tbuckley/cabot-search huggingface dataset:
Sex steroidal regulation of uterine leiomyoma growth and apoptosis
Authors: T. Maruo
Journal: Human Reproduction Update (2004)

Uterine leiomyomas develop during the reproductive years and regress after menopause, indicating ovarian steroid‐dependent growth potential. Although the clinical and biochemical observations have traditionally supported an important role for estrogen in the promotion of leiomyoma growth, there is also increasing evidence to suggest the involvement of progesterone in the pathogenesis of leiomyoma. In this review, much attention has been paid to characterizing the molecular mechanisms of sex steroidal regulation of leiomyoma growth and apoptosis by evaluating the effects of sex steroids on the expression of growth factors and apoptosis‐related factors. The effects of GnRH agonist on the expression of these factors in leiomyoma are also described. 17β‐Estradiol up‐regulates epidermal growth factor (EGF) receptor, but down‐regulates p53 protein in leiomyoma cells, whereas progesterone augments EGF and Bcl‐2 protein, but inhibits insulin‐like growth factor (IGF‐I) and tumour necrosis factor (TNFα). Since it is now evident that EGF and IGF‐I act as local factors which stimulate leiomyoma growth, these findings suggest that progesterone may have dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival, depending on the local growth factor conditions around each leiomyoma. This may explain why the size of uterine leiomyomas during the use of levonorgestrel‐releasing intrauterine system (LNG‐IUS) increases in some but decreases in other instances. This may also explain why the size of leiomyomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones. Moreover, there is further evidence to suggest that the interactions between estrogen receptors and progesterone receptors may be involved in the modulation of gene transcription activity in leiomyoma. This review demonstrates that leiomyoma growth is integrally regulated by the complex cross‐talk between sex steroid hormones and growth factors.
Effect of Concanavalin A on Human Lymphoid Cell Lines and Normal Peripheral Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bruce F. Mackler
Journal: JNCI Journal of the National Cancer Institute (1972)

Concanavalin A (Con A) increased the thymidine incorporation levels of normal, human, peripheral blood lymphocytes cultivated without serum. The marked increases were maximum at 72 hours and proportional to the concentration of Con A. The maximum responses induced by low concentration (0.5–1.0 μg/ml)were 23- to 66-fold greater than their controls, whereas 50–100 μg/ml tended to be cytotoxic. Human lymphoid cell lines RPMI 4098, 1788, and 7249, cultured without serum supplementation, maintained high levels of spontaneous thymidine incorporation and viability up to 3 days. With low Con A concentrations, the thymidine incorporation levels of cell lines 1788 and 7249 were increased above their spontaneous incorporation levels. These stimulation responses to Con A were comparable to those of normal peripheral cells by several criteria. Higher Con A concentrations were cytotoxic for all 3 cell lines as well as for normal ones. The stimulatory and cytotoxic effects of Con A on these 2 lymphoid populations were inhibited by α-methyl-d-mannoside, an inhibitor of Con A binding to glycoproteins. The Con A activation and destruction of normal peripheral lymphocytes and lymphoid cell lines may have occurred through analogous mechanisms.—J Natl Cancer Inst 49: 935–941, 1972.
DKK1 promotes hepatocellular carcinoma cell migration and invasion through β-catenin/MMP7 signaling pathway
Authors: Liang Chen, Ming Li, Qian Li, Chao-jie Wang, Song-qiang Xie
Journal: Molecular Cancer (2013)

Recently several reports have indicated that elevated expression of DKK1 is tightly associated with the progression of hepatocellular carcinoma (HCC). However, the biological function of DKK1 in HCC has not yet been well documented.In this study, the role of DKK1 in tumor cell proliferation, migration and invasion was investigated using MTT, colony formation, wound scratch, transwell assays, and also human HCC samples.Both gain- and loss-of-function studies showed that DKK1 did not influence the tumor cell proliferation and colony formation, while dramatically promoted HCC cell migration and invasion. Subsequent investigations revealed that β-catenin was an important target of DKK1. The blocking of β-catenin by pharmacological inhibitor antagonized the function of DKK1, whereas introduction of β-catenin by transfection with plasmids or treatment with GSK3β inhibitor phenocopied the pro-migration and pro-invasion effects of DKK1. We further disclosed that DKK1 exerted its pro-invasion function, at least in part, by promoting β-catenin expression, in turn, upregulating the expression of matrix metalloproteinase 7 (MMP7), which was independent of the canonical Wnt signaling pathway. Moreover, introduction of MMP7 significantly enhanced the ability of HCC cells to invade extracellular matrix gel in vitro. Consistently, in human HCC tissues, DKK1 level was positively correlated with β-catenin expression, as well as tumor metastasis.Taken together, these results demonstrated that DKK1 is overexpressed in HCC; moreover, ectopic expression DKK1 promotes HCC cell migration and invasion at least partly through β-catenin/MMP7 signaling axis, suggesting that DKK1 may be a promising target for HCC therapy.
Malignant fibrous histiocytoma developing in a burn scar
Authors: T. YAMAMURA, K. AOZASA, T. HONDA, A. TAKADA, M. MAEDA, S. SANO
Journal: British Journal of Dermatology (1984)

