tbuckley/cabot-search huggingface dataset:
Increased susceptibility to heart failure in response to volume overload in mice lacking natriuretic peptide receptor-A gene
Authors: T NISHIKIMI, J HAGAMAN, N TAKAHASHI, H KIM, H MATSUOKA, O SMITHIES, N MAEDA
Journal: Cardiovascular Research (2005)

Contribution of the natriuretic peptide system to the development of heart failure (HF) in vivo was examined using mice lacking or having decreased natriuretic peptide receptor-A (NPRA), a guanylyl cyclase-linked receptor.Volume-overloaded HF was produced by aortocaval fistula in mice with wild-type (+/+), heterozygous (+/-), and homozygous null mutants (-/-) of the NPRA gene. Severity of HF was assessed 4 weeks after operation on the basis of organ weight, hemodynamics, echocardiographic indices, urinary variables, neurohumoral factors, and myocardial gene expression.There were no significant differences in lung weight, kidney weight, left ventricular end-diastolic pressure (LVEDP), left ventricular systolic function, or urinary variables among the three sham-operated groups; however, sham-operated (-/-) mice had higher blood pressure and individual cardiac chamber weights than did (+/+) mice. In contrast, (-/-) mice with aortocaval fistula had higher LVEDP, left and right ventricular weights, lung weight, and left ventricular dimension, as well as lower fractional shortening and urinary sodium and cyclic guanosine monophosphate (cGMP) excretion than did (+/+) mice with aortocaval fistula. In addition, ventricular mRNA expression of natriuretic peptides and beta-myosin heavy chain increased markedly only in (-/-) mice. Plasma atrial natriuretic peptide, renin, and aldosterone, but not cGMP, showed greater responses to aortocaval fistula in (-/-) mice than in (+/+) mice. Both sham-operated and aortocaval fistula NPRA (+/-) mice almost consistently showed a phenotype intermediate between those of NPRA (-/-) and NPRA (+/+) mice.These results provide genetic evidence that NPRA signaling protects against HF induced by volume overload in mice.
The Diagnosis of Depression
Authors: W. Mayer-Gross
Journal: BMJ (1954)

CHILDRENBRrrH 1949 was, however, of only slight degree.By and large, therefore, it would appear that there was not a great difference between the dental condition of these two groups of children examined at an interval of two years, though there was perhaps a little more caries in the 1951 group and rather less hypoplasia.Moreover, for each type of tooth there was a somewhat greater amount of caries associated with each grade of M-hypoplasia in this group, although within each of the groups the usual structure-caries relationship held-that is, the worse the structure the greater the liability to caries.We wish to thank the London County Council and the former and present School Medical Officers for permission respectively to carry out the survey and publish the results.We are also indebted to the head teachers and staffs of the schools for their willing help at the time of the inspections.Further, our thanks are due to the Medical Research Council for financing the work, to Dr. W. J. Martin for helpful
Phenotypic and functional characteristics of lymphocytes isolated from liver biopsy specimens from patients with active liver disease
Authors: Kensaku Hata, David H. van Thiel, Ronald B. Herberman, Theresa L. Whiteside
Journal: Hepatology (1992)

