tbuckley/cabot-search huggingface dataset:
Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice
Authors: Svitlana Kurinna, Sabrina A. Stratton, Wen-Wei Tsai, Kadir C. Akdemir, Weisong Gu, Pallavi Singh, Triona Goode, Gretchen J. Darlington, Michelle Craig Barton
Journal: Hepatology (2010)

Abstract The p53 family of proteins regulates the expression of target genes that promote cell cycle arrest and apoptosis, which may be linked to cellular growth control as well as tumor suppression. Within the p53 family, p53 and the transactivating p73 isoform (TA-p73) have hepatic-specific functions in development and tumor suppression. Here, we determined TA-p73 interactions with chromatin in the adult mouse liver and found forkhead box O3 ( Foxo3 ) to be one of 158 gene targets. Global profiling of hepatic gene expression in the regenerating liver versus the quiescent liver revealed specific, functional categories of genes regulated over the time of regeneration. Foxo3 is the most responsive gene among transcription factors with altered expression during regenerative cellular proliferation. p53 and TA-p73 bind a Foxo3 p53 response element (p53RE) and maintain active expression in the quiescent liver. During regeneration of the liver, the binding of p53 and TA-p73, the recruitment of acetyltransferase p300, and the active chromatin structure of Foxo3 are disrupted along with a loss of Foxo3 expression. In agreement with the loss of Foxo3 transcriptional activation, a decrease in histone activation marks (dimethylated histone H3 at lysine 4, acetylated histone H3 at lysine 14, and acetylated H4) at the Foxo3 p53RE was detected after partial hepatectomy in mice. These parameters of Foxo3 regulation are reestablished with the completion of liver growth and regeneration and support a temporary suspension of p53 and TA-p73 regulatory functions in normal cells during tissue regeneration. p53-dependent and TA-p73–dependent activation of Foxo3 was also observed in mouse embryonic fibroblasts and in mouse hepatoma cells overexpressing p53, TA-p73α, and TA-p73β isoforms. Conclusion: p53 and p73 directly bind and activate the expression of the Foxo3 gene in the adult mouse liver and murine cell lines. p53, TA-p73, and p300 binding and Foxo3 expression decrease during liver regeneration, and this suggests a critical growth control mechanism mediated by these transcription factors in vivo .
Breast Cancer Therapy: Exercising All Our Options
Authors: Vincent T. DeVita
Journal: New England Journal of Medicine (1989)

This issue of the Journal contains four articles important to the 70,000 women in the United States in whom node-negative breast cancer develops each year.1 2 3 4 They provide these women with an option—an option, however, that they can reasonably exercise only within the "therapeutic window" defined in the study protocols through which thousands of women pass each month.These studies are in essence the capstone of 32 years of clinical trials of treatment for breast cancer that began with the study of the postoperative use of thiotepa by the National Surgical Adjuvant Breast and Bowel Project in 1957.5 The trials that . . .
P5-11-09: High Concordance for Microarray Based Determination of ER, PR and HER2 Receptor Status and Local IHC/FISH Assessment Worldwide in 749 Patients.
Authors: J Wesseling, G Cusumano, C Tinterri, A Sapino, F Zanconati, M Lutke-Holzik, B Nguygen, K Deck, P Querzoli, T Perin, C Giardina, G Seitz, J Guinebretiere, J Barone, T Watanabe
Journal: Cancer Research (2011)

