tbuckley/cabot-search huggingface dataset:
Hug(h)e(s') ears: an unusual presentation of antiphospholipid syndrome
Authors: D O'GRADAIGH, D G I SCOTT, N LEVELL
Journal: Annals of the Rheumatic Diseases (1999)

Visual cues provide an important means for aerial creatures to ascertain their self-motion through the environment. In many insects including flies, moths and bees, wide-field motion-sensitive neurons in the 3rd optic ganglion are thought to underlie such motion encoding, however these neurons can only respond robustly over limited speed ranges. The task is more complicated for some species of dragonflies that switch between extended periods of hovering flight and fast-moving pursuit of prey and conspecifics, requiring motion detection over a broad range of velocities. Since little is known about motion processing in these insects, we performed intracellular recordings from hawking, emerald dragonflies (<i>Hemicordulia spp.</i>) and identified a diverse group of motion sensitive neurons that we named Lobula Tangential Cells (LTCs). Following prolonged visual stimulation with drifting gratings, we observed significant differences in both temporal and spatial tuning of LTCs. Cluster analysis of these changes confirmed several groups of LTCs with distinctive spatiotemporal tuning. These differences were associated with variation in velocity tuning in response to translated, natural scenes. LTCs with differences in velocity tuning ranges and optima may underlie how a broad range of motion velocities are encoded. In the hawking dragonfly, changes in LTCs tuning over time are therefore likely to support their extensive range of behaviours, from hovering to fast speed pursuits. <b>SIGNIFICANCE STATEMENT</b> Understanding how animals navigate the world is an inherently difficult and interesting problem. Insects are useful models for understanding neuronal mechanisms underlying these activities, with neurons that encode wide-field motion previously identified in insects such as flies, hawkmoths and butterflies. Like some Dipteran flies, dragonflies exhibit complex aerobatic behaviours such as hovering, patrolling and aerial combat. However, dragonflies lack halteres that support such diverse behaviour in flies. To understand how dragonflies might address this problem using only visual cues, we recorded from their wide-field motion sensitive neurons. We found these differ strongly in the ways they respond to sustained motion, allowing them collectively to encode the very broad range of velocities experienced during diverse behaviour.
Glucose and C-Peptide Changes in the Perionset Period of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1
Authors: Jay M. Sosenko, Jerry P. Palmer, Lisa Rafkin-Mervis, Jeffrey P. Krischer, David Cuthbertson, Della Matheson, Jay S. Skyler
Journal: Diabetes Care (2008)

OBJECTIVE—We examined metabolic changes in the period immediately after the diagnosis of type 1 diabetes and in the period leading up to its diagnosis in Diabetes Prevention Trial–Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS—The study included oral insulin trial participants and parenteral insulin trial control subjects (n = 63) in whom diabetes was diagnosed by a 2-h diabetic oral glucose tolerance test (OGTT) that was confirmed by another diabetic OGTT within 3 months. Differences in glucose and C-peptide levels between the OGTTs were assessed. RESULTS—Glucose levels increased at 90 (P = 0.006) and 120 min (P &amp;lt; 0.001) from the initial diabetic OGTT to the confirmatory diabetic OGTT (mean ± SD interval 5.5 ± 2.8 weeks). Peak C-peptide levels fell substantially between the OGTTs (median change −14.3%, P &amp;lt; 0.001). Among the 55 individuals whose last nondiabetic OGTT was ∼6 months before the initial diabetic OGTT, peak C-peptide levels decreased between these two OGTTs (median change −14.0%, P = 0.052). Among those same individuals the median change in peak C-peptide levels from the last normal OGTT to the confirmatory OGTT (interval 7.5 ± 1.3 months) was −23.8% (P &amp;lt; 0.001). Median rates of change in peak C-peptide levels were 0.00 ng · ml−1 · month−1 (P = 0.468, n = 36) from ∼12 to 6 months before diagnosis, −0.10 ng · ml−1 · month−1 (P = 0.059, n = 55) from 6 months before diagnosis to diagnosis, and −0.43 ng · ml−1 · month−1 (P = 0.002, n = 63) from the initial diabetic OGTT to the confirmatory diabetic OGTT. CONCLUSIONS—It seems that postchallenge C-peptide levels begin to decrease appreciably in the 6 months before diagnosis and decrease even more rapidly within 3 months after diagnosis.
THE PATHOGENESIS AND PATHOLOGY OF EXPERIMENTAL TYPE I PNEUMOCOCCIC PNEUMONIA IN THE MONKEY
Authors: Clayton G. Loosli
Journal: The Journal of Experimental Medicine (1942)