A case of malignant fibrous histiocytoma (MFH) developing in a burn scar is presented. The patient was burnt at 3 years of age and 25 years later, a rapidly growing tumour developed in the burn scar. MFH was diagnosed by light and electron microscopy and by an immunoperoxidase method. This complication of a burn scar has not been previously reported.
Experimental liver cirrhosis induced by alcohol and iron.
Authors: H Tsukamoto, W Horne, S Kamimura, O Niemelä, S Parkkila, S Ylä-Herttuala, G M Brittenham
Journal: Journal of Clinical Investigation (1995)

To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease.
Determinants of drug absorption in different ECMO circuits
Authors: E. D. Wildschut, M. J. Ahsman, K. Allegaert, R. A. A. Mathot, D. Tibboel
Journal: Intensive Care Medicine (2010)

The aim of this in vitro study was to evaluate potential determinants of drug loss in different ECMO circuits.Midazolam, morphine, fentanyl, paracetamol, cefazolin, meropenem and vancomycin were injected into three neonatal roller pump, two paediatric roller pump and two clinically used neonatal roller pump circuits, all with a silicone membrane, and two neonatal centrifugal pump circuits with polypropylene hollow-fibre membranes. Serial blood samples were taken from a post-oxygenator site. Drug recovery was calculated as the ratio between the determined and the theoretical maximum concentration. The latter was obtained by dividing dose by theoretical circuit volume.Average drug recoveries at 180 min in three neonatal silicone membrane roller pump circuits were midazolam 0.62%, morphine 23.9%, fentanyl 0.35%, paracetamol 34.0%, cefazolin 84.3%, meropenem 82.9% and vancomycin 67.8%. There was a significant correlation between the lipophilicity of the drug expressed as log P and the extent of drug absorption, p < 0.001. The recovery of midazolam and fentanyl in centrifugal pump circuits with hollow-fibre membrane oxygenator was significantly higher compared to neonatal roller pump circuits with silicone membranes: midazolam 63.4 versus 0.62%, fentanyl 33.8 versus 0.35%, p < 0.001. Oxygenator size and used circuits do not significantly affect drug losses.Significant absorption of drugs occurs in the ECMO circuit, correlating with increased lipophilicity of the drug. Centrifugal pump circuits with hollow-fibre membrane oxygenators show less absorption for all drugs, most pronounced for lipophilic drugs. These results suggest that pharmacokinetics and hence optimal doses of these drugs may be altered during ECMO.
A dose-response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients
Authors: AJ Schreurs, HE Sinninghe Damste, CS de Graaff, AP Greefhorst
Journal: European Respiratory Journal (1996)

The aim of this randomized, double-blind, parallel group study was to determine the lowest effective dose of 6, 12 and 24 microg formoterol fumarate dihydrate Turbuhaler b.i.d. compared with placebo. The 4 week treatment was preceded by a 1 week run-in period. Morning peak expiratory flow (PEF) before intake of the study drug was the primary variable. Patients recorded PEF, prior to and 15 min after intake of the study drug (immediate response), asthma symptoms, and use of rescue medication morning and evening. Of 221 patients (71 females and 150 males), 194 were included in the efficacy per protocol (PP) analysis; mean age 47 yrs, mean forced expiratory volume in one second (FEV1) 2.01 L (58% of predicted), mean FEV1 reversibility 27% at entry. Ninety percent used inhaled steroids. Compared with placebo, 6 microg formoterol b.i.d was found to be the lowest effective dose in the morning (p=0.008) and evening p=0.0041) PEF. The mean increases in PEF were 22 and 23 L x min-1 respectively, compared with placebo. After 6 microg formoterol, the mean immediate increase in morning PEF was 42 L x min-1 compared to an increase of only 9 L x min-1 after placebo (&lt;0.0001). All doses produced a statistically significant decrease in asthma symptoms, day and night, and the need for rescue medication at night. All doses were well-tolerated. In conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6 microg b.i.d.
Toward a Biosignature for Suicide
Authors: Maria A. Oquendo, Gregory M. Sullivan, Katherin Sudol, Enrique Baca-Garcia, Barbara H. Stanley, M. Elizabeth Sublette, J. John Mann
Journal: American Journal of Psychiatry (2014)

