tbuckley/cabot-search huggingface dataset:
Simultaneous Hypoglycemia and Acute Congestive Heart Failure
Authors: Georgebenzing, Williamschubert, Georgehug, Samuelkaplan
Journal: Circulation (1969)

Acute congestive cardiac failure and hypoglycemia were observed simultaneously in 27 patients with underlying heart disease. Seventeen of this group had the hypoplastic left heart syndrome, two had transposition of the great vessels, and four had hypoglycemia postoperatively. Liver biopsy in four patients revealed a marked reduction of hepatic glycogen both biochemically and electron microscopically but normal phosphorylase and glucose-6-phosphatase activity. Reduction of their dietary intake and gastrointestinal malabsorption caused by congestive cardiac failure are suggested as possible mechanisms for the observed hepatic glycogen depletion. Constant intravenous infusion of glucose is the method of choice for the treatment of patients with acute congestive cardiac failure and hypoglycemia rather than epinephrine or glucagon. Five patients recovered sufficiently following treatment of hypoglycemia and acute cardiac failure to be discharged from the hospital.
Abstract 1995: PTHrP drives tumor initiation signaling pathways in the PyMT model of breast cancer progression
Authors: Rui Zhang, Jiarong Li, Dunarel Badescu, Andrew Karaplis, Jiannis Ragoussis, Richard Kremer
Journal: Cancer Research (2018)

Abstract Parathyroid hormone-related peptide (PTHrP) was first discovered in cancer patients as the primary cause of malignancy associated hypercalcemia (MAH) &amp; is overexpressed in most human breast tumors. We previously showed that PTHrP ablation, in the MMTV-PyMT murine model of breast cancer progression can dramatically prolong tumor latency, slows tumor growth &amp; metastases. Here we examined the signaling pathways under the control of PTHrP in the pre-neoplastic stage of tumor development (hyperplasia) by generating MMTV-PyMT model in which the mammary epithelium, expressing membrane-targeted GFP, is distinguished from the membrane-targeted red fluorescent backlight of stromal &amp; nonepithelial-derived mammary tissues. We constructed Pthrpflox/flox; Cre+ mT/mG tumor mice (PTHrP conditional KO) &amp; Pthrpwt/wt; Cre+ mT/mG tumor mice (WT control). Next, we applied FACS to enrich the GFP+ mammary epithelial cells isolated from PTHrP KO &amp; control tissues for subsequent RNAseq analyses. We then examined differentially expressed genes (DEGs) by comparing purified cell populations from PTHrP KO &amp; control tissues. We identified 939 DEGs (p value &amp;lt;0.01) &amp; used DAVID bioinformatics resources to systematically analyze the KEGG pathways. Among the most significant pathways, extracellular matrix (ECM), focal adhesion,PI3K-Akt, RAS and WNT pathways were up-regulated in WT control cells compared to KO cells. In summary, PTHrP controls critical signaling pathways involved in breast cancer initiation at the pre-neoplastic stage &amp; suggests that PTHrP ablation is a promising therapeutic strategy in breast cancer. Citation Format: Rui Zhang, Jiarong Li, Dunarel Badescu, Andrew Karaplis, Jiannis Ragoussis, Richard Kremer. PTHrP drives tumor initiation signaling pathways in the PyMT model of breast cancer progression [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 1995.
Contribution of Endothelin-1 to Myocardial Injury in a Murine Model of Myocarditis
Authors: KohOno, AkiraMatsumori, TetsuoShioi, YutakaFurukawa, ShigetakeSasayama
Journal: Circulation (1999)

Background—Endothelin (ET) is one of the most important contributing factors in the pathophysiology of cardiovascular diseases. However, little is known about its role in myocarditis. Methods and Results—Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. Expression levels of ET-converting enzyme-1 (ECE-1) and prepro-ET-1 mRNA were significantly increased at 7 and 14 days after virus inoculation. Plasma and myocardial ET-1 levels were significantly higher in infected than noninfected mice between 5 and 14 days after virus inoculation. Immunohistochemical analyses revealed that not only endothelial cells and myocytes but also infiltrating mononuclear cells produced ET-1 protein at 7 days. Oral bosentan, a mixed ET-1 receptor antagonist, was administered after virus inoculation in doses of 0 (control group), 10, or 100 mg · kg−1 · d−1, and the animals were killed on day 14. Mean heart weight/body weight ratios were 8.3±1.8 versus 11.2±2.4 versus 10.8±2.4 in the bosentan 100 mg · kg...
Abstract 9421: Additional Wiping of the Skin With 70% Isopropil Alcohol Just Before Routine Povidone-Iodine Antisepsis Reduces Cardiac Implantable Electronic Device Infections
Authors: TakanoriTakahashi, JunichiShimotakahara, NobuhitoYagi, JunNakazato, TadayoshiMiyagi, MinoruWake, KazuhitoHirata
Journal: Circulation (2014)

