tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Anatomic Properties of Myocardial Bridge Predisposing to Myocardial Infarction”
Authors: YukioIshikawa, YoshikiyoAkasaka, KinjiIto, ToshiharuIshii, KoyuSuzuki, MiekoFujiwara, TakafumiOgawa, KazutoYamazaki, HitoshiNiino, MichioTanaka, KentaroOgata, ShojirohMorinaga, YoshiroEbihara, YutakaKawahara, HitoshiSugiura, ToshiroTakimoto, AkioKomatsu, ToshihitoShinagawa, KazuhiroTaki, HideakiSatoh, KazuakiYamada, MakiYanagida-Iida, ReikoShimokawa, KazuyukiShimada, ChiakiNishimura
Journal: Circulation (2010)
Sympathetic Denervation and Reinnervation After Arterial Switch Operation for Complete Transposition
Authors: ChisatoKondo, MakotoNakazawa, KazuoMomma, KiyokoKusakabe
Journal: Circulation (1998)

Background—Sympathetic cardiopulmonary nerves arise from the cervical sympathetic trunks and the stellate ganglia and subsequently course along the origin of the great arteries and the coronary arteries to innervate the ventricles. Therefore, the sympathetic nerves may be obligatorily interrupted by the arterial switch operation (ASO) for complete transposition of the great arteries. Methods and Results—To demonstrate and characterize the possible sympathetic denervation, 51 patients after ASO, 4.8 years old (range, 1 month to 10.1 years), underwent [123I]metaiodobenzylguanidine (MIBG) imaging of the sympathetic nerve terminal. MIBG uptake to the heart was graded by quantitative analysis using the heart-to-mediastinum (H/M) ratio of MIBG uptake. A quantitative criterion for absent uptake of MIBG was set to 1.48 in the H/M ratio. Four patients <1 month after ASO showed complete absence of MIBG uptake, which had been observed preoperatively. In contrast, 47 patients late after ASO (range, 15 months to 10.1 ...
Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T‐ALL like mutations
Authors: Xiaoli Mi, Gabriel Griffin, Winston Lee, Sanjay Patel, Robert Ohgami, Chi Young Ok, Sa Wang, Julia T. Geyer, Wenbin Xiao, Mikhail Roshal, Jacqueline S. Garcia, Lewis B. Silverman, Stephen E. Sallan, Jon C. Aster, Marian H. Harris, Olga K. Weinberg
Journal: American Journal of Hematology (2018)

Abstract The B/T subtype of mixed phenotype acute leukemia (B/T MPAL) is defined by co‐expression of antigens of both B‐ and T‐cell lineages on leukemic blasts. Although it has been suggested that multilineage antigen expression portends poor response to chemotherapy, the clinical characteristics and driver mutations that underlie the pathogenesis of this rare subtype of acute leukemia are scarcely known. We identified nine cases of B/T MPAL from multiple institutions and correlated clinical and immunophenotypic findings with next‐generation sequencing data. We report that B/T MPAL commonly presents with lymphadenopathy in adolescence and young adulthood. While the tumors have diverse cytogenetic and genomic perturbations, recurrent acquired aberrations include mutations in the putative transcriptional regulator PHF6 and the JAK‐STAT and Ras signaling pathways. Alterations were also identified in genes encoding hematopoietic transcription factors, cell cycle regulators/tumor suppressors, and chromatin modifying enzymes. The genomic landscape of B/T MPAL strongly resembles that of T‐ALL subgroups associated with early developmental arrest, while genetic alterations that are common in B‐ALL were rarely seen. Two‐thirds of the patients responded to ALL‐based chemotherapy with or without stem cell transplantation. Our observations lay the groundwork for further study of the unique biology and clinical trajectory of B/T MPAL.
Calmodulin Regulation of Excitation-Contraction Coupling in Cardiac Myocytes
Authors: DongmeiYang, Long-ShengSong, Wei-ZhongZhu, KhalidChakir, WeiWang, CaihongWu, YibinWang, Rui-PingXiao, S.R. WayneChen, HepingCheng
Journal: Circulation Research (2003)

Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key molecules involved in excitation-contraction (EC) coupling. In the present study, we report that adenoviral expression of a mutant CaM lacking all of its four Ca2+-binding sites, CaM(1-4), at a level 6.5-fold over endogenous CaM markedly increases the amplitude and abbreviates the decay time of Ca2+ transients and contraction in cultured rat ventricular myocytes. To determine the underlying mechanisms, we examined the properties of L-type Ca2+ channels, Ca2+/CaM-dependent protein kinase II (CaMKII), and phospholamban (PLB) in the sarcoplasmic reticulum (SR). We found that CaM(1-4) expression markedly augmented L-type Ca2+ current amplitude and slowed its inactivation. Surprisingly, overexpression of CaM(1-4) increased CaMKII activity and phosphorylation of PLB-Thr-17. Moreover, CaM(1-4) elevated diastolic Ca2+ and caffeine-labile Ca2+ content of the SR. Inhibition of CaMKII by KN-93 or a myristoylated autocamtide-2 related inhibitory...
Abstract 23087: Applying the FOURIER Trial amongst Real-world Cardiovascular Disease Patients: The Cardiovascular Health in Ambulatory Care Research Team (CANHEART) PCSK9 Study
Authors: Dennis T Ko, Anam M Khan, Gynter Kotrri, Maria Koh, Anna Chu, Peter C Austin, Harindra C Wijeysundera, Jack V Tu
Journal: Circulation (2017)

Background: FOURIER demonstrated a 15% reduction in cardiovascular CV events for patients with CVD. With its high cost, healthcare systems are faced with the potential impact of adopting PCSK9 inhibitors in practice. The goal of this study was to evaluate eligibility, preventable events and incremental costs if FOURIER is applied to the real-world. Methods: The CANHEART cohort is a population-based database of the entire Ontario adult population created by merging multiple individual-level data sources (www.canheart.ca). CVD patients who were alive and 40- 85 years as of January 1 st 2008, and had a cholesterol measurement were included. Similar eligibility for PCSK9 inhibitors with FOURIER was applied. Our primary outcome was a composite of CV death, MI, unstable angina, stroke or coronary revascularization. Number of preventable events was estimated by applying FOURIER’s observed hazard ratio to our cohort’s survival function. The cost to prevent an event was calculated as the cumulative healthcare cost for each patient, assuming PCSK9 inhibitor costs $8,000 CAD (~$6,000 USD)/yr. Results: Of 1.5 million individuals in CANHEART, 62,729 (4.3%) had a history of CVD and 38,348 (2.6% of entire population, 61% of CVD patients) met FOURIER eligibility. Mean age was 66 years, 69% were men, 78% had a history of MI, and 31% were on high dose statins. Within 3 years, 11.9% of patients experienced a primary outcome. PCSK9 inhibitor uptake by all CVD patients was estimated to reduce primary events by 1.9% (746 events avoided) at a cost of $1.14 million CAD per event. Projected event rates, absolute risk reductions and PCSK9 associated costs are shown in the Table . Conclusions: In this large population-based cohort, 2.6% of individuals and 61% of CVD patients fulfil FOURIER criteria for PCSK9 inhibitor use. While the absolute anticipated benefit of adopting this new therapy was similar to that observed in clinical trials, it is associated with substantial costs to prevent each event.
Involvement of Rho-Kinase–Mediated Phosphorylation of Myosin Light Chain in Enhancement of Cerebral Vasospasm
Authors: MotohikoSato, EiichiTani, HirokazuFujikawa, KozoKaibuchi
Journal: Circulation Research (2000)

Abstract—Subarachnoid hemorrhage (SAH) often induces a long-term narrowing of the cerebral artery called cerebral vasospasm. Myosin light chain (MLC) in the spastic basilar artery was reported previously to be phosphorylated by Ca2+/calmodulin-dependent MLC kinase. Because Rho-kinase, which is activated by the small GTPase Rho, phosphorylates not only MLC but also myosin phosphatase at its myosin-binding subunit (MBS), thus inactivating myosin phosphatase, we examined whether Rho-kinase is involved in the development of vasospasm. Cerebral vasospasm was produced in the canine basilar artery by a 2-hemorrhage method, and vasocontractions were induced by topical application of 80 mmol/L KCl or 0.5 μmol/L serotonin to the canine basilar artery exposed transclivally. The phosphorylation of MLC in the basilar artery was increased concurrently with an enhancement in the intensity of vasospasm with the passage of time after SAH. In addition, Rho-kinase in the basilar artery was activated concurrently with an inc...
Abstract 1210: Trend in the incidence of gynecologic malignancies in Federal Teaching Hospital Abakaliki: A 5-year review
Authors: Joseph Agboeze, Robinson Onoh, Matthew Igwe
Journal: Cancer Research (2018)

