tbuckley/cabot-search huggingface dataset:
Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy
Authors: Giovanni Gambaro, Anna P. Venturini, Douglas M. Noonan, Walter Fries, Giuliana Re, Spiridione Garbisa, Carla Milanesi, Alessandro Pesarini, Arturo Borsatti, Egidio Marchi, Bruno Baggio
Journal: Kidney International (1994)
Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study
Authors: S. Carlsson, M. Assel, D. Sjoberg, D. Ulmert, J. Hugosson, H. Lilja, A. Vickers
Journal: BMJ (2014)

To determine the relative risks of prostate cancer incidence, metastasis, and mortality associated with screening by serum prostate specific antigen (PSA) levels at age 60.Population based cohort study.General male population of Sweden taking part in a screening trial in Gothenburg or participating in a cardiovascular study, the Malmö Preventive Project.The screened group consisted of 1756 men aged 57.5-62.5 participating in the screening arm of the Gothenburg randomized prostate cancer screening trial since 1995. The unscreened group consisted of 1162 men, born in 1921, participating in the Malmö Preventive Project, with PSA levels measured retrospectively in stored blood samples from 1981.PSA screening versus no screening.Incidence rate ratios for the effect of screening on prostate cancer diagnosis, metastasis, and death by PSA levels at age 60.The distribution of PSA levels was similar between the two cohorts. Differences in benefits by baseline PSA levels were large. Among men with baseline levels measured, 71.7% (1646/2295) had a PSA level <2 ng/mL. For men aged 60 with PSA level <2 ng/mL, there was an increase in incidence of 767 cases per 10,000 without a decrease in prostate cancer mortality. For men with PSA levels ≥ 2 ng/mL, the reduction in cancer mortality was large, with only 23 men needing to be screened and six diagnosed to avoid one prostate cancer death by 15 years.The ratio of benefits to harms of PSA screening varies noticeably with blood PSA levels at age 60. For men with a PSA level <1 ng/mL at age 60, no further screening is recommended. Continuing to screen men with PSA levels >2 ng/mL at age 60 is beneficial, with the number needed to screen and treat being extremely favourable. Screening men with a PSA level of 1-2 ng/mL is an individual decision to be based on a discussion between patient and doctor.
Triple negative breast cancer: a phase 2, multi-center, open-label, randomized trial of gemcitabine/carboplatin (G/C), with or without BSI-201, a PARP inhibitor.
Authors: J O'Shaughnessy, M Yoffe, C Osborne, J Blum, C Rocha, V Ossovskaya, B Sherman, C Bradley
Journal: Cancer Research (2009)

Abstract Abstract #2120 Background: PARP is a critical enzyme of cell proliferation and DNA repair and BSI-201 has been shown to be a potent inhibitor of PARP-1 in humans. Triple negative breast cancer (TNBC) shares important features with BRCA1-related breast cancer, a validated target for PARP inhibition. Our studies demonstrate that PARP-1 gene expression is statistically significantly upregulated in TNBC compared with normal breast tissue. The primary objective of this study is to assess the Clinical Benefit Rate (CBR=CR+PR+SD &amp;gt; 6 months) of Gemcitabine/Carboplatin with or without BSI-201 in patients with TNBC.&amp;#x2028; Methods: Eligible subjects are ≥ 18 years old who had received ≤ 2 prior chemotherapies for metastatic disease with histologically documented breast cancer that is ER-negative, PR-negative, and HER2-negative. Patients were randomized (1:1 ratio) to one of 2 study arms: a) arm 1: G/C alone; b) arm 2: BSI-201 + G/C. G/C was given on days 1 and 8; G = 1000 mg/m2, C at an AUC=2. In study arm 2, BSI-201 was administered I.V. twice weekly (days 1, 4, 8 and 11) at a dose of 5.6 mg/kg. Cycles were defined as being 21 days in duration. Modified RECIST criteria are used to assess tumor response every 6 weeks (every 2 cycles). Subjects who have progressive disease may crossover to receive BSI-201 and continue G/C. Archived tissue samples were retrieved for the assay of cancer related genes including PARP-1 by multiplex quantitative RT-PCR.&amp;#x2028; Results: To date, 50 subjects have been enrolled and treated for up to 8 cycles of therapy. Overall 39 of 50 (78%) subjects experienced at least 1 adverse event. The frequency and nature of the AE's do not differ between the two treatment groups. Gene expression profiling results from the first 28 patients enrolled confirm that the cancers of patients enrolled have uniformly low hormone receptor expression, variable HER2 receptor expression and significant upregulation of PARP-1 compared with normal breast tissue.&amp;#x2028; Conclusions: This is the first randomized study of a PARP inhibitor in cancer patients. BSI-201 is safe and well tolerated when given in combination with G/C and adverse events observed were consistent with the known safety profiles of G / C regimens. An updated evaluation of toxicity profile and PARP-1 expression analysis will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2120.
Histopathological Features of the Kidney after Acute Renal Failure from Melamine
Authors: Ning Sun, Ying Shen, Le-jian He
Journal: New England Journal of Medicine (2010)

