tbuckley/cabot-search huggingface dataset:
Abstract 411: Absence of leukotriene B4 receptor-1 promotes colon tumorigenesis in the ApcMin/+ mice by modulating gut microbiota
Authors: Venkatakrishna R. Jala, Paramahamsa Maturu, Elangovan Krishnan, Steven P. Mathis, Krishnaprasad Subbbarao, Sobha R. Bodduluri, Min Wang, Alfred B. Jenson, Mary L. Proctor, Haribabu Bodduluri
Journal: Cancer Research (2011)

Abstract Leukotriene B4, a potent lipid mediator of inflammation acts through the G-protein coupled receptor, BLT1. The BLT1-/- mice displayed substantial protection in inflammatory disease models of arthritis, asthma and atherosclerosis. To examine the role of BLT1 in progression of cancers known to be promoted by inflammation, we crossed the BLT1-/- mice onto mice with a heterozygous mutation in the adenomatous polyposis coli (ApcMin/+) gene. The BLT1-/-ApcMin/+ mice demonstrated an increase in the rate of spontaneous intestinal tumor development and accelerated mortality. Unlike ApcMin/+ mice that develop mostly small intestinal tumors the BLT1-/-ApcMin/+ mice developed large colonic adenomas. Tumors from the BLT1-/-ApcMin/+ mice showed increased rates of proliferation, decrease in apoptosis and an increase in the expression of tumor promoting inflammatory markers such as TNF-α and CXCL1 and COX2 when compared to tumors from the ApcMin/+ mice. Microarray analysis of transcriptome showed that the paradoxical increase in inflammation in tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infections. The expression of angiogenins, a class of antibacterial proteins was significantly reduced in tumors from BLT1-/-ApcMin/+ mice. Further, analysis of gut flora (by 16S ribosomal DNA sequences) identified major differences in microbiome colonizing the BLT1-/-ApcMin/+ and ApcMin/+ mice. BLT1-/-ApcMin/+ mice rederived and raised under germ-free conditions are completely protected from colon cancer development. To examine the role of Toll-like receptor mediated signaling events involved in tumor promotion in the absence of BLT1, we developed BLT1/MyD88 double deficient mice. The BLT1-/-MyD88-/- mice were highly susceptible to lethal neonatal infections indicating the cooperative interactions between TLR and leukotriene pathways in host response. These BLT1-/-MyD88-/- mice could be rescued by treatment with a broad-spectrum antibiotic. The MyD88-/-ApcMin/+ mice are highly protected from intestinal cancers. The BLT1-/-MyD88-/-ApcMin/+ mice are also highly protected indicating that BLT1-mediated host defense acts upstream of MyD88-mediated tumor promoting inflammation. While both BLT1 and MyD88 are important in host defense only the MyD88 but not BLT1 activated pathways are required to initiate tumor promoting inflammation. These results identify novel roles for gut microbiota in promoting colon cancer and for BLT1 in preventing the colon cancer development by shaping the gut microbiome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 411. doi:10.1158/1538-7445.AM2011-411
The Low Risk of Hepatitis B in Rural Hospitals-Reply
Authors: Reginald F. Finger
Journal: JAMA (1985)

<h3>In Reply.—</h3> Lange and Kreider have suggested that even though the risk of hepatitis B virus infection in rural health care workers is low, vaccination of those with frequent blood exposure should be recommended because the relative risk of such exposure is increased threefold. In our study, when those workers who had ever lived in a city were excluded, that relative risk disappeared (see Table, column 2). The risk of HBV infection in all blood exposure groups was low (overall, 2.1%). This figure is comparable with the background prevalence in rural areas cited by Lange and Kreider (1.9%). This suggests that the relative risk in high-blood-exposure groups, among rural health workers, comes not from their work-place exposure in the rural hospital but from some source in the cities in which many previously lived. To withhold publication of the data, or to make a recommendation inconsistent with the data, simply in
Biochemistry of intestinal development.
Authors: S J Henning
Journal: Environmental Health Perspectives (1979)

