tbuckley/cabot-search huggingface dataset:
Focal Adhesion Kinase Silencing Augments Docetaxel-Mediated Apoptosis in Ovarian Cancer Cells
Authors: Jyotsnabaran Halder, Charles N. Landen, Susan K. Lutgendorf, Yang Li, Nicholas B. Jennings, Dominic Fan, Gina M. Nelkin, Rosemarie Schmandt, Michael D. Schaller, Anil K. Sood
Journal: Clinical Cancer Research (2005)

Abstract Objective: Docetaxel causes cell death through induction of apoptosis; however, cell death characteristics for docetaxel have not yet been fully elucidated. We examined the role of focal adhesion kinase (FAK) cleavage in docetaxel-mediated apoptosis. Methods: FAK degradation after treatment with docetaxel was determined in both taxane-sensitive (HeyA8 and SKOV3) and taxane-resistant (HeyA8-MDR and SKOV3-TR) ovarian cancer cell lines by Western blot analysis. Cell growth was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. FAK-targeting small interfering RNA (siRNA) was used to decrease FAK expression. Apoptosis and caspase activity were determined using commercially available kits. Results: SKOV3 and HeyA8 cell lines were both sensitive to docetaxel (IC50 levels, 1-6.2 nmol/L), whereas the SKOV3-TR and HeyA8-MDR cells were resistant (IC50 ≥ 250 nmol/L for both). Docetaxel induced high rates of apoptosis in SKOV3 and HeyA8 cells (84% and 66% apoptosis, respectively) but minimal apoptosis (5-8%) in SKOV3-TR and HeyA8-MDR cells. Similarly, FAK was cleaved in SKOV3 and HeyA8 cells in response to docetaxel treatment but unchanged in the resistant cells. Caspase-3 and caspase-8 activity also increased significantly in docetaxel-treated SKOV3 and HeyA8 cells but not in the taxane-resistant cells. DEVD-fmk (caspase-3 blocker) was able to block both FAK cleavage and apoptosis mediated by docetaxel in SKOV3 and HeyA8 cells. FAK siRNA transfection resulted in 70% to 90% decrease in FAK levels in all cell lines within 72 hours. FAK silencing augmented docetaxel-mediated growth inhibition (5- to 8-fold increase) and apoptosis in both of the taxane-sensitive and taxane-resistant cell lines. Conclusions: Docetaxel induces FAK cleavage, mediated through activation of caspase-3, in taxane-sensitive ovarian cancer cells but not in taxane-resistant cells. The absence of FAK degradation may contribute to cell survival in taxane-resistant cells. FAK silencing promotes the in vitro efficacy of docetaxel in both taxane-sensitive and taxane-resistant cell lines and may serve as a novel therapeutic approach.
Kenya eye safari
Authors: D. Orr, I. Cox
Journal: BMJ (1998)

Time might not exactly stand still in Mudogashe but neither does it move apace. The river has dried up but will flow again with the advent of the seasonal rains. And the rains will bring the return of the cattle, which have been sent far away in search of grazing.

This is Kenya's north eastern province, a huge expanse of scrub and semidesert populated by pastoralists. We have flown to this desolate place with a medical team from Kenya's oldest hospital, the Presbyterian Church of East Africa Hospital, established in 1908 at Kikuyu near the capital, Nairobi. On board are two British eye specialists: Dr Mark Wood, director of the hospital's eye unit, and Dr Roger Gray, a consultant retinal ophthalmologist from Somerset who regularly visits Kenya to help train eye surgeons. They are accompanied by an ophthalmic assistant and a nurse.

The trip to Mudogashe is part of a programme of bimonthly flying safaris which brings the eye unit all over Kenya, as well as to Somalia and Sudan. The unit uses the word safari in its true Swahili meaning of journey. Like much of the unit's work, this mission has been funded by a German aid agency, the Christian Blind Mission, which has a fundraising and information office in Cambridge.

