tbuckley/cabot-search huggingface dataset:
Interleukin-6 attenuates agonist-mediated calcium mobilization in murine osteoblastic cells.
Authors: J Green, S Schotland, Z Sella, C R Kleeman
Journal: Journal of Clinical Investigation (1994)

Interleukin-6 (IL-6) is a multifunctional cytokine which is made by osteoblasts and has diverse effects on bone metabolism. We studied the interaction of IL-6 with the Ca2+ and cAMP signaling systems in the osteoblastic cell line UMR-106 and in primary osteoblastic cultures derived from neonatal rat calvariae. IL-6 did not alter basal intracellular calcium concentration ([Ca2+]i) but inhibited Ca2+ transients induced by parathyroid hormone (PTH), prostaglandin E2 (PGE2), and endothelin-1 in both dose- (100-400 U/ml) and time- (4-48 h) dependent manners. The effect of the cytokine was abolished by the tyrosine kinase inhibitor, herbimycin A (50 ng/ml). The IL-6 effect on the Ca2+ message system was related to suppressed production of hormonally induced inositol 1,4,5-triphosphate and inhibition of Ca2+ release from intracellular stores. Hormonally induced calcium entry pathways (estimated by using Mn2+ as a surrogate for Ca2+) were not, however, altered by the cytokine. IL-6 did not modulate cAMP generation in osteoblasts. With respect to osteoblast function, IL-6, although having no effect on cell proliferation by itself, greatly enhanced the antiproliferative effect of PGE2 and PTH. Because the production of IL-6 in osteoblasts is stimulated by calciotropic hormones (e.g., PTH and PGE2), the suppressive effect of the cytokine on hormonally induced Ca2+ transients may serve as an autocrine/paracrine mechanism for modulating the effect of hormones on bone metabolism.
Abstract P1-04-10: Assessment of circulating tumor cells (CTC) by RT/PCR as a surrogate marker for PFS in metastatic breast cancer (MBC)
Authors: MM Saber, AA Bahnasy, HM El-Zawahry, NM Allahloubi, MA El-Moetii, RM Abd El Fatah, S Aid, M Ghareeb
Journal: Cancer Research (2013)

Abstract Background: Despite significant improvements in the treatment of metastatic breast cancer (MBC), it remains an incurable disease. The presence of circulating tumor cells (CTC) predicts for progression free survival (PFS) in (MBC) patients. We hypothesized that the change in level of CTCs can be a good surrogate marker for PFS. Methods: CTC level was determined by flow cytometry (FCM) in the blood of MBC female patients with measurable or non-measurable evaluable disease excluding CNS metastasis 1) before starting taxanes (Docetaxel or Paclitaxel) regimen, 2) after the first cycle, and 3) at assessment of the disease after 3-4 cycles. The breast origin was further confirmed through assessment of CK19, mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) in the separated CTCs by quantitative real time PCR (QRT-PCR). CTC level and level of these markers were correlated with the clinical features of the patients, response to treatment and PFS. Results: Sixty-six female patients were enrolled between May 2010 and Jan. 2011. The median age was 48.9 years and duct carcinoma was the main pathologic subtype. After a median follow up period of 20 months, median PFS was 6 months. There was a very strong relation between the selection marker CK-19 and the breast cancer markers (p value = 0.0001). Patients with baseline CTC &amp;lt; 4 had significantly higher median, 6 months and 1 year PFS when compared with those with CTC ≥ 4 (p value = 0.03) while CTC levels did not correlate with PFS in the 2nd &amp; 3rd samples respectively (p value = 0.28). Also patients whose CTC level decreased after treatment had significantly prolonged median PFS compared to patients whose CTC level increased (10 versus 4 months, p = 0.007). Conclusions: CTCs; measured by RT-PCR were strongly predictive of PFS in MBC. CTC also could be of a great potential value in early assessment of response to chemotherapy after the 1st cycle especially in non-measurable lesions. Key Words: Circulating tumor cells, metastatic breast cancer, progression free survival and RT-PCR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-10.
Sexually dimorphic nonreproductive behaviors as indicators of endocrine disruption.
Authors: Bernard Weiss
Journal: Environmental Health Perspectives (2002)

