tbuckley/cabot-search huggingface dataset:
MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress
Authors: Mildred Felder, Arvinder Kapur, Jesus Gonzalez-Bosquet, Sachi Horibata, Joseph Heintz, Ralph Albrecht, Lucas Fass, Justanjyot Kaur, Kevin Hu, Hadi Shojaei, Rebecca J Whelan, Manish S Patankar
Journal: Molecular Cancer (2014)

Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3–5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.
A CASE OF RECURRENT HERPES ZOSTER
Authors: J. LEURER
Journal: British Journal of Dermatology (1957)

Journal Article A CASE OF RECURRENT HERPES ZOSTER Get access J. LEURER, M.D. (Zürich) J. LEURER, M.D. (Zürich) Department of Internal Medicine, Shaarei Zedek General Hospital, Jerusalem Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 7-8, 1 July 1957, Pages 282–283, https://doi.org/10.1111/j.1365-2133.1957.tb13269.x Published: 01 July 1957
Effect of physical activity on cartilage development in healthy kids
Authors: G Jones, K Bennell, F M Cicuttini
Journal: British Journal of Sports Medicine (2003)

Current evidence supports a prescription of vigorous physical activity for optimum joint development in children

Physical activity in childhood has many health benefits. In the musculoskeletal area, physical activity leads to substantial gains in bone mass, at least some of which are maintained into later life.1 The most opportune time for intervention appears to be the prepubertal and early pubertal years.1–4 However, much less is known about joint development. Recently, advances in magnetic resonance imaging have allowed an accurate in vivo assessment of hyaline cartilage in joints. Most studies have been of the knee, but methods for hip and hand assessment have also been validated. Magnetic resonance imaging is accurate and highly reproducible with coefficients of variation of 2–3%.5,6

Development of articular hyaline cartilage in the knee appears to be a very dynamic process.6 Physical activity has been shown to be associated with cartilage development both cross sectionally and longitudinally in randomly selected healthy children without knee pain or injury.5,6 Cross sectionally, physical activity was a significant explanatory factor for cartilage volume at all knee sites ( R 2 7–14%).5 The most striking association was with vigorous activity in the …
Cyclic Nucleotides: Mediators of Bacterial Toxin Action in Disease
Authors: JOEL MOSS
Journal: Annals of Internal Medicine (1984)

In several bacterial diseases, the clinical, laboratory, and histologic findings result from the elaboration by the organism of a toxic product that binds to and may enter the host cell to alter its metabolism. In some cases, the intracellular mediators of toxin action are the cyclic nucleotides, cyclic adenosine 5′-monophosphate (cAMP) and cyclic guanosine 5′-monophosphate (cGMP), the ubiquitous second messengers through which numerous hormones, neurotransmitters, and drugs exert their effects. Certain toxins act by enhancing the activity of cellular enzymes that synthesize cAMP or cGMP; and others, by themselves catalyzing cAMP synthesis after entering the cell. Studies of the mechanism of action of these toxins have helped in deciphering the enzymatic components within animal cells that are responsible for cyclic nucleotide synthesis, degradation, and function as well as in understanding the pathogenesis of the diseases in which they are involved.
Antioxidants Improve Impaired Insulin-Mediated Glucose Uptake and Prevent Migration and Proliferation of Cultured Rabbit Coronary Smooth Muscle Cells Induced by High Glucose
Authors: Kenichi Yasunari, Masakazu Kohno, Hiroaki Kano, Koji Yokokawa, Mieko Minami, Junichi Yoshikawa
Journal: Circulation (1999)

Background —To explore the role of intracellular oxidative stress in high glucose–induced atherogenesis, we examined the effect of probucol and/or α-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). Methods and Results —Chronic high-glucose-medium (22.2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB–mediated VSMC migration, [ 3 H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and α-tocopherol significantly suppressed high glucose–induced increase in VSMC migration, cell number, and [ 3 H]thymidine incorporation. Probucol and α-tocopherol suppressed high glucose–induced elevation of the cytosolic ratio of NADH/NAD + , phospholipase D, and membrane-bound protein kinase C activation. Probucol, α-tocopherol, and calphostin C improved the high glucose–induced suppression of insulin-mediated [ 3 H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, α-tocopherol, suramin, and calphostin C. Conclusions —These findings suggest that probucol and α-tocopherol may suppress high glucose–induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD + , phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.
Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.
Authors: F Niimura, P A Labosky, J Kakuchi, S Okubo, H Yoshida, T Oikawa, T Ichiki, A J Naftilan, A Fogo, T Inagami
Journal: Journal of Clinical Investigation (1995)