Introduction: Cardiovascular Implantable Electronic Device(CIED) Infections are one of the most serious complication after CIED implantation or replacement. To prevent infection, appropriate skin antisepsis and perioperative antibiotic prophylaxis at CIED implantation/replacement are important. But the most optimal antisepsis for CIED surgery is not well defined. Then we assessed whether additional wiping of the skin with 70% isopropyl alcohol just before routine skin antisepsis with povidone-iodine reduces the incidence of CIED infection. Methods: Consecutive 473 cases of CIED implantation or generator replacement from Jan.2008 to Dec.2013 at one community hospital were divided into two groups according to preoperative skin antisepsis with 70% isopropyl alcohol wipes lasting for at least 1 minute just before povidone-iodine scrub and paint(IPA group, n=183), or povidone-iodine only(No IPA group, n=290). All cases received perioperative antibiotic prophylaxis 30 minute before and 6 hours after procedure. ...
Hypoxic Stress Induces Cardiac Myocyte–Derived Interleukin-6
Authors: KeikoYamauchi-Takihara, YoshijiIhara, AtsushiOgata, KazuyukiYoshizaki, JunichiAzuma, TadamitsuKishimoto
Journal: Circulation (1995)

Background Hypoxic and ischemic stresses cause a series of well-documented changes in myocardial cells and tissues, including loss of contractility, changes in lipid and fatty acid metabolism, and irreversible membrane damage leading to eventual cellular death. Activated neutrophils are considered to be involved in this myocardial cellular injury. By stimulation of the neutrophils with chemotactic factors, canine neutrophils can be induced to adhere to isolated cardiac myocytes only if the myocytes have been previously exposed to cytokines such as tumor necrosis factor–α, interleukin (IL)-1, and IL-6. Methods and Results To examine the possible involvement of IL-6 in ischemia-reperfusion injury, we used cultured rat neonatal cardiac myocytes to study the effects of hypoxic stress on the production of IL-6 by cardiac myocytes. Unstimulated cardiac myocytes (3×105 cells per dish) produced 320 pg IL-6 over 4 hours in vitro (ie, biological activity equal to 320 pg recombinant IL-6, as detected by bioassay usi...
Phase II study of lenvatinib in patients with differentiated, medullary, and anaplastic thyroid cancer: Final analysis results.
Authors: Shunji Takahashi, Naomi Kiyota, Tomoko Yamazaki, Naoko Chayahara, Kenji Nakano, LINA INAGAKI, Kazuhisa Toda, Tomohiro Enokida, Hironobu Minami, Yoshinori Imamura, Tatsuya Sasaki, Takuya Suzuki, Katsuki Fujino, Corina Dutcus, Makoto Tahara
Journal: Journal of Clinical Oncology (2016)

