tbuckley/cabot-search huggingface dataset:
East African running dominance: what is behind it?
Authors: Bruce Hamilton
Journal: British Journal of Sports Medicine (2000)

Take home message 

The periodic domination of middle and long distance running by different regions of the world is not a new phenomenon. Researchers are yet to confirm a genetic or physiological advantage in being a middle or long distance runner of East African origin, and it is most likely that the reasons for their success are many. The belief that East African success is due to uncontrollable stable factors will perpetuate the current level of domination. 

East African middle and long distance runners are currently the dominant force in athletics. As well as dominating the track events at the last several Olympic Games, they are also dominant on the American and European road racing circuit and world cross country events. Although many physiological and anatomical factors have been proposed to explain East African dominance, research into these variables has not yet revealed any definitive advantage for the African. Traditional social and cultural factors have often been described as “advantageous”, and, although these factors may be to a greater or lesser extent involved in the East African dominance, it is probable that both the African and caucasian psychology or “mindset” are now additional important factors in maintaining that dominance. Like Scandinavian distance runners in the early 20th century, who won 28 of 36 possible Olympic medals over 5000 and 10 000 m, the East Africans have developed an aura of invincibility, both in their own minds and the minds of their caucasian opponents. Caucasians world wide are searching for proof of the physical advantage of the East Africans while handing them on a platter a psychological advantage which, until removed, will perpetuate the current state.

Many factors have been described to explain both the dominance of East African middle and long distance runners and West African sprinters. Many of these …
Experimental Human Scurvy
Authors: F. W. Fox
Journal: BMJ (1941)

Credit risk transfer (CRT) instruments offer important diversification benefits but may magnify shocks since they disperse risk, across both financial and non-financial sectors. Exposures to CRT instruments, such as credit derivatives, are difficult to track, given the lack of public data on this activity. This article proposes a simple method for estimating institutional exposures to credit derivatives, using readily-available and timely financial markets data. The results suggest the existence of a strong “home bias” in the exposures of institutions. Moreover, major financial institutions tend to have less risky exposures in Europe, but have riskier exposures in North America. Importantly, the findings on individual institutions appear to have been broadly borne out by revelations during the recent turmoil in global credit markets. <b>TOPICS:</b>CLOs, CDOs, and other structured credit, credit default swaps, financial crises and financial market history
Preclinical Testing of Clinically Applicable Strategies for Overcoming Trastuzumab Resistance Caused by PTEN Deficiency
Authors: Chien-Hsing Lu, Shannon L. Wyszomierski, Ling-Ming Tseng, Meng-Hong Sun, Keng-Hsueh Lan, Christopher L. Neal, Gordon B. Mills, Gabriel N. Hortobagyi, Francisco J. Esteva, Dihua Yu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We have previously shown that PTEN loss confers trastuzumab resistance in ErbB2-overexpressing breast cancer using cell culture, xenograft models, and patient samples. This is a critical clinical problem because trastuzumab is used in a variety of therapeutic regimens, and at the current time, there are no established clinical strategies to overcome trastuzumab resistance. Here, we did preclinical studies on the efficacy of clinically applicable inhibitors of the Akt/mammalian target of rapamycin (mTOR) pathway to restore trastuzumab sensitivity to PTEN-deficient cells. Experimental Design: Cell culture and xenograft models were used to test a panel of clinically applicable, small-molecule inhibitors of the Akt/mTOR signal transduction pathway, a critical pathway downstream of ErbB2, and identify compounds with the ability to restore trastuzumab sensitivity to PTEN-deficient cells. Results: When trastuzumab was combined with the Akt inhibitor triciribine, breast cancer cell growth was inhibited and apoptosis was induced. In a xenograft model, combination therapy with trastuzumab and triciribine dramatically inhibited tumor growth. The combination of trastuzumab and the mTOR inhibitor RAD001 also slowed breast cancer cell growth in vitro and in vivo. Conclusions: Combining trastuzumab with inhibitors of the Akt/mTOR pathway is a clinically applicable strategy and combinations of trastuzumab with triciribine or RAD001 are promising regimens for rescue of trastuzumab resistance caused by PTEN loss.
Actions of lidocaine on transmembrane potentials of subendocardial Purkinje fibers surviving in infarcted canine hearts.
Authors: J D Allen, F J Brennan, A L Wit
Journal: Circulation Research (1978)

