tbuckley/cabot-search huggingface dataset:
SCL/TAL1 Regulates Hematopoietic Specification From Human Embryonic Stem Cells
Authors: Pedro J Real, Gertrudis Ligero, Veronica Ayllon, Veronica Ramos-Mejia, Clara Bueno, Ivan Gutierrez-Aranda, Oscar Navarro-Montero, Majlinda Lako, Pablo Menendez
Journal: Molecular Therapy (2012)

Determining the molecular regulators/pathways responsible for the specification of human embryonic stem cells (hESCs) into hematopoietic precursors has far-reaching implications for potential cell therapies and disease modeling. Mouse models lacking SCL/TAL1 (stem cell leukemia/T-cell acute lymphocytic leukemia 1) do not survive beyond early embryogenesis because of complete absence of hematopoiesis, indicating that SCL is a master early hematopoietic regulator. SCL is commonly found rearranged in human leukemias. However, there is barely information on the role of SCL on human embryonic hematopoietic development. Differentiation and sorting assays show that endogenous SCL expression parallels hematopoietic specification of hESCs and that SCL is specifically expressed in hematoendothelial progenitors (CD45(-)CD31(+)CD34(+)) and, to a lesser extent, on CD45(+) hematopoietic cells. Enforced expression of SCL in hESCs accelerates the emergence of hematoendothelial progenitors and robustly promotes subsequent differentiation into primitive (CD34(+)CD45(+)) and total (CD45(+)) blood cells with higher clonogenic potential. Short-hairpin RNA-based silencing of endogenous SCL abrogates hematopoietic specification of hESCs, confirming the early hematopoiesis-promoting effect of SCL. Unfortunately, SCL expression on its own is not sufficient to confer in vivo engraftment to hESC-derived hematopoietic cells, suggesting that additional yet undefined master regulators are required to orchestrate the stepwise hematopoietic developmental process leading to the generation of definitive in vivo functional hematopoiesis from hESCs.
Novel endoscopic hemostasis technique for use during endoscopic submucosal dissection
Authors: S. Enomoto, N. Yahagi, M. Fujishiro, M. Oka, N. Kakushima, M. Iguchi, K. Yanaoka, K. Arii, H. Tamai, Y. Shimizu, M. Omata, M. Ichinose
Journal: Endoscopy (2007)

Endoscopic mucosal resection techniques have now evolved to include endoscopic submucosal dissection [1-3]. Although this technique enables larger tumors to be resected en bloc with adequate margins, a high complication rate due to bleeding, especially arterial bleeding, has become apparent [4]. In a considerable number of cases of bleeding that occur during endoscopic submucosal dissection the bleeding source cannot be identified because of a blood-filled field. The hemostatic method used during endoscopic submucosal dissection should secure a sufficient visual field to see the bleeding lesion, should be easy to perform, and should be capable of reliably stopping arterial bleeding. With these requirements in mind, we have developed a method of endoscopic hemostasis for use during endoscopic submucosal dissection that consists of high-frequency hemostatic forceps (HDB2422W; Pentax, Tokyo, Japan) (Figure [1 a]) and an endoscope equipped with a water-jet system (Pentax EG-2931/SA-P2) (Figure [1 b]).
Plasma concentration of coupling factor 6 and cardiovascular events in patients with end-stage renal disease
Authors: Tomohiro Osanai, Masayuki Nakamura, Satoko Sasaki, Hirofumi Tomita, Masayuki Saitoh, Hiroshi Osawa, Hideaki Yamabe, Shuichi Murakami, Koji Magota, K.E.N. Okumura
Journal: Kidney International (2003)
Maintenance and break of immune tolerance against human factor VIII in a new transgenic hemophilic mouse model
Authors: Pauline M. van Helden, Sabine Unterthurner, Corinna Hermann, Maria Schuster, Rafi U. Ahmad, Alexandra N. Schiviz, Markus Weiller, Gerhard Antoine, Peter L. Turecek, Eva M. Muchitsch, Hans Peter Schwarz, Birgit M. Reipert
Journal: Blood (2011)
Southall appeals to overturn GMC's rulings against him
Authors: C. Dyer
Journal: BMJ (2009)

Lawyers for the paediatrician David Southall this week accused the General Medical Council of reversing the burden of proof and requiring him to prove his innocence, as he launched a High Court appeal against a finding of serious professional misconduct.

