tbuckley/cabot-search huggingface dataset:
STAT3 silencing inhibits glioma single cell infiltration and tumor growth
Authors: M. Priester, E. Copanaki, V. Vafaizadeh, S. Hensel, C. Bernreuther, M. Glatzel, V. Seifert, B. Groner, D. Kogel, J. Weissenberger
Journal: Neuro-Oncology (2013)

Diffuse infiltration remains the fulcrum of glioblastoma's incurability, leading inevitably to recurrence. Therefore, uncovering the pathological mechanism is imperative. Because signal transducer and activator of transcription 3 (STAT3) correlates with glioma malignancy and predicts poor clinical outcome, we determined its role in glioma single cell infiltration and tumor growth. STAT3 was silenced in Tu-2449 glioma cells via lentiviral gene transfer. Target gene expression was measured by real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Microvilli were visualized by staining with wheat germ agglutinin. Migration and invasion were measured by Scratch and Matrigel chamber assays. Diffuse infiltration was studied in 350-μm-thick organotypic tissue cultures over 14 days using cells tagged with enhanced green fluorescent protein and live confocal laser scanning microscopy. Survival of tumor-bearing syngeneic, immunocompetent B6C3F1 mice was analyzed by Kaplan–Meier plots. STAT3 silencing reduced cell migration and invasion in vitro and stopped single cell infiltration ex vivo, while STAT3-expressing cells disseminated through the neuropil at ∼100 µm/day. STAT3 silencing reduced transcription of several tumor progression genes. Mice with intracranial STAT3 knockdown tumors had a significant (P< .0007) survival advantage over controls, yielding 27% long-term survival. STAT3 knockdown reduced podoplanin expression 50-fold and inhibited concurrent microvilli formation. STAT3 knockdown tumors exhibited a weaker podoplanin immunoreactivity compared with controls. Podoplanin staining was diffuse, preferentially at tumor margins, and absent in normal brain. Our results show compelling evidence that STAT3 is a key driver of diffuse infiltration and glioma growth and might therefore represent a promising target for an anti-invasive therapy.
Cardiomyocyte cell cycle control and growth estimation in vivo—an analysis based on cardiomyocyte nuclei
Authors: Stuart Walsh, Annica Pontén, Bernd K. Fleischmann, Stefan Jovinge
Journal: Cardiovascular Research (2010)

Adult mammalian cardiomyocytes are traditionally viewed as being permanently withdrawn from the cell cycle. Whereas some groups have reported none, others have reported extensive mitosis in adult myocardium under steady-state conditions. Recently, a highly specific assay of 14C dating in humans has suggested a continuous generation of cardiomyocytes in the adult, albeit at a very low rate. Mice represent the most commonly used animal model for these studies, but their short lifespan makes them unsuitable for 14C studies. Herein, we investigate the cellular growth pattern for murine cardiomyocyte growth under steady-state conditions, addressed with new analytical and technical strategies, and we furthermore relate this to gene expression patterns. The observed levels of DNA synthesis in early life were associated with cardiomyocyte proliferation. Mitosis was prolonged into early life, longer than the most conservative previous estimates. DNA synthesis in neonatal life was attributable to bi-nucleation, therefore suggesting that cardiomyocytes withdraw from the cell cycle shortly after birth. No cell cycle activity was observed in adult cardiomyocytes and significant polyploidy was observed in cardiomyocyte nuclei. Gene analyses identified 32 genes whose expression was predicted to be particular to day 3–4 neonatal myocytes, compared with embryonic or adult cells. These cell cycle-associated genes are crucial to the understanding of the mechanisms of bi-nucleation and physiological cellular growth in the neonatal period.
Variation in the attitudes of dialysis unit medical directors toward decisions to withhold and withdraw dialysis.
Authors: A H Moss, C B Stocking, G A Sachs, M Siegler
Journal: Journal of the American Society of Nephrology (1993)