The pathogenesis of lobar consolidation and microscopic pathology of induced Type I pneumococcic pneumonia in a series of fourteen monkeys, killed at close intervals of time after infection, have been studied. The inflammatory process which resulted in consolidation was primarily intraalveolar and intrabronchial. The pneumococci spread within the air spaces as a result of the dissemination of the infected edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspiration during breathing. The pneumonic process within the air spaces developed and progressed independently of the reaction in the interstitial tissues. The organisms spread to the interstitial tissue secondarily from the alveolar spaces. Once in the interstitial tissues they appeared to be the important source of infection producing bacteremia but not important in the mechanism by which consolidation was produced. The exudate cells came chiefly from the blood. The large mononuclear cells which replaced the polymorphonuclear leucocytes were derived principally from the hypertrophy and transformation of lymphocytes and monocytes into macrophages after they entered the exudate in the early stages of the disease. The part the local septal cells played as the source of the macrophages could not be accurately determined. The reaction of the septal cells appeared to be chiefly one of swelling without detachment and occasional proliferation to form binucleated attached cells. To follow the transformation of the hematogenous mononuclear cells into macrophages in the exudate, the inflammatory reaction must be examined at frequent intervals during the first 36 hours of the disease. The similarity of the pathogenesis of lobar consolidation in human pneumonia to that observed in the experimentally induced disease in monkeys and dogs was discussed.
Blockade of MMP14 Activity in Murine Breast Carcinomas: Implications for Macrophages, Vessels, and Radiotherapy
Authors: Eleanor I. Ager, Sergey V. Kozin, Nathaniel D. Kirkpatrick, Giorgio Seano, David P. Kodack, Vasileios Askoxylakis, Yuhui Huang, Shom Goel, Matija Snuderl, Alona Muzikansky, Dianne M. Finkelstein, Daniel T. Dransfield, Laetitia Devy, Yves Boucher, Dai Fukumura, Rakesh K. Jain
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Matrix metalloproteinase (MMP) 14 may mediate tumor progression through vascular and immune-modulatory effects.
Erythroid Inhibition by the Leukemic Fusion AML1-ETO Is Associated with Impaired Acetylation of the Major Erythroid Transcription Factor GATA-1
Authors: Youngjin Choi, Kamaleldin E. Elagib, Lorrie L. Delehanty, Adam N. Goldfarb
Journal: Cancer Research (2006)

Abstract Human acute myeloid leukemias with the t(8;21) translocation express the AML1-ETO fusion protein in the hematopoietic stem cell compartment and show impairment in erythroid differentiation. This clinical finding is reproduced in multiple murine and cell culture model systems in which AML1-ETO specifically interferes with erythroid maturation. Using purified normal human early hematopoietic progenitor cells, we find that AML1-ETO impedes the earliest discernable steps of erythroid lineage commitment. Correspondingly, GATA-1, a central transcriptional regulator of erythroid differentiation, undergoes repression by AML1-ETO in a nonconventional histone deacetylase–independent manner. In particular, GATA-1 acetylation by its transcriptional coactivator, p300/CBP, a critical regulatory step in programming erythroid development, is efficiently blocked by AML1-ETO. Fusion of a heterologous E1A coactivator recruitment module to GATA-1 overrides the inhibitory effects of AML1-ETO on GATA-1 acetylation and transactivation. Furthermore, the E1A-GATA-1 fusion, but not wild-type GATA-1, rescues erythroid lineage commitment in primary human progenitors expressing AML1-ETO. These results ascribe a novel repressive mechanism to AML1-ETO, blockade of GATA-1 acetylation, which correlates with its inhibitory effects on primary erythroid lineage commitment. (Cancer Res 2006; 66(6): 2990-96)
Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia
Authors: ANDREW H. HENDERSON, ALBERT S. MOST, WILLIAM W. PARMLEY, RICHARD GORLIN, EDMUND H. SONNENBLICK
Journal: Circulation Research (1970)

