tbuckley/cabot-search huggingface dataset:
In Vitro Alpha-Fetoprotein Synthesis by Monkey Hepatocellular Carcinoma
Authors: Gerald L. Princler, K. Robert McIntire, Richard H. Adamson
Journal: JNCI Journal of the National Cancer Institute (1978)

Five monkeys were treated ip with N-nitrosodiethylamine (DENA), and one was treated with 1-nitrosopiperidine (PIP), starting within 2 months of birth, until hepatocellular carcinoma (HCC) developed. All animals except the PIP-treated monkey had much elevated serum alpha-fetoprotein (AFP) values. Fresh, minced, biopsy-derived tumor was cultured with L-[14C]leucine and L-[14C]lysine. Synthesis of AFP was determined by radioimmunoassay and by specifically precipitable [14C]AFP. Good agreement between these two parameters was obtained for the 4 DENA-induced tumors synthesizing AFP in culture. Tumor from 1 DENA-treated monkey did not synthesize AFP. In addition, neither normal liver nor tumor from the PIP-treated monkey showed AFP synthesis. Rates of synthesis were 0.37-5.50 ng AFP/mg tumor/day, or 0.0012-0.0183 pg AFP/cell/day (if one assumes 3.0 X 10(5) cells/mg tissue) over 48 or 72 hours. Different nodules from the same animal had similar rates of synthesis. For tumors that synthesized AFP in culture, a positive correlation was generally found between rate of synthesis and serum AFP level. The rate of in vitro AFP synthesis observed was lower than that of immunoglobulin synthesis in human myeloma or of AFP synthesis in a rat HCC, but it was close to the estimated rate of AFP synthesis in a monkey HCC line in long-term culture.
Response to Comment on Wong et al. Real-Time Continuous Glucose Monitoring Among Participants in the T1D Exchange Clinic Registry. Diabetes Care 2014;37:2702–2709
Authors: Jenise C. Wong, Nicole C. Foster, David M. Maahs, Dan Raghinaru, Richard M. Bergenstal, Andrew J. Ahmann, Anne L. Peters, Bruce W. Bode, Grazia Aleppo, Irl B. Hirsch, Lora Kleis, H. Peter Chase, Stephanie N. DuBose, Kellee M. Miller, Roy W. Beck, Saleh Adi
Journal: Diabetes Care (2015)

We thank Price et al. (1) for their comments on our recent article exploring use of continuous glucose monitoring (CGM) in the T1D Exchange Clinic Network registry (2). We acknowledge, as we did in the original article, that the experience of participants included in our study was based on older generations of CGM devices and agree with Price et al. that newer generations …
Bariatric surgery is linked to more diabetes remission than lifestyle intervention alone, study finds:
Authors: Jacqui Wise
Journal: BMJ (2015)

Two thirds of obese patients with type 2 diabetes who had a gastric bypass did not need any diabetes drugs three years after their operation, a US study published in JAMA Surgery has shown. The research also found that a third of patients who had less invasive gastric banding showed remission of their diabetes.1

The trial, conducted at the University of Pittsburgh Medical Center in Pennsylvania, examined outcomes among 61 obese patients with type 2 diabetes who were randomised into three groups. One group …
Fossil fuel companies and climate change: the case for divestment
Authors: T. Tillmann, J. Currie, A. Wardrope, D. McCoy
Journal: BMJ (2015)

Share holder action isn’t working and time is running out

Climate change is likely to have a negative effect on human health through diverse pathways, including extreme weather events and heat waves, the spread of disease vectors to previously temperate climates, and disruption of the water cycle causing drought, famine, conflict, and mass migration.1 To prevent this we need to rapidly replace our dependence on fossil fuel energy with renewables. A debate has emerged within the health community about the best way to stimulate such change.