The patients wait quietly. There are many more people than expected but this is perhaps not …
Endogenous antigen presentation by autoantigen-transfected Epstein-Barr virus-lymphoblastoid cells. I. Generation of human thyroid peroxidase-reactive T cells and their T cell receptor repertoire.
Authors: A Martin, R P Magnusson, D L Kendler, E Concepcion, A Ben-Nun, T F Davies
Journal: Journal of Clinical Investigation (1993)

To develop a model for endogenous thyroid autoantigen presentation, we transfected EBV-transformed B lymphoblastoid cell lines (EBV-LCL), established from patients with autoimmune thyroid disease and normal controls, with cDNA for the human thyroid autoantigen thyroid peroxidase (hTPO). hTPO-antigen presentation to patient peripheral blood T cells was demonstrated after stimulation in vitro for 7 d with irradiated hTPO-transfected or untransfected autologous EBV-LCL. Anti-hTPO-reactive T cells were subsequently cloned in the presence of irradiated, autologous hTPO-transfected EBV-LCL and IL-2.10 T cell-cloned lines exhibited specific hTPO-induced proliferation (stimulation indices of 2.1-7.9) towards autologous hTPO-transfected EBV-LCL, and were subjected to human T cell receptor (hTCR) V gene analysis, using the PCR for the detection of V alpha and V beta hTcR gene families. The results indicated a preferential use of hTCR V alpha 1 and/or V alpha 3 in 9 of the 10 lines. In contrast, hTCR V beta gene family use was more variable. These data demonstrate a model for the endogenous presentation of human thyroid peroxidase in the absence of other thyroid specific antigens. The high frequency of antigen-specific T cells obtained from PBMC using this technique will facilitate further studies at both the functional and hTCR V gene level.
The Occurrence of Rheumatoid Factor in Synovial Fluid.
Authors: G. P. Rodnan
Journal: Annals of Internal Medicine (1963)

s1 April 1963The Occurrence of Rheumatoid Factor in Synovial Fluid.G. P. Rodnan, M.D., F.A.C.P., C. H. Eisenbeis, M.D. (Associate), A. S. Creighton, B.S.G. P. Rodnan, M.D., F.A.C.P.Search for more papers by this author, C. H. Eisenbeis, M.D. (Associate)Search for more papers by this author, A. S. Creighton, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-738_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough the presence of rheumatoid factor in the blood serum of patients with rheumatoid arthritis has now been well studied, comparatively little information is available concerning the occurrence of this material in synovial fluid. In the present investigation the concentrations of rheumatoid factor and gamma globulin in synovial fluid have been compared to the values found in simultaneous samples of serum from 68 patients with rheumatoid arthritis and 15 patients with other forms of joint disease.In the majority of patients with active rheumatoid arthritis and a positive serum agglutination reaction, the synovial fluid reaction was also positive, usually in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Pa. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 738-738KeywordsAttentionBloodGlobulinsRheumatoid arthritisSynovial fluid Issue Published: 1 April 1963 PDF DownloadLoading ...
Tackling mental health in Sierra Leone
Authors: Joe Asare, Lynne Jones
Journal: BMJ (2005)

A pilot scheme has recently introduced basic mental health care to a remote area of west Africa that has never before received orthodox mental interventions. The organisers of the scheme, Lynne Jones and Joe Asare , describe its structure and assess its results

Despite the emphasis on mental health in the World Health Report of 2001, and the subsequent revolution in mental health care in many countries, the citizens of some countries in Africa have little or no access to mental health care.

The west African state of Sierra Leone went through a civil war lasting 15years that ended in 2002. With only one psychiatrist, two trained psychiatric nurses, and a population of four million, the country was in a weak position to deal with the mental health needs of its population during the years of reconstruction.

A survey by the World Health Organization in Sierra Leone in 2002 found that 2% of the population was psychotic; 4% had severe depression; 4% had substance misuse; 1% had mental retardation; and 1% had epilepsy. WHO advocated the creation of community based mental health services.

As a result, the International Medical Corps, a global humanitarian charity, applied and got funding from the Bureau of Population Refugees, and Migration, of the US State Department, to pilot a community based mental health project in the remote rural area of Kailahun, on the border with Liberia and Guinea.

Kailahun is a district of about 300 000 people in eastern Sierra Leone. The area …
Prevalence of Osteoporosis in High- and Low-Fluoride Areas in North Dakota
Authors: Daniel S. Bernstein
Journal: JAMA (1966)