Abstract Background The level of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression is predictive for prognosis and/or treatment response in breast cancer patients. However, differences in fixation and IHC and subjective interpretation can substantially affect the accuracy and reproducibility of the results. The commercially available TargetPrint test measures the mRNA expression level of ER, PR and HER2 and provides high quality second opinion for local IHC/FISH assessment. This study compares results from the microarray-based TargetPrint with IHC and FISH (for HER2 IHC2+) generated by local standard procedures. Methods Prospective tumor samples were collected for 749 patients diagnosed with breast cancer stage I to IV between February 2008 and January 2011. The mRNA level of ER, PR and HER2 (TargetPrint) was assessed in the Agendia laboratories (Agendia Inc, Irvine, CA; Agendia BV, Amsterdam, the Netherlands) in fresh tumor samples submitted from 22 hospitals from Europe, New Zealand, Japan and US. The results of the IHC/FISH assessments performed according to the local standards at the hospitals were compared to the quantitative gene expression readouts. Results Of the 749 samples, IHC assessment was unknown for 5 ER samples and 4 PR samples; FISH was unknown for 24 samples. TargetPrint read out was not assessed for HER2 for 11 samples. Median age of these patients was 61 years. Comparison of IHC and gene expression read out by TargetPrint showed a concordance of 95% for ER; 82% for PR and 91% for HER2. In this study, only 4% of all IHC ER positive samples were classified negative by microarray. In contrast, 14% of IHC ER negative samples were classified positive by microarray. However for HER2, 28% of IHC/FISH HER2 positive samples were classified negative by microarray and 5% of IHC/FISH HER2 negative samples were classified positive by microarray. Samples with discordant classifications for TargetPrint and local assessment are being reviewed in greater detail by a central pathologist. Conclusions Microarray based readout of ER, PR and HER2 status using TargetPrint is highly comparable to local IHC and FISH analysis in 749 analyzed samples in various hospitals worldwide. The results indicate mRNA expression read out for ER, PR and HER2 by TargetPrint provides high quality second opinion for local IHC/FISH assessment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-09.
Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings.
Authors: D W Ferguson, W J Berg, J S Sanders, P J Roach, J S Kempf, M G Kienzle
Journal: Circulation (1989)

Digitalis glycosides exert both excitatory and inhibitory autonomic actions in animals and produce vasoconstriction in normal humans but produce vasodilation in heart failure patients. To determine whether or not these contrasting vascular responses are due to differing autonomic actions of the drug, we compared the responses to intravenous administration of Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23 +/- 1 years) and eight patients with moderate-to-severe heart failure (mean age, 52 +/- 5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic nerve activity to muscle (MSNA) were measured during 5-minute periods before (control) and 20 minutes after drug administration. In the heart failure patients, Cedilanid-D significantly increased systolic and pulse pressures, whereas mean arterial pressure was unchanged. There was a decrease in right atrial pressure and a tendency for a decrease in pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac index increased by 24 +/- 7%. Short-term administration of digitalis in these heart failure patients produced a fall in forearm vascular resistance (from 37.6 +/- 8.2 to 31.8 +/- 8.1 units, p less than 0.05) and an early, profound, and sustained decrease in MSNA (from 831.0 +/- 118.4 to 474.4 +/- 103.6 units/100 heart beats, p less than 0.01). Digitalis glycosides produced different vascular and MSNA responses in the normal subjects. In the normal volunteers, the drug significantly increased systolic, mean, and pulse pressures and decreased central venous pressure and heart rate. Despite the significant increase in arterial pressure, there was no change in forearm vascular resistance (from 11.7 +/- 1.0 to 12.7 +/- 1.0 units, p = NS) or MSNA (from 494.8 +/- 88.5 to 369.1 +/- 60.5 units/100 heart beats, p = NS), suggesting a sympathoexcitatory response in normal subjects. To determine whether or not the digitalis-induced sympathoinhibition in the heart failure patients was simply due to an inotropic effect (stimulation of inhibitory cardiac mechanoreceptors), we studied the responses of seven additional patients with heart failure before and during administration of dobutamine (3.4 +/- 0.4 micrograms/kg/min). Dobutamine produced a 34 +/- 3% increase in cardiac index, no significant change in systemic arterial pressures, a decrease in pulmonary artery diastolic and right atrial pressures, and no change in heart rate or forearm vascular resistance (from 30.2 +/- 4.3 to 26.5 +/- 4.7 units, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
Estimated rate of prostacyclin secretion into the circulation of normal man.
Authors: G A FitzGerald, A R Brash, P Falardeau, J A Oates
Journal: Journal of Clinical Investigation (1981)

