tbuckley/cabot-search huggingface dataset:
Characteristic features of ageing in Korean women’s hair and scalp
Authors: S.N. Kim, S.Y. Lee, M.H. Choi, K.M. Joo, S.H. Kim, J.S. Koh, W.S. Park
Journal: British Journal of Dermatology (2012)

Background The effect of age on hair properties has previously been investigated in white and Japanese women; however, little is known of the age-related characteristic features of hair in Korean women. Objectives To determine the ageing features of Korean women's hair by examining physical and biological factors in sufficient numbers of participants. Methods In total, 150 healthy Korean women (aged 23–69 years) living in Seoul were allocated to five age-graded groups. Age-related changes of various features of the scalp and hair shaft were measured, including hair density, diameter, tensile strength and lustre, and grey-hair ratio. The hair-shaft compositions of minerals, amino acids and steroid hormones were analysed by high-performance liquid chromatography. Results Hair-loss parameters (hair density, diameter and tensile strength) and hair lustre decreased significantly with age, beginning in the subjects' 40s. The hair-whiteness value increased significantly with age, beginning in their 60s, due to an increase in the ratio of grey hair. Calcium and magnesium levels greatly exceeded the reference ranges and declined in an age-dependent manner, while potassium and phosphorus levels increased with age. No age-related change of hair-shaft amino acid content was evident. The contents of sterols and their metabolites (cholesterol, desmosterol, lanosterol and pregnenolone) increased significantly with age, but there was no correlation between the examined sex steroids and age. Conclusions These results show that intrinsic ageing produces diverse changes in the hair and scalp features of Korean women from their 40s, and the ageing features of Korean women's hair could be partially different from that of women in other countries.
NO-dependent CaMKII activation during β-adrenergic stimulation of cardiac muscle
Authors: Daniel A. Gutierrez, Miguel Fernandez-Tenorio, Jakob Ogrodnik, Ernst Niggli
Journal: Cardiovascular Research (2013)

During β-adrenergic receptor (β-AR) stimulation, phosphorylation of cardiomyocyte ryanodine receptors by protein kinases may contribute to an increased diastolic Ca2+ spark frequency. Regardless of prompt activation of protein kinase A during β-AR stimulation, this appears to rely more on activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), by a not yet identified signalling pathway. The goal of the present study was to identify and characterize the mechanisms which lead to CaMKII activation and elevated Ca2+ spark frequencies during β-AR stimulation in single cardiomyocytes in diastolic conditions. Confocal imaging revealed that β-AR stimulation increases endogenous NO production in cardiomyocytes, resulting in NO-dependent activation of CaMKII and a subsequent increase in diastolic Ca2+ spark frequency. These changes of spark frequency could be mimicked by exposure to the NO donor GSNO and were sensitive to the CaMKII inhibitors KN-93 and AIP. In vitro, CaMKII became nitrosated and its activity remained increased independent of Ca2+ in the presence of GSNO, as assessed with biochemical assays. β-AR stimulation of cardiomyocytes may activate CaMKII by a novel direct pathway involving NO, without requiring Ca2+ transients. This crosstalk between two established signalling pathways may contribute to arrhythmogenic diastolic Ca2+ release and Ca2+ waves during adrenergic stress, particularly in combination with cardiac diseases. In addition, NO-dependent activation of CaMKII is likely to have repercussions in many cellular signalling systems and cell types.
Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea?
Authors: B. Lefebvre, J-L. Pépin, J-P. Baguet, R. Tamisier, M. Roustit, K. Riedweg, G. Bessard, P. Lévy, F. Stanke-Labesque
Journal: European Respiratory Journal (2008)

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B 4 is a lipid mediator involved in atherogenesis. In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB 4 production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB 4 production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB 4 production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB 4 production, which was measured by liquid chromatography–tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls. LTB 4 production was increased in OSA patients compared with controls. LTB 4 levels correlated with the mean and minimal arterial oxygen saturation ( S a,O 2 ). LTB 4 production correlated with luminal diameter data in patients with a mean S a,O 2 of ≤94% but not with IMT. Lastly, CPAP significantly reduced LTB 4 production by 50%. Leukotriene B 4 production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B 4 could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics
Authors: M Hoshino, Y Nakamura
Journal: European Respiratory Journal (1997)

There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation
Authors: Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (2007)

