tbuckley/cabot-search huggingface dataset:
Abstract 816: Low-Amplitude, High Frequency Electrical Stimulation of the Infarct Region Decreases Matrix Metalloproteinase Abundance and Increases Levels of Tissue Inhibitors of the Metalloproteinases and Collagen Content
Authors: Rupak Mukherjee, William T Rivers, Rebecca A Plyler, Christy Beck, Eileen I Chang, Robert G Matthews, Christine N Koval, Jean Marie Ruddy, Francis G Spinale
Journal: Circulation (2008)

Discordant alterations in the balance between matrix metalloproteinases (MMP) and endogenous MMP inhibitors (TIMPs) within a myocardial infarct (MI) contribute to alterations in LV geometry and ultrastructure, which lead to LV wall thinning at the MI region. While systemic pharmacological approaches can globally alter LV remodeling post-MI, a targeted regional approachto modify MMP/TIMP balance and MI structure has not been explored. We tested the hypothesis that application of localized high frequency stimulation (LHFS) using low amplitude electrical pulses within a formed MI scar would alter MMP/TIMP levels and prevent MI thinning. A uniform and discrete MI was surgically induced in pigs (n=17). At 3 wks post-MI, pigs were randomized for LHFS (n=7, electrical stimulation at 240 bpm, using 0.8V, 0.05ms pulses at the center of the MI region) or unstimulated (UNSTIM, n=10). At 4 wks post-MI, LV wall thickness (echo), and stiffness (piezoelectric crystals with LV preload reduction) were measured. MMP-2, MMP-9, TIMP-1 (zymography or immunoblotting) levels, and fibrillar collagen content (COLL, histology) in the remote and MI regions were determined and normalized to values in LV samples obtained from non-MI pigs (n=5, 100%). LV wall thickness at the MI region was higher with LHFS than UNSTIM (0.89±0.07 vs 0.67±0.08 cm, p&lt;0.05). With LHFS, MMP-2 levels were lower, and TIMP-1 and COLL levels higher than UNSTIM values in the MI region (TABLE ). Myocardial stiffness in the MI region was higher with LHFS than UNSTIM (14.70±2.08 vs 9.11±1.24, respectively, p&lt;0.05). These findings, for the first time, demonstrate that sub-threshold electrical stimulation of the MI region altered MMP/TIMP balance and collagen content, which directly affected LV wall thickness and stiffness. Thus, LHFS may represent a novel, selective means to favorably modify MI scar remodeling and attenuate the progressive LV wall thinning that occurs post-MI.
Gaps in Perception Between Patients and Physicians Regarding Symptomatology and Treatment Attitudes for Myeloproliferative Neoplasms: MPN LANDMARK SURVEY
Authors: Ruben Mesa, Carole B Miller, Maureen Thyne, James Mangan, Sara Goldberger, Salman Fazal, Xiaomei Ma, Wendy Wilson, David G Dubinski, John Boyle, John O Mascarenhas
Journal: Blood (2014)
Abstract 16287: Genetic Deletion of Pim Causes Premature Cardiac Senescence
Authors: Shabana Din, Michael McGregor, Brandi Bailey, Sadia Mohsin, Daniele Avitabile, Natalie Gude, Mark A Sussman
Journal: Circulation (2011)

