tbuckley/cabot-search huggingface dataset:
High Plasma Concentration of Remnant Lipoprotein Cholesterol in Obese Children and Adolescents
Authors: Yong Jun Choi, Young Eun Jo, Yun Kyung Kim, Sang Mi Ahn, Sun Hye Jung, Hae Jin Kim, Yoon-Sok Chung, Kwan Woo Lee, Dae Jung Kim
Journal: Diabetes Care (2006)

OBJECTIVE—Remnant lipoproteins (RLPs) are the products of the lipolytic degradation of triglyceride-rich lipoproteins produced by the liver and intestine. Recent studies have demonstrated that RLPs are correlated with cardiovascular risk. We assessed the relationship between obesity and RLP and evaluated the factors related to RLP in children and adolescents. RESEARCH DESIGN AND METHODS—We measured BMI, waist circumference, blood pressure, body fat mass, total abdominal fat, visceral and subcutaneous fat areas, fasting glucose, insulin, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and RLP cholesterol in 135 children and adolescents (67 boys and 68 girls). Plasma RLP fractions were isolated using an immunoaffinity gel containing specific anti–apolipoprotein (apo) B-100 and anti–apoA-I antibodies. Based on the BMI percentile, the subjects were divided into two groups: normal (&amp;lt;85th percentile) and overweight (≥85th percentile). RESULTS—RLP cholesterol was significantly correlated with age, sex, BMI, waist circumference, systolic and diastolic blood pressures, visceral and subcutaneous fat areas, visceral-to-subcutaneous fat area ratio, total cholesterol, triglycerides, HDL cholesterol, apoB, and homeostasis model assessment of insulin resistance (HOMA-IR). According to the multivariate regression analysis, triglycerides (β = 0.928, P &amp;lt; 0.001) were independently correlated with RLP cholesterol. After excluding lipid profiles as an independent variable, the multivariate regression analysis revealed that HOMA-IR (β = 0.231, P = 0.007) and systolic blood pressure (β = 0.169, P = 0.046) were independently associated with RLP cholesterol. CONCLUSIONS—RLP cholesterol was significantly higher in obese children and adolescents. Triglycerides, systolic blood pressure, and insulin resistance were related to RLP cholesterol.
Emerging Links between E2F Control and Mitochondrial Function
Authors: Elizaveta V. Benevolenskaya, Maxim V. Frolov
Journal: Cancer Research (2015)

The family of E2F transcription factors is the key downstream target of the retinoblastoma tumor suppressor protein (pRB), which is frequently inactivated in human cancer. E2F is best known for its role in cell-cycle regulation and triggering apoptosis. However, E2F binds to thousands of genes and, thus, could directly influence a number of biologic processes. Given the plethora of potential E2F targets, the major challenge in the field is to identify specific processes in which E2F plays a functional role and the contexts in which a particular subset of E2F targets dictates a biologic outcome. Recent studies implicated E2F in regulation of expression of mitochondria-associated genes. The loss of such regulation results in severe mitochondrial defects. The consequences become evident during irradiation-induced apoptosis, where E2F-deficient cells are insensitive to cell death despite induction of canonical apoptotic genes. Thus, this novel function of E2F may have a major impact on cell viability, and it is independent of induction of apoptotic genes. Here, we discuss the implications of these findings in cancer biology.
Non-cardiogenic pulmonary oedema due to the intravenous administration of clove oil
Authors: C. M Kirsch, G. G Yenokida, W. A Jensen, R. Wendland, H. Suh, M. Bourgault
Journal: Thorax (1990)

Abstract Intravenous injection of clove oil induced non-cardiogenic pulmonary oedema, which was managed successfully with a conservative diagnostic and therapeutic approach.
Elevated anal squamous cell carcinoma risk associated with benign inflammatory anal lesions
Authors: C Nordenvall
Journal: Gut (2005)