To the Editor: An 8-month-old male infant was admitted on June 28, 2008, with prolonged anuria and mild coma. The child had been fed with Sanlu brand milk powder since he was 1 week of age. Initial laboratory data revealed markedly abnormal results that included a potassium level of 8.12 mmol per liter, a total carbon dioxide level of 9.0 mmol per liter, a blood urea nitrogen level of 137 mg per deciliter (49 mmol per liter of urea), and a creatinine level of 10.3 mg per deciliter (908 μmol per liter). Abdominal ultrasonography revealed bilateral urinary calculi causing acute . . .
Whatever Happened to Chastity?
Authors: George F. Snell
Journal: JAMA (1980)

<h3>To the Editor.—</h3> A voice of opposition needs to be heard. Although Yehudi Felman, MD (1979;241:2517), documents the alarming extent of sexually transmitted diseases (STD) and teenage pregnancy, one of his proposed solutions is offensive to me both as parent and physician. Felman proposes widespread condom advertisements in newspapers, magazines, and television. He suggests that organized medicine and public health officials exert pressure on the media to reverse the policy of not considering condom use suitable for public advertising. Felman also speaks for an emphasis on the condom's contraceptive value in the public school sex education curriculum. Bergman supports this plea, suggesting that a few choice spots on Monday-night football would really get the message across. I do not refute the efficacy of the condom, but I am appalled at the willingness of medical professionals to accept promiscuous sexual conduct—and even to promote it. Media advertising must influence behaviors somewhat.
Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis
Authors: Christian R. Loehberg, Tiia Thompson, Michael B. Kastan, Kirsteen H. Maclean, Dean G. Edwards, Frances S. Kittrell, Daniel Medina, Orla M. Conneely, Bert W. O'Malley
Journal: Cancer Research (2007)

Abstract The use of agents to prevent the onset of and/or the progression to breast cancer has the potential to lower breast cancer risk. We have previously shown that the tumor-suppressor gene p53 is a potential mediator of hormone (estrogen/progesterone)-induced protection against chemical carcinogen–induced mammary carcinogenesis in animal models. Here, we show for the first time a breast cancer–protective effect of chloroquine in an animal model. Chloroquine significantly reduced the incidence of N-methyl-N-nitrosourea–induced mammary tumors in our animal model similar to estrogen/progesterone treatment. No protection was seen in our BALB/c p53-null mammary epithelium model, indicating a p53 dependency for the chloroquine effect. Using a human nontumorigenic mammary gland epithelial cell line, MCF10A, we confirm that in the absence of detectable DNA damage, chloroquine activates the tumor-suppressor p53 and the p53 downstream target gene p21, resulting in G1 cell cycle arrest. p53 activation occurs at a posttranslational level via chloroquine-dependent phosphorylation of the checkpoint protein kinase, ataxia telangiectasia-mutated (ATM), leading to ATM-dependent phosphorylation of p53. In primary mammary gland epithelial cells isolated from p53-null mice, chloroquine does not induce G1 cell cycle arrest compared with cells isolated from wild-type mice, also indicating a p53 dependency. Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis. [Cancer Res 2007;67(24):12026–33]
Renal tubular responsiveness to atrial natriuretic peptide in sodium-retaining chronic caval dogs. A possible role for kinins and luminal actions of the peptide.
Authors: L Legault, P Cernacek, M Levy, E Maher, D Farber
Journal: Journal of Clinical Investigation (1992)