Roentgenograms of the lateral lumbar area of the spine were obtained from 1,015 subjects over age 45 who were residing in North Dakota. Three hundred lived in an area where the fluoride content of the water supply was high, 4 to 5.8 ppm, and 715 in an area where it was low, 0.15 to 0.3 ppm. Evidence of osteoporosis, reduced bone density, and collapsed vertebrae was substantially higher in the low-fluoride area, especially in women. Visible calcification of the aorta was significantly higher in the lowfluoride area, particularly in men. Limited information on milk and cheese consumption does not indicate that differences in calcium consumption are a significant factor. Fluoride consumption is important in the prevention of osteoporosis and may also play a significant role in preventing calcification of the aorta.
Essential Hypertension in Men and Women
Authors: RICHARD V. LEE
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 January 1988Essential Hypertension in Men and WomenRICHARD V. LEE, M.D., GORAN ENHORNING, M.D.RICHARD V. LEE, M.D.Search for more papers by this author, GORAN ENHORNING, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-1-148_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Messerli and associates (1) document physiologic differences in mild essential hypertension between men and women, without mentioning the perturbations in cardiovascular physiology unique to women—namely, pregnancy and the syndromes of preeclampsia. Normal gestation decreases peripheral vascular resistance and increases circulating blood volume. Recent reports (2, 3) indicate a role for insulin resistance and hyperinsulinemia in the pathogenesis of essential hypertension. Adipose tissue, greater in women than in men, contributes to insulin resistance. Mammalian pregnancy produces placentally mediated insulin resistance, and pregnancy-associated hypertension is commoner in women with gestational diabetes. However, pregnancy-associated hypertension spontaneously occurs only in bipeds,...References1. MESSERLI F, GARAVAGLIA G, SCHMIEDER R, SUNDGAARD-RIISE K, NUNEZ B, and AMODEO C. Disparate cardiovascular findings in men and women with essential hypertension. Ann Intern Med. 1987;107:158-61. LinkGoogle Scholar2. FERRANNINI E, BUZZIGOLI G, and BONADONNA R. Insulin resistance in essential hypertension. N Engl J Med. 1987;317:350-7. CrossrefMedlineGoogle Scholar3. LANDSBERG L. Insulin and hypertension: lessons from obesity. N Engl J Med. 1987;317:378-9. CrossrefMedlineGoogle Scholar1. ROWE J, YOUNG J, MINAKER K, STEVENS A, PALLOTTA J, and LANDSBERG L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 1981;30:219-25. CrossrefMedlineGoogle Scholar2. MESSERLI F, SUNDGAARD-RIISE K, REISIN E, DRESLINSKI G, DUNN F, and FROHLICH E. Disparate cardiovascular effects of obesity and arterial hypertension. Am J Med. 1983;74:808-12. CrossrefMedlineGoogle Scholar3. MESSERLI F. Cardiopathy of obesity—a not-so-Victorian disease. N Engl J Med. 1986;314:57-62. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: RICHARD V. LEE, M.D.; GORAN ENHORNING, M.D.Affiliations: Children's Hospital of Buffalo Buffalo, NY 14222 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1988Volume 108, Issue 1Page: 148-148KeywordsBlood volumeCardiovascular physiologyGestational diabetesHyperinsulinemiaHypertensionInsulin resistancePathogenesisPeripheral vascular resistancePreeclampsiaPregnancy ePublished: 1 December 2008 Issue Published: 1 January 1988 PDF downloadLoading ...
Two key messages were overlooked in article on personal health budgets
Authors: M. McKee
Journal: BMJ (2013)

It was unfortunate that Chinthapalli overlooked the key message of our paper on the Dutch experience with personal health budgets-that their availability is being scaled back radically because of escalating costs and widespread abuse. 1 2Another key issue was overlooked.Many view personal health budgets as the beginning of a process, initiated by the Health and Social Care Bill, whereby at some point in the future each of us will be allocated a fixed amount to purchase insurance, with the requirement to top up anything that is not covered.This would be consistent with views expressed previously by various Conservative politicians. 3 What may seem like a good idea could easily become a Trojan horse.
Light from surgical microscope may damage retina during eye surgery
Authors: B. Merz
Journal: JAMA (1982)

Ophthalmologists may inadvertently injure patients' retinas during eye surgery, warns Joseph L. Calkins, MD, assistant professor of ophthalmology at Johns Hopkins University School of Medicine, Baltimore. During a symposium on light toxicity at the recent joint meeting of the American Academy of Ophthalmology and the International Congress of Ophthalmology in San Francisco, Calkins said that the disturbing incidence of cystoid macular edema in patients who have undergone cataract surgery may possibly be the result of prolonged exposure to the light source in a surgical microscope. In an interview with<i>JAMA</i>MEDICAL NEWS, Calkins cited studies indicating that 40% to 50% of routine cataract extractions are followed by cystoid macular edema detectable by fluorescein angiography shortly after surgery (<i>Invest Ophthalmol</i>1975;14:68-72,<i>Ann Ophthalmol</i>1971;3:1234-1240). "This condition often masks as normal postsurgical blurred vision," he explained. The tipoff comes when the blurring persists longer than it should. He continued, "In most cases,
Coping with Fear of Long-Term Complications in Diabetes mellitus: A Model Clinical Program
Authors: Angela Zettler, Gabriele Duran, Sabine Waadt, Peter Herschbach, Friedrich Strian
Journal: Psychotherapy and Psychosomatics (1995)