The association between benign anal lesions and anal cancer is still unclear. Few data from large cohort studies are available.We conducted a register based retrospective cohort study including 45,186 patients hospitalised for inflammatory anal lesions (anal fissures, fistulas, and perianal abscesses) as well as 79,808 haemorrhoid patients, from 1965 to 2002. Multiple record linkages identified all incident anal (squamous cell carcinoma only) and colorectal cancers through to 2002. Relative risk was estimated by standardised incidence ratio (SIR), the ratio of observed number of cases divided by that expected in the age, sex, and calendar year-matched general Swedish population.There was a distinct incidence peak in the first three years of follow up among patients with inflammatory lesions. SIR then levelled off at around 3 and remained at this level throughout follow up (SIR during years 3-37 of follow up was 3.3 (95% confidence interval 1.8-5.7)). A similar initial incidence peak was observed among haemorrhoid patients but was confined to the first year; SIR was 2.8 in the second year, and then it decreased further and was close to unity in the following years (SIR during years 3-37 was 1.3 (95% confidence interval 0.7-2.1)). Among inflammatory lesion and haemorrhoid patients, a significantly increased risk of colorectal cancer was observed only in the first year after hospitalisation.Inflammatory benign anal lesions are associated with a significantly increased long term risk of anal cancer. In contrast, haemorrhoids appear not to be a risk factor for this malignancy.
Expression of a <i>CALM-AF10</i> Fusion Gene Leads to <i>Hoxa</i> Cluster Overexpression and Acute Leukemia in Transgenic Mice
Authors: David Caudell, Zhenhua Zhang, Yang Jo Chung, Peter D. Aplan
Journal: Cancer Research (2007)

Abstract To assess the role of the CALM-AF10 fusion gene in leukemic transformation in vivo, we generated transgenic mice that expressed a CALM-AF10 fusion gene. Depending on the transgenic line, at least 40% to 50% of the F1 generation mice developed acute leukemia at a median age of 12 months. Leukemic mice typically had enlarged spleens, invasion of parenchymal organs with malignant cells, and tumors with myeloid markers such as myeloperoxidase, Mac1, and Gr1. Although most leukemias were acute myeloid leukemia, many showed lymphoid features, such as CD3 staining, or clonal Tcrb or Igh gene rearrangements. Mice were clinically healthy for the first 9 months of life and had normal peripheral blood hemograms but showed impaired thymocyte differentiation, manifested by decreased CD4+/CD8+ cells and increased immature CD4−/CD8− cells in the thymus. Hematopoietic tissues from both clinically healthy and leukemic CALM-AF10 mice showed up-regulation of Hoxa cluster genes, suggesting a potential mechanism for the impaired differentiation. The long latency period and incomplete penetrance suggest that additional genetic events are needed to complement the CALM-AF10 transgene and complete the process of leukemic transformation. [Cancer Res 2007;67(17):8022–31]
Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells
Authors: Yukiko Ueda, Nicole F. Neel, Evemie Schutyser, Dayanidhi Raman, Ann Richmond
Journal: Cancer Research (2006)

Abstract The CXC chemokine receptor 4 (CXCR4) contributes to the metastasis of human breast cancer cells. The CXCR4 COOH-terminal domain (CTD) seems to play a major role in regulating receptor desensitization and down-regulation. We expressed either wild-type CXCR4 (CXCR4-WT) or CTD-truncated CXCR4 (CXCR4-ΔCTD) in MCF-7 human mammary carcinoma cells to determine whether the CTD is involved in CXCR4-modulated proliferation of mammary carcinoma cells. CXCR4-WT-transduced MCF-7 cells (MCF-7/CXCR4-WT cells) do not differ from vector-transduced MCF-7 control cells in morphology or growth rate. However, CXCR4-ΔCTD-transduced MCF-7 cells (MCF-7/CXCR4-ΔCTD cells) exhibit a higher growth rate and altered morphology, potentially indicating an epithelial-to-mesenchymal transition. Furthermore, extracellular signal-regulated kinase (ERK) activation and cell motility are increased in these cells. Ligand induces receptor association with β-arrestin for both CXCR4-WT and CXCR4-ΔCTD in these MCF-7 cells. Overexpressed CXCR4-WT localizes predominantly to the cell surface in unstimulated cells, whereas a significant portion of overexpressed CXCR4-ΔCTD resides intracellularly in recycling endosomes. Analysis with human oligomicroarray, Western blot, and immunohistochemistry showed that E-cadherin and Zonula occludens are down-regulated in MCF-7/CXCR4-ΔCTD cells. The array analysis also indicates that mesenchymal marker proteins and certain growth factor receptors are up-regulated in MCF-7/CXCR4-ΔCTD cells. These observations suggest that (a) the overexpression of CXCR4-ΔCTD leads to a gain-of-function of CXCR4-mediated signaling and (b) the CTD of CXCR4-WT may perform a feedback repressor function in this signaling pathway. These data will contribute to our understanding of how CXCR4-ΔCTD may promote progression of breast tumors to metastatic lesions. (Cancer Res 2006; 66(11): 5665-75)
The GMC, racism, and complaints against doctors
Authors: F. Godlee
Journal: BMJ (1996)

