tbuckley/cabot-search huggingface dataset:
The Etiology of Incapacitating, Brittle Diabetes
Authors: David S Schade, Denise A Drumm, William C Duckworth, R Philip Eaton
Journal: Diabetes Care (1985)

Incapacitated brittle diabetic subjects are a small subset of insulin-dependent diabetic individuals who are unable to maintain a normal lifestyle because of frequent disruptions secondary to severe hypergly-cernie and/or hypoglycemic episodes. Thirty incapacitated patients were referred for evaluation because the cause of their diabetic instability could not be determined by their personal physicians despite extensive patient training in correct diabetes management, frequent hospitalizations for observation, and multiple diagnostic testing. From the 30 patients, a diagnostic algorithm was developed (described in the companion article) from which the etiology of brittle diabetes could be established in 29. This article provides the clinical characteristics of each of the 30 patients, a description of the etiologie categories of brittle diabetes, and the clinical follow-up from the time that the etiologie diagnosis was established and treatment recommended. Although extensive medical records were sent with each patient, without prospective objective testing under rigidly controlled conditions, the correct etiologie diagnosis would not have been evident from the clinical presentation of the patient. Of equal importance in identifying the etiology of brittle diabetes was the acceptance and cooperation of the referring physician in providing close follow-up and repeat insulin challenge testing when necessary. In this referred patient population, eight subjects had factitious disease, eight were malingering, seven had communication deficits, two had gastroparesis, two had systemic insulin resistance, two had miscellaneous causes of brittle diabetes, and one patient remained undiagnosed. Using a prospective algorithmic approach to determine the etiology of brittle diabetes, not only is the cause of diabetic instability almost always identifiable, but a significant improvement in lifestyle is achieved in greater than 50% of the incapacitated individuals.
Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma in diethylnitrosamine-treated rats
Authors: Marie-Pierre Bralet, Virginie Pichard, Nicolas Ferry
Journal: Hepatology (2002)

The question whether hepatocellular carcinoma (HCC) arises from dedifferentiation of mature hepatocytes or from proliferation of liver stem cells is still debated. In the present study, we used retroviral-mediated genetic labeling to investigate the fate of mature hepatocytes in rats after administration of diethylnitrosamine (DEN). Mature hepatocytes were genetically labeled by intravenous injection of retroviral vectors containing the Escherichia coli β-galactosidase gene coupled to a nuclear localization signal ( nls-LacZ) 1 day after partial hepatectomy. Liver biopsies performed after completion of hepatic regeneration showed that 18.3% of hepatocytes expressed the nls-LacZ transgene. Rats were then treated with DEN in drinking water for 12 weeks and sacrificed between 98 and 151 days after the onset of DEN administration. Clones of β-galactosidase positive cells were observed, half of which (53%) also expressed the placental form of glutathione- S -transferase (GSTp), a marker of preneoplastic cells. HCCs of various sizes expressing GSTp were present in all animals. Careful examination of 90 HCCs revealed that 16 (17.7%) also expressed nls-LacZ . This figure precisely matched the proportion of labeled hepatocytes before DEN treatment (18.3%). In conclusion, a random clonal origin of HCC from mature hepatocytes is seen in the DEN model of hepatocarcinogenesis.
Fat land: how Americans became the fattest people in the world
Authors: Samuel Klein
Journal: Journal of Clinical Investigation (2004)

America is suffering an epidemic of obesity and we are fast catching up. The challenge to the US food industry in the 1970s was that their population was growing more slowly than their food supply. The answer was supersized portions, fast food, too little exercise, take-aways, the constant drip-feed of saturated fat and sugar, producing a society in which 61 per cent of the population is overweight. Heart disease, cardiovascular problems, strokes and above all diabetes are the result. This is an account of the history and biology of the fattening of America at the moment when it is emerging as a political issue too.
Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth
Authors: Michael Quante, Shui Ping Tu, Hiroyuki Tomita, Tamas Gonda, Sophie S.W. Wang, Shigeo Takashi, Gwang Ho Baik, Wataru Shibata, Bethany DiPrete, Kelly S. Betz, Richard Friedman, Andrea Varro, Benjamin Tycko, Timothy C. Wang
Journal: Cancer Cell (2011)
A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism
Authors: Janine L. Coombes, Karima R.R. Siddiqui, Carolina V. Arancibia-Cárcamo, Jason Hall, Cheng-Ming Sun, Yasmine Belkaid, Fiona Powrie
Journal: The Journal of Experimental Medicine (2007)