Elevated levels of endogenous angiotensin can cause hypertensive nephrosclerosis as a result of the potent vasopressor action of the peptide. We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg-1-). Postnatally, Atg-1- animals show a modest delay in glomerular maturation. Although Atg-1- animals are hypotensive by 7 wk of age, they develop, by 3 wk of age, pronounced lesions in the renal cortex, similar to those of hypertensive nephrosclerosis. In addition, the papillae of homozygous mutant kidneys are reduced in size. These lesions are accompanied by local up-regulation of PDGF-B and TGF-beta1 mRNA in the cortex and down-regulation of PDGF-A mRNA in the papilla. The study demonstrates an important requirement for angiotensin in achieving and maintaining the normal morphology of the kidney. The mechanism through which angiotensin maintains the volume homeostasis in mammals includes promotion of the maturational growth of the papilla.
Warfarin continuation was better than heparin bridging during pacemaker or ICD surgery
Authors: Thomas DeLoughery
Journal: Annals of Internal Medicine (2013)

Source Citation Birnie DH, Healey JS, Wells GA, et al; for the BRUISE CONTROL Investigators. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368:2084-93. 23659733
The Influence of Alcohol on Viral and Isoproterenol Cardiomyopathy
Authors: Y. Morin, P. E. Roy, S. M. Mohiuddin, P. K. Taskar
Journal: Cardiovascular Research (1969)

Journal Article The Influence of Alcohol on Viral and Isoproterenol Cardiomyopathy Get access Y. Morin, Y. Morin † From the Institute of Cardiology, Laval University and Hospital, Quebec, Canada † Institute of Cardiology, Laval University and Hospital, 2725, Ste-Foy Road, Quebec 10, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. E. Roy, P. E. Roy From the Institute of Cardiology, Laval University and Hospital, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar S. M. Mohiuddin, S. M. Mohiuddin From the Institute of Cardiology, Laval University and Hospital, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar P. K. Taskar P. K. Taskar From the Institute of Cardiology, Laval University and Hospital, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 3, July 1969, Pages 363–368, https://doi.org/10.1093/cvr/3.3.363 Published: 01 July 1969 Article history Received: 13 January 1969 Published: 01 July 1969
Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice.
Authors: S Takahashi, L Fossati, M Iwamoto, R Merino, R Motta, T Kobayakawa, S Izui
Journal: Journal of Clinical Investigation (1996)

To investigate the respective roles of Th1 and Th2 cells in the pathogenesis of lupus-like autoimmune disease, we have analyzed the spontaneous and antigen-induced productions of IgG1 vs IgG2a and IgG3 subclasses in relation to the mRNA expression of INF-gamma (Th1 cytokine promoting IgG2a and IgG3 production), IL-4 (Th2 cytokine promoting IgG1 production), and IL-10 (Th2 cytokine) in CD4+ T cells from lupus-prone MRL mice. For this purpose, two paired sets of MRL mice were chosen for the comparison of these parameters: (a) MRL-lpr/lpr (lpr for lymphoproliferation) and its recently described substrain with a prolonged survival, termed MRL-lpr/lpr.ll (ll for long lived) and (b) MRL male mice bearing the Yaa (Y-linked autoimmune acceleration) gene (MRL.Yaa) with an accelerated disease and their male counterparts lacking the Yaa gene. We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4+ T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies. These data suggest that an imbalance towards Th1 predominance may play a significant role in the acceleration of lupus-like autoimmune disease in MRL mice.
Diseases of the Aortic Arch and Brachiocephalic Arteries
Authors: Fritz Dalith
Journal: JAMA (1963)

PREVIOUS STUDIES 1-4 have disclosed structural changes of preferential location in the aortic arch and in the brachiocephalic arteries in aged persons. They are situated in the internal carotid artery, right and left, immediately cranial to or at its origin from the common carotid artery; in the right subclavian artery at its origin from the innominate artery; and in the aortic arch at the levels of the origin of the innominate artery, the origin of the left subclavian artery, and the insertion of the ligamentum arteriosum (Fig 1, 1-6).They consist of calcified foci, radiographically demonstrable, and intimai depressions at the levels of the calcifications, often with corresponding protrusions on the adventitial surface of the media, visible on direct inspection. These areas show increased translucency when viewed by the transillumination. Atheromatous plaques of varying sizes, together with varying degrees of stenosis, form at these levels. Histological examination confirms the presence of atherosclerosis with fibrous intimai
Doctors warned to be wary of new drugs
Authors: D. Josefson
Journal: BMJ (2002)

Doctors should be wary of starting their patients on newly approved drugs, because of the high rate of adverse side effects that go undetected until late in the post-marketing surveillance period, a new study says ( JAMA 2002;287:2215-20).

