tbuckley/cabot-search huggingface dataset:
Abstract 2254: FIP200 regulation by hypoxia in brain endothelial cells
Authors: Niladri S. Kar, Russell Tipps, Haifeng Yang, Candece L. Gladson
Journal: Cancer Research (2012)

Abstract Angiogenesis is a prominent characteristic of glioblastoma tumors. Hypoxia occurs in glioblastoma tumors and is thought to promote angiogenesis largely through a HIF-dependent mechanism. The effect of hypoxia on survival proteins expressed by endothelial cells (ECs), such as focal adhesion kinase interacting protein of 200kDa (FIP200, also known as RB1CC1), has received little attention. We recently reported that the expression of FIP200 is increased in the angiogenic endothelial cells of glioblastoma tumors. FIP200 can promote cell survival through its promotion of autophagy, or by inhibiting Pyk2 activation and Pyk2-mediated apoptosis. We found that hypoxia upregulated FIP200 protein expression and that this upregulation of FIP200 was independent of the downregulation of ARNT, suggesting it was HIF-independent. We then examined the post-translational modification of FIP200 and whether it was differentially regulated in hypoxia. We found that FIP200 is degraded in the proteosome in normoxia, and that there may be alterations in the proteosomal degradation pathway in hypoxia that contribute, in part, to the elevated FIP200 protein level. Understanding the mechanism for the increased expression of FIP200 in hypoxia may provide future therapeutic targets for new anti-angiogenic therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2254. doi:1538-7445.AM2012-2254
Global Fund calls for increased AIDS funding
Authors: Peter Mozynski
Journal: BMJ (2005)

As heads of state and government prepare for the upcoming 2005 World Summit in New York on 14-16 September, marking the 60th anniversary of the United Nations, there are concerns that many of the millennium development goals are seriously off track, especially those concerned with reversing the spread of HIV and AIDS.

The UN Human Development Report Office released preliminary figures in June projecting that the UN millennium development goals will be missed by a wide margin in Africa ( BMJ 2005;330: 1350, 11 Jun).

Last week, …
Metformin reduced CV events compared with glipizide in patients with type 2 diabetes and CAD
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2013)

Source Citation Hong J, Zhang Y, Lai S, et al; SPREAD-DIMCAD Investigators. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2012 Dec 10. [Epub ahead of print] 23230096
Pathological effects of intra-arterial blood transfusions in dogs
Authors: G. WRIGHT
Journal: Cardiovascular Research (1975)

During storage, large cellular aggregates and clots formed in venous blood but not in arterial blood. Contrary to previous opinions, the intra-arterial transfusion of blood containing aggregates and clots did not cause focal brain damage and the presence of aggregates was not essential for the post-transfusion development of cerebral petechial and other minor haemorrhages.
Sensitivity, Specificity, and Predictive Values in the 'Sensitivity and Specificity of Clinical Diagnostics'
Authors: Douglas K. Miller
Journal: JAMA (1989)

To the Editor.—  There was a confusing explanation of sensitivity and specificity in the article by Anderson et al 1 in the March 17 issue. Assuming proper use of the terms true positives, true negatives, false positives , and false negatives , sensitivity and specificity are defined correctly in the Methods section and in the footnote to Table 1. However, it appears that the correct positions of false negatives and false positives were switched in Table 1 (Table).  This distinction is important, because if the data for all subsequent tables were analyzed as described in the published Table 1, then what is reported as the sensitivity is actually the predictive value of a positive, and the reported clinical accuracy of a positive diagnosis is actually the sensitivity. A similar switch would also have occurred with the specificity and the clinical accuracy of a negative diagnosis.
Abnormal growth hormone release in response to human pancreatic growth hormone releasing factor in acromegaly.
Authors: G M Besser, L H Rees, J A Wass, M O Savage, A Grossman, N Lytras
Journal: BMJ (1983)

