tbuckley/cabot-search huggingface dataset:
Bile acids suppress the secretion of very-low-density lipoprotein by human hepatocytes in primary culture
Authors: Y Lin, R Havinga, H J Verkade, H Moshage, M J Slooff, R J Vonk, F Kuipers
Journal: Hepatology (1996)

The existence of a relationship between bile acid and triacylglycerol metabolism in humans has been established, but the underlying mechanism and its physiological relevance have remained unclear. We have studied the effects of bile acids on the secretion of very-low-density lipoprotein (VLDL)-associated triacylglycerol, using [3H]glycerol labeling technique, and apolipoprotein B (apoB) in human hepatocytes in primary culture. Human hepatocytes secrete nascent VLDL with an average diameter of about 40 nm. Lipid composition of the particles resembles that reported for plasma VLDL, with the exception of a markedly lower cholesterylester content. In 24-hour cultured human hepatocytes, physiological (i.e., portal) concentrations of taurocholic acid (10 to 200 mumol/L) suppressed [3H]triacylglycerol secretion dose dependently. The degree of inhibition highly correlated (r = .87, P < .01) with taurocholic acid content of the cells of different preparations (n = 7). ApoB secretion was inhibited by taurocholic acid to a similar extent as [3H]triacylglycerol secretion (r = .93, P < .01). Lipid composition of secreted VLDL particles did not change during taurocholic acid-induced suppression. No effects on intracellular apoB, [3H]triacylglycerol, triacylglycerol, and cholesterol mass were observed, nor did taurocholic acid affect protein synthesis, albumin secretion, or lactate dehydrogenase (LDH) release. Cellular cholesteryl ester (CHE) mass, however, was markedly reduced. Our results show that bile acids strongly interfere with the assembly or secretion of VLDL particles by human hepatocytes, suggesting a physiological function of the enterohepatic circulation of bile acids in the regulation of postprandial serum lipid levels.
At the Source: Treating Heart Failure by Altering Muscle Motor Function
Authors: Jeanne James, Jeffrey Robbins
Journal: Circulation Research (2011)

A new study in Science provides proof of the principle for directly modulating the cardiac muscle's motor, myosin, as a therapeutic target in heart failure.][3] Although HF can take many forms, 4,5 it is most commonly associated with decreased cardiac contractility and is, therefore, referred to as systolic HF (sHF). 6Current therapeutic strategies rely on blocking neurohormonal activation by inhibiting associated pathways or by receptor blockade using either ␤-adrenergic or aldosterone blockers. 7,8Alternatively, some therapies are directed at increasing cardiac contractility in an effort to restore sufficient blood flow, usually by activating second messenger signaling pathways that increase cardiomyocyte calcium levels and augment sarcomere contraction. 9Both strategies suffer from a lack of specificity in that they target proteins upstream of the actual contractile events that underlie force production.Affecting important signaling pathways or receptor-ligand interactions can impact cellular function and perturb homeostasis in ways unrelated to the contractile apparatus, leading to undesirable side effects, such as hypotension, tachycardia, and even arrhythmias that can lead to sudden death. 10ecognizing the significant limitations of current therapeutic modalities, Malik and co-workers have directed their efforts at directly modulating cardiac contractility by tuning motor function at the source, the myosin heavy chain.The cardiac myosin heavy chains are encoded by two genes, MYH6, which encodes ␣ myosin heavy chain, and MYH7, which encodes ␤ myosin heavy chain, the latter being the predominant isoform in human ventricle.Although having greater than 90% amino acid homology, the two proteins differ significantly at the biochemical level.In comparison
Photocrosslinkable <i>Kappa</i>‐Carrageenan Hydrogels for Tissue Engineering Applications
Authors: Silvia M. Mihaila, Akhilesh K. Gaharwar, Rui L. Reis, Alexandra P. Marques, Manuela E. Gomes, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2012)

