tbuckley/cabot-search huggingface dataset:
Rupture of the diaphragm
Authors: L. A. Christiansen, P. Stage, E. Bille Brahe, S. Bertelsen
Journal: Thorax (1974)

<b>Christiansen, L. A., Stage, P., Bille Brahe, E., and Bertelsen, S. (1974).</b><i>Thorax</i>, <b>29</b>, 559-563. <b>Rupture of the diaphragm.</b> A 23-year series of 25 patients with rupture of the diaphragm is presented. Symptoms, diagnostic procedures, and treatment are mentioned. A high index of suspicion of the diagnosis of ruptured diaphragm is most important in patients with a history of trauma. Familiarity with the signs on the plain chest film is important. Furthermore, we advocate an additional examination, that is diagnostic pneumoperitoneum, in all cases of suspected rupture of the diaphragm. If doubt still exists, we consider the final diagnostic procedure of choice to be exploratory thoracotomy until proof of the complete reliability of diagnostic pneumoperitoneum has been established.
Factors that modify the association between knee pain and mobility limitation in older women: the Women's Health and Aging Study
Authors: S E Lamb
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To investigate the influence of pain severity, knee extensor muscle weakness, obesity, depression, and activity on the association between recent knee pain and limitation of usual and fast paced walking, and ability to rise from a chair. <h3>METHODS</h3> A cross sectional analysis of 769 older women (mean age 77.8, range 65–101) with physical disability, but no severe cognitive impairment. Severity of knee pain in the past month was classified as none, moderate, or severe. Mobility was measured using timed performance tests. <h3>RESULTS</h3> The prevalence of recent knee pain was 53% (408/769). One third of the women with pain reported it to be severe. In general, knee pain was only significantly associated with limited mobility if severe. Obesity, activity and, to a lesser extent, depression intensified the effects of pain. Knee extensor weakness did not. Obesity was a distinctive risk factor in that it substantially increased the risk of mobility limitation, but only in women with pain. In women who had severe pain, activity (walking more than three city blocks in the past week) increased the risk of walking disability more than inactivity. Depression had a minor, but statistically significant effect on walking ability, but not the ability to rise from a chair. <h3>CONCLUSION</h3> In older women with recent knee pain, a high pain severity score, obesity, and activity are important factors that increase the risk of mobility limitation.
Renin in Rats with Spontaneous Hypertension
Authors: SUBHA SEN, ROBERT R. SMEBY, F. Merlin BUMPUS
Journal: Circulation Research (1972)

An age-dependent study of plasma renin activity (PRA), kidney renin activity (KRA), and plasma renin substrate was carried out in rats with spontaneous hypertension during the prehypertensive, the early hypertensive, and the established hypertensive phases of their disease. PRA and KRA were both significantly elevated before and during the initial phase of hypertension and normal or subnormal during the established phase. In normal controls, neither KRA nor PRA was significantly different during the entire growth period. Plasma renin substrate was elevated throughout the growth period in rats with hypertension. This relationship between renin and blood pressure suggests that renin may play a primary role, possibly along with other factors, in the initiation of hypertension in rats with spontaneous hypertension.
Unbalanced X chromosome mosaicism in B cells of mice with X-linked immunodeficiency.
Authors: M H Nahm, J W Paslay, J M Davie
Journal: The Journal of Experimental Medicine (1983)

The immunodeficiency in CBA/N mice is reflected by abnormal development of a subset of B lymphocytes. However, it is not clear how xid, the mutant gene in CBA/N mice, affects the development of this subset. Specifically, it is not known if the xid gene influences the development of the B cell subset directly or indirectly by providing the improper developmental milieu through effects on other cells. We investigated this question using female mice heterozygous for two x chromosomal genes, xid and Pgk-1 (phosphoglycerate kinase-1). Since females are mosaic because of x chromosome inactivation, their lymphocytes can be studied for the choice of the x chromosome, using the two PGK-1 isoenzymes as the cytological marker. We find that B lymphocytes in the spleen prefer the x chromosome without xid while the remaining splenocytes and cells from other tissues do not. This suggests that xid affects B lymphocytes directly and not through their developmental milieu. Furthermore, our data suggest that the precursors for IgG1- and IgG3-producing cells may be both few and different.
Regulation of Bcl-2 Family Proteins During Development and in Response to Oxidative Stress in Cardiac Myocytes
Authors: Stuart A. Cook, Peter H. Sugden, Angela Clerk
Journal: Circulation Research (1999)