The use of this technique for diagnosing pneumocystis pneumonia does not seem to be widely known in Great Britain, and we were unaware of its use in such cases until it was brought to our attention by Dr C Danel from Paris.Its use was first described in 1974 by Drew et all using a catheter and later by Kelly et a12 and Even et al3 using a fibreoptic bronchoscope.The success rate seems to be almost 1000% with no false positives.The lavaged fluid is centrifuged, and the cells stained with methenamine silver stain, which shows the pneumocysts clearly.We have used the technique in one suspected case, and it was gratifying to be able to have a definite positive result within three hours of the bronchoscopy.Lung biopsy samples taken at the same time eventually were also positive, but in future we plan not to run the small, but appreciable, risk of transbronchial biopsy in such cases.
Influenza in a Partially Immunized Aged Population
Authors: Frederick L. Ruben
Journal: JAMA (1974)

Influenza caused by the A/England virus occurred in a home for the aged where an A/Hong Kong vaccine had been given. One hundred eight persons developed febrile respiratory illnesses. Attack rates and death rates were similar in vaccinees and nonvaccinees. However, vaccinees had shorter febrile illnesses than nonvaccinated individuals (<i>P</i>&lt;.001). In persons on one floor who were almost wholly unvaccinated, a more serious illness prevailed for reasons obscure. Yet the difference was so obvious that addition of these figures to the others would have necessitated a different overall interpretation. (<i>JAMA</i>230:863-866, 1974)
YPEL3, a p53-Regulated Gene that Induces Cellular Senescence
Authors: Kevin D. Kelley, Kelly R. Miller, Amber Todd, Amy R. Kelley, Rebecca Tuttle, Steven J. Berberich
Journal: Cancer Research (2010)

Abstract Cellular senescence, the limited ability of cultured normal cells to divide, can result from cellular damage triggered through oncogene activation (premature senescence) or the loss of telomeres following successive rounds of DNA replication (replicative senescence). Although both processes require a functional p53 signaling pathway, relevant downstream p53 targets have been difficult to identify. Discovery of senescence activators is important because induction of tumor cell senescence may represent a therapeutic approach for the treatment of cancer. In microarray studies in which p53 was reactivated in MCF7 cells, we discovered that Yippee-like-3 (YPEL3), a member of a recently discovered family of putative zinc finger motif coding genes consisting of YPEL1-5, is a p53-regulated gene. YPEL3 expression induced by DNA damage leads to p53 recruitment to a cis-acting DNA response element located near the human YPEL3 promoter. Physiologic induction of YPEL3 results in a substantial decrease in cell viability associated with an increase in cellular senescence. Through the use of RNAi and H-ras induction of cellular senescence, we show that YPEL3 activates cellular senescence downstream of p53. Consistent with its growth suppressive activity, YPEL3 gene expression is repressed in ovarian tumor samples. One mechanism of YPEL3 downregulation in ovarian tumor cell lines seems to be hypermethylation of a CpG island upstream of the YPEL3 promoter. We believe these findings point to YPEL3 being a novel tumor suppressor, which upon induction triggers a permanent growth arrest in human tumor and normal cells. Cancer Res; 70(9); 3566–75. ©2010 AACR.
Urinary microalbumin excretion and preterm birth.
Authors: P N Baker, G A Hackett
Journal: BMJ (1993)

teams to care for those with HIV infection or on the part of patients to use their general practitioners but because of a reluctance of hospital based teams to transfer responsibility to their colleagues in the community.The current arrangements for allocating funds to hospital based providers offer few incentives for HIV specialists to work with primary care teams.The failure to allocate resources to providers in the community must be urgently addressed by purchasers if general practitioners and district nurses are to be encouraged to participate in shared care for patients with HIV infection.
The Ebola epidemic is ongoing in West Africa and responses from China are positive
Authors: Jing-Min Zhao, Shi-Jun Dong, Jin Li, Jun-Sheng Ji
Journal: Military Medical Research (2015)