Rationale:  Cardiac aging is defined as increased cellular senescence and loss of survival signaling within cardiomyocytes and the cardiac stem cell population. To prevent myocardial, aging it is important to reverse the characteristic aging phenotype. Pim-1 is a cardioprotective kinase downstream of AKT, and has been shown to be pro-proliferative and anti-apoptotic. Pim-1 mediated antagonism of myocardial aging will lead to a decrease in cardiac senescence, maintain contractile performance, and prolong the lifespan of an organism.   Objective:  Demonstrate that myocardial senescence is antagonized by Pim-1 mediated signaling and loss of Pim-1 activity leads to premature aging of the myocardium and associated decline in cardiac performance.   Methods and Results:  Pim Triple KnockOut (PTKO) mice, in which all three isoforms of Pim are genetically deleted, develop premature phenotypic hallmarks of myocardial senescence. Elevated levels of the tumor suppressor p53 and senescence marker p16 are present in hearts of PTKO mice at two months of age as seen by western blot and confocal microscopy. Increased p16 expression is consistent with observed induction of Ets-1, a transcription factor that activates p16 transcription in PTKO cardiac samples by western blot. Levels of Id1 and Id2, positive transcriptional regulators of the cell cycle, are decreased in hearts of PTKO mice. Hemodynamic analyses reveal impaired cardiac function in PTKO mice at two months of age. Conversely, cardiac specific overexpression of Pim1-kinase attenuates the senescent phenotype. Hypoxia treatment of neonatal rat cardiomyocytes infected with Pim-1 encoding adenovirus results in reduction of p16 accumulation as seen by qRT-PCR. Pim-1 overexpression increases expression of c-myc, thereby upregulating Id2 and inhibits p16 induced senescence. Cardiac Pim-1 transgenic mice show a delay in the onset of senescence as evidenced by decreased frequency of p16 positive cells in the myocardium by confocal microscopy.   Conclusion:  Pim-1 inhibits cardiac senescence and is important for maintaining cardiac function. Therefore, selective manipulation of Pim-1 should be pursued as a therapeutic target to promote and extend myocardial cellular lifespan and function.
Abstract 19592: Coronary Thin-Capped Atheromata Exhibit Increased Expression of Interstitial Collagenases in Regions of Persistently Low Endothelial Shear Stress: A Serial, in vivo Natural History Study in Pigs.
Authors: Konstantinos C Koskinas, Galina K Sukhova, Aaron B Baker, Yiannis S Chtzizisis, Michael I Papafaklis, Ahmet U Coskun, Michael Jonas, Guo-Ping Shi, Peter Libby, Elazer R Edelman, Peter H Stone, Charles L Feldman
Journal: Circulation (2010)

Background: The mechanisms underlying the focal formation of coronary thin cap atheromata (TCA) remain elusive. Endothelial shear stress (ESS) critically influences individual plaque progression. I...
Near-continuous temozolomide and low-dose weekly CCNU: A novel chemotherapy regimen with activity in malignant gliomas resistant to dose-dense temozolomide alone.
Authors: H. M. Strik, C. H. Bock, K. Kallenberg
Journal: Journal of Clinical Oncology (2010)

e12544 Background: Alkylating chemotherapy with CCNU is active in recurrent glioma, but may be antagonized by anti-alkylating MGMT. Here, we present feasibility and activity of a novel regimen aiming at depletion of MGMT with lower dose, near-continuous temozolomide followed by low-dose weekly CCNU to treat recurrent malignant gliomas resistant to dose-dense temozolomide. Methods: 11 consecutive patients with recurrent malignant gliomas (4 glioblastomas, 3 gliosarkomas, 4 anaplastic gliomas) were treated: 6 males (55%), 5 females (45%); mean age at first diagnosis was 55.9 (19-76) years; median Karnofsky Performance Status 70%; nine patients were treated for a second, two for first recurrence. All patients were pretreated with dose-dense temozolomide (day 1-21/28 or 1-5/7, initial dose 100 mg/m2). Nine of the 11 patients were switched without delay from dose-dense temozolomide monotherapy to combined near-continuous temozolomide (50-60 mg/m2 day 1-5/7) plus weekly low-dose CCNU (40mg fix dose at day 6/7). Results: in total, 32 cycles of chemotherapy were applied. The combination was well tolerated in terms of nausea and fatigue. Blood counts decreased continuously, enabling a gradual dose adaptation. Hematological WHO grade 3+4 toxicity occurred in 5/11 patients (45%), two of them were symptomatic. One patient had a prolonged elevation of liver enzymes which improved partially after termination of levetiracetam. Best responses after ≥ 2 months were: 1 complete and 2 partial remissions (27%), 3 stable diseases (27%), 5 progressive diseases (46%). Median overall survival after start of chemotherapy was 4.5 months, progression-free survival at six months (PFS 6) was 18%, overall survival from first diagnosis 23.5 months. Conclusions: In spite of adverse prognostic signs, the objective remissions indicate activity of combined near-continuous temozolomide and low-dose weekly CCNU after failure of dose-dense temozolomide alone. Hematotoxicity, though, has to be controlled vigorously. The results have to be controlled in a larger, prospective series. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Medac Schering-Plough
Abstract 14: Japanese Emergency Medical System Achieves Good Result in Resuscitation of Out-of-Hospital Cardiac Arrest without Drug Administration. A Population Based Analysis, Sapporo Japan.
Authors: Tomoyuki Sato, Kei Yamazaki, Akio Endo, Katsutoshi Sano, Toshinao Matsui, Shinji Uegaki, Naomi Henzan, Masaki Okada, Hiroshi Makise, Yasumi Igarashi, Noriyoshi Kato, Masaki Togashi, Hitoshi Kano
Journal: Circulation (2006)

