scholarly journals The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 848
Author(s):  
Goh-Eun Chung ◽  
Hyo-Eun Park ◽  
Min-Joo Kim ◽  
Min-Sun Kwak ◽  
Jong-In Yang ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Muscle Mass ◽  
Liver Stiffness ◽  
Bioelectrical Impedance ◽  
Class Ii ◽  
Class I ◽  
Dependent Manner ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
Dose Dependent

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78; class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95; class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

scholarly journals Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: a systematic review and meta-analysis

F&S Reviews ◽  
2021 ◽  
Author(s):  
Nadia A. du Fossé ◽  
Marie-Louise P. van der Hoorn ◽  
Nina H. Buisman ◽  
Jan M.M. van Lith ◽  
S askia le Cessie ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pregnancy Loss ◽  
Meta Analysis ◽  
Dependent Manner ◽  
Increased Risk ◽  
Dose Dependent ◽  
Paternal Smoking

scholarly journals The association of hepatic steatosis and fibrosis with heart failure and mortality

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiyun Park ◽  
Gyuri Kim ◽  
Hasung Kim ◽  
Jungkuk Lee ◽  
You-Bin Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
General Population ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Patient Group ◽  
Cox Regression ◽  
Nonalcoholic Fatty Liver ◽  
Fatty Liver Index ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. Methods We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. Results A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05). Conclusion Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality.

Evidence for HLA-related susceptibility for stroke in children with sickle cell disease

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3562-3567 ◽  
Author(s):  
Lori A. Styles ◽  
Carolyn Hoppe ◽  
William Klitz ◽  
Elliott Vichinsky ◽  
Bertram Lubin ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Cerebral Infarction ◽  
Sickle Cell ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Increased Risk ◽  
Mri Scans ◽  
Comparison Of The Results

Abstract Cerebral infarction occurs in one quarter of all children with sickle cell anemia (SCA). There is an increased risk of stroke in siblings with SCA, suggesting genetic factors may influence risk of stroke. The authors investigated whether HLA type was associated with risk of stroke in children with SCA. Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic resonance imagining (MRI)–documented evidence of cerebral infarction, and the remaining 31 patients had negative MRI scans. Comparison of the results of HLA typing between the SCA patients with a positive and those with a negative MRI documented that the 2 groups differed with respect to the class I HLA-B (P = .012), and the class II HLA-DRB1 (P = .0008) and DQB1 (P = .029). Susceptibility associations at the HLA-DRB1 locus included both DR3 alleles, where DRB1*0301 and *0302 were both associated with an increased risk of stroke. Protective associations were found in the DR2 group, where DRB1*1501 was protective for stroke. DQB1*0201, which is in linkage disequilibrium with DRB1*0301, was also associated with stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501, was protective. Specific HLA alleles may influence the risk of stroke in children with SCA. HLA typing may prove useful in identifying SCA patients at higher risk for stroke.

GFI1 Is a Tumor Suppressor in Myeloid Progenitors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2942-2942
Author(s):  
Aditya Chaubey ◽  
Shane Hormon ◽  
Chinavenmeni S. Velu ◽  
Tristan Bourdeau ◽  
Jinfang Zhu ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Myeloid Leukemia ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Increased Risk ◽  
Myeloid Leukemias ◽  
Dose Dependent ◽  
Anterior Posterior

Abstract In severe congenital neutropenia (SCN) patients and mice with Growth factor independent-1 (Gfi1) loss of function, arrested progenitors are suspended in a hyperproliferative state while terminal granulpoiesis is blocked. SCN patients are at increased risk for the development of acute myeloid leukemia. We demonstrate that Gfi1 directly targets HoxA9, Pbx1 and Meis1 during normal myelopoiesis. Gfi1−/− progenitors exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and increased persistence in vivo and in vitro. Limiting HoxA9 alleles corrects, in a dose dependent manner, in vivo and in vitro phenotypes observed with loss of Gfi1. Moreover, in a manner conserved in Drosophila anterior/posterior patterning, we demonstrate that these factors can compete for occupancy of DNA sequences encoding composite Gfi1-HoxA9-Pbx1-Meis1 binding sites. Finally, the expression of Gfi1 and HoxA9 are inverse and stratify human myeloid leukemias, suggesting a role for HoxA9- Gfi1 antagonism in human AML. In agreement with this, a myeloproliferative disorder progresses into a rapid, lethal and transplantable myeloid leukemia in a Gfi1−/− setting. We conclude that the lifespan and oncogenic transformation of hematopoietic progenitor cells is regulated through a conserved competition between Gfi1 and HoxA9-Pbx1-Meis1.