Foxp3+ regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3+ T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-β can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103+ mesenteric lymph node dendritic cells (DCs) that induce the devel opment of Foxp3+ T reg cells. Importantly, promotion of T reg cell responses by CD103+ DCs is dependent on TGF-β and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.
Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma
Authors: Elise A. Olsen, Youn H. Kim, Timothy M. Kuzel, Theresa R. Pacheco, Francine M. Foss, Sareeta Parker, Stanley R. Frankel, Cong Chen, Justin L. Ricker, Jean Marie Arduino, Madeleine Duvic
Journal: Journal of Clinical Oncology (2007)

To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes.Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated.Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE.Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.
The Emergence of lncRNAs in Cancer Biology
Authors: John R. Prensner, Arul M. Chinnaiyan
Journal: Cancer Discovery (2011)

The discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. In humans, the identification of abundant long ncRNA (lncRNA) >200 bp has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs.
Class I Histone Deacetylase-Selective Novel Synthetic Inhibitors Potently Inhibit Human Tumor Proliferation
Authors: Jung-Hyun Park, Yeonjoo Jung, Tai Young Kim, Sang Gyun Kim, Hyun-Soon Jong, Jung Weon Lee, Dae-Kee Kim, Jong-Soo Lee, Noe Kyeong Kim, Tae-You Kim, Yung-Jue Bang
Journal: Clinical Cancer Research (2004)

Abstract We have developed previously a class of synthetic hybrid histone deacetylase (HDAC) inhibitors, which were built from hydroxamic acid of trichostatin A and pyridyl ring of MS-275. In this study we evaluated the antitumor effects of these novel hybrid synthetic HDAC inhibitors, SK-7041 and SK-7068, on human cancer cells. Both SK-7041 and SK-7068 effectively inhibited cellular HDAC activity at nanomolar concentrations and induced the time-dependent hyperacetylation of histones H3 and H4. These HDAC inhibitors preferentially inhibited the enzymatic activities of HDAC1 and HDAC2, as compared with the other HDAC isotypes, indicating that class I HDAC is the major target of SK-7041 and SK-7068. We found that these compounds exhibited potent antiproliferative activity against various human cancer cells in vitro. Growth inhibition effect of SK-7041 and SK-7068 was related with the induction of aberrant mitosis and apoptosis in human gastric cancer cells. Both compounds induced the accumulation of cells at mitosis after 6 h of treatment, which was demonstrated by accumulation of tetraploid cells, lack of G2 cyclin/cyclin-dependent kinase inactivation, and higher mitotic index. After 12 h of treatment, apoptotic cells were increased through mitochondrial and caspase-mediated pathway. Finally, in vivo experiment showed that SK-7041 or SK-7068 was found to reduce the growth of implanted human tumors in nude mice. Therefore, based on isotype specificity and antitumor activity, SK-7041 and SK-7068 HDAC inhibitors are expected to be promising anticancer therapeutic agents and need additional clinical development.
Cost-effectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study
Authors: Mark Jit, Marc Brisson, Allison Portnoy, Raymond Hutubessy
Journal: The Lancet Global Health (2014)

BackgroundIntroduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support.MethodsWe developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects.FindingsIn validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries.InterpretationLarge between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions.FundingWHO.
Infusion of Reconstituted High-Density Lipoprotein Leads to Acute Changes in Human Atherosclerotic Plaque
Authors: James A. Shaw, Alex Bobik, Andrew Murphy, Peter Kanellakis, Peter Blombery, Nigora Mukhamedova, Kevin Woollard, Stuart Lyon, Dmitri Sviridov, Anthony M. Dart
Journal: Circulation Research (2008)

