tbuckley/cabot-search huggingface dataset:
Abstract 1054: The role of DNMT1 in the DNA damage response
Authors: Gun Eui Lee, Keith D. Robertson
Journal: Cancer Research (2012)

Abstract DNA methyltransferases (DNMTs) are proteins reponsible for establishing and maintaining genome-wide patterns of DNA methylation, an epigenetic signature regulating gene expression and genome integrity. DNMT1 is regarded as the maintenance enzyme while DNMT3A/3B are involved in the de novo synthesis of DNA methylation pattern. Besides its known role in copying methylation during replication, DNMT1 has been reported to be involved in the DNA damage response by recruitment to damaged sites on DNA. However, the mechanism of how DNMT1 takes part in DNA damage repair (DDR) remains to be elucidated. Our previous study showed that DNMT1 is an early responder to DNA double-strand breaks and interacts with components of the DDR machinery (Ha, KS et al, 2011, Hum. Mol. Genet., 20 (1): 126-140). In order to further characterize the role of DNMT1 in DDR, we analyzed DNMT1 in cis and trans. In our previous study, we observed that DNMT1 is recruited to DNA damage sites rapidly and transiently. Since DNMT1 is present throughout the cell cycle, this rapid and transient localization suggests that, upon DNA damage, in order to localize on DNA damage sites, a fraction of the DNMT1 protein pool might be modified and/or its complement of binding partners transiently altered. To this end, we purified DNMT1 from mammalian cells before and after ionizing radiation and analyzed its post-translational modifications (PTMs) by mass spectrometry. DNMT1 shows multiple unique patterns of PTMs including acetylation and methylation before and after ionizing radiation. In order to characterize trans-acting partners of DNMT1 after DNA damage, we purified DNMT1 complexes after protein cross-linking and used mass spectrometry to determine the identity of interacting factors. Consistent with changes in the localization and PTM patterns on DNMT1 in the presence and absence of DNA damage, several known and novel DNMT1-protein interactions are also altered in cells with damaged DNA. Finally, in order to understand the role of DNMT1 in the DDR mechanism in a physiological context, we used siRNA to acutely reduce levels of DNMT1 in the presence and absence of DNA damage. Knock-down of DNMT1 reduced the activation of DDR signaling molecules such as ATM, CHK1, and γ-H2AX in a colon cancer cell line. Collectively, our results demonstrate that DNMT1 is a critical molecule involved in coordinating DNA damage signaling with DNA repair mechanisms. 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 1054. doi:1538-7445.AM2012-1054
Reflex sympathetic dystrophy associated with squamous cell carcinoma of the lung.
Authors: M Prowse, C M Higgs, C Forrester-Wood, N McHugh
Journal: Annals of the Rheumatic Diseases (1989)

Reflex sympathetic dystrophy was the presenting feature in an otherwise occult case of non-metastatic squamous cell carcinoma of the lung which improved on surgical removal of the primary tumour. Reflex sympathetic dystrophy, therefore, should be considered an occasional manifestation of a paraneoplastic syndrome warranting a thorough search for underlying malignancy.
Mechanism of cardiovascular changes produced in cats by activation of the central nervous system with picrotoxin.
Authors: J A DiMicco, T Prestel, D L Pearle, R A Gillis
Journal: Circulation Research (1977)

The mechanism of cardiovascular changes produced by activation of the central nervous system with picrotoxin (2 mg/kg, iv) was studied in chloralose-anesthetized cats.Effects occurred in two phases.During the early phase, there were decreases in arterial blood pressure and heart rate, and in a few cats, bradyarrhythmias.These changes were transient and superceded by an increase in arterial blood pressure and, in most cases, ventricular tachyarrhythmias.The early phase changes were mediated primarily by the cardiac vagus nerve whereas the later phase changes were mediated primarily by sympathetic nerves and the adrenal medulla.The ventricular tachyarrbythmias were unaffected by pretreatment with atropine, bilateral vagotomy, or beta adrenergic blocking agents.On the other hand, bilateral extirpation of the stellate ganglia and adrenal glands prevented the ventricular arrhythmias from occurring.In addition, administration of drugs that blocked alpha adrenergic receptors effectively counteracted picrotoxin-induced ventricular arrhythmias.These results indicate that the centrally induced ventricular arrhythmias were mediated by cardiac sympathetic nerves and/or release of catecholamines from the adrenal medulla.More importantly, these results indicate that one cannot equate beta adrenergic blockade with elimination of sympathetic influence on the heart.Finally, sympathetically induced arrhythmias resistant to beta adrenergic blockade appear to respond to drugs that block cardiac adrenergic alpha receptors.
Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2
Authors: György Baffy, Chen-Yu Zhang, Jonathan N. Glickman, Bradford B. Lowell
Journal: Hepatology (2002)