cannot expect to continue dining at an elite high table.There is insufficient land and protein supplement (whether as cereal, fish, or mammalian scraps) to enable a beef enriched global diet.The supplies of fossil fuel energy and water required for intensive livestock production are huge.So is the demand for forests to be denuded to create pastoral land in Central America to produce lean beef for McDonald's burgers.12A unit of beef energy produced in western (and, increasingly, east Asian) factory farms requires an input of around 6-7 units of cereal grain energy.8Smil argues that "diets high in meat are a very recent aberration unsustainable on a global scale."'i Epidemiological studies indicate that vegetarians live a little longer than meat eaters."3 14We should therefore expect that a world diet of modest meat content would bring widespread gains in human health-both directly and by averting the adverse social and environmental consequences of intensive meat production.'4These complex ecological issues portend far reaching and challenging policy decisions.Currently, however, we are preoccupied with the unsettling risks to public health from British beef already eaten.And in the political arena the find- ings of the parliamentary Joint Agriculture and Health Select Committee seem unlikely to go beyond the puny immediacies of economic and political face saving.We thus risk overlooking the wider ecological and public health implications of our mass produced, meat enriched diet.For over one hundred millennia food supplies and, more recently, food production methods have been central to the ecological sustainability of human societies.5In the coming millennium we will need to think even more in those terms.
Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.
Authors: Monte A Greer, Gay Goodman, Richard C Pleus, Susan E Greer
Journal: Environmental Health Perspectives (2002)

Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.
Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis
Authors: R Imrich
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To assess basal function and responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with ankylosing spondylitis during dynamic testing. <b>Methods:</b> Insulin induced hypoglycaemia (IIH) (Actrapid HM 0.1 IU/kg, as intravenous bolus) was induced in 17 patients and 11 healthy controls matched for age, sex, and body mass index. Concentrations of glucose, adrenocorticotrophic hormone (ACTH), cortisol, insulin, dehydroepiandrosterone sulphate (DHEAS), 17α-hydroxyprogesterone, interleukin 6 (IL-6), and tumour necrosis factor α (TNFα) were determined in plasma. <b>Results:</b> Comparable basal cortisol levels were found in the two groups, with a trend to be lower in ankylosing spondylitis. In the ankylosing spondylitis group, there were higher concentrations of IL-6 (mean (SEM): 16.6 (2.8) pg/ml <i>v</i> 1.41 (0.66) pg/ml in controls; p&lt;0.001) and TNFα (8.5 (1.74) pg/ml <i>v</i> 4.08 (0.42) pg/ml in controls; p&lt;0.01). Glucose, insulin, ACTH, DHEAS, and 17α-hydroxyprogesterone did not differ significantly from control. The IIH test was carried out successfully in 11 of the 17 patients with ankylosing spondylitis, and the ACTH and cortisol responses were comparable with control. General linear modelling showed a different course of glycaemia (p = 0.041) in the ankylosing spondylitis patients who met the criteria for a successful IIH test compared with the controls. <b>Conclusions:</b> The results suggest there is no difference in basal HPA axis activity and completely preserved responsiveness of the HPA axis in patients with ankylosing spondylitis. The interpretation of the different course of glycaemia during IIH in ankylosing spondylitis requires further investigation.
Hospital Volume, Complications, and Cost of Cancer Surgery in the Elderly
Authors: Hari Nathan, Coral L. Atoria, Peter B. Bach, Elena B. Elkin
Journal: Journal of Clinical Oncology (2014)

