tbuckley/cabot-search huggingface dataset:
Oxidative Mitochondrial DNA Damage and Deletion in Hepatocytes of Rejecting Liver Allografts in Rats: Role of TNF-α *
Authors: Yuichi Nagakawa, George Melville Williams, Qizhi Zheng, Akihiko Tsuchida, Tatsuya Aoki, Robert A. Montgomery, Andrew S. Klein, Zhaoli Sun
Journal: Hepatology (2005)

Abstract An orthotopic liver transplant model in the rat was used to evaluate the role of tumor necrosis factor alpha (TNF-α) in liver transplant rejection. There were significantly increased levels of TNF-α mRNA and parallel increases in 8-hydroxy-2′ deoxyguanosine (8-OHdG) indicative of oxidative DNA damage present 7 to 12 days after transplantation. Cells staining positively for 8-OHdG were localized to the cytoplasm of hepatocytes adjacent to the TNF-α expressing inflammatory cells in the portal areas or in patches surrounded by inflammatory cells in the hepatic sinusoids. Significantly more cells staining for 8-OHdG were found in the allogeneic grafts that were strongly rejected than in the syngeneic controls or in the grafts placed in species that accepted the allograft permanently after a rejection episode. TUNEL reactivity lagged 2 days behind peak reactivity for 8-OHdG. On day 12 after transplantation, many cells stained for both 8-OHdG and TUNEL, indicating that the cells suffering oxidative DNA injury were undergoing apoptosis or death. Oxidative injury resulted in mtDNA deletion consisting of 4,834 base-pairs. Studies of hepatocytes cultured from normal rats displayed dose-dependent relationships between TNF-α concentration and 8-OHdG and mtDNA mutation. Repetitive intraperitoneal injection of Enbrel, a TNF receptor blocker, significantly decreased hepatocyte 8-OHdG levels and the frequency of deleted mtDNA while greatly extending graft survival time. In conclusion , the data presented implicate TNF-α as being capable of causing oxidative DNA damage and mtDNA mutation in hepatocytes. (Hepatology 2005;42:208–215.)
Detection of New-Onset Choroidal Neovascularization Using Optical Coherence Tomography
Authors: Diana V. Do, Emily W. Gower, Sandra D. Cassard, David Boyer, Neil M. Bressler, Susan B. Bressler, Jeffrey S. Heier, Joan L. Jefferys, Lawrence J. Singerman, Sharon D. Solomon
Journal: Ophthalmology (2012)
Specific β <sub>2</sub> AR Blocker ICI 118,551 Actively Decreases Contraction Through a G <sub>i</sub> -Coupled Form of the β <sub>2</sub> AR in Myocytes From Failing Human Heart
Authors: Haibin Gong, Hong Sun, Walter J. Koch, Thomas Rau, Thomas Eschenhagen, Ursula Ravens, Jürgen F. Heubach, Dawn L. Adamson, Sian E. Harding
Journal: Circulation (2002)

Background — We have observed direct (noncatecholamine-blocking) negative inotropic effects of the selective β 2 -adrenoceptor (AR) antagonist ICI 118,551 in myocytes from failing human ventricle. In this study we characterize the effect in parallel in human myocytes and in myocytes from animal models where β 2 ARs or G i proteins are overexpressed. Methods and Results — Enzymatically isolated, superfused ventricular myocytes were exposed to βAR agonists and antagonists/inverse agonists, and contraction amplitude was measured. ICI 118,551 decreased contraction in ventricular myocytes from failing human hearts by 45.3±4.1% (n=20 hearts/31 myocytes, P &lt;0.001) but had little effect in nonfailing hearts (4.9±4%, n=5 myocytes/3 hearts). Effects were significantly larger in patients classified as end-stage. Transgenic mice with high β 2 AR number and increased G i levels had normal basal contractility but showed a similar negative inotropic response to ICI 118,551. Overexpression of human β 2 AR in rabbit myocytes using adenovirus potentiated the negative inotropic effect of ICI 118,551. In human, rabbit, and mouse myocytes, the negative inotropic effects were blocked after treatment of cells with pertussis toxin to inactivate G i , and overexpression of G i α 2 induced the effect de novo in normal rat myocytes. Conclusions — We hypothesize that ICI 118,551 binding directs the β 2 AR to a G i -coupled form and away from the G s -coupled form (ligand-directed trafficking). ICI 118,551 effectively acts as an agonist at the G i -coupled β 2 AR, producing a direct negative inotropic effect. Conditions where β 2 ARs are present and G i is raised (failing human heart, TGβ 2 mouse heart) predispose to the appearance of the negative inotropic effect.
June Almeida (née Hart)
Authors: Joyce Almeida
Journal: BMJ (2008)

