tbuckley/cabot-search huggingface dataset:
Abstract 4473: Coronary Flow Velocity Pattern Immediately after Percutaneous Coronary Intervention Predicts True Left Ventricular Aneurysm in Patients with Acute Anterior Myocardial Infarction
Authors: Atsushi Yamamuro, Takashi Akasaka, Shuichiro Kaji, Koichi Tamita, Minako Katayama, Makoto Kinoshita, Natsuhiko Ehara, Atsushi Kobori, Takeshi Kitai, Takafumi Yamane, Yoshimori An, Kite Kim, Syunsuke Funakoshi, Noriyuki Kimura, Tomoko Tani, Kazuaki Tanabe, Shigefumi Morioka, Yutaka Furukawa
Journal: Circulation (2008)

Aggressive management of acute myocardial infarction (AMI), including prompt reperfusion, may diminish the incidence of true left ventricular (LV) aneurysm; however, it has been reported that even if successful reperfusion is achieved in epicardial coronary arteries, microvascular dysfunction causes insufficient reperfusion of the infracted myocardium, leading to LV dysfunction. Recent studies have shown that microvascular damage can be assessed quantitatively from coronary flow velocity (CFV) patterns immediately after successful reperfusion. The purpose of this study was to examine whether the CFV patterns may predict the risk of true LV aneurysm formation following successful percutaneous coronary intervention (PCI). Two hundred and one consecutive patients with first anterior AMI who underwent successful PCI were subjected to CFV measurement immediately after PCI with Doppler guidewires. The CFV spectrum provided systolic peak velocity (cm/s, SPV) and diastolic deceleration time (ms, DDT). Left ventriculogram obtained 6 months after the infarction was analyzed to measure the LV volume index. True LV aneurysm was defined as a deformity of the infarct segment that was apparent during diastole as well as during systole, and demonstrated diastolic contour abnormality. Patients were divided into the two groups: those subsequently complicated by true LV aneurysm (n=42; group 1) and those without true LV aneurysm (n=159; group 2) CFV analysis immediately after PCI showed significantly lower SPV (−29 ± 17 vs. 5 ± 22 cm/s; p&lt;0.001) and shorter DDT (317 ± 156 vs. 665 ± 204 ms; p&lt;0.001) in group 1 than in group 2. The optimal cutoff values to predict true LV aneurysm formation were −20 cm/s for SPV and 400 ms for DDT (sensitivity=0.83, specificity=0.82; and sensitivity=0.81, specificity=0.87, respectively). SPV and DDT correlated to the LV end-diastolic volume index obtained 6 months after AMI (r= −0.67; p&lt;0.001 and r = −0.78; p&lt;0.001, respectively). CFV pattern of infarct-related coronary artery immediately after PCI predicts true LV aneurysm formation, and enables accurate risk stratification in patients with anterior AMI.
Abstract 3175: Plasma Tansforming Growth Factor Beta as a Biochemical Marker to Predict the Recurrence of Atrial Fibrillation After Surgical Maze
Authors: Young Keun On, Dae-Hee Shin, Jin-Oh Choi, Yong Hwan Park, Sang Yeub Lee, Ki-Ick Sung, PyoWon Park, Jidong Sung, Eun-Seok Jeon, June Soo Kim, Jeong Euy Park
Journal: Circulation (2007)