Abstract Kappa carrageenan (κ‐CA) is a natural‐origin polymer that closely mimics the glycosaminoglycan structure, one of the most important constituents of native tissues extracellular matrix. Previously, it has been shown that κ‐CA can crosslink via ionic interactions rendering strong, but brittle hydrogels. In this study, we introduce photocrosslinkable methacrylate moieties on the κ‐CA backbone to create physically and chemically crosslinked hydrogels highlighting their use in the context of tissue engineering. By varying the degree of methacrylation, the effect on hydrogel crosslinking was investigated in terms of hydration degree, dissolution profiles, morphological, mechanical, and rheological properties. Furthermore, the viability of fibroblast cells cultured inside the photocrosslinked hydrogels was investigated. The combination of chemical and physical crosslinking procedures enables the formation of hydrogels with highly versatile physical and chemical properties, while maintaining the viability of encapsulated cells. To our best knowledge, this is the first study reporting the synthesis of photocrosslinkable κ‐CA with controllable compressive moduli, swelling ratios and pore size distributions. Moreover, by micromolding approaches, spatially controlled geometries and cell distribution patterns could be obtained, thus enabling the development of cell‐material platforms that can be applied and tailored to a broad range of tissue engineering strategies.
A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast
Authors: Elizabeth H Bayne, Dominika A Bijos, Sharon A White, Flavia de Lima Alves, Juri Rappsilber, Robin C Allshire
Journal: Genome biology (2014)

Heterochromatin plays important roles in the regulation and stability of eukaryotic genomes. Both heterochromatin components and pathways that promote heterochromatin assembly, including RNA interference, RNAi, are broadly conserved between the fission yeast Schizosaccharomyces pombe and humans. As a result, fission yeast has emerged as an important model system for dissecting mechanisms governing heterochromatin integrity. Thus far, over 50 proteins have been found to contribute to heterochromatin assembly at fission yeast centromeres. However, previous studies have not been exhaustive, and it is therefore likely that further factors remain to be identified. To gain a more complete understanding of heterochromatin assembly pathways, we have performed a systematic genetic screen for factors required for centromeric heterochromatin integrity. In addition to known RNAi and chromatin modification components, we identified several proteins with previously undescribed roles in heterochromatin regulation. These included both known and newly characterised splicing-associated proteins, which are required for proper processing of centromeric transcripts by the RNAi pathway, and COP9 signalosome components Csn1 and Csn2, whose role in heterochromatin assembly can be explained at least in part by a role in the Ddb1-dependent degradation of the heterochromatin regulator Epe1. This work has revealed new factors involved in RNAi-directed heterochromatin assembly in fission yeast. Our findings support and extend previous observations that implicate components of the splicing machinery as a platform for RNAi, and demonstrate a novel role for the COP9 signalosome in heterochromatin regulation.
Pathogenesis of Preeclampsia
Authors: Brett C. Young, Richard J. Levine, S. Ananth Karumanchi
Journal: Annual Review of Pathology Mechanisms of Disease (2010)

Preeclampsia is a systemic syndrome that occurs in 3 to 5% of pregnant women and classically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. The only known cure is delivery of the placenta. Recent discoveries, however, have led to important advances in understanding the pathogenesis of the condition. Placental antiangiogenic factors are upregulated and disrupt the maternal endothelium. This change in the normal angiogenic balance toward an antiangiogenic state can result in hypertension, proteinuria, glomerular endotheliosis, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and cerebral edema—the clinical signs of preeclampsia and eclampsia. The regulation of these antiangiogenic factors in the placenta is unknown. The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease.
Reoperation for bronchial carcinoma.
Authors: A Gabler, S Liebig
Journal: Thorax (1980)

After a primary operation for bronchial carcinoma, 17 patients underwent reoperation for local recurrence or intrathoracic metastasis (nine squamous cell, five alveolar cell, and three adenocarcinomas). The average interval between the first and second operation was 23 months (range: six to 48 months). Twelve patients had a pneumonectomy after an initial ipsilateral lobectomy. Five patients underwent contralateral wedge excision after initial lobectomy or wedge excision. Three patients died within 30 days of the reoperation. Eight of the remaining 14 patients died subsequently, the time of survival averaging 18 months (range: three to 54 months). Six patients are still alive, two having survived their reoperation for more than five years. Reoperation for recurrent bronchial carcinoma is rarely performed, but it should be considered in all cases where patients survive operation for lung cancer if the primary operation was thought to be radical.
uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection
Authors: Lily Yang, Hari Krishna Sajja, Zehong Cao, Weiping Qian, Laura Bender, Adam I. Marcus, Malgorzata Lipowska, William C. Wood, Y. Andrew Wang
Journal: Theranostics (2014)

Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers.The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients.In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border.Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes.Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins.Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells.Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells.Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery.
Humidifiers: the use of biocides and lung disease
Authors: C A C Pickering
Journal: Thorax (2014)

Over the last two decades several publications have reported outbreaks of interstitial lung disease caused by inhalational exposure to a chemical, usually at work, but occasionally in a domestic situation. These outbreaks frequently follow a change in formulation, which may be minor,1 of a chemical already being used in the workplace, or a change in process leading to its aerosolisation.