More than 10% of new drugs approved by the Food and Drug Administration (FDA) have serious side effects that are not discovered on initial testing and marketing, says the study, led by Dr Karen Lasser and Dr Paul Allen of the Department of Medicine at Cambridge Hospital in Cambridge, Massachusetts.

The investigators analysed 548 drugs approved by the FDA from 1975 to 1999. The list …
New molecular test can diagnose tuberculosis in less than two hours
Authors: John Zarocostas
Journal: BMJ (2010)

A new, automated molecular test for tuberculosis enables relatively unskilled healthcare workers in resource poor settings to diagnose the disease and accurately detect drug resistant strains in most cases in less than two hours, a research study shows.

The New England Journal of Medicine study found that a single test correctly identified 98% of people who tested positive to currently used tests, being both smear test positive and culture positive (doi:10.1056/NEJMoa0907847). The new test gave a positive result in more than 70% of people with smear negative and culture positive disease, which commonly occurs in people coinfected with HIV. It also correctly identified resistance to rifampicin in 98% of patients.

The results came from testing sputum of 1462 people with symptoms suggestive of tuberculosis who were recruited in five centres: Lima, Peru; Baku, Azerbaijan; Cape Town and Durban, South Africa; and …
Association of Testosterone and Sex Hormone–Binding Globulin With Metabolic Syndrome and Insulin Resistance in Men
Authors: Chaoyang Li, Earl S. Ford, Benyi Li, Wayne H. Giles, Simin Liu
Journal: Diabetes Care (2010)

We sought to assess the associations of testosterones and sex hormone-binding globulin (SHBG) with metabolic syndrome and insulin resistance in men.We defined metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Among men aged >or=20 years who participated in the Third National Health and Nutrition Examination Survey (n = 1,226), the Cox proportional hazards model was used to estimate the prevalence ratio and 95% CI of metabolic syndrome according to circulating concentrations of testosterones and SHBG.After adjustment for age, race/ethnicity, smoking status, alcohol intake, physical activity level, LDL cholesterol, C-reactive protein, and insulin resistance, men in the first quartile (lowest) (prevalence ratio 2.16 [95% CI 1.53-3.06]) and second quartile of total testosterone (2.51 [1.86-3.37]) were more likely to have metabolic syndrome than men in the fourth quartile (highest, referent group) (P < 0.001 for linear trend). Similarly, men in the first quartile of SHBG (2.17 [1.32-3.56]) were more likely to have metabolic syndrome than men in the fourth quartile (P = 0.02 for linear trend). No significant associations of calculated free testosterone (P = 0.31 for linear trend) and bioavailable testosterone (P = 0.11 for linear trend) with metabolic syndrome were detected after adjustment for all possible confounders.Low concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance.
THE RECOGNITION OF EARLY CHANGES IN THE LARYNX IN TUBERCULOSIS
Authors: W. E. CASSELBERRY
Journal: JAMA (1913)

Not differing from tuberculosis elsewhere, the first definite change provoked by the bacillus in the larynx is an infiltration of the mucosa and submucosa by a diffusion of small, round, mononuclear cells, interspersed among which are collections of epithelioid and lymphoid cells in the form of tubercles, which are deposited, in large part, in the connective tissue beneath the epithelial and structureless layers, and hence near enough to the surface to change its aspect in form and feature. Accordingly, the recognition of early changes in tuberculosis of the larynx will be promoted by keeping in mind: First, the disposition of tubercles and tuberculous nodules to assume a globular form, which gives the surface of the infiltration, also termed hyperplasia, a mammillated aspect. Secondly, their disposition to excite verrucous and granulomatous formations which, though ordinarily delayed till the stage of ulceration, may make an earlier appearance and give the surface a
A SUCCESSFUL CASE OF CÆSAREAN SECTION.Read in the Section of Obstetrics and Diseases of Women, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: GILES S. MITCHELL
Journal: JAMA (1893)

Until the last decade the Cæsarean section occupied a doubtful place between conservative and sacrificial midwifery. Puzos, the distinguished author and obstetrician, writing in 1875 concerning Cæsarean section makes the following statement: "This operation has cost the lives of all the unhappy, ignorant women who have undergone it in Paris since the beginning of this century." And he adds, "it is still practiced." Even Robert Barnes, whose name is a household word with the medical profession, in the last edition of his work on Obstetric Operations, uses the following language in speaking of it: "It is resorted to with a feeling akin to despair for the fate of the mother, which is scarcely tempered by the hope of rescuing the child. It is looked upon by the great majority of obstetricians as the last desperate resource, as the most forcible example of that kind of surgery which John Hunter regarded
An Analysis of 388 Cases of Rheumatoid Arthritis
Authors: J. G. Sclater
Journal: Annals of the Rheumatic Diseases (1943)

