tbuckley/cabot-search huggingface dataset:
The Low Molecular Weight Apo(a) Phenotype Is an Independent Predictor for Coronary Artery Disease in Hemodialysis Patients
Authors: FLORIAN KRONENBERG, ULRICH NEYER, KARL LHOTTA, EVI TRENKWALDER, MARTIN AUINGER, ANDREAS PRIBASNIG, THOMAS MEISL, PAUL KÖNIG, HANS DIEPLINGER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Patients with end-stage renal disease treated by hemodialysis have a tremendous risk for cardiovascular complications that cannot be explained by traditional atherosclerosis risk factors. Lipoprotein(a) (Lp(a)), a risk factor for these complications in the general population, is significantly elevated in these patients. In this study, it was determined whether Lp(a) and/or the genetically determined apo(a) phenotype are risk predictors for the development of coronary artery disease in these patients. A cohort of 440 unselected hemodialysis patients were followed for a period of 5 yr independent of the cause of renal disease, duration of preceding treatment, and the preexistence of coronary artery disease at study entry. Coronary events defined as definite myocardial infarction, percutaneous transluminal coronary angioplasty, aortocoronary bypass, or a stenosis &gt;50% in the coronary angiography were the main outcome measure. Sixty-six (15%) of the 440 patients suffered a coronary event during follow-up. In univariate analysis, patients with events were significantly older and showed a trend to lower HDL cholesterol concentrations, and higher apolipoprotein B and Lp(a) concentrations without reaching significance. Apo(a) phenotypes of low molecular weight, however, were significantly more frequent in patients with compared to those without events (43.9% versus 21.9%, P &lt; 0.001). The other lipids, lipoproteins, and apolipoproteins were similar in both groups. Multiple Cox proportional hazards regression analysis found age and the apo(a) phenotype to be the best predictors for coronary events during the observation period, independent of whether patients with a preexisting coronary artery disease or an age &gt;65 yr at the study entry or both were excluded from the analysis. Diabetes mellitus was a risk factor only in presence of a low molecular weight apo(a) phenotype. The genetically determined apo(a) phenotype is a strong and independent predictor for coronary events in hemodialysis patients. Apo(a) phenotyping might be helpful to identify hemodialysis patients at high risk for coronary artery disease.
Surrogate End Point for Prostate Cancer-Specific Mortality After Radical Prostatectomy or Radiation Therapy
Authors: A. V. D'Amico, J. W. Moul, P. R. Carroll, L. Sun, D. Lubeck, M.-H. Chen
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: The relationship between prostate-specific antigen (PSA)–defined recurrence and prostate cancer–specific mortality remains unclear. Therefore, we evaluated the hypothesis that a short post-treatment PSA doubling time (PSA-DT) after radiation therapy is a surrogate end point for prostate cancer–specific mortality by analyzing two multi-institutional databases. Methods: Baseline, treatment, and follow-up information was compiled on a cohort of 8669 patients with prostate cancer treated with surgery (5918 men) or radiation (2751 men) from January 1, 1988, through January 1, 2002, for localized or locally advanced, non-metastatic prostate cancer. We used a Cox regression analysis to test whether the post-treatment PSA-DT was a prognostic factor that was independent of treatment received. All statistical tests were two-sided. Results: The post-treatment PSA-DT was statistically significantly associated with time to prostate cancer–specific mortality and with time to all-cause mortality (all PCox<.001). However, the treatment received was not statistically significantly associated with time to prostate cancer–specific mortality after PSA-defined disease recurrence for patients with a PSA-DT of less than 3 months (PCox = .90) and for patients with a PSA-DT of 3 months or more (PCox = .28) when controlling for the specific value of the PSA-DT. Furthermore, after a PSA-defined recurrence, a PSA-DT of less than 3 months was statistically significantly associated with time to prostate cancer–specific mortality (median time = 6 years; hazard ratio = 19.6, 95% confidence interval = 12.5 to 30.9). Conclusion: A post-treatment PSA-DT of less than 3 months and the specific value of the post-treatment PSA-DT when it is 3 months or more appear to be surrogate end points for prostate cancer–specific mortality after surgery or radiation therapy. We recommend that consideration be given to initiating androgen suppression therapy at the time of a PSA-defined recurrence when the PSA-DT is less than 3 months to delay the imminent onset of metastatic bone disease.
The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21Waf1/Cip1
Authors: P.E. Beattie, L.E. Finlan, N.M. Kernohan, G. Thomson, T.R. Hupp, S.H. Ibbotson
Journal: British Journal of Dermatology (2005)

