tbuckley/cabot-search huggingface dataset:
Self-experimentation as a source of new ideas: Ten examples about sleep, mood, health, and weight
Authors: Seth Roberts
Journal: Behavioral and Brain Sciences (2004)

Little is known about how to generate plausible new scientific ideas. So it is noteworthy that 12 years of self-experimentation led to the discovery of several surprising cause-effect relationships and suggested a new theory of weight control, an unusually high rate of new ideas. The cause-effect relationships were: (1) Seeing faces in the morning on television decreased mood in the evening (>10 hrs later) and improved mood the next day (>24 hrs later), yet had no detectable effect before that (0–10 hrs later). The effect was strongest if the faces were life-sized and at a conversational distance. Travel across time zones reduced the effect for a few weeks. (2) Standing 8 hours per day reduced early awakening and made sleep more restorative, even though more standing was associated with less sleep. (3) Morning light (1 hr/day) reduced early awakening and made sleep more restorative. (4) Breakfast increased early awakening. (5) Standing and morning light together eliminated colds (upper respiratory tract infections) for more than 5 years. (6) Drinking lots of water, eating low-glycemic-index foods, and eating sushi each caused a modest weight loss. (7) Drinking unflavored fructose water caused a large weight loss that has lasted more than 1 year. While losing weight, hunger was much less than usual. Unflavored sucrose water had a similar effect. The new theory of weight control, which helped discover this effect, assumes that flavors associated with calories raise the body-fat set point: The stronger the association, the greater the increase. Between meals the set point declines. Self-experimentation lasting months or years seems to be a good way to generate plausible new ideas.
STAT3-Mediated Autophagy Dependence Identifies Subtypes of Breast Cancer Where Autophagy Inhibition Can Be Efficacious
Authors: Paola Maycotte, Christy M. Gearheart, Rebecca Barnard, Suraj Aryal, Jean M. Mulcahy Levy, Susan P. Fosmire, Ryan J. Hansen, Michael J. Morgan, Christopher C. Porter, Daniel L. Gustafson, Andrew Thorburn
Journal: Cancer Research (2014)

Autophagy is a protein and organelle degradation pathway that is involved in diverse diseases, including cancer. Recent evidence suggests that autophagy is a cell survival mechanism in tumor cells and that its inhibition, especially in combination with other therapy, could be beneficial but it remains unclear if all cancer cells behave the same way when autophagy is inhibited. We inhibited autophagy in a panel of breast cancer cell lines and found that some of them are dependent on autophagy for survival even in nutrient rich conditions without any additional stress, whereas others need autophagy only when stressed. Survival under unstressed conditions is due to cell type-specific autophagy regulation of STAT3 activity and this phenotype is enriched in triple-negative cell lines. This autophagy-dependency affects response to therapy because autophagy inhibition reduced tumor growth in vivo in autophagy-dependent but not in autophagy-independent breast tumors, whereas combination treatment with autophagy inhibitors and other agent was preferentially synergistic in autophagy-dependent cells. These results imply that autophagy-dependence represents a tumor cell-specific characteristic where autophagy inhibition will be more effective. Moreover, our results suggest that autophagy inhibition might be a potential therapeutic strategy for triple-negative breast cancers, which currently lack an effective targeted treatment.
Liver-Specific pRB Loss Results in Ectopic Cell Cycle Entry and Aberrant Ploidy
Authors: Christopher N. Mayhew, Emily E. Bosco, Sejal R. Fox, Tomohisa Okaya, Pheruza Tarapore, Sandy J. Schwemberger, George F. Babcock, Alex B. Lentsch, Kenji Fukasawa, Erik S. Knudsen
Journal: Cancer Research (2005)

