (PCNSL) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) can share clinical features and may be indistinguishable, even after brain biopsy. We encountered a case of Epstein-Barr virus-positive (EBV+) PCNSL recurrence in a patient with clinical features of CLIPPERS, and repeat brain biopsy was required to reach the correct diagnosis. Four years after the initial diagnosis and treatment of PCNSL, "peppering" punctate enhanced lesions with transient steroid responsiveness were detected during brain magnetic resonance imaging (MRI). A second brain biopsy supported a diagnosis of CLIPPERS, while a third biopsy confirmed the diagnosis of recurrent PCNSL.

Non-aneurysmal Subarachnoid Hemorrhaging: A Rare Cause of Death in a Patient with Multiple System Atrophy.

Sudden death as a result of multiple system atrophy (MSA) is usually attributed to vocal cord paralysis or disruption of breathing owing to the degeneration of the brainstem respiratory centers. However, the exact pathophysiology of sudden death is still unclear. In addition, specific causes of sudden death are not always investigated by an autopsy. We herein report a patient with MSA and non-aneurysmal subarachnoid hemorrhaging, which is believed to be a rare cause of death in this setting. Without an autopsy, our case would likely have been diagnosed as sudden death due to vocal cord paralysis. To develop effective strategies to prevent sudden death, a post-mortem investigation is important in order to exclude known structural causes of death.

Polymorphism in microRNA-binding site in HNF1B influences the susceptibility of type 2 diabetes mellitus: a population based case-control study.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified many SNPs associated with type 2 diabetes mellitus (T2DM). However, the functional roles for most of the SNPs have not been elucidated. MicroRNAs (miRNAs) are key regulators of gene expression involved in the development and progression of various diseases including T2DM. In this study, we investigated whether commonly occurring SNPs modulate miRNA-directed regulation of gene expression, and whether such SNPs in miRNA-binding sites are associated with the susceptibility for T2DM. METHODS: Genotypes of eleven 3' untranslated region (UTR) SNPs of seven susceptibility genes for T2DM were determined in 353 T2DM patients and 448 control subjects. In addition, the interactions of miRNAs with the 3'UTR in the hepatocyte nuclear factor 1ß (HNF1B) gene were investigated using luciferase reporter assays. RESULTS: One 3'UTR SNP (rs2229295) in the HNF1B gene was significantly associated with T2DM, and the frequency of an A allele (rs2229295) in T2DM patients was decreased compared with that in controls. Luciferase reporter assays showed that the SNP (rs2229295) altered the binding of two miRNAs (hsa-miR-214-5p and hsa-miR-550a-5p). CONCLUSIONS: We have detected the interactions of hsa-miR-214-5p/hsa-miR-550a-5p and the 3'UTR SNP of the HNF1B gene by in vitro luciferase reporter assays, and propose that the binding of such miRNAs regulates the expression of the HNF1B gene and the susceptibility of T2DM.

Comparison of efficiency between FLPe and Cre for recombinase-mediated cassette exchange in vitro and in adenovirus vector production.

Cre and FLP recombinases mediate not only specific deletions and insertions, but also the recombinase-mediated cassette exchange (RMCE) reaction, which is used in cell biotechnology including ES cells and mouse genetics. However, comparison of efficiencies for Cre and FLP in RMCE has not been made. We here examined the detailed process of RMCE with Cre and FLP in vitro using mutant loxP 2272 and three mutant FRTs (FRT G, FRT H, and FRT F3) and then quantitatively compared the RMCE reactions in vitro. Interestingly, in the in vitro reactions, the RMCE efficiency of Cre reached a plateau level of approximately 5% and did not proceed further, whereas that of FLPe reached approximately 12-13%, showing that FLPe reached a higher level of efficiency than Cre possibly when they were supplied at a very high concentration. Moreover, we quantitatively compared the production efficiency of E1-deleted adenovirus vector using the RMCE method with Cre or FLP. The results showed that FLPe was again found more efficient than Cre in RMCE reaction. Thus, although Cre is considered more active than, or similar to, FLPe, it may not be necessarily true for RMCE reaction. Possible reasons explaining these results are discussed.

Genetic diversity of the MHC class-II DQA gene in brown bears (Ursus arctos) on Hokkaido, Northern Japan.

To investigate genetic diversity of a major histocompatibility complex (MHC) gene in the brown bear (Ursus arctos) population on Hokkaido Island, northern Japan, we cloned and sequenced parts of exon 2 and intron 2 of the MHC class-II DQA gene from 32 brown bears. According to strict criteria for allele identification established by mammalian MHC nomenclature committees, four DQA types (Urar-DQA*01 to Urar-DQA*04) were identified. Of the four, however, Urar-DQA*04 had a 12-bp deletion not detected in a cDNA analysis, indicating that this is a pseudogene at a distinct locus generated by gene duplication. The nucleotide sequences of the other three DQA alleles, which were expressed (because detected from cDNA), were very similar, indicating lower DQA variation In the Hokkaido brown bear population than in other mammals. We attribute this low genetic diversity to (1) some limited effect of possible balancing selection; (2) bottlenecks and inbreeding after migration and isolation of the Hokkaido brown bear population from the Eurasian Continent; (3) a much slower evolutionary rate in DQA than in other MHC genes in the Hokkaido brown bear population.