tbuckley/cabot-search huggingface dataset:
Abstract 2536: VEGF as a potential survival factor for keratinocytes following UV exposure <i>in vivo</i>
Authors: Kelly E. Nye, Monica K. Lachey, Allison E. Parent, Traci A. Wilgus
Journal: Cancer Research (2012)

Abstract Non-melanoma skin cancer (NMSC) is the most prevalent type of cancer. These cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are primarily caused by chronic exposure to ultraviolet light (UV) from the sun. Vascular endothelial growth factor (VEGF) is produced by the skin in response to UV and is known to promote NMSC indirectly through the induction of angiogenesis. Evidence is emerging that VEGF can also promote skin carcinogenesis by directly affecting epidermal keratinocytes and tumor cells. In addition, epidermal keratinocytes express VEGFR-1 and proliferate and migrate directly in response to VEGF. In endothelial cells, VEGF functions as a potent survival factor by inhibiting apoptosis; however, it is not known if VEGF promotes survival in keratinocytes. Keratinocytes undergo apoptosis in response to UV exposure, a process that can be disrupted during carcinogenesis. Here, the role of VEGF and VEGFR-1 in keratinocyte and SCC-13 tumor cell survival after UV exposure was explored. Neutralizing VEGF or VEGFR-1 activity or adding VEGF did not affect UV-induced apoptosis, suggesting that VEGF-VEGFR-1 signaling is not important for keratinocyte or SCC-13 survival in vitro. The role of VEGFR-1 in keratinocyte survival was also examined in vivo. Mice with VEGFR-1-deficient keratinocytes (K14-Cre/VEGFR-1fl/fl) were generated and exposed to a single acute dose of UV light. Keratinocytes in the epidermis of K14-Cre/VEGFR-1fl/fl mice showed a significant increase in apoptosis 24 hours following UV exposure compared to K14-Cre/VEGFR-1+/+ controls. Future studies will investigate skin carcinogenesis in K14-Cre/VEGFR-1fl/fl mice chronically exposed to UV light. Overall, these results suggest that VEGFR-1 mediates the survival of keratinocytes exposed to acute UV in vivo and points to a mechanism by which VEGF could directly promote skin carcinogenesis. 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 2536. doi:1538-7445.AM2012-2536
Public health and the 1991 census
Authors: V S Raleigh, R Balarajan
Journal: BMJ (1994)

against the use of race or ethnic groups as variables except in research into the impact of racism and disadvantage due to cultural differences on the use and provision of health care.2It was specifically to address inequalities that "ethnic" data were included as part of the contract minimum datasets, which provider units in the NHS will have to generate for each patient.The proposed categories are based on those used by the Office of Population Censuses and Surveys-a political and pragmatic classification designed for a census rather than to demarcate sociocultural differences.14The chief medical officer is clear that these broad categories may not be sensitive enough to identify important local variations.15The availability of such data will, however, lead to a host of papers looking at "ethnicity" and, for example, hospital admissions, length of stay, and use of services.These papers will be limited by the doubtful validity of the variables, their mutability, and their substantial confounding by socioeconomic and educational status- information not recorded in the contract minimum data- set.To discover why different groups have different experiences of health and what can be done to redress the balance we need to disentangle the influences of racism, education, unemployment, and social deprivation.A thorough investigation of the validity of current classifications is urgently needed; in the meantime, science could be greatly improved by adopting the methodological rigour expected elsewhere in medical research.This would include a discussion of the relevance of collecting data on ethnic group; a description and explanation of the categories, how they are to be used, and the logic underlying them; and the measurement of possible confounders.Any hypothesis should be consistent with the conceptual framework used-whether biological, socio- logical, or interactional.In 1991 Bhopal and colleagues called for a wide debate to establish internationally acceptable principles guiding classification and description of ethnic groups.'2In this issue Senior and Bhopal give nine recommendations on how to make ethnicity a sounder epidemiological variable.If these guidelines were to be followed then new research in this field might start to be comparable and could improve our understanding of differences in health between ethnic groups.
Phasic effects of repetitive vagal stimulation on atrial contraction.
Authors: P J Martin, J R Levy, S Wexberg, M N Levy
Journal: Circulation Research (1983)

