Successful laparoscopic extirpation of a large omental lipoblastoma in a child

Omental lipoblastoma is extremely rare among benign tumors. We herein report the case of a child who underwent laparoscopic extirpation of a large omental lipoblastoma. A 4‐year‐old girl was diagnosed with an intra‐abdominal solid tumor. Abdominal imaging revealed a fat density mass that was well encapsulated and measured 18 × 15 × 7.5 cm in size. Considering the MRI findings and movability of the tumor, we strongly suspected that the lesion was an omental lipoblastoma. We initially decided to perform laparoscopic exploration and, if possible, extirpation of the solid tumor sequentially. A total of five trocars were used, and the tumor was found to originate from the omentum. We successfully performed complete resection of the tumor laparoscopically. A histological examination revealed lipoblastoma. For large abdominal tumors in children, the laparoscopic approach is recommended as the first procedure when the tumor is preoperatively considered to be benign and resectable.     

Lnk prevents inflammatory CD8+ T‐cell proliferation and contributes to intestinal homeostasis

The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and Lnk^?/? mice have expanded B‐cell, megakaryocyte, and hematopoietic stem‐cell populations. Moreover, mutations in the LNK gene are found in patients with myeloproliferative disease, whereas LNK polymorphisms have recently been associated with inflammatory and autoimmune diseases, including celiac disease. Here, we describe a previously unrecognized function of Lnk in the control of inflammatory CD8⁺ T‐cell proliferation and in intestinal homeostasis. Mature T cells from newly generated Lnk–Venus reporter mice had low but substantial expression of Lnk, whereas Lnk expression was downregulated during homeostatic T‐cell proliferation under lymphopenic conditions. The numbers of CD44^hiIFN‐γ⁺CD8⁺ effector or memory T cells were found to be increased in Lnk^?/? mice, which also exhibited shortening of villi in the small intestine. Lnk^?/? CD8⁺ T cells survived longer in response to stimulation with IL‐15 and proliferated even in nonlymphopenic hosts. Transfer of Lnk^?/? CD8⁺ T cells together with WT CD4⁺ T cells into Rag2‐deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell‐mediated intestinal tissue destruction.     

The Structures of the E22Δ Mutant-Type Amyloid-β Alloforms and the Impact of E22Δ Mutation on the Structures of the Wild-Type Amyloid-β Alloforms

相似文献   

Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin

Background

The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

Methods

A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.

Results

Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p????0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5???g/kg/week to 1?C3% with a dose of <1.5???g/kg/week (p????0.001), and at week 12 the rate had decreased from 44% with a dose of ??1.2???g/kg/week to 18% with a dose of <1.2???g/kg/week (p?=?0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54?C66% of patients given <1.2???g/kg/week (p????0.001), and these patients accounted for 64% of the non-responders.

Conclusions

The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.     

Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction

BackgroundTenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in the adult heart but transiently reappears under various pathologic conditions to play important roles in tissue remodeling. It is unclear whether serum TN-C levels add prognostic information independent from traditional prognostic markers.Methods and ResultsWe assessed 239 patients with first ST-segment elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured serum TN-C and plasma B-type natriuretic peptide (BNP) levels on day 5 after admission and compared long-term clinical outcome. During the follow-up period (24.3 ± 13 months), 54 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that serum TN-C (hazard ratio 2.92, 95% confidence interval [CI] 1.55–5.67; P < .001) and plasma BNP levels (hazard ratio 1.84, 95% CI 1.17–2.97; P = .008) were significant independent predictors for cardiac events after adjustment for multiple confounders. The combination of TN-C and BNP resulted in an increase of the c-statistic from 0.821 to 0.877 (P < .001) and an integrated discrimination improvement gain of 14.0% (P < .001).ConclusionsSerum TN-C level on day 5 after admission is potentially useful for early risk stratification after AMI beyond established prognostic markers.     

Enhanced exon 2 skipping caused by c.910G>A variant and alternative splicing of MEFV genes in two independent cases of familial Mediterranean fever

Most reported cases of familial Mediterranean fever (FMF) involve missense mutations of MEFV concentrated within exon 10. We experienced two independent pedigrees of a unique variant in the MEFV gene that might cause excessive exon 2 skipping due to enhanced alternative splicing. In this study, we tried to elucidate the molecular mechanism of the MEFV variant as a cause of the FMF phenotype. Peripheral blood was obtained from volunteers and two patients with homozygous c.910G>A variant of the MEFV gene. MEFV messenger RNA (mRNA) expression patterns in mononuclear cells and granulocytes were compared using forward and reverse primers from exons 1 and 3, respectively. Expression profiles of pyrin were examined by transfecting wild-type and variant MEFV genes into HEK293T cells. Expression of normal-sized mRNA was extremely reduced in these patients, whereas that of aberrant short mRNA, deleting exon 2 (Δex2), was significantly increased. Immunohistochemical and immunoblotting analyses revealed a truncated immunoreactive pyrin protein in cells transfected with Δex2 cDNA. The MEFV gene c.910G>A variant results in accelerated aberrant splicing with abnormal protein size, presumably leading to anomalous pyrin function. This is the first report to show that an MEFV variant other than missense mutation is responsible for the FMF phenotype.     

Fall Risk Index predicts functional decline regardless of fall experiences among community‐dwelling elderly

Aim: The 21‐item Fall Risk Index (FRI‐21) has been used to detect elderly persons at risk for falls. The aim of this longitudinal study was to evaluate the FRI‐21 as a predictor of decline in basic activities of daily living (BADL) among Japanese community‐dwelling elderly persons independent of fall risk. Methods: The study population consisted of 518 elderly participants aged 65 years and older who were BADL independent at baseline in Tosa, Japan. We examined risk factors for BADL decline from 2008 to 2009 by multiple logistic regression analysis on the FRI‐21 and other functional status measures in all participants. We carried out the same analysis in selected participants who had no experience of falls to remove the effect of falls. Results: A total of 45 of 518 participants showed decline in BADL within 1 year. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05–1.20), FRI‐21 ≥ 10 (OR 3.81, 95% CI 1.49–9.27), intellectual activity dependence (OR 3.25, 95% CI 1.42–7.44) and history of osteoarthropathy (OR 3.17, 95% CI 1.40–7.21) were significant independent risk factors for BADL decline within 1 year. FRI‐21 ≥ 10 and intellectual activity dependence (≤3) remained significant predictors, even in selected non‐fallers. Conclusion: FRI‐21 ≥ 10 and intellectual activity dependence were significant predictive factors of BADL decline, regardless of fall experience, after adjustment for confounding variables. The FRI‐21 is a brief, useful tool not only for predicting falls, but also future decline in functional ability in community‐dwelling elderly persons. Geriatr Gerontol Int 2012; ??: ??–?? .