6088 Background: Thyroid cancer is classified into differentiated (DTC), medullary (MTC), and anaplastic (ATC) types. Lenvatinib (LEN) significantly prolonged progression-free survival (PFS) vs placebo in the phase III SELECT trial of patients (pts) with 131I-refractory DTC (RR-DTC). Initial results of this phase 2 trial (Study 208) of LEN in RR-DTC, MTC, and ATC were reported with a cutoff date of 15 Jun 2014. Here we report the final results of this study. Methods: This was a single-arm, open-label, phase 2 study conducted in Japan with an updated data cutoff of 9 Jul 2015. Pts received LEN 24 mg/d in 28-d cycles until progressive disease or development of unacceptable toxicity. Primary endpoint was safety; secondary endpoint was efficacy as assessed by PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Results: 51 Pts, including 25 pts with RR-DTC (previously 23), 9 pts with MTC, and 17 pts with ATC (previously 11) were enrolled. All pts had at least one treatment-emergent adverse event (TEAE). The most common any-grade TEAEs included hypertension (90%), decreased appetite (78%), palmar-plantar erythrodysaesthesia syndrome (77%), fatigue (73%), proteinuria (61%), stomatitis (57%), and diarrhea (55%). Incidences of Grade 3 and 4 TEAEs were similar among subgroups (RR-DTC, 72%; MTC, 100%; ATC, 88%). Of note, only 1 pt discontinued treatment due to a TEAE. There were 4 fatal serious AEs, all considered unrelated to LEN. Tumor shrinkage occurred in most pts, including pts with ATC. Median duration of treatment was 5.5 mos (range, 0.7–33.1) for pts with ATC; 8 received LEN for more than 6 mos. Efficacy parameters are shown in the table below. Conclusions: In this study, LEN showed tumor shrinkage in almost all pts with advanced thyroid cancer, including pts with ATC. Toxicities were manageable with dose modifications. LEN efficacy especially in ATC warrants further investigation. Clinical trial information: NCT01728623. RR-DTC (n = 25) MTC (n = 9) ATC (n = 17) Median PFS (95% CI)―mos. 25.8 (18.4–NE) 9.2 (1.8–NE) 7.4 (1.7–12.9) Median OS (95% CI)―mos. 31.8 (31.8–NE) 12.1 (3.8–NE) 10.6 (3.8–19.8) ORR―n (%)* 17 (68) 2 (22) 4 (24) DCR―n (%) 25 (100) 9 (100) 12 (71) NE, not evaluable. *All partial responses.
Abstract 4695: Murine tumor growth suppression through CD8+CTLs via activated DEC-205+dendritic cells by sequential administration of α-galactosylceramide in vivo
Authors: Hideki Kogo, Hidemi Takahashi, Eiji Uchida
Journal: Cancer Research (2018)

Abstract Cancer immunotherapy is mediated by the effective priming and activation of tumor-specific class I major histocompatibility complex molecule-restricted CD8+ cytotoxic T lymphocytes. DEC-205+ dendritic cells can cross-present the epitopes of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8+ CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of insufficient CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 mice and do not prime CD8+ CTLs. Here, we show that the growing of tumors was suppressed by activated CD8+ CTLs with tumor-specific cytotoxicity through the administration of the glycolipid α-galactosylceramide, which is a compound known to stimulate invariant natural killer T cells and selectively activate DEC-205+ DCs. Moreover, we demonstrated that sequential repetitive intraperitoneal inoculation of α-GalCer every 48 hour appeared to convert tolerogenic DEC-205+ DCs into immunogenic DCs with a higher expression of co-stimulatory molecules and a greater cross-presentation capacity, which primed CTL precursors and induced tumor-specific CD8+ CTLs within the tumor environment without activating iNKT cells. These findings provide a new basis for cancer immunotherapy to convert tolerogenic DEC-205+ DCs within tumors into immunogenic DCs via the sequential administration of an immuno-potent lipid/glycolipid, and activated immunogenic DCs expressing sufficient suitable co-stimulatory molecules will prime and activate tumor-specific CD8+ CTLs within the tumor to control tumor growing. Citation Format: Hideki Kogo, Hidemi Takahashi, Eiji Uchida. Murine tumor growth suppression through CD8+CTLs via activated DEC-205+dendritic cells by sequential administration of α-galactosylceramide in vivo [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 4695.
Abstract 4779: Rogaratinib, a small molecule pan-FGFR inhibitor potently inhibits FGFR4-phosphorylation and exerts anti-tumor efficacy in vivo and in vitro
Authors: Oliver Politz, Sylvia Gruenewald, Alexander Walter, Franziska Siegel, Arne Scholz, Sebastian Bender, Christoph Kneip, Peter Ellinghaus
Journal: Cancer Research (2018)