Abstract Background: Gynecological malignancies are common and are among the leading causes of cancer-related deaths worldwide Objective: To determine the trend in the incidence of gynaecological malignancies in Federal Teaching Hospital, Abakaliki, Nigeria. Methods: This was a retrospective study. The study population was the patients diagnosed of gynaecological cancers at the Federal Teaching Hospital, Abakaliki between January, 2012 to December 2015. Data were extracted from case notes of patients, discharge books and the operating theatre record books. The data were analyzed using Epi Info version 7.1.4 and the results expressed in descriptive statistics by simple percentages. Results: There were 2528 gynaecological admissions during the period. There were 97 women who had genital tract malignancies giving an incidence of 3.8% of gynaecological admissions. Cervical cancer was the most common female genital tract malignancy occurring in 68% of gynaecological cancers, followed by ovarian cancer (11.3%), Endometrial cancer (8.3%), Vulva cancer (6.2%),Choriocarcinoma (4.1%), and the least was leiomyosarcoma (1.0%). The mean age was 54.2 ±11.9 years.The incidences of cervical, ovarian vulva and endometrial cancers showed a steady increase over the period. Choriocarcinoma did not show a significant change in incidence. Conclusion: This study showed the rising incidences of gynaecological cancers. Cancer of the cervix is the commonest gynaecological malignancy and most patients presented late. Cervical cancer screening programmes, early detection and awareness campaign is highly recommended. Citation Format: Joseph Agboeze, Robinson Onoh, Matthew Igwe. Trend in the incidence of gynecologic malignancies in Federal Teaching Hospital Abakaliki: A 5-year review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1210.
Characteristics and Distribution of M Cells in Arterially Perfused Canine Left Ventricular Wedge Preparations
Authors: Gan-XinYan, WataruShimizu, CharlesAntzelevitch
Journal: Circulation (1998)

Background—Much of the characterization of the M cell to date has been accomplished using isolated tissues and cells. This study uses an arterially perfused wedge preparation to examine the characteristics and distribution of M cells within the anterior wall of the canine left ventricle under more physiological conditions. Methods and Results—Floating microelectrodes were used to record transmembrane action potentials simultaneously from epicardial, M region, and endocardial or subendocardial Purkinje sites in isolated arterially perfused canine left ventricular wedge preparations. A transmural ECG was recorded concurrently. M cells with the longest action potentials were found in the deep subendocardium in wedge preparations isolated from the anterior wall of the left ventricle. Fairly smooth transitions in action potential duration (APD) were observed except in the region between epicardium and deep subepicardium. Tissue resistivity increased 2.8-fold in this region and much more modestly in the deep su...
Abstract 18854: Markers of Bone Metabolism and Cardiovascular Mortality in Ischaemic Cardiomyopathy
Authors: Martin RGrubler, NicolasVerheyen, JohannesSchmid, AstridFahrleitner-Pammer, LorenzRäber, AndreasTomaschitz, StefanPilz, WinfriedMärz
Journal: Circulation (2016)

Background: In patients with ischaemic cardiomyopathy high rates of fracture related mortality have been reported. A growing body of evidence suggests a complex interaction between heart failure, congestion, limited physical activity and bone health. More so, recent studies showed that increased markers of bone metabolism, i.e. Beta CrossLaps (CTX) and Osteocalcin (OC), are associated with reduced LV systolic function and increased LV stiffness. Nevertheless, whether CTX and OC are associated with cardiovascular (CV) mortality and pro-brain-natriuretic peptide levels (proBNP) in ischaemic cardiomyopathy is still debated. Methods: We analysed participants of a prospective cohort study of patients referred to coronary angiography at a tertiary care centre in Germany between 1997 and 2000. Indications for coronary angiography were based on clinical routine, most commonly chest pain, dyspnoea or second to non-invasive tests. For the current analysis only patients with an LV-EF < 50% and 2- or 3-vessel coronar...
Abstract SY38-01: Inflammation-induced neutrophil extracellular traps (NETs) awaken dormant cancer in the lung microenvironment
Authors: Mikala Egeblad
Journal: Cancer Research (2018)