Measures of cognitive and other behaviors not specifically related to reproduction are often sex-linked. Males and females perform differently on many tasks and often interact with members of their species in dissimilar ways. If such differences are diminished, reversed, or widened by prenatal chemical exposures, a reasonable inference is that exposure interfered with sexual differentiation of the brain, largely, but not exclusively, through interference with the actions of gonadal hormones. Explicit recognition of sex differences in performance is not a prominent feature of toxicity testing, however, except for reproduction studies, and is not a recognized criterion in developmental neurotoxicity testing. In contrast to the low visibility accorded sex differences in testing protocols for the assessment of developmental neurotoxicity, the literature is filled with examples showing that the developing male and female respond differently to many chemical agents, with subsequent expression in behavior. Quite often, even when such differences are reported, further analyses are not carried out nor are subsequent studies conducted for clarification. Moreover, many investigators include only male subjects. Both polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) studies provide several examples of striking differences between the behavioral responses of male and female offspring to developmental exposure. They offer examples, as well, of how to approach the study and analysis of such differences. Given the societal importance of risk assessments applied to potential developmental neurotoxicants, studies should be deemed questionable if they fail to include outcome measures based on sexual dimorphisms in nonreproductive behaviors.
Self-Report Questionnaire Scores in Rheumatoid Arthritis Compared with Traditional Physical, Radiographic, and Laboratory Measures
Authors: Theodore Pincus
Journal: Annals of Internal Medicine (1989)

Study Objective: To assess whether scores on a simple self-report questionnaire to depict the clinical status of patients with rheumatoid arthritis are correlated with traditional measures of physical, radiographic, laboratory, functional, and global status. Design: The self-report questionnaire was administered at the same time the following variables were assessed: American Rheumatism Association functional class, joint count, hand radiograph, erythrocyte sedimentation rate, rheumatoid factor titer, walking time, grip strength, button test, and global self-assessment. Setting: University rheumatology clinic, the rheumatology clinic of a Veterans Administration hospital, and a private rheumatology practice. Patients: The study included 259 patients who met the criteria
CONTINUOUS SUBMERSION IN THE TREATMENT OF INFECTED WOUNDS OF THE EXTREMITIES.
Authors: FRED. J. HODGES
Journal: JAMA (1896)

Within the sound of my voice to-day are not a few of the men who have been conspicuous in their efforts to place surgery upon a rational basis; to earn for it a place among the true sciences. To such there can be no name so illustrious that its glamour can blind them to the defects of any surgical proposition or procedure, nor can I believe they will fail to consider and weigh the suggestions of even the humblest within the ranks. Before such a body, not easily influenced by sentiment or selfish considerations, but zealous always for the best interests of our profession, I appear to briefly submit and support the proposition, that in continuous submersion we have the most rapid, thorough and reliable treatment for infected wounds of the extremities yet devised. We are told that continuous submersion, by which I mean the submersion of a part for
Abstract 2625: MGCD0103, an oral isotype-selective HDAC inhibitor, has antitumor activity via the induction of the expression of Annexin A1 on AML1/ETO AML <i>in vitro</i> and <i>in vivo</i>
Authors: Daisuke Nameki, Norio Masuko, Ryouto Fujita, Shin Sugiura, Yasuji Yamamoto, Kazuhisa Minamiguchi, Ken-Ichi Matsuo
Journal: Cancer Research (2011)