On one side, the British Medical Association, the Climate and Health Council, and Medact (together with a growing movement outside the health community) are calling for divestment from fossil fuel companies. Such withdrawal of investments should send a clear signal to policy makers and the public that fossil fuel companies are no longer legitimately supporting the general public interest and need to be better regulated.2 Others, however—including the Wellcome Trust and the Gates Foundation—argue that as active shareholders in fossil fuel companies they can change the companies’ practices through dialogue and constructive engagement.3

Although the two sides disagree on how best to change the behaviour of these companies, there …
The Genetic Mosaic
Authors: G Findlay
Journal: Journal of the Royal Society of Medicine (1993)

Blaschko's lines are the acknowledged markers which represent the patterns of systematized naevi. Their interpretation has remained mysterious, because certain special features which they exhibit are impossible to reconcile with any known anatomical system in the human body. It is proposed that by changing one's views on the nature and growth of the dermatome, the patterns of zoster, and the behaviour of tissue mosaicism, the major difficulties hitherto experienced will be overcome.
Abstract 15747: Lack Of Serine Exoprotease Dipeptidyl Peptidase-4 Activity Antagonizes Pressure-overload-induced Systolic Dysfunction Predominantly By Glucagon-like Peptide-1/camp Axis.
Authors: Toshimasa Shigeta, Yasuko K Bando, Akio Monji, Xianwu Cheng, Morihiko Aoyama, Toko Mitsui, Takahiro Okumura, Toyoaki Murohara
Journal: Circulation (2011)

RATIONALE  Dipeptidyl peptidase-4 (DPP4) is a serine exoprotease that degradates SDF-1α and glucagon-like peptide-1 (GLP-1). GLP-1 enhances myocardial contractility and DPP-4 inhibition improves cardiac remodeling after myocardial infarction in rodent models. However, it remains unclear whether the lack of DPP4 may intervene the pressure-overload heart failure.   METHODS & RESULTS  Male spontaneous DPP4-null rats (10 wk old) and age-matched DPP4-positive counterparts were allocated into 2 groups: control (DP(-) and DP(+)) and transaortic constriction-induced pressure-overload heart failure (DP(-)/TAC and DP(+)/TAC). Echocardiography revealed the impaired systolic function (EF=53.8%) and prolonged mitral deceleration time in DP(+)/TAC (42.0±7.3 msec), those were restored in DP(-)/TAC (EF=74.3%, Dct= 34.0±1.2msec). Histological analysis revealed increases in interstitial fibrosis and tissue hypoxia detected by pimonidazole in DP(+)/TAC(5 fold increase vs DP(+)). Coronary capillary density was reduced and cardiomyocyte size was increased in DP(+)/TAC. Cardiac HIF-1α level was elevated in DP(+)/TAC, which were restored in DP(-)/TAC. Cardiac SDF-1α level was increased both in DP(+)/TAC and DP(-)/TAC ( Fig.1A ). GLP-1 level was reduced in DP(+)/TAC heart, which was restored in DP(-)/TAC ( Fig.1B ). Cyclic AMP concentration in cardiac extract obtained from DP(+)/TAC was reduced and DP(-)/TAC exhibited no decline in cyclic AMP level. Administration of exendin-4 (a GLP-1 receptor agonist, 24 nmole/kg/day for 40days) restored the systolic dysfunction in DP(+)/TAC with concomitant elevation of cyclic AMP without affecting cardiac SDF-1α level nor capillary density.   CONCLUSION  Lack of DPP4 activity ameliorates pressure-overload heart failure. GLP-1 predominantly restores pressure-overload heart failure through cAMP-mediated mechanisms independently from the SDF-1α-mediated coronary angiogenesis.
Bronchial reactivity to histamine and bradykinin is unchanged after rhinovirus infection in normal subjects
Authors: Q A Summers, P G Higgins, I G Barrow, D A Tyrrell, S T Holgate
Journal: European Respiratory Journal (1992)

