tbuckley/cabot-search huggingface dataset:
Thiazolidinediones as potent inducers of hepatocyte growth factor
Authors: Wataru Ito, Shigeharu Ueki, Masahide Takeda, Tomomi Tanigai, Hiroyuki Kayaba, Junichi Chihara
Journal: Hepatology (2009)

To date, increasing evidence indicates that the thiazolidinediones (TZDs) have benefits in certain conditions of chronic liver disease, including nonalcoholic steatohepatitis.1, 2 TZDs are selective agonists for the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) that have potent anti-inflammatory effects on hepatic stellate cells (HSCs). For instance, exposing HSCs to TZDs resulted in reversion of most features of the activated phenotype of HSCs, reduction in the expression of matrix proteins, and blocking of the secretion of proinflammatory chemokines.2 We offer an additional important mechanism for the development of a molecular target of PPARγ, i.e., PPARγ agonist-induced hepatocyte growth factor (HGF) may have an essential part in the protection from chronic liver injury. HGF has been shown to suppress liver cirrhosis, hepatocyte apoptosis, and production of transforming growth factor-β.3 Previously, Li et al. clearly demonstrated that PPARγ agonists strongly stimulate HGF promoter and subsequent gene/protein expression in mesangial cells.4 Indeed, we observed that peripheral blood mononuclear cells produce a significant amount of HGF in the supernatants by stimulation with TZDs, which are blocked by a selective PPARγ antagonist (Fig. 1). This evidence suggests that, in the presence of a PPARγ agonist, both tissue and immune cells could produce HGF at an inflammatory locus and probably in blood circulation. In this context, we read with interest the article by Aoyama et al.,5 which showed that pioglitazone treatment augumented the hepatic proliferative response in KK-Ay mice in response to partial hepatectomy. Future studies are needed to explore the connection between PPARγ and HGF, and such investigations would contribute to progress in understanding the mechanisms of the efficacy of TZDs in chronic liver disease. Density gradient–separated peripheral blood mononuclear cells from healthy subjects (n = 4) were suspended at 1 × 106 cells/mL in Roswell Park Memorial Institute 1640 medium with 10% fetal bovine serum, and stimulated with PPARγ agonists for 24 hours. The PPARγ antagonist GW9662 was added to the mononuclear cells 30 minutes prior to PPARγ agonists. The concentration of HGF in culture supernatants was measured using an enzyme-linked immunosorbent assay kit (R&D Systems, Minneapolis, MN). The bars indicate standard errors. *P < 0.05 versus unstimulated control. #P < 0.05 versus without PPARγ antagonist. Wataru Ito M.D., Ph.D.*, Shigeharu Ueki M.D., Ph.D.*, Masahide Takeda M.D., Ph.D.*, Tomomi Tanigai M.D.*, Hiroyuki Kayaba M.D.*, Junichi Chihara M.D., Ph.D.*, * Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Outcomes of endoscopic submucosal dissection for early gastric cancer with special reference to validation for curability criteria
Authors: O. Goto, M. Fujishiro, S. Kodashima, S. Ono, M. Omata
Journal: Endoscopy (2009)

See also: Commentaire de travail de O. Goto et al., pp. 118Endoscopy 2009; 41(02): 250-251DOI: 10.1055/s-0032-1306729
Gypsies and American Medical Care
Authors: JAMES D. THOMAS
Journal: Annals of Internal Medicine (1985)

Gypsies are a cohesive cultural group who may have difficult relations with the American medical community. There are several hundred thousand Gypsies in this country; they maintain a private society with an internal moral code and legal system. There is a strong cultural basis for obesity, tobacco use, fatty diet, and inbreeding among Gypsies. These traits predispose them to hypertension, diabetes, hyperlipidemia, and occlusive vascular disease. When ill they present a striking dichotomy of primitive fears of disease process with surprising sophistication for medical terms and the workings of the hospital hierarchy. Specific recommendations are made for more effective and compassionate relations with Gypsy patients.
Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop.
Authors: H C van Zaanen, R P Koopmans, L A Aarden, H J Rensink, J M Stouthard, S O Warnaar, H M Lokhorst, M H van Oers
Journal: Journal of Clinical Investigation (1996)

In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28. Daily dose: 5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo.
Immunologic Analysis of Lymphoid Tumors
Authors: Max D. Cooper
Journal: New England Journal of Medicine (1980)