60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng.kg-1.min-1) with a natriuresis (TIVC-NR; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in delta UNaV (62 mu eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct.
Statins in liver disease: A molehill, an iceberg, or neither?
Authors: Curtis K. Argo, Paola Loria, Stephen H. Caldwell, Amedeo Lonardo
Journal: Hepatology (2008)

A growing number of chronic liver disease patients, especially those with metabolic syndrome–associated nonalcoholic fatty liver disease or hepatitis C virus–associated dysmetabolic syndrome, will take statins to prevent cardiovascular disease. As a result, clinicians will weigh complex issues raised by the interaction of statins with liver metabolism in these disorders. In this article, we critically review data concerning statins and liver pathophysiology with an emphasis on nonalcoholic fatty liver disease and hepatitis C virus, while also touching on other chronic liver diseases. Basic research interests include statins' mechanism of action and their effects on cholesterol-related cell signaling pathways and angiogenesis. From the clinical standpoint, many chronic liver diseases increase cardiovascular risk and would undeniably benefit from sustained statin use. The false alarms and security accompanying aminotransferase monitoring, however, are disturbing in light of the scarcity of data on statins' long-term effects on liver histology. Although some actions of statins might eventually prove to be particularly useful in nonalcoholic steatohepatitis, hepatitis C virus, or hepatocellular carcinoma, others may prove harmful. The lack of definitive data makes a fully informed decision impossible. Research using histological endpoints is urgently needed to determine the indications and contraindications of this extraordinary class of agents in patients with chronic liver disease. (HEPATOLOGY 2008;48:662–669.)
5-HT2CRs Expressed by Pro-Opiomelanocortin Neurons Regulate Energy Homeostasis
Authors: Yong Xu, Juli E. Jones, Daisuke Kohno, Kevin W. Williams, Charlotte E. Lee, Michelle J. Choi, Jason G. Anderson, Lora K. Heisler, Jeffrey M. Zigman, Bradford B. Lowell, Joel K. Elmquist
Journal: Neuron (2008)

Drugs activating 5-hydroxytryptamine 2C receptors (5-HT2CRs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT2CR deficiency (2C null) and mice with 5-HT2CRs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT2CR expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT2CR-melanocortin circuitry in the long-term regulation of energy balance.
Agencies need to work together on general practitioner staffing
Authors: M. Leigh
Journal: BMJ (1998)

Editor—The general findings of the paper by Taylor and Leese on the recruitment of general practitioners1 are in accord with those of the Medical Practices Committee's pilot study of recruitment to partnership vacancies of 1994 and its recruitment surveys of 1995 and 1996.2 3 Over the past three years these studies have shown a progressive difficulty in recruiting good quality general practitioners, an observation reflected in the recent increase in requests to the committee for extension of time to find a partner. None …
A CASE OF DEFECT IN THE VENTRICULAR SEPTUM AND STENOSIS OF THE PULMONARY CONUS IN A MAN THIRTY-TWO YEARS OLD, WITH DEMONSTRATION OF THE HEART.
Authors: JOSEPHINE E. YOUNG
Journal: JAMA (1897)

lower part of the ileum.The intestine below the stricture was very small, flat and empty, while above it was remarkably dilated, looking like a distended colon, its wall, from hypertrophy, being as thick as that of the stomach.A lateral anastomosis was made between the loop above and the one below the stric- ture, about 30 cm. being excluded from the intestinal current.Senn's large size decalcified bone plates were used in the operation.The recovery from the
A Study of lupus erythematosus with particular reference to generalized discoid lupus
Authors: SEAN O'LOUGHLIN, ARNOLD L. SCHROETER, ROBERT E. JORDON
Journal: British Journal of Dermatology (1978)