In biochemical terms, the rat small intestine is relatively immature at birth and for the first two postnatal weeks. Then during the third week a dramatic array of enzymic changes begins, and by the end of the fourth week the intestine has the digestive and absorptive properties of the adult. Selective examples of these changes are discussed with emphasis on their implications for toxicological studies. The review also includes a detailed consideration of the roles of the dietary change of weaning and of glucocorticoid and thyroid hormones in the regulation of intestinal development.
Have we taken the hippocampus out of context?—Reply
Authors: K.A. McNish, J.C. Gewirtz, M. Davis
Journal: Trends in Cognitive Sciences (1998)

In our recent article examining the role of the hippocampus in contextual fear conditioning, we developed a paradigm which produced contextual freezing and fear-potentiated startle that was specific to a context previously paired with shock[ 1 McNish K.A. Gewirtz J.C. Davis M. Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle. J. Neurosci. 1997; 17: 9353-9360 Crossref PubMed Google Scholar ]. Lesions of the central nucleus of the amygdala blocked both freezing and fear-potentiated startle, consistent with the notion that this structure is critically involved in mediating conditioned fear responses. In contrast, lesions of the dorsal hippocampus disrupted contextual freezing, but had no effect on fear-potentiated startle. Based on these results, we concluded that despite a disruption of freezing, fear to the context was preserved in animals with hippocampal lesions.
Abstract PD09-09: The Akt inhibitor MK-2206 is an effective radio-sensitizer of p53 deficient triple negative breast cancer (TNBC) cells.
Authors: EP Connolly, Y Sun, KC Chao, TK Hei
Journal: Cancer Research (2012)

Abstract Purpose: Triple negative breast cancer (TNBC) is an aggressive tumor with a higher locoregional recurrence compared to estrogen receptor (ER) positive breast cancer. Mutations in the PI3K/Akt/mTOR pathway leading to up-regulation of Akt occur with high frequency in TNBC. Hyperactive Akt is associated with increase radiation resistance, mediated through inhibition of apoptosis and up-regulation of DNA damage-induced G2 arrest. p53 plays a key role in mediating G1 cell cycle arrest following genotoxic stress such as radiation; p53-deficient cells however must rely on alternate mechanisms for cell cycle arrest in S- and G2-phases. Inhibition of Akt therefore would be expected to act in a synthetic lethal fashion to radiosensitize p53 deficient TNBC cells by decreasing their ability to arrest in G2. Given that p53 mutations occur in 44% of TNBC this may be an effective strategy for radiosensitizing TNBC. Methods: Experiments were conducted using MDA-MB-468, MDA-MB-231 and SUM 149 cells, all well established models for p53-deficient TNBC. Cells were treated with MK-2206, a potent allosteric Akt inhibitor, alone or in combination with increasing doses of radiation from 0–8 Gy. In vitro studies preformed included; cell survival assays, MTT assay, immunoblot analysis of key proteins, FACS analysis for cell cycle, apoptosis, and gH2AX staining. Results: We found that the combination of IR and Akt inhibition by MK-2206 is synergistic. MK-2206 inhibited both endogenous and radiation-induced Akt activation and phosphorylation of its down-stream targets. Decreased clonogenic survival was seen after 2 or 24 hours pretreatment with MK-2206 as well as decreased viability by MTT assay. Cell cycle analysis demonstrates MK-2206 decreases the proportion of cells in G2/M arrest following irradiation, as well as induced a greater proportion of apoptosis. Evaluation of the DNA damage response pathway demonstrated decreased levels of total DNA-PK, as well as a delayed DNA damage response. Conclusions: These studies demonstrate that targeted inhibition of Akt effectively radiosensitizes p53 deficient TNBC cells lines, possibly through a synthetic lethal effect on the DNA damage response. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD09-09.
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis
Authors: Ying Zhang, Oded Foreman, Dennis A. Wigle, Farhad Kosari, George Vasmatzis, Jeffrey L. Salisbury, Jan van Deursen, Paul J. Galardy
Journal: Journal of Clinical Investigation (2012)

Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy by restraining the activity of the anaphase-promoting complex (APC). The deubiquitinase USP44 was identified as a key regulator of APC activation; however, the physiological importance of USP44 and its impact on cancer biology are unknown. To clarify the role of USP44 in mitosis, we engineered a mouse lacking Usp44. We found that USP44 regulated the mitotic checkpoint and prevented chromosome lagging. Mice lacking Usp44 were prone to the development of spontaneous tumors, particularly in the lungs. Additionally, USP44 was frequently downregulated in human lung cancer, and low expression correlated with a poor prognosis. USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry. These functions required direct binding to the centriole protein centrin. Our data reveal a new role for the ubiquitin system in mitotic spindle regulation and underscore the importance of USP44 in the pathogenesis of human cancer.
Clinical governance in sports medicine
Authors: P McCrory
Journal: British Journal of Sports Medicine (2003)