During the past decade, the classification of lymphoid tumors has undergone drastic revision. This change was heralded in the 1960's by the discovery that lymphocytes could be divided into thymus-derived (T) and bursa-derived or bone-marrow-derived (B) cells and by evidence indicating that most tumors with lymphoid morphology had origins in one or the other pathway of differentiation.1 Since then, detection of practical markers for human T cells (such as the ability to bind to sheep erythrocytes and surface differentiation antigens) and for B cells (immuno-globulin determinants) has allowed discrimination of tumors affecting these two pathways.2 For example, acute lymphoblastic leukemias, . . .
In vivo stimulation of the insulin receptor kinase in human skeletal muscle. Correlation with insulin-stimulated glucose disposal during euglycemic clamp studies.
Authors: G R Freidenberg, S L Suter, R R Henry, D Reichart, J M Olefsky
Journal: Journal of Clinical Investigation (1991)

To assess the relationship between insulin receptor (IR) kinase activity and insulin action in vivo in humans, we measured glucose disposal rates (GDR) during a series of euglycemic clamp studies. Simultaneously, we measured IR kinase activity in IRs extracted from skeletal muscle obtained by needle biopsy at the end of each clamp. By preserving the phosphorylation state of the receptors as it existed in vivo at the time of biopsy, we could correlate GDR and IR kinase in skeletal muscle. Eight nondiabetic, nonobese male subjects underwent studies at insulin infusion rates of 0, 40, 120, and 1,200 mU/m2 per min. Kinase activity, determined with receptors immobilized on insulin agarose beads, was measured at 0.5 microM ATP, with 1 mg/ml histone, followed by SDS-PAGE. Insulin increased GDR approximately sevenfold with a half-maximal effect at approximately 100 microU/ml insulin and a maximal effect by approximately 400 microU/ml. Insulin also increased IR kinase activity; the half-maximal effect occurred at approximately 500-600 microU/ml insulin with a maximal 10-fold stimulation over basal. Within the physiologic range of insulin concentrations, GDR increased linearly with kinase activation (P less than 0.0006); at supraphysiologic insulin levels, this relationship became curvilinear. Half-maximal and maximal insulin-stimulated GDR occurred at approximately 20 and approximately 50% maximal kinase activation, respectively. These results are consistent with a role of the kinase in insulin action in vivo. Furthermore, they demonstrate the presence of a large amount of "spare kinase" for glucose disposal.
An Analysis of Activation in Human Atria
Authors: J. A. ABILDSKOV, J. A. CRONVICH, G. E. BURCH
Journal: Circulation (1955)

The P wave and PsÊ-loop were derived from coplanar outlines of the contour of seven human atria, including left atrial enlargement, in which it was assumed that the process of depolarization spread in a radial fashion from the sinoatrial node. The "derived" planar projections of the P waves of the standard leads and PsÊ-loops were similar in relative amplitude and general contour to those recorded electrocardiographically and vectorcardiographically prior to death.
Grounding predictive coding models in empirical neuroscience research
Authors: Tobias Egner, Christopher Summerfield
Journal: Behavioral and Brain Sciences (2013)

Abstract Clark makes a convincing case for the merits of conceptualizing brains as hierarchical prediction machines. This perspective has the potential to provide an elegant and powerful general theory of brain function, but it will ultimately stand or fall with evidence from basic neuroscience research. Here, we characterize the status quo of that evidence and highlight important avenues for future investigations.
Points: Chronic prostatitis
Authors: R. Maskell
Journal: BMJ (1987)

s eloquent description of Mary McDaid, dead in bed at 33 (25 July, p 265), set me thinking about where Mary and her like were represented in the evaluation of a shared diabetes care scheme reported by Dr John Day's group (20 June, p 1590)-perhaps among those for whom it was agreed that "improved control could not be achieved" or among the 40-60% of patients who do not consult specialists for diabetes care?The authors do not tell us how many patients fell into each group, nor how they fared over the next two years.The disappointing physical deterioration that occurred over the two years might have been mainly in that group where doctors had settled for poorer blood glucose control.The authors, and others (18 July, p 214), have proposed various solutions to improve the organisation of diabetic care including "greater con- centration on patient advice."Attempts at blanket patient advice have not met with much success in changing patient behaviour, and it would seem rational to tailor the advice to the specific needs of different groups of patients.We should take Mary's statement, that "it was all right for doctors with their fancy talk," into account in her management.Studies of patient outcome would also be better interpreted if they classified patients by their health beliefs and health seeking behaviour as well as their blood glucose values, and took this classification into account in the analysis.
A Note on the Method of Using Haffkine's Prophylactic
Authors: M. M. T. Christie
Journal: BMJ (1900)