Studies have shown a reduction in plaque volume and change in plaque ultrasound characteristics after 4 infusions of reconstituted high-density lipoprotein (rHDL). Whether rHDL infusion leads to acute changes in plaque characteristics in humans is not known. Patients with claudication scheduled for percutaneous superficial femoral artery revascularization were randomized to receive 1 intravenous infusion of either placebo or rHDL (80 mg/kg given over 4 hours). Five to 7 days following the infusion, patients returned and revascularization was performed including atherectomy to excise plaque from the superficial femoral artery. Twenty patients (17 males) average age, 68±10 years (mean±SD) were recruited. Eleven patients had a history of documented coronary artery disease, all patients were on aspirin, and 18 were on statins. Ten of the patients received rHDL and 10 placebo. There was significantly less vascular cell adhesion molecule-1 expression (28±3% versus 50±3%; P &lt;0.05) and a reduction in lipid content in the plaque of HDL-treated subjects compared to placebo. The level of HDL cholesterol increased by 20% after infusion of rHDL and the capacity of apolipoprotein B–depleted plasma to support cholesterol efflux increased. Intravenous infusion of a single dose of reconstituted HDL led to acute changes in plaque characteristics with a reduction in lipid content, macrophage size, and measures of inflammation. These changes may contribute to the cardioprotective effects of HDL.
Preconditioning and Adenosine Protect Human Proximal Tubule Cells in an In Vitro Model of Ischemic Injury
Authors: H. Thomas Lee, Charles W. Emala
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Renal ischemic reperfusion injury results in unacceptably high mortality and morbidity during the perioperative period. It has been recently demonstrated that ischemic preconditioning or adenosine receptor modulations attenuate renal ischemic reperfusion injury <i>in vivo</i>. An <i>in vitro</i> model of ischemic renal injury was used in cultured human proximal tubule (HK-2) cells to further elucidate the protective signaling cascades against renal ischemic reperfusion injury. ATP depletion preconditioning (1 h of antimycin A and 2-deoxyglucose treatment followed by 1 h of recovery), adenosine, an A<sub>1</sub> adenosine receptor selective agonist, or an A<sub>2a</sub> adenosine receptor selective agonist significantly attenuated subsequent severe ATP depletion injury of HK-2 cells. In contrast, an adenosine receptor antagonist failed to prevent protection induced by ATP depletion preconditioning. Cytoprotection by ATP depletion preconditioning or A<sub>1</sub> adenosine receptor activation was prevented by inhibitors of extracellular signal-regulated mitogen-activated kinases, protein kinase C, and tyrosine kinases. The A<sub>1</sub> and A<sub>2a</sub> adenosine receptor-mediated cytoprotection were also dependent on G<sub>i/o</sub> proteins and PKA activation, respectively. It is concluded that ATP depletion preconditioning and A<sub>1</sub> and A<sub>2a</sub> adenosine receptor activation protect HK-2 cells against severe ATP depletion injury via distinct signaling pathways.
Mitotic Cell Death by Chromosome Fragmentation
Authors: Joshua B. Stevens, Guo Liu, Steven W. Bremer, Karen J. Ye, Wenxin Xu, Jing Xu, Yi Sun, Gen Sheng Wu, Sureyya Savasan, Stephen A. Krawetz, Christine J. Ye, Henry H.Q. Heng
Journal: Cancer Research (2007)

Cell death plays a key role for both cancer progression and treatment. In this report, we characterize chromosome fragmentation, a new type of cell death that takes place during metaphase where condensed chromosomes are progressively degraded. It occurs spontaneously without any treatment in instances such as inherited status of genomic instability, or it can be induced by treatment with chemotherapeutics. It is observed within cell lines, tumors, and lymphocytes of cancer patients. The process of chromosome fragmentation results in loss of viability, but is apparently nonapoptotic and further differs from cellular death defined by mitotic catastrophe. Chromosome fragmentation represents an efficient means of induced cell death and is a clinically relevant biomarker of mitotic cell death. Chromosome fragmentation serves as a method to eliminate genomically unstable cells. Paradoxically, this process could result in genome aberrations common in cancer. The characterization of chromosome fragmentation may also shine light on the mechanism of chromosomal pulverization.
Rosette formation between murine lymphocytes and erythrocytes. A new locus in the H-2 region.
Authors: D Primi, G K Lewis, R Triglia, J W Goodman
Journal: The Journal of Experimental Medicine (1979)