Nonalcoholic fatty liver disease (NAFLD), a prevalent condition associated with obesity, has the potential of evolving into end-stage liver disease. The biochemical mechanisms that define the progression of NAFLD are not well known, but reactive oxygen species (ROS) have been implicated in this process. Uncoupling protein (UCP) 2 is a mitochondrial inner-membrane protein that mediates proton leak, uncouples adenosine triphosphate (ATP) synthesis, and negatively regulates ROS production. UCP2 expression is increased in various animal models of NAFLD. Up-regulation of UCP2 may compromise cellular ATP levels and worsen liver damage, or it may be protective by ROS reduction in NAFLD. This study aimed to obtain a definitive answer as to whether increased UCP2 expression contributes to NAFLD. UCP2-/- mice were exposed to obesity by crossbreeding with ob/ob mice and by long-term high-fat feeding to study the effect of UCP2 deficiency on the outcome of NAFLD. Steatohepatitis score of crossbred mice (ob/ob/ko) was similar to that of ob/ob mice at 25 weeks. No compensatory increase was observed in the expression of UCP5 in ob/ob/ko livers. To unmask the effects of absent leptin and its potential proinflammatory actions, steatosis was also induced in UCP2-/- mice by a high-fat diet continued for 6 months. Serum alanine aminotransferase (ALT) levels remained normal, and the steatohepatitis score in UCP2-/- mice was the same as in wild-type controls. We conclude that increased expression of UCP2 in the livers of mice with genetically or diet-induced obesity exerts neither protective nor deleterious effects on the severity of fatty liver disease.
Backache and the Guillain-Barre syndrome.
Authors: R Grant
Journal: BMJ (1986)

and influential paper because we are also com- paring inpatient versus outpatient treatment techniques (albeit with entirely different clients).We acknowledge that the outpatient programme in our study was less intensive than that of Edwards and Guthrie (paragraph 3 in Discussion) and that more intensive outpatient methods may lead to improved outcome (final paragraph, Discus- sion); (d) again, Dr McBride appears to have misunderstood the purpose of our study.We were evaluating the success of different detoxification procedures per se and neither intending nor attempting any long term follow up study.
Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis.
Authors: F M Giardiello, G J Offerhaus, D H Lee, A J Krush, A C Tersmette, S V Booker, N C Kelley, S R Hamilton
Journal: Gut (1993)

Familial adenomatous polyposis has been associated with several extraintestinal cancers, but the relative and absolute risks of these malignancies have not been determined. Extraintestinal cancers reportedly associated with adenomatous polyposis (thyroid gland, adrenal gland, pancreas, and biliary tract) were identified in polyposis patients and their at risk relatives in The Johns Hopkins Registry. The incidence rates of identified tumours were then compared with the general population through person year analysis with adjustment for population. For comparison, the incidence rates of the two most common cancers not associated with polyposis (breast cancer in women and lung cancer) were also calculated. There was an increased relative risk of thyroid cancer (relative risk 7.6; 95% confidence limits (CL) 2.5-17.7) and pancreatic adenocarcinoma (relative risk 4.46; 95% CL 1.2-11.4) in polyposis patients and at risk relatives. The absolute risk was 26.8 and 21.4 cases/100,000 person years, respectively. No cases of adrenal or biliary cancer were found in this cohort. There was no increased relative risk of lung cancer (95% CL 0.04-1.4) or breast cancer (95% CL 0.04-1.4) over the general population. The relative risks of thyroid and pancreatic cancer are increased in familial adenomatous polyposis, but the absolute lifetime risk is low. Screening for pancreatic cancer may not be worthwhile with currently available methods, but careful physical examination of the thyroid gland is warranted along with consideration for ultrasonography.
In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).
Authors: Diana M Papoulias, Sergio A Villalobos, John Meadows, Douglas B Noltie, John P Giesy, Donald E Tillitt
Journal: Environmental Health Perspectives (2002)

Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development.
Conservative party pledges to scrap performance targets
Authors: Lynn Eaton
Journal: BMJ (2007)

The Conservative party says it will scrap much of the Whitehall red tape in primary care and hand responsibility to GPs for their own budgets—and for deciding where patients should be sent for treatment. 