We investigated the effects of rhinovirus (RV) infection on airways reactivity. Twenty seven normal volunteers (11 atopic) were inoculated with RV 2 or RV EL. The provocative concentrations of histamine and bradykinin required to produce a 15% fall in the forced expiratory volume in one second (FEV1) (PC15FEV1) were measured before, 7 and 21 days after inoculation. Infection was determined by a fourfold rise in anti-viral antibody titre and by viral culture from nasal washings. Peak expiratory flow rate (PEF) was recorded three days before and for 21 days after inoculation. All subjects underwent the first two bronchial challenges, and 22 the third challenge. For the whole group and for atopic subjects, there were significant correlations between the PC15 values for bradykinin and histamine (r = 0.82 and r = 0.85, respectively). Twenty subjects were infected; six had clinical colds. For the 16 infected subjects who had all three challenges, the median (range) PC15FEV1 for the histamine challenges was 36 (0.89-64), 62 (1.5-64) and 34 (0.94-64) mg.ml-1, respectively, and 32 mg.ml-1 for each bradykinin challenge (range: 0.015-32, 0.088-32 and 0.033-32). There were no significant differences between study days for PC15FEV1 histamine or bradykinin for the whole group, the infected subjects, those with clinical colds or for those infected with either RV subtype. There was no significant change in mean daily PEF after viral infection. We conclude that airways reactivity to histamine and bradykinin is unchanged after experimental RV infection in normal volunteers.
Phase II study of sunitinib in patients with recurrent and/or metastatic squamous head and neck carcinoma: The GORTEC 2006–01 study
Authors: J. H. Machiels, S. Henry, S. Zanetta, M. Kaminsky, N. Michoux, E. Bompas, A. Dillies, S. Faivre, S. Schmitz, J. Guigay
Journal: Journal of Clinical Oncology (2009)

6024 Background: Up to 90% of head and neck squamous cell carcinoma (HNSCC) express the vascular endothelial growth factor (VEGF) or the VEGF receptors (VEGFR) 1–3. Angiogenic factors could have prognostic implication making anti-angiogenic therapies an attractive treatment modality. Sunitinib inhibits multiple tyrosine kinase receptors including VEGFR1–3 and PDGFR. Methods: Palliative HNSCC in PD after platinum therapy received sunitinib 37.5 mg/day continuously. The primary endpoint was the disease control rate (SD, PR, CR) at 6–8 wks. A two-stage design was used (Simon; a = 0.15,b = 0.10, H0 = 10%, H1 = 25%) meaning that at least 6 patients out of 37 should achieve a SD. Dynamic contrast enhanced (DCE) magnetic resonance (MR) perfusion-weighted imaging before and 6 wks after treatment initiation was performed on a 3T system. Results: 37 pts (M/F:28/9;PS 0/1:5/32) were included.11 pts were not evaluable by imaging due to rapid clinical PD (7 pts) or toxicity (4 pts) and were considered in PD.PR was found in 1 pts, SD in 18, and PD in 18 (RECIST). Among the SD, 6 had a minor response and 5 had an unconfirmed PR (maximum % reduction in sum of the largest diameters: 2%, 4%, 7%, 10%, 16%, 17%, 30%, 45%, 48%, 65%, 73%). PR could not be confirmed due to PD within 4 wks (3 pts) or treatment termination due to toxicity (2 pts). 4 pts had MR DCE monitoring. In 3, a significant decrease in the volume transfer constant Ktrans measuring the tumor perfusion and endothelial permeability was found during sunitinib treatment. The main Gr3–4 toxicities (N pts) were fatigue (12), tumor bleedings (2), LVEF decrease (2), hypertension (2). Gr5 tumor bleedings occurred in 4 pts. Other local complications included apparition/worsening of tumor skin ulceration or tumor fistula in 15 pts. Conclusions: This trial met its primary endpoint with modest activity of sunitinib in HNSSC. The rate of complications (i.e., fatal bleedings) outlines the importance of a better patient selection. DCE-MRI may be useful to predict response. No significant financial relationships to disclose.
Pegylated liposomal anti-eIF3c shRNA-vinorelbine formulation (SEVINA-V) inhibits oncogenic protein translational initiation and oncogene addiction inducing apoptosis in HRBC chemoresistant to taxanes
Authors: John Giannios, P. Ginopulos
Journal: Clinical Cancer Research (2007)