PROPHYLACTIC. 6C~IL,, 1 243 states that in 475 cases treated a recovery-percentage of 39 was obtained.From the comparatively small number of trials of serum inoculations hitherto reported, neither serum seems to come up to what might be expected from a specific treatment.Lustig's serum does not appear to be so efficacious as that of Yersin.This is possibly accounted for in a way similar to Metchnikoffs explanation of the difference in Yersin's serums referred to above.A horse treated with a nucleo- proteid extracted from the dead microbes would be immunised with even less efficiency than one treated with the killed microbes together with their metabolic products, and a horse immunised in this way was shown to give a less powerful serum than,one immunised with the living microbes.Com- pared in this way with Haffkine's prophylactic, the latter is the greater success as a scientific preparation.
The Humanities in Medical Education
Authors: KENNETH S. WARREN
Journal: Annals of Internal Medicine (1984)

The importance of humanities in general education is generally acknowledged. With respect to premedical education, a major impediment has been the belief that gaining admittance to medical school is exceedingly difficult and, therefore, a student must major in the sciences. In compensation, the humanities have been introduced in medical schools either through compressed 6-year programs or as curricular or extracurricular options. Studies have shown, however, that approximately 50% of all applicants are admitted to medical schools and that the relatively small proportion of students who have majored in the humanities do somewhat better than average. With respect to medical schools, results of an examination of programs throughout the country suggest that strong extracurricular rather than curricular programs should be developed for the humanities.
Experimental models in peritoneal dialysis: A European experience
Authors: Norbert Lameire, Wim Van Biesen, Mieke Van Landschoot, Tao Wang, Olof Heimbürger, Jonas Bergström, Bengt Lindholm, Liesbeth P.H. Hekking, Carin E.G. Havenith, Robert H.J. Beelen
Journal: Kidney International (1998)
AIDS Drug Programs Tighten Belts Even as Medications Are Shown to Curb Contagion
Authors: Richard Trubo
Journal: JAMA (2011)

THE TROUBLED ECONOMY IS CREATing funding shortfalls for AIDS Drug Assistance Programs (ADAPs), even as financial difficulties increase the need for help among some of the low-income HIV/AIDS patients who rely on these programs to supply their medication. Meanwhile, the need for such programs continues to intensify in the wake of a recent large-scale international study that demonstrated the effectiveness of oral antiretroviral drugs in safeguarding the uninfected sexual partners of individuals with HIV infection. The trial showed protective benefits when these drugs were taken by HIV-positive persons with an immune system that was still relatively uncompromised (the immediate-treatment group). Data from this randomized controlled trial from the HIV Prevention Trials Network (HPTN) were released in May, earlier than the scheduled 2015 completion date for the study, because of the markedly positive results. The ongoing trial (HPTN 052) is now being modified to offer antiretroviral therapy to all HIV-infected study participants in the deferred-treatment group, according to Myron S. Cohen, MD, chair of the study and director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill.
Abstract C61: GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN
Authors: Wan-Ting Chen, Genyuan Zhu, Kyle Pfaffenbach, Gary Kanel, Bangyan Stiles, Amy S. Lee
Journal: Cancer Research (2013)

Abstract Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling, and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas, and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. Phosphatase and tensin homolog (PTEN), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cPf/f78f/f). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months cPf/f78f/f livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis, and liver injury, implying that GRP78 protects the liver against PTEN-null mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cPf/f78f/f livers. Strikingly, bile duct cells in cPf/f78f/f livers maintained wild-type GRP78 level while adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective c-Jun N-terminal protein kinase activation, β-catenin downregulation, along with platelet-derived growth factor receptor α upregulation, which was unique to cPf/f78f/f livers at 6 months. Development of both HCC and CC were accelerated and evident in cPf/f78f/f livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, livers of Albumin-Cre; Grp78f/f (c78f/f) mice showed no malignancy even at 14 months. These studies reveal GRP78 is a novel regulator for PTEN-loss mediated liver injury and cancer progression. Citation Format: Wan-Ting Chen, Genyuan Zhu, Kyle Pfaffenbach, Gary Kanel, Bangyan Stiles, Amy S. Lee. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C61.
Abstract 3410: Inhibitors of Skp2 E3ligase stabilize nuclear p27kip1 for regain of growth regulation in cancer.
Authors: Savvas C. Pavlides, Kuang-Tzu Huang, Lily Wu, Bo R. Rueda, Stephanie V. Blank, Khushbakhat R. Mittal, Timothy Cardozo, Leslie I. Gold
Journal: Cancer Research (2013)

