tbuckley/cabot-search huggingface dataset:
Exercise, Glucose Transport, and Insulin Sensitivity
Authors: Laurie J. Goodyear, Barbara B. Kahn
Journal: Annual Review of Medicine (1998)

Physical exercise can be an important adjunct in the treatment of both non–insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non–insulin-dependent diabetes mellitus.
Growth-Inhibitory Effects of Human Anti-Insulin-Like Growth Factor-I Receptor Antibody (A12) in an Orthotopic Nude Mouse Model of Anaplastic Thyroid Carcinoma
Authors: Zhuoying Wang, Geetika Chakravarty, Seungwon Kim, Yasemin D. Yazici, Maher N. Younes, Samar A. Jasser, Alfredo A. Santillan, Corazon D. Bucana, Adel K. El-Naggar, Jeffrey N. Myers
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The insulin-like growth factor-I receptor (IGF-IR) and its ligands have been implicated in the pathogenesis and progression of various cancers, including those arising in the thyroid gland. We therefore evaluated whether the IGF-IR could serve as a potential target for therapy of anaplastic thyroid carcinoma (ATC). Experimental Design: The expression and activation of the IGF-IR and some of its downstream signaling pathway components were evaluated in both human thyroid cancer specimens and thyroid cancer cell lines. The therapeutic potential of a humanized monoclonal antibody (A12) directed against IGF-IR was assessed in vitro and in vivo in an orthotopic model of ATC. Tumor volume and overall survival time were analyzed to evaluate the efficacy of A12 in vivo. Results: IGF-IR was overexpressed in 94% of the thyroid cancers. Blockade of IGF-IR with A12 was effective in attenuating IGF-IR signaling both in vitro and in vivo. However, the inhibitory effects of A12 on cell proliferation were cell line dependent, as those ATC cell lines that had detectable levels of pIGF-IR were more sensitive to A12 treatment. A12 was equally effective in vivo, where it brought ∼57% (P = 0.041) inhibition in tumor volume. The concomitant use of A12 and irinotecan produced additive effects and resulted in a 93% (P &amp;lt; 0.001) reduction in tumor volume. Blocking IGF-IR blocked Akt phosphorylation and decreased proliferation and microvessel density but increased apoptosis within the tumor xenografts. Our results also highlighted a previously undefined IGF-IR-mediated antiangiogenic effect on tumor-associated endothelium in thyroid cancers. Conclusion: Blocking the IGF-IR with A12 seems to be a potential avenue for treating patients with ATC by its direct antitumor effects and its effects on the tumor vasculature.
Proactive Telephone Counseling for Smoking Cessation: Meta-analyses by Recruitment Channel and Methodological Quality
Authors: F. Tzelepis, C. L. Paul, R. A. Walsh, P. McElduff, J. Knight
Journal: JNCI Journal of the National Cancer Institute (2011)