Background High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm−2) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes. Objectives To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. Methods Five adult volunteers were exposed to dose series of UVA1 (10–100 J cm−2) and, for comparison, narrowband UVB (TL-01) (25–550 mJ cm−2) and solar-simulated radiation (SSR) (5·6–30 J cm−2) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF. Results UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean ± SD cell count per HPF 16 ± 10), no p53 activation and very little evidence of p21 expression (mean ± SD cell count per HPF 5·3 ± 7), in contrast to TL-01 (mean ± SD cell count per HPF of 11·83 ± 2·1 SBCs, 146·3 ± 38 for Do-1, 26·6 ± 15 for serine 15, 14·9 ± 12 for serine 392 and 77·9 ± 30 for p21) or SSR irradiation (mean ± SD cell count per HPF of 3·5 ± 1·2 SBCs, 147·5 ± 62 for Do-1, 54 ± 50 for serine 15, 38·9 ± 18 for serine 392 and 56·7 ± 30 for p21). Conclusions These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.
Erythropoietin in cardioprotection: does it have a future or is it all in the past?
Authors: J. L. Mehta
Journal: Cardiovascular Research (2008)

Over the past two decades, we have seen a gradual reduction in mortality from myocardial infarction due in a large part to the advent of revascularization and other cardioprotective strategies. However, myocardial infarction is still the most common cause of morbidity, related primarily to the loss of left ventricular function and mortality. A host of novel strategies are being examined to limit myocardial infarct size. Towards that goal, several investigators have suggested that erythropoietin (EPO) therapy may hold a new promise. The article by Kobayashi et al. in the current issue of Cardiovascular Research describes a new drug delivery protocol for the use of EPO in the post-myocardial infarction setting.1

### 2.1 Preclinical studies

It is well known that EPO stimulates the plasma haemoglobin concentration in patients with cancers or renal disease. Receptors for EPO have been shown to be present on vascular smooth muscle cells, endothelial cells, and cardiomyocytes,2 and EPO appears to exert its effect on myocardial function by stimulating EPO receptors on cardiomyocytes.

Previous studies have shown that EPO administration reduces the myocardial infarct size after ischaemia.3,4 Gao et al. 5 showed that treatment with a long-acting EPO preparation as late as 24 h after the onset of the ischaemic process provided a significant reduction in myocardial … 

*Corresponding author. Tel: +1 501 296 1401; fax: +1 501 686 6180. E-mail address : mehtajl{at}uams.edu
Effect of allergic sensitization on clinical course of patients with COPD in the Hokkaido COPD cohort study
Authors: Masaru Suzuki, Satoshi Konno, Hironi Makita, Kaoruko Shimizu, Masaharu Nishimura
Journal: European Respiratory Journal (2014)

Introduction : An allergic phenotype has been reported to be associated with risk of exacerbations in patients with COPD using data from cohort studies conducted in the United States (Jamieson, D.B. et al. Am J Respir Crit Care Med 2013; 188:187-192).   Aim : To assess whether the presence of allergic sensitization is associated with worse baseline characteristics and/or clinical course of patients with COPD in a 5-year prospective observational cohort study.   Methods : A total of 268 subjects (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; GOLD 4, 5%) who participated in the Hokkaido COPD cohort study conducted in Japan were included for this analysis. Allergic sensitization was evaluated at enrollment by the presence of serum specific IgE for inhaled antigens measured by MAST assay.  Results : 67 COPD subjects (25%) had allergic sensitization to at least one inhaled antigen. The presence of allergic sensitization to at least one antigen was not associated with any of lung function (post-bronchodilator FEV 1  %predicted), airway reversibility, CT emphysema score, and quality of life (SGRQ score) at baseline, and annual decline in FEV 1  and exacerbation frequency during the follow-up period. On the other hand, subjects with allergic sensitization to pollens or fungi had better baseline lung function and lower airway reversibility compared with those without allergic sensitization to them.   Conclusion : In this study, the presence of allergic sensitization was not associated either with worse baseline characteristics or with clinical course of patients with COPD.
Long-Term Solid Cancer Risk Among 5-Year Survivors of Hodgkin's Lymphoma
Authors: David C. Hodgson, Ethel S. Gilbert, Graça M. Dores, Sara J. Schonfeld, Charles F. Lynch, Hans Storm, Per Hall, Froydis Langmark, Eero Pukkala, Michael Andersson, Magnus Kaijser, Heikki Joensuu, Sophie D. Fosså, Lois B. Travis
Journal: Journal of Clinical Oncology (2007)

