tbuckley/cabot-search huggingface dataset:
Autophagic Clearance of Mitochondria in the Kidney Copes with Metabolic Acidosis
Authors: Tomoko Namba, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Takeshi Yamamoto, Jun Matsuda, Harumi Kitamura, Fumio Niimura, Taiji Matsusaka, Hirotsugu Iwatani, Isao Matsui, Junya Kaimori, Hidetaka Kioka, Yoshitaka Isaka, Hiromi Rakugi
Journal: Journal of the American Society of Nephrology (2014)

Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent protein–tagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH4Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule–specific autophagy-deficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3–tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy.
Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study
Authors: H. Soto Parra, R. Cavina, F. Latteri, A. Sala, M. Dambrosio, G. Antonelli, E. Morenghi, M. Alloisio, G. Ravasi, A. Santoro
Journal: Annals of Oncology (2002)
Intracoronary Injection of In Situ Forming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine
Authors: Jonathan Leor, Shmuel Tuvia, Victor Guetta, Ferenc Manczur, David Castel, Udi Willenz, Örs Petneházy, Natali Landa, Micha S. Feinberg, Eli Konen, Orly Goitein, Orna Tsur-Gang, Mazal Shaul, Lea Klapper, Smadar Cohen
Journal: Journal of the American College of Cardiology (2009)

This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 ± 0.1 mm vs. 1.9 ± 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.
Advancing Surgical Vision with Fluorescence Imaging
Authors: Maximilian Koch, Vasilis Ntziachristos
Journal: Annual Review of Medicine (2016)

Surgical success depends on the accuracy with which disease and vital tissue can be intraoperatively detected. However, the dominant visualization approach, i.e., human vision, does not see under the tissue surface and operates on low contrast between sites of disease, such as cancer, and the surrounding tissue. Intraoperative fluorescence imaging is emerging as a highly effective method to improve surgical vision and offers the potential to be intergrated seamlessly into the normal workflow of the operating room without causing disruption or undue delay. We review and compare two critical fluorescence imaging directions: one that uses nonspecific fluorescence dyes, addressing tissue perfusion and viability, and one that uses targeted agents, interrogating pathophysiological features of disease. These two approaches present detection sensitivity challenges that may differ by orders of magnitude and require different detection strategies. Nevertheless, fluorescence imaging provides the surgeon with previously unavailable real-time feedback that improves surgical precision and can become essential for interventional decision-making.
Using vital signs to diagnose impaired consciousness: cross sectional observational study
Authors: M. Ikeda
Journal: BMJ (2002)

To determine whether any vital signs can be used to quickly identify brain lesions in patients with impaired consciousness.Cross sectional observational study.Emergency department of an urban hospital, Japan.529 consecutive patients (mean age 65 years) presenting with impaired consciousness (score <15 on the Glasgow coma scale) during 2000.The receiver operating characteristic curve was used to quantify the relation between the vital signs on arrival and the final diagnosis of a brain lesion. Stratum specific likelihood ratios were calculated to define strata with optimal discriminating power.312 (59%) had a brain lesion which accounted for the impaired consciousness. The area under the receiver operating curve for systolic blood pressure was 0.90 (SE 0.01), indicating significantly higher accuracy (P<0.01) in the identification of a brain lesion than using diastolic pressure 0.82 (0.02) or pulse rate 0.63 (0.03). Likelihood ratios for systolic blood pressure lower than 90 mm Hg were less than 0.04, and those for systolic pressure higher than 170 mm Hg were greater than 6.09.Systolic blood pressure is useful for diagnosing brain lesions in patients with impaired consciousness.
Individual differences and Pearson's r: Rationality revealed?
Authors: Joachim Krueger
Journal: Behavioral and Brain Sciences (2000)

Regardless of the clarity of the patterns they produce, individual differences in reasoning cannot validate norms of rationality. With improved reliability, these correlations will simply reveal which sorts of biases go together and which predict the intelligence of the decision maker. It seems necessary, therefore, to continue efforts to define rational thought independently of intelligence.
Functional Analysis of NBC1 Mutants Associated with Proximal Renal Tubular Acidosis and Ocular Abnormalities
Authors: Shoko Horita, Hideomi Yamada, Jun Inatomi, Nobuo Moriyama, Takashi Sekine, Takashi Igarashi, Yoko Endo, Majed Dasouki, Mesiha Ekim, Lihadh Al-Gazali, Mitsunobu Shimadzu, George Seki, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2005)

