tbuckley/cabot-search huggingface dataset:
Abstract 3056: Amplification of the BP1 homeobox gene in familial breast cancer with BRCA1/2 mutations
Authors: Silma R. Pereira, Marcia M.C. Oliveira, Bassem R. Haddad, Patricia E. Berg, Luciane R. Cavalli
Journal: Cancer Research (2011)

Abstract Background: BP1 is a homeobox gene which was reported to be amplified and overexpressed in breast tumors with poor clinical outcome. Its exact role and function in breast tumorigenesis is not known and no studies have investigated its role in familial breast cancer cases. BP1 is located on 17q21, a chromosomal region that is altered in a high percentage of breast tumors; CGH analysis of the 17q region demonstrated gains in 50% and 85% of BRCA1 and BRCA2 mutated familial breast tumors, respectively. BP1 has been found to be overexpressed in breast cancer cells defective in double-strand break repair by homologous recombination (BRCA defective) and has been shown to directly regulate BRCA1 expression. The above information formed our rationale to evaluate the amplification of BP1 in familial breast cancer patients with known BRCA1/2 mutation status. We hypothesized that BP1 would be preferentially amplified in BRCA1/2 mutations carriers and correlated with poor clinical prognostic factors. Methods: Three tissue microarrays, containing tumor tissues of a total of 67 familial breast cancer patients, with known BRCA1/2, ER and PR status and full clinical data, were obtained from the Familial Cancer Registry from Georgetown University. FISH analysis was performed using a specific BP1 FISH probe developed in our lab. Results: FISH scoring in 100 cells was performed in 87% of the patients. Amplification of BP1 was observed in 26% of the cases and was significantly correlated with the presence of mutations in the BRCA1/2 genes, as opposed to patients with full negative (FN), Jewish panel negative (JPN) and variant with unknown significance (VUS). BP1 amplification was also significantly correlated with large tumor size (&amp;gt;1.5cm) and poorly differentiated tumors. Upon stratification of the samples by histological type, a total of 173 lesions (from cores containing different lesions from the same patients) were analyzed. Similar frequencies of BP1 amplification were observed in invasive (24%) and ductal carcinoma in situ (23.6%) lesions. Conclusions: Our findings demonstrate that the BP1 homeobox gene is amplified in familial breast cancer patients and its amplification is correlated with the presence of mutations in the BRCA1/2 genes as well as poor clinical prognostic factors, such as large tumor size and poorly differentiated tumors. Studies evaluating the expression of BRCA1 and BP1 proteins in these samples are in progress, in order to identify possible mechanism of interactions and related pathways between BP1 positive and BRCA1 mutant tumors in familial breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3056. doi:10.1158/1538-7445.AM2011-3056
External assessment of health care
Authors: C. Shaw
Journal: BMJ (2001)

A rash of external inspection is affecting the delivery of health care around the world. Governments, consumers, professions, managers, and insurers are hurrying to set up new schemes to ensure public accountability, transparency, self regulation, quality improvement, or value for money. But what do we know of such schemes' evidence base, the validity of their standards, the reliability of their assessments, or their ability to bring improvements for patients, staff, or the general population?

### Box 1: Characteristics of effective external assessment programmes

Give clear framework of values —To describe elements of quality, and their weighting, such as the enablers and results defined by the European Foundation for Quality Management

Publish validated standards —To provide an objective basis for assessment

Focus on patients —To reflect horizontal clinical pathways rather than vertical management units

Include clinical processes and results —To reflect perceptions of patients, staff, and public

Encourage self assessment —To give time and tools to internalise assessment and development

Train the assessors —To promote reliable assessments and reports

Measure systematically —To describe and weight compliance with standards objectively

Provide incentives —To give leverage for improvement and response to recommendations

Communicate with other programmes —To promote consistency and reciprocity and to reduce duplication and burden of inspection

Quantify improvement over time —To demonstrate effectiveness of programme

Give public access to standards, assessment processes, and results —To be transparent and publicly accountable RETURN TO TEXT

In short, not much. The standards, measurements, and results of management systems have not been, and largely cannot be, subjected to the same rigorous scrutiny and meta-analysis as clinical practice. No one has published a controlled trial, and there are too many confounding variables to prove that inspection causes better clinical outcomes, although there is evidence that organisations increase their compliance with standards if these are made explicit. But experience and consensus are gradually being codified into guidelines to …
An Introduction to the Philosophical Presuppositions of the Animal Liberation/Rights Movement
Authors: Richard P. Vance
Journal: JAMA (1992)