The vagus nerves of anesthetized dogs were stimulated once each cardiac cycle with a brief burst of pulses, and the timing of the stimulus bursts was changed by a fixed increment on successive cardiac cycles. The effects of such vagal stimulation on atrial contraction depended on the number of pulses per stimulus burst, on the interval between pulses within the burst, and on the timing of the stimulus bursts within the cardiac cycle. The vagal stimulus bursts had the least negative inotropic effect when they were given less than 100 msec before the next atrial depolarization, and they were most effective when given about 330 msec before the next atrial depolarization. This dependence of the inotropic response on the timing of the vagal activity within the cardiac cycle indicates that the following conditions must prevail with respect to the vagal innervation of the atrium: (1) the acetylcholine released from the vagal nerve endings is hydrolyzed at a critically rapid rate in the atrial tissues, (2) the neurally released acetylcholine must exert its major influence on atrial contraction during some preferential fraction of the cardiac cycle (presumably, during depolarization), and (3) after a vagal stimulus of a given strength, the concentration of acetylcholine in the region of the myocardial cells will attain its maximum value during this critical phase of the cardiac cycle when the vagal stimuli are given at the optimal time in the cardiac cycle.
Cholesterol and Clinical Decisions
Authors: BRUCE R. ZIMMERMAN
Journal: Annals of Internal Medicine (1979)

Letters and Corrections1 May 1979Cholesterol and Clinical DecisionsBRUCE R. ZIMMERMAN, M.D.BRUCE R. ZIMMERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-5-851_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Kannel and associates in the January issue provide an excellent review of the epidemiologic data relating lipids and lipoproteins to atherosclerosis (1). On the whole, the statistical significance obtained in these studies is impressive. Unfortunately, I believe that in the segment of their paper relating to clinical implications, the difference between statistical and clinical significance is not emphasized strongly enough and their recommendations will lead to an unnecessary increase in medical costs. As can be clearly seen in their Figure 2, most patients with or without coronary heart disease have total serum cholesterol values ranging from 150...Reference1. KANNELCASTELLIGORDON WWT: Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med 90:85-91, 1979 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Mayo Clinic Rochester, MN 55901 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1979Volume 90, Issue 5Page: 851-851KeywordsAtherosclerosisCholesterolClinical epidemiologyCoronary heart diseaseLipidsLipoproteins Issue Published: 1 May 1979 PDF DownloadLoading ...
Thrombocytopenic Purpura after Smallpox Vaccination
Authors: T. E. Meindersma, S. I. de Vries
Journal: BMJ (1962)

MEA JOUTISHThe results of administering amiphenazole to 16 patients are given.Carbon dioxide tension was lowered significantly in eight cases, and this was associated with an increase in ventilation.It is suggested that amiphenazole has a place in the treatment of carbon dioxide retention.Although the effects are noted with smaller doses, it is advisable that 150 mg.should be given intravenously, and the results suggest that there might be a place for continuing the drug intramuscularly for some time.I thank Dr. J. V. Hurford, under whose care some of the
Reflections on the Postmortem Audit
Authors: Hartmann H. R. Friederici
Journal: JAMA (1988)

IN 1919, The Institute of Medicine of Chicago formed a committee on necropsies in the belief that "the interest of a hospital in necropsies is an important index of its efficiency in treating disease and of the grade of work done in the hospital."<sup>2</sup>For 69 years, this committee has compiled annual statistics on the frequency of autopsies in the metropolitan Chicago area. In 1967, Stenn<sup>3</sup>published a summary of the committee's activities and a graph illustrating the steady increase in autopsy rates in Chicago area hospitals over 50 years (Fig 1). From an overall rate of 11% in 1919, the number of necropsies performed in hospitals that reported had increased to 51.2% in 1965, when 14 506 postmortem examinations were performed on 28 350 patients who had died in the hospital. Stenn concluded that this interest in the postmortem audit meant that physicians were sincere in wanting
Accidental hypothermia. Associated diagnoses and prognosis in a common problem
Authors: L. D. Hudson
Journal: JAMA (1974)

Sixteen patients with accidental hypothermia were admitted to the medical service of a general hospital in a one-year period. Analysis of the clinical status of the patients and the associated disease states showed that the underlying disease was more important in determining survival than the method of rewarming. Seven of eight patients with marked underlying organ system disease died, while all eight patients without severe organic disease survived even though the degree of hypothermia and time required for rewarming were similar in the two series. Slow passive rewarming is adequate therapy for most hypothermic patients, and major therapeutic efforts should be directed at underlying disease processes rather than the physiologic response to hypothermia.
Oxidative stress pathways in noncancerous human liver tissue to predict hepatocellular carcinoma recurrence: A prospective, multicenter study
Authors: Shinji Tanaka, Kaoru Mogushi, Mahmut Yasen, Daisuke Ban, Norio Noguchi, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Masakazu Yamamoto, Norihiro Kokudo, Tadatoshi Takayama, Seiji Kawasaki, Michiie Sakamoto, Shigeki Arii
Journal: Hepatology (2011)