Rat papillary muscles were used to study the influence of glucose (5 m M ), linoleate (1 to 1.75 m M ), octanoate (0.5 to 1.75 m M ) and pent-4-enoic acid (1 to 5 m M ) on mechanical performance under oxygenated, hypoxic and anoxic conditions. The buffer solution contained 0.3 m M albumin. Free fatty acids (FFA) (1.0 to 1.75 m M ) did not alter mechanical performance under oxygenated conditions. During hypoxia or anoxia, FFA (0.5 to 1.75 m M ) depressed contractility and increased resting force; glucose improved mechanical performance and modified the depressant effects of FFA. The depressant effect of the nonmetabolized FFA, pentenoic acid, was similar to that of other FFA. This suggests that the effect was mediated directly by FFA or acyl CoA derivatives rather than their metabolic products, and that it might be due to a detergent effect or calcium binding by FFA present in excess of intracellular FFA binding capacity at low pH. Force development during anoxia could be augmented by calcium, implying that the reduced ability of the myofilaments to contract could not be attributed entirely to a reduction of high energy stores.
Let there be light! Lighting levels for dermatological examination
Authors: I. Coltart, G. Lewis, D. Taylor, S. Burge
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, Good lighting is fundamental for clinical examination. Ideally skin should be examined in daylight1 but if this is not possible patients should be examined under bright artificial lighting with a spectrum approaching that of natural sunlight. The Chartered Institution of Building Services Engineers building standards for artificial illumination that are used by most U.K. hospitals do not specify the lighting required for examination of the skin.2 However, German Standard DIN 5035 recommends a general light intensity of 500 lx and examination lighting of more than 1000 lx for dermatological examination.3 We have compared lighting in clinical areas with the ideal of bright sunlight and with the German Standard DIN 5035 recommended for dermatological examination. Light intensity measurements were made using a luxmeter (Stock No. 610‐815; RS Components Ltd, Corby, Northamptonshire, U.K.). Measurements were taken at beds in the Accident and Emergency (A&E) Department (near windows and internal bays), six medical wards (near windows and internal bays), the medical outpatient clinic (two rooms) and the dermatology outpatient clinic (three rooms) (total = 64 beds or outpatient examination couches).
Anti–Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials
Authors: Andrea Willer, Joachim Gerß, Thorsten König, Dieter Franke, Hans-Jürgen Kühnel, Günter Henze, Arendt von Stackelberg, Anja Möricke, Martin Schrappe, Joachim Boos, Claudia Lanvers-Kaminsky
Journal: Blood (2011)
Effect of heliox breathing on flow limitation in chronic heart failure patients
Authors: M. Pecchiari, T. Anagnostakos, E. D'Angelo, C. Roussos, S. Nanas, A. Koutsoukou
Journal: European Respiratory Journal (2009)

Patients with chronic heart failure (CHF) exhibit orthopnoea and tidal expiratory flow limitation in the supine position. It is not known whether the flow-limiting segment occurs in the peripheral or central part of the tracheobronchial tree. The location of the flow-limiting segment can be inferred from the effects of heliox (80% helium/20% oxygen) administration. If maximal expiratory flow increases with this low-density mixture, the choke point should be located in the central airways, where the wave-speed mechanism dominates. If the choke point were located in the peripheral airways, where maximal flow is limited by a viscous mechanism, heliox should have no effect on flow limitation and dynamic hyperinflation. Tidal expiratory flow limitation, dynamic hyperinflation and breathing pattern were assessed in 14 stable CHF patients during air and heliox breathing at rest in the sitting and supine position. No patient was flow-limited in the sitting position. In the supine posture, eight patients exhibited tidal expiratory flow limitation on air. Heliox had no effect on flow limitation and dynamic hyperinflation and only minor effects on the breathing pattern. The lack of density dependence of maximal expiratory flow implies that, in CHF patients, the choke point is located in the peripheral airways.
FTY720, a Synthetic Sphingosine 1 Phosphate Analogue, Inhibits Development of Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Jerzy-Roch Nofer, Martine Bot, Martin Brodde, Paul J. Taylor, Paul Salm, Volker Brinkmann, Theo van Berkel, Gerd Assmann, Erik A.L. Biessen
Journal: Circulation (2007)

