tbuckley/cabot-search huggingface dataset:
Relationship of endothelial function to birth weight in humans.
Authors: A S McAllister, A B Atkinson, G D Johnston, D R McCance
Journal: Diabetes Care (1999)

Low birth weight has been associated with hyperlipidemia, hypertension, diabetes, and coronary heart disease in adult life, but the precise mechanism is debated. The endothelium is thought to play a pivotal role in each of the above conditions with abnormalities being detectable before the development of overt disease. To investigate the possibility that endothelium has a role in mediating the excessive risk of adult vascular disease associated with low birth weight, endothelial function was assessed in young healthy adults who were either of low or normal birth weight at term.Twelve low birth weight (2.2 +/- 0.05 kg, mean +/- SEM) subjects (six men/six women; age 28 +/- 0.2 years) and twelve age- and sex-matched normal birth weight (3.3 +/- 0.07 kg) control subjects were studied. The L-arginine-nitric oxide pathway was assessed in the forearm vascular bed by using venous occlusion plethysmography during intra-arterial brachial infusion of acetylcholine, sodium nitroprusside, norepinephrine, and NG-monomethyl-L-arginine (L-NMMA). Von Willebrand factor, a noninvasive marker of endothelial dysfunction, was also measured. Comparisons were made using Student's t test.Von Willebrand factor was significantly elevated in low birth weight compared with normal birth weight subjects (136.9 +/- 12.7 vs. 95.6 +/- 9.5%; P = 0.016). The groups did not differ in the responses to acetylcholine (P = 0.76), sodium nitroprusside (P = 0.84), norepinephrine (P = 0.21), or L-NMMA (P = 0.35).The finding of elevated von Willebrand factor in low birth weight subjects is suggestive of endothelial cell injury but does not appear to be associated with dysfunction of the L-arginine-nitric oxide pathway.
Azacitidine induces profound genome-wide hypomethylation in primary myelodysplastic bone marrow cultures but may also reduce histone acetylation
Authors: M Grövdal, M Karimi, M Tobiasson, L Reinius, M Jansson, K Ekwall, J Ungerstedt, J Kere, D Greco, E Hellström-Lindberg
Journal: Leukemia (2013)
Altered Stoichiometry of FKBP12.6 Versus Ryanodine Receptor as a Cause of Abnormal Ca <sup>2+</sup> Leak Through Ryanodine Receptor in Heart Failure
Authors: Masafumi Yano, Kaoru Ono, Tomoko Ohkusa, Masae Suetsugu, Masateru Kohno, Takayuki Hisaoka, Shigeki Kobayashi, Yuji Hisamatsu, Takeshi Yamamoto, Michihiro Kohno, Naoya Noguchi, Shin Takasawa, Hiroshi Okamoto, Masunori Matsuzaki
Journal: Circulation (2000)

Background —In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca 2+ -ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506–binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. Methods and Results —SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B max values for [ 3 H]dihydro-FK506 to those for [ 3 H]ryanodine binding. In normal SR, the molar ratio was 3.6 (≈1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca 2+ leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca 2+ leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca 2+ leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. Conclusions —An abnormal Ca 2+ leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca 2+ leak might possibly cause Ca 2+ overload and consequent diastolic dysfunction, as well as systolic dysfunction.
TV: Living with Cancer
Authors: R. Camidge
Journal: BMJ (2001)

BBC 1, 15 October until 19 November, 10.35 pm Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> ![Graphic][4]</img> Oncologists never seem to get as many presents from their patients as surgeons do. Since I doubt that, as specialists, oncologists are somehow not as nice as surgeons, then there must be an alternative explanation. In Living with Cancer , Glenford, a young man with metastatic sarcoma, suggests a possible reason for this when he observes that “cancer has no beginning and no end.” Oncologists rarely get to finish the job and say goodbye while the patient is still alive because, even when treatment has eradicated all detectable signs of malignancy, cancers have a habit of coming back. How people live between clinic appointments with this kind of uncertainty—literally living with their cancer—is one motivation behind this remarkable new television series. The format of the series is refreshingly … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
THE CAUSE OF HYPERPIESIA: PRESENTATION OF A HYPOTHESIS
Authors: C. P. Donnison
Journal: BMJ (1934)