The prediction of cancer recurrence holds the key to improvement of the postoperative prognosis of patients. In this study, the recurrence of early-stage hepatocellular carcinoma (HCC) after curative hepatectomy was analyzed by the genome-wide gene-expression profiling on cancer tissue and the noncancerous liver tissue. Using the training set of 78 cases, the cytochrome P450 1A2 (CYP1A2) gene in noncancerous liver tissue was identified as the predictive candidate for postoperative recurrence (hazard ratio [HR], 0.447; 95% confidence interval [CI], 0.249-0.808; P = 0.010). Multivariate analysis revealed the statistically significant advantage of CYP1A2 down-regulation to predict recurrence (odds ratio, 0.534; 95% CI, 0.276-0.916; P = 0.036), and the expression of CYP1A2 protein was confirmed immunohistochemically. An independently multi-institutional cohort of 211 patients, using tissue microarrays, validated that loss of expression of CYP1A2 in noncancerous liver tissue as the only predictive factor of recurrence after curative hepatectomy for early-stage HCC (HR, 0.480; 95% CI, 0.256-0.902; P = 0.038). Gene set-enrichment analysis revealed close association of CYP1A2 down-regulation with oxidative stress pathways in liver tissue ( P &lt; 0.001, false discovery rate [FDR] = 0.042; P = 0.006, FDR = 0.035). Our results indicate these pathways as the molecular targets to prevent recurrence, as well as the potential prediction of the super high-risk population of HCC using liver tissue. (Hepatology 2011;54:1273–1281)
Serum Esterolytic Activity in a Wide Variety of Diseases
Authors: Victor W. Groisser, Frances Rauch, Martin Floch, Jerome Bobruff
Journal: New England Journal of Medicine (1966)

THERE have been several recent reports suggesting the diagnostic value of measuring the hydrolysis of two arginine substrates, benzoyl-L-arginine ethyl ester (BAEE)1 and benzoyl arginine amide (BAA)2 , 3 by serum of patients with acute pancreatitis and carcinoma of the pancreas. Although more than one component of serum has been shown to be capable of hydrolyzing these substrates, it has been suggested that trypsin may be elevated in pancreatic disease and could conceivably account for the enhanced hydrolysis of the arginine substrates. In any event, if significant hydrolysis could be established in one or both of these diseases, an appreciable diagnostic advance . . .
Doctor is cleared of manslaughter for prescribing penicillin to man who said he was allergic
Authors: C. Dyer
Journal: BMJ (2008)

A locum GP who prescribed penicillin V (phenoxymethylpenicillin) to a 73 year old man who died after taking the drug has been cleared of manslaughter. The jury at Plymouth Crown Court unanimously found Mitra Nikkhah not guilty after two hours of deliberation.

Dr Nikkhah, 41, was accused of the manslaughter of David Townsend by gross negligence. The prosecution case was that she prescribed the drug despite a warning by Mr Townsend and his wife that he was allergic to it and that he had gone into anaphylactic shock and died as a result.

Mr Townsend died in May 2006 after …
Open letter to the National Blood Service
Authors: A. Melville
Journal: BMJ (2002)

EDITOR—Another invitation to give blood has arrived, bringing with it a now familiar wash of guilt. I have not given since last July, and I am not sure whether I shall ever do it again. My sister, whose rare blood group makes her contribution particularly valuable, will not go either, and for the same reasons.

We both had blood taken by someone who was not competent to do the job. We both suffered pain and extensive bruising. Giving blood is not pleasant but it …
Is the level of Brain Natriuretic Peptide correlated with VO<sub>2</sub>max and O<sub>2</sub> pulse in patients with heart failure?
Authors: M. Feola, A. Deorsola, A. Vado, E. Menardi, L. Riva, A.M. Bramardi, U. Milanese, E. Uslenghi
Journal: European Journal of Heart Failure (2000)
Down-regulation of Androgen Receptor by 3,3′-Diindolylmethane Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells
Authors: Mohammad M.R. Bhuiyan, Yiwei Li, Sanjeev Banerjee, Fakhara Ahmed, Zhiwei Wang, Shadan Ali, Fazlul H. Sarkar
Journal: Cancer Research (2006)