Liver-derived lymphocytes were isolated from 73 liver biopsy specimens obtained from patients with chronic active liver disease and from six samples of normal liver. Mean absolute numbers (±S.E.M) of liver-derived lymphocytes recovered from needle biopsy specimens by mild enzymatic digestion of the liver tissue varied from 0.7 ± 0.3 × 10/mm in allografts being rejected to 8.9 ± 0.9 × 10/mm in chronic non-A, non-B hepatitis. By two-color flow cytometry, T lymphocytes (CD3+) were the major liver-derived lymphocyte population in all biopsy specimens. The mean CD4/CD8 ratio (0.6 ± 0.2) was similar for liver-derived lymphocytes obtained from samples of normal or diseased liver. However, activated (human leukocyte antigen DR+) T cells were significantly (p < 0.05) increased in liver-derived lymphocytes obtained from liver disease specimens than they were in samples from normal livers. Natural killer cells were less numerous than T cells in specimens obtained from diseased livers, with the mean natural killer/T cell ratio ranging from a low of 0.1 in allograft rejection to a high of 0.8 ± 0.3 in primary sclerosing cholangitis. Liver-derived lymphocytes isolated from diseased liver contained significantly fewer (p < 0.05) CD3−CD56+ or CD56+CD16−natural killer cells than did those obtained from normal liver samples. Natural killer activity was consistently detectable in liver-derived lymphocytes obtained from specimens of normal or diseased livers. Moreover, natural killer activity in the liver did not differ significantly from that in either normal or patient peripheral blood. Spontaneous cytotoxic activity against natural killer-resistant targets, Daudi cells, was detectable but low in liver-derived lymphocytes obtained from specimens of both normal and diseased livers. In liver-derived lymphocytes obtained from livers with chronic active liver disease, the proportion of natural killer cells was reduced; T lymphocytes were more prominent and displayed human leukocyte antigen DR antigens more frequently than in end-stage liver disease. (HEPATOLOGY 1992;15:816–823).
Lapatinib Antitumor Activity Is Not Dependent upon Phosphatase and Tensin Homologue Deleted on Chromosome 10 in ErbB2-Overexpressing Breast Cancers
Authors: Wenle Xia, Intisar Husain, Leihua Liu, Sarah Bacus, Shermini Saini, Janice Spohn, Karen Pry, Ron Westlund, Steven H. Stein, Neil L. Spector
Journal: Cancer Research (2007)

Abstract Trastuzumab antitumor activity in ErbB2-overexpressing breast cancers seems to be dependent upon the presence of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a phosphatase that dampens phosphatidylinositol 3-kinase-Akt signaling. Consequently, PTEN deficiency, which occurs in 50% of breast cancers, predicts for resistance to trastuzumab monotherapy. Here, we show that lapatinib, a small-molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, exerts its antitumor activity in a PTEN-independent manner. Steady-state phosphorylated ErbB2 (p-ErbB2) and p-Akt (S473) protein levels were inhibited within 30 min following lapatinib but not in response to trastuzumab in BT474 and Au565 cells (two ErbB2-overexpressing breast cancer cell lines that are sensitive to the proapoptotic effects of lapatinib). Whereas trastuzumab reportedly inhibits SRC phosphorylation (Y416), which in turn reduced SRC-ErbB2 protein interactions, lapatinib had no effect on either variable. To assess the potential functional role that PTEN might play in lapatinib antitumor activity, we selectively knocked down PTEN in BT474 and Au565 cells using small interfering RNA transfection. Loss of PTEN did not affect induction of tumor cell apoptosis by lapatinib in either cell line. In addition, lapatinib inhibited Akt phosphorylation in MDA-MB-468 cells, an ErbB1-expressing/ErbB2 non-overexpressing breast cancer line, despite their PTEN-null status. Moreover, patients with ErbB2-overexpressing inflammatory breast cancers responded to lapatinib monotherapy regardless of PTEN status. Thus, lapatinib seems to exert its antitumor activity in ErbB2-overexpressing breast cancers in a PTEN-independent manner. These data emphasize the importance of assessing PTEN status in tumors when selecting ErbB2-targeted therapies in patients with breast cancer. [Cancer Res 2007;67(3):1170–5]
Avascular Bone Necrosis
Authors: George X. Trimble
Journal: JAMA (1961)