Abstract MGCD0103 is a non-hydroxamate and an orally available isotype-selective HDAC inhibitor (HDACi) whose clinical activity has been shown in multiple phase II trials in patients with relapsed or refractory Hodgkin lymphoma, high-risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). It has previously been shown that FK-228, class I selective HDACi, and SAHA, isotype-nonselective HDACi, activate apoptosis through induction of pro-apoptotic protein annexin A1 on t(8;21) translocated AML cells which produce AML1-ETO fusion protein (AML1/ETO AML). To determine whether the existence of t(8;21) translocation in AML affect on the efficacy of MGCD0103, we explored the action of MGCD0103 on anti-tumor activity in AML1/ETO AML and AML1/ETO-negative AML xenograft models in mice in vivo and investigated the putative mechanism of the efficacy.MGCD0103 was orally administrated to the NOD SCID mice implanted with AML1/ETO AML xenograft or AML1/ETO-negative AML xenograft using an intermittent dosing regimen (3 times a week) for 3 weeks. Tumor volume was calculated during the treatment and tumor weight at final date was measured for final evaluation. In addition, we measured not only the activity of apoptosis related factor, caspase-3/7, but also the expression of pro-apoptotic protein annexin A1 that induced by MGCD0103 in vitro and in vivo. Further understanding of the mechanism of MGCD0103, we assessed the acetylated histone in the promoter region of annexin A1 using ChIP assay in vitro whether its induction is derived from the histone acetylation activity of MGCD0103. MGCD0103 showed a strong growth inhibition of the tumor in the AML1/ETO AML xenograft. There were significant decreases in the AML1/ETO AML tumor volume and weight in the MGCD0103 treated group compared with the control group, but not in the AML1/ETO-negative AML xenograft. Caspase-3/7 was strongly activated and the expression of annexin A1 was significantly induced in the MGCD0103 treated AML1/ETO AML cells. In addition, histone of annexin A1 promoter region in AML1/ETO AML tended to be acetylated more than the AML1/ETO-negative AML cells by MGCD0103. These data possibly indicate that the strong anti-tumor effect was derived from the direct effect of MGCD0103 that leads apoptosis of the AML1/ETO AML cells through the induction of acetylation of annexin A1 promoter. Selection of AML patients with t(8;21) translocation may leads good therapeutic outcome of MGCD0103 in AML treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2625. doi:10.1158/1538-7445.AM2011-2625
AN OCCASIONAL TYPE OF LOUD SYSTOLIC MURMUR IN CARDIOSCLEROSIS
Authors: SELIAN NEUHOF
Journal: JAMA (1918)

By cardiosclerosis, I refer to marked pathologic changes involving the cardiac muscle, the valves, the aorta, and involving the coronaries and their branches. The damage is rarely equally distributed among these structures. Frequently the aorta and coronary system are the most affected.  Although the auscultatory phenomena to be described are more often present in the senile, the middle-aged are also occasionally affected by a cardiosclerotic process which produces physical signs exactly as in the aged.  The senile cases of this type possessed all the usual characteristics of marked generalized arteriosclerosis: thickened, palpable and tortuous arteries, usually a slight increase in the systolic blood pressure, and a trace of albumin and a few casts in the urine. Cardiac failure was sometimes, though by no means invariably, present. As demonstrated by the physical examination and corroborated by roentgenograms, the cardiac area was enlarged. Pulsation of the aortic arch was usually well marked;
Selected Techniques in Interventional Radiology
Authors: Robert I. White
Journal: JAMA (1981)

AN OUTGROWTH of diagnostic angiography was the realization that an intravascular catheter could be used for much more than delineating arterial and venous anatomy. Viewed in its simplest form, interventional radiology is considered any selective catheter technique adopted for treatment. Such techniques include intravascular infusion of vasodilators or vasoconstrictors or mechanical dilatation or occlusion of a vascular bed. Chemotherapeutic agents can be infused for palliation of metastatic neoplasms, and modified angiographic catheters, needles, and guide wires are used for drainage procedures in the biliary and urinary tract. The following material highlights some of these advances in interventional radiology and also describes developments that are likely to occur in the next decade. <h3>Percutaneous Transluminal Angioplasty (PTA)</h3> Just 16 years ago, in 1964, Dotter and Jadkins<sup>1</sup>described the technique employing telescoping catheters to recanalize atherosclerotic stenoses of the femoral arteries. The technique was preserved and further developed by the pioneering efforts
The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R&gt;Q154 amino acid substitution
Authors: Brian R. Curtis, Nancy J. Cox, Mia J. Sullivan, Anuar Konkashbaev, Krista Bowens, Kirk Hansen, Richard H. Aster
Journal: Blood (2009)
THE CURE OF CRIPPLED CHILDREN: PROPOSED NATIONAL SCHEME
Authors: R. Jones, G. R. Girdlestone
Journal: BMJ (1919)