Increasingly, physicians who treat patients with renal failure are deciding with patients and families whether to withhold or withdraw dialysis. These decisions as well as those concerning whether medical directors of dialysis units felt prepared to make them were studied using three hypothetical scenarios. A questionnaire survey of 524 physician medical directors of adult chronic dialysis units throughout the United States was conducted. They were asked about decisions to withdraw dialysis from a competent patient and a patient with severe dementia, about decisions to withhold dialysis from a permanently unconscious patient, and also about their use of ethics committees to reach these decisions. Three hundred eighteen (61%) responded. Most, 92%, indicated that their units would usually honor a competent patient's request to stop dialysis. There was less agreement about whether to start dialysis in permanently unconscious patients; 83% would withhold dialysis, and 17% would provide it. There was the least agreement about continuing dialysis in patients with dementia; 32% would stop dialysis, and 68% would continue it. Ninety-four percent of medical directors reported that they felt prepared to decide about withholding and withdrawing dialysis. Eighty percent said they might consult a Network ethics committee for difficult decisions. Almost all medical directors of dialysis units believe that they are prepared to make decisions to withhold and withdraw dialysis. Nevertheless, this study revealed significant variation in their attitudes toward these decisions. Practice guidelines and consultation with ethics committees might assist dialysis unit medical directors in making these decisions more uniformly and in a way that promotes patient benefit.
ELECTRON MICROSCOPIC STUDIES ON STREPTOCOCCI
Authors: John Swanson, Konrad C. Hsu, Emil C. Gotschlich
Journal: The Journal of Experimental Medicine (1969)

The presence of M antigens on group A streptococci is associated with hairlike fimbriae that cover the surface of the streptococcal cell wall and are demonstrable by electron microscopy. These fimbriae also may be associated with R antigen. Like M protein, the surface fimbriae are destroyed by trypsin treatment and reappear when "trypsinized" streptococci are reincubated in fresh, trypsin-free broth. Ferritin-conjugated, type-specific antibodies localize on homologous M+ cells in a pattern suggestive of several M antigenic sites along the length of individual surface fimbria. The M-associated fimbriae remain on the residual cell wall after removal of the bulk of group-specific polysaccharide through nitrous acid extraction. This suggests attachment of the fimbriae to the mucopeptide and minor polysaccharide components remaining in the nitrous acid-extracted wall. The pattern of localization of ferritin-conjugated antibodies on homologous streptococci before and after trypsin exposure and upon reincubation of the trypsinized cells in fresh medium suggests the following hypothesis: M antigen is secreted by the cell, is partially excreted through the otherwise intact cell wall, and is bound by the wall so that M protein occupies a peripheral, exposed position on the surfaces of the streptococcal cell wall.
Michael William Wellesley Wood
Authors: John O’Shea
Journal: BMJ (2008)

Michael Wood was probably one of the most highly respected physicians of his time on the Wirral both by colleagues and patients.

He had wanted an appointment in the London area and came to the Wirral as second best. He did not regret his luck, and London’ s loss was the Wirral’s gain.

Born in Birmingham, the son of an engineer, he was educated at Marlborough College, where he played rugby and hockey. He proceeded to Cambridge and then to St Mary’s, where he qualified. His house officer appointment was at hospital in Basingstoke. The second world war interrupted, and he served in the Royal Air Force as a medical officer at the headquarters of the second tactical air force. He then became a medical registrar at St Mary’s and the West Middlesex …
Proliferative Lesions of the Exocrine Pancreas: Relationship to Corn Oil Gavage in the National Toxicology Program
Authors: S L Eustis, G A Boorman
Journal: JNCI Journal of the National Cancer Institute (1985)