<h3>To the Editor:—</h3> The contribution by Dr. E. Dubois, "Avascular Bone Necrosis Associated with Systemic Lupus Erythematosus," inThe Journal, Oct. 22, 1960, page 966, is timely, since femoral head necrosis has been the topic of a number of very recent publications. Some months ago Dr. D. Polhemus, attending physician at the Los Angeles Children's Hospital, informed me that he had noted in children an association between avascular necrosis of the femoral head and systemic lupus erythematosus (S.L.E.). He mentioned, too, similar observations by Doctor Dubois in adults at Los Angeles County General Hospital, which are referred to briefly in an earlier report inThe Journal, Aug. 13, 1960, page 1633. As a result, I reviewed some of the pertinent information available to me. In his article, previously mentioned, Dubois states that "aseptic necrosis of the bone has never been described heretofore in S.L.E. or rheumatoid arthritis, a closely related
Some Clinical Aspects of Social Medicine
Authors: Ida M. Cannon
Journal: New England Journal of Medicine (1946)

THE English language sometimes seems to obstruct the processes of thinking. Words may become impoverished, or they may become so weighted with a variety of meanings that when they reach the auditory equipment of a dozen persons they carry twelve different meanings and so cloud mutual understanding. "Social" is one of those words. It would have been helpful to me in tackling the subject of social medicine if I could have known beforehand what the term "social" as related to medicine means to each of you. One has only to refer to the dictionary to find the reason for some . . .
Eulogy for a Quality Measure
Authors: Thomas H. Lee
Journal: New England Journal of Medicine (2007)

On May 8, 2007, one of the best-known quality measures in health care was put to rest. The percentage of patients with acute myocardial infarction who receive a prescription for beta-blockers within 7 days of hospital discharge has been used to evaluate U.S. managed care plans since 1996. This measure will no longer be reported by the National Committee for Quality Assurance (NCQA) because it is simply no longer needed — a development that offers encouragement and important lessons.The data in the graph show why the NCQA Committee on Performance Measurement voted unanimously to retire the beta-blocker measure. A decade . . .
Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management
Authors: Girish C. Mohan, Peter A. Lio
Journal: JAMA Dermatology (2015)

Atopic dermatitis (AD) is a common skin condition treated by dermatologists, allergists, pediatricians, and primary care physicians. Several treatment guidelines and therapeutic parameters exist for the management of this disease. Health care professionals may be unaware of guidelines created by specialty organizations other than their own.To review, compare, and contrast the most recent AD management guidelines.The guidelines for AD management published by the American Academy of Dermatology 2014 work group were compared with those created by the 2012 Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. International guidelines created by the 2012 European Task Force on Atopic Dermatitis and the 2013 Asia-Pacific Consensus Group for Atopic Dermatitis were also considered.Several differences among the guidelines suggest that there may be disparity in the perceptions of AD between US dermatologists and allergists and health care professionals in other areas of the world. There are notable differences among the guidelines regarding the recommendations for the use of diluted bleach baths, vitamin D, and environmental modifications.Comparison of different guidelines may ultimately augment knowledge of treatment strategies and enhance realization of biases in the understanding and management of AD.
Abstract 446: Cross-talking of hypoxia stress with IGF-1R signaling in cancer stem cell formation (germline lineage)
Authors: Yen-Hua Huang, Yi-Chun Chen, Shu-Liang Chiang, Thai-Yen Ling, Te-Sheng Chang
Journal: Cancer Research (2010)