Hospital surgical volume has been shown to correlate with short-term outcomes after cancer surgery, but the relationship between volume and cost of care is unclear. We sought to characterize variation in payments for cancer surgery and assess the relationship between hospital volume and payments.Using 2000 to 2007 Surveillance, Epidemiology, and End Results-Medicare data, we assessed risk-adjusted 30-day episode Medicare payments for elderly patients undergoing one of six procedures for resection of cancer. Payments for the index hospitalization, readmissions, physician services, emergency room visits, and postdischarge ancillary care were analyzed, as were data on 30-day mortality and complications.The analysis included 31,191 colectomies, 2,670 cystectomies, 1,514 pancreatectomies, 2,607 proctectomies, 12,228 prostatectomies, and 10,151 pulmonary lobectomies. There was substantial variation in cost; differences between the first and third terciles of cost varied from 27% for cystectomy to 40% for colectomy. The majority of variation (66% to 82%) was attributable to payments for the index admission rather than readmissions or physician services. There were no meaningful associations between total risk-adjusted payments and hospital volume. Surgical mortality was low, but complication rates ranged from 10% (prostatectomy) to 56% (lobectomy). Complication rates were not correlated with hospital volume, but occurrence of complications was associated with 47% to 70% higher costs.We found substantial variation in Medicare payments for these six cancer procedures. Cost was strongly associated with postoperative complications and primarily driven by differences in the cost of the index hospitalization. Efforts to prevent and cost-effectively manage complications are more likely to reduce costs than volume-based referral of cancer surgery alone.
Increase in the level of macrophage colony-stimulating factor in patients with systemic lupus erythematosus
Authors: P T Yang, W G Xiao, L J Zhao, J Lu, L M He, H KASAI, M Ito
Journal: Annals of the Rheumatic Diseases (2007)

Macrophage colony-stimulating factor (M-CSF) primarily regulates the survival, proliferation and function of macrophages.1 Studies on MRL- Faslpr mice demonstrate that M-CSF plays a pivotal role in kidney injury.2–4 Increased glomerular expression of M-CSF mRNA and protein was also reported in lupus nephritis patients.5 This study was conducted to examine for the first time the serum M-CSF level and its mRNA expression in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients.

The subjects included 21 adult patients with active SLE (SLE disease activity index (SLEDAI) ⩾8 or an increase in SLEDAI ⩾3), 11 with inactive …
Altered composition of fatty acids exacerbates hepatotumorigenesis during activation of the phosphatidylinositol 3-kinase pathway
Authors: Yotaro Kudo, Yasuo Tanaka, Keisuke Tateishi, Keisuke Yamamoto, Shinzo Yamamoto, Dai Mohri, Yoshihiro Isomura, Motoko Seto, Hayato Nakagawa, Yoshinari Asaoka, Motohisa Tada, Miki Ohta, Hideaki Ijichi, Yoshihiro Hirata, Motoyuki Otsuka, Tsuneo Ikenoue, Shin Maeda, Shuichiro Shiina, Haruhiko Yoshida, Osamu Nakajima, Fumihiko Kanai, Masao Omata, Kazuhiko Koike
Journal: Journal of Hepatology (2011)
Immunochemotherapy with Intensive Consolidation for Primary CNS Lymphoma: A Pilot Study and Prognostic Assessment by Diffusion-Weighted MRI
Authors: Matthew J. Wieduwilt, Francisco Valles, Samar Issa, Caroline M. Behler, James Hwang, Michael McDermott, Patrick Treseler, Joan O'Brien, Marc A. Shuman, Soonmee Cha, Lloyd E. Damon, James L. Rubenstein
Journal: Clinical Cancer Research (2012)

We evaluated a novel therapy for primary central nervous system lymphoma (PCNSL) with induction immunochemotherapy with high-dose methotrexate, temozolomide, and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADC(min)) derived from diffusion-weighted MRI (DW-MRI) in patients treated with this regimen.
Transplantation of Mesenchymal Stem Cells Overexpressing RANK-Fc or CXCR4 Prevents Bone Loss in Ovariectomized Mice
Authors: Sun Wook Cho, Hyun Jin Sun, Jae-Yeon Yang, Ju Yeon Jung, Jee Hyun An, Hwa Young Cho, Hyung Jin Choi, Sang Wan Kim, Seong Yeon Kim, Dohee Kim, Chan Soo Shin
Journal: Molecular Therapy (2009)

