tbuckley/cabot-search huggingface dataset:
Adamantyl-Substituted Retinoid-Related Molecules Bind Small Heterodimer Partner and Modulate the Sin3A Repressor
Authors: Lulu Farhana, Marcia I. Dawson, Mark Leid, Li Wang, David D. Moore, Gang Liu, Zeben Xia, Joseph A. Fontana
Journal: Cancer Research (2007)

Abstract 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437/AHPN) and 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC/MM002) are inducers of apoptosis of malignant cells both in vitro and in vivo. Numerous mechanisms have been proposed for how these compounds exert this effect. This report shows that AHPN/3-Cl-AHPC binds specifically to the orphan nuclear receptor small heterodimer partner (SHP; NR0B2), and this binding promotes interaction of the receptor with a corepressor complex that minimally contains Sin3A, N-CoR, histone deacetylase 4, and HSP90. Formation of the SHP-Sin3A complex is essential for the ability of AHPN and 3-Cl-AHPC to induce apoptosis, as both knockout SHP and knockdown of Sin3A compromise the proapoptotic activity of these compounds but not other apoptosis inducers. These results suggest that AHPN/3-Cl-AHPC and their analogues are SHP ligands and their induction of apoptosis is mediated by their binding to the SHP receptor. [Cancer Res 2007;67(1):318–25]
Water content and its intracellular distribution in intact and saline perfused rat hearts revisited
Authors: M Aliev
Journal: Cardiovascular Research (2002)

Precise estimation of cellular water content is a necessary basis for quantitative studies of metabolic control in the heart; however, marked discrepancies in water spaces of heart tissue are found in the literature. Reasons for this wide diversity are analyzed, and the conclusion is that the most probable value of total intracellular water content is 615 ml H2O/kg of wet mass (wm) and intracellular content of dry substance is 189 g/kg wm in intact in vivo rat heart. An extracellular water of 174 ml per kg wm and 22 g of dry mass per kg wm in vascular and interstitium spaces account for the rest of the tissue mass. These values can be directly related to normoosmotic saline perfused hydrated hearts, characterized by water accumulation in the extracellular spaces. Due to essentially intact heart cells, the experimentally determined dry mass, water and metabolite contents of these hydrated hearts can be extrapolated to the original morphological configuration of an intact heart muscle before the onset of edema. Such an 'extrapolated' heart is defined as a standardized perfused heart (SPH). SPH is the heart in its original morphological configuration, characterized by cell density and cellular water contents of the intact heart, but with perfusate in the extracellular spaces. The total cellular water is distributed in the cell compartments of SPH and intact hearts according to volumes of particular compartments and density of their dry mass. The volumes of bulk water phases in different organelles, accessible to diffusion of low molecular metabolites, were obtained after corrections for the fraction of 'bound' water of 0.3 g per g of compartmental dry mass content. The diffusible water spaces are proposed to be 321, 55, 153, 21 and 8 ml/kg wm for myofibrils, sarcoplasm, mitochondria, sarcoplasmic reticulum and nuclei, respectively. The SPH model allows direct comparison of metabolic data for intact and perfused hearts. We used this model to analyze the penetration of extracellular marker into cells of intact and hydrated perfused rat hearts.
Escitalopram, Problem-Solving Therapy, and Poststroke Depression
Authors: Olaf Schulte-Herbrüggen
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Listening to a Different Drummer
Authors: Lester S. King
Journal: JAMA (1989)

IN 1928, when I entered medical school, my role model was William James. He had taken a medical degree, and then, without ever having practiced, devoted himself to psychology, and finally to philosophy. Such a career sequence seemed admirable to an undergraduate who had majored in philosophy and psychology in college, and the exploration of that path was attractive. I was no stranger to a life in medicine, for my father was a general practitioner, and an older brother had preceded me to medical school. The first 2 years, everyone had said, could be quite dull and disagreeable, and I gritted my teeth for that first rite of passage, the course in anatomy. <h3>The First 2 Years</h3> This course, which included embryology and a few lectures on medical history, was indeed dull. However, within the first 2 months I had an illumination. A surprise examination caught me unprepared, and some
Transgenic rescue of insulin receptor–deficient mice
Authors: Haruka Okamoto, Jun Nakae, Tadahiro Kitamura, Byung-Chul Park, Ioannis Dragatsis, Domenico Accili
Journal: Journal of Clinical Investigation (2004)