The rate of secretion of prostacyclin (PGI2) into the circulation of normal man was estimated by measurement of the 2,3-dinor-6-keto-PGF1 alpha (D) and 15-keto-13,14-dihydro-2,3-dinor-6-keto-PGF1 alpha (KDD) urinary metabolites of PGI2. Subjects received 6-h intravenous infusions of vehicle alone and PGI2 at 0.1, 0.4, and 2.0 ng/kg per min in random order. The fractional elimination of the metabolites was independent of the rate of PGI2 infusion. 6.8 +/- 0.3% of the infused PGI2 appeared as D and 4.1 +/- 0.4% as KDD. The regression of infused PGI2 upon the quantities of the two metabolites excreted in excess of control values permitted estimation of the rate of entry of endogenous PGI2 into the circulation corresponding to a given quantity of metabolite excreted. Using the quantities excreted in the 24 h from commencement of the infusions the estimated rates were 0.08 +/- 0.02 ng/kg per min from D and 0.10 +/- 0.03 from KDD. Studies with exogenous PGI2 suggest that infusion rates 2--4 ng/kg per min are required to achieve the threshold for inhibition of platelet function (ex vivo) in man. Although not precluding a role for PGI2 in local platelet-vessel wall interactions, the much lower estimates obtained in this study suggest that endogenous PGI2 is unlikely to act as a circulating antiplatelet agent in healthy man.
Sunlight prevents cancer, study says
Authors: O. Dyer
Journal: BMJ (2002)

Insufficient exposure to ultraviolet radiation may be an important risk factor for cancer in western Europe and North America, according to the author of a new study that directly contradicts official advice about sunlight.

The research, published this week in the journal Cancer (2002;94:1867-75), examined cancer mortality in the United States. Deaths from a range of cancers of the reproductive and digestive systems were approximately twice as high in New England as in the south west, despite a diet that varies little between regions.

An examination of 506 …
The Abnormal Lipoprotein of Cholestasis
Authors: Richard J. Havel
Journal: New England Journal of Medicine (1971)

Recent studies have defined the physical and chemical characteristics of a unique lipoprotein that accumulates in the plasma of patients with obstructive jaundice.1 2 3 4 This lipoprotein accounts for the hyperlipidemia long known to accompany intrahepatic or extrahepatic biliary obstruction. Improved technics have shown that the abnormal particle contains little or no nonpolar lipid (cholesteryl esters and triglycerides). It consists chiefly of a 1:1 molar mixture of cholesterol and phospholipids (mainly lecithin) and of less than 5 per cent protein. By negative-staining electron microscopy with potassium phosphotungstate, the abnormal particle appears as a disk of about 100 by 500 Å. Its flattened . . .
REPORT OF TWO CASES OF HEART DISEASE.
Authors: JOHN M. BATTEN
Journal: JAMA (1898)

a patient past middle life who is the subject of gout, alcoholism or a wasting disease, if in addition to the above we find atheromatous changes in the blood ves- sels, or degeneration elsewhere, such as arcus senilis, together with weak, irregular and at times intermit- tent permanently slow or fast pulse.Presence of angina pectoris, edema of the feet, Cheyne-Stokes res- piration, with pseudo-apoplectic attack, all t?nd to confirm a suspicion of fatty heart.
Outcomes of elderly <i>de novo</i> acute myeloid leukemia treated by a risk‐adapted approach based on age, comorbidity, and performance status
Authors: Jae‐Ho Yoon, Byung‐Sik Cho, Hee‐Je Kim, Jung‐Ho Kim, Seung‐Hwan Shin, Seung‐Ah Yahng, Sung‐Eun Lee, Ki‐Seong Eom, Yoo‐Jin Kim, Seok Lee, Chang‐Ki Min, Seok‐Goo Cho, Dong‐Wook Kim, Jong‐Wook Lee, Woo‐Sung Min, Chong‐Won Park
Journal: American Journal of Hematology (2013)

