tbuckley/cabot-search huggingface dataset:
Abstract P6-05-03: Evaluation of predictive markers for clinical outcome after neoadjuvant radiochemotherapy in breast cancer
Authors: C Matuschek, E Boelke, C Nestle-Krämling, V Speer, H Prisack, PA Gerber, H Bojar, W Audretsch, S Roth, W Budach
Journal: Cancer Research (2013)

Abstract BACKGROUND: Neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) is an innovative method in treating patients. Proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. In this subgroup analysis long-term clinical outcome data and predictive factors were analyzed. PATIENTS AND METHODS: During 1991-1998, a total of 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or -in case of breast conservation- a 10-Gy interstitial boost with (192)Ir after loading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The impact of age, tumor grade, nodal status, hormone and growth factor receptor status (ER, PR, EGFR), p53, ki-67, HER2/neu, and bcl-2 on pathological complete response pCR and disease-free survival were examined in uni- and multivariate terms. RESULTS: Hormone receptor status, proliferative activity, bcl-2, EGFR-status and clinical tumor size had a significant impact on predicting neoadjuvant therapy success. Age, cN, grading, p53, and HER2/neu status failed to reach a significant correlation to complete remission. All examined immunohistochemical factors with the exception of EGFR, and all clinical factors displayed an univariately significant impact on DFS (disease free survival). Particularly, while HER-2/neu had no predictive value for pCR it displayed the highest impact on DFS after complete response (n = 92), even in a multivariate setting with clinical tumor size and nodal status. Complementary, p53 was the most superior immunhistochemical factor for prognosis after neoadjuvant incomplete remission (n = 223). CONCLUSION: Her2/neu is a predictive marker for overall survival independent from the pCR. It has no predictive value for the pCR. P53 is a prognostic marker for patients with incomplete remission. Prospective studies are needed to evaluate their use for decisions to further individualize adjuvant treatment after neoadjuvant radiochemotherapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-03.
532. Effects of a New YB-1 Dependent Adenovirus (XVir) in Human Prostate Cancer Cell Lines and in a Xenograft Mouse Model
Authors: Klaus Mantwill, Nadia Koehler-Vargas, Alexandra Bernshausen, Uwe Treiber, Rudolf Hartung, Bernd Gansbacher, Per Sonne Holm
Journal: Molecular Therapy (2005)

The treatment of locally advanced and especially metastatic hormone refractory prostate cancer is a major therapeutic challenge due to the development of a multidrug resistance phenotype. The use of oncolytic adenoviruses represents a promising new avenue of treatment for this type of cancer. The translocation of the transcription factor YB-1 by adenoviral E1B55k and E4ORF6 is a key element in activating the adenoviral E2-Late-promoter and consequently in replication of adenoviruses. Therefore an E1-minus, YB-1 dependent, replicating oncolytic adenovirus, XVir, was developed, containing the expression cassette CMV-E1B55k-IRES-E4ORF6. This adenovirus exhibits oncolytic potency in all tumor cell lines tested so far. We now demonstrate the cytocidal efficacy of Xvir in a set of prostate cancer cell lines (LNCaP, DU145, PC3) by crystal violet stain (1-100 plaque-forming units, pfu/cell) in vitro. The application of XVir alone resulted in complete cytolysis in all three cell lines and could be achieved at lower pfu/cell, when combined with radiotherapy or chemotherapy. Additionally, a xenograft mouse model with DU145 tumors was established. The intratumoral application of XVir led to a strong tumor growth inhibition and tumor regression in vivo.
A Series of Cases of Arthrotomy for the Relief of Pain, and for Removal of Synovial Fringes, Loose Bodies, and Fibro-Cartilages
Authors: C. B. Lockwood
Journal: BMJ (1899)

ARTHROTOMY.VMZDILCLL OURNAL I 2 05 when working for his Miranda.For my own part, " the mis- tress which I serve quickens what's dead, and makes my labours pleasures."We who make up the Medical Society are members of an essentially active profession, and while we remain in our prime let us do our best here actively.For age, like infancy, is mostly passive, or, as Edgar reminds us in King Lear:Mei must endure Their going hence, even as their coming hither; RIPENESS is all.NOTES AND REFERENCES.1 Diary of the Rev. John WVard, A.J., Vicar of Stratford-on-Avon, extending from I648 to I679.The Society's Library possesses a copy of the same, printed anid publislhcd by Colbourn of Great Marlborough Street in I839 (long out of prinlt).Mr. Sidney Lee's valuable work, jeast publislhed
THE PREVENTION OF SCARLET FEVER
Authors: GEORGE F. DICK
Journal: JAMA (1924)