Sports ruling bodies should introduce clinical governance to ensure best practice treatment for athletes no matter what their sport nor where they play

In these days where corporate governance seems a watchword for dubious practice within multinational companies, such terms often are bandied around without much thought given to their meaning. A similar word, clinical governance, is used within medicine particularly by administrators and funding bodies who set their own agendas within health care.

In 1998, the National Health Service (NHS) introduced into the United Kingdom namely, the concept of clinical governance. This was used to denote the systematic coordination and promotion of activities that contribute to continuous improvement of quality of care.1

The broad elements that make up the panoply of clinical governance include the processes of clinical audit, risk management, professional development and patient participation. As such, clinical governance requires better communication systems, organisational change and a paradigm shift on the part of clinicians toward more open and impartial evaluation of clinical care and its outcomes.2 It is worth observing, albeit sadly for the traditionalists, that this laudable …
Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein
Authors: Florian Klein, Christian Gaebler, Hugo Mouquet, D. Noah Sather, Clara Lehmann, Johannes F. Scheid, Zane Kraft, Yan Liu, John Pietzsch, Arlene Hurley, Pascal Poignard, Ten Feizi, Lynn Morris, Bruce D. Walker, Gerd Fätkenheuer, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2012)

Two to three years after infection, a fraction of HIV-1-infected individuals develop serologic activity that neutralizes most viral isolates. Broadly neutralizing antibodies that recognize the HIV-1 envelope protein have been isolated from these patients by single-cell sorting and by neutralization screens. Here, we report a new method for anti-HIV-1 antibody isolation based on capturing single B cells that recognize the HIV-1 envelope protein expressed on the surface of transfected cells. Although far less efficient than soluble protein baits, the cell-based capture method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i). The new epitope is expressed on the cell surface form of the HIV-1 spike, but not on soluble forms of the same envelope protein. Moreover, the new antibodies complement the neutralization spectrum of potent broadly neutralizing anti-CD4 binding site (CD4bs) antibodies obtained from the same individual. Thus, combinations of potent broadly neutralizing antibodies with complementary activity can account for the breadth and potency of naturally arising anti-HIV-1 serologic activity. Therefore, vaccines aimed at eliciting anti-HIV-1 serologic breadth and potency should not be limited to single epitopes.
Cost of Long-Term Complications of Deep Venous Thrombosis of the Lower Extremities: An Analysis of a Defined Patient Population in Sweden
Authors: David Bergqvist
Journal: Annals of Internal Medicine (1997)

Little information is available on the epidemiology and economic effect of long-term complications developing after deep venous thrombosis.To determine the extent of, timing of, and treatment costs associated with long-term complications developing after deep venous thrombosis of the lower extremities.15-year retrospective cohort study.County hospital in Sweden.257 patients with deep venous thrombosis and 241 age- and sex-matched controls without deep venous thrombosis.Data on use of health care resources and costs of inpatient and outpatient care, pharmaceutical agents, and treatment of complications.After 15 years of follow-up, 35% of the patients with thrombosis and 57% of the controls were alive. Two hundred forty-two complications were reported among the patients with thrombosis, and 25 similar events were reported among the controls. The average expected present value of the health care cost of treating complications of thrombosis was estimated to be about $4659 in the patients with thrombosis and $375 in the controls. In controls, primary deep venous thrombosis cost about $6000; thus, the additional long-term health care cost of post-thrombotic complications is about 75% of the cost of primary deep venous thrombosis.The economic effect of post-thrombotic complications is considerable. The use of measures to prevent thromboembolism and its long-term complications are justified on both clinical and economic grounds.
Knox: The Anatomist
Authors: Lester S. King
Journal: JAMA (1966)