CAL-101, a Potent Selective Inhibitor of the p110δ Isoform of Phosphatidylinositol 3-kinase, Attenuates Pathway Signaling, Induces Apoptosis, and Overcomes Signals From the Microenvironment In Cellular Models of Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3926-3926 ◽  
Author(s):  
Sarah A Meadows ◽  
Adam Kashishian ◽  
Dave Johnson ◽  
Volker Diehl ◽  
Brian Lannutti
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Stromal Cells ◽  
Specific Inhibitor ◽  
Lymphocytic Leukemia ◽  
Class I ◽  
Clinical Activity ◽  
Dependent Manner ◽  
Cellular Models ◽  
Dose Dependent

Abstract Abstract 3926 Phosphatidylinositide 3-kinases (PI3Ks) are a family of lipid kinases that are involved in signaling events which control a diverse number of cellular processes. The class I kinases contain 4 isoforms designated p110α, β, δ, γ, and are activated by cell surface receptors. Aberrant regulation of the PI3K signaling pathway is frequently observed in human malignancies including those of hematological origin. CAL-101 is an oral p110δ-specific inhibitor which has shown preclinical and clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This compound is a potent p110δ inhibitor (EC50 of 65 nM in a whole-blood assay) with >200-fold selectivity over the other class I PI3K isoforms and no activity against Class II and III PI3K family members or other PI3K-related proteins, including mTOR and DNA-PK. Prior in vitro NHL studies revealed that CAL-101 induces caspase-dependent apoptosis, and inhibits CD40L-, BAFF-, CXCL12- and CXCL13-derived survival signals in cellular models (Lannutti BJ, et al., Blood 2010). To investigate the potential role of p110δ in Hodgkin lymphoma (HL) we screened a number of HL cell lines for p110δ isoform expression and constitutive PI3K pathway activation. We report high levels of p110δ protein and activated Akt in 5 of 5 HL cell lines evaluated (L428, L540, L591, L1236, KM-H2). Inhibition of p110δ with CAL-101 treatment of cell lines resulted in a reduction of Akt phosphorylation and a decrease in cellular viability. Because previous studies have established the importance of signals from the microenvironment for the survival and proliferation of malignant cells as well as for their resistance to standard therapies, we investigated the effect of p110δ inhibition by CAL-101 in HL cell line-stroma cocultures. In this setting, CAL-101 overcame tumor cell growth induced by coculture of HL cells with bone marrow stromal cells. In addition, CAL-101 induced dose-dependent apoptosis of HL cells at 48 hours. Furthermore, stromal cell coculture resulted in increased CCL5, CCL17, and CCL22 levels; productions of these chemokines by HL cells cultured in the presence of stromal cells were reduced by CAL-101 in a dose-dependent manner. These results indicate that specific inhibition of p110δ may disrupt signals between HL cells and their microenvironment, thereby providing the preclinical rationale for clinical evaluation of CAL-101 as a novel therapeutic approach in patients with Hodgkin lymphoma. Disclosures: Meadows: Calistoga Pharmaceuticals: Employment. Kashishian:Calistoga Pharmaceuticals: Employment. Johnson:Calistoga Pharmaceuticals: Employment. Lannutti:Calistoga Pharmaceutical Inc.: Employment.

Evidence for HLA-related susceptibility for stroke in children with sickle cell disease

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3562-3567
Author(s):  
Lori A. Styles ◽  
Carolyn Hoppe ◽  
William Klitz ◽  
Elliott Vichinsky ◽  
Bertram Lubin ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Cerebral Infarction ◽  
Sickle Cell ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Increased Risk ◽  
Mri Scans ◽  
Comparison Of The Results

Cerebral infarction occurs in one quarter of all children with sickle cell anemia (SCA). There is an increased risk of stroke in siblings with SCA, suggesting genetic factors may influence risk of stroke. The authors investigated whether HLA type was associated with risk of stroke in children with SCA. Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic resonance imagining (MRI)–documented evidence of cerebral infarction, and the remaining 31 patients had negative MRI scans. Comparison of the results of HLA typing between the SCA patients with a positive and those with a negative MRI documented that the 2 groups differed with respect to the class I HLA-B (P = .012), and the class II HLA-DRB1 (P = .0008) and DQB1 (P = .029). Susceptibility associations at the HLA-DRB1 locus included both DR3 alleles, where DRB1*0301 and *0302 were both associated with an increased risk of stroke. Protective associations were found in the DR2 group, where DRB1*1501 was protective for stroke. DQB1*0201, which is in linkage disequilibrium with DRB1*0301, was also associated with stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501, was protective. Specific HLA alleles may influence the risk of stroke in children with SCA. HLA typing may prove useful in identifying SCA patients at higher risk for stroke.

