tbuckley/cabot-search huggingface dataset:
Mouse hepatocyte overexpression of NF‐κB‐inducing kinase (NIK) triggers fatal macrophage‐dependent liver injury and fibrosis
Authors: Hong Shen, Liang Sheng, Zheng Chen, Lin Jiang, Haoran Su, Lei Yin, M. Bishr Omary, Liangyou Rui
Journal: Hepatology (2014)

Damaged, necrotic, or apoptotic hepatocytes release damage-associated molecular patterns that initiate sterile inflammation, and liver inflammation drives liver injury and fibrosis. Here we identified hepatic nuclear factor kappa B (NF-κB)-inducing kinase (NIK), a Ser/Thr kinase, as a novel trigger of fatal liver inflammation. NIK is activated by a broad spectrum of stimuli. It was up-regulated in injured livers in both mice and humans. In primary mouse hepatocytes, NIK overexpression stimulated, independently of cell injury and death, release of numerous chemokines and cytokines that activated bone marrow-derived macrophages (BMDMs). BMDMs in turn secreted proapoptotic molecules that stimulated hepatocyte apoptosis. Hepatocyte-specific expression of the NIK transgene triggered massive liver inflammation, oxidative stress, hepatocyte apoptosis, and liver fibrosis, leading to weight loss, hypoglycemia, and death. Depletion of Kupffer cells/macrophages reversed NIK-induced liver destruction and death.the hepatocyte NIK-liver immune cell axis promotes liver inflammation, injury, and fibrosis, thus driving liver disease progression.
Effect of Cortisone on Skin Maintained in Organ Culture&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ronald W. Gillette, Angelica Findley, Herbert Conway
Journal: JNCI Journal of the National Cancer Institute (1961)

Full-thickness auricular skin from adult mice was maintained in organ culture and treated with cortisone acetate for periods up to 4 weeks. The skin was floated on a complex protein medium by a technique that has been previously described. Successful grafting of the skin back to the original donor was considered a reliable criterion of the preservation of its structural integrity while in culture. Ninety-six organ cultures were maintained and subsequently grafted at weekly intervals. Cortisone acetate was added to half the cultures in an attempt to suppress the process of cell modulation in the connective-tissue layers. Gross and microscopic observations revealed that the disorganizing process occurring in the untreated cultures of skin was suppressed substantially in the cultures treated with cortisone. After 3 weeks in vitro, none of the control cultures could be autografted successfully, but 83 percent of the grafts treated with cortisone were transplanted successfully. It was apparent that cortisone acetate is effective in slowing the processes responsible for the degenerative modifications of organized skin in vitro. The effects of other steroid compounds are currently under study.
Lesson of the Week: Adult epiglottitis: prompt diagnosis saves lives
Authors: M J Stuart, T J Hodgetts
Journal: BMJ (1994)

* Morality from adult epilottis may be reduced by prompt action, which requires increased awareness of the disease's existence

Acute epiglottitis is a well recognised life threatening infectious disease of children. It is so uncommon in adults that many doctors are unaware of its existence, and few have experience of a case. Failure to diagnose epiglottitis early in adults undoubtedly contributes to its continuing mortality, which may be higher than in children.1 We report two cases of adult epiglottitis seen over three years in this emergency department. In one case diagnosis was prompt and the patient survived, and in the other epiglottitis was not diagnosed and the patient died.

### Case 1

In July 1990 a 35 year old white man referred himself to the emergency department on a weekday afternoon, having suffered for five days with a sore throat that had started two days after returning from holiday in Portugal. In the morning the pain had increased and he had difficulty in swallowing and had experienced rigors. The triage nurse observed that he had a painful throat and was shaking. He had a high fever (39.4°C) and was noted to be only mildly distressed. His pharynx was inflamed, with minimal tonsillar enlargement; he had bilateral upper cervical lymphadenopathy. A senior house officer diagnosed a bacterial upper respiratory tract infection. Despite the history of rigors no blood cultures or throat swabs were taken, and the patient was discharged with phenoxymethyl-penicillin 500mg to be taken four times daily, having been advised to see his …
Mortality in Patients with Hemophilia: Changes in a Dutch Population from 1986 to 1992 and 1973 to 1986
Authors: Mattanja Triemstra
Journal: Annals of Internal Medicine (1995)