Objective: Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. Method: The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. Results: Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. Conclusions: The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.
Food and fatty acid intake and atopic disease in adults
Authors: M.A. Trak-Fellermeier, S. Brasche, G. Winkler, B. Koletzko, J. Heinrich
Journal: European Respiratory Journal (2004)

The aim of the study was to assess the relationship between dietary intake of selected foods and fatty acids with atopic disease prevalence in adults. Data from the European Community Respiratory Health Survey in Erfurt, combined with a 3‐day weighed records dietary survey, was used. Complete data was available from 469 males and 333 females aged 20–64 yrs. Multiple logistic regression was applied comparing the highest with the lowest quartile of dietary exposures and linear trends were tested stratified by sex. In males, margarine intake and a high ratio of omega‐6 to omega‐3 fatty acids were positively associated with hay fever. In females, a high intake of total fat, palmitoleic and oleic acids were positively associated with sensitisation. A high total fat, high monounsaturated fatty acid and high oleic acid consumption were positively associated with hay fever. Whilst an excessive intake of fat or imbalance in fat intake, particular of monounsaturated fatty acids, increased the risk for hay fever and allergic sensitisation in females, mostly no significant associations were found for males. Dietary factors were mostly not related with prevalence rates of bronchial hyperresponsiveness and atopic eczema either in males or in females.
The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia
Authors: P Malfertheiner
Journal: Gut (2005)

Helicobacter pylori infection and gastro-oesophageal reflux disease (GERD) account for most upper gastrointestinal pathologies with a wide spectrum of clinical manifestations. The interplay of both conditions is complex, in part intriguing, and has become a matter of debate because of conflicting results. The cardia is an area where both H pylori and abnormal GERD exert their damaging potential, inducing inflammation and its consequences, such as intestinal metaplasia. While the role of intestinal metaplasia within columnar lined epithelium (Barrett's oesophagus) in the context of GERD is well established as a risk for neoplasia development, the role of intestinal metaplasia at the cardia in the context of H pylori infection is unclear. A particular challenge is the distinction of intestinal metaplasia as a consequence of GERD or H pylori if both conditions are concomitant. Available data on this issue, including follow up of a small patient series, are presented, but more studies are required to shed light on this issue because they will help to identify those patients that need surveillance.
NATURAL GAS AND EUSTACHIAN INFLAMMATION.
Authors: JOHN JOHNSON KYLE
Journal: JAMA (1898)

Some few weeks ago it was my pleasure to read a paper before the Western Ophthalmological, Otological, Laryngological and Rhinological Association, calling attention to the effect of natural gas upon the conjunctiva. I now desire, in a general way, to show wherein the natural gas from the Indiana field is a potent factor in causing catarrhal inflammation of the whole pneumatic system, with special reference to the Eustachian tube. The gas from Indiana differs from that of the New York or Pennsylvania field, in that it contains sulphuretted hydrogen, and in burning the process of combustion is not so complete. Eighty-five per cent. of the natural gas is marsh gas, which is composed of 75 per cent, by weight of carbon and 25 per cent, of hydrogen. The products of combustion, which differ in every case, are carbon dioxid, water vapor, sulphur dioxid, trioxid, nitrogen oxids and ammonia sulphate. The
A severe but reversible refractory sprue
Authors: X Dray
Journal: Gut (2005)

Original treatments, including corticosteroids, azathioprine, infliximab, ciclosporin, and interleukin 10 have been occasionally reported in refractory sprue patients with unsatisfactory results.1–8 We report on the clinical and histological efficacy of anti-T chemotherapy (pentostatine) in a patient with a refractory sprue complicated by an ulcerative and stenotic jejunitis.

