tbuckley/cabot-search huggingface dataset:
Abstract 2134: Bone-targeted MMP inhibitors for the treatment of multiple myeloma.
Authors: Gemma Shay, Marilena Tauro, Antonio Laghezza, Paolo Tortorella, Lori A. Hazlehurst, Conor C. Lynch
Journal: Cancer Research (2013)

Abstract Multiple Myeloma (MM) is a plasma cell malignancy that is hallmarked by areas of extensive bone destruction. Our group, and others have recently shown that individual host or tumor derived MMP-2 and MMP-9 play an important role in the progression of many cancers in the bone microenvironment, including MM. These data support the design of selective inhibitors of individual MMPs for the treatment of multiple myeloma. Previous clinical trials with broad-spectrum matrix metalloproteinase (MMP) inhibitors failed, arguably because the precise roles of individual MMPs had not been fully appreciated. Therefore, in the current study, we have developed novel bone seeking MMP inhibitors (BMMPIs) that are highly selective to MMP-2 and structurally are based on the bone targeting bisphosphonate, Tiludronate. In vitro, BMMPIs showed greater enzyme inhibition, and specificity for MMP-2 than previously synthesized bisphosphonates (e.g. Zoledronate, Etidronate and Tiludronate) with Ki values in the nanomolar range. Further treatment of the 5TGM1 mouse MM cell line with low micromolar concentrations of the BMMPI inhibitors significantly reduced cell viability through inhibition of cell growth (p&amp;lt;0.05). In vivo, 5TGMI tumor-bearing mice receiving BMMP inhibitors three times a week, showed significant increase in overall survival compared to vehicle and tiludronate treated mice over 80 days (p&amp;lt;0.05). This was associated with a reduction in tumor burden and protection from tumor-associated bone loss compared to vehicle treated mice as measured by x-ray and histomorphometry. These data suggest that given the roles for MMPs in tumor progression in bone, that our novel BMMPIs may be effective in the treatment of MM. We predict that MMP-2 specific BMMPIs may be more effective than current clinically used bisphosphonates for the treatment of MM, and may eliminate undesirable side effects of broad-spectrum MMP inhibitors due to their high specificity and bone seeking nature. We are currently continuing to characterize these BMMPI both as single agents, and in combination with existing MM treatments (eg. Bortezomib) for the treatment and eradication of MM. Citation Format: Gemma Shay, Marilena Tauro, Antonio Laghezza, Paolo Tortorella, Lori A. Hazlehurst, Conor C. Lynch. Bone-targeted MMP inhibitors for the treatment of multiple myeloma. [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 2134. doi:10.1158/1538-7445.AM2013-2134
Perfusion of isolated tubules of the shark rectal gland. Electrical characteristics and response to hormones.
Authors: J N Forrest, F Wang, K W Beyenbach
Journal: Journal of Clinical Investigation (1983)

Both the mammalian thick ascending limb of Henle's loop and the shark rectal gland actively transport Cl against an electrochemical gradient by mechanisms involving hormone-sensitive NaCl transport. In contrast to mammalian renal tubules, individual tubules of the shark rectal gland previously have not been perfused in vitro. Using a combination of renal slice and microdissection techniques we were able to isolate and perfuse single rectal gland tubules without the use of enzyme treatment. Single tubules consistently generated lumen-negative transepithelial voltages (Vt) of -1.8 mV when perfused and bathed with identical shark Ringer's solution. The addition of cyclic AMP, vasoactive intestinal peptide (VIP), and adenosine to the bath increased Vt to -7.5, -9.0, and -4.3 mV, respectively (all P less than 0.02 compared with paired controls). Each stimulation could be reversed by addition by furosemide to the bath. The adenosine response was inhibited by theophylline, a specific inhibitor of adenosine receptors. The tubules had a low transepithelial electrical resistance of 12-26 omega X cm2 and exhibited a transepithelial permselectivity for small cations. These results indicate that tubules of the rectal gland can be perfused in vitro and have receptors for VIP and adenosine. Cyclic AMP and secretagogues hyperpolarize the membrane consistent with electrogenic chloride transport, and these effects are reversed by furosemide, an inhibitor of coupled sodium-potassium-chloride co-transport. The response of Vt to cyclic AMP and furosemide, the transepithelial electrical resistance, and the cation selective permeability of tubules are remarkably similar to measurements in perfused mammalian thick ascending limbs.
Amitriptyline and Fluphenazine for Painful Diabetic Neuropathy
Authors: Daniel Ritter
Journal: JAMA (1986)