The role of different tissues in insulin action and their contribution to the pathogenesis of diabetes remain unclear. To examine this question, we have used genetic reconstitution experiments in mice. Genetic ablation of insulin receptors causes early postnatal death from diabetic ketoacidosis. We show that combined restoration of insulin receptor function in brain, liver, and pancreatic β cells rescues insulin receptor knockout mice from neonatal death, prevents diabetes in a majority of animals, and normalizes adipose tissue content, lifespan, and reproductive function. In contrast, mice with insulin receptor expression limited to brain or liver and pancreatic β cells are rescued from neonatal death, but develop lipoatrophic diabetes and die prematurely. These data indicate, surprisingly, that insulin receptor signaling in noncanonical insulin target tissues is sufficient to maintain fuel homeostasis and prevent diabetes.
Good News about Oral Contraceptives
Authors: Nancy E. Davidson, Kathy J. Helzlsouer
Journal: New England Journal of Medicine (2002)

The development of oral contraceptives stands as a major advance in women's health in the past century. By virtue of their ability to prevent pregnancy in 99 percent of women who use them properly, oral contraceptives have revolutionized reproductive choices for women. But concern about possible adverse effects persists — especially concern about breast cancer, because of laboratory and epidemiologic evidence linking steroid hormone exposure to breast cancer.1 The Cancer and Steroid Hormone (CASH) study, a landmark case–control study reported in the Journal in 1986, did not show any association between oral-contraceptive use and breast cancer (relative risk, 1.0; 95 . . .
An Antiinflammatory Effect of Salmeterol, a Long-acting β<sub>2</sub> Agonist, Assessed in Airway Biopsies and Bronchoalveolar Lavage in Asthma
Authors: XUN LI, CHRIS WARD, FRANCIS THIEN, ROS BISH, TIFFANY BAMFORD, XIANGHUA BAO, MICHAEL BAILEY, JOHN W. WILSON, E. HAYDN WALTERS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The addition of long-acting β2 agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 –500 μ g/d) to 12 wk of supplementary treatment with salmeterol (50 μ g twice daily) or fluticasone (100 μ g twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased “allergic” airway inflammation, but conversely with a complementary antieosinophil effect. Li X, Ward C, Thien F, Bish R, Bamford T, Bao X-H, Bailey M, Wilson JW, Walters EH. An antiinflammatory effect of salmeterol, a long-acting β2 agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma.
Admission for and mortality from primary venous thromboembolism in women of fertile age in Denmark, 1977-95
Authors: L. Mellemkjar, H. T. Sorensen, L. Dreyer, J. Olsen, J. H Olsen
Journal: BMJ (1999)

Epidemiological studies indicate that use of third generation oral contraceptives increases the risk of venous thromboembolism more than does use of second generation oral contraceptives. 1-3Critics have suggested that this finding may be confounded by indication, since third generation pills were considered to be safer and were therefore perhaps prescribed more often to women at high risk.If confounding by indication is the only explanation for the observed association, the incidence of venous thromboembolism in the population should not have changed when prescribing patterns changed from second generation to third generation pills with no increase in overall use of oral contraceptives.Vandenbroucke et al and Thomas reported increasing mortality from venous thromboembolism among young women in the Netherlands and in England and Wales from the mid-1980s to the 1990s, when the use of third generation pills was increasing. 4 5 Since mortality from venous thromboembolism depends on both aetiological and prognostic factors, however, it may be more appropriate to look at incidence.In Denmark, roughly a quarter of women aged 15-44 used oral contraceptives during the 1980s and the beginning of the 1990s.The first third generation oral contraceptive, containing desogestrel, was released in 1984, and the third generation preparations containing gestodene and norgestimate were introduced in 1988 and 1990, respectively.Use of third generation pills represented 0.2% of the total use of oral contraceptives in 1984, 17% in 1988, 40% in 1990, and 66% in 1993.
HIV treatment in children brought into line with that in adults
Authors: D. Josefson
Journal: BMJ (1997)

The treatment of children with AIDS should be brought into line with that of adults, according to new draft guidelines from the United States's Department of Health and Human Services.

Historically, because of toxicity and dosage concerns, children with AIDS have been denied the potent drugs routinely prescribed to adults with AIDS. Consensus has been growing that this relative neglect is unfair, especially with the advent of triple therapy with antiretrovirals and protease inhibitors that can lower viral loads to undetectable levels.