C26    Introduction:  eIF3c is required for the initiation of protein translation, and directly interacts with mTOR activating eIF4e, which is overexpressed in breast cancer. mTOR activates the PI3K/AKT signal transduction pathway, which mediates cell proliferation through activation of growth and survival factors. Furthermore, bcl-2 overexpression inhibits apoptosis causing oncogene addiction and chemoresistance.   Materials and Methods:  We developed xenograft animal models from taxane-chemoresistant hormone refractory breast cancer (HRBC) overexpressing eIF3c, 4EBP1, and bcl-2. We formulated pegylated liposomal anti-eIF3c shRNA vinorelbine (SEVINA-V). Pegylation circumvented RES elimination. The human HRBC xenograft animal models were treated with SEVINA-V.   Results:  Post-treatment, triggering the RNAi pathway through the expression of small hairpin RNA (shRNA) molecules has efficiently silenced the RNA helicase activity of eIF3c disabling cellular cap-dept scanning/initiation. There was subsequent inhibition of PI3K/AKT/mTOR pathway blocking binding of IGFR, PDGFR, EGFR, and HER family receptors in the tumor cell membrane. Inhibition of mTOR prevented downstream activation of mRNA translation and blocked ribosome biogenesis inhibiting S6K1 and 4E-BPI, which led to inhibition of ribosomal protein, elongation factors, and ODC/cyclinD1, respectively. Thus, 4E-BPI-- which was induced by taxanes causing chemoresistance-- was inhibited. There was upregulation of p53 and cycline/CDK2-p27 inhibiting CDK1/2 and cyclinD1 activity. Signal transduction initiated by VEGF was inhibited, and translation of c-myc and anti-apoptotic FLIPs was blocked. Vinorelbine phosphorylated bcl-2, leading to its inactivation and subsequent circumvention of oncogene addiction. Also, vinorelbine blocked cell cycle at G2/M. Transmission electron microscopy exhibited PCD type I, II, and III leading to a bystander killing effect.   Conclusion:  With administration of SEVINA-V, we have achieved oncogene transcriptional intervention in HRBC resistant to taxanes via protein translational inhibition of eIF3c downstream of mTOR dependent pathways, which led to apoptosis in synergy with the chemotherapeutic agent vinorelbine and circumvented oncogene addiction.
Modeling leiomyosarcoma in the mouse
Authors: Eva Hernando, Silvia Menendez, Maria E. Dudas, Elizabeth Charytonowicz, Igor Matushansky, Robert G. Maki, Pier P. Pandolfi, Carlos Cordon-Cardo
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4848 