We demonstrate that all-trans retinoic acid (RA) induces FoxP3+ adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (α4β7+ CC chemokine receptor 9+) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor–β1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4+ T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation.
Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy
Authors: M. Colleoni, G. Viale, D. Zahrieh, L. Bottiglieri, R.D. Gelber, P. Veronesi, A. Balduzzi, R. Torrisi, A. Luini, M. Intra, S. Dellapasqua, A. Cardillo, R. Ghisini, G. Peruzzotti, A. Goldhirsch
Journal: Annals of Oncology (2007)
Increased Expression of Membrane Type 3-Matrix Metalloproteinase in Human Atherosclerotic Plaque
Authors: Hiroyasu Uzui, Alice Harpf, Ming Liu, Terence M. Doherty, Arun Shukla, Ning-Ning Chai, Pinky V. Tripathi, Stefan Jovinge, Douglas J. Wilkin, Kamlesh Asotra, Prediman K. Shah, Tripathi B. Rajavashisth
Journal: Circulation (2002)

Background— Matrix metalloproteinases (MMPs) are thought to play a prominent role in atherogenesis and destabilization of plaque. Pericellularly localized membrane-type (MT)-MMPs activate secreted MMPs. We investigated the hypothesis that MT3-MMP is expressed in human atherosclerotic plaques and is regulated by locally produced inflammatory cytokines and oxidized low-density lipoprotein (Ox-LDL). Methods and Results— Expression and cellular localization of MT3-MMP in normal and atherosclerotic human coronary arteries were examined using specific antibodies. Abundant MT3-MMP expression was noted in medial smooth muscle cells (SMCs) of normal arteries. In atherosclerotic arteries, MT3-MMP expression was observed within complex plaques and colocalized with SMCs and macrophages (Mφ). Cultured human monocyte-derived Mφ constitutively expressed MT3-MMP mRNA and proteolytically active protein, as demonstrated by mRNA analyses, immunoblotting, and gelatin zymography, respectively. Ox-LDL, tumor necrosis factor-α, or macrophage colony-stimulating factor caused dose- and time-dependent increases in steady-state levels of MT3-MMP mRNA in cultured Mφ. This correlated with a 2- to 4-fold increase in levels of MT3-MMP immunoreactive protein and enzymatic activity in Mφ membranes. Confocal microscopy and flow cytometry confirmed induction and spatial distribution of MT3-MMP protein from intracellular domains to the Mφ plasma membrane by Ox-LDL, tumor necrosis factor-α, or macrophage colony-stimulating factor. Conclusions— MT3-MMP is expressed by SMCs and Mφ in human atherosclerotic plaques. Proinflammatory molecules cause a progressive increase in the expression of MT3-MMP in cultured Mφ. Our results suggest a mechanism by which inflammatory molecules could promote Mφ-mediated degradation of extracellular matrix and thereby contribute to plaque destabilization.
The Role of S100P in the Invasion of Pancreatic Cancer Cells Is Mediated through Cytoskeletal Changes and Regulation of Cathepsin D
Authors: Hannah J. Whiteman, Mark E. Weeks, Sally E. Dowen, Sayka Barry, John F. Timms, Nicholas R. Lemoine, Tatjana Crnogorac-Jurcevic
Journal: Cancer Research (2007)

Abstract Up-regulation of S100P, a member of the S100 calcium-binding protein family, is an early molecular event in the development of pancreatic cancer and it is expressed at high levels in both precursor lesions and invasive cancer. To gain more insight into the molecular mechanisms underlying the functional roles of this protein, we stably overexpressed S100P in the Panc1 pancreatic cancer cell line and identified the consequent changes in global protein expression by two-dimensional difference in-gel electrophoresis. The observed changes in target proteins were confirmed by Western blot analysis and immunofluorescence, whereas their functional effect was investigated using motility and invasion assays. In this study, we have shown that overexpression of S100P led to changes in the expression levels of several cytoskeletal proteins, including cytokeratins 8, 18, and 19. We have also shown disorganization of the actin cytoskeleton network and changes in the phosphorylation status of the actin regulatory protein cofilin. Additionally, we have shown that overexpression of S100P leads to increased expression of another early pancreatic cancer marker, S100A6, as well as the aspartic protease cathepsin D, both of which are involved in cellular invasion. Functional studies showed that the increased invasive potential of S100P-overexpressing cells was at least partially due to the increase in cathepsin D expression. In summary, our data suggest that these changes could contribute to the metastatic spread of pancreatic cancer and may explain the devastating prognosis of this disease. [Cancer Res 2007;67(18):8633–42]
DNA Replication Stress as a Hallmark of Cancer
Authors: Morgane Macheret, Thanos D. Halazonetis
Journal: Annual Review of Pathology Mechanisms of Disease (2015)

Human cancers share properties referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most pervasive. The sustained proliferation hallmark can be explained by mutations in oncogenes and tumor suppressors that regulate cell growth, whereas the escape from apoptosis hallmark can be explained by mutations in the TP53, ATM, or MDM2 genes. A model to explain the presence of the three hallmarks listed above, as well as the patterns of genomic instability observed in human cancers, proposes that the genes driving cell proliferation induce DNA replication stress, which, in turn, generates genomic instability and selects for escape from apoptosis. Here, we review the data that support this model, as well as the mechanisms by which oncogenes induce replication stress. Further, we argue that DNA replication stress should be considered as a hallmark of cancer because it likely drives cancer development and is very prevalent.
From synthetic modeling of social interaction to dynamic theories of brain–body–environment–body–brain systems
Authors: Tom Froese, Hiroyuki Iizuka, Takashi Ikegami
Journal: Behavioral and Brain Sciences (2013)