Abstract The liver exhibits an exquisitely controlled cell cycle, wherein hepatocytes are maintained in quiescence until stimulated to proliferate. The retinoblastoma tumor suppressor, pRB, plays a central role in proliferative control by inhibiting inappropriate cell cycle entry. In many cases, liver cancer arises due to aberrant cycles of proliferation, and correspondingly, pRB is functionally inactivated in the majority of hepatocellular carcinomas. Therefore, to determine how pRB loss may provide conditions permissive for deregulated hepatocyte proliferation, we investigated the consequence of somatic pRB inactivation in murine liver. We show that liver-specific pRB loss results in E2F target gene deregulation and elevated cell cycle progression during post-natal growth. However, in adult livers, E2F targets are repressed and hepatocytes become quiescent independent of pRB, suggesting that other factors may compensate for pRB loss. Therefore, to probe the consequences of acute pRB inactivation in livers of adult mice, we gave adenoviral-Cre by i.v. injection. We show that acute pRB loss is sufficient to elicit E2F target gene expression and cell cycle entry in adult liver, demonstrating a critical role for pRB in maintaining hepatocyte quiescence. Finally, we show that liver-specific pRB loss results in the development of nuclear pleomorphism associated with elevated ploidy that is evident in adult mice harboring both acute and chronic pRB loss. Together, these results show the crucial role played by pRB in maintaining hepatocyte quiescence and ploidy in adult liver in vivo and underscore the critical importance of delineating the consequences of acute pRB loss in adult animals.
Differential Regulation of Soluble Guanylyl Cyclase Expression and Signaling by Collagens
Authors: Sergio De Frutos, Marta Saura, Mercedes Griera, Francisco Javier Rivero-Vilches, Carlos Zaragoza, Diego Rodriguez-Puyol, Manuel Rodriguez-Puyol
Journal: Journal of the American Society of Nephrology (2005)

Glomerular diseases are characterized by an abnormal synthesis of extracellular matrix proteins, such as collagen type I. Evidence that growth on collagen type I downregulates soluble guanylyl cyclase (sGC) expression and the responsiveness of human mesangial cells to nitric oxide (NO) by activating specific integrin signals involving integrin-linked kinase (ILK) is presented. Human mesangial cells were grown on collagen type I or IV for 24 to 72 h. Compared with collagen IV, growth on collagen I reduced the protein expression and NO-stimulated enzyme activity of sGC. This downregulation was effected at the level of transcription, because steady-state sGC mRNA expression was reduced on collagen I, but inhibition of transcription with Actinomycin D revealed no differences in transcript stability between the two culture conditions. Collagen I also reduced the capacity of cells to relax in response to NO after H2O2 challenge and inhibited NO-induced phosphorylation of vasodilator-activated phosphoprotein, a target of cyclic guanine monophosphate-dependent protein kinase. Examination of the surface expression of integrins, the receptors for extracellular matrix components, revealed that alpha1 and alpha2 integrin subunits were more abundant on cells that were grown on collagen IV and that surface expression of beta1 integrin did not vary with collagen type. However, growth on collagen I induced beta1 integrin to adopt its active conformation, and this activation of beta1 integrin was accompanied by increased activity of its downstream effector ILK. Dominant-negative suppression of ILK signaling relieved the suppression of sGC expression and NO-induced vasodilator-activated phosphoprotein phosphorylation induced by collagen I.
Trends in deaths from respiratory illness in children in England and Wales from 1968 to 2000
Authors: J R Panickar
Journal: Thorax (2005)

<b>Background:</b> Childhood mortality has decreased markedly over the last three decades. A study was undertaken to determine trends in deaths from respiratory illness in children in England and Wales. <b>Methods:</b> Mortality data collected by the Office for National Statistics were analysed. The data included all deaths registered from all causes in children aged between 28 days and 16 years in England and Wales from 1 January 1968 to 31 December 2000. The main outcome measures were overall and age-specific mortality rates due to all respiratory disorders and specific rates for pneumonia, asthma, cystic fibrosis (CF), and bronchiolitis. <b>Results:</b> In children aged 1–16 years the overall mortality rate (per 100 000 children) declined from 49.9 in 1968 to 16.3 in 2000, and rates due to respiratory illness fell from 8.6 to 1.3. The proportion of all deaths caused by respiratory illness in children aged 28 days to 16 years fell from 30.8% in 1968 to 9.9% in 2000. In post-neonatal infants (aged 28–364 days), the "all cause" mortality rate fell from 592.8 in 1968 to 176 in 2000 and the rates due to respiratory illness fell from 280 to 22.8. In 2000, pneumonia, asthma and CF together accounted for 73% of all respiratory deaths in 1–16 year olds. In this age group, mortality rates per 100 000 for pneumonia fell from 4.22 to 0.57, for asthma from 0.83 to 0.25, and for CF from 0.66 to 0.12 between 1968 and 2000. Over the same period mortality rates for pneumonia in post-neonatal infants fell from 165 to 6.78 per 100 000 and for CF from 4.88 to 0.33. Bronchiolitis mortality rates per 100 000 in post-neonatal infants fell from 21.47 in 1979 to 1.82 in 2000. <b>Conclusions:</b> Mortality rates due to all respiratory illnesses in children have fallen markedly in the last three decades. This decline has been more rapid than the overall decline in childhood mortality and respiratory diseases are now responsible for a smaller proportion of deaths in children. These data could provide a foundation for assessing the impact on mortality of future health initiatives such as the introduction of a universal pneumococcal vaccination programme in England and Wales.
Effects of left ventricular loading by negative intrathoracic pressure in dogs.
Authors: M J Hausknecht, K P Brin, M L Weisfeldt, S Permutt, F C Yin
Journal: Circulation Research (1988)