June Almeida (nee Hart) was internationally renowned virologist who pioneered new methods for viral imaging and diagnosis.

She was brought up in a flat in a tenement building in Glasgow, and, although shining academically, left school at 16 without funding to go to university. Nevertheless, she became an internationally renowned virologist whose skills in electron microscopy enabled her not only to identify viruses whose fine structure had hitherto been unknown but also to shed light on the pathogenesis of viral infections, and to pioneer and improve methods for viral diagnosis.

On leaving school in 1947, June became a laboratory technician in histopathology at the Glasgow Royal Infirmary on a salary of 25 shillings a week, and then got a job at St Bartholomew’s Hospital, London, working in the same discipline. She then married an artist and emigrated to Canada, where, by chance, there was a vacancy in the Ontario Cancer Institute in Toronto for an electron microscopy technician. Her skills soon became apparent, and, despite having no formal qualifications, …
Infection, Anergy and Cell-Mediated Immunity
Authors: Howard L. Bleich, Emily S. Boro, Fred S. Kantor
Journal: New England Journal of Medicine (1975)

THE purpose of this presentation is to discuss the mechanisms of anergy, defined here as a patient's failure to react to skin tests to which he has previously reacted. Anergy is differentiated from tolerance in that anergy is nonspecific, is usually transient and occurs in the presence of serum antibodies against antigens to which the patient is anergic. Recent experiments with bacterial and viral systems show the ubiquitous association of anergy with infection and hypersensitivity. These experiments suggest that anergy is a normal aspect of the immune response, sometimes so abbreviated as to be undetected, and that clinically detected anergy . . .
Aortic stenosis in children. Experience with echocardiographic prediction of severity.
Authors: R A Blackwood, K R Bloom, C M Williams
Journal: Circulation (1978)

Fifty-six children with aortic stenosis were investigated both by echocardiography and cardiac catheterization. The ratio of end-systolic wall thickness (Ws) to internal diameter (LVES) across the minor axis of the LV as determined by echocardiography and multiplied by a factor of 245 predicts left ventricular pressure (r = 0.83). Subtracting the arm systolic blood pressure from the predicted intraventricular systolic pressure (PISP) gives a predicted systolic pressure gradient (r = 0.91). The technique is found to be useful for both initial and sequential noninvasive assessment of aortic stenosis with normal LV function irrespective of the level of obstruction. It is shown to apply equally well to wide range of LV pressures, is independent of volume load, and is useful in predicting small gradients. Some common problems encountered with the measurements are examined in detail.
An Application of Computerized Asthma-Specific QOL in Korean Asthmatics
Authors: Kim Mi-Ae, Ye Young-Min, Park Jung-Won, Lee Jae-Hyun, Lee Soo-Keol, Kim Cheol-Woo, Jung Ki-Suck, Kim Joo-Hee, Yoo Hye-Soo, Lee Seung Ihm, Kim Seung-Hyun, Shin Yoo Seob, Park Hae-Sim
Journal: Journal of Allergy and Clinical Immunology (2013)
Liver Transplantation in Children Using Organ Donation After Circulatory Death
Authors: Johnny C. Hong, Robert Venick, Hasan Yersiz, Prawat Kositamongkol, Fady M. Kaldas, Henrik Petrowsky, Douglas G. Farmer, Vatche Agopian, Sue V. McDiarmid, Jonathan R. Hiatt, Ronald W. Busuttil
Journal: JAMA Surgery (2013)

