tbuckley/cabot-search huggingface dataset:
Large synovial cysts originating from the sternoclavicular joints in a patient with rheumatoid arthritis
Authors: A P Andonopoulos
Journal: Annals of the Rheumatic Diseases (2003)

Synovial cysts in rheumatoid arthritis (RA), most common in the popliteal fossa,1,2 have also been described in proximity to several other rheumatoid joints,3–9 but never the sternoclavicular joints.

We here describe, for the first time, the development of unusually large synovial cysts, from the disproportionately small sternoclavicular joints, in a 58 year old man, with a 27 year history of severe, seropositive, erosive, destructive, deforming, nodular RA. Over the years he had been treated, albeit erratically, with several disease modifying antirheumatic drugs (DMARDs), but he had been poorly followed up.

Seven months ago, while receiving d-penicillamine 500 mg/day and methylprednisolone 2 mg/day, he presented with a 10 cm long and 5 cm thick, fluctuant, non-tender, sausage-like mass over the right clavicle, and a smaller one, about 5 cm …
Age, Health, and Education Determine Supportive Care Needs of Men Younger Than 70 Years With Prostate Cancer
Authors: David P. Smith, Rajah Supramaniam, Madeleine T. King, Jeanette Ward, Martin Berry, Bruce K. Armstrong
Journal: Journal of Clinical Oncology (2007)

Purpose It is important to meet the supportive care needs of cancer patients to ensure their satisfaction with their care. A population-wide sample of men younger than 70 years and newly diagnosed with prostate cancer was surveyed to determine their unmet needs in five domains and the factors predicting them. Patients and Methods Eligible men were younger than 70 years and residents in New South Wales, Australia, with newly diagnosed histopathologically confirmed prostate cancer. Sixty-seven percent of eligible men diagnosed between October 2000 and October 2001 participated. Demographic, treatment, and self-reported health data were collected. Information on cancer stage, grade, and prostate-specific antigen was obtained from medical records. Logistic regression analyses determined patient and treatment variables that predicted higher unmet needs. Results More than half (54%) of men with prostate cancer expressed some level of unmet psychological need, and 47% expressed unmet sexuality needs. Nearly one fourth expressed a moderate or high level of unmet need with respect to changes in sexuality. Sexuality needs were independently predicted by being younger, having had a secondary school education only, having had surgery, and being married, living as married, or divorced. Uncertainty about the future was also an important area of unmet need. Conclusion Attention should be given to sexual and psychological needs in the early months after diagnosis or treatment of prostate cancer, particularly in younger men, those with less education, and those having surgery. Research into better ways of meeting these needs will enable us to meet them with as much rigor as we meet clinical treatment needs.
Endothelin-1 Potentiates Human Smooth Muscle Cell Growth to PDGF
Authors: Zhihong Yang, Nazmi Krasnici, Thomas F. Lüscher
Journal: Circulation (1999)

Background —Endothelin-1 (ET-1) is a potent vasoconstrictor. However, its mitogenic effects on vascular smooth muscle cells (SMCs) remain controversial. We investigated the role of ET-1 in human SMC growth and its synergistic effect with platelet-derived growth factor (PDGF). Methods and Results —Human aortic SMCs were cultured and cell proliferation was assayed by [ 3 H]thymidine incorporation. PDGF receptor expression, activation of mitogen-activated protein kinase (MAPK), cell cycle regulators such as cyclin-dependent kinase 2 (Cdk2), Cdk inhibitor (p27 Kip1 ), and retinoblastoma protein (pRb) were analyzed by immunoblotting. ET-1 on its own was unable to stimulate [ 3 H]thymidine incorporation but dramatically potentiated the effect of PDGF-BB up to 6-fold ( P &lt;0.001). Most of the potentiating effects (88%) were blocked by the ET A receptor antagonist LU135252 and slightly further blocked by the ET A/B receptor antagonist bosentan ( P &lt;0.05). ET-1 stimulated MAPK, but it neither potentiated PDGF-induced MAPK activation nor overexpressed PDGF receptors. In contrast to PDGF-BB, ET-1 had no regulatory effects on Cdk2, p27 Kip1 , and pRb. Conclusions —In human SMCs, ET-1 activates MAPK but has no mitogenic effects on its own. However, ET-1 markedly potentiates proliferation to PDGF, mainly via ET A receptors. This may represent an important function of ET-1 for vascular structural changes in patients and provide new therapeutic opportunities for ET-1 receptor antagonists.
Cardiorespiratory responses to dynamic exercise after human heart-lung transplantation.
Authors: M Estenne, G Primo, J C Yernault
Journal: Thorax (1987)