Abstract —Cardiac myocyte apoptosis is potentially important in many cardiac disorders. In other cells, Bcl-2 family proteins and mitochondrial dysfunction are probably key regulators of the apoptotic response. In the present study, we characterized the regulation of antiapoptotic (Bcl-2, Bcl-xL) and proapoptotic (Bad, Bax) Bcl-2 family proteins in the rat heart during development and in oxidative stress–induced apoptosis. Bcl-2 and Bcl-xL were expressed at high levels in the neonate, and their expression was sustained during development. In contrast, although Bad and Bax were present at high levels in neonatal hearts, they were barely detectable in adult hearts. We confirmed that H 2 O 2 induced cardiac myocyte cell death, stimulating poly(ADP-ribose) polymerase proteolysis (from 2 hours), caspase-3 proteolysis (from 2 hours), and DNA fragmentation (from 8 hours). In unstimulated neonatal cardiac myocytes, Bcl-2 and Bcl-xL were associated with the mitochondria, but Bad and Bax were predominantly present in a crude cytosolic fraction. Exposure of myocytes to H 2 O 2 stimulated rapid translocation of Bad (&lt;5 minutes) to the mitochondria. This was followed by the subsequent degradation of Bad and Bcl-2 (from ≈30 minutes). The levels of the mitochondrial membrane marker cytochrome oxidase remained unchanged. H 2 O 2 also induced translocation of cytochrome c from the mitochondria to the cytosol within 15 to 30 minutes, which was indicative of mitochondrial dysfunction. Myocytes exposed to H 2 O 2 showed an early loss of mitochondrial membrane potential (assessed by fluorescence-activated cell sorter analysis) from 15 to 30 minutes, which was partially restored by ≈1 hour. However, a subsequent irreversible loss of mitochondrial membrane potential occurred that correlated with cell death. These data suggest that the regulation of Bcl-2 and mitochondrial function are important factors in oxidative stress–induced cardiac myocyte apoptosis.
Molecular mechanism of hepatocellular injury in alpha1 antitrypsin deficiency
Authors: Frederick K. Askari
Journal: Hepatology (1995)

Liver injury in PiZZ α 1 -antitrypsin (α 1 -AT) deficiency probably results from toxic effects of the abnormal α 1 -AT molecule accumulating within the ER of liver cells. However, only 12-15% of individuals with this same genotype develops liver disease. Therefore, we predicted that other genetic traits that determine the net intracellular accumulation of the mutant α 1 -AT molecule would also determine susceptibility to liver disease. To address this prediction, we transduced skin fibroblasts from PiZZ individuals with liver disease or without liver disease with amphotropic recombinant retroviral particles designed for constitutive expression of the mutant α 1 -AT Z gene. Human skin fibroblasts do not express the endogenous α 1 -AT gene but presumably express other genes involved in postsynthetic processing of secretory proteins. The results show that expression of human α 1 -AT M gene was conferred on each fibroblast cell line. Compared to the same cell line transduced with the wild-type α 1 -AT M gene, there was selective intracellular accumulation of the mutant α 1 -AT Z protein in each case. However, there was a marked delay in degradation of the mutant α 1 -AT Z protein after it accumulated in the fibroblasts from ZZ individuals with liver disease (“susceptible hosts”) as compared to those without liver disease (“protected hosts”). Appropriate disease controls showed that the lag in degradation in susceptible hosts is specific for the combination of PiZZ phenotype and liver disease. Biochemical characteristics of α 1 -AT Z degradation in the protected hosts were found to be similar to those of a common ER degradation pathway previously described in model experimental cell systems for T-cell receptor α subunits and asialoglycoprotein receptor subunits, therefore, raising the possibility that the lag in degradation in the susceptible host is a defect in this common ER degradation pathway. Thus, these data provide evidence that other genetic traits that affect the fate of the abnormal α 1 -AT Z molecule, at least in part, determine susceptibility to liver disease. These data also validate a system for elucidating the biochemical/genetic characteristics of these traits and for examining the relevance to human disease of pathways for protein déradation in the ER.
Both in‐ and out‐hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH)
Authors: Kevin Damman, Tiny Jaarsma, Adriaan A. Voors, Gerjan Navis, Hans L. Hillege, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2009)
Postnatal Fetal and Adult Hemoglobin Synthesis in Early Preterm Newborn Infants
Authors: Harry Bard
Journal: Journal of Clinical Investigation (1973)