RHEUMATOID arthritis is described as a polyarticular disease which is characterised by pain and swelling of the small and medium-sized joints of the body.The onset is usually insidious, but it may be acute, and muscular wasting not only around the affected joints but also throughout the body is a striking feature.The incidence is stated to be greatest in the age period 20 to 40, and females are more frequently affected than males.It is a common experience, however, to find that this description by no means covers a great many of the cases of rheumatoid arthritis.For example, a man aged 65 to 70 may present an arthritis affecting wrists and metacarpal-phalangeal joints associated with muscular wasting.If such a clinical picture had been presented by a woman of 35 there would be no hesitation in making a diagnosis of rheumatoid arthritis, but can rheumatoid arthritis occur in a man of 70 ?Or again, a woman shortly after the menopause may develop pain, sweliing and limitation of movement, with muscular wasting, in both knees, and a diagnosis of menopausal arthritis may be suggested.A year later, however, the wrists and fingers may show the characteristic changes of rheumatoid arthritis, and the original diagnosis may have to be changed.Other variations such as the disease remaining mono- articular for some months before other joints become affected, or where stiffness in the region of the joints is more striking than actual pain and swelling, make the diagnosis of rheumatoid arthritis in some cases uncertain and difficult.Accordingly, in any analysis of cases of arthritis of the rheumatoid type it is essential that the criteria on which the diagnosis is made are clearly stated.In this series a case was considered to be an arthritis of the rheumatoid type if it showed the following features:1 The presence of persistent swelling of the peri-articular tissues in the region of more than one joint.2. The involvement, either primarily or subsequently, of the wrist, metacarpal-phalangeal joints, or interphalangeal joints.
Intravenous Administration of Oxytocin Under Nurse Supervision
Authors: Robert C. Goodlin
Journal: JAMA (1971)

To the Editor.—  During the past two years, management of parturients in the Stanford (Calif) University Hospital labor rooms has changed significantly. Prior to July 1969, intravenous oxytocin administration and examination of parturients were performed by staff physicians or obstetrics residents. Electronic fetal monitoring was seldom used. For the past year, obstetrics nurses generally have supervised intravenous administration of oxytocin and examined obstetrical patients. In 1969, 8% of the patients received oxytocin buccally, 2% intramuscularly given oxytocin, and 33% intravenously given oxytocin, of whom 86% were managed by physicians. During the last 12 months, in contrast, only 2% of the parturients received buccally given oxytocin, 0.5% intramuscularly given oxytocin, and 45% intravenously given oxytocin, of whom only 12% were managed even partially by obstetricians. Electronic fetal monitoring was used in 31% of the patients in labor. In addition to the reduced use of intrapartum oxytocin buccally and intramuscularly, the percentage
Epigenetic Alterations in Liver of C57BL/6J Mice after Short-Term Inhalational Exposure to 1,3-Butadiene
Authors: Igor Koturbash, Anne Scherhag, Jessica Sorrentino, Kenneth Sexton, Wanda Bodnar, Volodymyr Tryndyak, John R. Latendresse, James A. Swenberg, Frederick A. Beland, Igor P. Pogribny, Ivan Rusyn
Journal: Environmental Health Perspectives (2010)

1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides.In this study we tested the hypothesis that BD may be epigenotoxic (i.e., cause changes in DNA and histone methylation) and explored the possible molecular mechanisms for the epigenetic changes.We administered BD (6.25 and 625 ppm) to C57BL/6J male mice by inhalation for 2 weeks (6 hr/day, 5 days a week) and then examined liver tissue from these mice for signs of toxicity using histopathology and gene expression analyses. We observed no changes in mice exposed to 6.25 ppm BD, but glycogen depletion and dysregulation of hepatotoxicity biomarker genes were observed in mice exposed to 625 ppm BD. We detected N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua) adducts in liver DNA of exposed mice in a dose-responsive manner, and also observed extensive alterations in the cellular epigenome in the liver, including demethylation of global DNA and repetitive elements and a decrease in histone H3 and H4 lysine methylation. In addition, we observed down-regulation of DNA methyltransferase 1 (Dnmt1) and suppressor of variegation 3-9 homolog 1, a histone lysine methyltransferase (Suv39h1), and up-regulation of the histone demethylase Jumonji domain 2 (Jmjd2a), proteins responsible for the accurate maintenance of the epigenetic marks. Although the epigenetic effects were most pronounced in the 625-ppm exposure group, some effects were evident in mice exposed to 6.25 ppm BD.This study demonstrates that exposure to BD leads to epigenetic alterations in the liver, which may be important contributors to the mode of BD carcinogenicity.