tbuckley/cabot-search huggingface dataset:
Arterial Inflammation in Mice Lacking the Interleukin 1 Receptor Antagonist Gene
Authors: Martin J.H. Nicklin, David E. Hughes, Jenny L. Barton, Jan M. Ure, Gordon W. Duff
Journal: The Journal of Experimental Medicine (2000)

Branch points and flexures in the high pressure arterial system have long been recognized as sites of unusually high turbulence and consequent stress in humans are foci for atherosclerotic lesions. We show that mice that are homozygous for a null mutation in the gene encoding an endogenous antiinflammatory cytokine, interleukin 1 receptor antagonist (IL-1ra), develop lethal arterial inflammation involving branch points and flexures of the aorta and its primary and secondary branches. We observe massive transmural infiltration of neutrophils, macrophages, and CD4+ T cells. Animals appear to die from vessel wall collapse, stenosis, and organ infarction or from hemorrhage from ruptured aneurysms. Heterozygotes do not die from arteritis within a year of birth but do develop small lesions, which suggests that a reduced level of IL-1ra is insufficient to fully control inflammation in arteries. Our results demonstrate a surprisingly specific role for IL-1ra in the control of spontaneous inflammation in constitutively stressed artery walls, suggesting that expression of IL-1 is likely to have a significant role in signaling artery wall damage.
Rel/NF-κB transcription factors and the control of apoptosis
Authors: Gail E. Sonenshein
Journal: Seminars in Cancer Biology (1997)

The process of apoptosis is used to eliminate unwanted cells from a wide variety of organisms. Various extracellular signals, often converging in common intracellular pathways, can induce apoptosis in a cell-type-specific fashion. Recent work from several laboratories has demonstrated that Rel/NF-κB transcription factors regulate apoptosis in many cell types. In most cells, Rel/NF-κB transcription factors appear to mediate survival signals that protect cells from apoptosis; however, under some circumstances, activation of these factors may also promote apoptosis.
A randomized, double‐blind, placebo‐controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction
Authors: Hari K. Parthasarathy, Burkert Pieske, Marianne Weisskopf, Chris D. Andrews, Patrick Brunel, Allan D. Struthers, Thomas M. MacDonald
Journal: European Journal of Heart Failure (2009)

Aims To determine whether valsartan improves treadmill exercise time, in patients with symptomatic heart failure with a preserved ejection fraction (HFPEF), compared with placebo. Methods and results In this multicentred, double‐blind, 14‐week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force‐titrated up to 320 mg. A total of 152 patients were randomized ( V = 70, P = 82). Most patients had well‐controlled hypertension ( V = 91.2%, P = 89.0%) (mean baseline systolic BP ~130 mmHg) and &gt;50% were receiving an angiotensin‐converting enzyme inhibitor and/or beta‐blocker ( V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group ( n = 64) and 71.52% in the valsartan group ( n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion‐related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quality‐of‐life scores. Valsartan significantly lowered peak exercise systolic BP (−13.1 mmHg vs. placebo; P &lt; 0.001) and improved ratings of perceived exertion (Borg score) (−0.69 vs. placebo; P = 0.008). Conclusion In this population, which predominantly included patients with well‐controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well‐tolerated.
Patient-Reported Outcome Alert Monitoring
Authors: Brett D. Thombs, Carolyn Ells, Lee Black
Journal: JAMA (2014)

In their Viewpoint on ethical and logistic considerations of using patient-reported outcome (PRO) measures in research, Mr Kyte and colleagues1 discussed active PRO alert monitoring. In PRO alert monitoring, predefined thresholds for alert generation and action plans are established for when research participants report psychological or physical symptoms of potential concern.
Lay people's attitudes to treatment of depression: results of opinion poll for Defeat Depression Campaign just before its launch
Authors: R. G Priest, C. Vize, A. Roberts, M. Roberts, A. Tylee
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To investigate the attitudes of the general public towards depression before the Defeat Depression Campaign of the Royal Colleges of Psychiatrists and General Practitioners; these results form the baseline to assess the change in attitudes brought about by the campaign. <b>Design</b>: Group discussions generated data for initial qualitative research. The quantitative survey comprised a doorstep survey of 2003 people in 143 places around the United Kingdom. <b>Results</b>: The lay public in general seemed to be sympathetic to those with depression but reluctant to consult. Most (1704 (85%)) believed counselling to be effective but were against antidepressants. Many subjects (1563 (78%)) regarded antidepressants as addictive. <b>Conclusions</b>: Although people are sympathetic towards those with depression, they may project their prejudices about depression on to the medical profession. Doctors have an important role in educating the public about depression and the rationale for antidepressant treatment. In particular, patients should know that dependence is not a problem with antidepressants. <h3>Key messages</h3> Before beginning its five year task the campaign sought opinions from 2003 members of the public Most of the sample (78%) thought that antidepressants were addictive, and only 16% thought that they should be given to depressed people Most patients treated with antidepressants in primary care abandon taking them prematurely; fear of dependence is one likely explanation Patients should be informed clearly when antidepressants are first prescribed that discontinuing treatment in due course will not be a problem
Practical application of cellular bioenergetics to the care of aged skin
Authors: R. Osborne, R.S. Carver, L.A. Mullins, D.R. Finlay
Journal: British Journal of Dermatology (2013)