Introduction This report is the first official analyses from Sapporo to use the ‘Utstein template’ to report outcomes of out-of-hospital cardiac arrest (OHCA). Method We investigated prospectively ...
Abstract 15045: Endothelial Function Improves With Physical Fitness In Adolescents - Primary Cardiovascular Prevention Must Start In Childhood!
Authors: Ulrike M Muller, Katharina Machalica, Jennifer Adam, Volker Adams, Claudia Walther, Gerhard C Schuler
Journal: Circulation (2011)

Introduction: The decrease in physical activity over the past decades is one of the most important causes for the increase in overweight, obesity and cardiovascular risk factors in children. Endoth...
Soundings: Glimpses of the past
Authors: George Dunea
Journal: BMJ (2006)

Immersed in the story as I was while listening in the car on the way to work, I found myself wondering about what would happen to Mary Thorne. Was Frank Gresham going to propose or would he “marry money”? Would Mary herself give him up? I had long forgotten how it all ended, and listening to one episode at a time I felt each morning rather like Charles Dickens' readers, who would excitedly wait at the wharf in New York for the ship bringing the next episode of David Copperfield.

Doctor Thorne (1858) is Anthony Trollope's third Barchester chronicle, still read and relevant when so many once fashionable authors have sunk into oblivion. Marrying money and preserving distinctions of rank and blood are the predominant themes, but the book should also interest doctors, especially those discontented with present day arrangements.

Trollope's hero, Doctor Thorne, charges only seven shillings and sixpence for a visit and supplements his income by dispensing medicines that he himself mixes up. His rivals, or indeed enemies, are the fashionable Barchestesr physicians who charge several guineas and look down with contempt on the apothecary. Medical practice consists of calling at patients' houses, on a horse or in a horse carriage. Prescriptions are written for drugs that we may safely infer were mostly ineffective and sometimes harmful. When things get sticky the solution is to call in another doctor in consultation. The fashionable physicians will have nothing to do with their apothecary rival, but may on occasion call in a famous physician from London. Some patients are notoriously fickle, now calling in Dr Thorne, now his rivals.

The doctors' armamentarium is clearly limited. But they make up for this by spending much time with the patient, even staying all night if the patient is very ill or dying, especially if the patient is wealthy or important. The fashionable doctors write reports for a medical gazette. Dr Thorne manages the squire's money and gives sensible lifestyle advice.

An often quoted passage explains how to collect a fee without embarrassment. It should be done without a look, without a move of the facial muscles, with hardly an awareness “that the last friendly grasp has been made so much more precious by the touch of gold.” How much easier to receive a monthly pay cheque.
Enhanced paracellular transport of insulin can be achieved via transient induction of myosin light chain phosphorylation
Authors: Alistair Taverner, Ruggero Dondi, Khaled Almansour, Floriane Laurent, Siân-Eleri Owens, Ian M. Eggleston, Nikoletta Fotaki, Randall J. Mrsny
Journal: Journal of Controlled Release (2015)