There are many factors, both intrinsic and extrinsic to the left ventricle, that can affect its function when negative intrathoracic pressure is imposed. In this study, we examined whether the left ventricular response to the afterload imposed by negative intrathoracic pressure was similar to that imposed by partial aortic constriction. We used steady-state right heart bypass to control pulmonary venous return to the left ventricle and reflex blockade to maintain constant heart rate and contractility. To impose negative intrathoracic pressure we used a pressure chamber fitted over a midsternal thoracotomy, which allowed steady negative pressure to be applied to all intrathoracic surfaces. Left ventricular volumes were measured from biplane cineradiograms of multiple 1-mm markers implanted in the left ventricular midwall. With cardiac output and heart rate constant, we compared the left ventricular response to two different levels of negative intrathoracic pressure and to increasing aortic pressure by partial aortic constriction. In each case, negative intrathoracic pressure produced a rise in the left ventricular end-systolic and end-diastolic volumes as well as transmural pressures similar to the effects of partial aortic occlusion. Thus, when cardiac output, heart rate, and contractility are maintained constant and all external restraints on the left ventricle are removed, the left ventricle responds in a similar manner to an increase in hydraulic load whether produced by a decrease in intrathoracic pressure or by partial aortic occlusion.
Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation
Authors: Joseph Leventhal, Michael Abecassis, Joshua Miller, Lorenzo Gallon, Kadiyala Ravindra, David J. Tollerud, Bradley King, Mary Jane Elliott, Geoffrey Herzig, Roger Herzig, Suzanne T. Ildstad
Journal: Science Translational Medicine (2012)

Durable chimerism and donor-specific tolerance can be safely achieved without GVHD in HLA-mismatched donor/recipient pairs.
A Commentary on "The Pseudo-Regulation of American Psychiatry"
Authors: SHERVERT H. FRAZIER
Journal: American Journal of Psychiatry (1972)

The efforts leading up to the formation of the American Board of Psychiatry and Neurology in 1934 reflected the two professions' attempts to protect the public interest and to separate persons who were adequately trained in the two specialties from those who were self-declared specialists. While problems have developed in recent years, efforts toward improvement are under way through experimentation with recertification, a better and more relevant type of Board examination, and other means of evaluating the competence of psychiatrists and other physicians.
CD4+ T Cells Regulate Surgical and Postinfectious Adhesion Formation
Authors: Doo Ryeon Chung, Tanuja Chitnis, Ronald J. Panzo, Dennis L. Kasper, Mohamed H. Sayegh, Arthur O. Tzianabos
Journal: The Journal of Experimental Medicine (2002)