Several criteria to define fitness for induction chemotherapy in elderly acute myeloid leukemia (AML) have been proposed; however, no studies have reported outcomes according to the application of a risk-adapted approach. We treated 256 consecutive patients with elderly AML (≥60 years) with a risk-adapted approach based on age, comorbidity score (CS), and performance status (ECOG). Eighty-five low-risk patients (age ≤ 65 years and ECOG 0-1 with CS < 2), 86 intermediate-risk patients (age > 65 years or ECOG = 2 with CS < 2), and 85 high-risk patients (ECOG > 2 or CS ≥ 2) were treated with induction chemotherapies, including standard intensive regimens, abbreviated-scheduled regimens, and modified low-dose cytarabine with oral etoposide (mLDAC), respectively. Overall response rates (ORR; complete response and complete response with incomplete recovery) for these three groups were 71.8%, 60.5%, and 41.2%, respectively, without a significant difference in early death rate (17.6%, 25.6%, 23.5%, P = 0.415). Among three abbreviated-scheduled regimens, a gemtuzumab ozogamicin (GO)-containing regimen (n = 43) showed a similar ORR rate (72.1%) to the intensive regimen. After achieving remission, 142 patients went on postremission treatments, including reduced-intensity allogeneic transplantation (RIC, n = 41), standard consolidation (n = 71), and repeated mLDAC (n = 30) according to donor availability, age, ECOG, and CS. Multivariate analyses revealed that not only RIC, but also repeated mLDAC, resulted in significantly superior survival outcomes to standard consolidation independent of age, ECOG, and CS. Clinical benefits of mLDAC for high-risk patients and abbreviated induction with GO for intermediate-risk patients should be confirmed with further studies. Our results also suggest that RIC should be actively considered in elderly AML as a postremission treatment.
Quality of well-being predicts survival in lung transplantation candidates.
Authors: H C Squier, A L Ries, R M Kaplan, L M Prewitt, C M Smith, J M Kriett, S W Jamieson
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Predictors of survival were evaluated among 74 patients selected for a lung transplantation program. Each patient received the quality of well-being scale, a utility-based outcome measure that gives a score on a continuum ranging from 0 (for dead) to 1.0 (for optimum function), and a measure of depressive symptoms (Beck depression inventory). Over the course of follow-up, 24 patients died (ranging from listing date, 3 to 1, 110 d). Of the 49 patients who received lung transplantation, 13 died. In a multivariate analysis, the most significant predictor of survival was quality of well-being (relative risk = 0.454, p < 0.05). Lung transplant status, when entered as a time-dependent covariate (a function of how long the patient waited for surgery) was not a significant predictor of survival (relative risk = 0.942, p > 0.05). Depression was not a significant predictor of survival (relative risk = 0.961, p > 0.05). We conclude that health-related quality of life is a significant predictor of survival for patients with serious lung diseases.
Multiscale patterned transplantable stem cell patches for bone tissue regeneration
Authors: Jangho Kim, Won-Gyu Bae, Han-Wool Choung, Ki Taek Lim, Hoon Seonwoo, Hoon Eui Jeong, Khap-Yang Suh, Noo Li Jeon, Pill-Hoon Choung, Jong Hoon Chung
Journal: Biomaterials (2014)
Psychological Treatment of Erectile Disorders in Diabetic Patients
Authors: RAUL C. SCHIAVI
Journal: Annals of Internal Medicine (1980)

