tbuckley/cabot-search huggingface dataset:
In vivo tumor growth induces DNA damage in distal organs
Authors: Christophe Redon, Dieter Naf, Jennifer Dickey, Irina Kareva, Brittany Flood, Somaira Nowsheen, Alexandros Georgakilas, William Bonner, Olga Sedelnikova
Journal: Cancer Research (2008)

1888   Cancer biomarkers are helpful for early tumor diagnostics, cancer management, and prognosis of tumor outcome and recurrence. Current advances in cancer biology associate DNA damage with genome instability and oncogenic transformation and introduce the possibility of using DNA damage-associated proteins as cancer biomarkers. The bystander effect, in which directly irradiated cells transmit signals that induce DNA damage in unirradiated neighbors, is now well established. We recently found that various other sources of cell stress, including media from cancerous cells, resulted in histone H2AX phosphorylation in normal human cell cultures, which is one of the first responses to DNA DSBs. This suggests that the bystander effect may be part of a more general cellular stress response. Previous studies have also shown higher levels of closely spaced (clustered) oxidative DNA lesions (OCDLs) in mouse tissues not-directly exposed to X-rays and in cell cultures, implying a possible bystander effect.  We hypothesized that tumors growing  in vivo  may induce DNA damage in normal organs and peripheral blood mononuclear cells of the host, as a consequence of the bystander effect or induction of oxidative stress, and phosphorylated H2AX (γ-H2AX) and/or OCDLs can serve as a common indicator of this stress.  To test this hypothesis, 6 C57BL/6NCr mice from the Animal Production Area, NCI-Frederick, were subcutaneously injected with B16 melanoma cells obtained from the DCTD tumor repository, NCI (test cohort). As controls, 6 mice were left untreated (negative control cohort), and 6 additional mice were injected with a Freund’s adjuvant (inflammatory response control cohort). Tumor growth was monitored until tumor size approached 300 mg, after which the animals were sacrificed. Duodenum, liver, kidney, lung and ovary were touch-printed and sectioned; spleen and blood lymphocytes were isolated and cytospun. The presence and numbers of nuclear γ-H2AX foci were measured by immunofluorescent staining. γ-H2AX focal incidences increased in the duodenum of tumor-bearing mice (2.3 foci per cell (fpc) vs. 1 fpc in negative control and 0.9 in inflammatory response control cohorts; p in vivo  in this study, our observations have wider implications for understanding how tumor microenvironment contributes to accumulation of stress-related DNA damage, genome instability and carcinogenesis.
Abstract 2940: Assessment of Left Ventricular Function and Mass in Computed Tomography Coronary Angiography Using Dual Source Computed Tomography: Comparison to Magnetic Resonance Imaging
Authors: Christoph J Jensen, Markus Jochims, Peter Hunold, Jörg Barkhausen, Georg V Sabin, Oliver Bruder, Thomas Schlosser
Journal: Circulation (2007)

Background: Left ventricular function and mass are predictive markers in a variety of cardiovascular diseases.  Purpose: The aim of the study was to quantify left ventricular function and mass derived from retrospectively ECG-gated dual source computed tomography (DSCT) coronary angiography data sets in comparison to cardiac magnetic resonance imaging (CMR) as the reference standard.  Methods: 26 consecutive patients (mean age 55 ± 8 years) with suspected coronary artery disease underwent DSCT coronary angiography (Siemens Definition). Patients (n=11) whose heart rates exceeded 70 bpm received up to four vials (20 mg) of metoprolol i.v. before DSCT examination. Multiplanar reformations in short-axis orientation in end-systole and end-diastole were calculated from retrospectively ECG-gated axial contrast-enhanced CT images. Left ventricular ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), cardiac output (CO), and left ventricular myocardial mass (LVMM) were calculated and compared to volumetric measurements based on contiguous short-axis steady-state free precession cine MR sequences. Mean values were compared using a Wilcoxon sign rank test. P values   Results: Mean heart rate during DSCT examinations (60 ± 11 bpm) was significantly lower (p  Conclusion: Left ventricular volumes can reliably be assessed by dual source computed tomography compared to CMR. However, left ventricular mass measured by DSCT is significantly overestimated compared to CMR. Further studies are required to evaluate the impact of betablocker premedication on left ventricular function in DSCT examinations.
Chronic Insomnia
Authors: Michael H. Silber
Journal: New England Journal of Medicine (2005)