We compared the effects of lidocaine, 2 X 10(-5) M, on transmembrane resting and action potentials of Purkinje fibers on the endocardial surface of 24- to 72-hour-old myocardial infarcts in dogs with its actions and subendocardial Purkinje fibers in normal hearts. At both proximal (near the tip of the papillary muscle) and distal (toward the apex) recording sites in noninfarcted hearts, lidocaine had no significant effect on maximum diastolic potential (MDP) or Vmax. It shortened action potential duration (APD) only at the proximal site. In infarcted hearts, we arbitrarily divided Purkinje fibers at the infarcted distal site into two groups. Group I consisted of fibers which did not have a severely depressed MDP or Vmax but in which APD was markedly prolonged. Lidocaine had no effect on MDP of these fibers, significantly depressed Vmax, and shortened APD. Group II consisted of fibers in which MDP and Vmax were markedly reduced. Lidocaine also reduced Vmax of these fibers further (by 60%) without altering resting potential. In addition, lidocaine depressed pacemaker activity of Purkinje fibers in infarcts. The drug did not alter conduction of premature impulses in the subendocardial Purkinje network in normal hearts but increased the maximum delay of early premature impulses in Purkinje fibers in infarcted hearts and sometimes resulted in nondriven repetitive activity. Therefore, the effects of lidocaine on transmembrane potentials of Purkinje fibers in infarcts are different from its effects on fibers in normal hearts.
T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis
Authors: Zhenyue Hao, Brigitte Hampel, Hideo Yagita, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2004)

To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a more generalized manner demonstrated that the development of lymphoproliferative disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe lymphopenia over time, accompanied by up-regulation of FasL on activated T cells and apoptosis of peripheral lymphocytes. In addition, the mutant animals developed a fatal wasting syndrome caused by massive leukocyte infiltration in the lungs together with increased inflammatory cytokine production and pulmonary fibrosis. Inhibition of Fas–FasL interaction in vivo completely prevented the loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL-mediated interaction of activated, Fas-deficient T cells with Fas-expressing cells in their environment leads to break down of lymphocyte homeostasis and development of a lung disease strikingly resembling idiopathic pulmonary fibrosis in humans, a common and severe disease for which the mutant mice may serve as a first animal model.
Surveying the literature from animal experiments: Systematic review and meta-analysis are important contributions
Authors: Malcolm R Macleod, Shah Ebrahim, Ian Roberts
Journal: BMJ (2005)

EDITOR-We agree with Lemon and Dunnett that better methods of surveying the literature on animal experiments are needed,1 but we do not share their confidence in the utility of non-systematic reviews.In clinical trials, systematic review and meta-analysis have made important contributions to our understanding of sources of bias, and the quality of clinical trials has improved as a result.
MCF-7 Cells--Changing the Course of Breast Cancer Research and Care for 45 Years
Authors: A. V. Lee, S. Oesterreich, N. E. Davidson
Journal: JNCI Journal of the National Cancer Institute (2015)

It is 45 years since a pleural effusion from a patient with metastatic breast cancer led to the generation of the MCF-7 breast cancer cell line. MCF-7 is the most studied human breast cancer cell line in the world, and results from this cell line have had a fundamental impact upon breast cancer research and patient outcomes. But of the authors for the nearly 25000 scientific publications that used this cell line, how many know the unique story of its isolation and development? In this commentary we will review the past, present, and future of research using MCF-7 breast cancer cells.
Geranylgeranylated Proteins are Involved in the Regulation of Myeloma Cell Growth
Authors: Niels W.C.J. van de Donk, Henk M. Lokhorst, Evert H.J. Nijhuis, Marloes M.J. Kamphuis, Andries C. Bloem
Journal: Clinical Cancer Research (2005)