The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. On August 8, 2014, the World Health Organization (WHO) declared the cross-country Ebola outbreak a Public Emergency of International Concern. China has had no confirmed cases of Ebola. In this paper, virologic characteristics, pathogenesis, clinical manifestations, laboratory examination and prophylactic vaccines and therapeutic drugs of Ebola are summarized. Importantly, active responses and actions from China are introduced. Moreover, the key issues in the future prevention and control of Ebola were also addressed.
Nonimmune interaction of leukocytes with platelets and megakaryocytes
Authors: Man‐Chiu Poon, Richard T. Parmley, Vivien Y‐H Chang‐Poon, Joseph H. Embry, Ronald L. Austin
Journal: American Journal of Hematology (1981)

Abstract Platelet–leukocyte interaction was observed in an asymptomatic woman. After incubation in the patient's EDTA‐plasma, autologous and allogeneic platelets adhered to the surfaces of neutrophils, monocytes, macrophages and, rarely, eosinophils. Monocytes, macrophages, and occasionally neutrophils phagocytosed platelets. Degranulation of peroxidase‐positive lysosomes into the platelet‐containing phagosome was demonstrated ultrastructurally. Bone marrow studies indicated that bands and earlier neutrophilic precursors did not participate in the reaction, and that neutrophils adhered to, and were rarely engulfed by megakaryocytes. Sequential exposure of the patient's EDTA‐plasma to platelets and leukocytes indicated that a nondialyzable factor(s) was first absorbed by platelets which then interacted with leukocytes. The reaction proceeded best in the presence of EDTA at 21°C, and was inhibited or dissociated by divalent cations or at 37°C. Metabolic integrity of both platelets and leukocytes was also essential for the reaction since each was inhibited by formalin fixation and partially inhibited by the metabolic inhibitor 2‐deoxyglucose. Formalin‐treated platelets continued to absorb the plasma factor(s). The plasma and the cell fractions were inactivated by periodate and nonspecific protease. Treatment of the platelets with trypsin or the leukocytes with neuraminidase diminished the interaction by 50%. The reaction was also interfered with by concanavalin A. Immunofluorescent and immunoabsorption studies failed to identify an immune component of this interaction. These findings indicate that the plasma factor(s) and the cell surface receptors are nonimmune glycoconjugates and consequently differ from previously documented cases of platelet‐leukocyte interaction.
Diphenylhydantoin and Alcohol Withdrawal
Authors: Peter K. Gessner
Journal: JAMA (1971)

<h3>To the Editor. —</h3> Finer (<b>215</b>:119, 1971) advances the use of diphenylhydantoin for the treatment of alcohol withdrawal, claiming that it is effective in preventing nonepileptic alcoholic seizures when administered with or without diazepam. Alcohol withdrawal presents clinically a difficult syndrome to manage and one which evidences a high mortality unless properly treated.<sup>1,2</sup>Although a wide variety of therapies have been advanced for its treatment, seldom have such therapies been subjected to careful clinical evaluation. Where such evaluation has been attempted only drugs pharmacologically related to ethanol, ie, sedative-hypnotic drugs, have been found to be uniformly effective.<sup>3,4</sup>Such drugs can be thought to substitute for ethanol, just as ethanol can substitute for barbiturates.<sup>5</sup>Other drugs such as promazine have been found to alleviate or mask some of the less-serious symptoms of alcohol withdrawal without effectively controlling the seizures, hallucinations, and hyperthermia, with resulting higher mortalities.<sup>3,4,6</sup>
Clinical Decision Making: Promoting the Jump From Theory to Practice
Authors: Annette Flanagin
Journal: JAMA (1990)

