tbuckley/cabot-search huggingface dataset:
Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene.
Authors: A M Hutt, G F Kalf
Journal: Environmental Health Perspectives (1996)

Chronic exposure of humans to benzene (BZ) causes acute myeloid leukemia (AML). Both BZ and therapy-related secondary AML are characterized by chromosomal translocations that may occur by inappropriate recombinational events. DNA topoisomerase II (topo II) is an essential sulfhydryl (SH)-dependent endonuclease required for replication, recombination, chromosome segregation, and chromosome structure. Topo II cleaves DNA at purine(R)/pyrimidine(Y) repeat sequences that have been shown to be highly recombinogenic in vivo. Certain antineoplastic drugs stabilize topo II-DNA cleavage complexes at RY repeat sequences, which leads to translocations of the type observed in leukemia. Hydroquinone (HQ) is metabolized to p-benzoquinone (BQ) in a peroxidase-mediated reaction in myeloid progenitor cells. BQ interacts wit SH groups of SH-dependent enzymes. Consequently, the aims of this research were to determine whether HQ and BQ are topo II inhibitors. The ability of the compounds to inhibit the activity of topo III was tested using an assay system that depends on the conversion, by homogeneous human topo II, of catenated kinetoplast DNA into open and/or nicked open circular DNA that can be separated from the catenated DNA by electrophoresis in a 1% agarose-ethidium bromide gel. We provide preliminary data that indicate that both HQ and BQ cause a time and concentration (microM)-dependent inhibition of topo II activity. These compounds, which potentially can form adducts with DNA, have no effect on the migration of the supercoiled and open circular forms in the electrophoretic gradient, and BQ-adducted KDNA can be decatenated by topo II. Using a pRYG plasmid DNA with a single RY repeat as a cleavage site, it was determined that BQ does not stimulate the production of linear DNA indicative of an inhibition of topo II religation of strand breaks by stabilization of the covalent topo III-DNA cleavage complex. Rather, BQ most probably inhibits the SH-dependent topo II by binding to an essential SH group. The inhibition of topo II by BQ has implications for the formation of deleterious translocations that may be involved in BZ-induced initiation of leukemogenesis.
Website of the week: Heart transplantation
Authors: D. Carnall
Journal: BMJ (2000)

US doctors can be contemptuously dismissive of “wait-list-ology,” but when the scarce resource is organs rather than money even highly insured Americans in fee for service settings have to join the queue. And this week the BMJ publishes evidence that suggests that, for heart transplantation at least, such waiting lists are far from straightforward. Deng and colleagues stratified candidates for heart transplantation according to their risk of dying on the waiting list: only high risk patients actually had less risk from surgery than being on the waiting list, and it seems possible that they have their chances of receiving an organ diluted by the presence of lower risk patients.

The Cardiothoracic Surgery Network delivers a huge bundle of exemplary content at ctsnet.org/. Its FAQs (frequently asked questions) on heart transplantation pulls no punches, is evidence based, and will be useful for generalists everywhere who would like to understand and explain the risks and benefits of transplantation to their patients. The site is targeted at medics, but there are links to high quality patient information materials at ctsnet.org/doc/2189. Multimedia content is also bundled on the site, but even on a fast internet connection picking up the proprietary RealPlayer multimedia software (a 7 Mb download) before failing to view the video of an innovative operative technique was a chore.