A microscopic review of pancreata from corn oil vehicle control and untreated control F344/N male rats in thirty-seven 2-year carcinogenesis studies was conducted to determine the extent and strength of the association of proliferative exocrine pancreatic lesions with corn oil gavage. The incidence of focal basophilic cellular change was similar in both untreated and vehicle control groups and was unrelated to corn oil gavage. The overall incidences of focal acinar hyperplasia and acinar adenoma were about five times greater in male rats that received the corn oil than in untreated rats (12.6 and 4.9% vs. 2.6 and 0.9%). This association was not consistent for each study group of vehicle controls. Over one-third (7/20) of the vehicle control groups had incidences of hyperplasia and adenoma no greater than the average rate for untreated male rats. There was no relationship between incidences of proliferative acinar lesions and the animal laboratory, the animal source, and the brand, lot, or peroxide level of the corn oil. The incidences of focal acinar hyperplasia and acinar adenoma were related to maximum mean body weights attained by the groups during the course of the study.
Control of murine Ly6Chigh monocyte traffic and immunosuppressive activities by atypical chemokine receptor D6
Authors: Benedetta Savino, Marina G. Castor, Nicoletta Caronni, Adelaida Sarukhan, Achille Anselmo, Chiara Buracchi, Federica Benvenuti, Vanessa Pinho, Mauro M. Teixeira, Alberto Mantovani, Massimo Locati, Raffaella Bonecchi
Journal: Blood (2012)
A retrospective study examining thrombolysis for occluded femoro-popliteal grafts – Is it worthwhile?
Authors: C.U. Abraham-Igwe, M.R.S. Siddiqui, L.T. Geddes, J. Halls, A. Irvine, N. Browning
Journal: International Journal of Surgery (2011)

To assess the effectiveness of catheter directed thrombolysis (CDT) in the treatment of acute graft occlusion.Tissue prothrombin activator (rt-PA) was the sole agent used for thrombolysis. This was infused through a 4F straight 65 cm catheter placed under ultrasound guidance. Following a pre-CDT angiogram, a catheter was placed just proximal to the distal anastomosis. An infusion of rt-PA was given over 24 h. An assessment of acute clinical success, limb salvage rates, patency rates and complication rates were made over a period of one year.80% (20/25) of grafts were successfully reopened immediately. 4/5 (80%) of the unsuccessful CDT cases required amputation within a few weeks. 60% (12/20) of successful CDT cases had an underlying stenotic lesion which required angioplasty. Limb salvage rate was 72% (18/25) at 12 months. There was no CDT related mortality. Secondary patency rate at 9 months was 76% (13/17).CDT can achieve reasonable results in this group of challenging patients and may be seen as a useful accessory in the vascular toolkit. However, precise indications for its use need further clarification.
Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women
Authors: J. S. Labus, E. A. Mayer, J. Jarcho, L. A. Kilpatrick, T. O. C. Kilkens, E. A. T. Evers, W. H. Backes, R.-J. M. Brummer, M. A. van Nieuwenhoven
Journal: Gut (2011)

<h3>Objective</h3> Alterations in serotonin signalling within the brain–gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD. <h3>Methods</h3> 12 healthy females (19–25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24–50 years). <h3>Results</h3> In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C. <h3>Conclusions</h3> The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.
PMO-205 Photographic confirmation of complete colonoscopy: Abstract PMO-205 Table 1
Authors: C Subbiah Somasundaram, D Ramanaden, A Baghomian, I Finnie
Journal: Gut (2012)

