tbuckley/cabot-search huggingface dataset:
Abstract 6: S1, a Bid-like BH3 mimetic, induces apoptosis by dynamic change of Mcl-1 and dependent on Bak, not Bax
Authors: Song Ting, Zhang Zhi Chao, Chang Xi Long
Journal: Cancer Research (2011)

Abstract Mcl-1 is a unique anti-apoptotic member of Bcl-2 family. Its expression has been demonstrated to seriously impede the most authentic BH3 mimetic ABT-737-induced apoptosis in multiple cancer cell lines. S1, which has been previously identified as a pan-Bcl-2 inhibitor and pure BH3 mimetic by our group, was investigated here to challenge Mcl-1's protection. Cell viability assay and apoptosis assay showed S1 exhibits robust anticancer effectiveness in three selected ABT-737-resistant cancer cell lines, SMMC-7721, HCT116 and K562 cells. In contract with ABT-737, S1-induced apoptosis is regardless of the baseline of Mcl-1 expression. Interestingly, it dynamically modulates Mcl-1 through a combination of proteasome and caspase-mediated pathway and this dynamical change is associated well with the resistance, apoptosis onset, and apoptosis burst out induced by S1. To investigate how Mcl-1 dynamics is related with apoptosis at molecular level, we performed time-sequence and dose-dependent analysis of cell viability, western blot, and co-immunoprecipitation experiments. We found the trafficking of Bcl-2 family members determines Mcl-1 dynamical change and in turn apoptosis. First of all S1 untethers Bax and Bim from Bcl-2, but Bim shifts to Mcl-1 which stabilizes Mcl-1 and enforces the binding with Bak. Only when Bak is released by enough dose of S1 or enough exposure time is Mcl-1 downregualted to allow apoptosis occur. Using shRNA, we identified both S1-induced apoptosis and Mcl-1 dynamical modulation depend on Bak, not Bax. As such, much distinct function of Bax and Bak in the S1-induced pathway was illustrated. While Bax can be fully compensated for by Bak, Bak could be partly compensated for by Bax. Consistently, Bax-deficient DU145 cell is sensitive to S1, whereas Bak-mutant MKN-28 cells is much more resistant. NMR analyses revealed that S1 highly mimic tBid to target the BH3-binding pocket of Mcl-1. Cytochrome c release assay in purified DU145 mitochondrial testified a nicely structural-to-functional mimic of tBid, but not Bim. The Bid-like property is also consistent with its Bak-dependent apoptosis induction. The in vitro model could be extended to an in vivo mouse xenograft model that S1 induces apoptosis through Mcl-1 dynamical modulation and released Bak is the biomarker of apoptosis. In conclusion, S1 could be a highly potent therapeutic molecule for the treatment of Mcl-1-driven cancer cells with a mechanism-based model. Bak could serve as a biomarker to specify cancer cells sensitive to S1. In addition, the highly tBid/Mcl-1 binding mimic property could be used to probe the sophisticated network of Bcl-2 family. 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 6. doi:10.1158/1538-7445.AM2011-6
Chronic Cardiac Compression (Chronic Constrictive Pericarditis)
Authors: J. R. CHAMBLISS, E. J. JARUSZEWSKI, B. L. BROFMAN, J. F. MARTIN, H. FEIL
Journal: Circulation (1951)

Sixty-one patients with chronic cardiac compression were studied critically, the largest series in the literature. All patients had pericardiectomy performed. The operative mortality was 18 per cent. Satisfactory result was obtained 72.1 per cent of the patients operated. Tuberculosis was the cause in 28.2 per cent. In most of the remaining cases the etiology was obscure. The symptoms, physical signs, and laboratory examinations are reported. The physiologic studies after operation demonstrate improved cardiac filling and emptying. The importance of diagnosis and the desirability of pericardiectomy are stressed. With antibiotic therapy there is less risk in operating patients with active infection and the compression syndrome.
Progress and Promise of Diabetes Research
Authors: Christopher D. Saudek
Journal: JAMA (2002)