Burke and Hare, the murderers who provided bodies for anatomical dissection, are well known to the modern audience, for the dramatic subject has received considerable attention in recent medical and nonmedical literature. However, the personality of Dr. Robert Knox, the hapless physician who purchased the cadavers from Burke and Hare, remains much less well known. Dr. Knox was a complex individual, a brilliant anatomist but not without flaws as a person. History seems to have cast him as a villain, but Miss Rae has sought to vindicate him from the calumnies that attach to his name. She has produced a readable and generally vivid portrait, not entirely convincing, to be sure, but one which conveys the strong spirit of the man and the tragedy which dogged his footsteps without breaking his spirit. While Miss Rae writes with considerable fluency, and often with charm, there are certain severe drawbacks. She is
A multi-step method for preparation of porcine small intestinal submucosa (SIS)
Authors: Jing-Cong Luo, Wei Chen, Xiao-He Chen, Ting-Wu Qin, Yong-Can Huang, Hui-Qi Xie, Xiu-Qun Li, Zhi-Yong Qian, Zhi-Ming Yang
Journal: Biomaterials (2010)
Abstract 15466: Genetically Elevated Bilirubin and Risk of Ischemic Heart Disease: a Mendelian Randomization Study of the General Population
Authors: Stefan Stender, Ruth Frikke-Schmidt, Borge G Nordestgaard, Anne Tybjaerg-Hansen
Journal: Circulation (2011)

Background: Elevated plasma bilirubin, an endogenous antioxidant, has been associated with reduced risk of ischemic heart disease(IHD) and myocardial infarction(MI) in mainly case-control studies. ...
Comparison of Bolus and Infusion Protocols for Determining Acute Insulin Response to Intravenous Glucose in Normal Humans
Authors: David K McCulloch, Polly J Bingley, Peters G Colman, Richard A Jackson, Edwin A M Gale
Journal: Diabetes Care (1993)

OBJECTIVE— To help standardize methodology for intravenous glucose tolerance testing in preclinical IDDM by comparing a 30-s bolus and a 3-min infusion of glucose. RESEARCH DESIGN AND METHODS— We tested 20 healthy nondiabetic adults at four centers (in Seattle, Boston, Melbourne, and London). Each subject had four intravenous glucose tolerance tests (two bolus and two infusion). The acute insulin response to glucose was calculated as the mean of the 1′ + 3′, the mean of 1′ to 10′, or as the integrated area from 0 to 10′. Glucose and insulin profiles and intrasubject coefficient of variation were compared. RESULTS— With the infusion protocol, the 1′ insulin was significantly higher, resulting in a higher acute insulin response to glucose when calculated as 1′ + 3′ (525 ± 66 vs. 376 ± 35 pM, P &amp;lt; 0.004). When calculated over 10 min, however, the acute insulin response to glucose was not different between protocols. In addition, the intrasubject coefficient of variation was significantly better when calculated over 10 min in both protocols, but no significant differences were noted between the bolus and infusion (infusion: AIRg [area from 0 to 10′] 10.4 ± 2.1% vs. AIRg [1′ + 3′] 14.9 ± 2.8%, P &amp;lt; 0.007; bolus: AIRg [area from 0 to 10′] 14.6 ± 2.8% vs. AIRg [1′ + 3′] 19.8 ± 3.5%, P &amp;lt; 0.007). Comparison of the insulin assays between the four centers showed close correlation and gave indistinguishable results in terms of within-subject coefficient of variation. Glucose profiles were similar in both protocols. Although the glucose values were lower with the bolus protocol from 4′ to 40′, the rate of fall from 10 to 30′ (and thus the rate of glucose disposal) was indistinguishable between the two. CONCLUSIONS— These data suggest that neither protocol gives significant advantage over the other. However, to allow comparison of the acute insulin response to glucose between different protocols used in centers around the world, the ICARUS 3-min infusion protocol is recommended, with acute insulin response to glucose calculated over 10 min after the end of glucose administration; this reduces the within-subject coefficient of variation and provides similar acute insulin response to glucose with both protocols.
Infection Prophylaxis in Acute Leukemia: A Comparison of Ciprofloxacin with Trimethoprim-Sulfamethoxazole and Colistin
Authors: ADRIAAN W. DEKKER
Journal: Annals of Internal Medicine (1987)