In a four day hearing that began on Tuesday 31 March Dr Southall is appealing against a GMC fitness to practise panel’s findings of fact, the misconduct ruling, and a decision to strike him off the medical register.

The fitness to practise panel, which had a lay majority, ruled in December 2007 that he had inappropriately accused a mother of murdering her child, kept “special case files” on …
Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery.
Authors: F F Weidinger, J M McLenachan, M I Cybulsky, J T Fallon, N K Hollenberg, J P Cooke, P Ganz
Journal: Circulation (1991)

BACKGROUND We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity. METHODS AND RESULTS New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone. CONCLUSIONS The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.
Language Barriers in Medicine
Authors: Thomas W. Chapman
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Woloshin and colleagues<sup>1</sup>are to be commended for advancing dialogue on language barriers. However, language barriers are just the apex of the complex social and cultural barriers that prevent people from obtaining the health care they need and deserve. As the United States grapples with immigrant, refugee, race, and class issues, rapidly changing demographics have revealed the present health care system to be out of step with the reality of values, history, and cultural or social complexity within communities. Opening Doors, a grant initiative jointly sponsored by the Robert Wood Johnson Foundation and the Henry J. Kaiser Family Foundation, supports replicable solutions to reduce sociocultural barriers to health care. One of our grantees, Asian Health Services, is implementing a language and cultural cooperative that will provide interpreters (skilled in cultural and linguistic telephone interpretation in Cantonese, Vietnamese, and Spanish) to area health care providers to
A dose-finding and pharmacokinetic study of I.V. vinflunine in combination with doxorubicin as first line treatment of metastatic breast cancer.
Authors: J Machiels, P Chollet, A Taleb, J Baurain, Y Humblet, F Mazzeo, K Zaman, F Kasiborski, J Bauer
Journal: Cancer Research (2009)

Abstract Abstract #6124 Background: VFL is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class. In a phase II study in anthracycline and taxane pretreated MBC patients (pts), an ORR of 30% observed. Given activity shown by DXR or VFL in MBC, we conducted a phase I study of the combination, define maximum tolerated dose (MTD), recommended dose (RD), safety (NCI CTC 2.0), PK interaction and efficacy (Recist).&amp;#x2028; Methods: 2 schedules investigated (VFL D1 with DXR D1, every 3 weeks and VFL Ds 1 and 8, with DXR Ds 1 and 8, every 3 weeks). Eligibility: Pts with MBC, previously untreated for metastatic disease; could have received adj/neoadjuvant with anthracycline-containing regimen, cumulative doses &amp;lt; 250 mg/m² for DXR, 450 mg/m² for EPI. Dose escalation used 3+3 design; PK samples were obtained for VFL and DXR to investigate potential interaction.&amp;#x2028; &amp;#x2028; Results: 32 patients were enrolled (15 patients in schedule 1 and 17 in schedule 2) and received escalating doses of VFL and DXR.&amp;#x2028; In schedule 1, 2 dose levels (DL) were investigated; At DL VFL250/DXR50, 8 pts were treated with 6 patients evaluable for DLT, where 2 DLTs were identified consisting of neutropenia &amp;lt; 0.1x109/l &amp;gt; 3 days and a neutropenic infection; then this DL was considered MTD; at the DL VFL250/DXR40, 7 pts were treated without developing DLTs then considered RD. 73 cycles were administered (median 6); Most frequent haematological toxicity was neutropenia, gr 3 in 1 pt and gr 4 in 11 pts. Main non-haematological adverse events were: nausea 80%, fatigue 73.3%, constipation 40%, vomiting 40%, anorexia 33.3%, stomatitis 20%, dyspnea 13.3%. Clinical activity: 7 pts (46.7%) had PR, and 4 pts (26.7%) SD. No PK interaction was detected.&amp;#x2028; In schedule 2, at DL VFL150/DXR25, 6 of 9 pts were evaluable in whom 2 Gr 4 neutropenia &amp;gt; 7 days occurred, (DL considered as MTD). In the DL below VFL120/DXR25, 6 of 8 pts were evaluable, only 1 Gr 4 neutropenia &amp;gt; 7 days occurred, (DL considered RD). A total of 89 cycles (median 6) were administered; neutropenia was the main haematological toxicity, with Gr ¾ in 14 pts (82.4%); main non-haematological toxicities: fatigue 82.4%, constipation 76.5%, nausea 76.5%, vomiting 64.7%, stomatitis 41.2%, dyspnea 41.2%, anorexia 35.3%; no episode of Gr 4 occurred.&amp;#x2028; Among 17 treated pts, 8 (47.1%) had PR and 6 (35.3%) SD. PK analysis ongoing.&amp;#x2028; Conclusion: RD for schedule 1 is VFL250/DXR40 on day 1, Q3W, for schedule 2, VFL120/DXR25 on days 1 and 8, Q3W. Overall VFL/DXR combination is feasible and toxicity was manageable, where haematological toxicity was frequent but reversible. Promising antitumour activity was detected. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6124.
Video illustration of staple gun use to rapidly repair on-field head laceration
Authors: J W Orchard
Journal: British Journal of Sports Medicine (2004)