Psychological and organic factors may interact in the impairment of erectile capacity. This interaction must be considered in the accurate assessment of the extent of organic defect and the choice of psychological approaches for treatment of diabetic men with erectile disorders. Psychosexual evaluation must be done to select patients for penile prosthetic implantation.
Green Tea Extract Modulates Actin Remodeling via Rho Activity in an <i>In vitro</i> Multistep Carcinogenic Model
Authors: Qing-Yi Lu, Yu-Sheng Jin, Allan Pantuck, Zuo-Feng Zhang, David Heber, Arie Belldegrun, Mai Brooks, Robert Figlin, JianYu Rao
Journal: Clinical Cancer Research (2005)

Abstract Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.
Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: A large multicenter AGEO study
Authors: Aziz Zaanan, Nicolas Williet, Mohamed Hebbar, Tienhan Sandrine Dabakuyo, Laetitia Fartoux, Touraj Mansourbakht, Olivier Dubreuil, Olivier Rosmorduc, Stéphane Cattan, Franck Bonnetain, Valérie Boige, Julien Taïeb
Journal: Journal of Hepatology (2012)
The Language of Experience
Authors: Jesse Michael Raiten
Journal: JAMA (2014)

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
Prevalence of the Congenital Long-QT Syndrome
Authors: Peter J. Schwartz, Marco Stramba-Badiale, Lia Crotti, Matteo Pedrazzini, Alessandra Besana, Giuliano Bosi, Fulvio Gabbarini, Karine Goulene, Roberto Insolia, Savina Mannarino, Fabio Mosca, Luigi Nespoli, Alessandro Rimini, Enrico Rosati, Patrizia Salice, Carla Spazzolini
Journal: Circulation (2009)

The prevalence of genetic arrhythmogenic diseases is unknown. For the long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published, but none was based on actual data. Our objective was to define the prevalence of LQTS.In 18 maternity hospitals, an ECG was performed in 44 596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of 28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28 (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%) with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed as affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17 of 43 080 white infants were affected by LQTS, demonstrating a prevalence of at least 1:2534 apparently healthy live births (95% confidence interval, 1:1583 to 1:4350).This study provides the first data-based estimate of the prevalence of LQTS among whites. On the basis of the nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis that this prevalence might be close to 1:2000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.
Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation
Authors: Y. Uchino, T. Fukushige, S. Yotsumoto, T. Hashiguchi, H. Taguchi, N. Suzuki, I. Konohana, T. Kanzaki
Journal: British Journal of Dermatology (2003)

Summary Background There are seven well-known lysosomal storage diseases that produce angiokeratoma corporis diffusum clinically. β-Mannosidosis (MANB1; OMIM248510), first reported in humans in 1986, is a rare hereditary lysosomal storage disease caused by a deficiency of the enzyme β-mannosidase. Since then, 13 cases of β-mannosidase deficiency in ten families have been described. A human β-mannosidase mutation has been reported only by Alkhayat et al. in 1998. Objectives To clarify its pathogenesis we did electron microscopic, biochemical and molecular biological investigations of a Japanese patient with β-mannosidosis. Methods Ultrastructural analyses, enzyme assays, cell culture and mRNA and genomic DNA were sequenced to find mutations in the β-mannosidase gene. Results Electron microscopy of skin biopsy specimens from the patient showed cytoplasmic vacuolation of lysosomes in blood and lymph vessels, endothelial cells, fibroblasts, secretory portions of eccrine sweat glands, neural cells and basal keratinocytes in the epidermis. This vacuolation was also observed in cultured keratinocytes and fibroblasts. Assays of seven enzyme activities in plasma and cultured skin fibroblasts showed a marked decrease of β-mannosidase activity. Sequencing the β-mannosidase cDNA revealed a four-base (ATAA) insertion between exons 7 and 8, resulting in a frameshift at codon 321 and termination at codon 325. Analysis of the patient's genomic DNA revealed a novel homozygous A(+1)→G splice site mutation in intron 7. Conclusions To our knowledge, this is the first case of β-mannosidosis reported in Japan and the second report in which a gene mutation is identified. The biological importance of β-mannose moieties in glycoproteins in basal keratinocytes is suggested.