A 46-year-old woman has a 15-year history of difficulty in falling asleep and staying asleep. It takes her two hours to fall asleep most nights, and when she falls asleep rapidly, she wakes at 2 a.m. and cannot go back to sleep. Her bedtime is 11 p.m., and going to bed later does not help her fall asleep more easily. She has no symptoms of sleep-disordered breathing or the restless legs syndrome and is otherwise well. How should her case be managed?
Upregulation of ErbB3 after chemotherapy lead to acquisition of gefitinib sensitivity in epidermal growth factor receptor (EGFR) mutation negative non-small-cell lung cancer cells
Authors: Shigeki Umemura, Hideki Katayama, Masahiro Tabata, Nagio Takigawa, Yoshiyuki Tokuda, Akiko Hisamoto, Yoshiro Fujiwara, Katsuyuki Kiura, Mitsune Tanimoto
Journal: Cancer Research (2006)

1266   Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been shown to be clinically active in heavily pretreated patients with non-small cell lung cancer (NSCLC). We established a pair of cell lines (EBC-2 and EBC-2/R) from one patient with NSCLC before and after receiving cisplatin-based chemotherapy (Lung Cancer 2002; 35: 305-314). The cell line established after receiving chemotherapy (EBC-2/R) was 2.3-fold resistance to cisplatin compared with the cell line established before receiving chemotherapy (EBC-2). Interestingly, EBC-2/R was 8.5-fold more sensitive to gefitinib compared with EBC-2. Both cells harbored no known EGFR mutations associated with gefitinib sensitivity. In gefitinib-sensitive EBC-2/R cells, expression of ErbB3 was significantly higher compaired with parental EBC-2 cells. Gefitinib exposure lead to inhibition of ErbB3 phosphorylation and growth inhibition in EBC-2/R cells. Thus, upregulation of ErbB3 seemed to associate with aquistion of gefitinib sensitivity in EBC-2R cells. To confirm this hypotheis, siRNA was used to knock down ErbB3 protein in EBC-2/R cells. The siRNA targeting the coding sequence of ErbB3 (siERBB3) was transiently transfected into EBC-2/R cells 48 hours before protein extraction and drug sensitivity test. The siERBB3-transfected EBC-2/R cells became 2.3-fold resistance to gefitinib compared with non-transfected EBC-2/R cells. Because transient knocking down of ErbB3 in EBC-2/R cells partially restored gefitinib resistance, it is considered that upregulation of ErbB3 after receiving cisplatin-based chemotherapy might associate with acquisition of gefitinib sensitivity.
第一次海湾战争后的健康问题 教训普遍适用，并非仅局限于那场战争
Authors: DanielClauw, 宋一芳, 林果为
Journal: BMJ (2004)

BMJ曾有两篇报道描述了1990～1991年海湾战争中英国退伍军人的长期健康状况。在文章中皇家海湾战争疾病研究组Hotopf等进行了另一项极好的研究，研究指出海湾冲突后11年，经历海湾战争的老兵健康状况仍比对照组差很多。Macfarlane等的文章中检测了海湾战争老兵的恶性疾病发生率，结果发现他们癌症的总发生率几乎等同于那些虽未服役但据报告暴露在如贫铀和杀虫
Abstract 979: Pioglitazone Reduces Chemokine Receptor 2 Expressions on CD14+ Cells, Circulating Natural Killer Cells, and Neointima Volume in Type 2 Diabetic Patients
Authors: Soon Jun Hong, Kyung-Mi Lee, Sung Tae Kim, Tae Jin Kim, Seong Mi Park, Chul Min Ahn, Jae Hyung Park, Jae Sang Kim, Wan Joo Shim, Do-Sun Lim
Journal: Circulation (2009)
Apoptotic death induced by TMZ and MX is due to apoptotic signals emanating from mitochondria DNA damage
Authors: Lili Liu, Jon Donze, Alina Bulgar, Stanton L. Gerson
Journal: Cancer Research (2004)