Premorbid body mass and mortality in patients with hepatocellular cancer: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 477-477 ◽  
Author(s):  
Arjun Gupta ◽  
Avash Das ◽  
Nivedita Arora ◽  
Kaustav Majumder ◽  
Preet Paul Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Morbid Obesity ◽  
Body Mass ◽  
Meta Analysis ◽  
Hepatocellular Cancer ◽  
Dependent Manner ◽  
Increased Risk ◽  
Reported Data ◽  
Dose Dependent ◽  
Related Mortality

477 Background: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid body mass index (BMI) and HCC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to March 2016, we identified observational studies reporting the association between premorbid BMI, and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing obese (BMI > 30 kg/m2) and overweight (BMI 25-29.9 kg/m2) categories with reference category using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: 9 studies were included in which 6,052 HCC deaths occurred in 1,599,453 cancer-free individuals at cohort inception. 5 studies reported data as obese vs. overweight vs. normal BMI, and 4 reported data as obese + overweight combined (BMI > 25 kg/m2). On meta-analysis, pre-morbid obesity was associated with higher HCC-related mortality, as compared to individuals with normal BMI (obese: aHR, 1.96; 95% CI, 1.46-2.46, I2= 37%; overweight: aHR, 1.08; 95% CI, 0.97-1.21, I2= 0%), in dose-dependent manner. This effect was stronger in males [3 studies, aHR, 2.50; 95% CI, 2.02-3.09] vs. females [2 studies, aHR, 1.45; 95% CI, 1.08-1.97]. This effect was seen primarily in Western populations [4 studies, aHR, 2.10; 95% CI, 1.77-2.48], but not in Asian population [1 study, aHR, 1.10; 95% CI, 0.63-1.92]. Conclusions: In this meta-analysis, there was a dose-dependent increase in HCC-related mortality with pre-morbid obesity, particularly in men, and in Western populations. Strategies targeting obesity-induced metabolic abnormalities may provide novel pathways for HCC therapy.

scholarly journals The Rab11-Family Interacting Proteins reveal selective interaction of mammalian recycling endosomes with the Toxoplasma parasitophorous vacuole in a Rab11- and Arf6-dependent manner

2021 ◽  
Author(s):  
Eric J Hartman ◽  
Julia D Romano ◽  
Isabelle Coppens
Keyword(s):  
Mammalian Cells ◽  
Parasitophorous Vacuole ◽  
Class Ii ◽  
Class I ◽  
Dependent Manner ◽  
Interacting Proteins ◽  
Cell Organelles ◽  
Recycling Endosome ◽  
Recycling Endosomes ◽  
Membrane Bound

After invasion of mammalian cells, the parasite Toxoplasma gondii multiplies in a self-made membrane-bound compartment, the parasitophorous vacuole (PV). We previously showed that intravacuolar Toxoplasma interacts with many host cell organelles, especially recycling endosomes, and further manipulates the host endocytic recycling through the sequestration of Rab11 vesicles into the PV. Mammalian Rab-PV interactions are likely mediated by Toxoplasma and host proteins that remain to be identified. In this context, we have examined the specificity of host Rab vesicle interaction with the PV by monitoring the recruitment of subtypes of Rab11 vesicles differing in their composition in Rab11-Family Interacting Proteins (FIPs). We found that vesicles with FIPs from Class I (FIP1C, FIP2, FIP5) or Class II (FIP3, FIP4) are distributed at the PV and detected to varying degrees inside the PV. The PV delivery of vesicles with FIPs from Class I, but not Class II, is Rab11-dependent. In addition to Rab11, FIP3 binds to Arf6, and vesicles associated with FIP3-Arf6 complexes are observed within the PV. Binding of FIP3 to either Rab11 or Arf6 significantly increases the internalization of vesicles into the PV. These data point to a selective process of host recycling endosome recognition and scavenging mediated by Toxoplasma.

scholarly journals Association of Maternal Serum 25-Hydroxyvitamin D Concentrations with Risk of Gestational Anemia

2017 ◽  
Vol 43 (4) ◽  
pp. 1526-1532 ◽  
Author(s):  
Yingdi Yuan ◽  
Zhiyong Cai ◽  
YaoYao Dai ◽  
Qin Hong ◽  
Xingyun Wang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Pregnant Women ◽  
Maternal Serum ◽  
Dependent Manner ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D ◽  
Nested Case Control ◽  
Dose Dependent ◽  
Prevalence Of Anemia

Background/Aims: Vitamin D deficiency has been shown to be associated with a greater prevalence of anemia in various healthy and diseased populations by a great deal of observational studies. However, less work has been done to explore this association in pregnant women. The aim of this study was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of gestational anemia in a large, nested case-control study. Methods: The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775 pregnant women affected with anemia and 1550 controls. Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with risk of gestational anemia. Results: We found the 25(OH)D concentrations was significantly lower in women affected with anemia than in controls. Logistic regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L, from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And the risk of anemia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95% CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D of 50.0 nmol/L existed for anemia. Conclusion: Maternal serum 25(OH)D < 50.0 nmol/L may be a risk factor for gestational anemia, and it should be monitored for the high-risk pregnant women.

Sign in / Sign up

Export Citation Format

Share Document