Two decades ago, Weed<sup>1</sup>suggested that since knowledge was endless and constantly changing, physicians primarily should be skilled observers, rather than repositories of information. After making key observations, physicians should proceed in a disciplined manner, following decision trees to each logical end, leaving no open loops. This approach exposed an entire generation of physicians to the problem-oriented approach and the problem-oriented medical record. Following that concept, we began a series called "Toward Optimal Laboratory Use" in<i>JAMA</i>in 1975.<sup>2</sup>Articles in this series have focused on newly developed formal approaches to clinical decision making, such as using algorithms and decision tables when investigating common clinical problems.<sup>3</sup> The status of clinical decision making continues to mature in theory. The Society for Medical Decision Making, now in its 10th year, publishes its own scholarly journal,<i>Medical Decision Making</i>. While decision theory has become more familiar, the diagnostic and therapeutic
Long-term Management of Venous Thromboembolism
Authors: Kenneth A. Bauer
Journal: JAMA (2011)

Numerous randomized clinical trials have compared various durations of anticoagulant therapy with a vitamin K antagonist (ie, warfarin) for an initial episode of venous thromboembolism (VTE). Despite major advances in understanding the pathophysiology of thrombosis and its genetic basis, clinical risk factors at presentation have emerged as the primary determinant of recurrence risk. Following a minimum of 3 months of anticoagulant therapy, patients with VTE in association with transient risk factors (eg, major surgery, trauma, pregnancy) have a low annual recurrence risk, while patients without identifiable provocative risk factors have a recurrence risk of approximately 25% at 4 years with the highest annual rates occurring in the first 2 years. Extending warfarin therapy is highly effective in preventing recurrences but is associated with increased rates of major and minor bleeding. Clinical decision making therefore requires individualized assessment of recurrence and bleeding risk, coupled with patient preference. After 3 months of anticoagulant therapy for a first episode of unprovoked VTE, male sex, age older than 65 years, and an elevated D-dimer level 1 month after discontinuing anticoagulant therapy are useful parameters in identifying patients with an increased recurrence risk. The case of Ms W, a woman with unprovoked venous thromboembolism and hemorrhagic event while receiving anticoagulation, is used to illustrate clinical decision making to determine ongoing treatment.
Alpha<sub>1</sub>-Antitrypsin Deficiency with Severe Panniculitis
Authors: HERBERT M. RUBINSTEIN
Journal: Annals of Internal Medicine (1977)

Two patients with profound decrease of alpha1-antitrypsin (PiZZ) presented with severe panniculitis (Weber-Christian disease); one had systemic panniculitis including pancreatitis. Another possible case is quoted from the literature. Although milder forms of panniculitis can have normal Pi phenotypes and alpha1-antitrypsin levels, the marked reduction of antiproteolytic activity found in PiZZ homozygotes may predispose to or aggravate the lesions of Weber-Christian disease.
Guidelines should reflect all knowledge, not just clinical trials
Authors: T. Zuiderent-Jerak, F. Forland, F. Macbeth
Journal: BMJ (2012)

Over the past 20 years, evidence based medicine has had a substantial influence on clinical decision making throughout the developed world. It now underpins healthcare policy and the burgeoning industry of clinical guideline development. Two problems have resulted. Firstly, so called high level evidence is increasingly equated with strong recommendations; and secondly, evidence other than that derived from randomised controlled trials (RCTs) is seen as intrinsically less valuable or reliable.

The concept of a hierarchy of evidence with RCTs at the top is deeply ingrained, despite Sackett and colleagues’ warning that evidence based medicine “is not restricted to randomised trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions.”1 They pointed out that RCTs and systematic reviews of RCTs will provide the most reliable evidence that a therapy will do more good than harm but acknowledged that “some questions about therapy do not require randomised trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted.” 