To the Editor.—  As a long-term user of amitriptyline and fluphenazine for chronic pain, I take issue with the recent article by Mendel et al. 1 Having taken this drug combination for approximately five years, I tried several times to discontinue its use because of undesirable side effects. Each time I did so, it was very apparent that it took ten to 12 days to reach maximal benefit as well as to lose all drug effect. With this in mind, I feel a valid study would require at least a month's trial of both drug and placebo, as well as an interval between trials of at least two weeks. The fact that my severe leg dysesthesias are the result of postsurgical spinal arachnoiditis rather than diabetic neuritis does not alter my opinion in any way.
Augenblick in Aruba
Authors: Robin Dibner
Journal: Annals of Internal Medicine (2011)

Ad Libitum21 June 2011Augenblick in ArubaRobin Dibner, MDRobin Dibner, MDFrom Lenox Hill Hospital, North Shore Long Island Jewish Health System, New York, NY 10075.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-12-201106210-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Sharing the innate draw to the source of our cells,our isotonic birthplace,on this heavenly morning,I watch the perched pelicans perform their ablutions,whitlocks glistening in the sun.The bronzed apples stroll by, outnumbering the pears.Some with zippered chests, on their second chances,sport gleaming talismans around their necks.But what of the tall thin man, toes in the water, spider fingers at his side? … and a quick glance confirms—the caved chest.Will he live to have his thorax splayed?I share Cassandra's ancient gift and curse …And with a moment's hesitation, walk by.Robin Dibner, MDLenox Hill Hospital, North Shore Long Island ... Author, Article, and Disclosure InformationAffiliations: From Lenox Hill Hospital, North Shore Long Island Jewish Health System, New York, NY 10075.Current Author Address: Robin Dibner, MD, Department of Medicine, Lenox Hill Hospital, North Shore Long Island Jewish Health System, 100 East 77th Street, New York, NY 10075. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 June 2011Volume 154, Issue 12Page: 837KeywordsCellsHospital medicineIsotonicitySportsThorax ePublished: 21 June 2011 Issue Published: 21 June 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
LSD, Alcohol, and Homicide
Authors: Robert L. Sadoff
Journal: JAMA (1973)

To the Editor.—  It has now come to my attention in two dramatic cases, both involving homicide, that alcohol ingestion following a series of LSD trips may have a stimulating effect on the flashback phenomena. In both cases, the individuals had had a number of experiences with LSD, with rarely an unfavorable reaction. Several months after the discontinuance of the LSD ingestion, but with increased alcohol intake, hallucinatory experiences of the flashback variety continued. In both instances the alcohol precipitated a psychotic reaction with hallucinations and delusions directly related to the violent behavior and consequent homicide.  In one case I introduced alcohol in a controlled test dose. I administered 95% ethyl alcohol mixed in a 3:1 solution with fruit juice. After 63 ml of the alcohol was ingested, the patient noted visual distortions characteristic of LSD intake, but not characteristic of alcohol intoxication. After 125 ml of alcohol was ingested,
Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin
Authors: Alison Maloney, Paul A. Clarke, Soren Naaby-Hansen, Rob Stein, Jens-Oliver Koopman, Akunna Akpan, Alice Yang, Marketa Zvelebil, Rainer Cramer, Lindsay Stimson, Wynne Aherne, Udai Banerji, Ian Judson, Swee Sharp, Marissa Powers, Emmanuel deBilly, Joanne Salmons, Michael Walton, Al Burlingame, Michael Waterfield, Paul Workman
Journal: Cancer Research (2007)