Most children acquire HIV during the perinatal period, a time when an infant's immune system is still developing. Maternal antibodies …
2. Identification of Different Modes of Viral Transport in the Non-Human Primate Brain after Convection-Enhanced Delivery of AAV Serotype Vectors
Authors: Marco A. Passini, Jie Bu, James C. Dodge, Lamya S. Shihabuddin, Tatyana V. Taksir, Denise A. Griffiths, John Bringas, Piotr Hadaczek, Mihaela Avramut, Seng H. Cheng, Krystof Bankiewicz
Journal: Molecular Therapy (2006)

Recombinant adeno-associated virus serotypes-1 and -2 encoding human acid sphingomyelinase were administered into multiple structures of the cynomolgus monkey brain using convection- enhanced delivery. One group of monkeys (n = 2) was injected with 30–100 ul of AAV2-hASM into the striatum, thalamus, motor cortex and hippocampus, and euthanized at 31 days post-injection. Transduction occurred in the four injected structures and in other regions that resulted in an expression pattern that spanned 50–60 mm, although the posterior aspects of the brain had only sporadic human ASM-positive cells. In situ hybridization experiments demonstrated that widespread transduction was aided, in part, by retrograde axonal transport of AAV2 and by movement of the viral vector through the perivascular space. A second group of monkeys (n = 2) was injected with 30-50 ul of AAV1-hASM into the same four structures, as well as into the occipital cortex and cerebellum to achieve more efficient transduction of caudal brain structures. At 35 days post-injection, widespread transduction by AAV1 was observed in both the injected structures and in other regions along the rostro-caudal axis of the brain, including robust transduction of posterior aspect of the brain. In situ hybridization experiments confirmed retrograde axonal transport of AAV1 to multiple regions of the brain, including the medulla oblongata that sends axonal projections to the cerebellum. Furthermore, the horizontal transduction pattern in the neuronal layers of the convoluted cortex strongly suggests that AAV1 (and AAV2) may become widely dispersed by moving along the outside of major white matter tracts. This study demonstrate that the topographical organization of the brain circuits, and the anatomical features of the Virchow-Robin space and white matter tracts, may be exploited to achieve widespread gene/protein delivery in the primate brain including remote regions of that are not accessible by surgery.
Pulseless Disease, or Takayashu's Disease
Authors: J. M. Pahwa, M. P. N. Pandey, D. P. Gupta
Journal: BMJ (1959)

Cases of unilateral absence of pulse due to aortic aneurysm have been known since 1757, when William Hunter described the condition, but bilateral absence of the arterial pulses is exceedingly rare.In 1908 Takayashu reported a peculiar case with cataracta complicata and unusual ocular findings.At the meeting at which the case was described Onishi and Kagoshima reported two similar cases, with the addition that radial pulsation was absent in one of the patients.It was not.however, until the review by Shimizu and Sano (1953) that this pulseless-disease-aortic-arch syndrome, or reversed coarctation, became recognized by Japanese ophthalmologists as a rare but definite entity.Since that time 69 cases have been reported from Japan, and 34 from Europe and America, including several in recent years.The present paper records a further case.the first one from India.Clinical Signs and Symptoms Clinically, pulseless disease is characterized by three cardinal signs; the most common is absence of palpable
Fly fisher's finger.
Authors: A C Wicks
Journal: BMJ (1984)

holds the reins.In her shadow is Chronus with a restraining hand on her left shoulder.The milk motif in association with Venus signifies serious contamination in classical paintings.Cupid shows interest and the two putti or cherubs in the right foreground share a wreath of laurels, symbol of virginity.And there is Minerva.Is she not resplendent in her everyday wear of plumed helmet, long spear, and breast plate fronted by the Gorgon Medusa's head, with hair replaced by serpents?Note how fittingly these serpents intertwine to suggest BMA membership.She is dressed just as she was when she is said to have leapt from Jupiter's brain, mature, on the day of her birth.And what of her looks?Was not Milton in his Comus right to describe her as of "noble grace"?Little wonder she thought herself fit to compete with Juno and Venus for Paris's golden apple.What is a nice girl like Minerva doing in such mixed company?Her past history is helpful.
Minimal Residual Disease Monitoring with High-Throughput Sequencing of T Cell Receptors in Cutaneous T Cell Lymphoma
Authors: Wen-Kai Weng, Randall Armstrong, Sally Arai, Cindy Desmarais, Richard Hoppe, Youn H. Kim
Journal: Science Translational Medicine (2013)

TCRB high-throughput sequencing can monitor response to therapy in a skin lymphoma patient population.
Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration
Authors: Yoshito Wada, Osamu Nakashima, Rumiko Kutami, Osamu Yamamoto, Masamichi Kojiro
Journal: Hepatology (1998)