Abstract To elucidate mechanisms of cancer metastasis and recurrence from minimal residual disease, we use intravital imaging allowing for long-term visualization of cancer cells and surrounding host cells in living mice. Using intravital imaging, we found that neutrophils, the most abundant type of leukocytes in blood, form neutrophil extracellular traps (NETs) near disseminated cancer cells in the lung of mice during experimental inflammation. NETs are pathogen-trapping structures generated by expulsion of the neutrophil's DNA with associated proteolytic enzymes in response to, e.g., infections. However, we found that metastatic breast cancer cells themselves can induce neutrophils to form metastasis-supporting NETs, in the absence of infection. We also found NETs in clinical samples of metastatic, triple-negative human breast cancer. Using mouse models, we determined that NETs promote metastasis by facilitating proteolytic extracellular matrix remodeling. Pharmacologic inhibition of NET formation or digestion of NETs with DNase I-coated nanoparticles markedly reduced lung metastases in mice. Our data suggest that induction of NETs is an important host-mediated mechanism of promoting metastasis and a potential therapeutic target. Citation Format: Mikala Egeblad. Inflammation-induced neutrophil extracellular traps (NETs) awaken dormant cancer in the lung microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY38-01.
Abstract 3154: Harnessing the adaptive potential of mechanoresponsive proteins to overwhelm pancreatic cancer dissemination and invasion
Authors: Alexandra Surcel, Eric S. Schiffhauer, Dustin G. Thomas, Qingfeng Zhu, Kathleen DiNapoli, Maik Herbig, Oliver Otto, Jochen Guck, Elizabeth Jaffee, Pablo A. Iglesias, Robert A. Anders, Douglas N. Robinson
Journal: Cancer Research (2018)

Abstract Metastatic disease is often characterized by altered cellular contractility and deformability, lending cells and groups of cells the flexibility to navigate through different microenvironments. This ability to change cell shape is driven in large part by the structural elements of the mechanobiome, which includes cytoskeletal proteins that sense and respond to mechanical stimuli. Here, we demonstrate that key mechanoresponsive proteins (those that accumulate in response to mechanical stress), specifically nonmuscle myosin IIA and IIC, α- actinin 4, and filamin B, are highly upregulated in pancreatic ductal adenocarcinoma cancer (PDAC) and in patient-derived pancreatic cancer cell lines. Their less responsive sister paralogs (myosin IIB, α-actinin 1, and filamin A) show a smaller dynamic range or disappear with PDAC progression. We demonstrate that these mechanoresponsive proteins directly impact cell mechanics using knockdown and overexpression cell lines. We further quantify the nonmuscle myosin II family members in patient-derived cell lines and identify a role for myosin IIC in the formation of transverse actin arcs in single cells and cortical actin belts in tissue spheroids. We harness the upregulation of myosin IIC and its impact of cytoskeletal architecture through the use of the mechanical modulator 4-hydroxyacetophenone (4-HAP), which increases myosin IIC assembly and stiffens cells. Here, 4-HAP decreases dissemination, induces cortical actin belts, and slows retrograde actin flow in spheroids. Finally, mice having undergone hemisplenectomies with PDAC cells and then treated with 4-HAP have a reduction in liver metastases. Thus, increasing the activity of these mechanoresponsive proteins (in this case, by increasing myosin IIC assembly) to overwhelm the ability of cells to polarize and invade may be an effective strategy to improve the five-year survival rate of pancreatic cancer patients, currently hovering around 6%. Citation Format: Alexandra Surcel, Eric S. Schiffhauer, Dustin G. Thomas, Qingfeng Zhu, Kathleen DiNapoli, Maik Herbig, Oliver Otto, Jochen Guck, Elizabeth Jaffee, Pablo A. Iglesias, Robert A. Anders, Douglas N. Robinson. Harnessing the adaptive potential of mechanoresponsive proteins to overwhelm pancreatic cancer dissemination and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3154.
Abstract LB-048: c-Kit enhances ovarian cancer stemness via upregulating phospho-PHB in the lipid raft domain of the plasma membrane
Authors: Shu-Mei Y. Liang, Chia-Hsun Fang, Pu-Yuan Chang, Chi-Ming Liang
Journal: Cancer Research (2018)