Of the several theories that hiLve been presented as an explanation of the common type of high blood pressure two alone receive an appreciable degree of general support.These are: (1) the toxaemic theory, and (2) the mental stress theory.The toxaemic theory may be subdivided into two groups, according to the suggested origin of the toxin.One suggestion is a focus of chronic infection, whilst the other postulates absorption of derivatives of protein digestion.The mental stress theory maintains that hyperpiesia arises as the result of an over-responsive vasomotor system consequent upon a high-pressure existence or of mental stress.The aetiological factors established regarcing hyper- piesia do not help much towards consideration of these theories, but one such factor, the geographical and racial distribution of the disease, affords some definite facts that require consideration when any theory is presented.The distribution of hyperpiesia is -not world-wide.The condition is exceedingly common in Europe and North America.In Egypt' it is common among certain classes, more particularly the educated, whilst among the hospital classes it is rare.It is rare among Chinese and Orientals,2 3 who have apparently lower average blood pressures than Europeans.Conception and Bulatao5
Combined Histopathological and Molecular Cytogenetic Stratification of Medulloblastoma Patients
Authors: Jayne M. Lamont, Charles S. McManamy, Andrew D. Pearson, Steven C. Clifford, David W. Ellison
Journal: Clinical Cancer Research (2004)

Abstract This study examined the utility of stratifying children with medulloblastomas by a combination of refined histopathological classification and molecular cytogenetic evaluation. Detailed histopathological classification of tumors from a cohort of patients (n = 87) composed mainly of children entered into the International Society of Pediatric Oncology (SIOP)/United Kingdom Children’s Cancer Study Group PNET3 trial (n = 65), included identification of the large cell/anaplastic phenotype. Fluorescence in situ hybridization was used to detect chromosome 17 abnormalities, losses of 9q22 and 10q24, and amplification of the MYCC and MYCN oncogenes. The large cell/anaplastic phenotype, which was present in 20% of medulloblastomas, emerged as an independent prognostic indicator. Loss of 17p13.3 (38% of medulloblastomas) was found across all of the histopathological variants, whereas MYCC/MYCN amplification (6%/8% of medulloblastomas) was significantly associated with the large cell/anaplastic phenotype. Both of these genetic abnormalities emerged as prognostic indicators. Loss of 9q22 was associated with the nodular/desmoplastic medulloblastoma variant, whereas loss of 10q24 was found in all of the variants. Together with metastatic tumor at presentation, the large cell/anaplastic phenotype, 17p13.3 loss, or high-frequency MYC amplification defined a high-risk group of children whose outcome was significantly (P = 0.0002) poorer than a low-risk group without these tumor characteristics. Combined evaluation of novel histopathological features and molecular cytogenetic abnormalities promises to allow stratification of patients with medulloblastoma, such that those likely to be cured will be spared the side effects of maximal therapy, which can be targeted at those with aggressive disease.
Abstract 4151: Real-time imaging of inter-cellular communication via exosomes
Authors: Kimi Homma, Atsushi Suetsugu, Takahiro Ochiya, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract Growing evidence suggests that extracellular microRNAs (miRNAs) stably exist in human body fluids, including plasma, saliva and urine, although ribonucleases (RNases) also circulate throughout the body. Therefore, miRNAs are excreted in RNase-resistant lipid vesicles, such as exosomes and apoptotic bodies, which can deliver gene-silencing signals between living cells in vitro and in vivo. However, very little is known about the exosome-mediated intra-cellular communication machinery. Here we demonstrate with labeling of exosomes with green fluorescent protein (GFP) linked to CD63, the transfer and incorporation of exosomes into recipient cells via indirect or direct contact with cells in a co-culture system. These findings suggest that secretory exosomes are transfered from cell to cell, transferring genetic information that can affect a wide array of biological events. 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 4151. doi:1538-7445.AM2012-4151
Circumstances around weapon injury in Cambodia after departure of a peacekeeping force: prospective cohort study
Authors: D. R Meddings, S. M O'Connor
Journal: BMJ (1999)