The intelligent prevention and treatment of a disease must depend on a definite knowledge of its cause.  When we began the study of scarlet fever, no organism had fulfilled all the requirements of Koch's laws, and it was generally considered a disease of unknown etiology.  A review of the literature of scarlet fever, in 1912, showed that two facts were apparently established: First, that hemolytic streptococci are practically constantly associated with scarlet fever. Second, that during the course of the disease, there is developed an immunity to hemolytic streptococci. This immunity had been demonstrated by the opsonic index, and complement fixation, and especially by means of the agglutination test. We were able to verify these facts by means of cultures and immune reactions reported in 1914 and 1916.  But the association of an organism with a disease, and even the development of immunity to it, do not constitute proof of
Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats
Authors: Hewang Lee, Yoshifusa Abe, Icksoo Lee, Shashi Shrivastav, Annabelle P. Crusan, Maik Hüttemann, Ulrich Hopfer, Robin A. Felder, Laureano D. Asico, Ines Armando, Pedro A. Jose, Jeffrey B. Kopp
Journal: Kidney International (2013)
In search of consensus.
Authors: T Smith
Journal: BMJ (1991)

benefit-whether this is an improvement in quantity or quality-seem to be excellent value.Those costing £10 000 for each year of benefit probably represent an unfair distribution of resources -a verdict likely to apply to many treatments costing between £1000 and £10000 for each year of benefit.All treatments of debatable value need economic as well as thorough clinical assessment, and oncologists and their colleagues in the laboratory need to develop bettex ways of predicting which patients will benefit from them.
The role of cytokines in the generation of skin lesions in dermatitis herpetiformis
Authors: M. GRAEBER, B.S. BAKER, J.J. GARIOCH, H. VALDIMARSSON, J.N. LEONARD, L. FRY
Journal: British Journal of Dermatology (1993)

Journal Article The role of cytokines in the generation of skin lesions in dermatitis herpetiformis Get access M. GRAEBER, M. GRAEBER Department of Dermatology. St Mary's Hospital. London. U.K. Search for other works by this author on: Oxford Academic Google Scholar B.S. BAKER, B.S. BAKER Department of Dermatology. St Mary's Hospital. London. U.K. Search for other works by this author on: Oxford Academic Google Scholar J.J. GARIOCH, J.J. GARIOCH Department of Dermatology. St Mary's Hospital. London. U.K. Search for other works by this author on: Oxford Academic Google Scholar H. VALDIMARSSON, H. VALDIMARSSON Department of Immunology, University of Iceland, Reykjavik Search for other works by this author on: Oxford Academic Google Scholar J.N. LEONARD, J.N. LEONARD Department of Dermatology. St Mary's Hospital. London. U.K. Search for other works by this author on: Oxford Academic Google Scholar L. FRY L. FRY Department of Dermatology. St Mary's Hospital. London. U.K. Dr L.Fry. St Mary's Hospital. London W2 INY, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 5, 1 November 1993, Pages 530–532, https://doi.org/10.1111/j.1365-2133.1993.tb00479.x Published: 01 November 1993 Article history Accepted: 13 May 1993 Published: 01 November 1993
Brahman Nallanathan Gobikrishnan
Authors: A. Hillman, J. Loudon, J. Tharumanayagam
Journal: BMJ (2011)

Brahman Nallanathan Gobikrishnan (“Gobi”) was born in Kandy, Ceylon (now Sri Lanka), but spent his childhood in New Zealand. He returned to his motherland to study medicine. After qualifying, Gobi worked in northern Sri Lanka, often in difficult circumstances during the protracted civil war. He …
1201 NEW INSIGHTS INTO THE MECHANISM OF ACTION OF INTERFERON-ALPHA AND BMS-790052: A MULTI-SCALE MATHEMATICAL MODELING APPROACH
Authors: H. Dahari, J. Guedj, L. Rong, R.E. Nettles, S.J. Cotler, T.J. Layden, A.S. Perelson
Journal: Journal of Hepatology (2011)
Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men.
Authors: J V Bjørnholt, G Erikssen, E Aaser, L Sandvik, S Nitter-Hauge, J Jervell, J Erikssen, E Thaulow
Journal: Diabetes Care (1999)