Mutations in the Na+-HCO3- co-transporter (NBC1) cause permanent proximal renal tubular acidosis (pRTA) with ocular abnormalities. However, little has been known about the relationship between the degree of NBC1 inactivation and the severity of pRTA. This study identified three new homozygous mutations (T485S, A799V, and R881C) in the common coding regions of NBC1. Functional analysis of these new as well as the known mutants (R298S and R510H) in Xenopus oocytes revealed a considerable variation in their electrogenic activities. Whereas the activities of R298S, A799V, and R881C were 15 to 40% of the wild-type (WT) activity, T485S and R510H, as a result of poor surface expression, showed almost no activities. However, T485S, like R510H, had the transport activity corresponding to approximately 50% of the WT activity in ECV304 cells, indicating that surface expression of T485S and R510H varies between the different in vitro cell systems. Electrophysiologic analysis showed that WT, R298S, and R881C all function with 2HCO3- to 1Na+ stoichiometry and have similar extracellular Na+ affinity, indicating that reduction in Na+ affinity cannot explain the inactivation of R298S and R881C. These results, together with the presence of nonfunctional mutants (Q29X and DeltaA) in other patients, suggest that at least approximately 50% reduction of NBC1 activity would be required to cause severe pRTA.
Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study
Authors: P Vineis, L Airoldi, F Veglia, L Olgiati, R Pastorelli, H Autrup, A Dunning, S Garte, E Gormally, P Hainaut, C Malaveille, G Matullo, M Peluso, K Overvad, A Tjonneland, F Clavel-Chapelon, H Boeing, V Krogh, D Palli, S Panico, R Tumino, B Bueno-De-Mesquita, P Peeters, G Berglund, G Hallmans, R Saracci, E Riboli
Journal: BMJ (2005)

To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death.Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC).303,020 people from the EPIC cohort (total 500,000) who had never smoked or who had stopped smoking for at least 10 years, 123,479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment.Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people.Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours).This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.
Interplay between troponin T phosphorylation and O-N-acetylglucosaminylation in ischaemic heart failure
Authors: Emilie Dubois-Deruy, Aude Belliard, Paul Mulder, Marion Bouvet, Caroline Smet-Nocca, Sébastien Janel, Frank Lafont, Olivia Beseme, Philippe Amouyel, Vincent Richard, Florence Pinet
Journal: Cardiovascular Research (2015)

AimsPrevious studies have reported that decreased serine 208 phosphorylation of troponin T (TnTpSer208) is associated with ischaemic heart failure (HF), but the molecular mechanisms and functional consequences of these changes are unknown. The aim of this study was to characterize the balance between serine phosphorylation and O-N-acetylglucosaminylation (O-GlcNAcylation) of TnT in HF, its mechanisms, and the consequences of modulating these post-translational modifications.
Mrp2 is essential for estradiol-17β(β-D -glucuronide)–induced cholestasis in rats
Authors: Liyue Huang, Johan W. Smit, Dirk K. Meijer, Mary Vore
Journal: Hepatology (2000)

The present study evaluates the roles of the multidrug resistance-1 P-glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance-associated protein-2 (Mrp2) in mediating cholestasis induced by estradiol-17β(β-d -glucuronide) (E 2 17G). Administration of [ 3 H]E 2 17G (18 nmol/g body weight) gave a similar degree of cholestasis and biliary excretion of E 2 17G-equivalents in wild-type and Mdr1a -/- /1b -/- mice. When expressed in Sf9 cells, Bsep-mediated adenosine triphosphate (ATP)-dependent transport of taurocholate (TC, 1 μmol/L) in membrane vesicles was 110% ± 12.5% and 108% ± 17.3% of control in the presence of 10 and 50 μmol/L E 2 17G, respectively, whereas in rat canalicular membrane, both E 2 17G and the choleretic estradiol-3-β-d -glucuronide (E 2 3G) inhibited ATP-dependent transport of TC to the same extent. Infusion of [ 3 H]E 2 17G (24 μmol) did not induce cholestasis in Mrp2-deficient TR − rats whereas 2 μmol of [ 3 H]E 2 17G inhibited bile flow by 51% in control Wistar rats. The maximal biliary concentration of E 2 17G was 3.5 and 2.5 mmol/L in control and TR − rats, respectively. However, 2.2 mmol/L of E 2 17G in bile is associated with inhibition of bile flow in control rats. These data show that (1) Mdr1a/1b are not essential for E 2 17G-mediated cholestasis, (2) direct inhibition of Bsep-mediated bile acid transport is not the mechanism for E 2 17G cholestasis, and (3) accumulation of E 2 17G in bile alone is not sufficient to induce cholestasis. These data indicate that the process of Mrp2-mediated transport of high concentrations of E 2 17G is essential for its induction of cholestasis.
Young adult sequelae of adolescent cannabis use: an integrative analysis
Authors: Edmund Silins, L John Horwood, George C Patton, David M Fergusson, Craig A Olsson, Delyse M Hutchinson, Elizabeth Spry, John W Toumbourou, Louisa Degenhardt, Wendy Swift, Carolyn Coffey, Robert J Tait, Primrose Letcher, Jan Copeland, Richard P Mattick
Journal: The Lancet Psychiatry (2014)
Potential Applications for Circulating Tumor Cells Expressing the Insulin-Like Growth Factor-I Receptor
Authors: Johann S. de Bono, Gerhardt Attard, Alex Adjei, Michael N. Pollak, Peter C. Fong, Paul Haluska, Luisa Roberts, Carrie Melvin, Madeline Repollet, David Chianese, Mark Connely, Leon W.M.M. Terstappen, Antonio Gualberto
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR. Experimental Design: An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR–positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma. Results: There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR–positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR–positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by &amp;gt;50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by &amp;gt;50%. Conclusions: IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer.
Experiences with Evaluating the Safety and Efficacy of Medical Technologies
Authors: Lincoln E. Moses, Byron Wm. Brown
Journal: Annual Review of Public Health (1984)