Hodgkin's lymphoma (HL) survivors are known to be at substantially increased risk of solid cancers (SC). However, no investigation has used multivariate modeling to estimate the relative risk (RR), excess absolute risk (EAR), and cumulative incidence for specific attained ages and ages at HL diagnosis.We identified 18,862 5-year HL survivors from 13 population-based cancer registries in North America and Europe. Poisson regression was used to evaluate the effects of age at diagnosis, attained age, latency, sex, treatment, and year of diagnosis on the RR and EAR of SC.Among 1,490 identified SC, 850 were estimated to be in excess. For most cancer sites, both RR and EAR decreased with age at HL diagnosis and showed strong dependencies on attained age. For a patient diagnosed at age 30 years and survived to > or = 40 years, modeled risks were significantly elevated for cancers of the breast (RR = 6.1), other supradiaphragmatic sites (RR = 6.0), and infradiaphragmatic sites (RR = 3.7); the largest RR (20-fold) was observed for malignant mesothelioma. Thirty-year cumulative risks of SC for men and women diagnosed at 30 years were 18% and 26%, respectively, compared with 7% and 9%, respectively, in the general population. For young HL patients, risks of breast and colorectal cancers were elevated 10 to 25 years before the age when routine screening would be recommended in the general population.Multivariable modeling demonstrates for the first time temporal changes in SC risk not evident in unadjusted analyses, and can facilitate the development of individualized risk assessment and the creation of screening strategies for early detection.
Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
Authors: Keiichi Inoue, Joanne Rispoli, Hanoch Kaphzan, Eric Klann, Emily I Chen, Jongpil Kim, Masaaki Komatsu, Asa Abeliovich
Journal: Molecular Neurodegeneration (2012)

Abstract Background Macroautophagy is an evolutionarily conserved mechanism for bulk intracellular degradation of proteins and organelles. Pathological studies have implicated macroautophagy defects in human neurodegenerative disorders of aging including Alzheimer’s disease and tauopathies. Neuronal deficiency of macroautophagy throughout mouse embryonic development results in neurodevelopmental defects and early postnatal mortality. However, the role of macroautophagy in mature CNS neurons, and the relationship with human disease neuropathology, remains unclear. Here we describe mice deficient in an essential macroautophagy component, Atg7, specifically within postnatal CNS neurons. Results Postnatal forebrain-specific Atg7 conditional knockout (cKO) mice displayed age-dependent neurodegeneration and ubiquitin- and p62-positive inclusions. Phosphorylated tau was significantly accumulated in Atg7 cKO brains, but neurofibrillary tangles that typify end-stage human tauopathy were not apparent. A major tau kinase, glycogen synthase kinase 3β (GSK3β), was also accumulated in Atg7 cKO brains. Chronic pharmacological inhibition of tau phosphorylation, or genetic deletion of tau, significantly rescued Atg7-deficiency-mediated neurodegeneration, but did not suppress inclusion formation. Conclusions These data elucidate a role for macroautophagy in the long-term survival and physiological function of adult CNS neurons. Neurodegeneration in the context of macroautophagy deficiency is mediated through a phospho-tau pathway.
Rubor, Calor, Tumor, Dolor
Authors: Bill Griffin
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
Fracture Risk after Parathyroidectomy among Chronic Hemodialysis Patients
Authors: Kyle D. Rudser, Ian H. de Boer, Annemarie Dooley, Bessie Young, Bryan Kestenbaum
Journal: Journal of the American Society of Nephrology (2007)