The intestinal epithelium functions to effectively restrict the causal uptake of luminal contents but has been demonstrated to transiently increase paracellular permeability properties to provide an additional entry route for dietary macromolecules. We have examined a method to emulate this endogenous mechanism as a means of enhancing the oral uptake of insulin. Two sets of stable Permeant Inhibitor of Phosphatase (PIP) peptides were rationally designed to stimulate phosphorylation of intracellular epithelial myosin light chain (MLC) and screened using Caco-2 monolayers in vitro. Apical application of PIP peptide 640, designed to disrupt protein–protein interactions between protein phosphatase 1 (PP1) and its regulator CPI-17, resulted in a reversible and non-toxic transient reduction in Caco-2 monolayer trans-epithelial electric resistance (TEER) and opening of the paracellular route to 4 kDa fluorescent dextran but not 70 kDa dextran in vitro. Apical application of PIP peptide 250, designed to impede MYPT1-mediated regulation of PP1, also decreased TEER in a reversible and non-toxic manner but transiently opened the paracellular route to both 4 and 70 kDa fluorescent dextrans. Direct injection of PIP peptides 640 or 250 with human insulin into the lumen of rat jejunum caused a decrease in blood glucose levels that was PIP peptide and insulin dose-dependent and correlated with increased pMLC levels. Systemic levels of insulin suggested approximately 3–4% of the dose injected into the intestinal lumen was absorbed, relative to a subcutaneous injection. Measurement of insulin levels in the portal vein showed a time window of absorption that was consistent with systemic concentration-time profiles and approximately 50% first-pass clearance by the liver. Monitoring the uptake of a fluorescent form of insulin suggested its uptake occurred via the paracellular route. Together, these studies add validation to the presence of an endogenous mechanism used by the intestinal epithelium to dynamically regulate its paracellular permeability properties and better define the potential to enhance the oral delivery of biopharmaceuticals via a transient regulation of an endogenous mechanism controlling the intestinal paracellular barrier.
Does age make a difference in the effects of physical health and social support on the outcome of a major depressive episode?
Authors: D C Hughes, D DeMallie, D G Blazer
Journal: American Journal of Psychiatry (1993)

The authors examined the effects of physical health and social support on 6-month outcome of a major depressive episode in 67 patients who were less than 60 years old and 46 patients who were 60 years old or older. They hypothesized that despite their higher rate of troublesome health problems, older patients would have fewer depressive symptoms at follow-up than would younger patients.The Center for Epidemiologic Studies Depression Scale (CES-D Scale) and a modified version of the National Institute of Mental Health Diagnostic Interview Schedule were used to gather data from inpatients and outpatients treated at Duke University Medical Center during a face-to-face interview at baseline and over the telephone at 6-month follow-up. At baseline, all patients met DSM-III-R criteria for a major depressive episode. Data analyses included bivariate and multivariate procedures.At baseline, the mean CES-D Scale scores of the two age groups were similar. As expected, the mean illness index score of the older patients was significantly higher and their mean impaired subjective social support score was slightly lower than those of the younger patients. At 6-month follow-up, the mean CES-D Scale score of the younger patients was above the depressive threshold, but the mean CES-D Scale score of the older patients was below the depressive threshold. The illness index and impaired subjective support measures were significant predictors of depressive symptoms at 6 months for the younger patients but not for the older patients.The authors conclude that older depressed patients have a more favorable prognosis than younger depressed patients. Predictors of outcome vary by age.
The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health
Authors: Philip J. Landrigan, Robert O. Wright, Jose F. Cordero, David L. Eaton, Bernard D. Goldstein, Bernhard Hennig, Raina M. Maier, David M. Ozonoff, Martyn T. Smith, Robert H. Tukey
Journal: Environmental Health Perspectives (2015)

The Superfund Research Program (SRP) is an academically based, multidisciplinary, translational research program that for 25 years has sought scientific solutions to health and environmental problems associated with hazardous waste sites. SRP is coordinated by the National Institute of Environmental Health Sciences (NIEHS). It supports multi-project grants, undergraduate and postdoctoral training programs, individual research grants, and Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR) grants.SRP has had many successes: discovery of arsenic's toxicity to the developing human central nervous system; documentation of benzene toxicity to hematologic progenitor cells in human bone marrow; development of novel analytic techniques such as the luciferase expression assay and laser fragmentation fluorescence spectroscopy; demonstration that PCBs can cause developmental neurotoxicity at low levels and alter the genomic characteristics of sentinel animals; elucidation of the neurodevelopmental toxicity of organophosphate insecticides; documentation of links between antimicrobial agents and alterations in hormone response; discovery of biological mechanisms through which environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and cancer; tracking the health and environmental effects of the attacks on the World Trade Center and Hurricane Katrina; and development of novel biological and engineering techniques to facilitate more efficient and lower-cost remediation of hazardous waste sites.SRP must continue to address the legacy of hazardous waste in the United States, respond to new issues caused by rapid advances in technology, and train the next generation of leaders in environmental health science while recognizing that most of the world's worst toxic hot spots are now located in low- and middle-income countries.
Book: The Baby Makers
Authors: K. Sharif
Journal: BMJ (1999)