THE ANIMAL liberation/rights movement (ALRM) poses a significant threat to the future of medical research. This threat is far greater than currently recognized by most physicians.<sup>1,2</sup>One of the strengths of the ALRM is its multifaceted nature.<sup>1-7</sup>Some activists attack research by picketing facilities, intimidate researchers via threatening mail or phone calls, or destroy property and threaten lives.<sup>3-5,8</sup>Others attack research through political, regulatory, and bureaucratic avenues, or use intimidating legal maneuvers.<sup>1,2,4,8</sup>Others criticize research by posing as objective professional organizations.<sup>1,2,9</sup>Finally, some professional philosophers provide justifications for ALRM activities.<sup>10-20</sup> Defenders of research often miss the mark in their analysis and criticisms, because political terrorist activities tend to draw attention away from careful consideration of ALRM's philosophical presuppositions.<sup>21-23</sup>As a result, we have consistently misjudged and underestimated the potential danger of the ALRM. From the beginning, the ALRM has been a<i>liberation movement</i>
Kinetics and cellular localisation of putrescine uptake in human lung tissue.
Authors: P H Hoet, D Dinsdale, C P Lewis, E K Verbeken, J M Lauweryns, B Nemery
Journal: Thorax (1993)

BACKGROUND--The polyamines (putrescine, spermidine, and spermine) are involved in cellular growth, proliferation, and differentiation. In the lungs of various species, polyamines are accumulated by an active uptake system which also mediates the uptake of cystamine and paraquat. In the rat lung putrescine uptake has been shown to be cell-specific, occurring predominantly in the alveolar epithelium. The aim of this study was to characterise the uptake of putrescine in human lung. METHODS--Lung tissue was obtained from 31 patients undergoing surgery for lung cancer. Slices (0.7 mm thick) from non-tumour containing lung parenchyma were incubated for 15-60 minutes in Krebs-Ringer phosphate buffer with various concentrations of putrescine (2.5 to 80 mumol/l) containing 0.1 microCi [1,4-14C]-putrescine. Uptake was assessed from tissue radioactivity. For autoradiographic imaging, slices were incubated for 30 minutes with 2.5 mumol/l putrescine containing 2.5 mCi [1,4n-3H]-putrescine. RESULTS--The accumulation of [14C]-putrescine into slices was time-dependent and energy-dependent, and obeyed saturation kinetics, with mean calculated values for Vmax (maximal rate of uptake) of 414 nmol/g/hour and for Km (medium concentration at which the rate of uptake is half Vmax) of 7.2 mumol/l, with a large interindividual variation. Competitive inhibition was observed on incubation with cystamine, which appears to have a high affinity for the uptake system since its calculated Ki (concentration of inhibitor at which the Km is doubled) was 3.2 mumol/l. Ultrastructural autoradiography showed labelling over both type I and type II cells of the alveolar epithelium, but not over the endothelium or any cells of the interstitium. Alveolar macrophages were also devoid of label. CONCLUSIONS--These results show that the human lung possesses an active uptake system for putrescine, and probably also cystamine, which is located in both cell types of the alveolar epithelium. These findings may be used to develop tests for the assessment of the alveolar epithelium.
Pharmacologic inhibitors of PI3K/Akt potentiate the apoptotic action of the antileukemic drug arsenic trioxide via glutathione depletion and increased peroxide accumulation in myeloid leukemia cells
Authors: Adrián M. Ramos, Carlos Fernández, Donna Amrán, Patricia Sancho, Elena de Blas, Patricio Aller
Journal: Blood (2005)
Change in Diastolic Left Ventricular Filling After One Year of Antihypertensive Treatment
Authors: Kristian Wachtell, Jonathan N. Bella, Jens Rokkedal, Vittorio Palmieri, Vasilios Papademetriou, Björn Dahlöf, Tapio Aalto, Eva Gerdts, Richard B. Devereux
Journal: Circulation (2002)

Background — It is well established that hypertensive patients with left ventricular (LV) hypertrophy have impaired diastolic filling. However, the impact of antihypertensive treatment and LV mass reduction on LV diastolic filling remains unclear. Methods and Results — Echocardiograms were recorded in 728 hypertensive patients with ECG-verified LV hypertrophy (Cornell voltage-duration or Sokolow-Lyon) at baseline and after 1 year of blinded treatment with either losartan or atenolol-based regimen. Systolic and diastolic blood pressures (BP) were reduced on average 23/11 mm Hg; isovolumic relaxation time and E/A ratio became more normal, and LV inflow deceleration time prolonged (all P &lt;0.001). Directionally opposite changes in isovolumic relaxation time (IVRT) and deceleration time indicate improvement in active LV relaxation and passive chamber stiffness during early diastole. Prevalences of normal LV filling increased, abnormal relaxation and pseudonormalization decreased, and restrictive filling pattern remained unchanged ( P &lt;0.05). Patients with reduction in LV mass had smaller left atrial diameter, shortened IVRT, increased E/A ratio, and prolonged LV inflow deceleration time (all P &lt;0.001). Patients without LV mass reduction had no change in diastolic filling parameters ( P =NS). IVRT shortening was independently associated with reduction in LV mass. Increase in E/A ratio was independently associated with reduction in diastolic BP, and increase in the deceleration time was independently associated with reduced end-systolic relative wall thickness. Conclusions — Antihypertensive therapy resulting in LV mass or relative wall thickness regression is associated with significant improvement of diastolic filling parameters related to active relaxation and passive chamber stiffness compared with patients without regression, independent of BP reduction; however, abnormalities of diastolic LV filling remain common.
Mechanical Inscription of the Vectorcardiogram
Authors: A. CALHOUN WITHAM, WM. F. HAMILTON
Journal: Circulation (1954)