Objective: To determine causes of death and mortality rates in patients with hemophilia over a period of 20 years, to assess changes in mortality, and to distinguish between hemophilia-related death and recent death induced by viral infections. Design: Cohort study of 919 patients followed from January 1986 to June 1992. Results were compared with outcomes of previous follow-up from 1973 to 1986. Setting: Consecutive national questionnaire surveys on hemophilia, using patient registries of the Netherlands Hemophilia Society and Dutch hemophilia centers. Patients: 919 males with hemophilia A or B who participated in a national questionnaire survey on hemophilia in 1985. Median duration of follow-up was 6.4 years, which yielded 5753 person-years of follow-up. The mean age at study entry was 30 years (range, 1 to 85 years). Measurements: Standardized mortality ratios, causes of death, median life expectancy, age-adjusted relative risks associated with the type or severity of hemophilia, presence of inhibitors, prophylaxis, and human immunodeficiency virus infection. Results: 45 patients (5%) died between January 1986 and June 1992; 22.6 patients had been expected to die. Thus, the overall standardized mortality ratio was 2.0. The overall median life expectancy was 66 years for the cohort studied from 1973 to 1986 and 68 years for the cohort studied from 1986 to 1992. When deaths related to viral infection were excluded, the life expectancy almost equaled that of the general male population. Between 1986 and 1992, 1 patient died of ischemic heart disease compared with the 5.2 who were expected to die of this disease. Infection with HIV was the strongest independent predictor of death (relative risk, 27.5 [95% CI, 5.7 to 132.8]). After adjustment for HIV infection, no other hemophilia-related risk factors were associated with the risk for death. Conclusions: The acquired immunodeficiency syndrome and hepatitis strongly influence mortality in patients with hemophilia. In the absence of viral infections, the life expectancy of patients with hemophilia would almost equal that of the general male population.
Long Non-Coding RNAs As Components Of The MYC Network In B Cell Lymphoma
Authors: Joost Kluiver, Melanie Winkle, Mina Tayari, Martijn Terpstra, Gertrud Kortman, Debora de Jong, Jantine Sietzema, Bart-Jan Kroesen, Klaas Kok, Anke van den Berg
Journal: Blood (2013)
Fgf10 is essential for limb and lung formation
Authors: Keisuke Sekine, Hideyo Ohuchi, Masanori Fujiwara, Masahiro Yamasaki, Tatsuya Yoshizawa, Takashi Sato, Naoko Yagishita, Daisuke Matsui, Yoshihiko Koga, Nobuyuki Itoh, Shigeaki Kato
Journal: Nature Genetics (1999)
Abstract 15847: Excitation-Contraction Coupling and IP3-Dependent Ca Signaling in Atrial Myocytes From Normal and Failing Hearts
Authors: Felix Hohendanner, Joshua T Maxwell, Stefanie Walther, Lothar A Blatter
Journal: Circulation (2014)

We studied excitation-contraction-coupling (ECC) and inositol-1,4,5-triphosphate (IP3) dependent Ca release in atrial myocytes from normal and heart failure (HF) rabbit hearts. Elementary Ca release events (Ca puffs) from IP3 receptors (IP3Rs) were detected in membrane-permeabilized myocytes after inhibition of ryanodine receptor mediated Ca sparks with tetracaine. Puff activity was induced by IP3 exposure and blocked by 2-aminoethoxydiphenyl borate (2APB), identifying their origin from IP3Rs. In normal myocytes puff activity was low and restricted to the cell periphery, whereas in HF myocytes their overall frequency was increased and puffs were more prominent in the cell center. In HF atrial myocytes, diastolic [Ca]i was increased and action potential (AP) induced Ca transients (CaTs) were larger in amplitude whereas no difference in sarcoplasmic reticulum Ca load was observed. Increased CaT amplitudes in HF myocytes were attenuated by 2APB or adenoviral expression of an IP3 sponge or 5’-phosphatase. Angiotensin II (AT) and photolytical release of caged IP3 increased diastolic [Ca]i in normal and HF myocytes whereas the effect was more pronounced in HF. The amplitude of CaTs was increased in the presence of AT or after IP3 uncaging in normal cells, however the opposite effect was observed in HF. The frequency of spontaneous Ca waves was higher in HF, and returned to normal levels after 2APB exposure. Nearly half of all Ca waves in normal cells, but
Evidence for the importance of host-derived osteopontin in distant metastasis of breast cancer using osteopontin-null mice
Authors: Akio Hiraki, Nobuyuki Hashimoto, Paul Williams, Maria Bunegin, Arlene Farias, Toshuyuki Yoneda
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3975 

