tbuckley/cabot-search huggingface dataset:
Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat.
Authors: S K Van Why, A S Mann, G Thulin, X H Zhu, M Kashgarian, N J Siegel
Journal: Journal of Clinical Investigation (1994)

Renal ischemia results in both a profound fall in cellular ATP and a rapid induction of the 70 kD heat-shock protein family, HSP-70. The present studies examined the relationship between cellular ATP and induction of the stress response in renal cortex. Cellular ATP, continuously monitored by in vivo 31P-NMR spectroscopy, was reduced and maintained at specific, stable levels in renal cortex by partial aortic occlusion for 45 min. Activation of heat-shock transcription factor (HSF) was detected by gel retardation assay and transcription was confirmed by Northern analysis. Activation of HSF was not present, and HSP-70 mRNA induction did not occur when ATP levels were maintained above 60% preocclusion (control) levels. Reduction in cortical ATP levels to 35-50% preocclusion values resulted in HSF activation and low-level expression of inducible HSP-70 mRNA. Cellular ATP of 20-25% control values resulted in a greater level of HSF activation and subsequent HSP-70 mRNA elaboration. HSF was activated at the end of 15 min of total occlusion. The studies indicate that a 50% reduction in cellular ATP in the renal cortex must occur before the stress response is detectable, that reduction of ATP below 25% control levels produces a more vigorous response, and that reperfusion is not required for initiation of a heat-shock response in the kidney. Cellular ATP, or the metabolic consequences associated with ATP depletion, may be a threshold factor for initiation of a stress response in the kidney.
First-Line Bevacizumab (Bev) Combination Therapy in Triple-Negative (TN) Locally Recurrent/Metastatic Breast Cancer (LR/MBC): Subpopulation Analysis of Study MO19391 in &amp;gt;2000 Patients (Pts).
Authors: C. Thomssen, J. Pierga, K. Pritchard, L. Biganzoli, H. Cortes-Funes, K. Petrakova, B. Kaufman, I. Smith
Journal: Cancer Research (2009)

Abstract Background: The combination of Bev with taxane-based therapy, anthracycline-based combination therapy, or capecitabine significantly improves progression-free survival versus chemotherapy alone in LR/MBC, as shown in three randomized, phase III trials (E2100, AVADO, RIBBON-1). Pts with TN LR/MBC appeared to derive similar benefit from Bev compared with non-TN pts in subanalyses of the E2100 and AVADO trials. We conducted a subpopulation analysis of TN pts treated with Bev combination therapy in the MO19391 observational study, which included a broader pt population reflecting general oncology practice.Methods: Pts with HER2-negative (or trastuzumab-pretreated HER2-positive) LR/MBC received first-line Bev 10 mg/kg q2w or 15 mg/kg q3w in combination with taxane-based therapy or other non-anthracycline-containing regimen, according to physician preference. Bev was continued until disease progression. The primary endpoint of MO19391 was safety. Secondary endpoints included time to progression (TTP) and overall survival.Results: 484 of the 2041 pts in MO19391 had TN LR/MBC and 1346 had non-TN disease. The remaining 211 had missing or unknown ER, PgR, or HER2 status and were excluded from this analysis. The proportion of pts with disease-free interval (DFI) ≤24 months was considerably higher in the TN population than in non-TN pts. As expected, the safety profile of Bev combination therapy showed no differences between the two subpopulations. The only pre-defined Bev adverse events of special interest reported at grade ≥3 in &amp;gt;1% of TN pts were hypertension (4.5%) and pulmonary embolism (1.4%). Baseline characteristics, treatment exposure, and efficacy are summarized below. Overall survival data are immature. TN (n=484)Non-TN (n=1346)Median age, years (range)52 (24–85)54 (21–93)DFI ≤24 months, %5525&amp;gt;3 metastatic lesions, %6470Mean duration of Bev, months (range)5.6 (0.0–21.0)7.6 (0.0–25.6)TTP* Events, n (%)297 (61)656 (50)Median, months (95% CI)7.1 (6.4–7.6)10.6 (10.0–11.1)Response rate, %*48.354.5Complete response9.66.9Partial response38.847.6*n=483 in the TN group; n=1322 in the non-TN groupConclusions: In this ongoing study, Bev combination therapy demonstrated a 48% response rate and median TTP of 7.1 months in pts with TN LR/MBC. Findings from this observational study are consistent with retrospective analyses of randomized phase III trials. Prospective trials evaluating Bev combination regimens in TN breast cancer (adjuvant and metastatic settings) are ongoing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6093.
Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma
Authors: Adam M Fontebasso, Simon Papillon-Cavanagh, Jeremy Schwartzentruber, Hamid Nikbakht, Noha Gerges, Pierre-Olivier Fiset, Denise Bechet, Damien Faury, Nicolas De Jay, Lori A Ramkissoon, Aoife Corcoran, David T W Jones, Dominik Sturm, Pascal Johann, Tadanori Tomita, Stewart Goldman, Mahmoud Nagib, Anne Bendel, Liliana Goumnerova, Daniel C Bowers, Jeffrey R Leonard, Joshua B Rubin, Tord Alden, Samuel Browd, J Russell Geyer, Sarah Leary, George Jallo, Kenneth Cohen, Nalin Gupta, Michael D Prados, Anne-Sophie Carret, Benjamin Ellezam, Louis Crevier, Almos Klekner, Laszlo Bognar, Peter Hauser, Miklos Garami, John Myseros, Zhifeng Dong, Peter M Siegel, Hayley Malkin, Azra H Ligon, Steffen Albrecht, Stefan M Pfister, Keith L Ligon, Jacek Majewski, Nada Jabado, Mark W Kieran
Journal: Nature Genetics (2014)
Fractures of the Femoral Neck Treated by Blind Nailing
Authors: JOHN W. O'MEARA
Journal: New England Journal of Medicine (1935)

Results in a group of fourteen fractures of the femoral neck, treated by accurately checked reduction and internal fixation, using the Smith-Petersen three-flanged nail and a small lateral incision, have been much more satisfactory than those obtained by other methods. The earlier recovery of function has been particularly pleasing.
Psychosocial interventions and opioid detoxification for drug misuse: summary of NICE guidance
Authors: Stephen Pilling, John Strang, Clare Gerada
Journal: BMJ (2007)

Drug misuse is an increasing problem that not only impairs the physical and mental health of people who misuse drugs but also negatively affects their families and wider society (for example, in its association with crime). Recently expanded drug services in the United Kingdom involve general practitioners to a considerable degree, who care for at least a third of opioid misusers in treatment. Many clinicians remain pessimistic, however, about the possible benefits of any treatment and how to engage drug users in treatment.1 This article summarises two new NICE guidelines that identify the most effective, safe detoxification regimens for primary and secondary care, the most cost effective psychosocial interventions, and effective ways to promote patient engagement.2 3 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, a range of consensus techniques is used to develop recommendations. In this summary, recommendations derived primarily from consensus techniques are indicated with an asterisk (*). ### Opioid detoxification #### General principles For all patients who are opioid dependent and have expressed an informed choice to become abstinent, services should:
Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C
Authors: Anna S. Lok, James E. Everhart, Adrian M. Di Bisceglie, Hae-Young Kim, Munira Hussain, Timothy R. Morgan
Journal: Hepatology (2011)

Previous studies have suggested that prior exposure to hepatitis B virus (HBV) infection may increase the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of this study was to compare the prevalence of previous or occult HBV infection in a cohort of hepatitis B surface antigen-negative patients with histologically advanced chronic hepatitis C in the United States who did or did not develop HCC. Stored sera from 91 patients with HCC and 182 matched controls who participated in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial were tested for hepatitis B core antibody (anti-HBc), hepatitis B surface antibody, and HBV DNA. Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA by way of real-time polymerase chain reaction. Anti-HBc (as a marker of previous HBV infection) was present in the serum of 41.8% HCC cases and 45.6% controls (P=0.54); anti-HBc alone was present in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum of only one control subject and no patients with HCC. HBV DNA (as a marker of occult HBV infection) was detected in the livers of 10.7% of HCC cases and 23.6% of controls (P=0.18).Although almost half the patients in the HALT-C Trial had serological evidence of previous HBV infection, there was no difference in prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or did not develop HCC. In the United States, neither previous nor occult HBV infection is an important factor in HCC development among patients with advanced chronic hepatitis C.
c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis
Authors: Lucia Knopfová, Petr Beneš, Lucie Pekarčíková, Markéta Hermanová, Michal Masařík, Zuzana Pernicová, Karel Souček, Jan Šmarda
Journal: Molecular Cancer (2012)