More relevantly, three major journals are freely available in full text through the site, and you can track down colleagues across the world using a highly efficient database of contact details. The European Association for Cardio-thoracic Surgery maintains its committee rosters on line, which should facilitate wider discussion if colleagues feed input by email to their representatives. It's perhaps not surprising that one of the most technical of specialties has a technically adept website; even if you're not a cardiothoracic surgeon there is much to learn from the architecture.
Passive smoking in utero: its effects on neonatal appearance
Authors: M. L Chiswick
Journal: BMJ (1987)

<h3>Objective:</h3> NA <h3>Background:</h3> A 39-year-old lady complained of epigastric pain for last seven months. Due to persistent pain, she underwent a contrast enhanced computed tomography of the abdomen which revealed a tumor in the head of the pancreas. Four months later, she started having insomnia along with continuous twitching in bilateral calves, angle of the mouth, chin and nostrils. In addition, she had severe bilateral leg pain which was associated with episodes of hyperhidrosis. Subsequently three months afterwards her tumor was resected. A diagnosis of solid pseudopapillary tumor of the pancreas was made on histopathology. However, her neurological symptoms persisted. On examination, the patient was distressed due to continuous leg pain. General physical examination was normal. Neurological examination revealed continuous rippling in the face, bilateral calves and tongue (Video 1). Rest of the neurological examination was normal. Her routine biochemistry, hematology and CSF examination were normal. HRCT chest did not reveal any thymoma. She underwent contrast enhanced MRI of the Brain with whole spine which was normal. Nerve conduction studies in all the four limbs were normal. Electromyography (EMG) revealed continuous spontaneous activity in the form of doublets, triplets, multiplets and fasciculation potentials in bilateral gastrocnemii and the genioglossus suggestive of peripheral nerve hyperexcitability (video 2). In view of the history, examination and EMG findings, a diagnosis of Morvan’s syndrome was suspected. Anti-CASPR2 antibodies were done and were positive. Treatment with intravenous methylprednisolone along with antiepileptics was instituted. However, her symptoms persisted, following which she received intravenous rituximab and her symptoms improved. Morvan’s syndrome has been associated with tumors of the thymus, lung, colon and prostate. To the best of our knowledge, this is the first case of Morvan syndrome associated with a pseudopapillary pancreatic tumor to be reported. High clinical suspicion and awareness of this rare potentially treatable is required. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> NA <b>Disclosure:</b> Prof. Dhamija has nothing to disclose. Dr. Saluja has nothing to disclose.
Immunolocalization of Epstein-Barr virus-related antigens in a case of sweat gland adenocarcinoma
Authors: K. Tanese, A. Ishiko, K. Hayase, T. Yoshida, K. Kishi, T. Yamada
Journal: British Journal of Dermatology (2009)

Journal Article Immunolocalization of Epstein–Barr virus‐related antigens in a case of sweat gland adenocarcinoma Get access K. Tanese, K. Tanese Departments of PathologyDermatology Search for other works by this author on: Oxford Academic Google Scholar A. Ishiko, A. Ishiko Dermatology Search for other works by this author on: Oxford Academic Google Scholar K. Hayase, K. Hayase Departments of Pathology Search for other works by this author on: Oxford Academic Google Scholar T. Yoshida, T. Yoshida Dermatology Search for other works by this author on: Oxford Academic Google Scholar K. Kishi, K. Kishi Plastic and Reconstruction Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku‐ku, Tokyo, 160‐8582, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Yamada T. Yamada Departments of Pathology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 3, 1 September 2009, Pages 694–697, https://doi.org/10.1111/j.1365-2133.2009.09319.x Published: 01 September 2009
New Evidence That Cigarette Smoking Remains the Most Important Health Hazard
Authors: Steven A. Schroeder
Journal: New England Journal of Medicine (2013)