The development of adhesions in the peritoneal and pelvic cavities, which commonly form after surgery or infection, cause significant morbidity and mortality. However, the pathogenesis of adhesion formation is still poorly understood. Because T cells are important in orchestrating fibrinogenic tissue disorders, we hypothesized that they play a critical role in the pathogenesis of peritoneal adhesion formation. Using a cecal abrasion surgical model in rodents, T cell depletion and adoptive transfer experiments demonstrated that this host response is dependent on CD4+ alphabeta T cells. These cells were also critical to adhesion formation associated with experimental intraabdominal sepsis. T cell transfer studies with mice deficient in signal transducer and activator of transcription (Stat)4 and Stat6 revealed that adhesion formation was dependent on a T helper 1 response. Activated T cells homed to the peritoneal cavity 6 hours after cecal abrasion surgery and predominated at this site during adhesiogenesis. Increased levels of the T cell-derived proinflammatory cytokine interleukin (IL)-17 and of neutrophil chemoattractant CXC chemokines macrophage inflammatory protein-2/CXCL8 and cytokine-induced neutrophil chemoattractant/CXCL1 were associated with adhesion formation. The production of these chemokines was dependent on T cells. Furthermore, the administration of neutralizing antibodies specific for IL-17 or the receptor that binds these CXC chemokines, CXC chemokine receptor 2, significantly reduced the degree of adhesion formation. These results demonstrate for the first time that the immunopathogenesis of adhesion formation is under the control of T cells and that T cell-derived cytokines and chemokines play important roles in the development of this deleterious host response.
A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0405
Authors: A Inoue, O Ishimoto, S Fukumoto, K Usui, T Suzuki, H Yokouchi, M Maemondo, M Kanbe, S Ogura, T Harada, S Oizumi, M Harada, S Sugawara, T Fukuhara, T Nukiwa
Journal: Annals of Oncology (2009)
THE DEGREE OF COMPENSATORY RENAL HYPERTROPHY FOLLOWING UNILATERAL NEPHRECTOMY
Authors: Lois L. MacKay, T. Addis, Eaton M. MacKay
Journal: The Journal of Experimental Medicine (1938)

Compensatory hypertrophy of the kidney in albino rats is increased by an increase in the protein intake. The effect is greater in old rats than young rats. Successive increases in the protein intake are followed by a reduction in the increase in the degree of compensatory renal hypertrophy.
AB0781 Clinical periodontal disease predicts the future development of chronic inflammatory arthritis.
Authors: M. Hashimoto, T. Yamazaki, M. Hamaguchi, T. Morimoto, M. Yamori, K. Asai, Y. Isobe, M. Mori, T. Matsuo, M. Furu, H. Ito, T. Fujii, C. Terao, K. Yamamoto, W. Yamamoto, K. Bessho, T. Mimori
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent reports suggest the correlation between rheumatoid arthritis (RA) and periodontal disease (PD). However, it is not clear whether PD affects the disease activity of arthritis or the future introduction of methotrexate (MTX) treatment in non-treated, undifferentiated arthritis patients. <h3>Objectives</h3> To study whether PD affects arthritis activity and introduction of MTX treatment in non-treated, undifferentiated arthritis patients. We also investigated the relationship between a representative periodontal bacteria, <i>Porphyromonas gingivalis (Pg),</i> and arthritis activity or anti-citrullinated protein (CCP) antibody. <h3>Methods</h3> We conducted a prospective cohort study in Kyoto University Hospital, Japan. We consequently enrolled patients who first visited the Rheumatic Disease Center without prior use of anti-rheumatic drugs or corticosteroids from May in 2011 to October in 2012. Arthritis disease activity (SDAI etc.) as well as anti-CCP antibody was systemically investigated by rheumatologists. Clinical parameters of PD (pocket depth, etc.) and subgingival plaque samples were collected by dentists and <i>Pg</i> genomic DNA was determined by Taqman q-PCR. Clinical PD was defined as maximal pocket depth more than 4 mm. We followed up all patients until January 2013. <h3>Results</h3> We enrolled 103 patients, and 11 patients with osteoarthritis 4 patients with remaining teeth less than 10 teeth were excluded from the analysis. PD was associated with higher arthritis disease activity (SDAI 12.9±1.3 in PD group vs 7.3±1.3 in non-PD group, p=0.017), even adjusted for age, sex, smoking, or tooth brushing habit (effect size 0.11, p=0.004). Presence of PD in the first visit was a risk factor for the introduction of MTX treatment in the clinical course (Log-rank p=0.013, Hazard risk 2.77 (95%CI 1.23-6.25)). Although the amount of <i>Pg</i> was associated with pocket depth, it did not correlate with SDAI (10.7±1.6 in PD group vs 10.7±1.3 in non-PD group) or introduction of MTX treatment (Log-rank p=0.72). Either clinical PD or <i>Pg</i> did not correlate with anti-CCP antibody titers in this cohort. <h3>Conclusions</h3> Clinical PD, but not the presence of <i>Pg,</i> was significantly associated with arthritis activity and predicts the future development of chronic inflammatory arthritis that requires MTX. <h3>Disclosure of Interest</h3> None Declared
Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice
Authors: Dennis Bruemmer, Alan R. Collins, Grace Noh, Wei Wang, Mary Territo, Sarah Arias-Magallona, Michael C. Fishbein, Florian Blaschke, Ulrich Kintscher, Kristof Graf, Ronald E. Law, Willa A. Hsueh
Journal: Journal of Clinical Investigation (2003)

Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis, ApoE–/–OPN+/+, ApoE–/–OPN+/–, and ApoE–/–OPN–/– mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared with ApoE–/–OPN+/+ mice, ApoE–/–OPN+/– and ApoE–/–OPN–/– mice developed less Ang II–accelerated atherosclerosis. ApoE–/– mice transplanted with bone marrow derived from ApoE–/–OPN–/– mice had less Ang II–induced atherosclerosis compared with animals receiving ApoE–/–OPN+/+ cells. Aortae from Ang II–infused ApoE–/–OPN–/– mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes in OPN–/– mice was impaired, and OPN–/– leukocytes exhibited decreased basal and MCP-1–directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II–infused ApoE–/–OPN–/– mice was decreased. Finally, Ang II–induced abdominal aortic aneurysm formation in ApoE–/–OPN–/– mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II–accelerated atherosclerosis and aneurysm formation.
Life Years Lost and Lifetime Health Care Expenditures Associated With Diabetes in the U.S., National Health Interview Survey, 1997–2000
Authors: Man-Yee Mallory Leung, Lisa M. Pollack, Graham A. Colditz, Su-Hsin Chang
Journal: Diabetes Care (2014)

OBJECTIVE This study analyzed the lifetime health care expenditures and life years lost associated with diabetes in the U.S. RESEARCH DESIGN AND METHODS Data from the National Health Interview Survey (NHIS), the Medical Expenditure Panel Survey from 1997 to 2000, and the NHIS Linked Mortality Public-use Files with a mortality follow-up to 2006 were used to estimate age-, race-, sex-, and BMI-specific risk of diabetes, mortality, and annual health care expenditures for both patients with diabetes and those without diabetes. A Markov model populated by the risk and cost estimates was used to compute life years and total lifetime health care expenditures by age, race, sex, and BMI classifications for patients with diabetes and without diabetes. RESULTS Predicted life expectancy for patients with diabetes and without diabetes demonstrated an inverted U shape across most BMI classifications, with highest life expectancy being for the overweight. Lifetime health care expenditures were higher for whites than blacks and for females than males. Using U.S. adults aged 50 years as an example, we found that diabetic white females with a BMI &amp;gt;40 kg/m2 had 17.9 remaining life years and lifetime health expenditures of $185,609, whereas diabetic white females with normal weight had 22.2 remaining life years and lifetime health expenditures of $183,704. CONCLUSIONS Our results show that diabetes is associated with large decreases in life expectancy and large increases in lifetime health care expenditures. In addition to decreasing life expectancy by 3.3 to 18.7 years, diabetes increased lifetime health care expenditures by $8,946 to $159,380 depending on age-race-sex-BMI classification groups.
Incorporation of the Terminal Phosphate of ATP into Membranal Protein of Rabbit Cardiac Sarcoplasmic Reticulum: CORRELATION WITH ACTIVE CALCIUM TRANSPORT AND STUDY OF THE EFFECTS OF CYCLIC AMP
Authors: Donald H. Namm, Edward L. Woods, Joan L. Zucker
Journal: Circulation Research (1972)

The transfer of the terminal phosphate of ATP to a material from the sarcoplasmic reticulum of cardiac muscle which can be precipitated by trichloroacetic acid was studied, and the relationship of this biochemical event to active Ca 2+ transport was examined. A component of the phosphoryl transfer reaction was stimulated specifically by Ca 2+ . Both the phosphorylation of the reticulum and the active sequestering of Ca 2+ were proportional to the Ca 2+ concentration between 10 -7 and 10 -5 M. The time course of both phenomena was similar. These and other observations relating Ca 2+ -dependent phosphorylation of the membrane of the sarcoplasmic reticulum with the activesequestering of Ca 2+ suggest that the phosphoryl transfer reaction may represent the formation of a carrier system which facilitates the inward flux of Ca 2+ against a concentration gradient. Cyclic AMP, theophylline, or the combination of these two agents did not influence the rate or extent of the phosphorylation of the sarcoplasmic reticulum. These results have led us to question the hypothesis that the cardiac sarcoplasmic reticulum is the site of action of cyclic AMP in its role as a mediator of cardiac inotropic effects.