Osteopontin (OPN) is overexpressed in various types of human cancers including breast, lung, colorectal, gastric, ovarian cancers and in melanoma. Most recently, it has been also found that OPN expression is elevated in pleural mesothelioma due to asbestos exposure. Accordingly, tumor-produced OPN has been implicated in malignant behaviors of these tumors. In support of this notion, animal studies including ours have shown that OPN promotes distant metastases. Of note, OPN is expressed in normal host tissues as well, raising the possibility that host-derived OPN can also influence tumor aggressiveness. To address this, we studied the 4T1 mouse breast cancer that produced large amounts of OPN and metastasized to bone and lung following orthotopic inoculation in syngeneic female Balb/c mice. We established 4T1 cells stably transfected with a firefly luciferase cDNA (4T1/luc) for quantitative assessment of tumor burden and with an anti-sense OPN cDNA (4T1/ASOPN/luc) or empty vector (4T1/EV/luc). OPN-deficient (OPN-/-) mice of Balb/c background were generously provided by Dr. Cantor. Orthotopic tumor formation of 4T1/EV/luc or 4T1/ASOPN/luc did not differ between WT and OPN-/- mice. In contrast, histological examination revealed that 4T1/EV/luc metastases to bone and lung were significantly decreased in OPN-/- mice compared with WT mice. Similarly, bone and lung metastases of 4T1/ASOPN/luc were also reduced in OPN-/- mice. Furthermore, the development of osteolytic lesions was markedly impaired in OPN-/- mice compared with WT mice following direct inoculation of 4T1 cells into the marrow cavity of tibiae. These results collectively suggest that the host-derived OPN enhances the capacity of 4T1 cell to spread to and colonize bone. To understand the mechanism underlying reduced distant metastases in OPN-/- mice, adherence, proliferation and apoptosis of 4T1 cells in plates coated with or without varying concentrations of OPN were examined. The attachment and growth of 4T1/EV/luc and 4T1/ASOPN/luc cells in OPN-coated plates were greater than non-coated plates. Furthermore, these cells displayed decreased apoptosis in OPN-coated plates. These results suggest that host-derived OPN contributes to the stimulation of arrest and colonization and protection from apoptosis of metastatic cancer cells in target organs. Taken together, our results using OPN-/- mice suggest that not only tumor-produced but also host-derived OPN is critical to bone and lung metastases in breast cancer. The results also suggest that OPN plays an important role in non-bone as well as bone metastases. Thus, OPN is a potential molecular target in designing the therapeutic interventions for metastatic breast cancer.
Production of Subcutaneous Sarcomas in Mice With Tars Extracted From Atmospheric Dusts
Authors: Joseph Leiter, Michael B. Shimkin, M. J. Shear
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Production of Subcutaneous Sarcomas in Mice With Tars Extracted From Atmospheric Dusts Get access Joseph Leiter, Joseph Leiter assistant chemist Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin, Michael B. Shimkin passed assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Shear M. J. Shear principal biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 2, October 1942, Pages 155–165, https://doi.org/10.1093/jnci/3.2.155 Published: 01 October 1942
Abstract P1-02-08: 18F-fluoro-2-deoxy-glucose positron emission tomography/ computed tomography evaluation shows the utility for predicting postoperative outcomes on Luminal types breast cancer patients
Authors: Kenjiro Aogi, Yoshifumi Sugawara, Sachiko Kiyoto, Takayuki Kadoya, Hideo Shigematsu, Norio Masumoto, Morihito Okada
Journal: Cancer Research (2015)