Everyone knows cigarette smoking is bad for you. Most people in the United States assume that smoking is on its way out. But the grim reality is that smoking still exerts an enormous toll on the health of Americans, as documented in two articles in this issue of the Journal.1,2 Both articles review mortality trends over time for men and women according to smoking status, and both confirm that smoking remains a huge threat to the public's health. Jha et al. review data from the U.S. National Health Interview Survey, which involved 113,752 women and 88,496 men 25 . . .
The disruption of bacterial membrane integrity through ROS generation induced by nanohybrids of silver and clay
Authors: Hong-Lin Su, Chih-Cheng Chou, Da-Jen Hung, Siou-Hong Lin, I-Chuan Pao, Jun-Hong Lin, Fang-Liang Huang, Rui-Xuan Dong, Jiang-Jen Lin
Journal: Biomaterials (2009)
Peripheral Direct Adjacent Lobe Invasion Non-small Cell Lung Cancer Has a Similar Survival to That of Parietal Pleural Invasion T3 Disease
Authors: Hao-Xian Yang, Xue Hou, Peng Lin, Hong Yang, Can-Guang Zeng, Tie-Hua Rong, Jian-Hua Fu
Journal: Journal of Thoracic Oncology (2009)
Abstract 2875: NF-κB signaling in myeloid cells limits urethane-induced lung tumorigenesis.
Authors: Allyson McLoed, Rinat Zaynagetdinov, Taylor Sherrill, Fiona Yull, Timothy Blackwell
Journal: Cancer Research (2013)

Abstract The transcription factor Nuclear Factor κB (NF-κB) is a master regulator of inflammation, and its activation is associated with tumorigenesis in a variety of cancers. Our group has shown that NF-κB signaling in lung epithelial cells is critical for lung tumor formation. However, the role of NF-κB in other cell types, such as myeloid cells, during lung carcinogenesis is uncertain. We hypothesized that NF-κB signaling in myeloid cells (macrophages, monocytes, and neutrophils) promotes lung tumorigenesis by facilitating lung inflammation. Surprisingly, we found that mice with myeloid cell-targeted IKKβ deletion (IKKβΔmye mice) developed significantly more tumors than wild-type (WT) mice 4 months following a single intraperitoneal (IP) injection of the lung carcinogen urethane (1g/kg). IKKβΔmye mice exhibited a paradoxical increase in the proinflammatory cytokines IL-1β, TNFα, and CXCL1 at 1 and 2 weeks after urethane treatment, and a more than 3-fold higher influx of CD11b+Ly-6G+ cells into IKKβΔmye lungs compared to WT lungs was observed by flow cytometry 1 week post-urethane. By 6 weeks after urethane, IKKβΔmye mice developed more lung inflammation than WT mice, which was accompanied by an increased burden of atypical adenomatous hyperplasia lesions. Flow cytometric analysis of inflammatory cell populations at this time point revealed a sustained increase in granulocytic cells, indicated by significantly higher numbers of CD11b+Gr-1hi cells in the lungs of IKKβΔmye mice compared to WT mice. Depletion of granulocytic cells using Ly-6G antibody treatment (50ug/weekly IP injection) during the first 6 weeks of urethane-induced lung carcinogenesis reduced lung NF-κB activation and lung tumor incidence in IKKβΔmye mice to levels observed in urethane-treated WT mice, indicating that granulocytic cells play an important role in lung tumorigenesis during early tumor development and may do so by limiting NF-κB activation in lung epithelial cells. Together, our data suggest that the impact of NF-κB signaling on lung tumorigenesis is cell type specific and that myeloid NF-κB signaling limits urethane-induced inflammation and lung tumorigenesis. Granulocytes are important players during early lung tumor promotion, and we propose that they promote lung carcinogenesis through interactions that increase survival and/or proliferation of mutated lung epithelial cells. Citation Format: Allyson McLoed, Rinat Zaynagetdinov, Taylor Sherrill, Fiona Yull, Timothy Blackwell. NF-κB signaling in myeloid cells limits urethane-induced lung tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2875. doi:10.1158/1538-7445.AM2013-2875
A Clinical Syndrome Simulating Poliomyelitis
Authors: Richard H. Young
Journal: New England Journal of Medicine (1947)