Although gratifying results have been obtained with heart- lung transplantation,1 the adaptation of the transplanted denervated lung to exercise has not been reported.We have therefore studied cardiorespiratory responses to dynamic exercise in one patient six months after the transplantation.Methods
Estimation of Nucleotide Diversity, Disequilibrium Coefficients, and Mutation Rates from High-Coverage Genome-Sequencing Projects
Authors: M. Lynch
Journal: Molecular Biology and Evolution (2008)

Recent advances in sequencing strategies have made it feasible to rapidly obtain high-coverage genomic profiles of single individuals, and soon it will be economically feasible to do so with hundreds to thousands of individuals per population. While offering unprecedented power for the acquisition of population-genetic parameters, these new methods also introduce a number of challenges, most notably the need to account for the binomial sampling of parental alleles at individual nucleotide sites and to eliminate bias from various sources of sequence errors. To minimize the effects of both problems, methods are developed for generating nearly unbiased and minimum-sampling-variance estimates of a number of key parameters, including the average nucleotide heterozygosity and its variance among sites, the pattern of decomposition of linkage disequilibrium with physical distance, and the rate and molecular spectrum of spontaneously arising mutations. These methods provide a general platform for the efficient utilization of data from population-genomic surveys, while also providing guidance for the optimal design of such studies.
Overexpression of FK506-Binding Protein FKBP12.6 in Cardiomyocytes Reduces Ryanodine Receptor–Mediated Ca <sup>2+</sup> Leak From the Sarcoplasmic Reticulum and Increases Contractility
Authors: Jürgen Prestle, Paul M.L. Janssen, Anita P. Janssen, Oliver Zeitz, Stephan E. Lehnart, Lorraine Bruce, Godfrey L. Smith, Gerd Hasenfuss
Journal: Circulation Research (2001)

Abstract —The FK506-binding protein FKBP12.6 is tightly associated with the cardiac sarcoplasmic reticulum (SR) Ca 2+ -release channel (ryanodine receptor type 2 [RyR2]), but the physiological function of FKBP12.6 is unclear. We used adenovirus (Ad)-mediated gene transfer to overexpress FKBP12.6 in adult rabbit cardiomyocytes. Western immunoblot and reverse transcriptase–polymerase chain reaction analysis revealed specific overexpression of FKBP12.6, with unchanged expression of endogenous FKBP12. FKBP12.6-transfected myocytes displayed a significantly higher (21%) fractional shortening (FS) at 48 hours after transfection compared with Ad-GFP–infected control cells (4.8±0.2% FS versus 4±0.2% FS, respectively; n=79 each; P =0.001). SR-Ca 2+ uptake rates were monitored in β-escin–permeabilized myocytes using Fura-2. Ad-FKBP12.6–infected cells showed a statistically significant higher rate of Ca 2+ uptake of 0.8±0.09 nmol/s − 1 /10 6 cells (n=8, P &lt;0.05) compared with 0.52±0.1 nmol/s − 1 /10 6 cells in sham-infected cells (n=8) at a [Ca 2+ ] of 1 μmol/L. In the presence of 5 μmol/L ruthenium red to block Ca 2+ efflux via RyR2, SR-Ca 2+ uptake rates were not significantly different between groups. From these measurements, we calculate that SR-Ca 2+ leak through RyR2 is reduced by 53% in FKBP12.6-overexpressing cells. Caffeine-induced contractures were significantly larger in Ad-FKBP12.6–infected myocytes compared with Ad-GFP–infected control cells, indicating a higher SR-Ca 2+ load. Taken together, these data suggest that FKBP12.6 stabilizes the closed conformation state of RyR2. This may reduce diastolic SR-Ca 2+ leak and consequently increase SR-Ca 2+ release and myocyte shortening.
The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance
Authors: David Vicent, Jacob Ilany, Tatsuya Kondo, Keiko Naruse, Simon J. Fisher, Yaz Y. Kisanuki, Sven Bursell, Masashi Yanagisawa, George L. King, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2003)

Insulin receptors (IRs) on vascular endothelial cells have been suggested to participate in insulin-regulated glucose homeostasis. To directly address the role of insulin action in endothelial function, we have generated a vascular endothelial cell IR knockout (VENIRKO) mouse using the Cre-loxP system. Cultured endothelium of VENIRKO mice exhibited complete rearrangement of the IR gene and a more than 95% decrease in IR mRNA. VENIRKO mice were born at the expected Mendelian ratio, grew normally, were fertile, and exhibited normal patterns of vasculature in the retina and other tissues. Glucose homeostasis under basal condition was comparable in VENIRKO mice. Both eNOS and endothelin-1 mRNA levels, however, were reduced by approximately 30–60% in endothelial cells, aorta, and heart, while vascular EGF expression was maintained at normal levels. Arterial pressure tended to be lower in VENIRKO mice on both low- and high-salt diets, and on a low-salt diet VENIRKO mice showed insulin resistance. Thus, inactivation of the IR on endothelial cell has no major consequences on vascular development or glucose homeostasis under basal conditions, but alters expression of vasoactive mediators and may play a role in maintaining vascular tone and regulation of insulin sensitivity to dietary salt intake.
Immunofluorescence and Histologic Studies of Virus-Induced Murine Lymphocytic Leukemias 2
Authors: Peter J. Dawson, Steven L. Dresler, A. Howard Fieldsteel
Journal: JNCI Journal of the National Cancer Institute (1976)