In human skin fibroblasts in vitro, procollagen-1 and NAD(+)/NADH were reduced in three strains of adult fibroblasts compared with neonatal fibroblasts. The levels of both procollagen-1 and NAD(+)/NADH were increased in the adult fibroblasts by treatment for 24 (NAD energy) or 48 h (procollagen-1) with a complex containing niacinamide, Pal-KTTKS peptide and an olive oil fatty acid derivative (Olivem(®)), especially in combination with a natural extract from dill (Lys'lastine V(®)). In one of the adult fibroblast strains evaluated, these changes in procollagen-1 and NAD(+)/NADH in response to the complex of bioactives were in parallel with increased expression of mRNA biomarkers related primarily to dermal matrix and basement membrane structure, including COL1A1, COL3A1, COL5A1, COL14A1, ELN and LOXL2, in addition to SOD2, NAMPT and TGFBR3; MMP1 was decreased in expression. In general, these mRNA biomarker effects were maintained or boosted by the addition of Lys'lastine V, particularly at 1%, and were similar to the fold changes in mRNA expression in neonatal compared with adult fibroblasts. These results indicate that the complex of niacinamide, Pal-KTTKS and Olivem, especially with addition of Lys'lastine V, increases the NAD(+)/NADH bioenergy level of adult skin fibroblasts in parallel with increased expression of skin structure biomarkers in vitro to levels similar to those in younger fibroblasts. Thus, niacinamide, Pal-KTTKS, Olivem and Lys'lastine V are promising bioactive candidates for inclusion in cosmetic formulations.
Electrophysiological study of cardiovascular neurons in the rostral ventrolateral medulla in rats.
Authors: D L Brown, P G Guyenet
Journal: Circulation Research (1985)

In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure elicited by intravenous injection of norepinephrine, aortic occlusion, or electrical stimulation of the hypothalamus, with 100% inhibition occurring at 148 mm Hg. Histograms of postsystolic activity showed that these units had pulse-synchronous rhythms which grew more prominent as arterial pressure increased. Furthermore, electrical stimulation of the superior laryngeal nerve, which elicited a vasodepressor response, strongly inhibited these units. Thus, these neurons were termed negatively correlated cardiovascular units. At least half of these cells project to or through the thoracic spinal cord. In addition, arterial pressure sensitivity is conveyed through carotid sinus and aortic arch afferents. Approximately half of the cardiovascular units are also excited by hypothalamic stimulation. Finally, analysis of neighboring cells showed that it is possible to distinguish between cardiovascular and respiratory units. These data are consistent with the concept of a medullary center which supports tonic sympathetic vasomotor tone and which mediates baroreceptor reflexes, as well as vascular responses of the defense reaction.
Encapsulated mesenchymal stem cells for in vivo immunomodulation
Authors: L Zanotti, A Sarukhan, E Dander, M Castor, J Cibella, C Soldani, A E Trovato, C Ploia, G Luca, M Calvitti, F Mancuso, I Arato, M Golemac, N Jonjic, A Biondi, R Calafiore, M Locati, G D'Amico, A Viola
Journal: Leukemia (2012)
The relationship of physique and body composition to strength in a group of physical education students.
Authors: P. Bale
Journal: British Journal of Sports Medicine (1980)