BACKGROUND Atrial remodeling leads to perpetuation of atrial fibrillation (AF). Structural remodeling in the form of fibrosis alters the substrate. The surgical Maze procedure was developed as a surgical treatment of AF. Our purpose was to evaluate the role of plasma NT-proBNP, hsCRP, TIMP-1(Tissue inhibitors of MetalloProteinase-1), TGF-β, MMP-3(Matrix MetalloProteinase-3), and pro-MMP-1in predicting the recurrence of AF after surgical Maze procedure. And we also evaluated the association of expression of CTGF, TGF-β, BNP, ANP, collagen-1α, and collagen-3α in LA with the recurrence of AF after surgical Maze procedure. METHODS Preoperative plasma NT-proBNP, hsCRP, TIMP, TGF-β, MMP-3, and pro-MMP-1 levels were measured in consecutive 86 patients (age 54±12 yrs) who underwent the open heart operation for valvular heart disease and surgical Maze procedure for AF. Moreover, we performed molecular examinations of CTGF, TGF-β, BNP, ANP, Collagen-1α, Collagen-3α in the resected left atrial tissues. Symptomatic AF documented by ECG or an episode of AF revealed at follow-up holter monitoring were considered atrial fibrillation recurrences. RESULTS At 1-year follow-up, 10 among 86 patients had persistence of AF. Patients with AF persistence had higher plasma TGF-β levels than the patients with sinus rhythm (0.44 ± 0.29 vs 0.32 ± 0.15 ng/ml) . Patients with AF persistence had higher messenger RNA expressions of Collagen-3α (0.21 ± 0.20 vs 0.12 ± 0.12, compared with internal standard GAPDH by RT-PCR) and lower messenger RNA expressions of ANP (0.31 ± 0.16 vs 0.60 ± 0.76, compared with internal standard GAPDH by RT-PCR ) in left atrial tissues. Multiple logistic regression analysis revealed that plasma TGF-β was independently associated with postoperative persistence of atrial fibrillation at 1 year follow-up after surgical Maze procedure. CONCLUSIONS Advanced atrial degenerative change might result in a decrease of atrial ANP secretion. Cardiac fibrosis might be a determinant of myocardial heterogeneity and the persistence of AF. Plasma TGF-β could predict the persistence of AF at 1 year follow-up after surgical Maze procedure.
Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia
Authors: P. B. Sinclair, E. P. Nacheva, M. Leversha, N. Telford, J. Chang, A. Reid, A. Bench, K. Champion, B. Huntly, A. R. Green
Journal: Blood (2000)
Pessimistic views of the NHS
Authors: N. Watson, K. Checkland
Journal: BMJ (1997)

Data are not now collected by ethnic group in South AfricaEditor-Claire Hilton notes that since April 1995 British hospitals have had to collect data on each patient's ethnic group. 1 In the United States this is standard practice.In the Morbidity and Mortality Weekly Report data on numerous variables relating to the health and ill health of black and white people are regularly given 2 -as also, on occasion, are data on Hispanics, American Indians, Inuits, and Pacific Islanders.In South Africa precisely the converse has occurred.Ethnic subdivisions have stopped appearing in reports from the Central Statistics Services, and thus mortalities are no longer given for the constituent populations (black, Asian, coloured (Eur-African-Malay), and white), only for the combined population.Additionally, in our big cities annual reports from public health departments provide only combined data on morbidity and mortality.Disadvantages are many.Recently, colleagues and I reviewed changes in the total death rate and the death rate from coronary heart disease in South African populations. 3 We found that, from 1978 to 1989, mortality from coronary heart disease fell by 56% in the white population and by 36% in each of the Indian and coloured populations.Because changes in mortality from this foremost "killer" are continuing we intended to update our information.But this is now precluded.Currently, desegregation does not apply to our national cancer registry.But if it did how, for example, could benefits from Papanicolaou smear tests be assessed?The incidences of cervical cancer in the black and coloured populations are among the highest in the world.The constituent populations of South Africa have a wider divergence in the occurrence of a variety of diseases than occurs in any other country: coronary heart disease, appendicitis, colon cancer, and hip fractures.Interethnic differences in the occurrence of disease, reactivity, and metabolism are well known elsewhere. 4 In South Africa the change to using combined data will make it harder to identify and quantify the target populations who are in most need of help, as well as severely stultifying research on the occurrence of disease and on combating it.Hilton is right, of course, that the level of treatment is affected by ethnic group.Recently, in the United States the effect of race and income on mortality and the use of services among beneficiaries of Medicare was investigated; both race and income were shown as having substantial prejudicial effects, that of race being much more pronounced than that of income. 5This is a matter of universal shame.
Abstract 15112: Viability and Ischemia Continue to Predict Outcomes: A Positron Emission Tomography Study of Patients with LV Dysfunction
Authors: Lee F Ling, Thomas Cook, Rory Hachamovitch, Demetrio R Flores, Weal Jaber, Richard Brunken, Manuel Cerqueira, Thomas H Marwick
Journal: Circulation (2011)

Aims The recent STICH trial showed lack of prognostic benefit of revascularization (RVS) of myocardium deemed viable by standard techniques. We evaluated the relationship and prognostic implication...
Transcripts of unknown function in eukaryotic cells: Lessons forgotten and re-learned.
Authors: Thomas R. Gingeras
Journal: Cancer Research (2006)