IT is unfortunately the case that -children suffering from orippling diseases and deformities of all 'kinds exist iu large numbers throupglout our country.The majority lie out of siglht in their homes; many are in workhouses or collected in homes for crippled chiildren, but many others are frequently to be met in our streets.The number of adult cripples.resultingfrom disease or deformity in clhild--hood is.a still more common object for our sympathy; and shlame is added when we realize that perlhaps three-foarths of these couli lhave rbeen cured, and most of the others .givenmuchb greater activity, if thieir condition had been recognized early and trated efficiently.There is no lack -of sympathy for these clhildren, but It muse be led into practical channels, and, after all, the comparative comfort of a cripples' home is but a half-measure.'Our sympathy .shouldbe directed towards the cure of the deformities and diseases from whicla they suffer, or, wlhere cure is beyond reaclh, the greatest improvement -that can be attained.This paper is written to dramw attention to this need and to ,bring forward proposals for the estab- lishmenet of a system' of orthopaedic hospitals and clinics for the active treatment of cripples, and more particularly of crippled.childten, througlout thfe country.In Shropshire a system of hospital and out-patient 'treatment such as is here to be described has been organized, owing to the pioneer work of Miss Hunt, wlho started the Children's Orthopaedic Hospital at Baschurch in 1900.As a direct consequence many hunareds of clhildren have been cured or greatly benefited.Further, througlh the out-patient clinics added more recently, many cases have been brought to light whichl would othierwise ,have remained unknown and untreated.Thus we have bbeen able'to realize more fully the great number of cases in very serious need of treatment.The proposals put forlard ,are thus not merely theordtical, but concert the multiplication of thlis organiza- tion throughout England aud Wales, and its general co ordination under the Ministry of Health.'The accompanying -table is compiled from the list of cases under treatment in -Shropshire, and at a dauglhter inftitution at Stoke in Staffordshire, -and represents fairly "the principal disabilities andthe three main groups in whlichl they may be included.'It will be seen tihat rikets, ana surgical tuberculosis taken 'togetlier account for 0-per cent. of the crippled cliildren under treatment 'in these areas.Of the causes
Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus
Authors: K. Ratheiser, B. Schneeweiß, W. Waldhäusl, P. Fasching, A. Korn, P. Nowotny, M. Rohac, H.P.O. Wolf
Journal: Metabolism (1991)
ABC of 1 to 7. Vomiting and acute diarrhoea.
Authors: H B Valman
Journal: BMJ (1981)

child.Although it may herald only the onset of a trivial illness, such as acute otitis media, ............vomiting may be the first symptom of a potentially inary tract infection (see later article) iset of acute appendicitis or intussusception (see earlier article oflo cinnh tyi :ute abdominal pain): .: itestinal obstruction (see earl'ier article on acute abdominal pain) ~~~~obstruction) or if he is drowsy or refusing feeds, h~ooping cough .... which may occur in meningitis.Diagnosis over the eningitis *. ......:... telephone without seeing a vomiting child may be Aective hepatitis ..... ..
A Comparison of Cardiac Output Determined by the Fick Procedure and a Direct Method Using the Rotameter
Authors: ROBERT D. SEELY, WILLIAM E. NERLICH, DONALD E. GREGG
Journal: Circulation (1950)

Experiments were performed on the anesthetized dog to determine the accuracy of the widely used Fick procedure. Cardiac output values, recorded by an optical rotameter, served as a reliable standard for comparison. Under the conditions of these experiments, comparisons showed excellent agreement. The average variation between the two series of the measurements was ±5 per cent. Twelve of thirteen comparisons agreed within less than ±8 per cent. This small deviation was within the range of error which might have existed on the basis of known technical inaccuracies.
852 A MUTATIONAL ANALYSIS OF THE INTERNAL RIBOSOME ENTRY SITE IN HEPATITIS C VIRUS IN PATIENTS TREATED WITH PEGYLATED INTERFERON WITH RIBAVIRIN
Authors: K. Ogata, K. Hara, T. Kashiwagi, T. Ide, R. Kumashiro, N. Hamada, H. Watanabe, M. Sata
Journal: Journal of Hepatology (2008)
Ruxolitinib leads to improvement of pulmonary hypertension in patients with myelofibrosis
Authors: A Tabarroki, D J Lindner, V Visconte, L Zhang, H J Rogers, Y Parker, H K Duong, A Lichtin, M E Kalaycio, M A Sekeres, S E Mountantonakis, G A Heresi, R V Tiu
Journal: Leukemia (2014)
Clinical Efforts to Combine Endocrine Agents with Targeted Therapies against Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 and Mammalian Target of Rapamycin in Breast Cancer
Authors: Stephen R.D. Johnston
Journal: Clinical Cancer Research (2006)