Abstract The promising antitumor activity of 17-allylamino-17-demethoxygeldanamycin (17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins. Gene expression microarray and proteomic analysis were used to profile molecular changes in the A2780 human ovarian cancer cell line treated with 17AAG. Comparison of results with an inactive analogue and an alternative HSP90 inhibitor radicicol indicated that increased expression of HSP72, HSC70, HSP27, HSP47, and HSP90β at the mRNA level were on-target effects of 17AAG. HSP27 protein levels were increased in tumor biopsies following treatment of patients with 17AAG. A group of MYC-regulated mRNAs was decreased by 17AAG. Of particular interest and novelty were changes in expression of chromatin-associated proteins. Expression of the heterochromatin protein 1 was increased, and expression of the histone acetyltransferase 1 and the histone arginine methyltransferase PRMT5 was decreased by 17AAG. PRMT5 was shown to be a novel HSP90-binding partner and potential client protein. Cellular protein acetylation was reduced by 17AAG, which was shown to have an antagonistic interaction on cell proliferation with the histone deacetylase inhibitor trichostatin A. This mRNA and protein expression analysis has provided new insights into the complex molecular pharmacology of 17AAG and suggested new genes and proteins that may be involved in response to the drug or be potential biomarkers of drug action. [Cancer Res 2007;67(7):3239–53]
Fatal All-Trans Retinoic Acid Pneumonitis
Authors: Kim Smith-Whitley
Journal: Annals of Internal Medicine (1993)

Letters15 March 1993Fatal All-Trans Retinoic Acid PneumonitisKim Smith-Whitley, MD and Beverley Lange, MDKim Smith-Whitley, MDSearch for more papers by this author and Beverley Lange, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-6-199303150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their article, Frankel and coworkers [1] describe a fulminant pneumonitis developing between days 2 and 21 in 9 of 35 adults treated with all-trans retinoic acid (TRA). Three of four patients responded to dexamethasone, 10 mg every 12 hours. We report a case of fatal TRA-associated pneumonitis that began on day 30 of TRA during tapering of high-dose dexamethasone for TRA-associated pseudotumor cerebri [2].On 31 July 1992, a 4-year-old girl participating in the randomized intergroup trial for acute promyelocytic leukemia began induction therapy with TRA at 45 mg/m2 daily. At diagnosis, she had disseminated intravascular ...References1. Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med. 1992; 117:292-6. Google Scholar2. Warrell RP, Frankel SR, Miller WH, Scheinberg DA, Itri LM, Hittelman WN, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans retinoic acid). N Engl J Med. 1991; 324:1385-93. Google Scholar3. Johnston I, Hawke S, Halmagyi M, Teo C. Disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculomegaly. Arch Neurol. 1991; 48:740-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDrug-Induced Intracranial HypertensionMesenchymal Stem Cells Induce Granulocytic Differentiation of Acute Promyelocytic Leukemic Cells via IL-6 and MEK/ERK PathwaysDiffuse Alveolar Hemorrhage in Acute Promyelocytic Leukemia Patients Treated with ATRA - A Manifestation of the Basic Disease or the TreatmentAcute respiratory distress syndrome due to all-trans retinoic acidToxicity of tretinoin in acute promyelocytic leukaemiaTretinoin 15 March 1993Volume 118, Issue 6Page: 472-473KeywordsLumbar punctureMagnetic resonance imagingParalysisPneumonitisRespiratory failureRetinoic acidThoraxThrombosisVasopressorsVentilators Issue Published: 15 March 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The Effect of CS-514 on Serum Lipids and Apolipoproteins in Hypercholesterolemic Subjects
Authors: Noriaki Nakaya
Journal: JAMA (1987)

CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia.
Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma
Authors: Fei Huang, Shinichiro Wachi, Philip Thai, Artem Loukoianov, Kin Hup Tan, Rosanna Malbran Forteza, Reen Wu
Journal: Journal of Allergy and Clinical Immunology (2008)
Endoscopic band ligation of rectal varices: a case series
Authors: N. Coelho-Prabhu, T. Baron, P. Kamath
Journal: Endoscopy (2010)