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
Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression
Authors: Konstantin Levay, Vladlen Z. Slepak
Journal: Journal of Clinical Investigation (2007)

We show here that the process of megakaryocytic differentiation requires the presence of the recently discovered protein tescalcin. Tescalcin is dramatically upregulated during the differentiation and maturation of primary megakaryocytes or upon PMA-induced differentiation of K562 cells. This upregulation requires sustained signaling through the ERK pathway. Overexpression of tescalcin in K562 cells initiates events of spontaneous megakaryocytic differentiation, such as expression of specific cell surface antigens, inhibition of cell proliferation, and polyploidization. Conversely, knockdown of this protein in primary CD34+ hematopoietic progenitors and cell lines by RNA interference suppresses megakaryocytic differentiation. In cells lacking tescalcin, the expression of Fli-1, Ets-1, and Ets-2 transcription factors, but not GATA-1 or MafB, is blocked. Thus, tescalcin is essential for the coupling of ERK cascade activation with the expression of Ets family genes in megakaryocytic differentiation.
Early-Onset Pneumonia after Cardiac Arrest
Authors: Sébastien Perbet, Nicolas Mongardon, Florence Dumas, Cédric Bruel, Virginie Lemiale, Bruno Mourvillier, Pierre Carli, Olivier Varenne, Jean-Paul Mira, Michel Wolff, Alain Cariou
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Although frequent, little is known about early-onset pneumonia that occurs in the postresuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, its influence on the occurrence of early-onset pneumonia is not well defined.Objectives: To describe the incidence, risk factors, causative agents, and impact on outcome of early-onset pneumonia occurring within 3 days after out-of-hospital cardiac arrest (OHCA).Methods: Retrospective analysis of a large cohort study of all patients successfully resuscitated after OHCA and admitted from July 2002 to March 2008 in two medical intensive care units (ICUs). Patients who presented accidental hypothermia or a known pneumonia before OHCA, or patients who died within the first 24 hours, were excluded.Measurements and Main Results: During this 6-year period, 845 patients were admitted after OHCA, and 641 consecutive patients were included. A total of 500 patients (78%) were treated with therapeutic hypothermia. In the first 3 days, 419 (65%) presented early-onset pneumonia. Multivariate analysis disclosed therapeutic hypothermia as the single independent risk factor of early-onset pneumonia (odds ratio, 1.90; 95% confidence interval, 1.28–2.80; P = 0.001). Early-onset pneumonia increased length of mechanical ventilation (5.7 ± 5.9 vs. 4.7 ± 6.2 d; P = 0.001) and ICU stay (7.9 ± 7.2 versus 6.7 ± 7.6 d; P = 0.001), but did not influence incidence of ventilator-associated pneumonia (P = 0.25), favorable neurologic outcome (P = 0.35), or ICU mortality (P = 0.26).Conclusions: After OHCA, therapeutic hypothermia is associated with an increased risk of early-onset pneumonia. This complication was associated with prolonged respiratory support and ICU stay, but did not significantly influence ICU mortality.
Finland's Medical System
Authors: ELI GOODMAN
Journal: Annals of Internal Medicine (1984)

Abroad1 January 1984Finland's Medical SystemELI GOODMAN, M.D.ELI GOODMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-1-152 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFinland, a young nation still developing its national identity and purpose, gained its independence only in 1917, having been ruled for nine centuries by Sweden and then Russia. Without much publicity, Finland has been making impressive economic gains, while serving as a moderating political force between the East and West. Finnish medicine reflects its country's quiet ascendancy to prominence and affluence.The health care system successfully meets the needs of a country with one of the world's highest standards of living, despite a relatively small size and population. All Finns have complete access to comprehensive medical and dental care. The... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1984Volume 100, Issue 1Page: 152-154KeywordsHealth care Issue Published: 1 January 1984 Copyright & Permissions© 1984 American College of PhysiciansPDF downloadLoading ...
Use of Busulfan in Myelogenous Leukemia during Pregnancy
Authors: Jacques L. Sherman, Robert V. Locke
Journal: New England Journal of Medicine (1958)