We examined the clinicopathologic features of 11 surgically resected hepatocellular carcinomas (HCCs) less than 3 cm in diameter with marked inflammatory cell infiltration (LHCCs). In comparison with the other 152 HCCs without such an infiltration (controls), there were no significant differences in male/female ratio, age, serum α-fetoprotein levels, and laboratory and imaging findings. All the 11 LHCC cases were hepatitis B surface antigen (HBsAg) negative and hepatitis C virus antibody positive. Among the 152 controls, 116 cases were also HBsAg negative and HCVAb positive and were referred to as HCV-only controls. The clinical features were not significantly different between the LHCC and the HCV-only controls. The LHCC group tended to have higher numbers of lymphocytes and monocytes in pre- and post-operative peripheral blood, but there were no significant group differences. Recurrence rate was 9.1% in the LHCC group, 47.7% in the controls and 47.5% in the HCV-only controls ( P &lt; .01). Five-year survival rate was 100% in the LHCC group, 65.1% in the controls and 68.1% in the HCV-only controls ( P &lt; .01). Histologically, remarkable inflammatory cell infiltration, mostly lymphocytic, was observed in the cancerous tissue of the LHCC group. Varying degrees of piecemeal necrosis of cancer nests produced by infiltrating lymphocytes were observed in all the 11 cases. Lymph follicle formation was also found in 10 of 11 cases (90.9%). Liver cirrhosis was associated in 6 LHCC cases (54.5%), in 117 control cases (77.0%), and in 91 HCV-only controls (78.4%). Tumor invasion into the portal vein in the vicinity of the tumor was found in 1 LHCC case (9.1%), in 54 controls (35.5%), and in 34 HCV-only controls (29.3%). Immunohistochemically, most of the infiltrating lymphocytes, other than those in the lymph follicle, were identified as T lymphocyte, and CD8 + T lymphocyte was more predominant than CD4 + T lymphocyte. Better prognosis of the LHCC group could attribute to the anti-tumor effect induced by cellular immunity of CD8 + and CD4 + T lymphocytes, and partly by humoral immunity of B cells which formed lymph follicles.
Abstract 1347: CXCR4 pathway associated with family history of melanoma.
Authors: Wenqing LI, Jiali Han, Hans Widlund, Mick Correll, Yaoyu Wang, John Quackenbush, Martin Mihm, Alvaro Laga Canales, Todd Golub, Yujin Hoshida, David Hunter, George Murphy, Thomas Kupper, Abrar Qureshi
Journal: Cancer Research (2013)

Abstract Background &amp; Aims: Inherited genetic variants involved in the etiology of melanoma predispose towards elevated risk of disease, but known allele variants only account for a limited fraction of family history-associated melanoma cases. Hence, there is a need to determine contributing allele variants associated with augmented risk and surrogate biomarkers, which can be used to discern family history-associated melanoma. Methods: Using data from the Nurses’ Health Study cohort, family history was defined as having one or more immediate family members diagnosed with melanoma. Secondary confirmation of melanoma cases were reviewed by pathology reports and tumor blocks collected by mail from across the United States. Genomic interrogation was accomplished through evaluating formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, using expression profiling on either a 6K or whole-genome (24K) Illumina gene chip. Gene Set Enrichment Analysis was performed separately for each batch to determine the differentially enriched pathways and key contributing genes. Results: The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF status, or Breslow thickness of the primary melanoma cases. Conclusion: We found that the CXCR4 pathway may constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives. Citation Format: Wenqing LI, Jiali Han, Hans Widlund, Mick Correll, Yaoyu Wang, John Quackenbush, Martin Mihm, Alvaro Laga Canales, Todd Golub, Yujin Hoshida, David Hunter, George Murphy, Thomas Kupper, Abrar Qureshi. CXCR4 pathway associated with family history of melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1347. doi:10.1158/1538-7445.AM2013-1347
1002-91 Plasma Endothelin-1 in Acute Phase of Kawasaki Disease Complicated with Coronary Aneurysm
Authors: Mamoru Ayusawa, Kensuke Karasawa, Tsunehisa Yamashita, Nobutaka Noto, Hideo Yamaguchi, Naokata Sumitomo, Tomoo Okada, Kensuke Harada
Journal: Journal of the American College of Cardiology (1995)
The Effect of Aging of Population on General Health Problems
Authors: Robert T. Monroe
Journal: New England Journal of Medicine (1953)

PEOPLE the world over are living for a longer time than they used to do. This is changing the age composition of society. It is altering the relative size of the many problems that society faces, and it creates new problems. Of these facts and the desirability of studying their significance and the best method of handling them there is a growing appreciation among leaders in business, labor and public administration. The interest of the medical profession in the health aspects is shown by the expanding work of organizations devoted to geriatrics and gerontology.Too many physicians, however, still equate . . .