Systematic reviews demonstrated that proactive telephone counseling increases smoking cessation rates. However, these reviews did not differentiate studies by recruitment channel, did not adequately assess methodological quality, and combined different measures of abstinence.Twenty-four randomized controlled trials published before December 31, 2008, included seven of active recruitment, 16 of passive recruitment, and one of mixed recruitment. We rated methodological quality on selection bias, study design, confounders, blinding, data collection methods, withdrawals, and dropouts, according to the Quality Assessment Tool for Quantitative Studies. We conducted random effects meta-analysis to pool the results according to abstinence type and follow-up time for studies overall and segregated by recruitment channel, and methodological quality. The level of statistical heterogeneity was quantified by I(2). All statistical tests were two-sided.Methodological quality ratings indicated two strong, 10 moderate, and 12 weak studies. Overall, compared with self-help materials or no intervention control groups, proactive telephone counseling had a statistically significantly greater effect on point prevalence abstinence (nonsmoking at follow-up or abstinent for at least 24 hours, 7 days before follow-up) at 6-9 months (relative risk [RR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43, P < .001, I(2) = 21.4%) but not at 12-15 months after recruitment. This pattern also emerged when studies were segregated by recruitment channel (active, passive) or methodological quality (strong/moderate, weak). Overall, the positive effect on prolonged/continuous abstinence (abstinent for 3 months or longer before follow-up) was also statistically significantly greater at 6-9 months (RR = 1.58, CI = 1.26 to 1.98, P < .001, I(2) = 49.1%) and 12-18 months after recruitment (RR = 1.40, CI = 1.23 to 1.60, P < .001, I(2) = 18.5%).With the exception of point prevalence abstinence in the long term, these data support previous results showing that proactive telephone counseling has a positive impact on smoking cessation. Proactive telephone counseling increased prolonged/continuous abstinence long term for both actively and passively recruited smokers.
Long-term survivors of small-cell lung cancer (SCLC): A French multicenter study
Authors: P Jacoulet, A Depierre, D Moro, A Rivière, B Milleron, E Quoix, E Ranfaing, D Anthoine, J J Lafitte, B Lebeau, J P Kleisbauer, F Massin, P Fournel, M Zaegel, J P Leclerc, G Garnier, E Brambilla, F Capron
Journal: Annals of Oncology (1997)
Gas Transfer and Pulmonary Blood Flow at Rest and during Exercise in Adults 21 Years after Preterm Birth
Authors: Indra Narang, Andrew Bush, Mark Rosenthal
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: After preterm birth, limited data exist in adulthood regarding alveolar–capillary growth and exercise capacity. Gas transfer at rest through exercise is a noninvasive measure of alveolar–capillary development.Objectives: To determine exercise capacity and gas transfer at rest and during exercise in ex-preterm adults.Methods: Ex-preterm subjects (n = 60; median gestation, 31.5 wk) recruited at birth underwent exercise testing at 21 years of age and were contemporaneously compared with 50 healthy control subjects.Measurements and Main Results: Subjects exercised on a cycle ergometer, and measurements of heart rate (HR), FRC, effective pulmonary blood flow (Q̇peff), stroke volume (SV), DlCO, V̇o2, arteriovenous oxygen difference (AVO), transit time (TT), respiratory rate (Rf), V̇co2, V̇e, Vt, and respiratory quotient (RQ) were made using a respiratory mass spectrometer. In the index study group and control subjects, the median DlCO (mmol/min/kPa/m2) at rest was 4.33 (95% confidence interval [CI], 4.18–4.62) and 4.75 (95% CI, 4.50–5.10), respectively (P = 0.01), and the median Q̇peff (L/min/m2) at rest was 3.26 (95% CI, 3.16–3.49) and 3.59 (95% CI, 3.43–3.81), respectively (P = 0.04). Q̇peff and DlCO values normalized during exercise but were reduced and lower than controls after a recovery period. No significant differences were found in exercise capacity between the groups.Conclusions: The data suggest a long-term effect of premature delivery on resting cardiac output and gas transfer, not due to abnormal cardiac or pulmonary function and with no evidence of exercise limitation.
Ruptured Mitral Chordae Tendineae
Authors: PHILIP J. OSMUNDSON, JOHN A. CALLAHAN, JESSE E. EDWARDS
Journal: Circulation (1961)

The present study presents pertinent clinical and pathologic findings in 20 cases of ruptured mitral chordae tendineae encountered at the Mayo Clinic between 1934 and 1958 inclusive. Mitral insufficiency results from the rupture of chordae tendineae, the severity being related to the number of chordae ruptured. The resulting heart disease may be severe and may progress to cardiac decompensation and death. Bacterial endocarditis was the major etiologic factor in rupture of the chordae tendineae in this study.
STUDIES ON THE MECHANISM OF IMMUNITY IN TYPHUS FEVER
Authors: M. Ruiz Castaneda
Journal: The Journal of Experimental Medicine (1936)