IMPORTANCE While orthotopic liver transplantation (OLT) is a durable life-saving treatment for patients with irreversible liver disease, the waiting list mortality rate for children younger than 6 years is 4 times higher than for children aged 11 to 17 years and adults owing to scarce availability of size-appropriate grafts for transplantation.OBJECTIVE To compare long-term outcomes for children (aged Յ18 years) undergoing OLT using grafts from donation after circulatory death (DCD) and donation after brain death (DBD). DESIGN, SETTING, AND PARTICIPANTSRetrospective study using case-control matched groups at a university transplant center.All patients aged 18 years and younger who underwent OLT using DCD organs between February 1, 1990, and November 30, 2010, at the University of California, Los Angeles, were matched in a 1 to 3 ratio with patients who received primary OLT from DBD donors within a 12-month period.Other matching criteria included recipient age, weight, cause of liver disease, and acuity of illness.Outcomes after OLT were compared for DCD (n = 7) and DBD (n = 21) donors.The median follow-up was 4.5 years. MAIN OUTCOMES AND MEASURESThe primary outcome measure was graft failure-free survival; the secondary end point was the development of ischemic cholangiopathy. RESULTSComparing DCD and DBD groups, recipient median age (28.4 vs 20.1 months, respectively; P = .80),weight (12.0 vs 11.6 kg, respectively; P = .87),Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score (19 vs 11, respectively; P = .48),and donor age (24.0 vs 13.1 months, respectively; P = .72)were similar.For the DCD donors, the median donor warm ischemia duration was 24 minutes.Liver test results were similar for both groups at 1 week and 3, 6, and 12 months following OLT.Ten-year patient and graft survival rates for both DCD and DBD were 100%.Neither ischemic cholangiopathy nor vascular complications occurred in the DCD group.Biliary anastomotic strictures occurred in 1 DCD patient and 3 DBD patients.CONCLUSIONS AND RELEVANCE Our study showed excellent long-term outcomes with liver transplantation in children using DCD organs.Use of liver grafts procured after circulatory death is an effective approach to expand the donor pool and remains an untapped resource for children with end-stage liver disease.
TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development
Authors: Anne Grosse-Wilde, Oksana Voloshanenko, S. Lawrence Bailey, Gary M. Longton, Uta Schaefer, Andreea I. Csernok, Günther Schütz, Erich F. Greiner, Christopher J. Kemp, Henning Walczak
Journal: Journal of Clinical Investigation (2008)

TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in established tumor cell lines but not nontransformed cells. Herein, we demonstrate a role for the apoptosis-inducing TRAIL receptor (TRAIL-R) as a metastasis suppressor. Although mouse models employing tumor transplantation have shown that TRAIL can reduce tumor growth, autochthonous tumor models have generated conflicting results with respect to the physiological role of the TRAIL system during tumorigenesis. We used a multistage model of squamous cell carcinoma to examine the role of TRAIL-R throughout all steps of tumor development. DMBA/TPA-treated TRAIL-R–deficient mice showed neither an increase in number or growth rate of benign papillomas nor an increase in the rate of progression to squamous cell carcinoma. However, metastasis to lymph nodes was significantly enhanced, indicating a role for TRAIL-R specifically in the suppression of metastasis. We also found that adherent TRAIL-R–expressing skin carcinoma cells were TRAIL resistant in vitro but were sensitized to TRAIL upon detachment by inactivation of the ERK signaling pathway. As detachment from the primary tumor is an obligatory step in metastasis, this provides a possible mechanism by which TRAIL-R could inhibit metastasis. Hence, treatment of cancer patients with agonists of the apoptosis-inducing receptors for TRAIL may prove useful in reducing the incidence of metastasis.
Decreased Ferroportin Promotes Myeloma Cell Growth and Osteoclast Differentiation
Authors: Zhimin Gu, He Wang, Jiliang Xia, Ye Yang, Zhendong Jin, Hongwei Xu, Jumei Shi, Ivana De Domenico, Guido Tricot, Fenghuang Zhan
Journal: Cancer Research (2015)