Sarcomas are a family of tumors of mesenchymal origin representing <1% of all human cancers. A subgroup of soft-tissue sarcomas is associated to defined chromosomal translocations and simple karyotypes, whereas the rest (including leiomyosarcomas) is characterized by complex genotypes and numerous chromosomal aberrations. To date, both the underlying genetic defects and the cell of origin of most human sarcomas remain unknown. Recently, alterations in the PI3K-Akt pathway have been identified in certain sarcoma subtypes. For instance, loss of heterozygosity of 10q23 (containing the PTEN genomic locus) has been frequently observed in human leiomyosarcomas. To determine the role of aberrant PI3K-Akt signaling in leiomyosarcoma pathogenesis, we have genetically inactivated PTEN in the smooth muscle lineage by crossing PTENlox/lox and SM22α-cre mice. Resultant animals carrying homozygous deletion of both PTEN alleles developed widespread smooth muscle hyperplasia, particularly affecting the urinary tract and the intestinal wall. Furthermore, we observed a very rapid onset (2-3 months of age) and elevated incidence of abdominal leiomyosarcomas. Importantly, some of them originate from the blood vessel walls, consistent with one of the sites of origin of these tumors in humans. We confirmed the smooth-muscle origin of these lesions by positive staining of well-established markers, such as desmin and smooth muscle actin. As expected, tumors display high levels of p-Akt and downstream effectors, indicative of constitutive Akt-mTOR signaling. In addition, we found a significant induction of p53 expression, confirming the p53-mediated anti-proliferative response subsequent to PTEN inactivation found in other tissue types. Taken together, our data reveal a novel critical role for the PTEN-Akt pathway in mesenchymal transformation and sarcomagenesis. These newly generated sarcoma models may enable the identification of secondary genetic or phenotypic events required for sarcoma progression and/or metastasis. Finally, we are currently performing pre-clinical studies in this model with new therapeutic compounds that target the Akt-mTOR pathway.
Patient satisfaction survey on bronchoscopy explanation
Authors: Rajesh Kumar Yadavilli, Ian Webster
Journal: European Respiratory Journal (2011)

Background: Bronchoscopy is routinely performed by the Chest physicians and is explained to the patients before they give written consent. We wanted to see if the patients undergoing the procedure at Royal Bolton hospital, UK were satisfied with our explanation and see if anxious patients need higher doses of sedation.

Methods: Patients were asked to fill the satisfaction questionnaire with 8 domains just before undergoing procedure. Interpreters were used for the non-English speaking patients.

Results: 61 patients, undergoing bronchoscopy between Jan 2009 to Jun 2009 answered survey questions with domains in (Table 1) rating their satisfaction between 1-10. Ratings >6 were considered good response except for domain 8 where <5 considered less anxious.

View this table:

Table 1





22% did not receive written leaflets.

Of 27 anxious patients, only 7 (26%) needed more sedation than the mean dose of 2 mg midazolam and 6/34 (18%) less anxious patients also had bigger doses.

Conclusions: Patients were generally satisfied with our bronchoscopy explanation. There is poor correlation between anxiety ratings and doses of sedation.

Educating trainees on broncoscopy explanation, repeating verbal information about procedure with patients at the time of consent and just before the test and giving written leaflets to all the patients at first explanation should improve overall satisfaction.
ALK-Positive Lymphoma: A Single Disease With a Broad Spectrum of Morphology
Authors: Daniel Benharroch, Zarouhie Meguerian-Bedoyan, Laurence Lamant, Chauki Amin, Laurence Brugières, Marie-Jose Terrier-Lacombe, Eugenia Haralambieva, Karen Pulford, Stefano Pileri, Stephan W. Morris, David Y. Mason, Georges Delsol
Journal: Blood (1998)
Clinical Predictors of Major Infections After Cardiac Surgery
Authors: Vance G. Fowler, Sean M. O’Brien, Lawrence H. Muhlbaier, G. Ralph Corey, T. Bruce Ferguson, Eric D. Peterson
Journal: Circulation (2005)