Thus, X-rays, IUDs, vaccines, physical therapy, aspirin, positive pressure breathing devices, appendectomy, alcohol aversion therapy, artificial hips, hemodialysis, and heart transplants all exem­ plify   as we (and many others) treat the term. Some activities in a hospital or clinic are excluded: billing practices, the hospital kitchen, and for-profit versus nonprofit incorporation are parts of the health care environment, but are not directly related to the individual patient's care. Safety is obviously a desirable property of any medical technology, but the concept is somewhat subtle. Analysis is likely to show that we always mean by that term, safe enough, considering . An effective treatment for a grave disease may entail an appreciable  of mortality, but be accepted with regard to safety because that  is small compared to the risks of the target disease, and no safer, effective therapy is known. For a headache remedy, the appropri­ ate safety standard is a tiny  of any dangerous side effects. But    is not an appropriate standard safety: first, because with bounded time and resources, and with ever present small probabilities of mistake, it is impossible actually to distinguish zero from other small positive risks; so  risk is an imaginary standard. Second, if some technology is safer than all known alternatives, then that fact may be decisive in itself. The foregoing should not
Human liver sinusoidal endothelial cells induce apoptosis in activated T cells: a role in tolerance induction
Authors: A Karrar, U Broome, M Uzunel, A R Qureshi, S Sumitran-Holgersson
Journal: Gut (2006)

The liver may have a role in peripheral tolerance, by serving as a site for trapping, apoptosis and phagocytosis of activated T cells. It is not known which hepatic cells are involved in these processes. It was hypothesised that liver sinusoidal endothelial cells (LSEC) which are strategically placed for participation in the regulation of sinusoidal blood flow, and express markers involved in recognition, sequestration and apoptosis, may contribute to peripheral tolerance by inducing apoptosis of activated T cells.By using immunoassays and western blot analysis, the fate of activated T cells when incubated with human LSEC isolated from normal healthy livers was investigated.Evidence that activated (approximately 30%) but not non-activated T cells undergo apoptosis on incubation with human LSEC in mixed cell cultures is provided. No difference in the results was observed when unstimulated and cytokine-stimulated LSEC were used. T cell-LSEC contact is required for induction of apoptosis. Apoptosis induced by LSEC was associated with caspase 8 and 3 activity and strong expression of the proapoptotic molecule Bak. Transforming growth factor beta (TGFbeta) produced constitutively by LSEC is partly responsible for the caspase-induced apoptosis, as neutralising antibodies to TGFbeta markedly attenuated apoptosis, up regulated the antiapoptotic molecule Bcl-2 and partially blocked caspase-3 activity.These findings broaden the potential role of LSEC in immune tolerance and homeostasis of the immune system. This study may provide insight for exploring the mechanisms of immune tolerance by liver allografts, immune escape by some liver pathogens including hepatitis C and pathogenesis of liver diseases.
The effect of moderate physical exercise on the plasma lipoprotein subfractions of male survivors of myocardial infarction.
Authors: F C Ballantyne, R S Clark, H S Simpson, D Ballantyne
Journal: Circulation (1982)

The effect of regular, moderate exercise on the lipoprotein subfractions of male survivors of myocardial infarction was studied. Nineteen men were randomly allocated to an incremental exercise program and 23 to a control group. Both groups were studied for 6 months. No change occurred in any lipoprotein class in the control group. In the trained group, total triglyceride and low-density lipoprotein (LDL) cholesterol concentrations decreased significantly (0.01 greater than p greater than 0.001 and 0.05 greater than p greater than 0.01, respectively) and high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 rose (both p less than 0.001). The concentration of the HDL2 subfraction increased with training (0.01 greater than p greater than 0.001) and HDL2 did not change. No relationship was found between changes in lipoproteins and treadmill exercise test performance. Thus, in survivors of myocardial infarction, exercise may alter plasma lipoprotein values beneficially.
Bipedalism, canine tooth reduction, and obligatory tool use
Authors: C. Loring Brace
Journal: Behavioral and Brain Sciences (2004)

Bipedalism in the earliest hominid specimens is always accompanied by the reduction of projecting canine teeth. Body size is smaller than chimpanzees or humans, but molar teeth are markedly larger. Use of a pointed stick for defensive purposes on the one hand, and digging for USOs on the other, may be why bipedalism was selected for. Passing such learned behavior to the next generation may have played a role in selecting for language.