tbuckley/cabot-search huggingface dataset:
Abstract 1090: Development of predictive biomarkers for anti-TGF-beta therapy
Authors: Yu-an Yang, Jia Weng, Michael Welsh, Heide L. Ford, Scott M. Lonning, Lalage Wakefield
Journal: Cancer Research (2011)

Abstract TGF-betas are pleiotropic growth factors with complex roles in tumorigenesis. The TGF-betas have many activities that could promote metastasis, including the enhancement of invasion and migration, the promotion of angiogenesis, and the suppression of immune surveillance. Overexpression of TGF-beta in many advanced human tumors correlates with metastasis and poor prognosis, and there is now considerable interest in developing TGF-beta antagonists for cancer therapy. Indeed, a Phase I oncology trial using a fully humanized anti-TGF-beta monoclonal antibody was recently successfully completed. There is now an urgent need for good predictive biomarkers for patient stratification in future clinical trials. Using different syngeneic mouse transplant models of metastatic breast cancer, we have found that anti-TGF-beta antibodies suppress metastasis in several models, including the widely-used 4T1 model. However, TGF-beta antibody treatment has no effect or even stimulates metastasis in other models. This panel of mouse models with differing responses to anti-TGF-beta therapy represents a powerful experimental platform for the identification of predictive biomarkers. Based on existing knowledge, we have assessed a number of plausible candidates. Global gene expression analyses have defined several distinct molecular subtypes of breast cancer with different clinical characteristics. The “Claudin-low” subtype is a particularly poor prognosis subset of the triple negative ER-PR-HER2- breast cancers. By definition these tumors have low claudin and E-cadherin expression and a mesenchymal phenotype. Since TGF-betas are strong inducers of the mesenchymal phenotype, the claudin-low subtype may represent a particularly good target for anti-TGF-beta therapy. Similarly, overexpression of the homeobox protein Six-1 has recently been shown to cause TGF-beta to switch from tumor suppressor to pro-metastatic factor in breast cancer and might also be a predictor of a positive therapeutic response to TGF-beta antagonism. Here we have assessed the claudin-low status of a number of mouse mammary tumor models, by RTQ-PCR for key markers, using cells cultured in vitro. In addition, we determined nuclear Six1 levels by Western blot. Neither claudin-low status nor Six1 expression were predictive of response to anti-TGF-beta therapy. We are assessing additional candidate biomarkers and moving forward with discovery approaches. 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 1090. doi:10.1158/1538-7445.AM2011-1090
Peyronie's Disease — A Presenting Complaint of the Carcinoid Syndrome
Authors: Carl H. Bivens, Raymond L. Marecek, Jerome M. Feldman
Journal: New England Journal of Medicine (1973)

ALTHOUGH the earliest clinical manifestations of the carcinoid syndrome are usually facial flushing and diarrhea, other symptoms may herald this syndrome. In the cases reported below the carcinoid syndrome was associated with another unusual condition, Peyronie's disease, or plastic induration of the penis. Since 1970 we have evaluated and cared for 12 patients with carcinoid tumors and hepatic metastasis. Although none of the five men with inactive carcinoid tumors had Peyronie's disease, two of the six men with the carcinoid syndrome also had Peyronie's disease. Case Reports Case 1. In November, 1971, a 46-year-old black man was evaluated because of . . .
Pattern of Cholesterol Ester Fatty Acids in Serum in Normal Subjects and in Patients with Essential Hypercholesterolemia
Authors: PER BJOÖRNTORP, BERTIL HOOD
Journal: Circulation Research (1960)

Sera from 10 patients with essential hypercholesterolemia on ad libitum diet have been analyzed for their content of polyunsaturated fatty acids in the cholesterol esters and the results compared with a matched group of normal subjects. Three cases were analyzed after corn oil substitution for other fats in the diet, and 2 of them were analyzed after addition of pyridoxine to the corn oil regimen. One patient was followed 18 months, and during that time he received a large dosage of corn oil. Patients with essential hypercholesterolemia had an absolute increase in the amount, but generally a lower percentage content of dienes in their cholesterol esters than normals. After the change to corn oil, the content of polyunsaturated fatty acids increased to levels sometimes considerably above those in the normal subjects, although the total serum cholesterol in one of these cases was by no means normalized. The addition of 100 mg. of pyridoxine to the corn oil regimen did not produce any further decrease in the serum cholesterol level and did not produce any changes in the fatty acid fractions. The absolute increase in the amount of polyunsaturated fatty acids in the cholesterol esters in essential hypercholesterolemia, particularly after an extremely high intake of unsaturated fat, speaks against factors causing an inhibition in esterification with polyenes as being of central importance.
Pathologist in G20 protest case faces more GMC charges
Authors: C. Dyer
Journal: BMJ (2010)

The pathologist who was criticised for his part in the investigation of the newspaper vendor Ian Tomlinson’s death during London’s G20 protests last year faces fresh allegations in a hearing at the General Medical Council.