Abstract Despite the initial efficacy of androgen deprivation therapy, most patients with advanced prostate cancer eventually progress to hormone-refractory prostate cancer, for which there is no curative therapy. Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3′-diindolylmethane (DIM) in prostate cancer cells. However, the molecular mechanism of action of DIM has not been investigated in androgen receptor (AR)–positive hormone-responsive and -nonresponsive prostate cancer cells. Therefore, we investigated the effects of B-DIM, a formulated DIM with greater bioavailability, on AR, Akt, and nuclear factor κB (NF-κB) signaling in hormone-sensitive LNCaP (AR+) and hormone-insensitive C4-2B (AR+) prostate cancer cells. We found that B-DIM significantly inhibited cell proliferation and induced apoptosis in both cell lines. By Akt gene transfection, reverse transcription-PCR, Western blot analysis, and electrophoretic mobility shift assay, we found a potential crosstalk between Akt, NF-κB, and AR. Importantly, B-DIM significantly inhibited Akt activation, NF-κB DNA binding activity, AR phosphorylation, and the expressions of AR and prostate-specific antigen, suggesting that B-DIM could interrupt the crosstalk. Confocal studies revealed that B-DIM inhibited AR nuclear translocation, leading to the down-regulation of AR target genes. Moreover, B-DIM significantly inhibited C4-2B cell growth in a severe combined immunodeficiency–human model of experimental prostate cancer bone metastasis. These results suggest that B-DIM-induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of AR, Akt, and NF-κB signaling. These observations provide a rationale for devising novel therapeutic approaches for the treatment of hormone-sensitive, but more importantly, hormone-refractory prostate cancer by using B-DIM alone or in combination with other therapeutics. (Cancer Res 2006; 66(20): 10064-72)
Portacaval Shunting and Upper Gastrointestinal Blood Flow
Authors: J. P. Delaney, R. L. Goodale, J. Cheng, O. H. Wangensteen
Journal: JAMA (1965)

Diversion of portal venous blood into the systemic circulation is associated with a high incidence of peptic ulcer in man. 1 Gastric secretory levels in patients with portacaval shunts are not above normal, but are probably elevated from preoperative values. 2 In the dog, portacaval shunting definitely enhances the rate of acid secretion by the stomach. 3 This has been shown to be due to a circulating substance, probably histamine. 4   The purpose of the present study was to determine, in the dog, changes in gastric, duodenal, pancreatic, and esophageal blood flows following creation of portacaval shunts. The radioisotope ( 42 K or 86 Rb) distribution method was used to measure tissue blood flows.  Materials and Methods  End-to-side portacaval anastomoses were constructed in nine healthy mongrel dogs. The control group consisted of 13 normal animals that had undergone no operation. All dogs were fed a standard diet of commercial dry cereal
Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy.
Authors: S M Catnach, A B Ballinger, M Stevens, P D Fairclough, R C Trembath, P L Drury, P J Watkins
Journal: Gut (1993)

Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated.
P943 DIFFERENCES IN CREATININE BETWEEN GENDERS COULD DISADVANTAGE INFECTED CIRRHOTIC WOMEN: THE NACSELD EXPERIENCE
Authors: J.S. Bajaj, J. O'Leary, K.R. Reddy, F. Wong, M. Fallon, S. Biggins, H. Patton, B. Maliakkal, P. Thuluvath, G. Garcia-Tsao, D. Koch, L. Thacker, P. Kamath
Journal: Journal of Hepatology (2014)
Problems of comprehensive shared diabetes care.
Authors: J L Day, H Humphreys, H Alban-Davies
Journal: BMJ (1987)

In its first year 747 diabetics were entered into a comprehensive shared care scheme in which general practitioners agreed to follow up their own patients. After two years patients were recalled to hospital for review through a computer based recall system. Analysis of the first 209 patients reviewed showed that the recall system worked well with failure to trace only eight patients. Six new cases of foot ulcer, 15 of retinopathy, 14 of macular degeneration, and 15 of raised blood pressure requiring treatment were detected at review. Sixty four patients appeared to have had no check on their diabetes during the two years. Of the 117 with written evidence in their cooperation books that they had received some diabetic supervision, many had had no measurement of weight (32), blood pressure (49), or urine (68) or blood glucose (70), and only 55 had had foot and 65 eye examination. This erratic and generally poor standard of supervision suggests that much tighter organisation is required within each practice, with time being set aside specifically for care of diabetics. Practice nurses could have an important role in the delivery and organisation of care.
Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation
Authors: Jason Webber, Robert Steadman, Malcolm D. Mason, Zsuzsanna Tabi, Aled Clayton
Journal: Cancer Research (2010)

There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses.