tbuckley/cabot-search huggingface dataset:
Molecular circuits, biological switches, and nonlinear dose-response relationships.
Authors: Melvin E Andersen, Raymond S H Yang, C Tenley French, Laura S Chubb, James E Dennison
Journal: Environmental Health Perspectives (2002)

Signaling motifs (nuclear transcriptional receptors, kinase/phosphatase cascades, G-coupled protein receptors, etc.) have composite dose-response behaviors in relation to concentrations of protein receptors and endogenous signaling molecules. "Molecular circuits" include the biological components and their interactions that comprise the workings of these signaling motifs. Many of these molecular circuits have nonlinear dose-response behaviors for endogenous ligands and for exogenous toxicants, acting as switches with "all-or-none" responses over a narrow range of concentration. In turn, these biological switches regulate large-scale cellular processes, e.g., commitment to cell division, cell differentiation, and phenotypic alterations. Biologically based dose-response (BBDR) models accounting for these biological switches would improve risk assessment for many nonlinear processes in toxicology. These BBDR models must account for normal control of the signaling motifs and for perturbations by toxic compounds. We describe several of these biological switches, current tools available for constructing BBDR models of these processes, and the potential value of these models in risk assessment.
Metastatic and Recurrent Hypernephroma Demonstrated by Isotope Angiography
Authors: HAROLD Simon
Journal: Clinical Nuclear Medicine (1977)

Three patients suspected of having recurrent hypernephroma and one patient with a pathologic fracture were studied with isotope angiography. Gamma camera images were obtained over the areas of interest during the vascular transit and demonstrated areas of isotope blush which correspond to malignant disease. This is a simple method of evaluating patients suspected of having metastatic and recurrent hypernephroma and may aid in directing angiography to suspicious sites during arteriographic evaluation of renal masses, planning treatment, or following the results of therapy.
LIFE-HISTORY OF ASCARIS LUMBRICOIDES
Authors: F. H. Stewart
Journal: BMJ (1920)

04A OF UNUSUAL TYPE.-.,-$.The initial dose in the enormous majority of cases was half a million.The daily weiglt has been found to be a satisfactory metlhod of conjrolling the dosage..The interval with small doses lhas been tlhree to four days; with larger doses a weel.Patients do not seem to have been quite so sensitive to the secondary organisms when present, but still great caution had to be exercised; streptococci were givenin doses-of half a million to 5 million and B. coli the same, Length of Treatmnent.
Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib
Authors: Matthias Mayerhofer, Karoline V. Gleixner, Julia Mayerhofer, Gregor Hoermann, Eva Jaeger, Karl J. Aichberger, Rene G. Ott, Khaled Greish, Hideaki Nakamura, Sophia Derdak, Puchit Samorapoompichit, Winfried F. Pickl, Veronika Sexl, Harald Esterbauer, Ilse Schwarzinger, Christian Sillaber, Hiroshi Maeda, Peter Valent
Journal: Blood (2007)
Is contact allergy to disperse dyes and related substances associated with textile dermatitis?
Authors: K. Ryberg, A. Goossens, M. Isaksson, B. Gruvberger, E. Zimerson, F. Nilsson, J. Björk, M. Hindsén, M. Bruze
Journal: British Journal of Dermatology (2008)

Background Disperse dyes (DDs) are the most common sensitizers among textile dyes, but there is little knowledge of the clinical relevance of positive patch test reactions. Objective To investigate if patient-reported textile-related skin problems can be explained by contact allergy to eight different DDs and/or to chemically related substances, by occupation or by atopic constitution, and if the skin problems are influenced by age or sex. Methods A questionnaire on textile-related skin problems was answered by 858 of 982 consecutively patch tested patients in Malmö, Sweden and in Leuven, Belgium. The baseline series used for patch testing was supplemented with a textile dye mix (TDM) consisting of the eight DDs and with the separate dyes. The association between textile-related skin problems and contact allergy to the DDs and other risk factors was investigated using multiple logistic regression analysis. Results Eighteen per cent of the patients suspected textiles as a cause of their skin problems. Atopic constitution and female sex were risk factors for skin reactions. Synthetic materials were the most common textiles to give skin problems. A significant association was found between self-reported textile-related skin problems and contact allergy to para-phenylenediamine (PPD) [adjusted odds ratio (OR) 2·1; 95% confidence interval (CI) 1·0–4·3]. A similar, but more imprecise, adjusted OR was found for TDM (OR 1·9; 95% CI 0·57–5·6). Contact allergy to black rubber mix was too rare to be evaluated. Conclusions Contact allergy to PPD was a more prevalent indicator for skin reactions to textiles than the TDM used in this study.
How Reliable Are <i>BRCA1/2</i> Mutation Estimates?
Authors: Kathleen E. Malone, David R. Doody, Li Hsu, Elaine A. Ostrander
Journal: Cancer Research (2007)

In Response: 

We read with interest the letter from McClain et al. ( [1][1]). Although our article ( [2][2]) focused primarily on the prevalence of mutations in cases and the relative importance of predictors of mutation carriership, we appreciate the interest in the population carrier frequency
Combination Therapy of Malaria
Authors: Charles N. Swisher
Journal: JAMA (1969)

To the Editor:—  The recent preliminary communication by Berman (207:128, 1969) suggests that the chloroquine-pyrimethamine-sulfisoxazole therapy reigmen forPlasmodium falciparummalaria should be given wider use as an alternative to the presently advocated quininepyrimethamine regimen. He supports this thesis with data showing a more rapid reduction in fever duration and no increase in recurrence rate with the chloroquine treatment.  I have recently reviewed the records of 160 patients following the chloroquine regimen and 250 patients following the quinine regimen during July through October 1968. Both groups were similar in age, race, and location of duty in South Vietnam, and cases were uncomplicated byP vivaxor other medical or surgical conditions.  In the two groups studied, I found no significant difference in time of onset of illness to time of treatment, duration of fever, or duration of symptoms. Although as Berman states, time of medication is six days for
Physiologic, metabolic, and muscle fiber type characteristics of musculus uvulae in sleep apnea hypopnea syndrome and in snorers.
Authors: F Sériès, C Côté, J A Simoneau, Y Gélinas, S St Pierre, J Leclerc, R Ferland, I Marc
Journal: Journal of Clinical Investigation (1995)

Upper airway dilator muscles play an important role in the pathophysiology of sleep apnea hypopnea syndrome (SAHS). The mechanical and structural characteristics of these muscles remain unknown. The aim of this study was to compare the physiologic, metabolic, and fiber type characteristics of one upper airway dilator muscle (musculus uvulae, MU) in 11 SAHS and in seven nonapneic snorers. The different analyses were done on MU obtained during uvulo-palato-pharyngoplasty. Snorers and SAHS differed only in their apnea + hypopnea indices (11.5 +/- 5.9 and 34.2 +/- 14.6/h, respectively, mean +/- SD). Absolute twitch and tetanic tension production of MU was significantly greater in SAHS than in snorers while the fatigability index was similar in the two groups. Protein content and anaerobic enzyme activities of MU were significantly greater in SAHS than in snorers; no difference was observed for aerobic enzyme activities. The total muscle fiber cross-sectional area of MU was significantly higher in SAHS (2.2 +/- 0.9 mm2) than in snorers (1.1 +/- 0.7 mm2). The surface occupied by type IIA muscle fibers of MU was larger in SAHS (2.00 +/- 0.96) than in snorers (0.84 +/- 0.63 mm2). We conclude that the capacity for tension production and the anaerobic metabolic activity of MU are greater in SAHS than in snorers.
The LRF transcription factor regulates mature B cell development and the germinal center response in mice
Authors: Nagisa Sakurai, Manami Maeda, Sung-Uk Lee, Yuichi Ishikawa, Min Li, John C. Williams, Lisheng Wang, Leila Su, Mai Suzuki, Toshiki I. Saito, Shigeru Chiba, Stefano Casola, Hideo Yagita, Julie Teruya-Feldstein, Shinobu Tsuzuki, Ravi Bhatia, Takahiro Maeda
Journal: Journal of Clinical Investigation (2011)

B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.
Plasma Adiponectin Does Not Correlate With Insulin Resistance and Cardiometabolic Variables in Nondiabetic Asian Indian Teenagers
Authors: Chamukuttan Snehalatha, Annasami Yamuna, Ambady Ramachandran
Journal: Diabetes Care (2008)

The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters.We studied 196 teenagers (94 boys, 102 girls) 12-18 years of age, selected from a cohort of 2,640 individuals from a cross-sectional school-based survey in Chennai, India. For comparison, adiponectin and plasma insulin were measured in 84 healthy adults. Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin resistance, anthropometry, and family history of diabetes were studied.Adiponectin showed a sex dimorphism, with girls having higher values (in microg/ml) (10.3 +/- 5.0) than boys (8.4 +/- 3.5) (P < 0.0001), and it showed a positive correlation with HDL cholesterol in boys only and not with other lipid parameters, insulin resistance, proinsulin, anthropometry, and family history of diabetes. In the adults, adiponectin correlated with fasting glucose and inversely with triglycerides.In Asian Indian adults and teenagers, adiponectin did not correlate directly with measures of insulin sensitivity, overweight, and other cardiometabolic variables. This was at variance with several reports in other populations showing an inverse association of adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic differences in the relationship of adiponectin with insulin sensitivity. The role of adiponectin in relation to action of insulin needs more detailed studies in Asian Indians.
SSRIs and heart defects in neonates
Authors: G. Klinger, P. Merlob
Journal: BMJ (2009)

In a population study, Pedersen and colleagues found a twofold increased risk of septal heart defects after first trimester exposure to selective serotonin reuptake inhibitors (SSRIs).1 The prevalence increased with citalopram or sertraline but not paroxetine or fluoxetine, and exposure to more than one type of SSRI posed the greatest …
The campaign about doctors and torture in Israel five years on
Authors: D. Summerfield
Journal: BMJ (2014)

We write as lead signatory (AM) and convenor (DS) on the second anniversary of a medical ethical campaign representing 725 doctors, including 115 professors, from 43 countries.1

The Declaration of Tokyo of the World Medical Association (WMA) obliges doctors to denounce and report torture whenever they encounter it. We asked the WMA to examine the record of the Israeli Medical Association (IMA), a WMA member, and thus the probity of the appointment of IMA president Yoram Blachar as …
"Vaccine hesitant" parents affect vaccination rates in some communities
Authors: J. A. Jacob
Journal: BMJ (2014)

<h3>Abstract</h3> Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of <i>Tet1</i> results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking <i>Tet1</i> in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and DNA hydroxymethylation profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. <i>Tet1</i>-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, <i>Itpr2</i> impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.
1022-104 Coronary Flow Velocity of Infarct-Related Arteries: Physiologic Differences Between Complete (TIMIIII) and Incomplete (TIMI 0, I, II) Anglographic Coronary Perfusion
Authors: Frank V. Aguirre, Thomas J. Donohue, Richard G. Bach, Eugene A. Caracciolo, Joseph A. Moore, Thomas Wolford, Alexander Khoury, Carol Mechem, Morton J. Kern
Journal: Journal of the American College of Cardiology (1995)
Serial Markers of Bone Turnover in Men with Metastatic Prostate Cancer Treated with Zoledronic Acid for Detection of Bone Metastases Progression
Authors: Michael Lein, Manfred Wirth, Kurt Miller, Hans-Udo Eickenberg, Lothar Weißbach, Katja Schmidt, Ulrike Haus, Carsten Stephan, Sven Meissner, Stefan A. Loening, Klaus Jung
Journal: European Urology (2007)
Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study
Authors: Chifumbe Chintu, Victor Mudenda, Sebastian Lucas, Andrew Nunn, Kennedy Lishimpi, Daniel Maswahu, Francis Kasolo, Peter Mwaba, Ganapati Bhat, Hiroshi Terunuma, Alimuddin Zumla
Journal: The Lancet (2002)
Oleander Interference in the Digoxin Radioimmunoassay in a Fatal Ingestion
Authors: John Osterloh
Journal: JAMA (1982)

An elderly woman allegedly ingested oleander leaves and died. Ventricular arrhythmias and asystole were unresponsive to cardiopulmonary resuscitation, pharmacologic agents, and cardioversion. The patient, who had no access to digoxin, had an initial serum digoxin concentration of 5.8 ng/mL. Cross-reactivities between oleander extract and pure oleandrin and digoxin in the digoxin radioimmunoassay were 100:1 and 29,000:1, respectively. We postulate that glycosides in oleander leaves produced the elevated serum digoxin concentration. Based on an assumed volume of distribution of the oleander glycosides of 1 L/kg, the calculated lethal dose absorbed by our patient was 200 times greater than lethal doses in several animal species and corresponded to the absorption of 4 g of oleander leaves.
Successful therapy with whole-lung lavage and autologous peripheral blood stem cell transplantation for pulmonary alveolar proteinosis complicating acute myelogenous leukemia
Authors: Akihiko Numata, Eijo Matsuishi, Kotaro Koyanagi, Shuji Saito, Yuichi Miyamoto, Koji Irie, Hisashi Gondo, Mine Harada
Journal: American Journal of Hematology (2006)

A 43-year-old man with acute myelogenous leukemia (AML) was found to be complicated with pulmonary alveolar proteinosis (PAP), which was confirmed by biochemical and histological findings. After achievement of complete remission of AML, he underwent whole-lung lavages twice between intensive chemotherapies. Subsequently, he received high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT), which was performed safely without any infections. He has been in remission for 25 months after transplant with no recurrence of PAP. Autologous PBSCT in combination with whole-lung lavage may be a promising strategy in the treatment of PAP associated with hematological malignancies. Am. J. Hematol. 81:107–109, 2006. © 2006 Wiley-Liss, Inc.
Whose Death Is It, Anyway
Authors: Paul Rousseau
Journal: Annals of Internal Medicine (1997)

Letters1 April 1997Whose Death Is It, AnywayPaul Rousseau, MDPaul Rousseau, MDVeterans Affairs Medical Center, Phoenix, AZ 85012Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-7-199704010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The essay by Hansot [1] on the obstacles she confronted carrying out her mother's advance directive during a life-ending stay in an intensive care unit is disconcerting and frightening. The blatant disregard for a patient's advance directives, as illustrated in this case, is unjustifiable and intolerable, as are the ignominious communication skills of many attending physicians. Admittedly, there are two sides to every story, but the apparent paucity of basic communication skills exhibited by these physicians has, in my opinion, become more prevalent in this technological era of medical care.Criticism of communication skills, however, must be ...References1. Hansot E. A letter from a patient's daughter. Ann Intern Med. 1996; 125:149-51. Google Scholar2. Buckman R. How To Break Bad News: A Guide for Health Care Professionals. Baltimore: Johns Hopkins Pr; 1993. Google Scholar Author, Article, and Disclosure InformationAffiliations: Veterans Affairs Medical Center, Phoenix, AZ 85012 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1997Volume 126, Issue 7Page: 585-586KeywordsAgingGeriatricsIntensive care units Issue Published: 1 April 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Incidence and prognosis of secondary ventricular fibrillation in acute myocardial infarction. Evidence for a protective effect of thrombolytic therapy. GISSI Investigators.
Authors: A Volpi, A Cavalli, E Santoro, G Tognoni
Journal: Circulation (1990)

