tbuckley/cabot-search huggingface dataset:
Xenotransplantation unlikely to reduce organ shortage in near future
Authors: Caroline White
Journal: BMJ (2001)

The possibility that diseases may be introduced into the general population by xenotransplantation cannot be ruled out on the basis of current evidence, a new report from the United Kingdom Xenotransplantation Interim Regulatory Authority has concluded.

Xenotransplantation of whole organs is unlikely to solve the shortage of organs for transplantation in the near future, as originally thought, it says. Long term rejection is still a problem, and cloning and genetic modification techniques to address this are still at an early stage.

The authority's third annual report said that while progress has been made, and research …
FG020326, a novel third generation P-glycoprotein inhibitor
Authors: Liwu Fu, Liming Chen, Yongju Liang, Xiaoping Yang
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2281 

Purpose: Successful chemotherapy is limited by multidrug resistance (MDR) phenomenon mainly mediated by the overexpression of P-glycoprotein 170 termed as P-gp that serves as an efflux pump removing various cytostatic drugs from the MDR cells. This study was designed to investigate FG020326, a novel imidazole derivative, reversing MDR in vitro and in vivo. Materials and Methods: We used tetrazolium (MTT) assay in combination with doxorubicin (Dox) accumulation study to evaluate the ability of FG020326 to reverse drug resistance in vitro in two human MDR cell lines MCF-7/adr, KBv200 and their parental drug sensitive cell lines MCF-7 and KB. KBv200 cell xenograft model was established to investigate the effect of FG020326 on reversing MDR in vivo . The function, expression and [3H]azidopine photoaffinity labeling of P-gp were measured to explore the mechanism of reversing MDR. The activity of CYP 3A4 was examined by HPLC with nifedipine as substrate of CYP 3A4. FG020326 pharmacokinetic and pharmacokinetic interaction with Dox in mice was investigated by HPLC. Results: FG020326 significantly enhanced the cytotoxicity of Dox and vincristine (VCR) to MCF-7/adr and KBv200, respectively. FG020326 exhibited at least 3-fold strong reversal MDR activity as positive control agent, verapamil. FG020326 also increased the intracellular accumulation of Dox in MCF-7/adr cells but it didn’t affect that in drug sensitive MCF-7 cells. In mice bearing the MDR KBv200 cell xenografts, co-administration of FG020326 significantly enhanced antitumor activity of VCR (inhibited rate is 54.2%) without increasing the toxicity. KBv200 cells treated by FG020326 results in the enhancement of Rhodamne 123 accumulation, the decrease of the expression of P-gp and the inhibition of [3H]azidopine photoaffinity labeling in concentration-dependent manner. FG020326 did not inhibit the activity of CYP 3A4 until 50μmol/L. FG020326 could expose the mice enough high plasma concentration required for effectiveness while did not affect on the pharmacokinetics of anticancer drug such as Dox. Conclusions : FG020326 was a potent MDR modulator not only in vitro but also in vivo and exhibited the characterizations of the third generation MDR modulator.
Endothelin Receptor Blockade in Congestive Heart Failure
Authors: Tsung O. Cheng
Journal: Circulation (2001)

To the Editor:Of the many new therapeutic agents for slowing the progression of congestive heart failure (CHF), other than antagonizing the renin-angiotensin-aldosterone system, blocking the endothelin receptors seems to be most promising.The two latest reports published in Circulation 1,2 render further support to this exciting concept.Endothelin may contribute to the symptoms associated with CHF.Patients with the lowest exercise capacity, as measured objectively by maximum oxygen consumption (V ˙O2 max) were those who had the highest plasma levels of endothelin-1 at the time of maximal exercise. 3This finding suggests that endothelin may play a role in limiting the ability of the peripheral vasculature to dilate during exercise and, thus, contribute to exercise intolerance in these patients. 4Therefore, the reduced exercise capacity of patients with CHF may be more than a derangement in central hemodynamic variables, such as decreased cardiac output and increased pulmonary artery wedge pressure.Several endothelin receptor antagonists have been developed.Tezosentan 1 is being developed specifically for the short-term intravenous treatment of acute CHF.Studies with LU135252 2 and bosentan 5 indicate that short-term treatment with bolus intravenous or oral dosages is associated with improved systemic
Abstract P114: The Impact of Obesity and Weight Loss on Nocturnal Blood Pressure Dipping
Authors: Arjun K Pandey
Journal: Circulation (2015)