To examine the circumstances surrounding weapon injury and combatant status of those injured by weapons.Prospective cohort study.Northwestern Cambodia after departure of United Nations peacekeeping force.863 people admitted to hospital for weapon injuries over 12 months.Annual incidence of weapon injury by time period; proportions of injuries inflicted as a result of interfactional combat (combat injuries) and outside such combat (non-combat injuries) by combatant status and weapon type.The annual incidence of weapon injuries was higher than the rate observed before the peacekeeping operation. 30% of weapon injuries occurred in contexts other than interfactional combat. Most commonly these were firearm injuries inflicted intentionally on civilians. Civilians accounted for 71% of those with non-combat injuries, 42% of those with combat related injuries, and 51% of those with weapon injuries of either type.The incidence of weapon injuries remained high when the disarmament component of a peacekeeping operation achieved only limited success. Furthermore, injuries occurring outside the context of interfactional combat accounted for a substantial proportion of all weapon injuries, were experienced disproportionately by civilians, and were most likely to entail the intentional use of a firearm against a civilian.
Balancing Thrombotic Events and Bleeding in Primary PCI
Authors: Shamir R Mehta
Journal: New England Journal of Medicine (2013)

Primary percutaneous coronary intervention (PCI) has become the preferred method of reperfusion for patients with ST-segment elevation myocardial infarction (STEMI) when the procedure can be performed promptly by experts. Anticoagulation is important in patients undergoing primary PCI because it prevents acute thrombus formation at the site of arterial injury and on PCI-related hardware.1 Major bleeding that is associated with antithrombotic therapy is independently associated with subsequent death and recurrent ischemic events, and this relationship may be causal.2,3 One approach to reduce bleeding is to use antithrombotic therapies with better safety profiles. In the Harmonizing Outcomes with Revascularization and Stents . . .
Cystic Lymphangiomatosis
Authors: GARY J. NOVETSKY, AVRUM J. EPSTEIN
Journal: Clinical Nuclear Medicine (1982)

Splenic lesions on Tc-99m SC scintigraphy are usually caused by lymphoma, infarctions, or tumor. A case of cystic lymphangiomatosis of the spleen, an extremely rare pathologic entity, causing similar splenic defects is presented and the preoperative diagnosis is discussed.
Use of Chlorpromazine in the Treatment of Nausea and Vomiting of Uremia
Authors: Dale G. Friend, James F. Cummins
Journal: New England Journal of Medicine (1954)

NAUSEA and vomiting, which are common complications of uremia, may cause only mild distress or may be of such severity as to create a distinct hazard to the patient. Nausea interferes with proper food intake, and frequently an inadequate, unbalanced diet results. Furthermore, the associated mental and emotional distress may prove most unpleasant to the patient, seriously exhausting him and undermining his ability to resist the disease. Persistent vomiting is dangerous and can lead to serious consequences if not properly and adequately controlled. It not only is capable of upsetting electrolyte balance, creating dehydration and exhausting the patient, but also . . .
Abstract 122: MiR-9-3 and miR-193a are targets for DNA methylation in non-small cell lung cancers
Authors: Gerwin Heller, Marlene Weinzierl, Christian Noll, Valerie Babinsky, Barbara Ziegler, Corinna Altenberger, Christoph Minichsdorfer, György Lang, Balazs Döme, Adelheid End-Pfützenreuter, Britt-Madeleine Arns, Yuliya Grin, Walter Klepetko, Christoph C. Zielinski, Sabine Zöchbauer-Müller
Journal: Cancer Research (2012)