Abstract Background The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells. Results Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix in vitro . c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. Conclusions This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.
265Generation of iPSC-based cardiomyocytes for investigating mechanisms of dilated cardiomyopathy due to Lamin A/C mutations
Authors: E Di Pasquale, H Nakahama, P Kunderfranco, M Miragoli, A Forni, R Roncarati, P Carullo, G Faggian, G Condorelli
Journal: Cardiovascular Research (2014)

Purpose: Dilated cardiomyopathy (DCM) is a primary disease of the heart muscle. It represents a major cause of heart failure, ultimately leading to heart transplantation. Approximately 30-50% of cases are familial. Several genes have been linked to DCM and, among these, mutations of Lamin A/C are the most common. Lamins are expressed in all somatic cells and control many cellular processes such as nuclear integrity, nucleo-cytoskeletal coupling, transcription and chromatin remodelling. However, the role of Lamin A in the heart and the consequences of its mutations in DCM need to be further elucidated.
Infant Birth Weight and Smoking Reduction
Authors: Kathryn Goldin
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The article by Li et al<sup>1</sup>presents an objective assessment of smoking behavior in relationship to birth weight. Randomization of patients into a control and an experimental group clearly indicates the value of the interventions provided to the experimental group. The protocol did not, however, randomize study subjects into smokers and nonsmokers. Therefore, self-selection bias was not precluded. One might reasonably wonder whether quitters and reducers might have practiced other positive behaviors as well. Parity, length of time between pregnancies, history of a previous preterm or low-birth-weight infant, maternal illness, and drug use during pregnancy were not taken into account. Since there was no reason to assume low birth weight or preterm birth for those infants for whom those outcomes were not known, leaving them out of the analysis might have been more appropriate.
Probing to Bone in Infected Pedal Ulcers-Reply
Authors: Adolf W. Karchmer
Journal: JAMA (1995)

In Reply.  —We thank Dr Nardone for his careful reading of our article and his thought-provoking comments.  There are, as noted, limitations (practical and ethical) to the tests to which diabetic patients can be subjected in order to ascertain the presence or absence of pedal osteomyelitis. Nevertheless, in evaluating the probe test, the issue is not having a single criterion standard, but rather knowing the true state of the patients regarding osteomyelitis. A histologic diagnosis of osteomyelitis is definitive. Ruling out osteomyelitis by histology, unless one has a large bone sample (as was the case in 11 [seven early, four delayed] of our osteomyelitis-negative cases), is difficult because of the significant risk for sampling error. Prolonged follow-up without recurrence of an infected ulcer in the absence of therapy for osteomyelitis is as definitive as any other test to rule out osteomyelitis in this population. Additionally, we included other available information
A method for rapid placing of small intestinal perfusion tubes.
Authors: M G Schmitt, C M Wood, K H Soergel
Journal: Gut (1974)

Small intestinal perfusion for studying intestinal absorption in man has been utilized for the past 12 years and has been adequately described (Whalen, Harris, Geenen, and Soergel, 1966; Fordtran, 1969).The technique requires a multilumen tube to be placed in the jejunum or ileum.A standard triplelumen perfusion tube is constructed of multiple polyvinyl tubes to whicha rubber bag containing mercury is attached.The subject swallows the weighted rubber bag and gastrointestinal motor activity 'pulls' the bag and attached tube to the desired level of the small intestine.Using the present standard tube, the shortest time required for passage of a jejunal tube is one to three hours and an ileal tube three to 12 hours; progress frequently is especially slow in patients with intestinal diseases.In some instances, the tube does not pass the pylorus for a period of
F-18 FDG PET Findings of Takayasu Arteritis Before and After Immunosuppressive Therapy
Authors: Masako Iwabu, Yuka Yamamoto, Hiroaki Dobashi, Tomohiro Kameda, Katsuharu Kittaka, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2008)