In healthy individuals, sleep is associated with at least a 10% dip in Blood Pressure (BP). A lack of nocturnal BP dipping (LND) or a rise of BP nocturnally (RBPN) is associated with an increased risk of many cardiovascular diseases including stroke, heart failure and renal failure. Limited therapies exist for individuals with a LND or a RBPN.  In this study, we examine a potential correlation between obesity and a lack of nocturnal BP dipping as well as the impact of weight loss on nocturnal BP patterns. We assessed the hypothesis that elevated BMI would correlate to LND or RBPN and that weight loss would improve nocturnal BP patterns.  We recruited 30 volunteers with a LND pattern, 30 volunteers with a RBPN pattern and 20 control volunteers, with a healthy nocturnal BP dip. Individuals with sleep apnea were excluded. 24-hour Ambulatory BP Monitor readings and BMI measurements were performed before and after a 2 month dietary and lifestyle intervention to reduce weight, employing the DASH diet and lifestyle program.  At baseline we observed a negative correlation between BMI and nocturnal BP dipping: The average BMI of the control group was 28.1 kg/m2. The average BMI of the LND group was 30.3 kg/m2 (mildly obese). The average BMI of the RBPN group was 35.3 kg/m2 (severely obese) (p  After the 2 month intervention, we observed that individuals who achieved a weight loss of 5% or more (who previously experienced abnormalities in nocturnal dip) had an average 8.4% dip in nocturnal BP, representing a significant improvement in nocturnal BP patterns. Those who did not achieve a 5% weight loss & those who gained weight had blood pressure that rose by 3.2% at night on average (p  The findings of this study suggest that obesity may contribute to nocturnal BP abnormalities and weight loss, through diet and lifestyle modifications, may improve nocturnal blood pressure patterns. The clinical implications of this strategy on the development or progression of cardiovascular diseases remain to be determined.
<i>The Doctor</i>: For Life and at the End of Life
Authors: Joanne Lynn
Journal: Annals of Internal Medicine (2015)

Letters2 June 2015The Doctor: For Life and at the End of LifeJoanne Lynn, MD, MA, MSJoanne Lynn, MD, MA, MSFrom Altarum Institute, Center for Elder Care and Advanced Illness, Washington, DC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5080-2 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Most persons in the United States will now die of multiple chronic conditions, with the timing of death being unclear until the last few days. Persons alive at 70 years of age face nearly 3 years of self-care disability in the last phase of their lives, with a series of private arrangements and health care supports. It seems that "palliative care" should not be mostly the province of specialists but a highly valued skill of virtually all physicians. Furthermore, it seems that Pizzo's comments (1) on the last part of life should focus more on nursing homes, ...Reference1. Pizzo PA. The Doctor: for life and at the end of life. Ann Intern Med. 2015;162:228-9. [PMID: 25486216] doi:10.7326/M14-2399 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Joanne Lynn, MD, MA, MSAffiliations: From Altarum Institute, Center for Elder Care and Advanced Illness, Washington, DC.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0137. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Doctor: For Life and at the End of Life Philip A. Pizzo The Doctor: For Life and at the End of Life Philip A. Pizzo The Doctor: For Life and at the End of Life Joseph Kash The Doctor: For Life and at the End of Life Joseph Kash Metrics 2 June 2015Volume 162, Issue 11Page: 804KeywordsAgingConflicts of interestDisabilitiesDisclosureHealth careLong-term careNursing homesPalliative care ePublished: 2 June 2015 Issue Published: 2 June 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 11275: Paradoxical Interventricular Septal Motion Predisposes to Late Gadolinium Enhancement of Ventricular Insertion Points in Pulmonary Hypertension
Authors: Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Asuka Yamada, Masaharu Nishimura
Journal: Circulation (2011)
Abstract 12880: Is Paradoxical Low Gradient Severe Aortic Stenosis a More Advanced form of Aortic Stenosis? New Insights Gained from the Measurement of Valvular Calcium Content by Use of 256-slice MDCT
Authors: Jamila Boulif, Bernhard L Gerber, Agnes Pasquet, David Vancraeynest, Sophie Pierard, Julie Melchior, Christophe de Meester, Siham Lazam, Jean-Louis Vanoverschelde
Journal: Circulation (2013)

Background: Paradoxical low gradient severe aortic stenosis (PLG SAS) is a recently described subset of aortic stenosis (AS) the clinical and prognostic implications of which are a matter of intens...
Abstract 19634: Deletion of Semaphorin 4d Protects Against Myocardial Ischemia-reperfusion Injury in Mice
Authors: Li Zhu, Xiaohui Liu, Dongzhou Xu, Tao Wang, Qiongyu Lu, Lijie Ren, Atsushi Kumannogoh, Lawrence Brass
Journal: Circulation (2014)