The intradermal inoculation of Mexican typhus virus into immune guinea pigs produces a local reaction which is similar in its appearance to the lesion observed in the skin of normal animals submitted to the same treatment. The reaction in the immune animal appears earlier and fades sooner than the lesion in the normal guinea pig. The inoculation of heat-killed or formalin-killed Rickettsiae produces no significant reactions at the site of the intradermal injection in typhus immune guinea pigs. The virus, inoculated intradermally, has been recovered from the local lesion 72 hours after the injection into typhus immune guinea pigs. Normal guinea pigs and persons without a history of typhus fever present a congestion and some swelling of the skin at the site of the intradermal injection of formalinized Mexican Rickettsiae. The reaction appears 24 hours after the inoculation and fades within 48 hours. Heating the formalinized Rickettsia suspensions at 70 degrees C. for 30 minutes renders them inactive in normal men and guinea pigs. From the experiments reported in this paper it seems that the reactions observed in typhus immune guinea pigs submitted to a second inoculation of typhus virus, belong to the group of reactions presented by tuberculous animals (Koch's phenomenon) and the accelerated takes shown by immune persons submitted to revaccination with vaccinia virus. A heat labile substance has been demonstrated in the formalinized Rickettsia bodies, which produces a reaction in the skin of normal men and guinea pigs.
Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia
Authors: Keunwook Lee, Ki Taek Nam, Sung Hoon Cho, Prathyusha Gudapati, Yoonha Hwang, Do-Sim Park, Ross Potter, Jin Chen, Emmanuel Volanakis, Mark Boothby
Journal: The Journal of Experimental Medicine (2012)

Notch plays critical roles in both cell fate decisions and tumorigenesis. Notch receptor engagement initiates signaling cascades that include a phosphatidylinositol 3-kinase/target of rapamycin (TOR) pathway. Mammalian TOR (mTOR) participates in two distinct biochemical complexes, mTORC1 and mTORC2, and the relationship between mTORC2 and physiological outcomes dependent on Notch signaling is unknown. In this study, we report contributions of mTORC2 to thymic T-cell acute lymphoblastic leukemia (T-ALL) driven by Notch. Conditional deletion of Rictor, an essential component of mTORC2, impaired Notch-driven proliferation and differentiation of pre-T cells. Furthermore, NF-κB activity depended on the integrity of mTORC2 in thymocytes. Active Akt restored NF-κB activation, a normal rate of proliferation, and differentiation of Rictor-deficient pre-T cells. Strikingly, mTORC2 depletion lowered CCR7 expression in thymocytes and leukemic cells, accompanied by decreased tissue invasion and delayed mortality in T-ALL driven by Notch. Collectively, these findings reveal roles for mTORC2 in promoting thymic T cell development and T-ALL and indicate that mTORC2 is crucial for Notch signaling to regulate Akt and NF-κB.
Adenoviral Delivery of a Leukocyte-Type 12 Lipoxygenase Ribozyme Inhibits Effects of Glucose and Platelet-Derived Growth Factor in Vascular Endothelial and Smooth Muscle Cells
Authors: Mary Kim Patricia, Rama Natarajan, Alek N. Dooley, Felicia Hernandez, Jia-Li Gu, Judith A. Berliner, John J. Rossi, Jerry L. Nadler, Robert S. Meidell, Catherine C. Hedrick
Journal: Circulation Research (2001)

Abstract —The lipoxygenase (LO) pathway has been implicated as an important mediator of chronic glucose and platelet-derived growth factor (PDGF)-induced effects in the vascular system. Endothelial cells treated with 12LO products or cultured in high glucose showed enhanced monocyte adhesion, an important step in atherogenesis. We have previously reported that PDGF increased HETE levels in porcine aortic smooth muscle cells. Although several pharmacological inhibitors to the LO pathway are available, most lack specificity and may harbor undesirable side effects. Therefore, we developed a recombinant adenovirus expressing a hammerhead ribozyme (AdRZ) targeted against the porcine leukocyte-type 12LO mRNA to investigate the involvement of LO in glucose- and PDGF-mediated effects in vascular cells. Infection of porcine aortic endothelial cells with AdRZ reduced the level of glucose-enhanced 12LO mRNA expression as determined by quantitative, real-time reverse transcriptase–polymerase chain reaction. Reverse-phase HPLC and RIA analysis also revealed a corresponding decrease in glucose-stimulated 12HETE production in both the cellular and supernatant fractions. In the ribozyme-treated porcine aortic endothelial cells, there was marked inhibition of high glucose-stimulated monocyte adhesion. Infection with AdRZ also reduced PDGF-induced porcine aortic smooth muscle cell migration by approximately 50%. These studies demonstrate the efficacy of recombinant adenovirus expressing 12LO ribozyme in studying the effects of 12LO in vascular wall cells. They document an important role for the 12LO pathway in regulating inflammatory changes in endothelial cells and smooth muscle cells.
Enhancing tolerance to interval exercise in moderate-to-severe COPD
Authors: Daniela Bravo, Ana Gimenes, Beatriz Amorim, Maria Clara Alencar, J. Alberto Neder, Luiz Eduardo Nery
Journal: European Respiratory Journal (2014)