Abstract DNA methylation (referred to as methylation) is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of different malignant diseases including non-small cell lung cancers (NSCLC). Recently, it has been reported that besides protein encoding genes also microRNA (miRNA) encoding genes may be targets for methylation in NSCLCs, however, the number of known methylated miRNA genes is still small. To investigate the role of methylation on miRNA gene silencing in NSCLCs, we performed microarray expression analyses of 856 miRNA genes in NSCLC A549 cells before and after treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (Aza-dC) and with a combination of Aza-dC and the histone deacetylase inhibitor trichostatin A. Comparing microarray data of untreated and drug treated A549 cells, we identified 33 miRNA genes whose expression was upregulated after drug treatment and which are associated with a CpG island. Methylation of these miRNA genes was determined in 11 NSCLC cell lines by methylation-sensitive high resolution melting (MS-HRM) analysis and 30 of 33 (91%) miRNA genes were found to be methylated in at least 1 NSCLC cell line. In addition, methylation of the miRNA genes miR-9-3 and miR-193a was also analysed in primary tumors and corresponding non-malignant lung tissue samples of 101 stage I-III NSCLC patients and was found to be tumor-specific. Moreover, we compared miR-9-3 and miR-193a methylation results and clinico-pathological characteristics of NSCLC patients. We found a shorter disease-free survival of miR-9-3 methylated lung squamous cell carcinoma (LSCC) patients compared to miR-9-3 unmethylated LSCC patients by multivariate analysis (HR = 3.8, 95% CI = 1.3 to 11.2, p = 0.017) and a shorter overall survival of miR-9-3 methylated LSCC patients compared to miR-9-3 unmethylated LSCC patients by univariate analysis (p = 0.013). In conclusion, our results suggest that methylation is an important mechanism for silencing certain miRNA genes in NSCLCs and that miR-9-3 methylation may serve as a prognostic parameter in LSCC patients. 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 122. doi:1538-7445.AM2012-122
FORMALDEHYDE AS A PRACTICAL DISINFECTANT.
Authors: WALTER L. BIERRING
Journal: JAMA (1898)

The study of disinfectants and disinfection is of interest to all who are concerned in the preservation of public health. Recent years have afforded the means of placing this study upon more of a reliable and scientific basis. Frequent observation has noted the fact that although a certain disinfectant may be possessed of active germicidal properties in the laboratory, where it can generally be brought in direct contact with the microbe, it often fails signally when applied on a larger scale or for practical purposes. Recently formaldehyde has been brought forward with considerable enthusiasm as a disinfecting agent, and the series of experiments embodied in this paper were directed toward determining to a certain extent its utility in this respect. In connection with a cursory review of the existing literature on the subject, an effort has been made to draw into comparison the several agents and substances heretofore used more
Identification of Histamine Metabolite 1-methyl,4-imidazole Acetic Acid in Human Urine and its Absence in Status Asthmaticus
Authors: J. W. Kerr
Journal: BMJ (1964)

Lincomycin and Pristinamycin-Barber and Waterworth MEDICATJISHRNAL In spite of chemical differences, lincomycin has been shown to have an antibacterial activity similar to that of the macrolides, including partial cross-resistance.Pristinamycin has an activity that might have been predictedfrom its chemical similarity to ostreogrycin.
Randomized Comparison of Weekly Cisplatin or Protracted Venous Infusion of Fluorouracil in Combination With Pelvic Radiation in Advanced Cervix Cancer: A Gynecologic Oncology Group Study
Authors: Rachelle Lanciano, Alison Calkins, Brian N. Bundy, Groesbeck Parham, Joseph A. Lucci, David H. Moore, Bradley J. Monk, Dennis M. O'Connor
Journal: Journal of Clinical Oncology (2005)