Freddy Patel is accused of “irresponsible” conduct and deficient professional performance in carrying out postmortem examinations in 2002 of Sally White, a prostitute who was the first victim of the serial killer Anthony Hardy, dubbed the Camden Ripper.

Ms White’s naked body was found in Hardy’s flat in January 2002. Dr Patel (full name Mohmed Saeed Sulema Patel) reported that she had died of natural causes despite blood stains …
GLIOMA STEM CELL HOMING TO THE HUMAN SUBVENTRICULAR ZONE
Authors: N. Sanai, Y. Kusne, N. Su, S. Hemdan, Z. Mirzadeh, F.-D. Shi
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field) METHODS: Using intraoperatively-derived human tissue, we employ a combination of cell culture, FACS-sorting, and immunohistochemistry techniques to characterize human glioma and GSC homing to the SVZ, as well as identify new, targetable cytokine pathways relevant to this niche. RESULTS: Our analysis identifies glioma cells homing to human SVZ and co-opting the gap layer for tangential migration. Interestingly, we find that human SVZ-invasive glioma cells are 50-fold more likely to function as glioma stem cells. Organotypic slice culture and co-culture assays also identify chemotactic effects, associated integrins, and related extracellular matrix proteins of 3 SVZ-enriched ligands (EGF, PDGF-BB, and SDF1) known to drive pro-migratory glioma pathways. CONCLUSIONS: Despite its quiescence, the adult human SVZ retains the signaling machinery to support cell migration and these mechanisms may be co-opted by glioma stem cells during subependymal spread in humans. SECONDARY CATEGORY: n/a.
Randomized trial of interferon‐ and ribavirin‐free ombitasvir/paritaprevir/ritonavir in treatment‐experienced hepatitis C virus–infected patients
Authors: Kazuaki Chayama, Kazuo Notsumata, Masayuki Kurosaki, Ken Sato, Lino Rodrigues, Carolyn Setze, Prajakta Badri, Tami Pilot‐Matias, Regis A. Vilchez, Hiromitsu Kumada
Journal: Hepatology (2015)

Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end‐stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open‐label study evaluated an IFN‐ and RBV‐free regimen of once‐daily ombitasvir (ABT‐267), an NS5A inhibitor, plus paritaprevir (ABT‐450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment–experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18‐75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR 24 ) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR 24 rates were high (88.9%‐100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR 24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR 24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR 12 and SVR 24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%). Conclusion : In this difficult‐to‐treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection. (H epatology 2015;61:1523–1532)
Young people who self harm by cutting
Authors: J. H. Roberts, R. Pryke, M. Murphy, L. Russell
Journal: BMJ (2013)

Hayley, a 15 year old girl, comes to you about mild acne. You notice a scar just visible at wrist level. She is unaccompanied. There is a family history of depression and her parents are separated.

### History and her feelings

Hayley may have needed considerable courage to consult; missing this opportunity to discuss her situation, by being dismissive or (inadvertently) patronising, may heighten her sense of isolation and risk further escalation of self harm.

After dealing with her concerns about acne and suggesting a topical skin preparation (and review) ask permission to talk about the scar and show that you are interested in her emotional wellbeing.

Aim to create a non-judgmental environment where Hayley can sense that you are genuinely interested in her as an individual.

Explain that the consultation is confidential, unless serious concerns for her safety mean that you must act, but that you would always discuss this with her first. Explain that you could seek advice from your local safeguarding clinical lead without identifying Hayley in the first instance, …
US judge condemns health plan for not covering contraception
Authors: D. Josefson
Journal: BMJ (2001)

A health insurance plan offering cover for prescription drugs but not for contraceptives is guilty of sex discrimination and violation of the 1964 Civil Rights Act and the 1978 Pregnancy Discrimination Act, a federal judge in Seattle, Washington, has ruled.