A 38 year old man diagnosed with refractory sprue in June 2002 developed ulcerative jejunitis in July 2003. Diagnosis led on the following: malabsorptive diarrhoea resistant to a gluten free diet (GFD); severe malnutrition (body mass index (BMI) 14.3 kg/m2); albuminaemia 11 g/l; diffuse total villous atrophy associated with jejunal ulcerations and a major intestinal intraepithelial CD3+ CD8− T lymphocyte population (IEL) (fig 1A–C); clonal T cell receptor γ rearrangement; negative circulating antigliadin and antitransglutaminase IgA and IgG antibodies (total IgA and IgG were normal); hyposplenism; …
Circulation of Labeled Albumin Through the Aortic Wall of the Dog
Authors: LEROY E. DUNCAN, JEROME CORNFIELD, KATHERIN BUCK
Journal: Circulation Research (1959)

Data are presented which support the concept that albumin enters the inner layer of the aortic wall by passage from the lumen of the aorta across the intimal endothelium. The rate of movement of albumin from serum into the aortic wall is much greater proximally where the aorta is wide than distally where it is narrow. Thus the rate correlates with the circumferential tension to which the aortic wall is subjected. The hypothesis is advanced that circumferential tension acts as a major determinant of transendothelial transfer of proteins into the aorta by widening the endothelial intercellular spaces through which the transfer occurs.
Turning Off AKT: PHLPP as a Drug Target
Authors: Alexandra C. Newton, Lloyd C. Trotman
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Precise control of the balance between protein phosphorylation, catalyzed by protein kinases, and protein dephosphorylation, catalyzed by protein phosphatases, is essential for cellular homeostasis. Dysregulation of this balance leads to pathophysiological states, driving diseases such as cancer, heart disease, and diabetes. Aberrant phosphorylation of components of the pathways that control cell growth and cell survival are particularly prevalent in cancer. One of the most studied tumor suppressors in these pathways is the lipid phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome ten), which dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ), thus preventing activation of the oncogenic kinase AKT (v-akt murine thymoma viral oncogene homolog). In 2005, the discovery of a family of protein phosphatases whose members directly dephosphorylate and inactivate AKT introduced a new negative regulator of the phosphoinositide 3-kinase (PI3K) oncogenic pathway. Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) isozymes comprise a novel tumor suppressor family whose two members, PHLPP1 and PHLPP2, are deleted as frequently as PTEN in cancers such as those of the prostate. PHLPP is thus a novel therapeutic target to suppress oncogenic pathways and is a potential candidate biomarker to stratify patients for the appropriate targeted therapeutics. This review discusses the role of PHLPP in terminating AKT signaling and how pharmacological intervention would impact this pathway.
Ventilation inhomogeneity in children with cystic fibrosis and primary ciliary dyskinesia
Authors: Kent Green, Frederik Buchvald, Astrid Madsen, Per Gustafsson, Kim G. Nielsen
Journal: European Respiratory Journal (2012)

Rationale:   Ventilation inhomogeneity (VI) measured by multiple breath inert gas washout (MBW) are common findings in cystic fibrosis (CF) children with normal spirometry (1). Recently this was shown also in primary ciliary dyskinesia (PCD) (2). The lower morbidity in PCD vs. CF would suggest that small airway involvement is less severe in PCD. We therefore compared MBW indices reflecting peripheral airway involvement in children with CF and PCD.   Methods:   A cross sectional study was performed in 24 children with PCD and 25 with CF, matched by age and FEV1. N2 MBW in triplets (Exhalyzer D, EcoMedics AG) and spirometry were performed within one occasion in clinically stable patients. Lung Clearance Index (LCI), an index of global VI, and specific indices of VI arising in the conductive (Scond) and the acinar (Sacin) airway zones (2) were calculated and presented as z-scores based on new normative data (Houltz B et al, ERS abstract 2012). They were compared between patient groups using Mann-Whitney Test.   Results:   There was no significant difference in LCI, Scond and Sacin (z-scores) between the two patient groups, although LCI, z-scores tended to be higher in PCD (Table 1).   Conclusion:   In contrast to our expectations severity of peripheral airway involvement is similar in children with CF and PCD.  (1) Respiration 2009;78:339; (2) Thorax 2012;67:49.