Interval exercise (IE) may improve tolerance and compliance to exercise training in ventilatory-limited patients with COPD. It is currently unclear, however, which parameter(s) is (are) the most relevant to maximize patients9 tolerance to IE. Sixteen non-hypoxemic males with moderate-to-severe COPD underwent, on different days and in a randomized sequence, five cardiopulmonary exercise tests to the limit of tolerance (Tlim) or up to 30 min: a) a constant exercise (CE) test at 80% of the previously-determined peak work-rate (WR) and b) four 1:2 duty cycle IE tests (100% peak WR) in which both high-intensity exercise time (SHORT: 30 s, LONG: 60 s) and low-intensity exercise load (0 W or 40 W) varied. Tests were ranked according to Tlim: the frequency at which a given test was ranked the longest and the shortest defined a Tlim rank ratio. No patient tolerated the CE test for 30 min; in fact, this test was associated with the lowest Tlim and total work values (p  p≤0.05: * vs. CWR; § vs.LONG-0; † vs. SHORT-40; ‡ vs. LONG-40  In conclusion, tolerance to IE in patients with COPD can be further enhanced by avoiding loaded exercise in-between the high-intensity bouts. Long (60 s) and short (30 s) bouts are equally well tolerated by these patients.
The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes
Authors: Denis J. Dupré, Mélanie Robitaille, R. Victor Rebois, Terence E. Hébert
Journal: The Annual Review of Pharmacology and Toxicology (2008)

The role of Gbetagamma subunits in cellular signaling has become well established in the past 20 years. Not only do they regulate effectors once thought to be the sole targets of Galpha subunits, but it has become clear that they also have a unique set of binding partners and regulate signaling pathways that are not always localized to the plasma membrane. However, this may be only the beginning of the story. Gbetagamma subunits interact with G protein-coupled receptors, Galpha subunits, and several different effector molecules during assembly and trafficking of receptor-based signaling complexes and not simply in response to ligand stimulation at sites of receptor cellular activity. Gbetagamma assembly itself seems to be tightly regulated via the action of molecular chaperones and in turn may serve a similar role in the assembly of specific signaling complexes. We propose that specific Gbetagamma subunits have a broader role in controlling the architecture, assembly, and activity of cellular signaling pathways.
Prolonged Extracorporeal Circulation
Authors: T. Frederiksen, J. Rosen, I. H. Rygg, E. Christensen, F. Therkelsen
Journal: Thorax (1963)

Interest in prolonged perfusions has increased pari passu with the possibility of treating the more complicated cardiac deformities. Prolonged perfusions may be of interest also in functional disturbances arising during operations using the heart-lung machine, since it may be difficult to discontinue the perfusion before cardiac function is again satisfactory. Furthermore, the biological changes which take place during prolonged perfusion reflect, in an intensified degree, the changes that occur during an ordinary brief perfusion (Andersen, 1961). Even though the outcome is fatal after such a long-lasting perfusion, it is of interest to investigate the biochemical changes during the perfusion, especially if the patient has not succumbed to the perfusion. It is of even greater interest to ascertain whether the patient might have survived such a long-lasting perfusion had he not succumbed to other causes. A very prolonged perfusion in a patient who has survived has not yet been reported. This is not surprising, since prolonged extracorporeal circulation has usually been necessitated by a life-threatening condition. The data from a 12-hour perfusion are presented.
Presence–Absence Variation in A. thaliana Is Primarily Associated with Genomic Signatures Consistent with Relaxed Selective Constraints
Authors: Stephen J. Bush, Atahualpa Castillo-Morales, Jaime M. Tovar-Corona, Lu Chen, Paula X. Kover, Araxi O. Urrutia
Journal: Molecular Biology and Evolution (2013)