EXPERIENCE with the use of busulfan§ during the course of pregnancy is, apparently, extremely limited. A review of the literature disclosed only 1 previous case report, and personal communications with several large clinics have revealed no additional cases. Izumi1 reported the case of a thirty-one-year-old woman whose therapy with busulfan began about three months before conception. She was treated with maintenance therapy throughout pregnancy, and there was no evidence of disturbance of fetal granulopoietic function.Kenis et al.2 reported that the drug caused amenorrhea in a series of patients either during or after treatment, and in 1 young man, gonadal . . .
LEFT ATRIAL STRAIN RATE AS A PREDICTOR OF LOW EXERCISE CAPACITY IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS
Authors: Aurelio Carvalho Pinheiro, Veronica L. Dimaano, Lars Sorensen, Hsin-Yueh Liang, Hong-Chang Luo, Blaid K. Mbiyangandu, Roselle Abraham, Theodore Abraham
Journal: Journal of the American College of Cardiology (2012)
HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin
Authors: Isabella Abbate, Oreste Lo Iacono, Rosa Di Stefano, Giuseppina Cappiello, Enrico Girardi, Roberta Longo, Donatella Ferraro, Giorgio Antonucci, Vito Di Marco, Mariacarmela Solmone, Antonio Craxı̀, Giuseppe Ippolito, Maria R Capobianchi
Journal: Journal of Hepatology (2004)
Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies.
Authors: J M Ward, R Quander, D Devor, M L Wenk, E F Spangler
Journal: Environmental Health Perspectives (1986)

The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors included histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.
Genotype-4 hepatitis E in a human after ingesting roe deer meat in South Korea
Authors: Ja Yoon Choi, Jeong-Mi Lee, Yun Won Jo, Hyun Ju Min, Hyun Jin Kim, Woon Tae Jung, Ok Jae Lee, Haesun Yun, Yeong-Sil Yoon
Journal: Clinical and Molecular Hepatology (2013)

The recent increase in the number of cases of indigenous hepatitis E virus (HEV) infection highlights the importance of identifying the transmission routes for the prevention of such infections. Presented herein is the first case of acute HEV infection after ingesting wild roe deer meat in South Korea. A 43-year-old male presented with abdominal discomfort and jaundice. He had not recently traveled abroad, but had eaten raw roe-deer meat 6-8 weeks before the presentation. On the 7th day of hospitalization the patient was diagnosed with acute viral hepatitis E. Phylogenetic analysis of his serum revealed genotype-4 HEV. This case supports the possibility of zoonotic transmission of HEV because the patient appears to have been infected with genotype-4 HEV after ingesting raw deer meat. Keywords: Genotype 4 hepatitis E; Roe deer; South Korea
Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety
Authors: Justiniano Santos, Ramon Planas, Albert Pardo, Rosa Durández, Eduard Cabré, Rosa Maria Morillas, Maria Luisa Granada, José Angel Jiménez, Enrique Quintero, Miquel Angel Gassull
Journal: Journal of Hepatology (2003)
Germany's plans to reduce use of tobacco and alcohol provoke protests from industry and local politicians
Authors: N. Stafford
Journal: BMJ (2008)

Plans being drawn up by the German Ministry of Health to reduce alcohol and tobacco use have triggered strong protests from industry groups and politicians, with some of the sharpest criticism coming from the Bavarian health minister.

Proposals were debated at a hearing on 15 September in Berlin. the hearing was closed to the public and press but was attended by representatives of about 30 groups, including representatives from the German Medical Association (Bundesarztekammer), public health insurers, the public pension system, alcohol and tobacco industries, advertisers, sports associations, and addiction prevention groups.