Jack Challoner Channel 4 Books, £14.99, pp 176 ISBN 0752217011 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Baby making is supposed to be fun and—judging from this overpopulated planet—straightforward. Not so for the one in six infertile couples, an estimated 80 million worldwide. Their devastation may be like that of Rachel, the barren biblical character, who said: “Give me a child else I die.” Enter the baby makers; those who have dreamt of, … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Abstract 3776: IL-6 Deficient Mice are Protected from Diet-Induced Inflammation and Insulin Resistance in Heart
Authors: Hwi Jin Ko, Zhiyou Zhang, Dae Young Jung, John Y Jun, Zhexi Ma, Jason K Kim
Journal: Circulation (2008)

Circulating levels of inflammatory cytokines are elevated in obesity, and IL-6 is shown to regulate glucose metabolism in peripheral organs. Our recent study found that IL-6 reduces myocardial gluc...
Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants
Authors: Michele La Merrill, Claude Emond, Min Ji Kim, Jean-Philippe Antignac, Bruno Le Bizec, Karine Clément, Linda S. Birnbaum, Robert Barouki
Journal: Environmental Health Perspectives (2012)

Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects.AT appears to play diverse functions both as a modulator and as a target of POPs toxicity.
Abstract 3734: Differential Platelet Proteome Analysis Following Specific Activation Of Glycoprotein VI
Authors: Christian Schulz, Nina V Leuschen, Thomas Fröhlich, Michael Lorenz, Georg J Arnold, Steffen Massberg
Journal: Circulation (2008)

Background: Platelets play a key role in haemostasis and in the pathophysiology of various diseases including arterial thrombosis. Glycoprotein (GP)VI, the major platelet collagen receptor, mediates platelet activation and firm adhesion to collagen structures exposed at sites of vascular injury. Here, we determined the effects of specific activation of GPVI on the human platelet proteome by two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry. Methods and Results: Platelets from healthy human donors were isolated and purified. Platelets were stimulated with an activating monoclonal antibody specific for GPVI, or control IgG. Platelet proteins were subjected to 2D-DIGE with extensive software-assisted image analysis. Subsequent identification of the differentially abundant proteins was carried out by MALDI TOF/TOF MS and LC ESI-MS/MS. We identified 8 differentially regulated proteins associated with cell signaling, metabolism, organization and rearrangement of the cytoskeleton, and membrane trafficking. Differentially abundant proteins included pleckstrin, beta-centractin, src substrate cortactin, charged multivesicular body protein 3, aldose reductase and protein disulfide isomerase-associated 3 precursor. Conclusion: Specific platelet activation via GPVI results in the differential regulation of several proteins. The results provide further insight into the mechanisms that underlie platelet activation through the GPVI receptor, which may help to identify novel pharmacological targets.
Autocrine production of epithelial cell–derived neutrophil attractant-78 induced by granulocyte colony-stimulating factor in neutrophils
Authors: Sachiko Suzuki, Masanobu Kobayashi, Kouji Chiba, Iori Horiuchi, Jingxin Wang, Takeshi Kondoh, Satoshi Hashino, Junji Tanaka, Masuo Hosokawa, Masahiro Asaka
Journal: Blood (2002)
Suicide among U.S. women physicians, 1967-1972
Authors: Ferris N. Pitts, Arthur B. Schuller, Charles L. Rich, Andrew F. Pitts
Journal: American Journal of Psychiatry (1979)

The authors examined AMA records of the deaths of 751 women physicians during 1967-1972. Forty-nine (6.56%) committed suicide. The suicide rate for women physicians (40.7 per 100,000 per year) was higher than for men physicians and about four times that for white American women of the same age. From the known morbid risk for suicide among women with primary affective disorder, the authors calculated that about 65% of American women physicians have primary affective disorder.