<h3>Introduction</h3> Establishing intubation of caecum is an important aspect of quality indicator<sup>1</sup> of colonoscopy, BSG recommendation is that photographic and written confirmation of caecal intubation is kept. <h3>Aims</h3> Establishing reliability of photodocumentation of caecum as evidence of caecal intubation in a DGH setting. Reproducibility of findings. <h3>Methods</h3> A retrospective study of 100 consecutive endoscopic (single) caecal photographs documented by eight endoscopists (7 consultants, 1 SPR) were collected onto a spreadsheet. Nine endoscopists then independently scored the photographs anonymously using a range from 1 to 6 as tabulated to determine the strength of the photograph as displaying caecal intubation. Seven photographs were duplicated in sheet 1 and sheet 5 to assess intra-observer reproducibility. <h3>Results</h3> The results were as follows for the first part of the study: Intra observer variablity (numer of sets of pictures with difference in score of more than 1 point) was 5 out of 63 (7.93%) was good, but there was poor agreement between observers. <h3>Conclusion</h3> In 48% of assessments the photograph was assessed as either definitely caecum or likely caecum. These results are higher than found in some previous studies.<sup>2–5</sup> Factors including poor bowel preparation, caecal anatomy, patient tolerance of the procedure can influence the quality of photographs. It would be interesting to know if multiple photographs gave better results. Other methods including video (as opposed to still) photography 6, barium x-rays have also been recommended. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. Systematic quality control programme for colonoscopy in an endoscopy centre in Norway. <i>Tidsskr Nor Laegeforen</i> 2004;<b>124</b>:1402–5. 2. <b>Cirocco WC</b>, Rusin LC. Confirmation of cecal intubation during colonoscopy. Brooklyn, USA: Department of Surgery, S.U.N.Y.-H.S.C.B. 3. The caecum or not the caecum. <i>Eur J Gastroenterol Hepatol</i> 20;20(6):500-2. 4. <b>Thuraisingham AI</b>, Brown JL Anderson JT. What are the sensitivity and specificity of endoscopic photographs in determining completion of colonoscopy? Result from a questionnaire. <i>Eur J Gastroenterol Hepatol</i> 2008;<b>20</b>:567–71. 5. <b>Rex DK</b>. Still photography versus videotaping for documentation of cecal intubation: a prospective study. <i>Gastrointest Endosco</i> 2000;<b>51</b>:451–9. 6. <b>Rex DK</b>. Indiana USA: Division of Gastroenterology/Hepatology. Indiana University School of Medicine.
p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver
Authors: Svitlana Kurinna, Sabrina A. Stratton, Zeynep Coban, Jill M. Schumacher, Markus Grompe, Andrew W. Duncan, Michelle Craig Barton
Journal: Hepatology (2013)

Functions of p53 during mitosis reportedly include prevention of polyploidy and transmission of aberrant chromosomes. However, whether p53 plays these roles during genomic surveillance in vivo and, if so, whether this is done via direct or indirect means remain unknown. The ability of normal, mature hepatocytes to respond to stimuli, reenter the cell cycle, and regenerate liver mass offers an ideal setting to assess mitosis in vivo. In quiescent liver, normally high ploidy levels in adult mice increased with loss of p53. Following partial hepatectomy, p53(-/-) hepatocytes exhibited early entry into the cell cycle and prolonged proliferation with an increased number of polyploid mitoses. Ploidy levels increased during regeneration of both wild-type (WT) and p53(-/-) hepatocytes, but only WT hepatocytes were able to dynamically resolve ploidy levels and return to normal by the end of regeneration. We identified multiple cell cycle and mitotic regulators, including Foxm1, Aurka, Lats2, Plk2, and Plk4, as directly regulated by chromatin interactions of p53 in vivo. Over a time course of regeneration, direct and indirect regulation of expression by p53 is mediated in a gene-specific manner.Our results show that p53 plays a role in mitotic fidelity and ploidy resolution in hepatocytes of normal and regenerative liver.
Combined Screening: Blood Pressure and Cholesterol
Authors: James J. Burke
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The recent letter by Record and Record<sup>1</sup>describing a cholesterol screening program in Maine demonstrates a widespread misunderstanding about testing. Of the 1388 persons who were screened with on-site, finger-prick measurements of cholesterol level, 52% were considered to have values "above goal." Ten percent of these above-goal patients returned for followup cholesterol level testing after dietary counseling. Thirty-two of these 74 patients had reduced their cholesterol level by an average of 7%. The authors conclude that this reduction may translate into a 14% reduction in cardiovascular disease risk. When a group of patients is classified according to measurements, the groups that lie at either of the extremes can be subject to the phenomenon of "regression to the mean" on remeasurement. When remeasured, the mean of the extreme values will move closer to the initial mean of the total population. Much of the observed change noted in
US Institute of Medicine calls for greater commitment to global health
Authors: J. Hopkins Tanne
Journal: BMJ (2008)