Abstract Background: Hormonal receptor-positive, i.e. Luminal types, breast cancer has better prognosis compared with other phenotypes, but predictive factors for postoperative outcomes have been in research besides hormonal receptor expressions. 18F-fluoro-2-deoxy-glucose positron emission tomography/ computed tomography (18F-FDG PET/CT) using maximum standardized uptake value (maxSUV) has been reported its utility as one of predictive markers for relapse-free survival (RFS) on breast cancer patients. In this retrospective study, the utility of 18F-FDG PET/CT was evaluated on predicting postoperative outcomes especially on Luminal types breast cancer patients. Methods: Three hundred forty four breast cancer patients with clinical Stage I-III who underwent preoperative 18F-FDG PET/CT were enrolled between January 2006 and December 2011 in two institutes. Patients classified into Luminal types, Luminal A(166 patients): Estrogen receptor(ER)(+) or Progesterone receptor (PR)(+), human epidermal growth factor receptor type2 (HER2) (-), nuclear grade(NG)1-2 or Luminal B(96 patients): ER(+) or PR(+), HER2(-), NG3, were evaluated in this study. Moreover, patients were also divided in two groups according to cut-off maxSUV on receiver operating characteristic (ROC) analysis (≤4.0 group vs &amp;gt;4.0 group, AUC=0.830). Statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to be statistically significant. Results: Significant correlations were shown between maxSUV and clinical T-factor, nuclear grade, vascular invasion and presence or absence of recurrence (p&amp;lt;0.0001, p&amp;lt;0.0001, p=0.0181, and p=0.0056, respectively). In uni- and multivariate analyses using Cox model for recurrence, only maxSUV was shown to be significant (p=0.021 and p=0.043, respectively). In RFS, the maxSUV≤4.0 group showed significantly better prognosis compared to that of the maxSUV &amp;gt;4.0 group (p=0.003). Conclusion: 18F-FDG PET/CT using maxSUV was concluded to be useful for predicting postoperative prognosis on luminal types breast cancer patients. Citation Format: Kenjiro Aogi, Yoshifumi Sugawara, Sachiko Kiyoto, Takayuki Kadoya, Hideo Shigematsu, Norio Masumoto, Morihito Okada. 18F-fluoro-2-deoxy-glucose positron emission tomography/ computed tomography evaluation shows the utility for predicting postoperative outcomes on Luminal types breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-08.
The Role of Transforming Growth Factor β Signaling in Fibroblast‐like Synoviocytes From Patients With Oligoarticular Juvenile Idiopathic Arthritis: Dysregulation of Transforming Growth Factor β Signaling, Including Overexpression of Bone Morphogenetic Protein 4, May Lead to a Chondrocyte Phenotype and May Contribute to Bony Hypertrophy
Authors: AnneMarie C. Brescia, Megan M. Simonds, Suzanne M. McCahan, Paul T. Fawcett, Carlos D. Rose
Journal: Arthritis & Rheumatology (2013)

This study was designed to investigate the pathogenic contributions of fibroblast-like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA.FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease. Biologically relevant differentially expressed genes were confirmed by RNA and protein analysis.Exploration of global gene expression profiles of the JIA FLS revealed important dysregulated pathways, including the transforming growth factor β (TGFβ) signaling, as well as endochondral bone formation, cartilage formation, and β-catenin networks. Importantly, bone morphogenetic protein 4 (BMP-4) was significantly overexpressed in the JIA FLS. FLS from patients with oligoarticular JIA exhibit a chondrocyte phenotype, as evidenced by expression of type II collagen and aggrecan.Dysregulation of the pathways involved in the pathogenesis of oligoarticular JIA were revealed through gene expression profiling. JIA FLS displayed dysregulated TGFβ signaling and exhibited a hypertrophic chondrocyte phenotype. These characteristics, along with contributions from the β-catenin network may have implications for endochondral bone formation and local growth disturbances in oligoarticular JIA. Overexpression of BMP-4 in FLS from patients with oligoarticular JIA in particular may play an important role in disease pathogenesis, with a direct effect on functional outcome and with implications for future treatment.
Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c-jun-N-terminal kinase (JNK)-dependent and -independent signaling pathways
Authors: Behnam Saberi, Maria D. Ybanez, Heather S. Johnson, William A. Gaarde, Derick Han, Neil Kaplowitz
Journal: Hepatology (2013)