A professional rugby league player sustained a left eyebrow laceration during a match which immediately started to bleed. Within seconds he was taken to the sideline and had the laceration closed with six staples by the team doctor. Bleeding was arrested and he returned to play, taking the ball within 80 s of suffering the initial laceration, and within 40 s of the stapling procedure. This sequence was captured on video and appeared on television. The staples were removed after the match and the wound sutured. Repair of the wound was uneventful. The staple gun allows bleeding lacerations to be closed within seconds and for players to safely and quickly return to play, whilst minimising the risk of blood-borne infection transmission.
Acquisition of Selectin Binding and Peripheral Homing Properties by CD4+ and CD8+ T Cells
Authors: Huijuan Xie, Yaw-Chyn Lim, Francis W. Luscinskas, Andrew H. Lichtman
Journal: The Journal of Experimental Medicine (1999)

Different T cell subsets exhibit distinct capacities to migrate into peripheral sites of inflammation, and this may in part reflect differential expression of homing receptors and chemokine receptors. Using an adoptive transfer approach, we examined the ability of functionally distinct subsets of T cells to home to a peripheral inflammatory site. The data directly demonstrate the inability of naive T cells and the ability of effector cells to home to inflamed peritoneum. Furthermore, interleukin (IL)-12 directs the differentiation of either CD4+ or CD8+ T cells into effector populations that expresses functional E- and P-selectin ligand and that are preferentially recruited into the inflamed peritoneum compared with T cells differentiated in the presence of IL-4. Recruitment can be blocked by anti–E- and –P-selectin antibodies. The presence of antigen in the peritoneum promotes local proliferation of recruited T cells, and significantly amplifies the Th1 polarization of the lymphocytic infiltrate. Preferential recruitment of Th1 cells into the peritoneum is also seen when cytokine response gene 2 (CRG-2)/interferon γ–inducible protein 10 (IP-10) is used as the sole inflammatory stimulus. We have also found that P-selectin binds only to antigen-specific T cells in draining lymph nodes after immunization, implying that both antigen- and cytokine-mediated signals are required for expression of functional selectin-ligand.
A1.81 Mincle is not essential in T-cell independent arthritis models
Authors: Silvia Hayer, Birgit Niederreiter, Tetyana Shvets, Marije Koenders, Wim van den Berg, Josef Smolen, Kurt Redlich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> C-type lectin receptor Mincle (also known as Clecsf9, Clec4e) is expressed by monocytes, macrophages and dendritic cells and involved in immune response to various infections. Recent reports showed elevated levels of Mincle in synovial fluid and PBMCs from RA patients and a linkage of Mincle polymorphisms to lower susceptibility of RA in humans (GuoJP et al 2011;Wu X. Y et al 2012). <h3>Objectives</h3> (I) To assess the expression of Mincle in inflamed paws in experimental arthritis. (II) To investigate the role of mincle deficiency in the pathogenesis of inflammatory, erosive arthritis by investigating mincle<sup>-/-</sup> mice in human tumor necrosis factor transgenic (hTNFtg) arthritis model and the K/BxN serum transfer model. <h3>Methods</h3> Expression