DURING the week August 11 to 18, 1946, a total of 34 new cases of poliomyelitis were reported in Nebraska, 176 cases having been reported for that year. With serious epidemics in the neighboring States of Minnesota, South Dakota and Colorado, there was considerable apprehension on the part of the people of this area. On the front page each day the press reported the new cases and the precautions to be taken. In letters to editors, readers asked for a spraying of the City with DDT, and offered new epidemiologic theories. The terror that past generations manifested toward "the plague" . . .
Imaging His Pain
Authors: Loreen Herwaldt
Journal: Annals of Internal Medicine (2002)

Ad Libitum16 July 2002Imaging His PainLoreen Herwaldt, MDLoreen Herwaldt, MDIowa City, IA 52242-1081Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-2-200207160-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I know I've ... Author, Article, and Disclosure InformationAffiliations: Iowa City, IA 52242-1081Corresponding Author: Loreen Herwaldt, MD, University of Iowa Hospitals and Clinics, Department of Internal Medicine, 200 Hawkins Drive, Iowa City, IA 52242-1081. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 July 2002Volume 137, Issue 2Page: 128KeywordsComputed axial tomographyHospital medicineLesionsLungsPainRetinaRibsScarsSleepThorax ePublished: 16 July 2002 Issue Published: 16 July 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Shall The Journal be Removed to Washington?
Authors: Solon Marks
Journal: JAMA (1891)

<h3>To the Editor:</h3> —In regard to the removal ofThe Journalto Washington I am of the opinion that it would be a great mistake.The Journalis not only centrally located, but is ably edited, and a financial success. Under all these circumstances I am of the decided opinion that it should remain just where it is. Milwaukee, Wis., Feb. 17, 1891.
Leisure Sickness: A Pilot Study on Its Prevalence, Phenomenology, and Background
Authors: Ad J.J.M. Vingerhoets, Maaike van Huijgevoort, Guus L. van Heck
Journal: Psychotherapy and Psychosomatics (2002)

To explore the prevalence, phenomenology, and background of leisure sickness, i.e., the condition of people developing symptoms of sickness during weekends and/or vacations.In order to obtain an estimate of its prevalence, a representative Dutch sample consisting of 1,128 men and 765 women was asked to indicate to what extent they recognized themselves in our description of weekend and vacation sickness. For the investigation of the phenomenology and background of this condition and the characteristics of the patients suffering from it, questionnaire data were collected in new samples consisting of 114 cases and 56 controls. Questions referred to symptoms, onset, duration, appreciation of weekend and vacation activities, and appraisal of work and workload.In the case of male respondents, 3.6 and 3.2% recognized themselves in the description of the weekend and the vacation syndrome, respectively, compared with 2.7 and 3.2% women. Most frequently reported symptoms were headache/migraine, fatigue, muscular pains, and nausea. In addition, viral infections (flue-like, common cold) were often reported in relation to vacations. Cases had generally suffered from leisure sickness for over 10 years and the onset was associated with stressful conditions. They attributed their condition to difficulties with the transition from work to nonwork, stress associated with travel and vacation, as well as workload and personality characteristics. There were no significant group differences in the appreciation of weekend and leisure activities or lifestyle during days off. Most striking differences were found with respect to experienced workload, sense of responsibility, and inability to relax.Leisure sickness is a relatively common condition. Specific lifestyle factors or leisure activities seem to be less relevant for its development. Concerning risk factors, the data tend to point to high workload and person characteristics, namely, the inability to adapt to the nonworking situation, a high need for achievement, and a high sense of responsibility with respect to work. Future studies should be designed for testing specific hypotheses concerning the underlying mechanisms and evaluating the effectiveness of psychological and/or physical activity interventions.
Advances in the Treatment of Acute Myelogenous Leukemia
Authors: Robert Peter Gale
Journal: New England Journal of Medicine (1979)