Speaking this week, the party's leader, David Cameron, said they intended to replace nationally set targets, such as paying GPs based on the number of patients they treat for high blood pressure, with objectives that measure the overall benefit of treatments to the individual patient. 

“We won't just concentrate on the money going in but on what comes out as well,” said Mr Cameron. “We want to raise health outcomes to exceed the European average. Outcomes like the survival rate for cancer, strokes, and heart attacks. These are the real measures of good health care.” 

He …
The hit and miss of ISS and TRISS. Yorkshire Trauma Audit Group.
Authors: N Zoltie, F T de Dombal
Journal: BMJ (1993)

To measure interobserver variation in recording injury from case notes and its effect on calculating injury severity scores (ISS) from identical data and predicting probabilities of survival by using the combined trauma and injury severity score (TRISS).Observer variation study using injury severity scoring and subsequent calculation of probability of survival based on combined trauma and injury severity scores.16 patients with a range of injury severity scores, and 15 observers.There was a wide variation in recorded injury severity scores, the probability of two observers agreeing on the score being 0.28 (28%). The probability of any two observers agreeing over which severity band the patient should be in was 0.5 (50%). Observer variation was independent of the training and type of observer. Survival probability (calculated by combined trauma and injury severity scoring methodology from individual observers' scores) varied by over 0.2 in six of the 16 patients and by over 0.5 in three.There is wide observer variation in injury severity scoring, which highlights a potential fallibility in its use for trauma audit. The use of combined trauma and injury severity scoring for individual prediction of survival is potentially inaccurate except at the extremes of probabilities. The use of the 0.5 survival line on a combined trauma and injury severity score "pre-chart" is statistically and clinically inappropriate.
High-resolution autoradiographic localization of 3-methylcholanthrene-3H in the skin of Balb/c mice after topical application
Authors: M. C. BIBBY, GILLIAN M. SMITH
Journal: British Journal of Dermatology (1977)

Tritiated 3-methylcholanthrene (MC) was traced by electron microscope autoradiography in Balb/c mouse epidermis 24 h after topical application in vivo. Quantification of the autoradiographs indicated that the distribution of radioactivity was non-random. The frequency of silver grains was similar in both nuclei and cytoplasm of epidermal cells. A concentration of labelling was detected in association with nuclear and cell membranes but to a greater degree with the dermo-epidermal junction. Results are consistent with previous work on the binding of hydrocarbons to soluble proteins and nucleic acids. The significance of the association of radioactivity with the dermo-epidermal junction is discussed.
Laparoscopic Appendicectomy: Review of 331 Cases over 7 Years, in a Saudi Arabian Hospital
Authors: O. Tucker, S. Rashid Al Faqih, O. El Amin, A. Zaki
Journal: Endoscopy (2002)

Background and Study Aims: Laparoscopic appendicectomy had been well established by Semm before the popular breakthrough of laparoscopic cholecystectomy. The aim of this study was to evaluate the role of laparoscopy in the diagnosis and treatment of acute appendicitis. Patients and Methods: This is a retrospective study. Patients with signs and symptoms of suspected appendicitis necessitating surgery were selected for laparoscopic management between 1992 and 1999. Results: A total of 331 patients were recruited into the study, 184 (56 %) male and 147 (44 %) female. The appendix was successfully removed laparoscopically in 98 % of the patients. The median operating time was 63.3 minutes, and 93 % of the appendices removed were histologically abnormal. Postoperative complications occurred in 19 patients (6 %), and included wound infection (1 %), enterocutaneous fistula, pelvic abscess, hemorrhage, urinary tract infection, respiratory tract infection, incisional herniae and pain at trocar sites. The mean hospital stay was 2.31 days (range 1 - 10 days). Conclusion: Laparoscopic appendicectomy is a safe procedure with low morbidity. It is advantageous in obese patients, patients with other pathology, and patients with an unusual position of the appendix, and it has a low infection rate.
An 82-Year-Old Woman With Worsening Hypertension
Authors: Kenneth Rosenfield, Michael R. Jaff
Journal: JAMA (2008)