Studies were carried out during the postnatal period in infants born at or before the 32nd wk of gestation to determine the proportion of fetal hemoglobin (Hb F) and adult hemoglobin (Hb A) being synthesized, and to compare these studies to those previously reported on at birth from normal newborn infants 25-43 wk gestation. When the pretern infants reached the postconceptional age corresponding to term, their Hb A and Hb F synthesis was compared to a group of newborn infants at term. 53 blood samples from 25 preterm and 11 full-term infants were incubated in an amino acid mixture containing [14C]leucine, and column-chromatographed on DEAE-Sephadex for separation of Hb F and Hb A fractions. The completeness of the DEAE-Sephadex separation of Hb F and Hb A was confirmed by globin chain chromatography with the use of carboxymethylcellulose. The rate of transition from Hb F to Hb A synthesis postnatally in the preterm infants resembled that reflecting the in utero transition. At the postconceptional age corresponding to term, there was no difference in the relative amounts of Hb F and Hb A being synthesized by the preterm infants and by the term infants. The birth process did not alter the rate of transition from Hb F to Hb A.
Differential focus in causal and counterfactual thinking: Different possibilities or different functions?
Authors: David R. Mandel
Journal: Behavioral and Brain Sciences (2007)

Abstract In The Rational Imagination , Byrne proposes a mental models account of why causal and counterfactual thinking often focus on different antecedents. This review critically examines the two central propositions of her account, finding both only weakly defensible. Byrne's account is contrasted with judgment dissociation theory, which offers a functional explanation for differences in the focus of causal and counterfactual thinking.
Chronic Mastitis and Breast Cancer
Authors: W. S. Handley
Journal: BMJ (1938)

PLATE) X This history of a family of five sisters pursued by breast cancer covers a period of about nineteen years, during which, with regrettable gaps, hesitations, and refusals of advice, I have been jointly responsible with their own doctors for their defence against the family foe.It is known that their mother died at the age of 69 of cancer of the liver, and her mother at the age of 37 of abdominal cancer, probably gastric, since it was attended by persistent vomiting.In advising this family I have been guided by the follow- ing convictions.
Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab
Authors: N.C. Tebbutt, F. Murphy, D. Zannino, K. Wilson, M.M. Cummins, E. Abdi, A.H. Strickland, R.M. Lowenthal, G. Marx, C. Karapetis, J. Shannon, D. Goldstein, S.S. Nayagam, R. Blum, L. Chantrill, R.J. Simes, T.J. Price
Journal: Annals of Oncology (2011)
THE EFFECT OF THE VARIATION IN THE OSMOTIC TENSION AND OF THE DILUTION OF CULTURE MEDIA ON THE CELL PROLIFERATION OF CONNECTIVE TISSUE
Authors: Albert H. Ebeling
Journal: The Journal of Experimental Medicine (1914)

For the first few days of cultivation of connective tissue in hypertonic, hypotonic, and diluted medium, cell proliferation was stimulated. The first outgrowths of new cells in the modified media did not occur sooner than in normal medium. In hypertonic medium the density of the area of cell proliferation appeared to be greater than the control, but in hypotonic or diluted medium there seemed to be no increase in actual mass over the control. These observations confirm the conclusions of Carrel and Burrows, as well as those of Lambert. Subsequent to the first few days of cultivation in hypertonic medium the area of cell proliferation decreased and in a short time conditions developed which were unfavorable to growth, and finally resulted in death of the culture, unless it revived before this stage. Hypotonic medium after about ten days no longer caused more extensive areas of proliferating cells; but instead, the extent of new growth gradually decreased, and the culture merely remained alive unless revived. In diluted medium the extent of the area of cell proliferation remained greater with no actual increase in mass. The area of cell proliferation which is observed during the first few days in a culture of fresh tissue recently extirpated does not indicate the actual influence of modified media. It was only after continued cultivation of strains of connective tissue in these modified media that their influence on cell proliferation was determined.
MyoD Is a Tumor Suppressor Gene in Medulloblastoma
Authors: Joyoti Dey, Adrian M. Dubuc, Kyle D. Pedro, Derek Thirstrup, Brig Mecham, Paul A. Northcott, Xiaochong Wu, David Shih, Stephen J. Tapscott, Michael LeBlanc, Michael D. Taylor, James M. Olson
Journal: Cancer Research (2013)

While medulloblastoma, a pediatric tumor of the cerebellum, is characterized by aberrations in developmental pathways, the majority of genetic determinants remain unknown. An unbiased Sleeping Beauty transposon screen revealed MyoD as a putative medulloblastoma tumor suppressor. This was unexpected, as MyoD is a muscle differentiation factor and not previously known to be expressed in cerebellum or medulloblastoma. In response to deletion of one allele of MyoD, two other Sonic hedgehog-driven mouse medulloblastoma models showed accelerated tumor formation and death, confirming MyoD as a tumor suppressor in these models. In normal cerebellum, MyoD was expressed in the proliferating granule neuron progenitors that are thought to be precursors to medulloblastoma. Similar to some other tumor suppressors that are induced in cancer, MyoD was expressed in proliferating medulloblastoma cells in three mouse models and in human medulloblastoma cases. This suggests that although expression of MyoD in a proliferating tumor is insufficient to prevent tumor progression, its expression in the cerebellum hinders medulloblastoma genesis.
IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial
Authors: P. Emery, E. Keystone, H. P. Tony, A. Cantagrel, R. van Vollenhoven, A. Sanchez, E. Alecock, J. Lee, J. Kremer
Journal: Annals of the Rheumatic Diseases (2008)