The sequencing of multiple genomes of the same plant species has revealed polymorphic gene and exon loss. Genes associated with disease resistance are overrepresented among those showing structural variations, suggesting an adaptive role for gene and exon presence–absence variation (PAV). To shed light on the possible functional relevance of polymorphic coding region loss and the mechanisms driving this process, we characterized genes that have lost entire exons or their whole coding regions in 17 fully sequenced Arabidopsis thaliana accessions. We found that although a significant enrichment in genes associated with certain functional categories is observed, PAV events are largely restricted to genes with signatures of reduced essentiality: PAV genes tend to be newer additions to the genome, tissue specific, and lowly expressed. In addition, PAV genes are located in regions of lower gene density and higher transposable element density. Partial coding region PAV events were associated with only a marginal reduction in gene expression level in the affected accession and occurred in genes with higher levels of alternative splicing in the Col-0 accession. Together, these results suggest that although adaptive scenarios cannot be ruled out, PAV events can be explained without invoking them.
Richard III: a study in medical misrepresentation
Authors: Isabel Tulloch
Journal: Journal of the Royal Society of Medicine (2009)

King Richard III’s reign lasted a mere 25 months, yet he is undoubtedly one of the most notorious monarchs in English history. His reputation has been emblazoned in our memories as a consequence of Shakespeare’s theatrical presentation. In addition, his involvement in the Battle of Bosworth, one of the most publicized English conflicts, has ensured that he is not readily forgotten, given the flurry of Tudor propaganda constructed after his death. His reputation has taken a number of beatings over the centuries due to a series of unfortunate incidents in which he played a central role. The misfortune began in 1483, following the death of Richard’s illegitimate brother King Edward IV. Edward’s sons were too young to take the throne, so Richard became their protector. However, in the same year, Richard was crowned King after both of the young princes died under mysterious circumstances. Many believe that Richard played some part in their death. Shortly after, in 1484, Richard’s own son died, followed by his wife. Many suspected that Richard had poisoned her as she was too old to bear another child. It has been suggested that he wanted to marry his niece, who was still of childbearing age. In so doing, he would have been able to father another heir. Indeed, considerable conflict surrounded the issue of whether Richard should become King, with Henry Tudor claiming he was the rightful heir. This led to civil war in 1485, which was resolved by the Battle of Bosworth. This battle claimed the life of 33-year-old Richard and led to multiple assaults on his reputation during the reigns of the Tudor monarchs. Descriptions of Richard III
Serum carotenoids, vitamins A and E, and 8 year lung function decline in a general population
Authors: A Guénégou, B Leynaert, I Pin, G Le Moël, M Zureik, F Neukirch
Journal: Thorax (2006)

Background: Oxidative stress is thought to have a major role in the pathogenesis of airway obstruction. A study was undertaken to determine whether subjects with low levels of antioxidants (serum β-carotene, α-carotene, vitamins A and E) would be at a higher risk of accelerated decline in forced expiratory volume in 1 second (FEV1) as their lungs would be less protected against oxidative stress. Methods: 1194 French subjects aged 20–44 years were examined in 1992 as part of the European Community Respiratory Health Survey (ECRHS); 864 were followed up in 2000 and 535 (50% men, 40% lifelong non-smokers) had complete data for analysis. Results: During the 8 year study period the mean annual decrease in FEV1 (adjusted for sex, centre, baseline FEV1, age, smoking, body mass index and low density lipoprotein cholesterol) was 29.8 ml/year. The rate of decrease was lower for the subjects in tertile I of β-carotene at baseline than for those in the two other tertiles (−36.5 v −27.6 ml/year; p = 0.004). An increase in β-carotene between the two surveys was associated with a slower decline in FEV1. No association was observed between α-carotene, vitamin A, or vitamin E and FEV1 decline. However, being a heavy smoker (⩾20 cigarettes/day) in combination with a low level of β-carotene or vitamin E was associated with the steepest decline in FEV1 (−52.5 ml/year, p = 0.0002 and −50.1 ml/year, p = 0.010, respectively). Conclusions: These results strongly suggest that β-carotene protects against the decline in FEV1 over an 8 year period in the general population, and that β-carotene and vitamin E are protective in heavy smokers.