Abstract Phosphorylation of prohibitin (PHB) at threonine 258 (phospho-PHBT258) and tyrosine 259 (phospho-PHBY259) in human cancer-cell membranes is associated with an increase in the invasiveness and metastasis of cancer cells. Phospho-PHBY259 can regulate phospho-PHBT258 but not vice versa. Here, we found that stably overexpressing c-Kit in SKOV3 ovarian cancer cells (SKOV3_c-Kit) increased phospho-PHBY259, phospho-PHBT258 and PHB levels in the lipid raft domain of the plasma membrane. On the other hand, inhibition of c-Kit expression decreased PHB expression in SKOV3_c-Kit and Kuramochi ovarian cancer cells. Immunoprecipitation analysis showed that c-Kit interacts with PHB. SKOV3_c-Kit cells or SKOV3 cells overexpressing PHB in the lipid raft had higher levels of Notch3, NICD3 (Notch3 intracellular domain) and ABCG2 protein expression as compared to wild-type SKOV3 cells. Moreover, generation of SKOV3-G4 cells through serial passage of SKOV3 cells into nude mice ovary 4 times, revealed that the levels of c-Kit, Notch3, NICD3, phospho-PHBY259, phospho-PHBT258 and PHB in the lipid raft domain of SKOV3-G4 were significantly higher than wild-type SKOV3 cells. The SKOV3-G4 cells formed spheroids with stem cell-like properties such as higher expression of stem cell markers (Oct4, Nanog, SOX2). In addition, SKOV3-G4 cells exhibited more clonogenic potential and migration/invasion ability than wild-type SKOV3. These results suggest that c-Kit interacts with PHB in the lipid raft domain to phosphorylate PHB to increase invasiveness and stemness in ovarian cancer. Citation Format: Shu-Mei Y. Liang, Chia-Hsun Fang, Pu-Yuan Chang, Chi-Ming Liang. c-Kit enhances ovarian cancer stemness via upregulating phospho-PHB in the lipid raft domain of the plasma membrane [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-048.
Efficacy and safety of daylight photodynamic therapy after tailored pretreatment with ablative fractional laser or microdermabrasion: a randomized, side‐by‐side, single‐blind trial in patients with actinic keratosis and large‐area field cancerization
Authors: E. Wenande, W. Phothong, C. Bay, K.E. Karmisholt, M. Haedersdal, K. Togsverd‐Bo
Journal: British Journal of Dermatology (2018)

Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). Two ≥ 50‐cm2 side‐by‐side skin areas were randomized to receive a single treatment with AFL‐dPDT or MD‐dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2‐h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3‐month follow‐up. In 18 patients with 832 AKs, AFL‐dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD‐dPDT. Peaking at days 3–6, AFL‐PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL‐dPDT (P = 0·077), due to lower pretreatment‐related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD‐dPDT. AFL‐dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions.
Adrenomedullin Enhances Angiogenic Potency of Bone Marrow Transplantation in a Rat Model of Hindlimb Ischemia
Authors: TakashiIwase, NoritoshiNagaya, TakafumiFujii, TakefumiItoh, HatsueIshibashi-Ueda, MasakazuYamagishi, KunioMiyatake, ToshioMatsumoto, SoichiroKitamura, KenjiKangawa
Journal: Circulation (2005)

Background— Previous studies have shown that adrenomedullin (AM) inhibits vascular endothelial cell apoptosis and induces angiogenesis. We investigated whether AM enhances bone marrow cell–induced angiogenesis. Methods and Results— Immediately after hindlimb ischemia was created, rats were randomized to receive AM infusion plus bone marrow–derived mononuclear cell (MNC) transplantation (AM+MNC group), AM infusion alone (AM group), MNC transplantation alone (MNC group), or vehicle infusion (control group). The laser Doppler perfusion index was significantly higher in the AM and MNC groups than in the control group (0.74±0.11 and 0.69±0.07 versus 0.59±0.07, respectively, P<0.01), which suggests the angiogenic potency of AM and MNC. Importantly, improvement in blood perfusion was marked in the AM+MNC group (0.84±0.08). Capillary density was highest in the AM+MNC group, followed by the AM and MNC groups. In vitro, AM inhibited MNC apoptosis, promoted MNC adhesiveness to a human umbilical vein endothelial cell...