Fifty-six patients receiving remission induction treatment for acute leukemia were studied in a randomized trial comparing ciprofloxacin with trimethoprim-sulfamethoxazole plus Colistin for prevention of infections. Both groups received amphotericin B for antifungal prophylaxis. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections occurred in 28 patients receiving trimethoprim-sulfamethoxazole plus Colistin. No infections caused by gram-negative bacilli were seen in the ciprofloxacin group (p < 0.02). Ciprofloxacin prevented colonization with resistant gram-negative bacilli, but 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole plus Colistin (p < 0.01). Ciprofloxacin was better tolerated: 23 of 28 patients were highly compliant to the drug, compared with 15 of 28 patients in the trimethoprim-sulfamethoxazole group (p < 0.05). These results suggest that ciprofloxacin is a promising drug for the prevention of infection in patients with granulocytopenia.
A chicken sandwich leading to intensive care
Authors: R Som, R Wynne-Simmons, J Islam, S Lawman
Journal: BMJ (2009)

A 28 year old man presented to the accident and emergency department with central abdominal pain that had lasted just over a day and was “cramping” in nature. He had had bloody diarrhoea for three days, with increasing frequency and amount of blood. He had eaten a chicken sandwich purchased from a canteen the day before the onset of symptoms. There was no history of recent foreign travel or any important medical history. On examination he was found to be warm and well perfused, and his abdomen was soft, with mild generalised tenderness. On admission his full blood count, renal function and liver function tests were all within normal range. Three days after admission he had persistent bloody diarrhoea; his haemoglobin concentration had dropped by 40 g/l to 126 g/l. Colonoscopy and biopsies showed acute indeterminate colitis. His white cell count was 23.3×109/l, neutrophils 19.1×106/l, platelets 49×109/l, international normalised ratio 1.0, APTT (activated partial thromboplastin time)1.0, C reactive protein 256 mg/l, urea 19.7 mmol/l, creatinine 530 µmol/l, potassium 4.8 mmol/l, serum lactate dehydrogenase 3452 U/l. He quickly became anuric. ### Short answers
Recurrent Postcoital Lower-Extremity Streptococcal Erythroderma in Women
Authors: Richard T. Ellison
Journal: JAMA (1987)

Two women with underlying distortion of their lower-body lymphatic systems from neoplasia and surgery or radiation therapy had recurrent episodes of lower-extremity erythroderma temporally associated with sexual intercourse. Both women had vaginal colonization with<i>Streptococcus agalactiae</i>(group B); one was shown to have recurrent bacteremia with this organism at the time of the episodes. Erythroderma developed in these women possibly because of seeding of<i>S agalactiae</i>in the vaginal soft tissues during coitus. (<i>JAMA</i>1987;257:3260-3262)
Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury
Authors: Andrew. G. Reaume, Jeffrey L. Elliott, Eric K. Hoffman, Neil W. Kowall, Robert J. Ferrante, Donald R Siwek, Heide M. Wilcox, Dorothy G. Flood, M. Flint Beal, Robert H. Brown, Richard W. Scott, William D. Snider
Journal: Nature Genetics (1996)
Angiolymphoid hyperplasia with eosinophilia treated with anti-interleukin-5 antibody (mepolizumab)
Authors: M. Braun-Falco, S. Fischer, S-G. Plotz, J. Ring
Journal: British Journal of Dermatology (2004)

Sir, Angiolymphoid hyperplasia with eosinophilia (ALHE) is an unusual condition that usually manifests in young to middle‐aged caucasian adults as a single pinkish‐brown nodule, several centimetres in size, preferentially at the retroauricular area or as a group of smaller nodules distributed on the head and neck.1 In addition to tissue eosinophilia, some patients may develop peripheral blood eosinophilia and markedly elevated serum IgE levels, features typically seen in Kimura's disease.1 Treatment of ALHE is problematic, as the cause is unknown. Excision may be curative, but is difficult to perform in extensive cases.2 Alternative options including systemic corticosteroids, radiation, laser surgery, cryosurgery, cytotoxic agents and pentoxifylline have been tried with variable responses and relapses after withdrawal.3 As interleukin (IL)‐5, the major cytokine involved in production, mobilization and activation of eosinophils, has been found to be elevated in patients with ALHE,4, 5 blocking the interaction between IL‐5 and its receptor might be a reasonable therapeutic approach.