Preliminary results are reported on the efficacy of a behaviorally oriented group therapy (n = 17) intended to improve coping with fear of long-term complications in patients with diabetes mellitus. Treatment consisted of exposure in imagination, relaxation training and analysis of dysfunctional health beliefs. Pre-, posttreatment and 3-month follow-up measure showed significant improvements regarding fear, acceptance of chronic disease and work. The usefulness of such a treatment program and the necessarity for further research is discussed.
The effect of Gu-Sui-Bu (Drynaria fortunei J. Sm) immobilized modified calcium hydrogenphosphate on bone cell activities
Authors: Jui Sheng Sun, Guo Chung Dong, Chun Yu Lin, Shiow Yunn Sheu, Feng Huei Lin, Li Ting Chen, Walter Hong Shong Chang, Yng Jiin Wang
Journal: Biomaterials (2002)
ELEVATED ENDOTHELIAL CELL, PLATELET AND T-CELL MICROPARTICLES IN PSORIASIS MAY PROVIDE NOVEL LINK TO ATHEROSCLEROSIS
Authors: Nehal N. Mehta, Ron C. Li, Junko Takeshita, Lifeng Zhang, Abby S. VanVoorhees, Wade Rogers, Mackenzie Wilcox, Anna Raper, Jonni Moore, Joel M. Gelfand, Emile R. Mohler
Journal: Journal of the American College of Cardiology (2012)
Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG).
Authors: S A Liebhaber, M B Coleman, J G Adams, F E Cash, M H Steinberg
Journal: Journal of Clinical Investigation (1987)

An American black woman was found to have the phenotype of moderately severe alpha-thalassemia normally associated with the loss of two to three alpha-globin genes despite an alpha-globin gene map that demonstrated the loss of only a single alpha-globin gene (-alpha/alpha alpha). Several individuals in her kindred with normal alpha-globin gene mapping studies (alpha alpha/alpha alpha) had mild alpha-thalassemia hematologic values consistent with the loss of one to two alpha-globin genes. These data suggested the presence of a nondeletion alpha-thalassemia defect in this family which segregates with the intact alpha alpha gene cluster. An abnormally migrating and highly unstable alpha-globin gene product was demonstrated by in vitro translation of the reticulocyte mRNA from the proposita and this mutant alpha-globin protein was mapped to the alpha 2-globin gene by hybrid-selected translation. The abnormal alpha 2-globin gene was cloned and sequenced. A single base mutation that results in a premature termination codon was identified at codon 116 (GAG----UAG). The defined alpha-globin genotype of the proposita (-alpha/alpha 116UAG alpha) and the positioning of this nonsense mutation at the alpha 2-globin gene locus are fully consistent with the observed alpha-thalassemia phenotype.
???Plain Film??? Diagnosis of Ovarian Cyst
Authors: PERRY R. MANDEL, BRUCE I. SAXE
Journal: Clinical Nuclear Medicine (1979)

Nuclear images frequently include large areas of the patient which are unrelated to the specific organ system under study. The alert interpreter may discover clinically significant information from these portions of the image. This report describes the diagnosis of an ovarian cyst that was suggested by an absence of activity in the pelvis noted on routine rectillnear bone scan.
Rarity of Human T Helper 17 Cells Is due to Retinoic Acid Orphan Receptor-Dependent Mechanisms that Limit Their Expansion
Authors: Veronica Santarlasci, Laura Maggi, Manuela Capone, Valentina Querci, Luca Beltrame, Duccio Cavalieri, Elena D'Aiuto, Rolando Cimaz, Angela Nebbioso, Francesco Liotta, Raffaele De Palma, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
Journal: Immunity (2012)
Abstract 2406: Epigenetics of chromosomal breakage sites and translocations
Authors: Bharat Burman, Zhuzhu Zhang, Rebecca Burgess, Vassilis Roukos, Jason Lieb, Tom Misteli
Journal: Cancer Research (2014)