Although anorectal varices are a common complication of portal hypertension, there is no consensus on the optimal management of this condition. We present a retrospective case series of ten consecutive patients who underwent endoscopic variceal ligation (EVL) for rectal varices associated with hematochezia, at a single tertiary care center between 1995 and 2008. EVL was performed with a standard esophageal varices multi-shot band ligation device attached to a standard video upper endoscope. Of the ten patients who underwent EVL for rectal varices associated with hematochezia, four of the patients (40 %) experienced a re-bleeding event; in three this was controlled with repeat EVL, but one patient died of fatal hemorrhage from the rectal varices. There were no procedural complications. EVL may be an emerging therapeutic option for the management of hematochezia associated with rectal varices in patients with portal hypertension. Prospective studies are needed to determine the safety and efficacy of EVL in these patients.
Chasm of care
Authors: N. Campbell
Journal: BMJ (1997)

My father had not been well for some time and the eventual admission to hospital was not surprising. As a hospital consultant, well aware of the realities of the service over the extended Easter holiday, I was impressed by the care. A patient on a combined admission and cardiology ward, he was seen by a consultant every day. When I visited and asked to speak to one of the medical staff the ward sister asked if she would do. Following an informed, comprehensively detailed, accurate, and caring explanation I was left with no alternative but to agree absolutely.

With a combination of prosthetic heart valves, positive blood cultures, impaired renal function, and probable biliary sepsis, surgery and intensive care seemed avoidable only by an acceptance of …
Fractured femur and embolism.
Authors: E Smyth
Journal: BMJ (1971)

epithelial elements as the result of drug metabolite toxicity rather than as malignant change.Cyclophosphamide, in common with other cytotoxic agents, can under experimental conditions produce malignant change in laboratory animals.However, it is not one of those that has been known to produce malignancy in humans treated with cytotoxic drugs for non-malignant disease or for sup- pression of homograft rejection.However, one case of a second malignancy (myeloblastic leukaemia) occurring in a patient on long-term cyclophosphamide for a first malignancy (of the ovary) has been reported,3 and though this hazard may be less with cyclophosphamide than with certain other cytotoxic drugs, it should be borne in mind.-I am, etc.,
ON THE NATURE OF TRANSPLANTATION IMMUNITY IN THE ADENOVIRUS TUMOR SYSTEM
Authors: Leonard D. Berman
Journal: The Journal of Experimental Medicine (1967)

The existence of a virus-induced, virus-specific transplantation, antigen in adenovirus 12-induced CBA mouse tumors was demonstrated. The antigen is virus-specific, but not related to structural virion or T antigens. It is a weak antigen, and required immunization with whole, infectious adenovirus 12 to produce considerable immunity. Comparable immunity could not be achieved with homologous cellular or subcellular materials, but some indication of enhancement was produced with low tumor dose. Immunization required at least 2 wk and was mediated by immune lymphoid cells. Serum of immunized animals showed no demonstrable cytotoxicity or enhancement. Animals immunized with virus and Freund's adjuvant showed diminished transplantation immunity, although these animals were actively immunized against adenovirus type 12 structural virion antigens.
Value of Post-Therapy Whole-Body I-131 Imaging in the Evaluation of Patients with Thyroid Carcinoma Having Undergone High-Dose I-131 Therapy
Authors: WILLIAM G. SPIES, CONSTANCE H. WOJTOWICZ, STEWART M. SPIES, ALKA Y. SHAH, A MICHAEL ZIMMER
Journal: Clinical Nuclear Medicine (1989)

