SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.

Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.

Liver steatosis: concordance of MR imaging and MR spectroscopic data with histologic grade.

PURPOSE: To determine if the concordance of magnetic resonance (MR) imaging and MR spectroscopic data with histologic measures of steatosis is affected by histologic magnification level, tissue heterogeneity, or assessment of tissue area versus that of hepatocytes. MATERIALS AND METHODS: This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. In- and out-of-phase MR imaging and MR spectroscopic measures of steatosis were compared in 33 patients with nonalcoholic fatty liver disease and in 15 healthy volunteers. Concordance of MR imaging and MR spectroscopic data with histologic findings was assessed for (a) histologic examination at standard (×40 and ×100) versus high magnification (×200 and ×400), (b) heterogeneity and homogeneity of livers, and (c) percentage of tissue and hepatocytes that contained lipids. Evaluations included linear regression and Fisher exact tests. RESULTS: In- and out-of-phase MR imaging and MR spectroscopic data were well correlated (R2=0.93) and generally concordant with histologic measures. Patients in whom MR fat fractions were higher than expected compared with steatosis grades at standard magnification histologic examination were upgraded significantly more often when high magnification was used than were the remaining patients (100% [10 of 10] vs 47% [7 of 15], P<.01). MR imaging and MR spectroscopic data of homogeneous livers were significantly more likely than those of heterogeneous livers to be concordant with steatosis grades when high magnification was used (81% [13 of 16] vs 47% [8 of 17], P<.05). For all patients, percentage of fat in tissue was lower than that in hepatocytes, which affected individual patients, but not the overall correlation. CONCLUSION: MR imaging and MR spectroscopic data were generally concordant with histologic measures of steatosis. Discordance between them may reflect differences in magnification at histologic examination and in liver heterogeneity.

Ovarian-type stroma in hepatobiliary cystadenomas and pancreatic mucinous cystic neoplasms: an immunohistochemical study.

We compared immunohistochemical expression of hepatocyte growth factor (HGF), c-met, alpha-inhibin, estrogen receptor (ER), and progesterone receptor (PR) in 10 pancreatic mucinous cystic neoplasms (PMCNs), 8 hepatobiliary cystadenomas (HBCs), and 6 simple liver cysts (SLCs).All HBCs and PMCNs were in women (mean ages, 45.7 and 54.9 years, respectively; P > .05). All HBCs had abundant stroma; PMCN stromal density was more variable (score, 3.0 vs 1.8; P < .05). Stroma in HBCs had greater ER and PR staining (both P < .05) and more consistent, focal, strong reactivity for alpha-inhibin than PMCNs (P < .05). SLCs were found in men and women, lacked ovarian-type stroma, and were negative for ER, PR, and alpha-inhibin. HGF expression was not significantly different in the epithelium of HBCs, PMCNs, and SLCs; c-met expression in the epithelium of HBCs and PMCNs was significantly stronger than in SLCs (P < .05). Differences in stromal density and ER, PR, and alpha-inhibin immunoreactivity in HBCs and PMCNs suggest that different hormonal environments in the liver and pancreas contribute to stromal variation. Up-regulation of c-met in HBCs and PMCNs suggests c-met activation in the pathogenesis of pancreaticobiliary cystic neoplasms.

Entamoeba histolytica encephalitis diagnosed by PCR of cerebrospinal fluid.

Extra-intestinal amebiasis is secondary to invasive intestinal infections and usually results in an amebic liver abscess. Other organs, including lungs, brain, skin, spleen and kidneys, may be involved. Diagnosis of the cerebral infection is of the utmost importance and is most often made by detection of the organism at the time of brain biopsy or at autopsy. We report the first case of Entamoeba histolytica encephalitis diagnosed by PCR of the cerebrospinal fluid. The patient was treated successfully with metronidazole. PCR is an increasingly useful tool for the diagnosis of central nervous system infection and can provide rapid diagnosis.

The other group G Streptococcus: increased detection of Streptococcus canis ulcer infections in dog owners.

beta-Hemolytic Lancefield group G Streptococcus dysgalactiae and Streptococcus canis cannot be distinguished when only Lancefield typing is performed. Phenotypic testing and 16S rRNA gene sequencing identified S. canis associated with ulcer infections in dog owners. Because S. canis may be incorrectly identified (published biochemical descriptions are inconsistent), there may be an underestimation of the true number of infections. Identification of group G streptococci to the species level could have epidemiological and clinical implications.

Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall.

Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Most GISTs arise in the stomach and small bowel, whereas a small number occur elsewhere in the GI tract. Rare cases are identified outside the GI tract and are collectively known as extragastrointestinal stromal tumors (EGISTs). Because of their malignant potential and recent advances in the management of GISTs with imatinib mesylate (Gleevec, Glivec), it is imperative that these tumors are correctly diagnosed. In this study, we reviewed the clinical and pathologic characteristics of 3 cases of EGIST presenting as vulvovaginal/rectovaginal septal masses that were originally misdiagnosed, presumably due to their unusual anatomic locations. The original diagnoses were leiomyoma in one case and leiomyosarcoma in 2 cases. The lesions were localized to the rectovaginal septum () or vagina () and ranged from 4 to 8 cm in diameter. All 3 lesions had a spindle cell morphology that mimicked a smooth muscle tumor. Mitotic figures numbered from 12/50 to 16/50 high power fields (HPFs; median 15). Immunohistochemistry revealed that all 3 cases were strongly positive for KIT (CD117) and CD34 and negative for smooth muscle actin, desmin, pan-cytokeratin, and estrogen receptor. KIT sequence analysis revealed oncogenic mutations in all 3 cases. The first tumor recurred at 2 years and the second tumor recurred at 10 years; the third case is too recent for meaningful follow-up. EGISTs that present as gynecologic masses are rare but may be more common than is currently recognized. Misdiagnosis may lead to inappropriate therapy because conventional chemotherapy and radiotherapy are not effective in the treatment of GISTs, whereas imatinib mesylate (Gleevec, Glivec) has a proven role in managing these tumors. Thus, it is imperative to consider EGISTs in the differential diagnosis of mesenchymal neoplasms in the vulvovaginal/rectovaginal septum.