Fifty-three specialist women physical education students were measured anthropometrically and from these measurements somatotype and body composition were estimated. Leg, back and grip strength dynamometers were used to measure strength indices. Arm strength was calculated from each subject's pull-ups and push-ups and lung capacity was measured using a spirometer. The somatotype ratings and percent fat measurements indicate that the P.E. students are generally more muscular and less fat for their age than non-P.E. students. There was a strong relationship between percent fat and the endomorphy rating and a moderate relationship between lean body weight and mesomorphy. The moderate relationship of the strength variables with the muscular rating, whether expressed as mesomorphy or lean body weight, suggests that the higher a subject's muscular component the greater their dynamic strength.
STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease
Authors: Sydney X. Lu, Onder Alpdogan, Janine Lin, Robert Balderas, Roberto Campos-Gonzalez, Xiao Wang, Guo-Jian Gao, David Suh, Christopher King, Melanie Chow, Odette M. Smith, Vanessa M. Hubbard, Johanne L. Bautista, Javier Cabrera-Perez, Johannes L. Zakrzewski, Adam A. Kochman, Andrew Chow, Gregoire Altan-Bonnet, Marcel R. M. van den Brink
Journal: Blood (2008)
Mechanisms of action of retinoic acid in skin repair
Authors: C.E.M. GRIFFITHS, G.J. FISHER, L.J. FINKEL, J.J. VOORHEES
Journal: British Journal of Dermatology (1992)

The ability of topically applied retinoic acid to improve photoaged skin has stimulated research interest into its mechanism of action. Currently available assay systems are either in-vitro or mouse models, neither of which are truly representative of the in-vivo situation in man. Another drawback is that skin biopsies available from studies using retinoic acid to treat photoageing are of insufficient size to accomplish biochemical and molecular assays. In order to address these problems, a 4-day in-vivo retinoid assay has been developed which serves as a good predictive model for the chronic effects of retinoic acid on skin and helps to characterize the mechanism of action of retinoic acid.
Abstract 2693: Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean patients with metastatic renal cell carcinoma
Authors: Hye Ryun Kim
Journal: Cancer Research (2012)

Abstract Purpose: The aim of this study was to investigate the pharmacogenetic determinants of sunitinib-related toxicity and ethnic difference in metastatic renal cell carcinoma (mRCC) among Korean patients. Experimental Design: A pharmacogenetic study was performed in 65 patients with mRCC treated with sunitinib (50mg orally once daily for 4 weeks-on/2 weeks-off). Detailed data regarding the toxicity of sunitinib, including thrombocytopenia, neutropenia, anemia, and hand-foot syndrome (HFS) were prospectively collected in a clinical trial program (n=38) or general oncology practice (n=27) using sunitinib. A total of 12 genetic polymorphisms in 7 candidate genes (CYP1A1, ABCG2, ABCB1, PDGFRα, VEGFR2, RET, and FLT3) were analyzed for an association with treatment-related toxicity using Pearson-χ2 test. Results: Common grade 3 or 4 treatment-related toxicities were thrombocytopenia (36.9%), neutropenia (18.4%), anemia (7.7%), and HFS (12.3%). Patients carrying an ABCG2 421 A/A genotype developed significantly more grade 3 or 4 thrombocytopenia, neutropenia, and HFS: odds ratio [OR] 10.15; P=0.03, thrombocytopenia, OR 17.33; P=0.003, neutropenia, OR 33.60; and P=0.005, HFS. Conclusion: c.421C&amp;gt;A genetic polymorphism in the ABCG2 gene may be most associated with the risk of sunitinib-related toxicity in mRCC patients. Considering the high frequency of ABCG2 c.421C&amp;gt;A SNP in Asian individuals, this may lead to differential toxicities among ethnic groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2693. doi:1538-7445.AM2012-2693
Integrated use of minimal residual disease classification and IKZF1 alteration status accurately predicts 79% of relapses in pediatric acute lymphoblastic leukemia
Authors: E Waanders, V H J van der Velden, C E van der Schoot, F N van Leeuwen, S V van Reijmersdal, V de Haas, A J Veerman, A Geurts van Kessel, P M Hoogerbrugge, R P Kuiper, J J M van Dongen
Journal: Leukemia (2010)
Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.
Authors: D A Pyke, R D Leslie
Journal: BMJ (1978)

The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome.
Predictors of virologic response in combination therapy with interferon (IFN) alfa 2B plus ribavirin of recurrent hepatitis C after liver transplantation (LT)
Authors: B. Lavezzo, A. Franchello, A. Smedile, D. Cocchis, E. David, A. Barbui, A. Ottobrelli, M. Fadda, A. Brunati, M. Salizzoni, M. Rizzetto
Journal: Journal of Hepatology (2003)
Non-Catheter Technique Prostatectomies
Authors: B. A. Shorey
Journal: BMJ (1972)

An analysis is presented of 247 retropubic prostatectomies performed under hypotensive anaesthesia using a non-catheter technique wherever possible. The mortality rate was 2% which compares favourably with other series. A catheter was not used postoperatively in 67% of the patients operated on by the consultant in charge. Even when those operated on by the registrars in training are considered well over half did not require a catheter. It is suggested that this procedure should be adopted more widely in view of its safety, lack of complications, and increased patient comfort.
A HISTOLOGIC STUDY OF THE AUTO-ALLERGIC TESTIS LESION IN THE GUINEA PIG
Authors: Byron H. Waksman
Journal: The Journal of Experimental Medicine (1959)