Mice were inoculated with either the lymphatic leukemia virus associated with Friend and Rauscher viruses or with the Graffi or BALB/Tennant leukemia viruses. A total of 48 leukemic mice were examined histologically and by immunofluorescence. All four viruses induced a histologically similar disease that particularly involved the thymus-dependent lymphoid regions. Lymphocytes from the spleens and thy muses of leukemic animals were examined for Thy-1 antigen and immunoglobulins on the cell surface; all the leukemias were composed of T-cells and/or nonreactive cells lacking both the Thy-1 antigen and immu noglobulins. By immunofluorescence, the spleen and thymus from the same leukemic animal frequently showed different cell-surface markers, though no morphologic differences were seen in leukemias involving the different classes of lymphocytes.
The Effect of an Adrenal Inhibitor (SU 4885) on Gastric Secretion in Dogs
Authors: J. W. McIntosh, N. Anderson, H. L. Duthie, A. P. M. Forrest
Journal: Gut (1960)

There is considerable evidence that the adrenocortical steroids potentiate both human and canine gastric secretion. In this study, the action of the adrenocortical inhibitor, SU 4885, has been observed in dogs having separated pouches of the stomach. No effect was noted on the secretory responses to meat, histamine, or mecothane when the drug was given by single intravenous injection. However, the 24-hour output of acid was inhibited when the drug was given orally for a period of 10 to 14 days. While this effect may be due to the ability of the drug to inhibit adrenocortical function, there is no positive supporting evidence.
Haemorrhagic fever with renal syndrome in Germany
Authors: J. Pilaski, C. Ellerich, T. Kreutzer, A. Lang, W. Benik, A. Pohl-Koppe, L. Bode, E. Vanek, I.B. Autenrieth, K. Bigos, H.W. Lee
Journal: The Lancet (1991)
Detection of Breast Cancer and Abnormal Mammograms with a Rapid Point-of-Care Breath Test
Authors: M. Phillips, J.D. Beatty, R.N. Cataneo, J. Huston, P.D. Kaplan, R.I. Lalisang, P. Lambin, M.B.I. Lobbes, M. Mundada, N. Pappas
Journal: Annals of Oncology (2014)
Effect of Weight Loss on Magnetic Resonance Imaging Estimation of Liver Fat and Volume in Patients With Nonalcoholic Steatohepatitis
Authors: Niraj S. Patel, Iliana Doycheva, Michael R. Peterson, Jonathan Hooker, Tatiana Kisselva, Bernd Schnabl, Ekihiro Seki, Claude B. Sirlin, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2014)
Eustachian tube dysfunction in adults
Authors: R. Sproat, C. Burgess, T. Lancaster, P. Martinez-Devesa
Journal: BMJ (2014)

A 56 year old woman presents with a history of fullness in her ears and reduced hearing, which has persisted for three weeks. She often hears clicking when she swallows.

The eustachian tube is a cartilaginous and bony tube providing a connection between the nasopharynx and the middle ear. At rest, the eustachian tube is closed, but it opens on swallowing, yawning, sneezing, and the Valsalva manoeuvre due to contraction of palatine muscles. When the eustachian tube opens it facilitates equalisation of pressures between the external environment and the middle ear by allowing a bolus of air to pass through.

Dysfunction of the eustachian tube results in development of negative pressures within the middle ear, leading to transudation of fluid and a pro-inflammatory response. Consequentially, eustachian tube dysfunction is an important component of pathology of the middle ear, particularly acute otitis media and otitis media with effusion.

### History

Feeling of fullness in the ears— Eustachian tube dysfunction classically presents with a feeling of fullness in the ear, often associated with hearing loss. Eustachian tube dysfunction should be a diagnosis of exclusion as ear fullness can be the presenting feature in a wide variety of clinical entities of the external, middle, and inner ears. There is a requirement for …
Hormonal Regulation of Human Corticotropin-Releasing Hormone Gene Expression: Implications for the Stress Response and Immune/Inflammatory Reaction
Authors: NICHOLAS C. VAMVAKOPOULOS, GEORGE P. CHROUSOS
Journal: Endocrine Reviews (1994)