They also made clear that other questions, such as those about diagnostic tests and prognosis, can only be answered using other forms of evidence. In his 2008 Harveian oration, Michael Rawlins, chairman of the National Institute for Health and Clinical Excellence (NICE), elegantly analysed the strengths and …
Influences of Cardiorespiratory Fitness and Other Precursors on Cardiovascular Disease and All-Cause Mortality in Men and Women
Authors: Steven N. Blair, James B. Kampert, Harold Willis Kohl, Carolyn E. Barlow, Caroline A. Macera, Ralph S. Paffenbarger, Larry W. Gibbons
Journal: JAMA (1996)

To quantify the relation of cardiorespiratory fitness to cardiovascular disease (CVD) mortality and to all-cause mortality within strata of other personal characteristics that predispose to early mortality. DESIGN--Observational cohort study. We calculated CVD and all-cause death rates for low (least fit 20%), moderate (next 40%), and high (most fit 40%) fitness categories by strata of smoking habit, cholesterol level, blood pressure, and health status.Preventive medicine clinic.Participants were 25341 men and 7080 women who completed preventive medical examinations, including a maximal exercise test.Cardiovascular disease and all-cause mortality.There were 601 deaths during 211996 man-years of follow-up, and 89 deaths during 52982 woman-years of follow-up. Independent predictors of mortality among men, with adjusted relative risks (RRs) and 95% confidence intervals (CIs), were low fitness (RR, 1.52;95% CI, 1.28-1.82), smoking (RR, 1.65; 95% CI, 1.39-1.97), abnormal electrocardiogram (RR, 1.64;95% CI, 1.34-2.01), chronic illness (RR, 1.63;95% CI, 1.37-1.95), increased cholesterol level (RR, 1.34; 95% CI, 1.13-1.59), and elevated systolic blood pressure (RR, 1.34; 95% CI, 1.13-1.59). The only statistically significant independent predictors of mortality in women were low fitness (RR, 2.10; 95% Cl, 1.36-3.21) and smoking (RR, 1.99; 95% Cl, 1.25-3.17). Inverse gradients were seen for mortality across fitness categories within strata of other mortality predictors for both sexes. Fit persons with any combination of smoking, elevated blood pressure, or elevated cholesterol level had lower adjusted death rates than low-fit persons with none of these characteristics.Low fitness is an important precursor of mortality. The protective effect of fitness held for smokers and nonsmokers, those with and without elevated cholesterol levels or elevated blood pressure, and unhealthy and healthy persons. Moderate fitness seems to protect against the influence of these other predictors on mortality. Physicians should encourage sedentary patients to become physically active and thereby reduce the risk of premature mortality.
Characterization of lipase activities in obese Pima indians. Decreases with weight reduction.
Authors: J S Reitman, F C Kosmakos, B V Howard, M R Taskinen, T Kuusi, E A Nikkila
Journal: Journal of Clinical Investigation (1982)

Adipose tissue and muscle lipoprotein lipase and postheparin hepatic and lipoprotein lipase activities have been measured in a group of 21 Pima Indian males over a wide range of body weight to determine the relationship between obesity and these lipase activities. There was a significant positive correlation between adipose tissue lipoprotein lipase and obesity; muscle and postheparin lipoprotein lipase and hepatic lipase were not related to degree of obesity. Fasting insulin levels were not related to any of the measurements of lipase activity. There were racial differences in adipose and postheparin lipoprotein lipase activities; both were significantly lower in the Pimas as compared with a group of weight-matched Caucasian males. Lipase activities were remeasured in eight subjects after a period of weight reduction including several weeks of stabilization at the reduced weights. After the period of weight reduction adipose tissue lipoprotein lipase declined in all subjects. Hepatic lipase also declined in all but two patients. Muscle and postheparin lipolytic activities were not affected by weight loss. The data indicate that (a) there are racial differences in adipose tissue lipoprotein lipase; and (b) the elevated adipose lipoprotein lipase associated with obesity, like many other biochemical variables in the obese state, returns toward normal after weight reduction.
Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma
Authors: F Liao, Y-C Hsu, S-H Kuo, Y-C Yang, J-P Chen, P-N Hsu, C-W Lin, L-T Chen, A-L Cheng, C S J Fann, J-T Lin, M-S Wu
Journal: Blood Cancer Journal (2014)

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r2=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4+ T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.