SY02-01   The current status of the functional annotations associated with the human genome is in an unfinished state. The majority of current genome annotations are heavily protein coding gene centric. This focus on protein coding genes intrinsically influences current perceptions of how the genome is structured and regulated. This view of the genome also has an underlying supposition that transcripts with very little coding potential are not biologically important. However, recent experiments analyzing the sites of transcription across large sections of the human genome have led to the conclusion that the current human genome annotations can not account for the amounts of empirically detected transcription. (Kapranov, et al. 2002, 2005); Rinn, et al., 2003, Kampa, et al., 2004, Martone, et al., 2003, Cawley et al., 2004Bertone, et al., 2004, Cheng, et. al, 2005). Most of the detected unannotated transcription is composed of RNAs with very little coding capacity (
KLF6(Krüppel-like factor 6) is a significant prognostic factor in node-positive non-small cell lung cancer (NSCLC)
Authors: Hiromichi Katakura, Kazumasa Takenaka, Masatsugu Nakagawa, Hiromi Wada, Fumihiro Tanaka
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4542 

Purpose: Kruppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcriptional factor, which has been suggested to be a candidate of tumor suppressor gene in some tumors such as prostate cancer and astrocytic glioma. Some experimental studies have suggested that KLF6 is frequently down-regulated and can induce apoptosis in non-small cell lung cancer (NSCLC). Here, we evaluated the clinical significance in resected NSCLC. Methods: A total of 152 completely resected NSCLC patients were reviewed, and KLF6 expression was evaluated immunohistochemically. Results: KLF6 expression status was not significantly correlated with any patient characteristic or any other biomarker (i.e. microvessel density, proliferative activity, or incidence of apoptotic cell death). For all patients, there was no significant difference according to KLF6 expression status(p=0.287). However, subset analysis revealed that positive KLF6 expression was a significant favorable prognosis in node-positive (N1-2) patients (Fig.), especially in p-stage IIIA patients (5-year survival rates, 23.8% for KFL-6-negative and 61.1% for KLF6-positive; p=0.038). A multivariate analysis confirmed that KLF6 status was a significant and independent prognostic factor in node-positive NSCLC. Conclusion: KLF6 was a favorable prognostic factor in node-positive (N0-1) NSCLC, but not in node-negative (N0) disease.
Heregulin: A new shelterin component at human telomeres
Authors: Javier A. Menendez, Louisa Benboudjema, Miguel A. Rubio, Luciano Vellon, Judith Campisi, Ruth Lupu
Journal: Cancer Research (2006)

4995  Telomere length, shape and function depend on a six subunits protein complex (TRF1, TRF2, TIN2, hRap1, TPP1 and POT1) recently referred as shelterin. We here describe a novel human telomere-associated protein, the tumor-promoting growth factor Heregulin (HRG). Utilizing the yeast two-hybrid system to identify HRG-interacting proteins in a human mammary gland cDNA library, a reactive clone was found to encode hRap1, a known association factor of TRF2. DNA sequencing and deletion mapping revealed that the hRap1’s linker domain, a region previously suggested recruiting negative regulators of telomere length, was essential for interaction between hRap1 and HRG. Double immunofluorescence microscopy revealed that the transfected green fluorescence protein (GFP)-tagged HRG and the endogenous HRG both co-localized not only with hRap1 but also with the hRap1’s partner TRF2. This interaction was reproduced in vivo in human cancer cells as immunoprecipitation of endogenous HRG from cell nuclei extracts was able to specifically pull down TRF2. Forced overexpression of HRG in HRG-negative cancer cells increased the rate of telomere shortening and resulted in increased levels of hRap1 and TRF2. Treatment of HRG-overexpressing cancer cells with HRG small interfering RNA led to telomere elongation and resulted in a decreased presence of hRap1 and TRF2. Our findings propose HRG as a novel shelterin team member that, by interplaying with hRap1 and TRF2, negatively regulates telomere length in human cancer cells.
Abstract 3877: The Magnitude and Temporal Dependence of Apoptosis Early After Myocardial Ischemia with or without Reperfusion
Authors: Christopher French, A.K.M. Tarikuz Zaman, Jeffrey L Spees, Douglas J Taatjes, Burton E Sobel
Journal: Circulation (2008)