Abstract Enhancing the benefit of endocrine therapy by overcoming de novo or acquired resistance remains an important goal in systemic breast cancer therapy. Progress continues to be made in elucidating the molecular pathways by which estrogen receptor–positive breast cancer cells escape from endocrine therapy. The increasing recognition of the roles of epidermal growth factor receptor (EGFR) and human EGFR2 in cross-talk activation of estrogen receptor signaling has led to studies aimed at identifying whether small-molecule tyrosine kinase inhibitors targeted against these receptors give additive or synergistic effects when combined with endocrine agents. Activation of the phosphatidylinositol-3-OH kinase/Akt pathway has also been associated with resistance to either tamoxifen or estrogen deprivation, and preclinical studies have shown that the mammalian target of rapamycin antagonist temsirolimus can restore endocrine sensitivity in breast cancer cells. Randomized phase II trials of aromatase inhibitors combined with EGFR/human EGFR2 tyrosine kinase inhibitors or mammalian target of rapamycin antagonists have been completed in both the neoadjuvant and advanced breast cancer settings. Larger phase III trials with both approaches are now in progress and have been powered to detect whether either strategy can significantly prolong time to disease progression compared with endocrine therapy alone. The correlation of molecular and clinical results from these ongoing studies will be important to establish appropriate biological variables for selecting those patients who may benefit most from this combined approach.
Recovery From Disability Among Community-Dwelling Older Persons
Authors: Susan E. Hardy
Journal: JAMA (2004)

Context Previous studies have found that a sizeable minority of newly disabled older persons recover independent function; however, long intervals between assessments have led to difficulty in determining the true incidence and duration of disability, and therefore in accurately characterizing the probability and course of recovery.Objectives To determine the rate of and time to recovery of independent function in community-dwelling older persons who become newly disabled in their activities of daily living (ADLs), to determine the duration of recovery, and to compare the likelihood of recovery among pertinent subgroups of older persons. Design, Setting, and ParticipantsProspective cohort study, with monthly assessments of ADL function, for 754 initially nondisabled, community-dwelling persons aged 70 years or older, performed in a small urban area from March 1998 to May 2003.Main Outcome Measures Demographic features, chronic conditions, cognitive function, and physical frailty were determined during comprehensive assessments at 18month intervals.Disability, defined as needing personal assistance with 1 or more key ADLs (bathing, dressing, walking, and transferring), was assessed during monthly telephone interviews.Results A total of 420 participants (56%) experienced disability during a median follow-up of 51 months.Of these participants, 399 (81%) recovered (ie, regained independence in all 4 ADLs) within 12 months of their initial disability episode, and a majority (57%) of these maintained independence for at least 6 months.Among participants who experienced 3 or more consecutive months of disability, a majority (60%) recovered, but only a third of these maintained independence for at least 6 months.Persons who were cognitively impaired, physically frail, or severely disabled (ie, in 3-4 ADLs) at onset were less likely to recover than those who were cognitively intact, nonfrail, or mildly disabled, respectively.Nonetheless, a majority of participants within each subgroup recovered.Conclusions Newly disabled older persons recover independent ADL function at rates far exceeding those that have been previously reported.Recovery from disability, however, is often short-lasting, suggesting that additional efforts are warranted to maintain independence in this high-risk group.
FLUORESCEIN AND FLUORESCIN.Read in the Section of Ophthalmology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May 5-8, 1801.
Authors: FRANK TRESTER SMITH
Journal: JAMA (1891)

These recent additions to our materia medica are closely allied chemically, both being products in the distillation of coal tar. They are of use from their faculty of coloring abraded surfaces of the cornea, thus enabling us to locate such abrasions rapidly and accurately. To the oculist this is of but little assistance, as he can readily diagnose these conditions by the methods now in use, and yet in some cases it is of assistance even to him, as in the extraction of small foreign bodies where we must get the substance between us and the iris, or against the black pupil. In these cases, the green ringaround the offending material enables us to see it in any position. Likewise, in cases where we have much photophobia, we can tell more quickly and easily to what extent the cornea is involved. In no other condition than that of abrasion of