Because of the available conflicting epidemiological data, we investigated the possible impact of fasting blood glucose as a risk factor for cardiovascular death in nondiabetic men. This study reports the results from a 22-year prospective study on fasting blood glucose as a predictor of cardiovascular death.Of the 1,998 apparently healthy nondiabetic men (aged 40-59 years), a total of 1,973 with fasting blood glucose < 110 mg/dl were included in the study in which also a number of conventional risk factors were measured at baseline.After 22 years of follow-up, 483 men had died, 53% from cardiovascular diseases. After dividing men into quartiles of fasting blood glucose level, it was found that men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. Even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness (Cox model), the relative risk of cardiovascular death for men with fasting blood glucose > 85 mg/dl remained 1.4 (95% CI 1.04-1.8). Noncardiovascular deaths were unrelated to fasting blood glucose level.Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.
Temporal Relation Between Ischemic Episodes and Activation of the Coagulation System in Unstable Angina
Authors: Luigi M. Biasucci, Giovanna Liuzzo, Giuseppina Caligiuri, Gaetano Quaranta, Felicita Andreotti, Giovanni Sperti, Willy van de Greef, Antonio G. Rebuzzi, Cornelis Kluft, Attilio Maseri
Journal: Circulation (1996)

Background Although a major role of coronary thrombosis in the pathogenesis of unstable angina has been demonstrated, the results of a series of studies have suggested that activation of the hemostatic system may not be confined to ischemic episodes. The purpose of this study was to investigate the temporal relation between ischemic episodes and activation of the coagulation system in unstable angina. Methods and Results Thrombin–antithrombin III (TAT) and prothrombin fragment 1+2 (F 1+2 ) levels were measured in 13 patients during spontaneous ischemic episodes (time 0, 5, and 15 minutes and 1 hour) to evaluate the time course of the activation of the coagulation system associated with the development of ischemia (protocol A). TAT and F 1+2 levels were also measured in 28 patients with unstable angina on admission to hospital (every 6 hours for 24 hours and daily for 3 days) to assess their temporal relation with ischemic episodes (protocol B). In protocol A, TAT and F 1+2 levels were elevated in 10 of 13 patients (77%) in at least 1 sample. The median value of TAT showed a peak at 5 minutes and returned to baseline within 15 minutes ( P &lt;.05), consistent with its plasma half-life of 5 minutes, whereas the median value of F 1+2 showed no significant changes, possibly because of its longer half-life, which tends to dampen sudden bursts of thrombin production. In protocol B, activation of the clotting system was found in 10 of 33 samples (30%) temporally related to ischemia and also in 23 of 150 (15%, P =.07) of those not temporally related to ischemia. Conclusions Our study demonstrates that patients with active unstable angina develop frequent bursts of thrombin production not necessarily associated with ischemic episodes and that, conversely, some ischemic episodes are not associated with evidence of thrombin activation.
Clinical Lecture on Amputation at the Hip-Joint: With Cases Illustrating the Use of the Lever for Controlling Haemorrhage
Authors: R. Davy
Journal: BMJ (1879)

pected confirmation of the opinion that the four pancreatic ferments are perfectly distinct bodies.The most complete, active, and convenient medicinal equivalents of pancreatic juicc are, however, the liquid' extracts of the gland.These may be prepared from the pancreas of the pig, with glycerine, with water, or with brine.The glycerine extract leaves nothing to desire on the score of activity, and it keeps perfectly; but the taste of glycerine is to some persons objectionable, and it seems sometimes to provoke nausea, and even vomiting.
Lung Scan in a Cardiac Patient with Glenn Anastomosis
Authors: SERAFIN TIU, DEBORAH M. FRIEDMAN, BARBARA KLEIN, EUGENIE F. DOYLE
Journal: Clinical Nuclear Medicine (1987)