The multicenter randomized study of the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico has provided the opportunity to analyze the impact of thrombolytic treatment on secondary ventricular fibrillation incidence in a large population of patients (11,712) with acute myocardial infarction. A reduction of about 20% in the frequency of secondary ventricular fibrillation was observed among patients allocated to thrombolytic treatment (streptokinase, 2.4% versus control, 2.9%; relative risk, 0.80; 95% confidence interval, 0.64-1.00). Streptokinase appeared to exert its protective effect specifically in patients treated within 3 hours of onset of symptoms (streptokinase, 2.6% versus control, 3.7%; relative risk, 0.71; 95% confidence interval, 0.53-0.95). This protection was essentially due to a reduced incidence of late ventricular fibrillation occurring after the first day of hospitalization. The 311 patients with secondary ventricular fibrillation represented an overall incidence of 2.7%. Such incidence was not related to infarct location or sex but was significantly more common in patients older than 65 years (3.3% versus 2.3% in younger patients). A significant excess of in-hospital deaths was found in patients with secondary ventricular fibrillation compared with those in the reference group (38% versus 24%; relative risk, 1.98; 95% confidence interval, 1.56-2.52). Conversely, secondary ventricular fibrillation was not a predictor of 1-year mortality for hospital survivors. Thrombolytic treatment with intravenous streptokinase affords protection against secondary ventricular fibrillation most probably by a limitation of infarct size. When the arrhythmia complicates the course of infarction, it is associated with an adverse short-term outcome, whereas the long-term prognosis is not influenced.
Kinins modulate the sodium-dependent autoregulation of renal medullary blood flow
Authors: B Nafz
Journal: Cardiovascular Research (1998)

Objective: In the recent past it has become clear that the kallikrein–kinin system is closely intertwined with long-term blood pressure regulation. It was shown that a kinin B2 receptor blockade leads to a sodium-dependent rise in blood pressure. The underlying mechanisms of this phenomenon, however, remain unclear. The osmotic gradient of the renal medulla is a prerequisite for the preservation of volume and sodium by the kidney. We thus hypothesized, that a kinin dependent modulation of medullary blood flow accounts for the influence of sodium on blood pressure. Methods: In 39 urethane anaesthetized rats pressure dependent regulation of whole kidney blood flow and cortical and medullary blood flow were estimated via laser-Doppler flux by a stepwise reduction of renal perfusion pressure to 30 mm Hg. Results: In controls (n=15), a reduction in renal perfusion pressure to 30 mm Hg lead to a concomitant reduction in whole kidney blood flow (25±3% of baseline) and cortical laser-Doppler flux (36±5% of baseline). In contrast, medullary laser-Doppler flux decreased only to 79±8% of the baseline level. Providing a 2% sodium chloride solution as drinking water over 5 days (n=12), resulted in a significantly lower capability to autoregulate medullary flow (50±6% of baseline, P<0.05). Acute subcutaneous administration of Hoe 140, a bradykinin B2 receptor antagonist (300 μg/kg bwt), restored autoregulation of medullary flow to almost normal levels (93±12% of baseline, P<0.01 versus high sodium diet alone, n=12). Conclusions: Our results indicate that B2 receptor blockade restores the attenuated autoregulation of medullary Doppler flux during sodium enriched diet. This, suggests that the kinin dependent impact of sodium on blood pressure regulation is mediated by modulations of medullary blood flow autoregulation.
Long term use of combined HRT doubles cancer risk
Authors: D. Spurgeon
Journal: BMJ (2003)

Women over the age of 65 who take combined oestrogen and progestogen hormone replacement therapy (HRT) for five to 15 years or more face a 100% increase in the risk of developing breast cancer, regardless of their pattern of progestogen use, says a new study ( JAMA 2003;289: 3254-63

Although it had been shown previously—with the early closing of an arm of the Women's Health Initiative study—that women taking the combined therapy have an increased risk of breast cancer ( BMJ 2002;325: 61), data on the long term use of the therapy and on the risks associated with patterns of use have been lacking.

The new study was undertaken to fill …