In 2006, paediatricians in South Korea became aware of a severe, rapid-onset interstitial pneumonitis in young children and infants; the disease responded very poorly to treatment, and mortality rates were close to 50%.2 Its seasonal presentation, with most cases presenting in the spring, raised the possibility of an infective aetiology; hypersensitivity pneumonitis was also considered. The failure to find any microbiological evidence for the former, and the distinct clinical and pathological features that distinguished it from the latter led to the consideration of other hypotheses. As a result, the Korean Centre for Disease Control set up a series of case-control studies designed to examine a wide variety of alternative environmental explanations. In early 2013, the findings of a small (n=16) study of affected children were published3; intriguingly, they indicated that all the cases, but just a third of the matched controls, had exposure to disinfectant used in domestic humidifiers, producing an OR of 2.73.

The epidemic …
Shoulder tendinitis and osteoarthrosis of the acromioclavicular joint and their relation to sports.
Authors: B Stenlund
Journal: British Journal of Sports Medicine (1993)

A sample of 207 men from the construction industry was studied using an epidemiological technique of cross-sectional design to investigate if sport activities involving the arms increase the risk of developing shoulder tendinitis or osteoarthrosis of the acromioclavicular joint. The relative risk for shoulder tendinitis was estimated to be 9.5 on the right side, and 4.9 on the left side for a lifetime of sport activity exceeding 8399 h. Subjects who reported both extremely high physical load from work and from sports had an estimated relative risk for signs of shoulder tendinitis of 5.9 on the right side and 10.4 on the left side. High sport activity yielded relative risks of 4.6 on the right side and 2.8 on the left side for osteoarthrosis of the acromioclavicular joint. The combination of high activity in sports and high exposure to load lifted during work yielded relative risks for osteoarthrosis of the acromioclavicular joint of 12.5 on the right side and 6.7 on the left side. There seems to be an increased risk for shoulder tendinitis and acromioclavicular osteoarthrosis for subjects who have been extremely active in sports, and an even higher risk for those who have been extremely active in sports and also report a high exposure to load lifted during work.
Incidence and Predictors of Low Chemotherapy Dose-Intensity in Aggressive Non-Hodgkin's Lymphoma: A Nationwide Study
Authors: Gary H. Lyman, David C. Dale, Jonathan Friedberg, Jeffrey Crawford, Richard I. Fisher
Journal: Journal of Clinical Oncology (2004)

To assess the incidence of and risk factors for reduced relative dose-intensity (RDI) in patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL).A nationwide survey was conducted of 567 oncology practices with data extracted from the records of 4,522 patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); CHOP-rituximab (CHOP-R); or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). The primary outcome was the average RDI for each regimen based on both planned and reference standards. Other assessments included the incidence of febrile neutropenia and patterns of colony-stimulating factor (CSF) use, as well as the average RDI in high-risk subgroups.Dose reductions > or = 15% occurred in 40% of patients and treatment delays > or = 7 days occurred in 24% of patients, resulting in 53% and 48% of patients receiving an RDI less than 85% of the minimum six-cycle and National Comprehensive Cancer Network guideline standards, respectively. Reduced RDI was more prevalent in older patients, with 60% of patients older than 60 years receiving RDI less than 85%. Multivariate analysis identified several independent predictors for reduced RDI, including age older than 60 years, advanced disease stage, poor performance status, and no prophylactic CSF use. Age was no longer a significant risk factor in patients who received prophylactic CSF.Patients with aggressive and potentially curable NHL treated with CHOP, CHOP-R, or CNOP frequently receive reduced RDI. Predictive models based on the risk factors identified for reduced RDI should enable the targeted use of appropriate supportive care, facilitating the delivery of full chemotherapy doses on schedule.
A clinicopathological study of reactive perforating collagenosis: report of 10 cases
Authors: R. Cerio, C.D. Calnan, E. Wilson-Jones
Journal: British Journal of Dermatology (1987)