Abstract Recent advances in cancer research suggest that there exist cancer stem cells (CSCs) in tumors. The resources of CSCs are still controversial; but the CSCs were originated from its stem cells have been hypothesized (like glioma CSCs and intestine CSCs). The niche stress such as hypoxia effect may provide external signals in stem cell transformation. However, mechanism in regulation of hypoxia-induced stem cell transformation still remains unclear. Our preliminary observations in human pluripotent testicular tumors (seminomas and embryonal carcinomas) showed a high expression level of hypoxia-inducible protein HIF-1α/HIF-2α as well as IGF protein in tissues. This observation strongly highlights the cross-talking of niche hypoxic stress and IGF-1 signaling in transformation of germline stem cells into pluripotent cancers. To address this point, we have successfully established a serum-free stem-niche cell co-culture system to generate pluripotent germline stem cells from neonatal mouse testis (AP+GSCs), and uncovered the role of IGF-1/IGF-1R signaling in germ cell pluripotency. Interestingly, while comparing with the normoxia (21 % O2), the AP+GSCs cells showed in a dramatically increase of alkaline phosphatase activity (AP), cell proliferation, HIF-1α, HIF-2α, Oct-4 protein expression, and pluripotent gene expression (such as Oct-4, Sox2, Nanog, Klf-4, and c-Myc) under hypoxia condition (5 % O2). Moreover, the IGF-1 and IGF-1R expression were also significantly increased under hypoxia. Further analysis by using PPP (a specific inhibitor of IGF-1R phosphorylation) and/or LY294002 (a specific PI3K inhibitor) treatment dramatically reduced the Oct-4 expression as well as HIF-1α/HIF-2α protein of AP+GSCs. These observations suggested the regulation of Oct-4/HIF-2α expression by IGF-1/IGF-1R signaling. In summary, our results demonstrated an up-stream regulation of stemness (Oct-4, Sox2, Nanog, and Klf-4) and tumor factor (c-Myc) by hypoxia which was cross-talking with IGF-1/IGF-1R signaling in stem cell transformation under hypoxia condition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 446.
Discordant Extracellular Superoxide Dismutase Expression and Activity in Neonatal Hyperoxic Lung
Authors: Lisa B. Mamo, Hagir B. Suliman, Brenda-Louise Giles, Richard L. Auten, Claude A. Piantadosi, Eva Nozik-Grayck
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Antioxidant defenses in the neonatal lung are required to adapt to the oxygen (O2)-rich postnatal environment, and oxidant/antioxidant imbalance is a predisposition to lung injury when high concentrations of inspired O2 are used in neonatal lung diseases. The lung's main extracellular enzymatic defense against superoxide, extracellular superoxide dismutase (EC-SOD), is closely regulated during development. In testing the hypothesis that developmental change in EC-SOD expression and activity in the immature lung would be disrupted by hyperoxia, we found a doubling of lung EC-SOD protein in newborn rats exposed to 95% O2 for 1 week. Furthermore, EC-SOD protein secretion increased, but EC-SOD enzyme activity did not change with O2 exposure. EC-SOD mRNA did not change at multiple points between 6 hours and 8 days. Lung EC-SOD recovered by immunoprecipitation after 1 week of O2 showed strong increases in protein nitrotyrosine and variable, nonsignificant differences in protein carbonyl content. These data provide the first direct evidence that EC-SOD is itself a target of nitration in hyperoxia, and offer a plausible explanation for low EC-SOD activity despite its increased secretion by O2-exposed neonatal lung.
How Common Is Reye's Syndrome?
Authors: Darryl C. DeVivo
Journal: New England Journal of Medicine (1983)

Twenty years ago, the seminal report by Reye et al. drew attention to "encephalopathy with fatty degeneration of the viscera."1 This clinical entity, now recognized throughout the world, is a major cause of noninfectious neurologic death after viral illness in children.2 The clinical syndrome is composed of two phases: an infectious phase followed within a few days by an encephalopathic phase. Influenza B or A and varicella account for most of the infections. The temporal constancy between the two phases is remarkable. Recurrent vomiting begins about five or six days after the onset of the infectious symptoms. The vomiting may . . .
Effects of gene transfer of urokinase-type plasminogen activator on extracellular matrix and ventricular remodeling in swine
Authors: Hiroshi Ashikaga, Michael Barr, Leslie J. Hsu, Thomas Dieterle, Masahiko Hoshijima, John Ross, Kenneth R. Chien, James W. Covell, Francisco J. Villarreal
Journal: Journal of the American College of Cardiology (2003)
Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death
Authors: Elisabetta Patorno
Journal: JAMA (2010)