Sabine Batzing, Germany’s federal drug commissioner based in the health ministry and the plan’s driving force, told the BMJ that it was needed to reduce German alcohol and tobacco consumption, which is among the highest in Europe. …
Effect of medical audit on prescription of palliative radiotherapy.
Authors: D Dodwell, M Bond, C Elwell, J Gildersleve, S Parmar, J Owens, A Bulman, A Crellin, D Ash
Journal: BMJ (1993)

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (<i>P</i> &lt; 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.
IgE binding to almond proteins in two CAP‐FEIA‐negative patients with allergic symptoms to almond as comparedto three CAP‐FEIA‐false‐positive subjects
Authors: G. Pasini, B. Simonato, M. Giannattasio, C. Gemignani, A. Curioni
Journal: Allergy (2000)

Background : Allergy to almonds has been frequently reported, but data on the identification of the almond allergens, as well as on the reliability of the methods for in vitro detection of specific IgE for these allergens, are scant. This study aimed to identify the almond allergens and to evaluate the reliability of the CAP‐FEIA as the standard system for detection of almond‐specific IgE with clinical significance. Methods : Immunoblotting performed with an almond‐protein extract was carried out on the sera of five patients who had previously been tested by the CAP‐FEIA system; two of these patients had tested negative with the CAP‐FEIA system but suffered life‐threatening laryngeal edema after eating almonds, whereas the other three subjects, who had tested positive with CAP‐FEIA, did not present any symptoms subsequent to almond ingestion. Results : The sera of the two symptomatic CAP‐FEIA‐negative patients had IgE that bound only to a 37‐kDa protein in immunoblotting. On the contrary, the sera of the three asymptomatic subjects all showed IgE binding to two almond proteins of 62 and 50 kDa, corresponding to the glycosylated components of the extract. Conclusions : The results here presented suggest that, at least for the examined subjects, the positivity to almond, as measured with a standard laboratory method, is due to the presence of the 62/50‐kDa glycoproteins with little or no immunologic significance, and not to the binding to the 37‐kDa polypeptide, which appears to be a true almond allergen.
Rapamycin inhibits human renal epithelial cell proliferation: Effect on cyclin D3 mRNA expression and stability
Authors: Nicolas Pallet, Eric Thervet, Delphine Le Corre, Bertrand Knebelmann, Patrick Nusbaum, Celine Tomkiewicz, Paul Meria, Jean-Pierre Flinois, Philippe Beaune, Christophe Legendre, Dany Anglicheau
Journal: Kidney International (2005)
Manpower planning-a selector's view.
Authors: E Welbourn
Journal: BMJ (1977)

an even greater incentive to do so. In September 1975 the estimated cost of training a medical student through to qualification was £28 000. (I do not attempt to calculate the effects of inflation by October 1977.) This itself underlines the responsibility placed on selectors to ensure that this expenditure is justified, not only when the newcomers enter medical education but also during their training and after qualification. Our duty, therefore, lies in doing the best we can for the applicant, for the general public and the NHS in due course, and for the taxpayers' pockets. Critics of the way that this responsibility is met may not be completely aware of the selection procedure. In describing the various stages of selection perhaps I shall be able to offer some advice to those preparing next year's candidates and at the same time extend some comfort and explanation to this year's unsuccessful applicants. Much of what you said agrees with reported experience on medical school selection.2 I have nothing but sympathy for the sentiments expressed when you state1:  . . many of my contemporaries have spent a miserable summer coming to terms with the rejection of a son or daughter by their chosen medical school. But I cannot let the next sentences pass without comment: Are the universities right to require such high academic standards from would-be doctors? . . . deans are unhappy at turning down enthusiastic, idealistic school-leavers simply on their A levels: but with so many good applicants ... how else can they choose ? We know that A level scores correlate with pass rates in subsequent examinations.... I should like to see far more variation in the courses offered by different universities. (My italics.) Selection may be considered in four stages: (a) selection of medicine as a career by the candidate; (b) selection by school careers staff of likely candidates coupled with advice on A level courses; (c) selection of medical schools by schools and candidates; (d) selection by medical school of suitable new entrants.