Abstract Fibroblast growth factor signaling plays an essential role in many physiological processes, including cell proliferation, survival, differentiation, migration, and apoptosis Over-activation of the pathway can lead to the development of various cancers. There are four different FGFR subtypes with over 20 ligands providing a very complex network of interactions and signaling. FGFR4 plays an important role in normal physiology such as myogenesis muscle regeneration and bile acid synthesis Activating mutations in the kinase domain of FGFR4 have been shown to mediate cancer development, for example, breast cancer, hepatocellular carcinoma (HCC) or rhabdomyosarcoma. Rogaratinib is a potent inhibitor of all FGFR subtypes with low nanomolar binding kinetics towards the four kinase domains. We explored the effect of rogaratinib on cell lines with high expression levels of FGFR4 mRNA, such as breast cancer cell line MDA-MB453 and rhabdomyosarcoma cell line SH30. We could show that the proliferation of these cell lines is potently inhibited by rogaratinib and accompanied with induction of apoptosis. The Mode-of-action analysis of rogaratinib activity in these cell lines showed inhibition of FGFR4-phosphorylation and downstream signaling at clinical relevant doses. The in vitro efficacy of rogaratinib in FGFR4 dependent cell lines was further observed as in vivo efficacy in xenograft models of rhabdomyosarcoma and HCC. Elevation of FGFR4 expression has been associated with resistance development in several cancer types such as breast cancer. In line with the observed anti-tumor efficacy of rogartinib in vitro and in vivo in breast cancer, sarcoma and HCC models, RNA in situ hybridization by RNAscope, revealed high FGFR4 mRNA expression in TMA's from these tumor types..) The combination of rogaratinib with standard-of-care provides further options for addressing resistance mechanisms mediated by elevated FGFR4 expression. In addition we have profiled a number of patient derived HCC xenograft models revealing the high efficacy of rogaratinib in models with elevated FGFR expression including FGFR4. Citation Format: Oliver Politz, Sylvia Gruenewald, Alexander Walter, Franziska Siegel, Arne Scholz, Sebastian Bender, Christoph Kneip, Peter Ellinghaus. Rogaratinib, a small molecule pan-FGFR inhibitor potently inhibits FGFR4-phosphorylation and exerts anti-tumor efficacy in vivo and in vitro [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 4779.
Periadventitial Adipose Tissue Plays a Critical Role in Vascular Remodeling
Authors: MinoruTakaoka, DaisukeNagata, ShinjiKihara, IichiroShimomura, YuKimura, YasuhikoTabata, YoshihikoSaito, RyozoNagai, MasatakaSata
Journal: Circulation Research (2009)

Rationale: Obesity is associated with a high incidence of cardiovascular complications. However, the molecular link between obesity and vascular disease is not fully understood. Most previous studies have focused on the association between cardiovascular disease and accumulation of visceral fat. Periadventitial fat is distributed ubiquitously around arteries throughout the body. Objective: Here, we investigated the impact of obesity on inflammation in the periadventitial adipose tissue and on lesion formation after vascular injury. Methods and Results: High-fat, high-sucrose feeding induced inflammatory changes and decreased adiponectin expression in the periadventitial adipose tissue, which was associated with enhanced neointima formation after endovascular injury. Removal of periadventitial fat markedly enhanced neointima formation after injury, which was attenuated by transplantation of subcutaneous adipose tissue from mice fed on regular chow. Adiponectin-deficient mice showed markedly enhanced lesion...
Corrigendum to “Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies” [J hepatol 67 (2017) 999–1008]
Authors: Jordi Bruix, Ann-Lii Cheng, Gerold Meinhardt, Keiko Nakajima, Yoriko De Sanctis, Josep Llovet
Journal: Journal of Hepatology (2018)
Mental Stress–Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction
Authors: Viola Vaccarino, Samaah Sullivan, Muhammad Hammadah, Kobina Wilmot, Ibhar Al Mheid, Ronnie Ramadan, Lisa Elon, Pratik M. Pimple, Ernest V. Garcia, Jonathon Nye, Amit J. Shah, Ayman Alkhoder, Oleksiy Levantsevych, Hawkins Gay, Malik Obideen, Minxuan Huang, Tené T. Lewis, J. Douglas Bremner, Arshed A. Quyyumi, Paolo Raggi
Journal: Circulation (2018)

Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown.
Increased Expression of Interleukin-1β and Monocyte Chemotactic and Activating Factor/Monocyte Chemoattractant Protein-1 in the Hypertrophied and Failing Heart With Pressure Overload
Authors: TetsuoShioi, AkiraMatsumori, YasukiKihara, MoriakiInoko, KohOno, YoshitakaIwanaga, TakehikoYamada, AtsushiIwasaki, KoujiMatsushima, ShigetakeSasayama
Journal: Circulation Research (1997)

Abstract Studies on the effects of proinflammatory cytokines on the heart suggest that they play some roles in the pathogenesis of congestive heart failure (CHF). To determine the involvement of proinflammatory cytokine in cardiac hypertrophy and CHF induced by mechanical overload, we investigated the expression of interleukin (IL)-1β and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the left ventricle (LV) of Dahl salt-sensitive (DS) rats that showed hypertrophy of the LV induced by hypertension and subsequently developed CHF. The IL-1β mRNA content in the LV of DS rats increased 3.9-fold when LV hypertrophy developed, and the increase reached 6.2-fold at the CHF stage compared with that of age-matched Dahl salt-resistant (DR) rats. The amount of IL-1β in the LV was positively correlated with the LV weight/body weight ratio. Most of the IL-1β immunoreactivity was localized in the endothelial cells and interstitial macrophages. The mRNA levels of MCAF in t...
CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient
Authors: Daniela Benati, Francesca Miselli, Fabienne Cocchiarella, Clarissa Patrizi, Marta Carretero, Samantha Baldassarri, Virginia Ammendola, Cristina Has, Stefano Colloca, Marcela Del Rio, Fernando Larcher, Alessandra Recchia
Journal: Molecular Therapy (2018)