A 17-year-old patient who had a previous Glenn anastomosis for surgical palliation of tricuspid atresia underwent perfusion and ventilation lung imaging to rule out pulmonary embolism. The study demonstrated an entire right upper lobe mismatch, which can be attributed to preferential flow to the right lower lobe as a consequence of a shunt between the superior vena cava and right pulmonary artery.
Hard Water and Coronary Disease
Authors: John B. Neal
Journal: JAMA (1963)

To the Editor:  —In the April 6 issue ofThe Journal, in the Questions and Answers section (184:85), there was a discussion about areas with hard water having a lower coronary mortality. The statistical studies by Schroeder mentioned in the discussion showed a negative correlation (protective effect) with contents of magnesium, calcium, bicarbonate, sulfate, fluoride, dissolved solids, the specific conductivity of water, and especially with pH. When considering an effect on coronary mortality, there is the possibility of a preventive effect on atherosclerosis, or an effect of preventing fatal arrhythmias, or an effect on blood clotting, to mention a few.  Magnesium and calcium have been used to treat cardiac arrhythmias. Magnesium is a vasodilator. It reduces the conductivity of the myocardium; it depresses the central nervous system. Some laboratory technicians place MgSO4on the finger before sticking for a platelet count, to prevent the platelets from agglutinating. Magnesium
Recurrent sustained ventricular tachycardia 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens.
Authors: L N Horowitz, M E Josephson, A Farshidi, S R Spielman, E L Michelson, A M Greenspan
Journal: Circulation (1978)

Twenty patients with recurrent sustained ventricular tachycardia (VT) underwent serial electrophysiological studies (EPS) 1) to determine the predictive value of the EPS in the selection of antiarrhythmic therapy, and 2) to establish the therapeutic efficacy of available antiarrhythmic agents. In each patient VT could be reproducibly initiated by programmed stimulation. After control EPS, the effects of several drugs (lidocaine, procainamide, quinidine, disopyramide and diphenylhydantoin) on the ability to initiate VT were assessed. An oral regimen was chosen on the basis of acute EPS and its effectiveness was evaluated by repeat EPS in 24--72 hours. Blood levels achieved acutely were used as guidelines to chronic therapy. In 14 patients the initiation of VT was prevented by the acute administration of one or more agents. In 13 of these patients, a chronic oral regimen based on these results prevented recurrence of VT with a three- to 27-month follow-up. In the remaining patient, oral therapy could not achieve blood levels of procainamide shown to be effective intravenously, and VT recurred. In six patients no single drug or drug combination was effective during acute EPS, and VT recurred in all while on therapy with the agent shown to make initiation of VT most difficult. Procainamide prevented VT in nine patients; quinidine in three patients; lidocaine in three patients; diphenylhydantoin in two patients; and disopyramide in one patient. The mean duration of EPS studies was 4.5 days. This study suggests that serial EPS provides rapid identification of successful antiarrhythmic therapy and can predict in which patients conventional therapy would be ineffective, thereby identifying patients requiring more aggressive modes of therapy.
Abstract 4258: Role of β2SP in asymmetric division and differentiation of intestine epithelial cells
Authors: Ying Li, Wilma Jogunoori, Wenguo Yao, Hong Cao, Bibhuti Mishra, Lopa Mishra
Journal: Cancer Research (2010)