Background— Major infections are infrequent but important complications of cardiac surgery. Predicting their occurrence is essential for future prevention. The objective of the current investigation was to create and validate a bedside scoring system to estimate patient risk for major infection (mediastinitis, thoracotomy or vein harvest site infection, or septicemia) after coronary artery bypass grafting. Methods and Results— Using the Society of Thoracic Surgeons National Cardiac Database, we analyzed 331 429 coronary artery bypass grafting cases from January 1, 2002, to December 31, 2003, to identify risk factors for major infection. Using logistic regression, 2 models were generated and validated using split-sample validation: (1) One limited to preoperative characteristics (preop model) and (2) one model including both preoperative and intraoperative characteristics (combined model). Major infection occurred in 11 636 patients (3.51%) (25.1% mediastinitis, 32.6% saphenous harvest site, 35.0% septicemia, 0.5% thoracotomy, 6.8% multiple sites). Patients with major infection had significantly higher mortality (17.3% versus 3.0%, P &lt;0.0001) and postoperative length of stay &gt;14 days (47.0% versus 5.9%, P &lt;0.0001) than patients without major infection. Both the preop model (c-index 0.697) and combined model (c-index: 0.708) successfully discriminated between high- and low-risk patients. A simplified risk scoring system of 12 variables accurately predicted risk for major infection. Conclusions– We identified and validated a model that can identify patients undergoing cardiac surgery who are at high risk for major infection. These high-risk patients may be targeted for perioperative intervention strategies to reduce rates of major infection.
Association Between Handedness and Type 2 Diabetes: The E3N Study
Authors: Fabrice Bonnet, Aurélie Affret, Marie-Christine Boutron-Ruault, Beverley Balkau, Françoise Clavel-Chapelon, Guy Fagherazzi
Journal: Diabetes Care (2015)

Some studies reported decreased longevity in left-handed individuals as compared with right-handed individuals without a clear underlying explanation. We examined the unexplored relationship between handedness and type 2 diabetes (T2D) among 65,732 women from the prospective Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) cohort study (1) between 1990 and 2008.

As compared with right-handed women, there was an increased risk of T2D …
Systemic Lupus Erythematosus with Anticardiolipin Antibodies and Lupus Anticoagulant Syndrome
Authors: Ali S M Jawad, H Berry
Journal: Journal of the Royal Society of Medicine (1985)

Case report A 25-year-old female Caucasian was seen in the rheumatology clinic in October 1983 because of pain and stiffness in her hands, feet and knees. Since January 1978 she had been treated by her general practitioner for arthralgia in her hands, feet and knees accompanied by morning stiffness lasting 2-3 hours. Non-steroidal anti-inflammatory drugs were prescribed and proved effective in relieving her symptoms. In September 1981 she developed deep vein thrombosis in the left leg which was confirmed by
Metabolic plasticity in CLL: adaptation to the hypoxic niche
Authors: K M Koczula, C Ludwig, R Hayden, L Cronin, G Pratt, H Parry, D Tennant, M Drayson, C M Bunce, F L Khanim, U L Günther
Journal: Leukemia (2015)

Metabolic transformation in cancer is increasingly well understood. However, little is known about the metabolic responses of cancer cells that permit their survival in different microenvironments. We have used a nuclear magnetic resonance based approach to monitor metabolism in living primary chronic lymphoid leukemia (CLL) cells and to interrogate their real-time metabolic responses to hypoxia. Our studies demonstrate considerable metabolic plasticity in CLL cells. Despite being in oxygenated blood, circulating CLL cells are primed for hypoxia as measured by constitutively low level hypoxia-inducible factor (HIF-1α) activity and modest lactate production from glycolysis. Upon entry to hypoxia we observed rapid upregulation of metabolic rates. CLL cells that had adapted to hypoxia returned to the 'primed' state when re-oxygenated and again showed the same adaptive response upon secondary exposure to hypoxia. We also observed HIF-1α independent differential utilization of pyruvate in oxygenated and hypoxic conditions. When oxygenated, CLL cells released pyruvate, but in hypoxia imported pyruvate to protect against hypoxia-associated oxidative stress. Finally, we identified a marked association of slower resting glucose and glutamine consumption, and lower alanine and lactate production with Binet A0 stage samples indicating that CLL may be divided into tumors with higher and lower metabolic states that reflect disease stage.
Abstract 748: Long-Term Survival of Dialysis Patients Undergoing Off-Pump versus On-Pump Coronary Artery Bypass Surgery in the United States
Authors: Charles A Herzog, Shuling Li
Journal: Circulation (2008)

Published data (Beckermann et al, J. Thorac Cardiovasc Surg. 2006) suggest superior outcomes in dialysis pts having coronary artery bypass surgery (CAB) without cardiopulmonary bypass (off-pump) co...