The ruling marks the first time that a federal court has ordered a self insured health care plan offered by a small business to provide contraceptive cover to its female employees. The verdict has been hailed as a landmark decision and may lead to wider prescription drug …
Significance of the transmural diminution in regional hydrogen ion production after repeated coronary artery occlusions.
Authors: K G Warner, S F Khuri, W Marston, S Sharma, M D Butler, S N Assousa, A J Saad, S Y Siouffi, P T Lavin
Journal: Circulation Research (1989)

Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15-minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions.
Exposure to Lead in Firing Ranges
Authors: Alf Fischbein
Journal: JAMA (1979)

Members of law enforcement agencies were examined for adverse health effects caused by their activities in firing ranges and exposure to lead. Central nervous system and gastrointestinal symptoms were prominent and correlated with blood lead and zinc protoporphyrin levels. Half the group had blood lead levels exceeding 40 μg/dL, and four (5%) exceeded 60 μg/dL. Environmental surveys of three firing ranges indicate that indoor facilities with insufficient ventilation may have considerable air lead concentrations with levels up to 900 μg/cu m or 4.5 times the current Occupational Safety and Health Administration standard for an eight-hour shift. Evaluation of lead effects should be taken into account in medical surveillance programs of firearms instructors. Zinc protoporphyrin determination has proved a suitable and practical way to assess biological effects among exposed persons and should be available at medical facilities responsible for the health of indoor firing range employees. (<i>JAMA</i>241:1141-1144, 1979)
Suppression of NZB/NZW murine nephritis by administration of a syngeneic monoclonal antibody to DNA. Possible role of anti-idiotypic antibodies.
Authors: B H Hahn, F M Ebling
Journal: Journal of Clinical Investigation (1983)

Suppression of circulating antibodies to double-stranded DNA was achieved in NZB/NZW f1 female mice by repeated administration of an IgG2a monoclonal antibody to DNA. Deaths from nephritis were delayed; glomerular deposition of IgG and of the cationic IgG DNA antibodies characteristic of murine lupus nephritis were diminished. Quantities of circulating antibodies to single-stranded DNA were not reduced compared with untreated or IgG myeloma-treated control mice. Antibodies directed against the monoclonal anti-DNA appeared in the circulation of treated mice after three inoculations of the idiotype. Those antibodies did not react with another monoclonal anti-DNA of the same allotype. One monoclonal anti-idiotypic antibody was obtained in hybridoma cultures derived from a spleen of a treated mouse. Cross-reactive or common idiotypes were found in 30-50% of NZB/NZW f1 sera and monoclonal DNA antibodies. Deletions of portions of the spectrotype of antibodies to DNA were found in sera containing anti-idiotypic antibodies, suggesting suppression of clones producing antibodies with isoelectric points similar to that of the immunizing idiotype. Deletions of some of the anti-idiotypic antibodies also occurred as the mice aged. Rheumatoid factors were not detectable in any sera. Therefore, administration of an antibody to DNA bearing an idiotype occurring with high frequency in NZB/NZW f1 females resulted in relatively specific suppression of the antibody response to double-stranded DNA, as well as suppression of nephritis. Reduction of anti-DNA synthesis by anti-idiotypic antibodies may have been an important suppressive mechanism. Experiments are in progress to test this hypothesis.
Urinary eosinophil protein X and serum eosinophil cationic protein in infants and young children with atopic dermatitis: Correlation with disease activity
Authors: Neri Pucci, Enrico Lombardi, Elio Novembre, Silvia Farina, Roberto Bernardini, Elisabetta Rossi, Tania Favilli, Alberto Vierucci
Journal: Journal of Allergy and Clinical Immunology (2000)
Clinton proposes patients' bill of rights
Authors: T. Rutter
Journal: BMJ (1997)

Last week the US president, Bill Clinton, proposed legislation designed to protect patients from poor or inadequate health care.

The Health Care Consumer Bill of Rights is the first major piece of health reform that the president has proposed since his failed attempts on health reform in his first term.

The bill is an attempt to address, in part, some of the many problems that patients who are enrolled …
Reliability of distance estimation by doctors and patients: cross sectional study
Authors: B. Sharrack, R. A C Hughes
Journal: BMJ (1997)