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of transplantation of mesenchymal stem cells (MSCs) overexpressing receptor activator of nuclear factor-kappaB (RANK)-Fc and CXC chemokine receptor-4 (CXCR4) using retrovirus on ovariectomy (OVX)-induced bone loss in mice. Ten-week-old adult female C57BL/6 mice were divided into six groups as follows: Sham-operated mice treated with phosphate-buffered saline (PBS) (Sham-op + PBS); OVX mice intravenously transplanted with syngeneic MSCs overexpressing RANK-Fc-DsRED and CXCR4-GFP (RANK-Fc + CXCR4); RANK-Fc-DsRED and GFP (RANK-Fc + GFP); CXCR4-GFP and DsRED (CXCR4 + RED); DsRED and GFP (RED + GFP); or treated with PBS only (OVX + PBS). Measurement of BMD showed that introduction of RANK-Fc resulted in significant protection against OVX-induced bone loss compared to treatment with PBS (-0.1% versus -6.2%, P < 0.05) at 8 weeks after cell infusion. CXCR4 + RED group also significantly prevented bone loss compared to OVX + PBS group (2.7% versus -6.2%, P < 0.05). Notably, the effect of RANK-Fc + CXCR4 was greater than that of RANK-Fc + GFP (4.4% versus -0.1%, P < 0.05) while it was not significantly different from that in CXCR4 + RFP group (4.4% versus 2.7%, P = 0.055) at 8 weeks. Transplantation of MSCs with control virus (RED + GFP group) also resulted in amelioration of bone loss compared to OVX + PBS group (-1.7% versus -6.2%, P < 0.05). Fluorescence-activated cell sorting (FACS) and real-time quantitative PCR (qPCR) analysis for GFP from bone tissue revealed enhanced cell trafficking to bone by co-overexpression of CXCR4. In conclusion, we have demonstrated that intravenous transplantation of syngeneic MSCs overexpressing CXCR4 could promote increased in vivo cell trafficking to bone in OVX mice, which could in itself protect against bone loss but also enhance the therapeutic effects of RANK-Fc.
Angiogenic Gene Therapy for Experimental Critical Limb Ischemia
Authors: Ichiro Masaki, Yoshikazu Yonemitsu, Akihisa Yamashita, Shihoko Sata, Mitsugu Tanii, Kimihiro Komori, Kazunori Nakagawa, Xiaogang Hou, Yoshiyuki Nagai, Mamoru Hasegawa, Keizo Sugimachi, Katsuo Sueishi
Journal: Circulation Research (2002)

Recent studies suggest the possible therapeutic effect of intramuscular vascular endothelial growth factor (VEGF) gene transfer in individuals with critical limb ischemia. Little information, however, is available regarding (1) the required expression level of VEGF for therapeutic effect, (2) the related expression of endogenous angiogenic factors, including fibroblast growth factor-2 (FGF-2), and (3) the related adverse effects due to overexpression of VEGF. To address these issues, we tested effects of overexpression of VEGF165 using recombinant Sendai virus (SeV), as directly compared with FGF-2 gene transfer. Intramuscular injection of SeV strongly boosted FGF-2, resulting in significant therapeutic effects for limb salvage with increased blood perfusion associated with enhanced endogenous VEGF expression in murine models of critical limb ischemia. In contrast, VEGF165 overexpression, 5-times higher than that of baseline on day 1, also strongly evoked endogenous VEGF in muscles, resulting in an accelerated limb amputation without recovery of blood perfusion. Interestingly, viable skeletal muscles of either VEGF165- or FGF-2–treated ischemic limbs showed similar platelet-endothelial cell adhesion molecule-1–positive vessel densities. Maturation of newly formed vessels suggested by smooth muscle cell actin–positive cell lining, however, was significantly disturbed in muscles with VEGF. Further, therapeutic effects of FGF-2 were completely diminished by anti-VEGF neutralizing antibody in vivo, thus indicating that endogenous VEGF does contribute to the effect of FGF-2. These results suggest that VEGF is necessary, but should be delicately regulated to lower expression to treat ischemic limb. The therapeutic effect of FGF-2, associated with the harmonized angiogenic effects seen with endogenous VEGF, provides important insights into therapeutic angiogenesis.
Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors☆☆☆★
Authors: I.Caroline Crocker, S.Edet Ohia, Martin K. Church, Robert G. Townley
Journal: Journal of Allergy and Clinical Immunology (1998)