It has been hoped and conjectured that in addition to improving the balance between myocardial oxygen supply and demand amelioration of apoptosis could preserve jeopardized ischemic myocardium destined to undergo necrosis (cell death). Assessment of apoptosis in experimental animals has been based generally on TUNEL assays. Unfortunately, TUNEL positivity occurs with oncotic, mitotic, and autophagic, as well as apoptotic cell death. Accordingly, we characterized the extent of apoptosis after transient or persistent ischemia with highly specific methods. Coronary artery occlusion with and without subsequent revascularization was induced in three groups of 10 week old C57BL/6 mice: those subjected to 1 hr or 4 hr transient ligation followed by 24 hr of reperfusion (1HTLR24H, 4HTLR24H); or 24 hr persistent ligation (24HPL). Apoptosis was quantified throughout the LV by TUNEL, single stranded DNA (ssDNA), and caspase 3 immunohistochemistry, electron microscopy (EM), and caspase 3 and 8 activities assessed biochemically. TUNEL staining markedly exceeded and did not correlate with ssDNA, caspase 3 staining, or apoptosis defined by EM in any group. It was lowest in the 1HTLR24H group (averaging 38.6 of cells ± 3.1% [SEM], n = 9) greater in the 4HTLR24H group (48.5 ± 3.1%, n = 9), and significantly greater than both in the 24HPL group (67.2 ± 4.3%, n = 9, p &lt; 0.01). ssDNA staining was minimal and similar in all three groups and significantly less than TUNEL staining (p &lt; 0.01) (1HTLR24H, 1.0 ± 0.2%, n = 9; 4HTLR24H, 0.8 ± 0.1%, n = 9; 24HPL, 2.9 ± 1.6%, n = 9). Caspase 3 activity/mg protein (1HTLR24H, 15.3 ± 12, n = 3; 4HTLR24H, 58.5 ± 4, n = 3; 24HPL, 56.5 ± 10, n = 3) was similar to that in normal hearts (53.2 ± 11, n = 4), as was caspase 8 activity. No cleaved caspase 3 was seen immunohistochemically, and only rare, definitively identified apoptotic cells were seen by EM in hearts from any group. Apoptosis is de minimus early after transitory or persistent ischemia contrary to its overestimated, large extent as judged from TUNEL. Thus, antiapoptotic interventions per se are not likely to preserve substantial amounts of jeopardized ischemic myocardium early after ischemic insults.
Abstract 15882: Ablation of E2F3 in Endothelial Cells Impairs the Functional Recovery of Heart and Limb from Ischemic Injury
Authors: Junlan Zhou, Min Wu, Min Cheng, Kentaro Jujo, Chan Boriboun, Tina Thorne, Raj Kishore, Douglas W Losordo, Gangjian Qin
Journal: Circulation (2011)

E2F family of transcription factors plays a central role in cell cycle control. However, our recent findings suggest that in endothelial cells (ECs), different E2F members have rather diverse funct...
Classification of Chinese breast cancer patients according to clinically relevant drug target markers
Authors: Jacqueline Liu, CH Su, FY Li, KL King, CY Hsia, HL Kao, SS Lo, YM Shyr, CW Wu, Ry Chen, CW Chi, C Lan, LC Lin, LM Tseng, WY Lui
Journal: Cancer Research (2008)

5490    BACKGROUND:  Microarray breast cancer classification and prognostication gene sets are a significant improvement over the previous TNM staging for such purposes, although these procedures are not commonly available in a pathology lab. Using conventional pathology laboratory techniques, we have formulated a breast cancer classification and potential treatment prediction system based on drug target markers.  METHODS:  From March 1st, 2006 to February 28th, 2007, we prospectively enrolled all newly diagnosed breast cancer patients presenting to the Taipei Veterans General Hospital, General Surgery Department. All specimen were evaluated for preselected drug target markers, including Her2/neu, topoisomerase 2α gene (T2α), and c-myc gene by fluorescence in situ hybridization, followed by T2α, topoisomerase I, thymidylate synthase, excision repair and cross complementing protein, tau, p53, c-myc, PTEN, CK5/6, CK8, and c-kit by immunohistochemistry (IHC).  RESULTS:  A total of 188 female patients with clinically invasive breast cancers were studied, they ranged in age from 26 to 79years, there were 6, 46, 85, 48 and 3 patients in stages 0 (DCIS), 1, 2, 3, and 4 respectively. Pathology showed that 95% had ductal carcinoma, with only 6 lobular, and 3 mucinous carcinomas. The 182 patients could be classified into 4 clinical groups. Her2/neu was amplified in 22.2% (40/182) of patients, but Her2 determination by immunohistochemistry in these patients showed a large discrepancy, being read as 0, 1+, 2+, 3+ in 2, 13, 7, and 20 patients respectively; T2α gene was co-amplified in 18 patients (13 had c-myc amplification) and deleted in 6 patients; t2α protein expression was not detectable in 5 cases, 4 of which had t2α gene deletion; p53 was over-expressed in 45% of cases. Triple negative (ER-, PR-, neu-) cases made up the second group of 17% (31/182) of patients, over-expression of T2α, p53, CK5/6 occurred in 90%, 52%, 56% respectively, c-myc amplification was detected in 2 cases. The third group was ER+, PR+, neu-, and made up 41.2% (75/182) of patients, 96%, 20%, 96% over-expressed T2α, p53, and CK8, 2 patients also had c-myc gene amplification. The 4 th  group of 34 patients (18%) were ER+/ PR- or ER-/PR+, and neu-, 65%, 32%, 90% over-expressed T2α, p53, and CK8, 3 patients also had c-myc gene amplification.  CONCLUSIONS:  Drug target marker stratification of breast cancer provides relevant information for classification, possibly prognostication, and potential treatment direction. Information from this study will form the basis for planning of future treatment trials.
Directed Alternative Splicing in Nijmegen Breakage Syndrome: Proof of Principle Concerning Its Therapeutical Application
Authors: Bastian Salewsky, Gabriele Hildebrand, Susanne Rothe, Ann Christin Parplys, Janina Radszewski, Moritz Kieslich, Petra Wessendorf, Harald Krenzlin, Kerstin Borgmann, André Nussenzweig, Karl Sperling, Martin Digweed
Journal: Molecular Therapy (2015)