The auto-allergic lesion in guinea pigs inoculated with homologous testis plus the Freund adjuvant was investigated histologically. The lesion was found to consist of disseminated foci of perivenous inflammation, lymphocytes and histiocytes predominating in the cellular infiltrate, with invasion of epididymal, rete, and seminiferous tubules and destruction of tubular contents. Guinea pigs up to 800 gm. showed a rapidly progressing diffuse hypo- or aspermatogenesis, which appeared to be secondary to the inflammatory disease. In these animals, the process resolved leaving an atrophic testis with few or no indications of the preceding inflammation and fibrotic scarring only in the rare instances in which actual necrosis of connective tissue elements had occurred. In 1200 gm. animals there was no general hypospermatogenesis and the late findings were limited to foci of aspermatogenesis. This disease then is an experimental auto-allergic orchitis followed by testicular atrophy without scarring. Its morphologic similarity to mumps orchitis and to sterility with "germinal cell aplasia" in man is commented on.
X-linked ichthyosis and ichthyosis vulgaris: comparison of their clinical features based on biochemical analysis
Authors: M. OKANO, Y. KITANO, K. YOSHIKAWA, T. NAKAMURA, Y. MATSUZAWA, T. YUASA
Journal: British Journal of Dermatology (1988)

Thirty cases of X-linked ichthyosis (XLI) and 32 cases of ichthyosis vulgaris (IV) were diagnosed by measuring the steroid sulphatase activity of peripheral blood lymphocytes or the electrophoretic mobility of serum LDL or both. The clinical features of the two conditions were then compared. In both diseases 60-66% of patients had a family history of the condition. Ichthyosis was noted at birth or immediately afterwards in 59% of the patients with XLI while it appeared in infancy in 68% of those with IV. Scales were mostly large and brown or dark brown in patients with XLI, while the majority of patients with IV had small brown or light brown scales. The distribution of the ichthyotic lesions differed in the two types of ichthyosis. On the trunk, the abdomen was more severely involved than the back in 63% of the cases with the XLI, whereas the back was more scaly than the abdomen in 44% of those with IV. On the extremities, the extensor surface was more severely affected than the flexor surface in both types. X-linked ichthyosis was characterized by the presence of lesions in the pre-auricular area, which were found in 93% of the cases with XLI, while only 17% of the IV patients had ichthyotic lesions at this site. Involvement of the preauricular area could be an important clinical feature for distinguishing XLI from IV.
Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples
Authors: Daniel A. Gorelick, Luke R. Iwanowicz, Alice L. Hung, Vicki S. Blazer, Marnie E. Halpern
Journal: Environmental Health Perspectives (2014)

Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart.We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization.We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver.The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.
Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.
Authors: Kevin J Trouba, Kristen M Geisenhoffer, Dori R Germolec
Journal: Environmental Health Perspectives (2002)

Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stress-induced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (stk25) and nicotine adenine dinucleotide phosphate [nad(p)h] quinone oxidoreductase gene expression were measured. The effect of glutathione reduction on arsenite-induced cytotoxicity and gene expression in NHEK also was evaluated by addition of l-buthionine-[S,R]-sulfoximine (BSO) to culture media. Results indicate the term LC(50) for arsenite is approximately 10-15 microM in NHEK and HEL30 keratinocytes and 30 microM in HaCaT keratinocytes. Compared with HaCaT and HEL30 keratinocytes, a nontoxic concentration of arsenite (2.5 microM) increases stk25 and nad(p)h quinone oxidoreductase gene expression in NHEK, an effect partially attenuated by BSO. These data indicate that NHEK and HaCaT/HEL30 keratinocytes have similar sensitivities toward arsenite-induced cytotoxicity but unique gene expression responses. They also suggest that arsenite modulates gene expression in NHEK involved in cellular signaling and other aspects of intermediary metabolism that may contribute to the carcinogenic process.
Outcome of ABO compatible versus identical blood type matching in cardiac transplant recipients on triple immunotherapy
Authors: Jon Kobashigawa, Lynne W. Stevenson, Erica Brownfield, Jaime Moriguchi, Nobuyuki Kawata, Lisa Leonard, Roxella Fandrich, Patricia Sbeehan, Davis Drinkwater, Hillel Laks
Journal: Journal of the American College of Cardiology (1991)