The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy.499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed.ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups.Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile.NCT00106522.
Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura.
Authors: K Sertl, T Takemura, E Tschachler, V J Ferrans, M A Kaliner, E M Shevach
Journal: The Journal of Experimental Medicine (1986)

In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.
Bone marrow transplantation reproduces the tristetraprolin-deficiency syndrome in recombination activating gene-2 (-/-) mice. Evidence that monocyte/macrophage progenitors may be responsible for TNFalpha overproduction.
Authors: E Carballo, G S Gilkeson, P J Blackshear
Journal: Journal of Clinical Investigation (1997)

Tristetraprolin-deficient [TTP (-/-)] mice exhibit a complex syndrome of myeloid hyperplasia, cachexia, dermatitis, autoimmunity, and erosive arthritis. Virtually the entire syndrome can be prevented by the repeated injection of anti-TNFalpha antibodies (Taylor, G.A., E. Carballo, D.M. Lee, W.S. Lai, M.J. Thompson, D.D. Patel, D.I. Schenkman, G.S. Gilkeson, H.E. Broxmeyer, B.F. Haynes, and P.J. Blackshear. 1996. Immunity. 4:445-454). In the present study, we transplanted bone marrow from TTP (-/-) and (+/+) mice into recombination activating gene-2 (-/-) mice. After a lag period of several months, marrow transplantation from the (-/-) but not the (+/+) mice resulted in the full syndrome associated with TTP deficiency, suggesting that hematopoietic progenitors are responsible for the development of the syndrome. Western blot analysis of supernatants from cultured TTP-deficient macrophages derived from the peritoneal cavity or bone marrow of adult TTP (-/-) mice, or from fetal liver, demonstrated an increased accumulation of TNFalpha after stimulation with LPS compared to control cells, and also increased accumulation of TNFalpha mRNA. This difference was not observed with cultured fibroblasts or T and B lymphocytes. These data suggest that macrophages are among the cells responsible for the effective excess of TNFalpha that leads to the pathology reported in TTP (-/-) animals, and that macrophage progenitors may be involved in the transplantability of this syndrome.
Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.
Authors: J M Olefsky
Journal: Journal of Clinical Investigation (1975)

We have studied the in vitro effects of dexamethasone on isolated rat adipocytes at concentrations of dexamethasone therapeutically achieved in man. Glucose oxidation, glucose transport, and insulin binding were assessed. In dexamethasone-treated cells, glucose oxidation was decreased by 30-40% both in the absence of insulin (basal state) and at low insulin levels (less than 25 mu/ML). At maximally effective insulin levels (over 100 muU/ml) no differences existed between control and treated cells. If glucose transport were the rate-limiting step for glucose oxidation in the basal state and at low (submaximal) insulin levels, but not at maximally effective insulin concentrations, then these data could be explained by postulating that dexamethasone has a direct affect on glucose transport and does not affect intracellular oxidative pathways. We tested this hypothesis by directly assessing glucose transport in dexamethasone-treated cells. Glucose transport was assessed by measuring the uptake of [14C]2-deoxy glucose. These studies demonstrated a 30-40% decrease in 2-deoxy glucose uptake by treated cells both in the basal state and at all insulin concentrations. Thus, a direct glucocorticoid effect on the glucose transport system seems to account for the decreased ability of dexamethasone-treated cells to oxidize glucose. Since dexamethasone treatment leads to decreased insulin binding to adipocytes in vivo, we examined the possibility that the in vitro decreases in insulin-mediated glucose transport could be due to decreased insulin receptors. Insulin binding to control and treated adipocytes was measured, and no differences were found. Therefore, in cntrast to previously reported in vivo studies, adipocytes treated in vitro with dexamethasone retain a normal ability to bind insulin. Thus, these studies suggest that all of the in vitro effects of dexamethasone on glucose oxidation are due to direct inhibition of the glucose transport system.
The Missed Patient With Diabetes: How access to health care affects the detection of diabetes
Authors: X. Zhang, L. S. Geiss, Y. J. Cheng, G. L. Beckles, E. W. Gregg, H. S. Kahn
Journal: Diabetes Care (2008)

OBJECTIVE—This study examined the association between access to health care and three classifications of diabetes status: diagnosed, undiagnosed, and no diabetes.