Semaphorin 4D (Sema4D) is expressed on the surface of many types of cells including platelets and T-cells. We have previously shown that Sema4D can be shed from the surface of activated platelets by the metalloprotease ADAM17 and that deleting Sema4D in mice inhibits platelet function and reduces lipid deposition in the aorta. Here we asked whether loss of Sema4D expression protects heart in an ischemia/reperfusion model in which the LAD is occluded for 45 min and then reperfused for 1 hour. The results show that there was no difference between Sema4D(-/-) and control (WT) mice with respect to heart size or the area at risk for infarction. However, we found a substantial decrease in infarct size when adjusted for either heart size (10.7% versus 30.2%, p
Book: Ethnicity: An Agenda For Mental Health
Authors: G. Simon
Journal: BMJ (2000)

Eds Dinesh Bhugra, Veena Bahl Gaskell (Royal College of Psychiatrists), £25, pp 240 ISBN 1 901242 15 Rating:![Graphic][1]</img> ![Graphic][2]</img> The chapters in this book attempt to address several timely questions: Are diagnostic categories developed in Britain and the United States appropriate for other national or ethnic groups? Why are certain ethnic groups overrepresented in secure inpatient facilities and underrepresented among those receiving outpatient care? How can the demand for diverse and non-traditional mental health services be reconciled with the mandate to provide services proved in randomised controlled trials? While the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Abstract P262: Evidence for association between SH2B1 gene variants and glycated hemoglobin in non-diabetic European American young adults: The Add Health study
Authors: Leslie A Lange, Misa Graff, Ethan M Lange, Kristin M Young, Kathleen M Harris, Andrea S Richardson, Karen L Mohlke, Kari E North, Penny Gordon Larsen
Journal: Circulation (2014)

Introduction: Glycated hemoglobin (HbA1c) is a marker of long-term glycemic control, and elevated HbA1c is a risk factor for type 2 diabetes and cardiovascular disease. Few genome-wide association studies(GWAS) have been performed for HbA1c, although very large scale GWAS for obesity, a related trait, have identified multiple loci that have been widely replicated. We tested 43 single nucleotide polymorphisms (SNPs) from 41 well-established obesity susceptibility gene regions for association with HbA1c in a nationally representative sample of European American (EA), African American (AA) and Hispanic American (HA) young adults. Methods: We performed association analysis in race-stratified models using data from participants (age 24-34 years, median age=28 years) from the National Longitudinal Study of Adolescent Health (Add Health) Study (n = 5641 EA; n = 1740 AA; n = 1444 HA) without type 2 diabetes. We tested for additive genotype effects at each locus using linear mixed models, including a random intercept for school and family clusters, and two levels of covariate adjustment (model 1: age, sex, smoking, and geographic region; model 2: model 1 covariates plus BMI). We used Bonferroni adjustment for 43 SNPs and considered P &lt; 0.0011 to be statistically significant. Results: Means (SD) for HbA1c % across the sample were 5.4(0.3) in EA, 5.7(0.4) in AA, and 5.5(0.3) in HA. We observed significant evidence for association with HbA1c for two SNPs near SH2B1 in EAs (rs4788102, P = 2.2x10-4; rs7359397, P = 9.8x10-4) for the model 1 adjustment, although both results were slightly attenuated after additional adjustment for BMI (rs4788102, P = 1.7x10-3; rs7359397, P = 4.6x10-3). No SNPs reached statistical significance after multiple test correction in either AAs or HAs. SH2B1 rs4788102 was nominally significant in AAs for the BMI-adjusted model (P = 0.02), although the estimated direction of effect was in the opposite direction as that observed in EAs. Conclusions: These results suggest that polymorphisms in the obesity gene SH2B1 , for which rare deletions and mutations have been observed in obese individuals with extremely high insulin resistance, are associated with HbA1c in EA young adults. Our findings further suggest these associations are largely independent of BMI.
CD8+ T cells mediate skin allergy to amoxicillin in a mouse model
Authors: A. Rozieres, M. Vocanson, K. Rodet, J. Benetiere, J. Bienvenu, F. Berard, A. Hennino, J.‐F. Nicolas
Journal: Allergy (2010)

Delayed allergic skin reactions to drugs are common iatrogenic diseases mediated by activation of specific T cells in the skin.To better understand the role of T cells in these diseases, we developed a mouse model of drug allergy induced by skin sensitization to amoxicillin (amox), a penicillin antibiotic frequently involved in delayed drug allergy.Whereas wild-type mice could not be sensitized to amox, CD4+ T-cell-deficient mice developed an amox-specific allergic skin response, mediated by IFN-gamma-producing CD8+ T cells. Amox-specific CD8+ T cells, induced in lymphoid organs at a high frequency during sensitization, were recruited in the skin upon challenge. CD8+ T cells were effectors of the allergic skin reaction to amox as in vivo treatment with depleting anti-CD8 mAbs abrogated the skin inflammatory reaction and as purified CD8+ T cells could adoptively transfer the allergic response to naive recipients.CD8+ T cells mediate penicillin skin allergy.
Preclinical pharmacology of novel substituted benzimidazoles - potent inhibitors of poly (ADP-ribose) polymerase
Authors: CR Calabrese, HD Thomas, MA Batey, T Boritzki, K Zhang, AW White, NJ Curtin, RJ Griffin, BT Golding, Z Hostomsky, AH Calvert, Newell
Journal: Clinical Cancer Research (1999)
13. Hot Spots for rAAV2 Vector Integration in Mice
Authors: Xiaodong Zhu, Juan Li, Xiao Xiao
Journal: Molecular Therapy (2004)