A modification of the vectorcardiographic method of studying electrical events is presented. Simultaneous scalar leads, taken by any vector lead system, are first recorded. The important time intervals, difficult or impossible to read from the loop itself, are measured from these tracings. Proper pairs of the scalar leads can then be rapidly integrated into vector loops by an easily constructed drawing board based on the pulley system. This instrument is described in detail. It is demonstrated that loops so derived do not appear to differ in their important characteristics from electronically integrated loops.
Effects on Rats of Prolonged Staple African Diet
Authors: J. Gillman
Journal: BMJ (1944)

This case is reported becatuse of the large number of parasites in the blood film and the severe clinical signs, in spite of which recovery followed. Clinical HistoryThe patient, a soldier aged 22, was admitted to a C.C.S. in North Africa on July 10, 1943.We subsequently learnt that while on local leave in North Africa he became ill, but attributed the illness to the heat and did not consult a medical officer.He had no clear memory of how he reached this C.C.S.; he last remembers travelling in a train with other soldiers, who finally took him to the central M.I. room of this area.He was admitted late at night, about five or six days after the onset of the illness.On examination he complained of headache and vomiting.He was drowsy but not un^onscious, and could answer questions reasonably well.The temperature was 102.4'F. The spleen was easily palpable.The urine was of normal colour.Blood slides showed a very heavy malarial infection.The thick film was crowded with parasites.Examination of the central parts and the edges of the thin film revealed that, on an average, 35%' of the red cells contained parasites.Of the infected cells 82% had one ring, 17% had two rings, and 1% had three or four rings per cell.Several crescents of Plasmiiodiiwnii falciparuino were also seen.He was given 10 gr. of quinine dihydrochloride in 20 c.cm. of water intravenously and 12 gr.by mouth at 11.30 p.m., the latter dose being repeated in six hours.Next day his condition was only fairly satisfactory; he was still drowsy, but he took 10 gr. of quinine six-hourly by mouth without vomiting.The temperature remained normal all day.A blood film showed large numbers of parasites to be still present.He took fluids fairlv well, but passed only very small amounts of urine.Early on the mor-ning of July 12 the patient was found to be qtmite unconscious, cold, and collapsed.The tongue was hard and
Nurse management of patients with minor illnesses in general practice: multicentre, randomised controlled trial
Authors: C. Shum
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess the acceptability and safety of a minor illness service led by practice nurses in general practice. <b>Design:</b> Multicentre, randomised controlled trial. <b>Setting:</b> 5 general practices in south east London and Kent representing semi-rural, suburban, and urban settings. <b>Participants:</b> 1815 patients requesting and offered same day appointments by receptionists. <b>Intervention:</b> Patients were assigned to treatment by either a specially trained nurse or a general practitioner. Patients seen by a nurse were referred to a general practitioner when appropriate. <b>Main outcome measures:</b> The general satisfaction of the patients as measured by the consultation satisfaction questionnaire. Other outcome measures included the length of the consultation, number of prescriptions written, rates of referral to general practitioners, patient9s reported health status, patient9s anticipated behaviour in seeking health care in future, and number of patients who returned to the surgery, visits to accident and emergency, and out of hours calls to doctors. <b>Results:</b> Patients were very satisfied with both nurses and doctors, but they were significantly more satisfied with their consultations with nurses (mean (SD) score of satisfaction 78.6(16.0) of 100 points for nurses <i>v</i> 76.4 (17.8) for doctors; 95% confidence interval for difference between means −4.07 to −0.38). Consultations with nurses took about 10 minutes compared with about 8 minutes for consultations with doctors. Nurses and doctors wrote prescriptions for a similar proportion of patients (nurses 481/736 (65.4%) <i>v</i> doctors 518/816 (63.5%)). 577/790 (73%) patients seen by nurses were managed without any input from doctors. <b>Conclusion:</b> Practice nurses seem to offer an effective service for patients with minor illnesses who request same day appointments.
Steroid Hormone Regulation of Nuclear Proto-oncogenes*
Authors: MARK SCHUCHARD, JAMES P. LANDERS, NICOLE PUNKAY SANDHU, THOMAS C. SPELSBERG
Journal: Endocrine Reviews (1993)