The classification of lupus erythematosus (LE) is difficult because of variable and multisystem involvement, occurrence of transitional forms, and overlapping with connective tissue disorders. One of the earliest attempts at classification was made by O'Leary (1934), who classified LE clinically into four main types: (1) chronic discoid lupus erythematosus (DLE), or fixed type with the typical erythematous, scaly, well‐demarcated eruption, usually showing follicular plugging and atrophy, confined to the head region; (2) generalized DLE, or chronic disseminated type differing from the localized discoid type in that the erythematous plaques are found not only on the head area but also below the neck region (O'Leary considered that constitutional systems were generally lacking in these two types); (3) subacute disseminated LE; and (4) acute disseminated LE. The last two categories reflect what we now call systemic lupus erythematosus (SLE) of varying severity. Many authors have used O'Leary's clinical classification, but progress in laboratory medicine—in particular the discovery of the LE cell—has led to other schemes, the most widely accepted at present being that related to the American Rheumatism Association's (ARA) preliminary criteria for the diagnosis of SLE (Cohen et al., 1971). These criteria have been criticized by many authorities because they do not include important data, such as those relative to the antinuclear antibody test, serum anti‐native‐DNA, serum complement levels, many neurological abnormalities, renal biopsy changes, and cutaneous immunofluorescent (IF) findings. However, Dubois (1974b) pointed out that all categorizations of LE are arbitrary, and he accepted the ARA criteria as a successful method for differentiating LE. This report involves the clinical and laboratory findings in 123 patients with LE seen at the Mayo Clinic during the 3‐year period 1971–1974 and an assessment of the validity and usefulness of O'Leary's classification.
Adipose-Specific Deletion of TFAM Increases Mitochondrial Oxidation and Protects Mice against Obesity and Insulin Resistance
Authors: Cecile Vernochet, Arnaud Mourier, Olivier Bezy, Yazmin Macotela, Jeremie Boucher, Matthew J. Rardin, Ding An, Kevin Y. Lee, Olga R. Ilkayeva, Cristina M. Zingaretti, Brice Emanuelli, Graham Smyth, Saverio Cinti, Christopher B. Newgard, Bradford W. Gibson, Nils-Göran Larsson, C. Ronald Kahn
Journal: Cell Metabolism (2012)
1118-78 Primary angioplasty versus facilitated intervention (tenecteplase plus stenting) in patients with ST elevated acute myocardial infarction: Final results of the GRACIA-2 trial
Authors: Francisco Fernandez-Aviles, Joaquin J Alonso, Alfonso Castro-Beiras, Javier Goicolea, Jesus Blanco, Juan Alonso, Juan Lopez-Mesa, Luis Diaz-Llera, Nicolas Vazquez, Rosa Hernandez, Armando Perez, Javier Moreu
Journal: Journal of the American College of Cardiology (2004)
Treatment of breast cancer before surgery will present pathologists with challenges
Authors: P A Trott, N Nasiri
Journal: BMJ (1997)