The inverted terminal repeats (ITRs) of Adeno-associated virus (AAV) play essential roles in viral DNA replication, packaging and integration. Flanking a coding region, the two ITRs are the only viral elements left in recombinant AAV (rAAV) vectors for gene delivery. The objective of this work is to dissect ITR elements to understand further how ITRs function, which will also help us to design better AAV vectors. Each 145 nt AAV ITR is composed of six sub-regions (A-B-B'-C-C'-A') forming a T-shaped self-base paired structure. To characterize the role of each ITR sub-region in viral DNA replication, packaging and integration, we generated a series of ITR deletion mutants from a pDD plasmid which has a single ITR flanked by two D regions containing the terminal resolution site. Deletions of B-B', C-C', or both does not affect viral DNA replication or packaging into infectious virus. Even when B-B', C-C', plus a part of the A region which does not include the Rep-binding site are all deleted, this ITR mutant can produce functional virus at an efficiency comparable to the parental plasmid containing a complete ITR. As expected, further deletion into the Rep-binding site abolishes viral DNA replication. Our quantitative analysis also shows that deletions of B-B', C-C', and A region not including Rep-binding site do not affect viral DNA integration into host chromosomes. These results suggest that the T-shaped secondary structure is dispensable.
Erectile Dysfunction in Obese Men—Reply
Authors: Katherine Esposito, Francesco Giugliano, Dario Giugliano
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Link With Heart Disease
Authors: Rebecca Voelker
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2745: Pharmacological characterisation of cell active inhibitors of Poly(ADP-ribose) glycohydrolase (PARG)
Authors: Dominic James, Allan Jordan, Nicola Hamilton, Alison McGonagle, Kate Smith, Alexandra Stowell, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie
Journal: Cancer Research (2014)

Abstract Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. Total PARG deficiency leads to cell death whilst PARG depletion, using RNAi, leads to pleiotropic effects such as PAR chain persistence, progression of single- to double-strand DNA lesions and NAD+ depletion. Whilst efforts to develop small molecule inhibitors of PARG activity have generally been hampered by poor physiochemical properties, off-target pharmacology and a lack of cell permeability, we have now developed a series of PARG inhibitors which have proved to be useful biological tool compounds. Displaying selective activity in both biochemical and, more importantly, cellular assays of PARG function, these derivatives have allowed an exploration of the phenotypes resulting from reversible, pharmacological PARG inhibition. Citation Format: Dominic James, Allan Jordan, Nicola Hamilton, Alison McGonagle, Kate Smith, Alexandra Stowell, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie. Pharmacological characterisation of cell active inhibitors of Poly(ADP-ribose) glycohydrolase (PARG). [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 2745. doi:10.1158/1538-7445.AM2014-2745
Providing letters to patients
Authors: N Hallowell, M D Lewars, N. Coni, J A Eaden, B Ward, J F Mayberry
Journal: BMJ (1998)

Editor—Essex raises some interesting points about the value of giving patients a written summary of their consultation.1 The practice of sending patients a letter summarising their consultation is very common in genetic counselling. 

A colleague and I have completed a qualitative interview study exploring patients’ attitudes about and their use of written summaries of their genetic consultations for hereditary breast and ovarian cancer.2 Like Essex, we found that patients responded very positively to these letters. Altogether 37 (93%) out of 40 patients in the sample said that the summary letter aided their understanding or recall of information that had been given in the clinic, or both. The written summary was also perceived as valuable because it could be shown to other clinicians to support the patient’s case for gaining access to breast or ovarian screening programmes, it reassured patients that they were taking appropriate action, and it contained information about other relatives’ risks. In addition, the written summary was also perceived as a useful tool for disseminating genetic information to other family members; 34 (85%) out of 40 patients said they had used, or intended to use, the written summary of their counselling session to facilitate the communication of genetic information to other biological relatives. 

On the basis of our findings we suggest that genetic counsellors send patients a letter summarising their consultations as this may result not only in an increase in the patient’s understanding, but may prevent the miscommunication of genetic information within the family. However, we feel that clinicians should be aware that providing patients with a written summary of their consultation may also have negative consequences. It may generate an inappropriate demand for referrals to genetic clinics from family members at low risk, and, more importantly, reading a letter written to the patient may cause needless anxiety among low risk family members.