A 73-year-old woman with a 3-month history of fever of unknown origin underwent F-18 FDG positron emission tomography (PET). The serum C-reactive protein was 9.62 mg/dL. Her systolic blood pressure was 120 and 96 mm Hg in the right and left arms, respectively. FDG PET images demonstrated intense FDG uptake in the aorta and bilateral subclavian and brachiocephalic arteries consistent with Takayasu arteritis. After 6 weeks of immunosuppressive therapy, a follow-up PET scan showed disappearance of the large vessel uptake of FDG. She was asymptomatic, with a normal C-reactive protein (0.06 mg/dL).
Clinical and Biological Differences Between Recurrent Herpes Simplex Virus and Varicella-Zoster Virus Infections
Authors: Stephen E. Straus
Journal: JAMA (1989)

<h3>SELECTED CASES</h3><h3>Case 1.—</h3> An otherwise healthy 34year-old woman presented to the National Institutes of Health Clinical Center, Bethesda, Md, for evaluation and management of recurrent genital herpes. Her infection had been acquired a year earlier as a result of a sexual relationship with a partner who denied herpetic infection. The patient was able to recall vividly the details of the initial herpetic episode because of its considerable physical and emotional impact. Numerous painful ulcerative lesions had appeared over the labia and perineum. Urinary retention required hospitalization and catheterization for 2 days. Cultures of the lesions showed herpes simplex virus type 2. Intravenous acyclovir sodium, 5 mg/kg, was administered three times daily for 3 days followed by 7 days of treatment at home consisting of 200-mg capsules five times a day. Infection recurred shortly after the patient completed treatment and about monthly thereafter. Mild tingling preceded each appearance of the
Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection
Authors: Mark S. Sulkowski, David F. Gardiner, Maribel Rodriguez-Torres, K. Rajender Reddy, Tarek Hassanein, Ira Jacobson, Eric Lawitz, Anna S. Lok, Federico Hinestrosa, Paul J. Thuluvath, Howard Schwartz, David R. Nelson, Gregory T. Everson, Timothy Eley, Megan Wind-Rotolo, Shu-Pang Huang, Min Gao, Dennis Hernandez, Fiona McPhee, Diane Sherman, Robert Hindes, William Symonds, Claudio Pasquinelli, Dennis M. Grasela
Journal: New England Journal of Medicine (2014)

All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.In this open-label study, we initially randomly assigned 44 previously untreated patients with HCV genotype 1 infection and 44 patients infected with HCV genotype 2 or 3 to daclatasvir at a dose of 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily, with or without ribavirin, for 24 weeks. The study was expanded to include 123 additional patients with genotype 1 infection who were randomly assigned to daclatasvir plus sofosbuvir, with or without ribavirin, for 12 weeks (82 previously untreated patients) or 24 weeks (41 patients who had previous virologic failure with telaprevir or boceprevir plus peginterferon alfa-ribavirin). The primary end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) at week 12 after the end of therapy.Overall, 211 patients received treatment. Among patients with genotype 1 infection, 98% of 126 previously untreated patients and 98% of 41 patients who did not have a sustained virologic response with HCV protease inhibitors had a sustained virologic response at week 12 after the end of therapy. A total of 92% of 26 patients with genotype 2 infection and 89% of 18 patients with genotype 3 infection had a sustained virologic response at week 12. High rates of sustained virologic response at week 12 were observed among patients with HCV subtypes 1a and 1b (98% and 100%, respectively) and those with CC and non-CC IL28B genotypes (93% and 98%, respectively), as well as among patients who received ribavirin and those who did not (94% and 98%, respectively). The most common adverse events were fatigue, headache, and nausea.Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1, 2, or 3, including patients with no response to prior therapy with telaprevir or boceprevir. (Funded by Bristol-Myers Squibb and Pharmasset (Gilead); A1444040 ClinicalTrials.gov number, NCT01359644.).
PLASMA PROTEIN PRODUCTION AS INFLUENCED BY PARENTERAL PROTEIN DIGESTS, VERY HIGH PROTEIN FEEDING, AND RED BLOOD CELL CATABOLISM
Authors: S. C. Madden, A. A. Kattus, J. R. Carter, L. L. Miller, G. H. Whipple
Journal: The Journal of Experimental Medicine (1945)