A. Cancer and oncogenes THE GROWTH and differentiation of a normal cell is controlled by a number of intricately complex regulatory events that are coordinated so as to meet the needs of the tissue and ultimately the organism as a whole. This intricate process of regulatory checks and balances malfunctions with cancer cells which replicate in a self-reliant manner that ultimately interferes with the growth and function of normal cells. At the cellular level, the transformation from the normal to the cancerous (neoplastic) state involves disruption of regulatory events required for normal cell function. Great strides have been made in the last few decades toward understanding the molecular mechanism(s) through which cancers develop. It is now thought that development of neoplastic growth results from the altered expression and/or function of a battery of genes that may play key roles in the regulation of cell growth and differentiation. In this respect, the group of genes termed the oncogenes have been the focus of intense study. Originally identified by their ability to induce neoplastic transformation, they are now recognized as mutant forms of the “normal” proto-oncogenes which play a central role in growth regulation in normal cells. Proto-oncogenes and their mutated counterparts thus provide an excellent cellular marker for not only studying the regulatory mechanisms orchestrating normal cellular events, but also for dissecting the molecular basis of neoplastic growth.
Synergistic anti-tumor activity of paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel in vitro and in vivo
Authors: Ding-Ding Guo, Cheng-Xiong Xu, Ji-Shan Quan, Chung-Kil Song, Hua Jin, Dae-Duk Kim, Yun-Jaie Choi, Myung-Haing Cho, Chong-Su Cho
Journal: Biomaterials (2009)
A Phase I Study of a 2-Day Lapatinib Chemosensitization Pulse Preceding Nanoparticle Albumin-Bound Paclitaxel for Advanced Solid Malignancies
Authors: Amy J. Chien, Julie A. Illi, Andrew H. Ko, Wolfgang M. Korn, Lawrence Fong, Lee-may Chen, Mohammed Kashani-Sabet, Charles J. Ryan, Jonathan E. Rosenberg, Sarita Dubey, Eric J. Small, Thierry M. Jahan, Nola M. Hylton, Benjamin M. Yeh, Yong Huang, Kevin M. Koch, Mark M. Moasser
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Systemic chemotherapy fails to access much of the tumor burden in patients with advanced cancer, significantly limiting its efficacy. In preclinical studies, brief high doses of tyrosine kinase inhibitors (TKI) targeting the human epidermal growth factor receptor (HER) family can prime tumor vasculature for optimal chemotherapeutic delivery and efficacy. This study investigates the clinical relevance of this approach. Experimental Design: A phase I clinical study of escalating doses of the HER TKI lapatinib given as a 2-day pulse before a weekly infusion of nab-paclitaxel (100 mg/m2) was conducted in patients with advanced solid tumors. Results: Twenty-five patients were treated. Treatment was associated with grade 1 to 2 toxicities including diarrhea, nausea, rash, neutropenia, neuropathy, fatigue, alopecia, and anemia. The two dose-limiting toxicities were grade 3 vomiting and grade 4 neutropenia, and the maximum tolerated dose of lapatinib was defined as 5250 mg/day in divided doses. Lapatinib concentrations increased with increasing dose. Dynamic Contrast Enhanced Magnetic Resonance Imaging studies in a subset of patients confirmed a decrease in tumor vascular permeability immediately following a lapatinib pulse. Sixty-five percent of evaluable patients experienced a partial or stable response on this therapy, 72% of whom were previously taxane-refractory. Conclusion: A 2-day pulse of high-dose lapatinib given before weekly nab-paclitaxel is a feasible and tolerable clinical regimen, suitable for testing this novel vascular-priming chemosensitization hypothesis developed in preclinical models. (Clin Cancer Res 2009;15(17):5569–75)
OCCURRENCE OF THE BORDETGENGOU BACILLUS
Authors: BJÖRN KRISTENSEN
Journal: JAMA (1933)

In continuation of previous investigations 1 issued from the Danish State Serum Institute, I have carried out some systematic studies on the occurrence of the Bordet-Gengou bacillus.  Since 1916, this institute has employed the coughingplate method introduced by Adolph H. Meyer for the bacteriologic diagnosis of whooping cough, and in Denmark this method is being used more and more.  Previously the results from a total of 2,811 suitable specimens have been compiled. In addition, I have examined 1,086 suitable specimens at the State Serum Institute during the period from Sept. 1, 1930, to March 1, 1931. All told, the material consists of 3,897 specimens, 2,144 of which came from pertussis patients. The results from these 2,144 examinations are given in table 1.  From the material of the serum institute it is difficult to say anything definite as to the occurrence of the Bordet-Gengou bacillus in the later stages of whooping