Background— Numerous in vitro studies suggest that sphingosine 1-phosphate (S1P), a bioactive lysosphingolipid associated with high-density lipoproteins, accounts at least partly for the potent antiinflammatory properties of high-density lipoprotein and, thereby, contributes to the antiatherogenic potential attributed to high-density lipoproteins. The present study was undertaken to investigate whether modulation of S1P signaling would affect atherosclerosis in a murine model of disease. Methods and Results— Low-density lipoprotein receptor–deficient mice on a cholesterol-rich diet were given FTY720, a synthetic S1P analogue, at low (0.04 mg/kg per day) or high (0.4 mg/kg per day) doses for 16 weeks. FTY720 dose-dependently reduced atherosclerotic lesion formation, both in the aortic root and brachiocephalic artery, and almost completely blunted necrotic core formation. Plasma lipids remained unchanged during the course of FTY720 treatment. However, FTY720 lowered blood lymphocyte count (at a high dose) and significantly interfered with lymphocyte function, as evidenced by reduced splenocyte proliferation and interferon-γ levels in plasma. Plasma concentrations of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-6, IL-12, and regulated on activation normal T cell expressed and secreted were reduced by FTY720 administration. Moreover, lipopolysaccharide-elicited generation of nitrite/nitrate and IL-6—two markers of classical (M1) macrophage activation—was inhibited, whereas IL-4–induced production of IL-1–receptor antagonist, a marker of alternative (M2) macrophage activation, was augmented in peritoneal macrophages from FTY720-treated low-density lipoprotein receptor–deficient mice. Conclusions— The present results demonstrate that an S1P analogue inhibits atherosclerosis by modulating lymphocyte and macrophage function, and these results are consistent with the notion that S1P contributes to the antiatherogenic potential of high-density lipoprotein.
Spontaneous release of angiotensin converting enzyme and interleukin 1 beta from peripheral blood monocytes from patients with rheumatoid arthritis under a serum free condition.
Authors: M Goto, M Fujisawa, A Yamada, T Okabe, F Takaku, M Sasano, K Nishioka
Journal: Annals of the Rheumatic Diseases (1990)

Angiotensin converting enzyme (ACE) and interleukin 1 activities were assayed simultaneously in the serum free medium from the unstimulated peripheral blood monocytes from 32 patients with rheumatoid arthritis (RA), 11 patients with osteoarthritis, and 25 normal controls matched for age and sex. Angiotensin converting enzyme activity was raised in most (29/32) patients with RA and interleukin 1 activity (most of which was interleukin 1 beta) was enhanced in 11/32 patients with RA, while monocytes from only two patients with osteoarthritis, but from none of the controls, secreted a small amount of ACE alone in the culture condition. Monocytes from patients with early RA (disease duration less than 3 years) released significantly more ACE and interleukin 1 than those from late stage RA (disease duration greater than or equal to 3 years).
K-Ras Promotes Growth Transformation and Invasion of Immortalized Human Pancreatic Cells by Raf and Phosphatidylinositol 3-Kinase Signaling
Authors: Paul M. Campbell, Angela L. Groehler, Kwang M. Lee, Michel M. Ouellette, Vladimir Khazak, Channing J. Der
Journal: Cancer Research (2007)

Abstract Mutational activation of the K-Ras oncogene is well established as a key genetic step in the development and growth of pancreatic adenocarcinomas. However, the mechanism by which aberrant Ras signaling promotes uncontrolled pancreatic tumor cell growth remains to be fully elucidated. The recent use of primary human cells to study Ras-mediated oncogenesis provides important model cell systems to dissect this mechanism. We have used a model of telomerase-immortalized human pancreatic duct-derived cells (E6/E7/st) to study mechanisms of Ras growth transformation. First, we found that human papillomavirus E6 and E7 oncogenes, which block the function of the p53 and Rb tumor suppressors, respectively, and SV40 small t antigen were required to allow mutant K-Ras(12D) growth transformation. Second, K-Ras(12D) caused growth transformation in vitro, including enhanced growth rate and loss of density dependency for growth, anchorage independence, and invasion through reconstituted basement membrane proteins, and tumorigenic transformation in vivo. Third, we determined that the Raf, phosphatidylinositol 3-kinase (PI3K), and Ral guanine nucleotide exchange factor effector pathways were activated, although extracellular signal-regulated kinase (ERK) activity was not up-regulated persistently. Finally, pharmacologic inhibition of Raf/mitogen-activated protein kinase/ERK and PI3K signaling impaired K-Ras–induced anchorage-independent growth and invasion. In summary, our studies established, characterized, and validated E6/E7/st cells for the study of Ras-induced oncogenesis. [Cancer Res 2007;67(5):2098–106]
Mouse genetics provides insight into folliculogenesis, fertilization and early embryonic development
Authors: A. Amleh
Journal: Human Reproduction Update (2002)