More than 5% of murine splenic lymphocytes form rosettes with syngeneic erythrocytes. This property was maximally expressed when the lymphocytes were cultured for 24 h before rosetting. About 70% of the rosetting lymphocytes were B cells and 30% were T cells on the basis of surface immunoglobulin and the Thy-1-antigen. Capping surface immunoglobulin had no effect on the capacity of lymphocytes to form rosettes, indicating that the receptor in question was not immunoglobulin. The capacity of lymphocytes to form rosettes with erythrocytes from other strains of mice was H-2 restricted. Extensive pairings of congenic and recombinant strains as donors of lymphocytes and erythrocytes showed that none of the known loci within the H-2 region-controlled rosetting. The involvement of regions on chromosome 17, telomeric or centromeric to H-2, was also excluded. The data were only compatible with the conclusion that this form of self-recognition is associated with a new locus (or loci) mapping between H-2G and H-2D.
RORγt+ IL-22-producing NKp46+ cells protect from hepatic ischemia reperfusion injury in mice
Authors: Elke Eggenhofer, Manije Sabet-Rashedi, Margareta Lantow, Philipp Renner, Jordi Rovira, Gudrun E. Koehl, Hans J. Schlitt, Edward K. Geissler, Alexander Kroemer
Journal: Journal of Hepatology (2015)
IMMUNOSUPPRESSION OF MICE INJECTED WITH HETEROLOGOUS ANTI-IMMUNOGLOBULIN HEAVY CHAIN ANTISERA
Authors: Dean D. Manning, John W. Jutila
Journal: The Journal of Experimental Medicine (1972)

Neonatal injection of mice with rabbit anti-micro antiserum has been shown to produce complete loss of direct and indirect plaque-forming responses to sheep erythrocytes as well as loss of serum IgM and severe depressions of all other serum immunoglobulins. Similar injection of anti-gamma1gamma2 or anti-gamma1 antibodies effects a loss of the indirect response but induces relatively minor alterations in serum Ig levels. Delaying initiation of anti-micro treatment until young adulthood results in a somewhat diminished effect on plaque-forming responses and serum Ig levels but triggers the release of high serum levels of an aberrant micro-bearing protein. Anti-micro suppression of genetically thymusless mice indicates that at least part of the target cells for suppression are bone marrow derived. A working hypothesis for the maturation of humoral antibody-producing cell lines as it relates to these data is discussed.
The ACAT Inhibitor CP-113,818 Markedly Reduces Amyloid Pathology in a Mouse Model of Alzheimer's Disease
Authors: Birgit Hutter-Paier, Henri J. Huttunen, Luigi Puglielli, Christopher B. Eckman, Doo Yeon Kim, Alexander Hofmeister, Robert D. Moir, Sarah B. Domnitz, Matthew P. Frosch, Manfred Windisch, Dora M. Kovacs
Journal: Neuron (2004)
1155 IINTERLEUKIN 28B RS12979860 C/T POLYMORPHISM AND SERUM CHOLESTEROL AS PREDICTORS OF FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C AND PERSISTENTLY NORMAL TRANSAMINASES
Authors: E. Fornasiere, S. Cmet, D. Bitetto, A. Cussigh, E. Fumólo, S. Bignulin, E. Fontanini, C. Colletta, C. Vandelli, E. Ceriani, C. Smirne, E. Bignulin, E. Falleti, C. Fabris, P. Toniutto, M. Pirisi
Journal: Journal of Hepatology (2011)
Prognostic nomogram for predicting the 5-year probability of developing metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage II extremity osteosarcoma
Authors: M.S. Kim, S.-Y. Lee, T.R. Lee, W.H. Cho, W.S. Song, J.-S. Koh, J.A. Lee, J.Y. Yoo, D.-G Jeon
Journal: Annals of Oncology (2009)