The histogenesis of 10 patients with reactive perforating collagenosis (RPC) has been studied. All patients had had recurrent keratotic papules on exposed surfaces leaving varioliform scars since childhood. Seven patients were male and three female, ages ranging from 9–56 years (median 24 years) at presentation. Seven patients were Caucasian (two Portuguese) and three Asian. A familial history of RPC was obtained in two patients. The hands, forearms and, less frequently, the legs, face and trunk were affected. A striking event in one patient was the occurrence of widespread eruptive lesions of RPC on the trunk and limbs, following total body irradiation and cytotoxic therapy for leukaemia. Histopathoiogical studies (15 biopsies) indicated a primary acute necrolytic change affecting the epidermis and subepidermal tissues that stimulates an acute inflammatory reaction. Later, there is extrusion of basophilic necrotic material consisting of degenerate collagen interspersed within basophilic granular dermis from degenerating inflammatory cells. Special stains did not suggest involvement of elastic tissue or micro‐organisms. Our findings suggest that RPC represents a specific necrolytic inflammatory response to minor injury rather than a primary collagen disorder.
Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides
Authors: D. Abeni, M. Frontani, F. Sampogna, F. Sera, S. Bolli, R. Corona, G. Baliva, G. Russo
Journal: British Journal of Dermatology (2005)

There is a need for reliable, easily measurable laboratory markers that may help dermatologists to predict the course of mycosis fungoides (MF) when they first evaluate their patients.Our objective was to identify clinical, haematological or immunological parameters as predictors of mortality in patients with MF.We conducted a retrospective study on a prevalent cohort of 124 patients with MF hospitalized at IDI-IRCCS, Rome, Italy, from 1983 to 2001. We calculated the proportion of patients surviving (Kaplan-Meier product-limit estimates) 5 and 10 years after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model.Patients' survival was linked to age and staging (lower survival in older patients and in patients with staging IIB-IV). Higher numbers of white blood cells (WBC) and neutrophils, lower numbers of CD8+ lymphocytes, low haematocrit and lower levels of albumin were significantly associated with a lower survival probability. When simultaneously accounting for age and staging, CD8+ [HR = 3.02, 95% confidence interval (CI) 1.01-9.07 for CD8+ < 250 vs. > or = 600 cells microL(-1)] and WBC (HR = 2.59, 95% CI 0.96-6.96 for WBC > or = 9000 vs. < 6000 cells microL(-1)) were associated with survival. In addition, we observed an exceedingly high risk of death (HR = 12.40, 95% CI 3.11-49.43) for patients with a combination of WBC > or = 9000 and CD8+ < 600 cells microL(-1) vs. WBC < 9000 and CD8+ > or = 600 cells microL(-1)).The measurement of CD8+ cells and WBC in MF seems to be a promising criterion to predict survival, and possibly to support treatment decisions and inclusion of patients in randomized controlled trials.
Consensus statement on the use of rituximab in patients with rheumatoid arthritis
Authors: J S Smolen, E C Keystone, P Emery, F C Breedveld, N Betteridge, G R Burmester, M Dougados, G Ferraccioli, U Jaeger, L Klareskog, T K Kvien, E Martin-Mola, K Pavelka
Journal: Annals of the Rheumatic Diseases (2006)

A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell-targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis.
Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses
Authors: Kung-Chao Chang, Guan-Cheng Huang, Dan Jones, Ya-Hui Lin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphomas, accounts for 30% to 40% of all lymphoma cases. However, long-term survival by current chemotherapy was achieved in only 40% of patients, warranting the development of novel therapeutic strategies including T-cell immunotherapy. However, the level of baseline immune activation in DLBCL is unclear. Experimental Design: The density and distribution of dendritic cells and T cells in 48 cases of primary DLBCL was evaluated by immunohistochemistry. Results: Increased numbers of intratumoral CD1a+ dendritic cells and increased S100+ cells and CD45RO+ T cells around the edges of the tumors were seen in 10 of 48 (21%), 9 of 48 (19%), and 10 of 48 (21%) cases and these were correlated with a favorable prognosis (P = 0.015; P = 0.070, and P = 0.017, respectively), along with increased granzyme B+ T cells in tumor beds (P = 0.013). Increased peritumoral T cells were correlated with tumor expression of HLA-DR (r = 0.446; P = 0.002). Extranodal lymphomas showed fewer tumor-associated CD45RO+ T cells (r = −0.407; P = 0.001) and less conspicuous dendritic cell infiltrates. Conclusions: In DLBCL, the presence of baseline antitumor immune response is associated with favorable clinical outcome, and thus adjuvant T-cell immunotherapy may further boost treatment responses.