Prenylation is essential for membrane localization and participation of proteins in various signaling pathways. This study examined the role of farnesylated and geranylgeranylated proteins in the regulation of myeloma cell proliferation.Antiproliferative and apoptotic effects of various modulators of farnesylated and geranylgeranylated proteins were investigated in myeloma cells.Depletion of geranylgeranylpyrophosphate inhibited myeloma cell proliferation through accumulation of cells in G(1) phase of the cell cycle and loss of cells in S phase. In contrast, depletion of farnesylpyrophosphate had no or only minor effects. Furthermore, inhibition of geranylgeranyl transferase I activity was more effective in reducing myeloma cell growth when compared with inhibition of farnesyl transferase activity. This indicates that protein geranylgeranylation is important for myeloma cell proliferation and cell cycle progression through G(1). Geranylgeranylated target proteins involved in the control of proliferation include GTPases, such as Rac-1, Cdc42, and RhoA. Inhibition of Rho, Rac, and Cdc42 GTPases by toxin B reduced proliferation, without affecting cell viability, whereas specific inhibition of Rho GTPases by C3 exoenzyme was without effect. This suggests a role for Rac and/or Cdc42 GTPases in myeloma cell growth. Rac-1 activity was found in all myeloma cell lines and was suppressed by the depletion of intracellular pools of geranylgeranylpyrophosphate, whereas interleukin-6 rapidly induced Rac-1 activation. Furthermore, dominant-negative Tat-Rac-1 reduced myeloma cell proliferation, whereas constitutively active Tat-Rac-1 enhanced proliferation.These results indicate that protein geranylgeranylation is essential for myeloma cell proliferation and suggest that Rac-1 is a regulator of myeloma cell growth.
On the relation between counterfactual and causal reasoning
Authors: Barbara A. Spellman, Dieynaba G. Ndiaye
Journal: Behavioral and Brain Sciences (2007)

Abstract We critique the distinction Byrne makes between strong causes and enabling conditions, and its implications, on both theoretical and empirical grounds. First, we believe that the difference is psychological, not logical. Second, we disagree that there is a strict “dichotomy between the focus of counterfactual and causal thoughts.” Third, we disagree that it is easier for people to generate causes than counterfactuals.
The role of vitamin D in regulating the severity and duration of murine lung injury
Authors: Sian Lax, Dhruv Parekh, Rachel Dancer, David Thickett
Journal: European Respiratory Journal (2013)

Introduction  Vitamin D has been shown to modulate both innate and adaptive immune responses. Our research suggests patients with or at risk of developing acute lung injury (ALI) are severely vitamin D deficient/insufficient. As there are no licensed treatments for ALI we investigated the effect of vitamin D deficiency in a murine model of ALI to understand its mechanistic drivers.  Methods  Vitamin D deficiency in wild type (WT) mice was established using a vitamin D deficient diet. Combining this with intra-tracheal instillations of LPS (50µg) we analysed inflammation within the lungs of these mice compared to those fed on a vitamin D sufficient diet. In addition, systemic vitamin D supplementation was assessed by IP injection of cholecalciferol prior to LPS instillation.  Results  Compared to WT, vitamin D deficient mice had elevated lung damage at 24 and 48h post IT-LPS; increased Permeability Index (p=0.007, p=0.018) and RAGE expression (p=0.007, p=0.001). At 48h post IT-LPS vitamin D deficient mice had a build-up of apoptotic neutrophils (p=0.038), increased BALF granulocytes (p=0.042), elevated CXCL1/KC (p=0.012) and decreased oxygen saturation (p=0.016). Furthermore, pre-treatment of mice with normal vitamin D levels, with cholecalciferol reduced lung inflammation - fewer BALF granulocytes (7.6x10 5  to 4.3x10 5 , p=0.135), and neutrophils (81% to 72%, p=0.068) 48h post IT-LPS (n=6).  Conclusion  Our data indicate that vitamin D deficiency significantly augments both the severity and duration of murine lung injury and exogenous vitamin D reduces lung responses to LPS even in mice with normal vitamin D levels. These data support the use of vitamin D to both prevent and potentially treat established ALI.
Epidermal Grafting Using a Novel Suction Blister–Harvesting System for the Treatment of Pyoderma Gangrenosum
Authors: Nicholas A. Richmond, Sonia A. Lamel, Liza R. Braun, Alejandra C. Vivas, Thomas Serena, Robert S. Kirsner
Journal: JAMA Dermatology (2014)