Abstract Synthetic approaches to social interaction support the development of a second-person neuroscience. Agent-based models and psychological experiments can be related in a mutually informing manner. Models have the advantage of making the nonlinear brain–body–environment–body–brain system as a whole accessible to analysis by dynamical systems theory. We highlight some general principles of how social interaction can partially constitute an individual's behavior.
Integrative Genomic Profiling of Human Prostate Cancer
Authors: Barry S. Taylor, Nikolaus Schultz, Haley Hieronymus, Anuradha Gopalan, Yonghong Xiao, Brett S. Carver, Vivek K. Arora, Poorvi Kaushik, Ethan Cerami, Boris Reva, Yevgeniy Antipin, Nicholas Mitsiades, Thomas Landers, Igor Dolgalev, John E. Major, Manda Wilson, Nicholas D. Socci, Alex E. Lash, Adriana Heguy, James A. Eastham, Howard I. Scher, Victor E. Reuter, Peter T. Scardino, Chris Sander, Charles L. Sawyers, William L. Gerald
Journal: Cancer Cell (2010)
Resorption of calcification in primary pulmonary tuberculosis
Authors: J. B. Morrison
Journal: Thorax (1970)

During a long-term follow-up of 10 to 17 years on 383 children aged 2 months to 15 years suffering from primary pulmonary tuberculosis with consolidation-collapse of lung segments, apparent calcification was noted to have disappeared in whole or in part from the lungs and/or lymph nodes of 68 children. This finding was most common in those under 6 years of age on entry to the study, 23·4% compared with 4·5% over six years.
A Lecture on "HOW DO DRUGS ACT?"
Authors: W. L. Brown
Journal: BMJ (1933)

In the same way sympathetic stimulation has been A Lecture found to produce an' 'adrenaline-like" substance in other ON structures besides the adrenal medulla.I say adrenaline-"HOW DO DRUGS ACT?" * like, for Cannon has shown that it is not exactly the same as adrenaline.Some synmpathetic effects are stimulating, BY | others inhibitory.While adrenaline reproduces all these,
PIG-A -- The Target Gene in Paroxysmal Nocturnal Hemoglobinuria
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1994)

A rare disease merits general attention if it is associated with extraordinary clinical manifestations, unusual laboratory findings, or an instructive molecular defect. Paroxysmal nocturnal hemoglobinuria (PNH) has all three. Its clinical hallmark, black urine on arising from sleep, is graphic testimony to intravascular hemolysis during the night. Even more peculiar is the hemolysis that occurs after blood from a patient with PNH is mixed with acidified serum or ordinary table sugar. The molecular abnormality in PNH, described by Miyata et al. in this issue of the Journal (see pages 249 to 255), not only informs us about this unusual disease . . .
Chronic Effects of Lovastatin and Bezafibrate on Cortical and Medullary Hemodynamics in Deoxycorticosterone Acetate-Salt Hypertensive Mice
Authors: VOLKMAR GROSS, WOLFGANG SCHNEIDER, WOLF-HAGEN SCHUNCK, EERO MERVAALA, FRIEDRICH C. LUFT
Journal: Journal of the American Society of Nephrology (1999)

Cholesterol synthesis inhibitors and fibrates both exercise effects that could influence BP and renal function in hypertension. To test this issue, transit-time ultrasound flow probes, implanted optical fibers, and laser-Doppler flowmetry were used for measurements of total and regional renal blood flows in lovastatin (40 mg/kg body wt) and bezafibrate (50 mg/kg body wt) chronically treated deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Total renal blood flow was well autoregulated between 70 and 150 mmHg (approximately 3.5 ml/min per g kidney weight in DOCA-salt mice). Both lovastatin and bezafibrate increased renal blood flow to a range between 4.7 and 5.5 ml/min per g kidney weight. In the renal perfusion pressure ranges investigated, renal vascular resistance increased in lovastin- and bezafibrate-treated DOCA-salt mice, but not as steeply as in vehicle-treated DOCA-salt mice. During a stepwise increase in renal perfusion pressure in lovastatin-treated DOCA-salt mice, medullary blood flow increased up to 130% of baseline values, which was not seen in vehicle- or bezafibrate-treated mice. After extracellular volume expansion with 1% saline, 1 ml over 1 min, total renal blood flow was also higher in lovastatin- or bezafibrate-treated DOCA-salt mice, whereas medullary blood flow increased more steeply in lovastatin-, compared with bezafibrate- or vehicle-treated mice. Systemic BP was significantly decreased in lovastatin-treated DOCA-salt mice compared with vehicle-treated mice. Lovastatin prevented histologic evidence for hemostasis in the medullary circulation of DOCA-salt mice. The results suggest that both lovastatin and bezafibrate diminished DOCA-salt-induced reductions in total renal blood flow. Lovastatin also abolished the perturbed medullary blood flow reactions to increased perfusion pressure or to volume expansion. Finally, lovastatin decreased systemic BP in DOCA-salt mice. These data suggest that cholesterol synthesis inhibition or fibrate treatment improve disturbed renal function in a mouse model of salt-dependent hypertension.
Accelerated Evolution of CES7, a Gene Encoding a Novel Major Urinary Protein in the Cat Family
Authors: G. Li, J. E. Janecka, W. J. Murphy
Journal: Molecular Biology and Evolution (2010)