Abstract The adult intestinal epithelium of the gastrointestinal tract has a well-defined organizational structure. The epithelium can be divided into two regions, a functional region that houses differentiated cells (villi) and a proliferative region (crypts of Lieberkühn) that represents the epithelial stem cell niche. In the small intestine, finger-like projections protrude from the floor of the intestine, forming villi. Multiple proliferative crypts surround each villus base. All epithelial cells that populate the villus originate from these crypts. Multipotent epithelial stem cells reside in the crypts and give rise to four principal epithelial lineages: absorptive enterocytes, mucin secreting-goblet cells, peptide hormone secreting enteroendocrine cells, and Paneth cells. Three of these cell lineages differentiate as they migrate up and out of the crypts onto the adjacent villus. The fourth lineage, Paneth cells, differentiates with a downward migration to reside at the base of the crypt. It is believed that these different cell types are generated by asymmetric cell divisions of stem/progenitor cells. However, the molecular mechanisms of how stem cells differentiate into four different cell types are only partially understood. Aim: in the current study, we evaluated the role of β2SP (β2 spectrin) in the differentiation and asymmetric division of stem/progenitor cells in normal intestine epithelium. Results: Our preliminary data showed that the number of secreting-goblet cells and peptide hormone secreting enteroendocrine cells was reduced in β2SP+/− mice compared to the wt mice. The number of cells undergo asymmetric division was also 3 folds lower in β2SP+/− mice than in wt mice. In in vitro studies, polarization of Par3 and PKCζ was impaired in β2SP−/− MEF cells. The coimmunoprecipitation assay demonstrated that β2SP directly bound to Par3 and actin in normal intestine epithelial cells, indicating that β2SP was involved in the spindle orientation and positioning during the asymmetric division of intestine epithelial cells. Conclusion: β2SP interacts with Par3 and regulates spindle orientation and polarization in the process of cell division, thereby contributing to the differentiation and asymmetric division of intestinal stem/progenitor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4258.
Antiandrogenic pesticides disrupt sexual characteristics in the adult male guppy Poecilia reticulata.
Authors: E Baatrup, M Junge
Journal: Environmental Health Perspectives (2001)

Environmental contaminants have been identified as endocrine disruptors through their antiandrogenic activity. Thus, as androgen receptor antagonists, the fungicide vinclozolin and the principal DDT metabolite p,p'-DDE have been demonstrated to induce demasculinization in rats. Whether this is also the case in fish remains to be demonstrated. For a period of 30 days, groups of adult male guppies were exposed to vinclozolin, p,p'-DDE, or the therapeutic antiandrogen flutamide (used as positive control) applied to the fodder at concentrations between 0.1 and 100 microg/g fodder. Subsequently, sexual characteristics of relevance to the male reproductive capacity were measured and compared with untreated control fish. All three chemicals caused profound alterations at increasing levels of biological organization, even in these fully matured males. At the cellular level, the three compounds induced a significant reduction in the number of ejaculated sperm cells. At the organ level, the sexually attractive orange-yellow coloration was reduced in area and discolored, and treated fish also had smaller testes. Further, at the organismal level, computer-aided behavior analyses demonstrated a severe disruption in male courtship behavior. We conclude that this demasculinization is consistent with an antiandrogenic action of vinclozolin and p,p'-DDE and is likely to compromise reproductive capability in this fish.
Effect of cardiac A1 adenosine receptor overexpression on sarcoplasmic reticulum function
Authors: R Zucchi
Journal: Cardiovascular Research (2002)

Objective: We investigated the effect of A1 adenosine receptor overexpression, which has been reported to increase myocardial tolerance to ischemia-reperfusion injury, on sarcoplasmic reticulum (SR) Ca2+ handling. Methods: Transgenic mouse hearts (∼300-fold A1 adenosine receptor overexpression) and wild-type mouse hearts were perfused in the Langendorff mode and subjected either to 80 min of aerobic perfusion or to 30 min of aerobic perfusion, 20 min of global ischemia and 30 min of reperfusion. The hearts were then homogenized and used to assay SR oxalate-supported 45Ca2+ uptake and [3H]–ryanodine binding. Results: Transgenic hearts showed increased resistance to ischemia-reperfusion, as shown by lower diastolic tension (1.5±0.2 vs. 2.6±0.1 g, P<0.05) and higher recovery of developed tension (45±3 vs. 30±4% of the baseline, P<0.05) following ischemia-reperfusion. Under baseline conditions, oxalate-supported 45Ca2+ uptake was lower in transgenic hearts, owing to reduced Vmax (10.6±2.0 vs. 17.8±2.7 nmol/min per mg of protein, P<0.05), and the difference was preserved after ischemia-reperfusion (10.0±1.0 vs. 15.7±2.5 nmol/min per mg of protein, P<0.05). No significant difference in [3H]–ryanodine binding was observed. Conclusions: A1 adenosine receptor overexpression is associated with a decreased rate of active Ca2+ transport into the SR. We hypothesize that changes in SR function may cause a depletion of the SR Ca2+ pool, which might protect from ischemic injury by delaying the development of cytosolic Ca2+ overload during ischemia.