<h3>Context</h3>In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs.<h3>Objective</h3>To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants.<h3>Design</h3>A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug.<h3>Setting and Patients</h3>Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006.<h3>Main Outcome Measures</h3>Cox proportional hazards models and propensity score–matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine.<h3>Results</h3>The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297 620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine.<h3>Conclusion</h3>This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.
Cardiac Effects of Intracoronary Arterial Injections of Nicotine
Authors: JAMES W. WEST, SANTIAGO V. GUZMAN, SAMUEL BELLET
Journal: Circulation Research (1958)

The effects of intracoronary arterial injections of nicotine on coronary blood flow, myocardial contractility, cardiac rhythm and the QRS-T complex of the electrocardiogram were studied in intact dogs. The results indicate that nicotine stimulates intrinsic cardiac structures producing parasympathomimetic, sympathomimetic and Bezold-Jarisch reflex responses. The role of these intracardiac receptors is discussed in relation to the circulatory effects resulting from the ingestion of nicotine.
Increased Serum Levels of Advanced Glycation End Products (AGEs) in Children and Adolescents With IDDM
Authors: Tore J Berg, Knut Dahl-Jørgensen, Peter A Torjesen, Kristian F Hanssen
Journal: Diabetes Care (1997)

OBJECTIVE To investigate whether the serum levels of advanced glycation end products (AGEs) are increased in IDDM children and adolescents and to study the effect of puberty on serum levels of AGEs (S-AGEs). RESEARCH DESIGN AND METHODS A total of 68 children and adolescent IDDM patients (age, 13.3 ± 4.0 years; duration of diabetes, 5.0 ± 3.6 years; HbA1c, 8.2 ± 2.0%; Tanner stage [public hair], 1 vs. 2–5, 24/42) recruited from the pediatric outpatient clinic at Aker University Hospital were compared with 25 healthy nondiabetic control subjects. S-AGEs were measured by a fluoremetric immunoassay. RESULTS S-AGEs were significantly elevated in the diabetic group when compared with the control group (14.4 ± 3.5 vs. 11.7 ± 3.0 U/ml, P &amp;lt; 0.002). A significant correlation (r = 0.26, P &amp;lt; 0.04) was found between S-AGEs and HbA1c in the diabetic group but not in the control group. No significant correlation was found between S-AGEs and the duration of diabetes in the diabetic group or S-AGEs and blood glucose concentration or age in either group. We found no difference between S-AGEs in boys and girls and in prepubertal and pubertal diabetic or control subjects. CONCLUSIONS S-AGEs are increased in young patients with diabetes before puberty. Since AGEs are linked to the pathogenesis of vascular complications, this observation suggests that the pathological processes leading to diabetic late complications start even before puberty.
Ethics assessment as an adjunct to risk assessment in the evaluation of developmental neurotoxicants.
Authors: B Weiss
Journal: Environmental Health Perspectives (2001)

The conduct of experimental studies in humans is governed by a body of principles whose main precepts have evolved over the past few decades. Three of these provide the foundations for judging the ethical adequacy of such an experiment. One addresses the question of who receives the benefits of the research and who bears its burdens (justice). A second requires that the research maximize the potential benefits to the subjects and minimize the risk of harm (beneficence). The third, the source of guidelines for informed consent, requires that subjects enter into the research voluntarily and with adequate information (respect for persons). Unlike research conducted to evaluate drugs, however, environmental exposures to potentially toxic chemicals do not survey those exposed for their consent, nor do they provide an appropriate calculus for measuring risks and benefits, which typically involve two different populations. Especially for exposure to developmental neurotoxicants, where the risk-benefit incompatibility can be so striking, another element may need to be incorporated into risk characterization: a process of ethics assessment. A scheme for doing so can be derived from the procedures of fuzzy logic, which allow rules to be formulated that are applicable to ethical principles. Such an approach incorporates some of the tenets of the precautionary principle.
Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone
Authors: Aiwei Yao-Borengasser, Vijayalakshmi Varma, Robert H. Coker, Gouri Ranganathan, Bounleut Phanavanh, Neda Rasouli, Philip A. Kern
Journal: Metabolism (2010)