Abstract Iron homeostasis is disrupted in multiple myeloma, a difficult-to-cure plasma cell malignancy with lytic bone lesions. Here, we systematically analyzed iron gene expression signature and demonstrated that mRNA expression of iron exporter ferroportin (FPN1) is significantly downregulated in myeloma cells and correlates negatively with clinic outcome. Restoring expression of FPN1 reduces intracellular liable iron pool, inhibits STAT3-MCL-1 signaling, and suppresses myeloma cells growth. Furthermore, we demonstrated that mRNA of FPN1 is also downregulated at the initial stages of osteoclast differentiation and suppresses myeloma cell–induced osteoclast differentiation through regulating iron regulator TFRC, NF-κB, and JNK pathways. Altogether, we demonstrated that downregulation of FPN1 plays critical roles in promoting myeloma cell growth and bone resorption in multiple myeloma. Cancer Res; 75(11); 2211–21. ©2015 AACR.
Electrophysiological effects of left ventricular hypertrophy. Effect of calcium and potassium channel blockade.
Authors: P R Kowey, T D Friechling, J Sewter, Y Wu, A Sokil, J Paul, J Nocella
Journal: Circulation (1991)

To define the arrhythmogenic effects of left ventricular hypertrophy (LVH) in the intact heart, we carried out a detailed electrophysiological assessment in our previously validated feline aortic-banding model and then tested the effects of agents that blocked either the slow inward calcium or voltage-dependent potassium channel.We measured intraventricular and interventricular conduction times, excitability thresholds, ventricular effective refractory periods, and monophasic action potential duration at several sites in cats with LVH as well as in concurrent control (sham-operated) cats. In addition, we assessed vulnerability to ventricular arrhythmia using direct measurement of ventricular fibrillation (VF) thresholds and by standard techniques of programmed stimulation. Despite finding no difference between LVH and sham-operated cats in mean values for several electrophysiological parameters, the former group was significantly more vulnerable to VF, with more spontaneous VF and lower VF thresholds. Compared with the sham controls, LVH cats also had a greater dispersion of effective refractory period (35 +/- 11 versus 12 +/- 4 msec, p less than 0.01) and monophasic action potential duration at 90% repolarization (69 +/- 25 versus 39 +/- 7 msec, p less than 0.02). Verapamil had no significant effect on these electrophysiological parameters, nor did it affect VF threshold. However, risotilide, an inhibitor of the voltage-dependent potassium channel, narrowed dispersion of the effective refractory period and monophasic action potential duration concomitant with a marked reduction in ventricular vulnerability.LVH has a pronounced effect on dispersion of refractoriness and repolarization and renders the ventricle more vulnerable to fibrillation. Blockade of the voltage-dependent potassium channel, but not the slow inward calcium channel, narrows the dispersion of recovery of excitability and protects against VF.
IM-10 * EFFECTS OF T-CELL TGF- SIGNALING ABROGATION ON SURVIVAL IN PEDIATRIC GLIOMA
Authors: J. Breunig, M. Danielpour, R. Levy, M. Dutra-Clarke
Journal: Neuro-Oncology (2015)

We have been investigating the effects of immune system modulation on brain tumor survival in animal models of pediatric malignancies. For example, TGF-β is produced by various tumor types and dampens the response of the immune system, preventing recognition of tumor cells. Thus, we crossed mice with T-cell-specific TGF-β blockade (CD4-TGFβRII-DNR) with a mouse model of medulloblastoma (SmoA1 transgenic mice) and analyzed offspring. We noted dramatic infiltration of T cells into the tumor and coincident improvement in survival of these mice. Furthermore, there was a striking change in T cell phenotype—notably a large increase in memory T cells in double transgenic mice, which are in principle able to mount anti-tumor immunity. We've been employing a novel piggyBac model of forebrain glioma to rapidly generate tumors from patient driver genes. Interestingly, using genome-wide analysis, many members of the TGF-β ligand family are upregulated by tumor cells and these secreted ligands appear to be the principle immunosuppressive molecules expressed by the tumor propagating population. Given the survival-promoting role of T cell TGF-β signaling blockade in our medulloblastoma model, we have generated de novo tumors in CD4-TGFβRII-DNR mice using our in vivo piggyBac system and are investigating the applicability of this strategy in pediatric forebrain glioma.
The Inference of Stepwise Changes in Substitution Rates Using Serial Sequence Samples
Authors: Alexei Drummond, Roald Forsberg, Allen G. Rodrigo
Journal: Molecular Biology and Evolution (2001)