levels of Mincle mRNA was determined in inflamed paws from hTNFtg and IL1<sup>-/-</sup>IL6<sup>-/-</sup>hTNFtg mice by qPCR. To study the role of mincle deficiency in experimental arthritis, we generated mincle<sup>-/-</sup>hTNFtg mice as well as their hTNFtg littermates. Mice were weekly assessed for clinical signs of arthritis from week 4 to 11 after birth. We quantitatively analysed inflammatory joint destruction in H&amp;E, TRAP and TB stained sections from hind paws. The effect of mincledeficiency was also evaluated in the K/BxN serum transfer model. Therefore, <i>mincle<sup>-/-</sup></i> and <i>mincle<sup>+/+</sup></i> mice received i.v. injections of K/BxN serum on day 1 and day 3. Animals were assessed from day1 to 12 for clinical signs of arthritis. Quantitative histopathological analysis were performed as above mentioned in hind paws. <h3>Results</h3> We found elevated mRNA expression levels of mincle in paw extracts from hTNFtg mice and reduced levels in <i>IL1<sup>-/-</sup>IL6<sup>-/-</sup></i>hTNFtg mice. However, by generating <i>mincle<sup>-/-</sup></i>hTNFtg mice, we found no marked difference in clinical course of arthritis compared to their hTNFtg littermates from week 5 to week 11 after birth. Moreover, histological analysis revealed similar extends in synovial inflammation, subchondral bone erosions and cartilage damage indicating that mincle is not essentially involved in the pathogenesis of TNF-mediated inflammatory, erosive arthritis. In addition, the transfer of K/BxN serum into <i>mincle<sup>-/-</sup></i> animals revealed no significant difference in clinical signs compared to their <i>mincle<sup>+/+</sup></i> littermates. Likewise, we found no marked difference in the extend of synovial inflammation, bone and cartilage destruction in hind paws between <i>mincle<sup>-/-</sup></i> and <i>mincle<sup>+/+</sup></i> animals. <h3>Conclusion</h3> Lacking of C-type lectin receptor mincle does not modulate the pathogenesis of T-cell independent, innate immunity driven arthritis models indicating that mincle is not essentially involved in innate immune responses in the pathogenesis of rheumatoid arthritis.
Turning the Tables on Probe Pressures—Go With the Flow, Abandon the Scan?-Reply
Authors: Louis R. Caplan
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Fluke is correct. Transcranial Doppler probes measure blood velocities and not pressures as my recent review of this subject stated.<sup>1</sup>I thank him for pointing out the error in the figure caption. In my article on stroke, I shared with<i>JAMA</i>readers my present management rules. The rationale for using anticoagulants has been elaborated on elsewhere in more detail.<sup>2,3</sup>I use heparin-warfarin anticoagulation for some vascular lesions, short term for acute thrombotic oculusions of large arteries, and longer term for cardiogenic embolism and severe flow-reducing stenosis of large arteries. In patients with acute ischemia in either circulation, I often use heparin acutely (when not contraindicated medically) until the cause of the ischemia has been clarified. Unfortunately, the use of anticoagulants or any other treatments for these indications has not been tested scientifically.<sup>4</sup>There are no data that support or refute these uses, so clinicians
An alternative to QALYs: the saved young life equivalent (SAVE)
Authors: E. Nord
Journal: BMJ (1992)