Abstract Chromosomal translocations are genetic hallmarks of most cancer cells. Translocations require the formation of DNA double-strand breaks (DSBs) at two or more genomic loci, followed by the illegitimate joining of broken chromosomal ends through DNA repair. There is increasing evidence that translocations occur at non-random sites in the genome, suggesting that certain regions of the genome are more susceptible to DNA breakage than others. We hypothesize that altered chromatin structure predisposes genomic sites to DNA breakage and translocations. To identify chromatin features that facilitate translocations, we have mapped histone modifications and DNase I hypersensitive sites (DHSs) at translocation-prone regions in anaplastic large cell lymphoma (ALCL) precursor cells. We find enrichment of active histone marks and a decrease in repressive marks near frequent translocation breakpoints. In a complementary approach using genome-wide histone modification mapping we have identified altered chromatin features at common leukemia and lymphoma breakpoints in CD34+ hematopoietic stem cells. In order to directly test the role of chromatin features in DNA breakage susceptibility, we have developed a protein-DNA tethering system that allows us to create local chromatin domains at pre-defined sites in the genome containing inducible DSB sites in vivo. By measuring the amount of DSBs using ligation-mediated PCR, we find that histone modifying enzymes that create active chromatin marks generally increase breakage susceptibility; however, repressive marks do not necessarily decrease breakage susceptibility. This suggests the involvement of other factors in breakage susceptibility. Taken together, these experiments provide first insights into the role of chromatin structure in the formation of nonrandom chromosomal breaks and the mechanisms that lead to clinically relevant translocations. Citation Format: Bharat Burman, Zhuzhu Zhang, Rebecca Burgess, Vassilis Roukos, Jason Lieb, Tom Misteli. Epigenetics of chromosomal breakage sites and translocations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2406. doi:10.1158/1538-7445.AM2014-2406
Study of glucose‐6‐phosphate dehydrogenase: History and molecular biology
Authors: Ernest Beutler
Journal: American Journal of Hematology (1993)

Abstract Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was discovered in the 1950s. The history of the development of knowledge about G6PD deficiency is reviewed here. In the first decade after its discovery, the clinical manifestations of G6PD deficiency began to be understood. In the second decade, attention was focused on the degree of variability of this enzyme and the distinction of the various biochemical variants from one another. In the last decade, it has been possible to understand the mutations that effect this enzyme at the DNA level. Some 40 different mutations have now been characterized. Analysis of these mutations indicates that, while diversity sometimes exists within a mutation considered biochemical homogeneous, more often variants thought to be distinct prove to be identical. The study of G6PD mutations is beginning to provide insight into structurefunction relationships. © 1993 Wiley‐Liss, Inc.
Motor Nerve Conduction Velocity in Systemic Diseases
Authors: Willibald Nagler
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The EDITORIAL "Motor Nerve Conduction Velocity in Systemic Diseases" (<b>218</b>:91, 1971) deserves some comment. Motor nerve conduction velocities are an indicator of the peripheral nerves ability to conduct an electrical stimulus, but do not reflect neural tissue damage quantitatively. Helmholtz in 1870 had already described the peripheral nerves ability to carry an electrical stimulus with a speed of 50 meters/sec. To this date, the physicial properties of the peripheral nerve structure, which effect a conduction of an electrical current at a certain speed, are not well defined or understood. With the introduction of sophisticated electronic devices, the performance of nerve conduction velocity studies became a rather simple technical task. Many institutions now have the technical equipment and skilled personnel to test conduction of motor and sensory nerves. The methods used at present allow only the fastest-conducting A-fibers to be measured. Impairment of the B and C
Atraumatic non-distorting pyloric sphincter pressure studies.
Authors: A J McShane, C O'Morain, J R Lennon, J B Coakley, B G Alton
Journal: Gut (1980)

Conflicting claims have been made regarding the physiological characteristics of the pyloric sphincter. Pyloric sphincter pressures were studied in 32 patients under basal conditions, after stimulation with HCl and posture changes. At gastroscopy a 2 mm diameter manometer catheter was placed in the duodenum and three to five hours later the catheter was withdrawn slowly with continuous manometry. Lower esophageal sphincter pressures fell within the expected range but there was no definite evidence of a pressure barrier at the pylorus in any group of patients. The technique caused no patient discomfort and minimal distortion of the region under study, indicating that the pylorus is usually patent with a lumenal diameter greater than 2 mm.