Patient 1 A woman in her 40s without other significant medical history presented in 2013with an 8-month history of an exquisitely painful ulcer on thedistal left lateral leg. Shenoted that the lesionbeganas “a small red bump” that she believedtobean insectbite.Aphysician at another institutionperformedan incision anddrainage to treat a suspected abscess andprescribedoral antibiotics, but the lesiondeteriorated. Abiopsyperformed in 2012hadnonspecific results and Gram, acid-fast, and Fite stains were negative for organisms. Venous and arterial insufficiencywere excludedby lower limb duplexultrasound.She receivedadiagnosisofpyodermagangrenosum(PG)andwasprescribedprednisone60mgdailyandtopical clobetasol propionate ointment, 0.05%, to the wound edges. On referral,physicalexaminationrevealedasharplydemarcatedulcerwith purple undermined borders, consistent with the PG diagnosis. The prednisonedosagewas taperedbecauseof adverse effects, and cyclosporine 400 mg daily and weekly leg compression were initiated. Although the inflamed undermined borders improved, the wound failed to reduce in size after 2months of therapy (Figure 1).
Altered phosphorylated signal transducer and activator of transcription profile of CD4+CD161+ T cells in asthma: Modulation by allergic status and oral corticosteroids
Authors: Yael Gernez, Rabindra Tirouvanziam, Khoa D. Nguyen, Leonard A. Herzenberg, Alan M. Krensky, Kari C. Nadeau
Journal: Journal of Allergy and Clinical Immunology (2007)
Studies on Carcinogenesis of Human Prostate. III. Long-Term Explant Culture of Normal Prostate and Benign Prostatic Hyperplasia: Transmission and Scanning Electron Microscopy<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref>
Authors: Barry M. Heatfield, Hayato Sanefuji, Benjamin F. Trump
Journal: JNCI Journal of the National Cancer Institute (1982)

Ultrastructural changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were compared. Explants of normal prostate obtained at immediate autopsy of young adults or of BPH obtained at the time of surgery were maintained as long as 24 weeks in vitro. Ultrastructural changes occurring in epithelial cells during culture were monitored by transmission and scanning electron microscopy. Essentially identical results were found for normal prostate and BPH. During the first week of culture, secretory epithelial cells degenerated and sloughed into the acinar lumen, resulting in an accumulation of necrotic debris. During this period, however, epithelial cells with ultrastructural characteristics of basal cells remained viable, repopulated glandular structures, migrated from glands and ducts, and epithelialized adjacent cut surfaces. eventually covering the explant. On explant surfaces, these basal cells initially were squamous-like, but they later became typically cuboidal, polygonal, or sometimes columnar and formed an epithelium, two cells or more thick. Epithelium with similar features lined acini within explants. Epithelial cells at the surface or within explants were distinguished by the presence of microvilli, junctional complexes, multiple Golgi complexes, well-developed rough endoplasmic reticulum, polyribosomes, nuclei with prominent nucleoli, orthodox mitochondria, scattered tonofilaments, and a basal lamina. Some epithelial cells extended from the lumen to the basal lamina; others were oriented along the basal lamina and did not extend to the lumen. By 1–2 weeks in vitro, these epithelial cells began synthesis of mucus-like material. At later intervals of culture, microvilli were shortened and mucosubstances were reduced. During culture, the stroma became progressively hypocellular and necrotic. In summary, explant-cultured epithelial cells of normal human prostate or BPH were similar ultrastructurally and were found to originate from basal cells, which alone survive culture conditions.
Risk Stratification Using Computed Tomography Coronary Angiography in Patients Undergoing Intermediate-Risk Noncardiac Surgery
Authors: Jong-Hwa Ahn, Jeong Rang Park, Ji Hyun Min, Ju-Tae Sohn, Seok-Jae Hwang, Yongwhi Park, Jin-Sin Koh, Young-Hoon Jeong, Choong Hwan Kwak, Jin-Yong Hwang
Journal: Journal of the American College of Cardiology (2013)
Chronic Constriction of the External and Internal Carotid Arteries in Dogs: Its Effect on the Blood Pressure
Authors: PAUL KEZDI
Journal: Circulation Research (1960)