Editor—Richard Epstein's editorial on treating breast cancer before carrying out surgery raises the question of how breast surgeons will feel about withholding lumpectomy from many of their patients with newly diagnosed cancer.1 Another, perhaps more important, question is how pathologists will feel. The best predictor of tumour behaviour is an assessment of tumour size, histopathological grade, and lymph node status. This has been established as a powerful indicator of prognosis, notably by a group …
Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer
Authors: Hui Ding, Gustavo Helguera, José A. Rodríguez, Janet Markman, Rosendo Luria-Pérez, Pallavi Gangalum, Jose Portilla-Arias, Satoshi Inoue, Tracy R. Daniels-Wells, Keith Black, Eggehard Holler, Manuel L. Penichet, Julia Y. Ljubimova
Journal: Journal of Controlled Release (2013)
The Effects of Aging on the Hepatic Microsomal Mixed–Function Oxidase System of Male and Female Monkeys
Authors: Alan G. Maloney, Douglas L. Schmucker, Donald S. Vessey, Rose K. Wang
Journal: Hepatology (1986)

Studies were conducted to determine the effects of aging on certain biochemical andbiophysical properties of the hepatic microsomes and on the kinetic properties of a constituent drug–metabolizing enzyme and a heme protein in a nonhuman primate. Outbred male and female rhesus monkeys ( Macaque mulatta ) ranging in age from 1 to 25 years were employed as animal models. There was considerable individual variability, but no significant age or sex–related changes in (1) the concentration of microsomal protein or (2) the content of the cytochromes P–450. Although the oldest animals examined for NADPH cytochrome c (P–450) reductase activity were only 19 years of age, the specific activity of this important enzyme increased rather than decreased during aging. There were only minor changes in the total phospholipid content of the microsomes and none in the distribution profile of the major phospholipid classes. However, the microsomal cholesterol content increased sufficiently to cause a rise in the cholesterol/phospholipid ratio between 16 and 25 years of age. The fluidity of the membrane lipid domain exhibited a concomitant decline as measured by electron spin resonance spectroscopy. There was no apparent correlation between age–related changes in these physicochemical properties of the microsomes and the in vitro activities of the constituent drug–metabolizing enzymes or heme proteins. Furthermore, the marked disparities between the data obtained in inbred male rodents and those from outbred primates suggest that the extrapolation of the former to humans is of questionable value with respect to liver drug metabolism.
Book Review Lung Cancer: Principles and Practice Second edition. Edited by Harvey I. Pass, James B. Mitchell, David H. Johnson, Andrew T. Turrisi, and John D. Minna. 1177 pp., illustrated. Philadelphia, Lippincott Williams &amp; Wilkins, 2000. $169. 0-7817-1791-4
Authors: Roger Stupp
Journal: New England Journal of Medicine (2001)
Plasmid transfer for enhancing degradation capabilities.
Authors: B E Rittmann, B F Smets, J A MacDonald, D A Stahl
Journal: Environmental Health Perspectives (1995)

The kinetics of plasmid conjugation for the TOL and RP4 plasmids depend strongly on the donor cells' specific growth rate and substrate concentration, both of which determine the cells' energy availability. Although transfer rates can be large when energy availability is high, normal biological processes have low energy availability. Therefore, we propose and evaluate preliminarily a simple scheme to create a small zone of high energy availability.
Unsatisfactory representation of regional specialties
Authors: P R R Clarke, W A Kennedy
Journal: BMJ (1982)

epidemiological data since the answers being given are worthless for this.One must conclude therefore that this must be a further attempt at restricting abortion by attempting to dissuade doctors from performing abortions for anything other than strict medical con- ditions.This is against the repeated wishes of Parliament, the medical profession, and opinion polls and is an attempt to limit the clinical freedom of a doctor.This new form needs to be abandoned and any new one introduced only after consideration of the existing law and the views of people knowledgeable about the subject and with a clear idea of its intentions.
P675 RISK PREDICTORS FOR LIVER CANCER AND CIRRHOSIS AMONG CHRONIC HEPATITIS B PATIENTS WITH UNDETECTABLE HEPATITIS B VIRAL LOADS
Authors: J. Liu, H.-I. Yang, M.-H. Lee, R. Batrla-Utermann, C.-L. Jen, S.-N. Lu, L.-Y. Wang, S.-L. You, C.-J. Chen
Journal: Journal of Hepatology (2014)