Deficiency of basement membrane heterotrimeric laminin 332 component, coded by LAMA3, LAMB3, and LAMC2 genes, causes junctional epidermolysis bullosa (JEB), a severe skin adhesion defect. Herein, we report the first application of CRISPR/Cas9-mediated homology direct repair (HDR) to in situ restore LAMB3 expression in JEB keratinocytes in vitro and in immunodeficient mice transplanted with genetically corrected skin equivalents. We packaged an adenovector carrying Cas9/guide RNA (gRNA) tailored to the intron 2 of LAMB3 gene and an integration defective lentiviral vector bearing a promoterless quasi-complete LAMB3 cDNA downstream a splice acceptor site and flanked by homology arms. Upon genuine HDR, we exploited the in vitro adhesion advantage of laminin 332 production to positively select LAMB3-expressing keratinocytes. HDR and restored laminin 332 expression were evaluated at single-cell level. Notably, monoallelic-targeted integration of LAMB3 cDNA was sufficient to in vitro recapitulate the adhesive property, the colony formation typical of normal keratinocytes, as well as their cell growth. Grafting of genetically corrected skin equivalents onto immunodeficient mice showed a completely restored dermal-epidermal junction. This study provides evidence for efficient CRISPR/Cas9-mediated in situ restoration of LAMB3 expression, paving the way for ex vivo clinical application of this strategy to laminin 332 deficiency.
Abstract 1410: Clarithromycin Inhibited MMP-9 Activation and Attenuated Acute and Chronic Rejection in Murine Cardiac Allografts
Authors: Jun-ichi Suzuki, Masahito Ogawa, Kiyoshi Takayama, Mitsuaki Isobe
Journal: Circulation (2007)

Background: Matrix metalloproteinases (MMPs) are critical in the development of inflammation and tissue remodeling. MMP-9 is a key member of MMPs and the level is associated with the rejection of heart transplantation. Clarithromysin (CAM), a major macrolide antibiotic, has been many biological functions including MMP regulation. However, little is known about the effect of CAM in heart transplantation via MMP-9. Methods and Results: To clarify the role of MMPs regulated by CAM in the progression of rejection, we orally administered CAM (100mg/kg) into murine cardiac allograft recipients. CAM improved acute rejection judged by graft survival (control: 7.3+/−0.2 days n=8; CAM: 9.7+/−0.2 days n=8; P&lt;0.05) and by myocardial cell infiltrating area (control: 35.7+/−1.9% n=9; CAM: 19.7+/−3.0% n=9, P&lt;0.05) in a total allomismatch combination. 8 weeks after transplantation, CAM significantly suppressed the development of graft arterial disease (5.1+/−3.0%, n=6) compared to that of non-treatment (25.1+/−6.3%, n=6; P&lt;0.05) in the class II mismatch combination. Immunohistochemically, non-treated allografts showed enhanced expression of T-cells, macrophages, MMP-9 and NF-kappaB while CAM decreased these positive cell numbers. RPA also revealed that CAM-treated allografts significantly attenuated the expression of proinflammatory cytokines such as IFN-gamma, IL-6, IL-10 and IL-15 compared with non-treated grafts. In situ zymography indicated that enhanced MMPs activities were observed in non-treated hearts, while CAM suppressed the levels. In vitro study showed that CAM inhibited the expression of MMP-9 using Western blot and RT-PCR in cytokine stimulated macrophages and SMCs. The effects of inhibited MMP-9 by CAM suppressed SMCs migration (native: 23.5+/−4.5 cells, control: 97.0+/− 5.0, CAM: 53.4+/−4.5, P&lt;0.05) and proliferation (native: 0.44+/−0.01OD, control: 0.56+/−0.03, CAM: 0.44+/−0.004, P&lt;0.05) compared with control. Conclusion: CAM is useful to suppress allograft remodeling because it is critically involved in the prevention of cardiac rejection through the suppression of MMP-9.