Post-therapy whole-body I-131 images were compared to 5 mCi pretherapy diagnostic studies in 39 cases of well-differentiated thyroid carcinoma treated with I-131 to evaluate the utility of this procedure for the detection of residual thyroid tissue and functioning metastases. The post-therapy studies were performed immediately before hospital discharge, when the patient's whole-body retained dose had just fallen below 30 mCi. The mean therapeutic dose given was 121 mCi, and the mean interval between administration of the therapy dose and imaging was 2.4 days. In 18 cases (46.2%), the post-therapy images demonstrated either additional findings, such as unsuspected cervical node or pulmonary uptake, or more accurate localization of abnormalities seen on the diagnostic study. In 6 additional cases (15.4%), questionable new findings were noted. Although the precise implications of these additional findings are uncertain at present, they may have a significant effect on future patient management and follow-up. Therefore, the authors recommend that post-therapy imaging be included in the post-therapy evaluation of these patients. In addition, these findings would also suggest reevaluation of the advisability of using 1-2 mCi doses of I-131 for diagnostic whole-body imaging.
Identification of progastrin in gastrinomas, antrum, and duodenum by a novel radioimmunoassay.
Authors: S Pauwels, H Desmond, R Dimaline, G J Dockray
Journal: Journal of Clinical Investigation (1986)

Recent studies on the gene sequence encoding the human pyloric antral hormone, gastrin, indicate a precursor of 101 residues. We have now raised antibodies to a synthetic analogue corresponding to (Tyr)-human progastrin COOH-terminal pentapeptide. The antibodies could be used in radioimmunoassay to measure this peptide, but they did not react with corresponding fragments of procholecystokinin, porcine progastrin, or other human progastrin-derived peptides, notably heptadecapeptide gastrin (G17), and 34-residue gastrin (G34). Radioimmunoassay of human antral and duodenal extracts revealed a major peak of activity that corresponded to the native COOH-terminal fragment of progastrin, and occurred in approximately equimolar amounts with COOH-terminal G17 immunoreactivity. In addition, there was a minor peak of apparently higher molecular weight material. In some gastrinomas the latter material was the predominant immunoreactive form, and it occurred in higher molar concentrations than any other form of gastrin. Digestion of this material with trypsin liberated peptides that reacted with antibodies specific for the NH2-terminus of G34, and G17. On this basis the high molecular weight component was identified as a form of gastrin that extended from the COOH-terminus of the precursor to a point at least beyond the NH2-terminus of G34, and probably included the entire progastrin sequence. The results suggest differences in posttranslational processing pathways of progastrin in antrum, duodenum, and gastrinomas. They also indicate that the present experimental approach allows the identification of progastrin-like substances, which should open the way to studying the mechanisms of gastrin biosynthesis.
WHO report shows public health impact of violence
Authors: Susan Mayor
Journal: BMJ (2002)

More than 1.6 million people worldwide lost their lives to violence in 2000, says the first comprehensive review of the global impact of violence, published by the World Health Organization this week.

The report was developed to raise awareness of the impact of violence and to encourage a much wider role for public health in the response to violence. The report analysed data on morbidity and mortality associated with violence submitted by different countries to the WHO but acknowledges that the data represent only the tip of the iceberg. Data were also gathered from an extensive literature review of the impact of violence on health. The report took more than three years to develop, and 160 experts from around the world participated.

The report analyses violence in categories according to the person who committed the act, who the victims were, and what kind of violence they were subjected to. Around half the deaths in 2000 that were due to violence were suicides (815000 deaths), nearly a third were homicides (520000), and about a …
Fluoroquinolone use and resistance of Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2008
Authors: Aristine Cheng, Che-Kim Tan, Chen-Chen Chu, Yu-Tsung Huang, Chun-Hsing Liao, Wang-Huei Sheng, Po-Ren Hsueh
Journal: Journal of Infection (2012)
Chlorosis, anaemia, and anorexia nervosa.
Authors: I S Loudon
Journal: BMJ (1980)

A report is presented of a girl with Graves’ disease, which was diagnosed at the age of 1.7 years. The mother had no thyroid disease. The patient developed signs of hyperthyroidism shortly before her first birthday, and the most prominent manifestations were accelerated skeletal maturation and linear growth, and dilatation of the brain ventricles. The latter manifestation, which has not been reported previously, was reversible upon normalisation of thyroid function with antithyroid treatment for three years.