To assess the reliability and accuracy of distance estimated by doctors and patients.Comparison between estimated and measured distances of six familiar sites around Guy's Hospital, London.100 hospital consultants and 100 patients.Median (range) of estimated distances, and mean (SD) of the difference between estimated and measured distances.Both doctors and patients gave a wide range of estimates of distance. The estimates differed by up to 14.6-fold from the measured distances, and the difference between minimum and maximum estimates was up to 62.5-fold.Doctors and patients were inaccurate at estimating distances, which implies that estimates of distances walked are not reliable indicators of a person's health.
Sociodemographic Differences in Fast Food Price Sensitivity
Authors: Katie A. Meyer, David K. Guilkey, Shu Wen Ng, Kiyah J. Duffey, Barry M. Popkin, Catarina I. Kiefe, Lyn M. Steffen, James M. Shikany, Penny Gordon-Larsen
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Fiscal food policies (eg, taxation) are increasingly proposed to improve population-level health, but their impact on health disparities is unknown. <h3>Objective</h3> To estimate subgroup-specific effects of fast food price changes on fast food consumption and cardiometabolic outcomes. <h3>Design, Setting, and Participants</h3> Twenty-year follow-up (5 examinations) in a biracial US prospective cohort: Coronary Artery Risk Development in Young Adults (CARDIA) (1985/1986-2005/2006, baseline N = 5115). Participants were aged 18 to 30 years at baseline; design indicated equal recruitment by race (black vs white), educational attainment, age, and sex. Community-level price data from the Council for Community and Economic Research were temporally and geographically linked to study participants' home address at each examination. <h3>Main Outcomes and Measures</h3> Participant-reported number of fast food eating occasions per week, body mass index (BMI), and homeostasis model assessment insulin resistance (HOMA-IR) from fasting glucose and insulin concentrations. Covariates included individual-level and community-level social and demographic factors. <h3>Results</h3> In repeated measures regression analysis, multivariable-adjusted associations between fast food price and consumption were nonlinear (quadratic,<i>P</i> &lt; .001), with significant inverse estimated effects on consumption at higher prices; estimates varied according to race (interaction<i>P</i> = .04), income (<i>P</i> = .07), and education (<i>P</i> = .03). At the 10th percentile of price ($1.25/serving), blacks and whites had mean fast food consumption frequency of 2.20 (95% CI, 2.07-2.33) and 1.55 (1.45-1.65) times/wk, respectively, whereas at the 90th percentile of price ($1.53/serving), respective mean consumption estimates were 1.86 (1.75-1.97) and 1.50 (1.41-1.59) times/wk. We observed differential price effects on HOMA-IR (inverse for lower educational status only [interaction<i>P</i> = .005] and at middle income only [interaction<i>P</i> = .02]) and BMI (inverse for blacks, less education, and middle income; positive for whites, more education, and high income [all interaction<i>P</i> &lt; .001]). <h3>Conclusions and Relevance</h3> We found greater fast food price sensitivity on fast food consumption and insulin resistance among sociodemographic groups that have a disproportionate burden of chronic disease. Our findings have implications for fiscal policy, particularly with respect to possible effects of fast food taxes among populations with diet-related health disparities.
UNILATERAL CHOKED DISK DUE TO TONSILLAR INFECTION
Authors: O. R. Lourie
Journal: JAMA (1933)

To the Editor:  —Amicus Plato sed magis amicus veritas. As much as I respectThe Journal, I am opposed to the theory of focal infection. I hope that you will publish this letter on account of the two cases reported inThe Journal, April 22, by Drs. Wilson and Darkes entitled Unilateral Choked Disk Due to Chronic Tonsillar Infection.  A few years ago the physician who hesitated to recognize the correctness of the theory of focal infection was considered a doubting Thomas. Doubt has crept into the minds of many since.   My first objection is to using the word due without making clear the causal relationship between the choked disks and the foci of infection in the tonsils. The improvement after the removal of the tonsils is not sufficient as such a proof.  Even elimination of all other causes for the choked disks would be insufficient as such a proof.
AUTOMATED REAL-TIME 3D ECHOCARDIOGRAPHY OF LONGITUDINAL AND ROTATIONAL VOXEL MYOCARDIAL MECHANICS IMAGING: COMPARISON TO TAGGED-CMR AND FEATURE TRACKING-CMR
Authors: Xiao Zhou, Guang Zhi, Zhen Qian, Shizhen Liu, Wang Yang, Liquan Cheng, Ye Wang, Helene Houle, Paaladinesh Thavendiranathan, Randolph Martin, Mani Vannan
Journal: Journal of the American College of Cardiology (2013)
The Rape of the Phallus —A Sequel
Authors: Roy Cohn
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In recent years individuals as well as society in general have had great benefit from the practice of circumcision. I refer to the important role that foreskins played in the Robbins, Enders, and Weller early successful cultivation of poliovirus in nonnervous tissue (<i>Proc Soc Exp Biol Med</i><b>75</b>: 370, 1950). Virologists have long been aware of this unsung contribution to modern scientific research. <i>W. K. C. M.</i>: The incidence of paralytic poliomyelitis was much higher in those countries with the highest standards of hygiene, where circumcision was and is commonly practiced, particularly in the United States. On the other hand, the disease is rare in Nigeria and in most central African countries, where hygienic standards are low, and circumcision not in vogue. Does having a foreskin protect against paralytic polio? <i>Dear Dr. Morgan</i>:—I enjoyed your brief note in the July 19 issue of JAMA and quite