ACUTE myelogenous leukemia is a neoplastic disease characterized by the proliferation of myeloblasts and other immature cells of the granulocytic series. Because of the common origin of several hematopoietic cell lines, abnormalities of proliferation or differentiation of monocytes, red-cell precursors and megakaryocytes are frequently present. The variability in the morphologic features of acute myelogenous leukemia has led to the development of several systems of classification. A recent and widely accepted system, that of the joint French-American-British committee, is based on the predominant cell type involved (Table 1). Three forms of acute myelogenous leukemia with granulocytic differentiation are identified: M-l, which . . .
INJURIES OF THE BLADDER AND URETHRA IN WAR
Authors: A. Fullerton
Journal: BMJ (1916)

WOUNDS of the bladder and urethra have received very little attention on the part of writers on military surgery durilng the present war.It lhas been assumed, perhaps too lhastily, that there is nothing special to be said about the management of these injuries.During the last year I hiave seen most of those that have passed tlhrough my area, and, though the numlber has not been large com- pared with wounids in other regions of the body, some of tlho cases lhave been of great interest and importance, especially from the point of view of treatment.I gather from what I have seen that-there are practically only two lines of treatment adopted for these injuries at the casualty clearing stations-namely, (a} the tying in of a catheter, or (b) suprapubic cystostomy.Now, thouglh each of these methods has a definite place as a surgical procedure under suitable conditions, there seems to be a want of appreciation in the mind of operators of the objects to be attained by these methods, and the dangers attending their indiscriminate use.A few remarks on the types of injury usually met witlh and the lines of treat.inent I lhave found most beneficial may not, thierefore, be out of place, WOUNDS OF THE BLADDER.Wounds of tlhe bladder may be produced by bullets, slhrapnel, slhell, bombs, etc., and lhave certain dangers distinct from those produced by these missiles in other parts of the body.Tlle more ragged the edges and sur- faces of the nmissile, tlhe more likely is clothing and dirt to be carried in and produce tlle usual sepsis.Tlle missile may reach tlle bladder laterally, antero-posteriorly, or fromn above or below, and the track is often long and tortuous.Conmplications may occur in the form of frac- tures of the femur, pelvic bones, or spinal column; injuries to large vessels or nierves, injuries to the intestine, or extravasation of urine.A troublesome complication is involvement of the rectum, witlh the discharge of faeces into the bladder, of urine into the rectuim, or of botlh tllroualg tlle wound in the soft parts.Wounds of the bladder may be intra-or extra-peritoneal, or both, and eacll variety has special dangers and requires special treatment.The intraperitoneal wounds are, as a rule, reaclhed witlh comparative ease, wlhereas those outside tlle limits of the peritoneum may be quite inaccessible, especially those at the base and sides.The missile miiay stop slhort after wounding the bladder, it may enter and remnain in the viscus, or it may pass tllrouglh, leaving wounds of entry and exit.The wounds seen lhave beell of all sizes and shiapes, from small punctures to the most extensive laceration.Signs and .Symptoms.The signs and symptoms of injury to the bladder will, of course, vary with tlle position and extent of the wound and the concomitant injuries to other organs and structures.
Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer
Authors: Jermaine Coward, Hagen Kulbe, Probir Chakravarty, David Leader, Vessela Vassileva, D. Andrew Leinster, Richard Thompson, Tiziana Schioppa, Jeffery Nemeth, Jessica Vermeulen, Naveena Singh, Norbert Avril, Jeff Cummings, Elton Rexhepaj, Karin Jirström, William M. Gallagher, Donal J. Brennan, Iain A. McNeish, Frances R. Balkwill
Journal: Clinical Cancer Research (2011)

Abstract Purpose: We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. Experimental Design: We combined preclinical and in silico experiments with a phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer. Results: Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases showed that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6–producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, while seven others had periods of disease stabilization. In patients treated for 6 months, there was a significant decline in plasma levels of IL-6–regulated CCL2, CXCL12, and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies. Conclusion: IL-6 stimulates inflammatory cytokine production, tumor angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and clinical studies. Clin Cancer Res; 17(18); 6083–96. ©2011 AACR.