An alternative to QALYs: the saved young life equivalent (SAVE) Erik Nord Quality adjusted life years (QALYs) are based on the concept that the effectiveness of a health care pro- gramme is greater the more significant the health improvements it provides, the longer the patients get to enjoy the improvements, and the more patients who are helped.'`4The concept is put into practice in the so called health status index approach: life years in different states of illness or dysfunction are assigned values on a scale of 1-0 (healthy) to 0.0 (dead).The values reflect the quality of the states and allow morbidity and mortality improvements to be combined into a single weighted measure-that is, QALYs gained.For example, if a programme improves the health of individual A from 0 5 to 0 8 for one year and extends the life of individual B for five years in a 0-6 state, then a total of 3-3 QALYs will be gained ((0 8-0 5)+(5OxO6)=3 3).Cost per QALY gained (the so called "cost:utility ratio") may be calculated for different programmes.When prioritising between them the standard health economist recommendation is to rank the programmes from the lowest cost per QALY value to the highest and to select from the top until available resources are exhausted.'6 This paper argues that the health status index approach and the focusing on life years as units of measurement are main causes of public resentment against QALYs.7-'3A more direct procedure is outlined for assessing the social value of health care.Like QALYs it allows comparisons of different health care programmes in terms of cost:utility ratios.
Erythropoiesis in the anemia of bone marrow failure
Authors: Raymond Alexanian, Clarence Alfrey
Journal: Journal of Clinical Investigation (1970)

The quantitative relationship between red cell volume, erythropoietin level, and erythropoiesis was evaluated in 43 human beings. Results in normal man were compared with studies in patients with anemia from bone marrow failure and with polycythemia vera. The maximum erythropoietin excretion after bleeding normal men was similar to the basal levels found in patients with chronic anemia of similar magnitude. Although erythropoietin values were low in patients with polycythemia vera, bleeding evoked a normal response. In patients anemic from bone marrow failure, basal levels were elevated, and phlebotomy resulted in an increase consistent with the new level of anemia. These observations indicate that erythropoietin level is affected primarily by the degree of anemia and is not influenced by the duration of anemia. In normal subjects, a fivefold increase in urinary erythropoietin was associated with a doubling of erythropoiesis. Despite similar degrees of erythropoietin production, anemic patients with evidence of bone marrow in the lower extremities had greater red cell production. In patients with polycythemia vera, red cell production was inappropriately elevated with regard to the urinary erythropoietin excretion. Bone marrow maturation time was not shortened in patients anemic from bone marrow failure to the same degree as in bled, normal volunteers. In addition to an adequate level of erythropoietin production, normal bone marrow function is necessary for maximal shortening of maturation time.
The Cheshire cat phenomenon: effects of nonionizing electromagnetic radiation.
Authors: G Pinholster
Journal: Environmental Health Perspectives (1993)

Charles Graham exposes people to electric and magnetic fields, then tries to make sense of their seemingly nonsensical physio- logical responses."It's a very curious thing," Graham says, pondering what is known thus far about whether low-level electric and magnetic fields make people sick."In a sense, it's an incredible puzzle to solve, and many people are going at it in different ways."Graham's work and other studies could ultimately help solve the puzzle, revealing the relationship between peo- ple and the invisible force that surrounds us -the energy fields created by nonionizing electro- magnetic radiation.tainty.Like Alice in Wonderland, wandering through a surreal world of grinning cats and finding it "curiouser and curiouser" Graham and others investigating the possi- ble health effects of nonionizing electromagnetic radiation" (NIEMR) often find themselves in an uncharted world that's full of surprises.In analyzing physiological responses to electric and magnetic fields, contradictory findings are commonplace,