The US Institute of Medicine called on the incoming Democratic led administration and the president elect, Barack Obama, to increase funding for global health when setting US foreign policy and to coordinate efforts through a high level committee.

The institute is part of the US National Academies of Science, which advise the nation on science, engineering, and medicine. The study and report were sponsored by leading philanthropic organisations and several government departments. A second report, due to be published in the spring, will contain more detailed recommendations.

Harold Varmus, …
Abstract 2163: Single-site Left Ventricular Apex And Left Ventricular Septal Pacing For Long Term Maintenance Of Cardiac Contractility
Authors: Robert W Mills, Larry J Mulligan, Arne van Hunnik, Marion Kuiper, Anniek Lampert, Nick D Skadsberg, Frank van Wijk, Richard Cornelussen, Frits W Prinzen
Journal: Circulation (2008)

Objective: Conventional right ventricular (RV) apex pacing is associated with asynchronous activation and reduced left ventricular (LV) pump function. Previous studies have shown acute hemodynamic benefits over RV apex pacing by LV septal or LV apex pacing. We investigated whether this improvement translates into a long-term benefit and how acute LV function during single site LV pacing compares to biventricular pacing. Methods: After AV-nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex (n = 7), LV apex (n = 7), or LV mid-septum (n = 8; trans-ventricular septal approach). LV contractility (dP/dt max /P instantaneous ) was measured during normal ventricular conduction from atrial pacing (AP) and during ventricular pacing 1–3 hours and 16 weeks after implant. At 16 weeks, contractility was also measured after an acute switch from the implant site (IS) to the non-implanted apex (both for LV septal group) and to RV apex + LV lateral (BiV) pacing. Results: While acute and chronic RV apex pacing significantly reduced contractility (Figure a ; mean ± SD, *p&lt;0.05 contrasted to 1), LV pacing maintained contractility near AP levels. After 16 weeks of RV apex pacing, switching to LV apex pacing (but not BiV pacing) increased contractility (Figure b ). After 16 weeks of LV pacing, switching to RV apex pacing decreased contractility. Collectively, acute LV apex pacing enhanced contractility over acute BiV (p&lt;.001). Conclusions: Chronic LV apex and LV mid-septal pacing maintain contractility near normal levels, and at a higher level than RV apex pacing. Acutely, LV apex pacing improves contractility compared to BiV pacing.
CHARACTERISTICS OF STREPTOCOCCAL GROUP-SPECIFIC ANTIBODY ISOLATED FROM HYPERIMMUNE RABBITS
Authors: C. Kirk Osterland, Edward J. Miller, Walter W. Karakawa, Richard M. Krause
Journal: The Journal of Experimental Medicine (1966)

Intravenous immunization of New Zealand red rabbits with streptococcal group-specific bacterial vaccines yielded sera which possessed markedly elevated gamma-globulin. The sera of one rabbit immunized with Group A-variant vaccine possessed 55 mg/ml of gamma-globulin. The bulk of this gamma-globulin, identified as gamma(G)-globulin, was homogeneous by zone electrophoresis and of specificity directed against the Group A-variant carbohydrate antigen. L chains isolated from specific antibody obtained from an immune precipitate were distributed as a single band on starch gel electrophoresis, whereas the normal gamma-globulin traveled as a diffuse smear. These data suggest that the rabbit streptococcal Group A-variant antibodies possess a limited range of physicochemical properties and electrophoretic mobility compared to that generally observed for the normal complement of gamma-globulin.