Abstract In many human cancers, the tumor suppressor, p27kip1 (p27), a cyclin-dependent kinase inhibitor critical to cell cycle arrest, undergoes perpetual ubiquitin-mediated proteasomal degradation by the E3 ligase complex SCF-Skp2/Cks1 and/or cytoplasmic mislocalization; lack of nuclear p27 causes aberrant cell cycle progression and cytoplasmic p27 can mediate cell migration/metastasis. We previously showed that estrogen (E2) induces Skp2-dependent degradation of p27 and cell proliferation in primary endometrial epithelial cells (EECs) and endometrial carcinoma (ECA) cell lines (e.g., ECC-1) suggesting a pathogenic mechanism for type I endometrial carcinoma (ECA), an estrogen (E2)-linked cancer. The current studies show that treatment of ECC-1 cells with small molecule inhibitors of Skp2/Cks1 E3 ligase activity (Skp2E3LIs) increase protein levels of p27, increase p27 half-life by 6 hours and inhibit cell proliferation (IC50 10μM). Two of five SKP2E3LIs, designated as C2 and C20 specifically increase p27 in the nucleus while decreasing p27 in the cytoplasm in both ECC-1 cells and primary ECA cells. In addition, C2 and C20 prevent both E2-induced proliferation and degradation of nuclear p27. These data suggest that Skp2E3LIs can function in the nucleus to prevent E2-induced degradation of p27 in primary ECA cells to regain growth control by directly blocking p27 ubiquitylation and subsequent degradation. Skp2E3LIs enable a chemical biology approach to understanding the functional significance of the ubiquitin pathway in p27-mediated cell cycle regulation and importantly, are the first specific proteasome inhibitors that pharmacologically target the binding interaction between the E3ligase, SCF-Skp2/Cks1 and p27 to prevent its ubiquitylation and subsequent degradation. These targeted inhibitors represent a major therapeutic advancement over general proteasome inhibitors for cancers characterized by SCF-Skp2/Cks1-mediated destruction of p27. Citation Format: Savvas C. Pavlides, Kuang-Tzu Huang, Lily Wu, Bo R. Rueda, Stephanie V. Blank, Khushbakhat R. Mittal, Timothy Cardozo, Leslie I. Gold. Inhibitors of Skp2 E3ligase stabilize nuclear p27kip1 for regain of growth regulation in cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3410. doi:10.1158/1538-7445.AM2013-3410
IgG/IgA pemphigus with IgG and IgA antidesmoglein 1 antibodies detected by enzyme-linked immunosorbent assay
Authors: N. Oiso, C. Yamashita, K. Yoshioka, M. Amagai, A. Komai, Y. Nagata, T. Hashimoto, M. Ishii
Journal: British Journal of Dermatology (2002)

Summary Pemphigus is an autoimmune mucocutaneous bullous disease characterized by autoantibodies against the cell surfaces of epidermal keratinocytes. Six cases with deposition of both IgG and IgA on keratinocyte cell surfaces have been reported in the recent literature. We provisionally termed these cases IgG/IgA pemphigus. We describe a 42‐year‐old Japanese woman with clinical and histopathological features resembling herpetiform pemphigus who demonstrated in vivo bound and circulating anticell surface autoantibodies of both IgG and IgA classes on immunofluorescence examination. Enzyme‐linked immunosorbent assay using baculovirus‐expressed recombinant desmoglein (Dsg) 1 and Dsg 3 showed that both IgG and IgA antibodies reacted with Dsg1. The reactivity was completely adsorbed with preincubation of serum with Dsg1 baculoprotein, further confirming the exclusive reactivity of both IgG and IgA antibodies with Dsg1. This is the second case of IgG/IgA pemphigus in which the human target antigens for both IgG and IgA antibodies have been unequivocally identified. This study provides further evidence that IgG/IgA pemphigus is a distinct disease entity.
GW25-e1527 Cardioprotective Effects of Angiotensin-Converting Enzyme 2 in Apolipoprotein E-Deficient Mice in Response to Angiotensin II
Authors: Jiu-Chang Zhong, Hai-Yan Jin, Xi-Yong Yu, Zhen-Zhou Zhang, Hui-Min Yu, Lai-Jiang Chen, Ying-Le Xu, Bei Song, Josef M. Penninger, Ping-Jin Gao, Gavin Y. Oudit
Journal: Journal of the American College of Cardiology (2014)