1540   The importance of the mitochondria in DNA damage agent induced apoptosis has become increasingly apparent, due to the fact that mitochondrial DNA is a critical target for damage from chemicals and oxidants and they are the central regulator of apoptosis. We have previously reported that methoxyamine potentiate cytotoxicity of temozolomide through the its ability to bind AP sites produced after removal of TMZ-induced abnormal bases, such as N7mG or N3mA, by DNA methylpurine glycosylase, leading to interruption of BER. In this study, we examined the impact of mitochondrial DNA damage on cell killing effect of TMZ and MX by measuring the formation N7mG DNA adducts and AP sites that are the DNA damages for BER. We also assayed the reduction of AP sites by MX that indicates the blockage of BER. N7mG DNA adducts were detected by HPLC in both mtDNA and nuclear DNA respectively after cells (colon cancer cell lines: HCT116 and SW480) were treated with TMZ (0-1500 μM) and with/without MX (12 mM) for 4 hr. The levels of N7mG DNA adducts were increased proportionally with the concentration of TMZ, however, the levels of N7mG were 3-5 fold higher in mtDNA than that in nuclear DNA. The combination of TMZ with MX did not affect the formation of N7mG adducts. AP site assay by ARP, which has similar reactivity to MX to bind AP sites, showed that MX reduced AP sites by 3-fold of AP sites generated by TMZ alone in either mtDNA and nuclear DNA. These data suggest that TMZ induces high levels of mtDNA damages and MX is able to blocking BER in mitochondria. Thus, mtDNA is the target for TMZ and MX. Decreased expression of Bcl-2 was observed 24 h after treatment with TMZ and MX, indicating the onset of apoptotic death mediated by Bcl-2, however, we suggest that the apoptotic signals are emanating from mitochondria DNA damages.
Lesson of the Week: Upper abdominal pain in pregnancy may indicate pre-eclampsia
Authors: C Barry, R Fox, G Stirrat
Journal: BMJ (1994)

Pre-eclampsia is one of the prime causes of maternal and perinatal morbidity and mortality. The syndrome is highly variable, and the clinical presentation is often atypical. We describe the case histories of three women who presented with epigastric pain as the first outward manifestation of the disorder and in whom the diagnosis was initially overlooked.

A 28 year old primigravida attended her general practitioner's surgery at 34 weeks' gestation with pain in the right upper quadrant, nausea, and vomiting. An antacid was prescribed for presumed reflux oesophagitis. Her blood pressure was not measured and her urine was not tested for protein. The symptoms persisted, and five days later she presented to the hospital antenatal clinic. On examination her blood pressure was 140/80 mm Hg and urine analysis showed proteinuria (2+). She had appreciable tenderness of the right hypochondrium. Further investigation disclosed a moderate thrombocytopenia (56x109/l) and raised serum concentrations of aspartate aminotransferase (225 U/l) and uric acid (0.37 mmol/l). Concentrations of haemoglobin, urea, alkaline phosphatase, and albumin all lay within the normal ranges for pregnancy. There was no evidence of haemolysis, and the standard clotting times were not prolonged. A midstream urine sample was clear of white and red cells at microscopy. Pre-eclampsia with raised liver enzyme concentrations and a low platelet count was diagnosed. As the cervix was unfavourable caesarean section was performed to deliver …
Prevalence of antibiotic resistance in pneumococci
Authors: P. Wilson, D Lewis, P. Jenks, S Hoque
Journal: BMJ (1996)

# Prevalence of resistance to penicillin is higher in east London … {#article-title-2}

EDITOR,—Alan P Johnson and colleagues report that the prevalence of intermediate or full resistance to penicillin was 3.9% in England and Wales in 1995 and that the prevalence of resistance to erythromycin was 8.6%.1 We have examined the prevalence of resistance of Streptococcus pneumoniae to common antimicrobial agents in two consecutive periods in east London.

In our first study we determined the antimicrobial susceptibilities of sequential clinical isolates of pneumococci obtained during January to September 1994. Seven (12%) of 60 …
Abstract 009: Plain Water and Total Beverage Intakes and Risk of Type 2 Diabetes in Young and Middle-aged Women
Authors: An Pan, Vasanti Malik, Walter C Willett, Frank B Hu
Journal: Circulation (2012)