This study examines the role of protein kinase C (PKC) and AMP-activated kinase (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse hepatocytes with broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected against APAP cytotoxicity despite sustained c-jun-N-terminal kinase (JNK) activation. Broad-spectrum PKC inhibitor treatment enhanced p-AMPK levels and AMPK regulated survival-energy pathways including autophagy. AMPK inhibition by compound C or activation using an AMPK activator oppositely modulated APAP cytotoxicity, suggesting that p-AMPK and AMPK regulated energy survival pathways, particularly autophagy, play a critical role in APAP cytotoxicity. Ro-31-8245 treatment in mice up-regulated p-AMPK levels, increased autophagy (i.e., increased LC3-II formation, p62 degradation), and protected against APAP-induced liver injury, even in the presence of sustained JNK activation and translocation to mitochondria. In contrast, treatment of hepatocytes with a classical PKC inhibitor (Go6976) protected against APAP by inhibiting JNK activation. Knockdown of PKC-α using antisense (ASO) in mice also protected against APAP-induced liver injury by inhibiting JNK activation. APAP treatment resulted in PKC-α translocation to mitochondria and phosphorylation of mitochondrial PKC substrates. JNK 1 and 2 silencing in vivo decreased APAP-induced PKC-α translocation to mitochondria, suggesting PKC-α and JNK interplay in a feed-forward mechanism to mediate APAP-induced liver injury. Conclusion: PKC-α and other PKC(s) regulate death (JNK) and survival (AMPK) proteins, to modulate APAP-induced liver injury. (Hepatology 2014;59:1543-1554)
Abstract 6166: Molecular Mechanisms of Right Ventricular Failure: A Role for Vascular Endothelial Growth Factor and Endoplasmic Reticulum Stress
Authors: Ramesh Natarajan, Herman J Bogaard, Donatas Kraskauskas, Norbert F Voelkel
Journal: Circulation (2008)

Background: Patients with severe chronic pulmonary hypertension (PH) frequently die from right ventricular (RV) failure. Traditionally, RV failure has been explained by the increase in afterload an...
Nanofibrous Spongy Microspheres Enhance Odontogenic Differentiation of Human Dental Pulp Stem Cells
Authors: Rong Kuang, Zhanpeng Zhang, Xiaobing Jin, Jiang Hu, Melanie J. Gupte, Longxing Ni, Peter X. Ma
Journal: Advanced Healthcare Materials (2015)

Dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF‐SMS), is developed for dentin regeneration. Biodegradable and biocompatible poly( l ‐lactic acid)‐block‐poly( l ‐lysine) are synthesized and fabricated into NF‐SMS using self‐assembly and thermally induced phase separation techniques. It is hypothesized that NF‐SMS with interconnected pores and nanofibers can enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF‐MS) without pore structure and conventional solid microspheres (S‐MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferate significantly faster on NF‐SMS than on NF‐MS or S‐MS ( p &lt; 0.05). Following in vitro odontogenic induction, all the examined odontogenic genes (alkaline phosphatase content, osteocalcin, bone sialoprotein, collagen 1, dentin sialophosphoprotein (DSPP)), calcium content, and DSPP protein content are found significantly higher in the NF‐SMS group than in the control groups. Furthermore, 6 weeks after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis shows that NF‐SMS support superior dentin‐like tissue formation compared to NF‐MS or S‐MS. Taken together, NF‐SMS have great potential as an injectable cell carrier for dentin regeneration.
Cost-Effectiveness in Health and Medicine, by M R Gold, J E Siegel, L B Russell, M C Weinstein
Authors: N. Freemantle
Journal: BMJ (1997)

M R Gold, J E Siegel, L B Russell, M C Weinstein: Oxford University Press, £36.50, pp 425 ISBN 0 195 10824 8

Most people considering spending a substantial sum of money on a car will try to identify the best deal, by expending time and effort on assessments in line with the scale of the decision. Viewed in this way, it becomes hard to argue against considering costs and benefits together when making decisions about health care, and not to do so in the NHS might be deemed irresponsible and wasteful. …
What not to do
Authors: George Dunea
Journal: BMJ (2000)

In 1968 Dr Richard Armour wrote an essay in JAMA in which he pretended to have found an old book, “being a study of certain curious categories of physicians.” There were four types. Firstly, the Ebullient, outgoing, exuding optimism and good cheer, backslapping, always encouraging and minimising his patients' illnesses. Next, the Lugubrious, entering the sickroom with a pained look like an undertaker coming to remove a body, speaking in a low sepulchral tone and always guarded about the outlook. …
111. A Chimeric Adenovirus Vector Encoding Reovirus Attachment Protein Sigma 1 Targets Cells Expressing Junctional Adhesion Molecule 1 and Sialic Acid
Authors: George T. Mercier, Jacquelyn A. Campbell, James D. Chappell, Terence S. Dermody, Thilo Stehle, Michael A. Barry
Journal: Molecular Therapy (2004)