Cauxin is a novel urinary protein recently identified in the domestic cat that regulates the excretion of felinine, a pheromone precursor involved in sociochemical communication and territorial marking of domestic and wild felids. Understanding the evolutionary history of cauxin may therefore illuminate molecular adaptations involved in the evolution of pheromone-based communication, recognition, and mate selection in wild animals. We sequenced the gene encoding cauxin, CES7, in 22 species representing all major felid lineages, and multiple outgroups and showed that it has undergone rapid evolutionary change preceding and during the diversification of the cat family. A comparison between feline cauxin and orthologous carboxylesterases from other mammalian lineages revealed evidence of strong positive Darwinian selection within and between several cat lineages, enriched at functionally important sites of the protein. The higher rate of radical amino acid replacements in small felids, coupled with the lack of felinine and extremely low levels of cauxin in the urine of the great cats (Panthera), correlates with functional divergence of this gene in Panthera, and its putative loss in the snow leopard. Expression studies found evidence for several alternatively spliced transcripts in testis and brain, suggesting additional roles in male reproductive fitness and behavior. Our work presents the first report of strong positive natural selection acting on a major urinary protein of nonrodent mammals, providing evidence for parallel selection pressure on the regulation of pheromones in different mammalian lineages, despite the use of different metabolic pathways. Our results imply that natural selection may drive rapid changes in the regulation of pheromones in urine among the different cat species, which in turn may influence social behavior, such as territorial marking and conspecific recognition, therefore serving as an important mechanism for the radiation of this group of mammals.
Academic integrity
Authors: J. Bird
Journal: BMJ (1995)

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Smith R. Questioning academic integrity. BMJ. 1994 Dec 17;309(6969):1597–1598. [Europe PMC free article] [Abstract] [Google Scholar]
Telomere maintenance mechanisms in malignant peripheral nerve sheath tumors: expression and prognostic relevance
Authors: L. Venturini, M. G. Daidone, R. Motta, G. Cimino-Reale, S. F. Hoare, A. Gronchi, M. Folini, W. N. Keith, N. Zaffaroni
Journal: Neuro-Oncology (2012)

This study investigated the prevalence and the prognostic relevance of the 2 known telomere maintenance mechanisms (TMMs), telomerase activity (TA) and alternative lengthening of telomeres (ALT), in malignant peripheral nerve sheath tumors (MPNST). In 57 specimens from 49 patients with MPNST (35 sporadic, 14 neurofibromatosis type 1-related), TA was determined using the telomeric repeat amplification protocol, and ALT was detected by assaying ALT-associated promyelocytic leukemia bodies (APB) and terminal restriction fragment (TRF) length distribution. TA or ALT (defined on the basis of APB) alone was found in 24.6% or 26.3% of the lesions, respectively, whereas 6 cases (10.5%) were TA+/ALT+. A concordance between APB and TRF results in defining the ALT status was observed in 44 of 57 cases (77.2%; P < .0001). TA was more frequently expressed in samples from patients with neurofibromatosis type 1 than in those with sporadic disease (60% vs 29.4%, P = 0.087). In the overall series, TA proved to be prognostic for 5-year disease-specific death (hazard ratio, 3.78; 95% confidence interval [CI], 1.60–8.95; P = .002), even when adjusted for the presence of neurofibromatosis type 1 (hazard ratio, 4.22; 95% CI, 1.804–9.874; P = .001) and margin status after surgery (hazard ratio, 5.78; 95% CI, 2.19–15.26; P < .001). Conversely, ALT did not significantly affect clinical outcome of MPNST using either APB expression (hazard ratio, 1.25; 95% CI 0.54–2.89; P = 0.605) or TRF distribution (hazard ratio, 0.57; 95% CI, 0.17–1.96; P = .375) as the detection approach. Our results indicate for the first time that both TMMs, TA and ALT, are present in MPNST and differentially affect patient prognosis.