Renal artery stenosis (RAS) is a common disorder in adults with atherosclerosis and is associated with hypertension, impaired renal function, congestive heart failure, and angina pectoris. The incidence of RAS is increasing because of the aging of the US population and increasing prevalence of atherosclerosis. The case of Mrs S, an 82-year-old woman with long-standing hypertension and unilateral RAS detected by magnetic resonance angiography, illustrates the challenges surrounding indications for revascularization. The discussion reviews the clinical presentation and natural history of RAS and strategies for diagnosis. The role of medical therapy, surgery, and endovascular therapy are reviewed, particularly in the context of guidelines and systematic reviews to help clinicians and patients facing this challenging decision.
Hepatic structure and function after modified jejunoileal bypass surgery for obesity.
Authors: J D Maxwell, I Sanderson, W H Butler, J C Gazet, T R Pilkington
Journal: BMJ (1977)

The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.
Immunological Reactivity in Patients with Carcinoma of Colon
Authors: R. C. Nairn, A. P. P. Nind, E. P. G. Guli, D. J. Davies, J. M. Rolland, A. R. McGiven, E. S. R. Hughes
Journal: BMJ (1971)

Sixty cases of colonic carcinoma have been investigated for antitumour immunoreactivity. The tests employed were blood lymphocyte reactivity and complement-dependent serum cytotoxicity against cultured tumour cells, and immunofluorescence for membrane staining of viable tumour cells and cytoplasmic staining of dried tumour cells in films. Nineteen cases were positive by one or more tests and the most frequent positive response, lymphocytotoxicity, was detected in 8 of the 24 cases tested in this way. The lymphocytotoxicity persisted in a case tested three times over a year. Immunoreactivity against tumour cell surface, as by lymphocyte or serum cytotoxicity or membrane immunofluorescence, was restricted to colonic carcinomas but there was an additional element of individual specificity; cross-reactivity with other tissues and tumours was not observed. Lymphocytes from regional lymph nodes were non-reactive even in a case with positive blood lymphocyte cytotoxicity against the carcinoma cells.
Celery soup causing severe phototoxity during PUVA therapy
Authors: M. J. Boffa, E. Gilmour, R. D. Ead
Journal: British Journal of Dermatology (1996)

Journal Article Celery soup causing severe phototoxity during PUVA therapy Get access M. J. Boffa, M. J. Boffa The Dermatology Centre, University of Manchester School of Medicine, Hope Hospital, Eccles Old Road, Manchester M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar E. Gilmour, E. Gilmour The Dermatology Centre, University of Manchester School of Medicine, Hope Hospital, Eccles Old Road, Manchester M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. D. Ead R. D. Ead The Dermatology Centre, University of Manchester School of Medicine, Hope Hospital, Eccles Old Road, Manchester M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 2, 1 August 1996, Page 334, https://doi.org/10.1111/j.1365-2133.1996.tb01182.x Published: 01 August 1996
Premedication for hypotensive anaesthesia.
Authors: P. J. Thompson
Journal: BMJ (1969)

Disappearance Of L-Dopa SIR,-Since your leading article (24 June 1967, p. 783) on the successful use of dopa in the treatment of Parkinsonism, as pre- viously reported in the New England fournal of Medicine,' there have been other reports of the efficiency of this mode of treatment.It has been glowingly reported by Alistair Cooke in the Guardian (3 February 1969) and splashed across the pages of Life maga- zine (11 October 1968).A controlled trial has recently been done in this country in post- encephalitic Parkinsonism and confirms the usefulness of the drug.' Unfortunately this drug has always been very difficult to obtain in this country, and in the last few months it has virtually dis- appeared.This is a disgraceful situation that is hard for a doctor to understand, but it seems to be based on the apathy of some drug houses and curious take-over activities behind the scenes, somewhat reminiscent of the Third Man, by others.Is it not time that the British pharmaceutical industry was mobilized to serve a pressing need ?-I am, etc.,
Tenosynovitis and Tendovaginitis
Authors: D. Ll. Griffiths
Journal: BMJ (1952)

<h3>Objective</h3> Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses. <h3>Design</h3> We conducted a prospective cohort analysis using the Truven MarketScan database (2009–2016) to estimate the incidence and prevalence of EoO in patients with Crohn’s disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses. <h3>Results</h3> Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p&lt;0.01; prevalence ratio (PR) 7.8, p&lt;0.01) or UC (IRR 3.5, p&lt;0.01; PR 5.0, p&lt;0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p&lt;0.01; PR 7.6, p&lt;0.01; UC: IRR 3.4, p&lt;0.01; PR 4.9, p&lt;0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p&lt;0.01). <h3>Conclusion</h3> Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.