It is frequently true that molecular sequences do not evolve in a strictly clocklike manner. Instead, substitution rate may vary for a number of reasons, including changes in selection pressure and effective population size, as well as changes in mean generation time. Here we present two new methods for estimating stepwise changes in substitution rates when serially sampled molecular sequences are available. These methods are based on multiple rates with dated tips (MRDT) models and allow different rates to be estimated for different intervals of time. These intervals may correspond to the sampling intervals or to a priori--defined intervals that are not coincident with the times the serial samples are obtained. Two methods for obtaining estimates of multiple rates are described. The first is an extension of the phylogeny-based maximum-likelihood estimation procedure introduced by Rambaut. The second is a new parameterization of the pairwise distance least-squares procedure used by Drummond and Rodrigo. The utility of these methods is demonstrated on a genealogy of HIV sequences obtained at five different sampling times from a single patient over a period of 34 months.
Incidental Visualization of Hepatic Hemangioma During Tc-99m (v) DMSA, Tl-201, and Tc-99m MDP Imaging
Authors: ISIK ADALET, MEHMET KOCAK, HARIKA OGUZ, FARUK ALAGOL, SEMA CANTEZ
Journal: Clinical Nuclear Medicine (1995)

The scintigraphic diagnosis of hemangloma is often made by demonstrating the accumulation of Tc-99 labeled RBCs. There have been very few reports about false-positive localization of hepatic hemangioma during scintigraphy. The authors present a patient with increased accumulation in the liver mimicking a liver metastasis on Tc-99m (V) DMSA, TI-201, and Tc-99m MDP imaging. These findings were in accordance with the information obtained from the patient's history that he had a hepatic hemangioma.
No Good Deed: A Story of Medicine, Murder Accusations, and the Debate Over How We Die
Authors: Natasha Bagdasarian
Journal: JAMA (2010)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Junior doctors asked for more data on hours worked
Authors: L Beecham
Journal: BMJ (1994)

The BMA's Junior Doctors Committee is asking all hospital junior doctors to supply details of the actual hours they work and the intensity of work so that comparisons can be made with the returns from regional task forces.

The committee, which is asking for questionnaires to be returned by 30 November, believes that there are still major problems in reaching the target set for 31 December. The government's figures are based on the hours for which junior doctors are contracted to work and do not, according to the JDC, reflect the hours doctors are working once time spent on early starts, late finishes, and cover for colleagues' absences is taken into account.

Under the new deal on doctors' hours no doctors should be on their feet and working for more than an average of 56 hours a week after that date. The hours should be reduced to 64 hours for those on a partial shift and to 72 hours for those on an on call rota.

One of the questions asks for information about the amount of rest doctors get when on call to show whether or not the majority of doctors are working an appropriate working pattern and being paid at an appropriate rate.

If they are able to do so the JDC would like doctors to name their base hospital or NHS trust so that details of problem posts and specialties can be sent to the relevant task force.

A new subcommittee of the BMA's Central Consultants and Specialists Committee has been formed to represent clinical and medical directors. …
Abstract 4621: Zfra regulates protein degradation and provides strong prevention against skin cancer
Authors: Nan-Shan Chang
Journal: Cancer Research (2011)

Abstract Zinc finger-like protein for regulating apoptosis (Zfra) is a 31-amino-acid protein, which participates in the mitochondrial pathway of apoptosis and affects the functions of tumor suppressors WWOX and p53. Here, synthetic full-length Zfra1-31, or truncated Zfra4-10, undergoes ladder-like self-polymerization by greater than 20-100 fold when phosphate ions are present in solutions (without catalytic enzymes). Upon encountering with Zfra, certain cellular proteins become “zfrated” and undergo degradation independently of the ubiquitin/proteasome system. Transiently overexpressed Zfra induces apoptosis of many types of cancer cells. Most strikingly, pre-injection of Zfra1-31 or Zfra4-10 via tail veins protects nude mice from growing cancer xenografts (e.g. melanoma and skin basal cell carcinoma cells). Alteration of Ser8 abolishes self-polymerization and cancer prevention, suggesting an essential role of Ser8 in protein zfration and degradation and cancer prevention. 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 4621. doi:10.1158/1538-7445.AM2011-4621