Over 90% of patients with Nijmegen breakage syndrome (NBS), a hereditary cancer disorder, are homoallelic for a 5 bp deletion in the NBN gene involved in the cellular response to DNA damage. This hypomorphic mutation leads to a carboxy-terminal protein fragment, p70-nibrin, with some residual function. Average age at malignancy, typically lymphoma, is 9.7 years. NBS patients are hypersensitive to chemotherapeutic and radiotherapeutic treatments, thus prevention of cancer development is of particular importance. Expression of an internally deleted NBN protein, p80-nibrin, has been previously shown to be associated with a milder cellular phenotype and absence of cancer in a 62-year-old NBS patient. Here we show that cells from this patient, unlike other NBS patients, have DNA replication and origin firing rates comparable to control cells. We used here antisense oligonucleotides to enforce alternative splicing in NBS patient cells and efficiently generate the same internally deleted p80-nibrin protein. Injecting the same antisense sequences as morpholino oligomers (VivoMorpholinos) into the tail vein of a humanized NBS murine mouse model also led to efficient alternative splicing in vivo. Thus, proof of principle for the use of antisense oligonucleotides as a potential cancer prophylaxis has been demonstrated. Over 90% of patients with Nijmegen breakage syndrome (NBS), a hereditary cancer disorder, are homoallelic for a 5 bp deletion in the NBN gene involved in the cellular response to DNA damage. This hypomorphic mutation leads to a carboxy-terminal protein fragment, p70-nibrin, with some residual function. Average age at malignancy, typically lymphoma, is 9.7 years. NBS patients are hypersensitive to chemotherapeutic and radiotherapeutic treatments, thus prevention of cancer development is of particular importance. Expression of an internally deleted NBN protein, p80-nibrin, has been previously shown to be associated with a milder cellular phenotype and absence of cancer in a 62-year-old NBS patient. Here we show that cells from this patient, unlike other NBS patients, have DNA replication and origin firing rates comparable to control cells. We used here antisense oligonucleotides to enforce alternative splicing in NBS patient cells and efficiently generate the same internally deleted p80-nibrin protein. Injecting the same antisense sequences as morpholino oligomers (VivoMorpholinos) into the tail vein of a humanized NBS murine mouse model also led to efficient alternative splicing in vivo. Thus, proof of principle for the use of antisense oligonucleotides as a potential cancer prophylaxis has been demonstrated.
Meduna and the origins of convulsive therapy
Authors: Max Fink
Journal: American Journal of Psychiatry (1984)

Convulsive therapy for dementia praecox was first used by the Hungarian neuropsychiatrist Ladislas Meduna in January 1934. On the 50th anniversary the author discusses the introduction of the treatment, the role of a theory of the biological antagonism between epilepsy and schizophrenia, and the contributions of Meduna, Sakel, Cerletti, and Bini. He also describes the changes in usage and methods and the impact of psychotropic drugs on the practice of convulsive therapy.