When blood plasma proteins are depleted by bleeding, with return of the washed red cells (plasmapheresis), it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. Certain protein digests given by vein may favor good production of plasma protein, as well as nitrogen and weight equilibrium, over long periods in these standardized dogs. These digests may be equally effective when given subcutaneously or intraperitoneally and more effective orally (one dog). Certain other digests may not be well utilized. The total nitrogen of the protein digests is better retained upon oral feeding than parenteral injection. Most of the excess nitrogen excretion is not in the urea and ammonia fraction of the urine. The rate of plasma protein production may reach as high as 1 gm./kilo/day in the dog when ample protein of good quality is fed. The products of catabolism of red blood cells in vivo may add to the production of plasma protein, at least during the administration of casein digest by vein.
ON A CASE OF THE PARTIAL REMOVAL OF THE SPLEEN.
Authors: HORACE M. DEEBLE
Journal: JAMA (1897)

One evening in May, 1889, about 7 o'clock, and while stationed at Fort Yates, North Dakota, I was summoned to the Indian hospital, three miles south of the post, to examine a 12-year-old Indian boy that had met with an accident. A short time before, the patient had been leading a pony to which was attached the usual lariat and picket-pin. From some cause or another the animal became frightened, and in its alarm violently jerked the lariat rope, which had the effect of sending the iron pin at its free end flying through the air and this struck the boy in the left side between the fifth and sixth ribs, inflicting an incised wound some fifteen centimeters in length. Through this opening protruded a tumor, which was dark in color, and measured in diameter about seven centimeters. Upon examining this it was seen that it could be nothing more
Binding of nickel to human epidermis in vitro
Authors: ANN FULLERTON, ANNIE HOELGAARD
Journal: British Journal of Dermatology (1988)

Human epidermis was homogenized, dried and incubated with nickel chloride solutions in the concentration range 0.008-3.4 mM/50 mg epidermis. Nickel uptake was found to occur according to the Freundlich adsorption isotherm, giving a slope of 0.55, indicating that nickel is associatively bound to constituents of the epidermis. The binding characteristics of cobalt were very similar to those of nickel, but the two metals were not found to compete significantly for binding sites in the epidermis. The metal-chelating agents, ethylenediamine tetra-acetic acid disodium, (Na-EDTA) L-histidine and D-penicilla-mine were tested for ability to remove nickel from its binding sites. Na-EDTA was found to be the most efficient, removing 70–90% of the nickel bound to the tissue. The possible clinical significance of these in vitro observations are discussed in relation to percutaneous absorption and allergic contact dermatitis.
The public health benefits of mobile phones
Authors: D. Lawlor
Journal: BMJ (2001)

The bread and butter of public health on call is identifying contacts in the case of suspected meningococcal disease. On the whole this is straightforward but can occasionally cause difficulties. Most areas that I have worked in include several universities, and during October it is common to experience the problem of contact tracing in the student population.

There are two main problems. The first is how to define household contacts when the index patient lives in a hall of residence containing several hundred students. Finding the appropriate university protocol and not being too …
De novo mutation of the myelin Po gene in Dejerine–Sottas disease (hereditary motor and sensory neuropathy type III)
Authors: Kiyoshi Hayasaka, Masato Himoro, Yukio Sawaishi, Kenji Nanao, Tsutomu Takahashi, Goro Takada, Garth A. Nicholson, Robert A. Ouvrier, Nobutada Tachi
Journal: Nature Genetics (1993)