After colonization of the gonad, mouse female germ cells enter into the prophase of the first meiotic division as a mid-gestational hallmark of gender. Perinatally, oocytes interact with granulosa cells to form primordial follicles which, with cyclic periodicity, enter into a 3-week growth phase that culminates in meiotic maturation and ovulation. Successful fertilization in the oviduct results in the onset of embryogenesis. Genes expressed in oocytes encode maternal factors that control many of these developmental processes. The establishment of mouse models in which specific genes have been disrupted offers robust insights into molecular mechanisms that control oogenesis, folliculogenesis, fertilization and early embryogenesis. Although relatively few developmental circuits have been characterized in genetic detail, the ongoing revolution in mouse genetics holds great promise. These model systems provide novel information into the molecular basis of the pathways required for oocyte-specific processes as well as for interactions with the temporally changing environment of female germ cells. The similarities between the mouse and human genomes provide assurance that this knowledge will rapidly translate into a better understanding of human reproduction.
Cardiomyocyte Cell Cycle Regulation
Authors: Kishore B.S. Pasumarthi, Loren J. Field
Journal: Circulation Research (2002)

Although rapid progress is being made in many areas of molecular cardiology, issues pertaining to the origins of heart-forming cells, the mechanisms responsible for cardiogenic induction, and the pathways that regulate cardiomyocyte proliferation during embryonic and adult life remain unanswered. In the present study, we review approaches and studies that have shed some light on cardiomyocyte cell cycle regulation. For reference, an initial description of cardiomyogenic induction and morphogenesis is provided, which is followed by a summary of published cell cycle analyses during these stages of cardiac ontology. A review of studies examining cardiomyocyte cell cycle analysis and de novo cardiomyogenic induction in the adult heart is then presented. Finally, studies in which cardiomyocyte cell cycle activity was experimentally manipulated in vitro and in vivo are reviewed. It is hoped that this compilation will serve to stimulate thought and experimentation in this intriguing area of cardiomyocyte cell biology.
Low Plasma Adiponectin Levels and Risk of Colorectal Cancer in Men: A Prospective Study
Authors: Esther K. Wei, Edward Giovannucci, Charles S. Fuchs, Walter C. Willett, Christos S. Mantzoros
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Adiponectin is an insulin-sensitizing hormone secreted by adipocytes. Levels of adiponectin are inversely associated with adiposity and insulin resistance. Because both adiposity and insulin resistance have been associated with risk of colorectal cancer, we hypothesized that adiponectin is associated with colorectal carcinogenesis. Methods: We evaluated the association between adiponectin and colorectal cancer among 18 225 men in the Health Professionals Follow-up Study who provided blood samples in 1994. Between blood collection and January 31, 2002, 179 incident colorectal cancer cases occurred. Each case patient was matched to two control subjects on year of birth and date of blood draw. Information on lifestyle factors and diet was collected using biennial questionnaires and food frequency questionnaires. Logistic regression models were used to estimate relative risks (RRs) and confidence intervals (CIs). All statistical tests were two-sided. Results: We observed a statistically significant inverse association between plasma adiponectin levels and risk of colorectal cancer (for the highest quintile [Q5] versus the lowest quintile [Q1], RR = 0.42, 95% CI = 0.23 to 0.78; Ptrend = .01). The association was only slightly attenuated after adjustment for body mass index (Q5 versus Q1, RR = 0.48, 95% CI = 0.25 to 0.90; Ptrend = .04) or for body mass index and other major risk factors for colorectal cancer (family history, physical activity, multivitamin use, smoking, alcohol, aspirin use, history of endoscopy, dietary calcium, folate, vitamin E, and vitamin D; Q5 versus Q1, multivariable RR = 0.50, 95% CI = 0.26 to 0.97; Ptrend = .08). Relative risks were not linear in any of the analyses; the second quintile had a lower relative risk than the lowest quintile, but further decreases in risk were not evident with increasing levels of adiponectin. Conclusions: In this prospective nested case–control study, men with low plasma adiponectin levels had a higher risk of colorectal cancer than men with higher levels. More prospective observational studies, particularly in women, and mechanistic studies are required to fully understand the relationship between adiponectin and carcinogenesis.