Introduction: Some caloric beverages (e.g., sugar-sweetened beverage and fruit juice) have been associated with an elevated risk of type 2 diabetes; therefore, substitution of these caloric beverages with non-caloric beverages such as plain water may be important for diabetes prevention. Few previous studies have examined the association between plain water or total beverage intake and risk of type 2 diabetes. Methods: We followed 82,900 women, aged 27-45 years and free of diabetes, cardiovascular disease and cancer at baseline, from 1991 to 2007. Diet, including various beverages, was assessed by food frequency questionnaires and updated every four years. Incident type 2 diabetes cases were confirmed by supplementary questionnaires. Cox proportional hazard models were used to calculate relative risks (RRs) and corresponding 95% confidence intervals (CIs), and we estimated the effect of “substituting” a serving of one beverage for another by including both as continuous variables in the same multivariable model. The difference in their beta coefficients and their variances and covariance were used to estimate the RR and 95% CI for the substitution effect. Results: During 1,294,196 person-years of follow-up, we documented 2,980 incident T2DM cases. After adjustment for age and body mass index, compared with the reference group (&lt;1 glass/d), the relative risks (RRs) and 95% confidence intervals (CIs) of type 2 diabetes according to categories of plain water consumption were 0.91 (0.81-1.02) for 1 glass/d, 0.91 (0.82-1.01) for 2-3 glasses/d, 0.98 (0.87-1.11) for 4-5 glasses/d, and 1.02 (0.89-1.18) for 6 or more glasses/d (P-for-trend=0.51). Further adjustment for other diabetes risk factors did not substantially alter the RRs. We estimated that substituting one serving/d of plain water for one serving/d of sugar-sweetened beverage or fruit juice was associated with a 10% (95% CI, 6%-13%) and 13% (95% CI, 7%-18%) lower risk of type 2 diabetes, respectively. In this cohort, no association was found for total beverage intake and risk of type 2 diabetes: compared with women who drank less than 6 servings/d of total beverage, the RRs (95% CIs) were 0.97 (0.87-1.09), 0.98 (0.88-1.10), 1.01 (0.89-11.5), and 0.99 (0.86-1.14) for women drank 6-8, 8-10, 10-12, and ≥12 servings/d of total beverages (P-for-trend=0.83). Conclusions: Increasing consumption of water per se was not associated with risk of type 2 diabetes, but substituting plain water for sugar-sweetened beverage or fruit juice was associated with a significantly lower risk of type 2 diabetes.
Syphilis surveillance and epidemiology in the United Kingdom
Authors: A A Righarts, I Simms, L Wallace, M Solomou, K. A. Fenton
Journal: Eurosurveillance (2004)

The aim of this article is to describe trends in infectious syphilis in the UK, and specifically the epidemiology of the London syphilis outbreak, the largest in the UK to date. Analysis of routine surveillance data from genitourinary medicine (GUM) clinics was performed as well as data collection through enhanced surveillance systems. There have been substantial increases in diagnoses of infectious syphilis between 1998 and 2003, with a 25-fold increase seen in men who have sex with men (MSM) (from 43 to 1028 diagnoses); 6-fold (138 to 860) in heterosexual men and 3-fold (112 to 338) in women. The national rise in syphilis was driven by a series of local outbreaks, the first of which occurred in 1997. To date, 1910 cases have been reported in the London outbreak, first detected in April 2001. High rates of HIV co-infection were seen among MSM, with MSM likely to be of white ethnicity and born in the UK. In contrast, heterosexuals were more likely to be of black ethnicity and born outside the UK. Most syphilis infections were acquired in London. MSM bear the brunt of the national resurgence in infectious syphilis. Substantial rises in male heterosexual cases has resulted in a divergence between male heterosexual and female cases, which now requires further investigation.
Abstract 14645: The Neutrophil to Lymphocyte Ratio Has the Long-Term Prognostic Value for the Prediction of Sudden Cardiac Death in Patients With Chronic Heart Failure, Irrespective of Ischemic or Non-Ischemic Origin
Authors: Takahisa Yamada, Takashi Morita, Yoshio Fukunami, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamomoto, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Circulation (2013)
Legalisation would have to be accompanied by personal responsibility
Authors: I. O. Azuonye
Journal: BMJ (1996)

EDITOR,—Richard Smith argues for the legalisation of those psychoactive substances whose distribution or possession is currently a crime.1 The argument is presented in terms of the impossibility of stopping people from wanting to take illicit drugs, the failure of prohibitionist policies, the desirability of a reduction in the costs of enforcement, the possibility of education about drugs, the attraction of purer preparations of drugs being manufactured by large companies, and the right of individuals to do what they …
Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells
Authors: L Boumsell, A Bernard, EL Reinherz, LM Nadler, J Ritz, H Coppin, Y Richard, L Dubertret, F Valensi, L Degos, J Lemerle, G Flandrin, J Dausset, SF Schlossman
Journal: Blood (1981)
Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity
Authors: Sean P. Saunders, Tara Moran, Achilleas Floudas, Felicity Wurlod, Agnieszka Kaszlikowska, Maryam Salimi, Emma M. Quinn, Christopher J. Oliphant, Gabriel Núñez, Ross McManus, Emily Hams, Alan D. Irvine, Andrew N.J. McKenzie, Graham S. Ogg, Padraic G. Fallon
Journal: Journal of Allergy and Clinical Immunology (2015)

Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development in a phenomenon known as the atopic march. Although genetic and environmental factors are known to contribute to AD and asthma, the mechanisms underlying the atopic march remain poorly understood. Filaggrin loss-of-function mutations are a major genetic predisposer for the development of AD and progression to AD-associated asthma.We sought to experimentally address whether filaggrin mutations in mice lead to the development of spontaneous eczematous inflammation and address the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency.Filaggrin mutant mice were generated on the proallergic BALB/c background, creating a novel model for the assessment of spontaneous AD-like inflammation. Independently recruited AD case collections were analyzed to define associations between filaggrin mutations and immunologic phenotypes.Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like inflammation with progression to compromised pulmonary function with age, reflecting the atopic march in patients with AD. Strikingly, skin inflammation occurs independently of adaptive immunity and is associated with cutaneous expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects with filaggrin mutations have an increased frequency of type 2 innate lymphoid cells in the skin in comparison with control subjects.This study provides new insights into our understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function.
Abstract P373: Cardiac Depolarization and Repolarization Changes with Mental Stress are Associated with Mental Stress- Induced Ischemia
Authors: Pratik M Pimple, Amit Shah, Ronnie Ramadan, Elsayed Z Soliman, Doug Bremner, Arshed Quyyumi, Viola Vaccarino
Journal: Circulation (2013)

Introduction: QRS duration and frontal QRS/T angle are simple and easily available electrocardiographic measures of cardiac depolarization and repolarization that predict cardiovascular disease (CVD) events and mortality. Such measures may be indicative of cardiac structural disease, ischemia, or primary conduction abnormalities. Mental stress-induced myocardial ischemia (MSI) is also associated with increased CVD risk, but the underlying mechanisms are unknown. We hypothesized that MSI is associated with stress-induced abnormalities in cardiac depolarization and repolarization, QRS duration and frontal QRS/T angle. Methods: We compared QRS duration &amp; frontal QRS/T angle during mental stress between coronary artery disease (CAD) patients who were MSI positive (MSI+) and CAD patients who were MSI negative (MSI-). For each MSI+ case (n=22), one or two MSI- controls were matched for age, gender and race- ethnicity (n=41). QRS duration and frontal QRS/T angle were automatically computed by a 12-lead ECG (GE MAC 5000). QRS/T angle was calculated as absolute minimal difference between the frontal R and T axes in patients with QRS duration &lt; 120 ms (n= 50). Mental stress was induced via speech stressor, and nuclear 99m-Tc-sestamibi gated Single-Photon Emission Computed Tomography (SPECT) was used to assess MSI. Results: Mean age was 65 years, 20 patients were black, and 55 were males. The two groups were similar in terms of demographics and past medical history. Both MSI+ and MSI- groups had similar QRS duration at baseline, but MSI+ patients had an adjusted 3.1 ms higher increase in QRS duration with mental stress than MSI- patients (95% CI: 0.5 to 5.7), after adjusting for CVD risk factors, hemodynamic changes during mental stress (blood pressure, heart rate), and baseline QRS duration. MSI+ patients had an adjusted 28.2 degrees larger QRS/T angle at baseline (95% CI: 2.5 to 53.9) compared to MSI- patients, but did not differ with regards to change in QRS/T angle with mental stress. However, among those with normal baseline conduction (QRS&lt;100 ms, n=36), MSI+ patients had an adjusted 17.8 degrees larger change in QRS/T angle with mental stress compared to MSI- patients (95% CI: 3.1 to 32.4). In patients with mildly abnormal conduction (QRS duration between 100 and 119 ms, n=14), no differences were found, p=0.059 for QRS duration x MSI interaction. Conclusion: CAD patients exhibit changes in cardiac depolarization and repolarization during acute mental stress. Those with MSI have greater baseline QRS/T angle and larger changes in QRS/T angle and QRS duration with mental stress. These findings may help to explain the pathophysiology linking mental stress and CVD, as well as the increased risk in patients with MSI.
Abstract 13616: Patient-Prosthesis Mismatch in Bioprosthetic Aortic Valve Replacements as Indicated by the American Society of Echocardiography Guidelines Predicts Long Term Survival
Authors: Satish J Chacko, Edwin C McGee, Patrick M McCarthy, Asimul H Ansari, Brittany Lapin, Richard Lee, S. C Malaisrie, Jyothy J Puthumana
Journal: Circulation (2011)

Background: The impact of patient-prosthesis mismatch (PPM) on long term mortality has not been clearly defined, with past studies reaching conflicting results. Historically, long term mortality ha...
AC133, a Novel Marker for Human Hematopoietic Stem and Progenitor Cells
Authors: Amy H. Yin, Sheri Miraglia, Esmail D. Zanjani, Graca Almeida-Porada, Makio Ogawa, Anne G. Leary, Johanna Olweus, John Kearney, David W. Buck
Journal: Blood (1997)