Concurrent chemoradiotherapy is the standard of care for locally advanced cervix cancer; the optimal chemotherapy regimen is not yet defined. This trial was designed to compare the outcome of protracted venous infusion (PVI) fluorouracil (FU) with standard weekly cisplatin and concurrent radiation therapy (RT).Patients with stage IIB, IIIB, and IVA cervical cancer with clinically negative aortic nodes were eligible. Pelvic RT dose was 45 Gy with a parametrial boost to involved sides of 5.4 to 9 Gy, and high- or low-dose rate intracavitary brachytherapy. Standard therapy was weekly cisplatin 40 mg/m2, and experimental therapy was PVI FU 225 mg/m2/d for 5 d/wk for six cycles during RT.The study was closed prematurely when a planned interim futility analysis indicated that PVI FU/RT had a higher treatment failure rate (35% higher) and would, most likely, not result in an improvement in progression-free survival compared with weekly cisplatin/RT. The PVI FU/RT arm continues to show a higher risk of treatment failure (relative risk [RR] unadjusted, 1.29) and a higher mortality rate (RR unadjusted, 1.37). There was no difference in pelvic treatment failure between regimens, but there was an increase in the failure rate at distant sites in the PVI FU arm.In this study, PVI FU does not show improved outcome over weekly cisplatin. Future research should explore combinations of FU with cisplatin, new radiosensitizers, and active drugs combined with RT to reduce the high rate of pelvic and distant treatment failure still seen in advanced cervix cancer.
Prostaglandins contribute to cardiovascular reflexes evoked by static muscular contraction.
Authors: C L Stebbins, Y Maruoka, J C Longhurst
Journal: Circulation Research (1986)

The purpose of this study was to determine the contribution of prostaglandins to the reflex cardiovascular responses induced by static contraction of the hind limb in cats, i.e., the exercise reflex. To accomplish this, the cardiovascular responses to hind limb contraction induced by electrical stimulation of spinal cord ventral roots L6-7 and S1 were compared before and after inhibition of prostaglandin synthesis (indomethacin, 2-6 mg/kg i.v., n = 5, or sodium meclofenamate, 2-6 mg/kg i.v., n = 5) or after injection of prostaglandin E2 into the hind limb arterial blood supply. Treatment with indomethacin attenuated the contraction-induced increase in mean arterial pressure and left ventricular dP/dt by 76% and 86%, respectively. Heart rate and average developed triceps surae muscle tension were unchanged. After administering sodium meclofenamate, the reflex response was attenuated to a similar degree. In the indomethacin-treated animals, injection of exogenous prostaglandin E2 (PGE2) partially restored the pressor and myocardial contractile responses. In 6 animals, treatment with exogenous PGE2 without prior inhibition of prostaglandin synthesis did not significantly augment the contraction-induced cardiovascular response. Using the radioactive microsphere technique, we measured skeletal muscle blood flow during contraction before and after treatment with indomethacin (n = 6) to determine if an indomethacin-induced alteration in blood flow could account for the attenuated contraction-induced cardiovascular response. Blood flow during static muscle contraction was not significantly altered by indomethacin. We conclude that prostaglandins contribute to the exercise reflex through an action on afferent nerve endings rather than through a regional vascular effect.
The epidemiology of gastrointestinal cancer with special reference to causation
Authors: J. Boyd, M. Langman, R. Doll
Journal: Gut (1964)

The epidemiology of gastrointestinal cancer with special reference to causation'A great deal of evidence is now available to show that the incidence of gastrointestinal cancer.variesfrom place to place and from time to time.Moreover, the incidence among migrant populations is, in general, intermediate between that found in their original homeland and that in the country to which they have emigrated.It is evident, therefore, that environmental factors play an important part in the development of these cancers and that many of them may be preventible. AETIOLOGICAL FACTORSGASTRIC CANCER The most striking observation relating to the incidence of gastric cancer is the rapid decline that has taken place in the U.S.A. during the last 30 years.A decrease has also occurred in many other countries, some, but not all, of which originally showed a high incidence, but it is not universal and there has been little or no change in Japan.In general the decrease has begun first and been more marked in women than in men.The incidence varies at least tenfold between different countries.The disease is common in Japan, Iceland, Finland, Poland, parts of the U.S.S.R., China and Chile, relatively rare in the white population of the U.S.A. and very rare in many parts of the native populations of Africa, South America, and India.Striking contrasts are provided by Uganda (rare) and part of Kivu province of the Congo (common) and in Java by the Chinese inhabitants (common) and the native Indonesians (rare).The incidence varies to a considerable extent within countries, and even within quite small countries.It is commoner in North Wales than in south-east England and in the Alpine and Pannonian plain regions of Slovenia than in the Mediterranean littoral.In general it is commoner in the northern parts of countries in the northern hemisphere than in the southern parts, although no such difference is revealed in Norway.