The impact of parathyroidectomy (PTX) on the long-term risks for hip and other fractures is unknown. Uncontrolled case series have reported an increase in bone mineral density after PTX. However, very low serum parathyroid hormone levels have been associated with decreased bone mineral density, adynamic bone disease, and fractures. This study compared long-term fracture rates among hemodialysis patients who underwent PTX with a matched control group. Data were obtained from the US Renal Data System. Patients who underwent a first PTX while receiving hemodialysis were matched with up to three control patients by age, race, gender, year of dialysis initiation, primary cause of renal failure, and the dosage of intravenous vitamin D used before PTX. Patients with a history of fracture or renal transplantation were excluded. Study outcomes were incident hip, vertebral, and distal radius-wrist fractures identified using hospitalization codes. Incident hip fracture rates in the PTX and matched control groups were 6.0 and 9.3 fractures per 1000 person-years, respectively. After adjustment, PTX was associated with a significant 32% lower risk for hip fracture (95% confidence interval 0.54 to 0.86; P = 0.001) and a 31% lower risk for any analyzed fracture (95% confidence interval 0.57 to 0.83; P < 0.001) compared with matched control subjects. Fracture risks were lower among hemodialysis patients who underwent PTX compared with matched control subjects. Surgical amelioration of secondary hyperparathyroidism may outweigh the risk of parathyroid hormone oversuppression in terms of bone health.
Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases
Authors: M. Kusters, V. Valentini, F.A. Calvo, R. Krempien, G.A. Nieuwenhuijzen, H. Martijn, G.B. Doglietto, E. del Valle, F. Roeder, M.W. Buchler, C.J.H. van de Velde, H.J.T. Rutten
Journal: Annals of Oncology (2009)
Prediction of Response to Preoperative Chemotherapy in Gastric Carcinoma by Metabolic Imaging: Results of a Prospective Trial
Authors: Katja Ott, Ulrich Fink, Karen Becker, Alexander Stahl, Hans-Joachim Dittler, Raymonde Busch, Hubert Stein, Florian Lordick, Thomas Link, Markus Schwaiger, Jörg-Rüdiger Siewert, Wolfgang A. Weber
Journal: Journal of Clinical Oncology (2003)

We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy.Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival.Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P =.002)This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.
Social and Clinical Issues in Geriatric Psychiatry
Authors: BERNARD A. STOTSKY
Journal: American Journal of Psychiatry (1972)

The author provides an overview of the social characteristics and problems of the aged and of the medical services that are available and the gaps therein. Among the social problems he deals with are housing, family relationships, and retirement. He describes various facilities for the care of geriatric patients, the problems in providing preventive care, and also discusses general therapeutic considerations, including the types of psychotherapy and pharmacotherapy that have been found most effective.
Functional Cardiac Deterioration During Development of Hemorrhagic Circulatory Deficiency
Authors: OSCAR A. GOMEZ, WILLIAM F. HAMILTON
Journal: Circulation Research (1964)

A massive infusion test has been devised to evaluate the functional capacity of the heart. In five dogs extensive surgical procedures followed by episodes of arterial hypotension at 30 mm Hg and lasting 90 minutes caused severe cardiac incapacity, which was demonstrated by failure of rate of cardiac work to increase throughout the infusion together with a large rise in left atrial pressure. This incapacity was not evident in tests made immediately after the hypotensive episode. The damage became more and more severe in tests performed 90 and 150 minutes after the end of the hypotension even though mean arterial pressure was maintained at 100 mm Hg. Operated control dogs did not show cardiac deterioration in tests timed as above. The rate of cardiac work continued to increase throughout the infusion with a relatively small rise of left atrial pressure. In a series of five dogs, flow to the coronary arteries and to those supplying the head and forelimbs was maintained by normal blood pressure while the rest of the animal was made hypotensive for 90 minutes. The arterial pressure in the whole animal was then returned to an average level of 100 mm Hg. Tests made at intervals after the hypotension showed equivocal evidence of cardiac deterioration. In another series of four dogs, prepared as above, the partial hypotension lasted 150 minutes before the arterial pressure was returned to normal. Tests at intervals after hypotension showed cardiac damage in all the animals and severe damage in three. Evidence is presented indicating that the peripheral vascular bed had deteriorated functionally as a result of 150 minutes of partial hypotension.
Asymmetric Evolution of Human Transcription Factor Regulatory Networks
Authors: Zhan Zhou, Jingqi Zhou, Zhixi Su, Xun Gu
Journal: Molecular Biology and Evolution (2014)

Changes in cis or trans regulatory regions are the major driving forces that underlie the evolution of gene expression. Transcription factors (TFs) are the main trans factors involved in transcriptional regulation. Here, we studied the divergence of upstream and downstream regulatory networks between duplicate TFs in light of the Encyclopedia of DNA Elements project. We found that the divergence of upstream regulatory networks was generally smaller than the divergence of downstream regulatory networks. Further analysis showed that the downstream regulatory circuits of duplicate TFs evolve faster in the early stage than the late stage after gene duplication. Upstream regulatory circuits are generally more conserved than downstream regulatory circuits in the early stage and in small TF families. Our results indicate the asymmetric evolution of upstream and downstream regulatory circuits between duplicate TFs, which suggest that after gene duplication, human TF families tend to evolve asymmetrically between coding regions and promoter regions.