Narrowing of the internal and external carotid arteries by a clamp does not lead to hypertension if the carotid sinus nerves remain intact. Subsequent disruption of the carotid sinus nerves results in hypertension. It is concluded that the cause of the chronic hypertension in dogs with constriction of the carotid sinus is not due to altered cerebral hemodynamics, but rather to disruption of the carotid sinus nerves.
1017 PREOPERATIVE HEPATECTOMY SIMULATION PROGRAM FOR CHOLANGIOCARCINOMA: APPLICATION TO LIVER RESECTION AND BILE DUCT RECONSTRUCTION
Authors: Y. Kondo, Y. Iimuro, T. Hirano, N. Kuroda, T. Okada, Y. Asano, K. Kinoshita, K. Suzumura, S. Hai, J. Fujimoto
Journal: Journal of Hepatology (2012)
Dynamic radionuclide imaging with 99mTc-sucralfate in the detection of oesophageal ulceration.
Authors: A J Mearns, G C Hart, J A Cox
Journal: Gut (1989)

Standard oesophageal scintigraphic techniques using 99mTc-colloids rarely identify oesophageal mucosal damage. Sucralfate can be labelled with 99mTc for the detection of oesophageal mucosal ulceration. This method uses two separate supine swallows of 10 MBq 99mTc-colloid in 10 ml, followed by a single supine swallow of 30 MBq 99mTc-sucralfate. The data are processed to give time-activity curves, mean transit times and condensed dynamic images. When oesophageal ulceration is detected, the time-activity curves using sucralfate show residual activity in the oesophagus after the transit time indicated by the colloid swallow. The condensed dynamic image shows a persistence of activity at the level of the ulceration. Erect sucralfate images taken immediately after the dynamic sequence show no oesophageal localisation. The results from a study of 62 patients have shown excellent correlation between the dynamic 99mTc-sucralfate images and endoscopy findings. Sequential sucralfate studies for healing also correlate well. The use of labelled sucralfate to detect oesophageal ulceration could modify the indications for endoscopy in gastrooesophageal reflux disease.
Activation of Histone Deacetylase 2 by Inducible Heat Shock Protein 70 in Cardiac Hypertrophy
Authors: Hae Jin Kee, Gwang Hyeon Eom, Hosouk Joung, Sera Shin, Ju-Ryoung Kim, Young Kuk Cho, Nakwon Choe, Bo-Woong Sim, Daewoong Jo, Myung Ho Jeong, Kyung Keun Kim, Jeong-Sun Seo, Hyun Kook
Journal: Circulation Research (2008)

Diverse cardiac diseases induce cardiac hypertrophy, which leads to dilatation and heart failure. We previously reported that hypertrophy can be blocked by class I histone deacetylase (HDAC) inhibitor, which prompted us to investigate the regulatory mechanism of class I HDACs. Cardiac hypertrophy was introduced by aortic banding, by infusion of isoproterenol or angiotensin II, or by swimming. Hypertrophic stimuli transiently elevated the activity of histone deacetylase-2 (Hdac2), a class I HDAC. In cardiomyocytes, forced expression of Hdac2 simulated hypertrophy in an Akt-dependent manner, whereas enzymatically inert Hdac2 H141A failed to do so. Hypertrophic stimuli induced the expression of heat shock protein (Hsp)70. The induced Hsp70 physically associated with and activated Hdac2. Hsp70 overexpression produced a hypertrophic phenotype, which was blocked either by siHdac2 or by a dominant negative Hsp70ΔABD. In Hsp70.1 −/− mice, cardiac hypertrophy and Hdac2 activation were significantly blunted. Heat shock either to cardiomyocytes or to mice activated Hdac2 and induced hypertrophy. However, heat shock-induced Hdac2 activation was blunted in the cardiomyocytes isolated from Hsp70.1 −/− mice. These results suggest that the induction of Hsp70 in response to diverse hypertrophic stresses and the ensuing activation of HDAC2 trigger cardiac hypertrophy, emphasizing HSP70/HDAC2 as a novel mechanism regulating hypertrophy.