EXPERIMENTAL support for the hypothesis that ACTH secretion is controlled by hypothalamic factors (1) was obtained in 1955 (2, 3). In 1981, a 41-amino acid C-terminal amidated peptide from ovine hypothalami stimulating pituitary ACTH release was identified in vitro and characterized (4). The biologically active form of this peptide, designated corticotropin-releasing hormone (CRH), and also frequently referred to as corticotropin-releasing factor (CRF), was synthesized and found to have potent ACTH-releasing actions in vivo (5). CRH is the only known permissive factor for the anterior pituitary release of ACTH in man (5, 6). It acts in synergy with arginine vasopressin (AVP) and, perhaps, other factors to regulate pituitary ACTH secretion and ultimately the activity of the pituitary-adrenal axis (7–9). Since its discovery, it has become evident that the role of CRH is much wider than initially thought. Coordination of the behavioral and physical components of the stress response and regulation of the immune/inflammatory reaction were shown to be major roles of this neuropeptide (10, 11).
Influence of Maternal Obesity on Insulin Sensitivity and Secretion in Offspring
Authors: Geltrude Mingrone, Melania Manco, Maria Elena Valera Mora, Caterina Guidone, Amerigo Iaconelli, Donatella Gniuli, Laura Leccesi, Chiara Chiellini, Giovanni Ghirlanda
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring. RESEARCH DESIGN AND METHODS—Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and β-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry. RESULTS—No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 ± 79.32 vs. 513.81 ± 70.70 ml−1 · min−1 · m−2 in women, P &amp;lt; 0.0001; 416.42 ± 76.17 vs. 484.242 ± 45.76 ml−1 · min−1 · m−2 in men, P &amp;lt; 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 ± 21.20 vs. 35.71 ± 10.02 nmol · m−2, P &amp;lt; 0.01) but did not differ significantly in women. β-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and β-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring. CONCLUSIONS—Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring.
Ventricular atrial natriuretic factor in the cardiomyopathic hamster model of congestive heart failure.
Authors: H A Franch, R A Dixon, E H Blaine, P K Siegl
Journal: Circulation Research (1988)

Cardiac atria are thought to be the principle source of plasma atrial natriuretic factor (ANF), a potent natriuretic and diuretic peptide. Whether other ANF production sites are recruited in disease states exhibiting elevated plasma ANF levels is not known. Accordingly, in the cardiomyopathic hamster, an animal model of congestive heart failure with high circulating levels of ANF, contribution of ventricular tissue to total cardiac ANF production and storage was investigated. Measurements were made of immunoreactive ANF in plasma and in atrial and ventricular extracts as well as ANF mRNA levels in the atria and ventricles from normal and cardiomyopathic golden Syrian hamsters. Plasma ANF levels were higher in cardiomyopathic than in control animals. The atrial concentration of ANF (per milligram atrial weight) was 50% and 83% lower in moderate and severe congestive heart failure, respectively, when compared with controls, while atrial ANF mRNA content of cardiomyopathic hamsters was not significantly different from normal hamsters. The ventricular concentration of ANF was 3 times and 7 times higher in animals in moderate and severe heart failure when compared with controls. In severe heart failure, ventricular ANF accounted for 23% of total cardiac stores of ANF. Ventricular ANF mRNA levels were 7 times and 13 times higher in hamsters in moderate and severe heart failure as compared with control animals. Therefore, significant increases in both ANF content and ANF mRNA in ventricles of hamsters in moderate to severe heart failure suggest that the ventricle could be an important source of ANF in congestive heart failure.
Early subcellular Ca2+ remodelling and increased propensity for Ca2+ alternans in left atrial myocytes from hypertensive rats
Authors: Florentina Pluteanu, Johannes Heß, Jelena Plackic, Yulia Nikonova, Judit Preisenberger, Alicja Bukowska, Ulrich Schotten, Andreas Rinne, Marie-Cecile Kienitz, Martin K.-H. Schäfer, Eberhard Weihe, Andreas Goette, Jens Kockskämper
Journal: Cardiovascular Research (2015)

Hypertension is a major risk factor for atrial fibrillation. We hypothesized that arterial hypertension would alter atrial myocyte calcium (Ca2+) handling and that these alterations would serve to trigger atrial tachyarrhythmias.Left atria or left atrial (LA) myocytes were isolated from spontaneously hypertensive rats (SHR) or normotensive Wistar-Kyoto (WKY) controls. Early after the onset of hypertension, at 3 months of age, there were no differences in Ca2+ transients (CaTs) or expression and phosphorylation of Ca2+ handling proteins between SHR and WKY. At 7 months of age, when left ventricular (LV) hypertrophy had progressed and markers of fibrosis were increased in left atrium, CaTs (at 1 Hz stimulation) were still unchanged. Subcellular alterations in Ca2+ handling were observed, however, in SHR atrial myocytes including (i) reduced expression of the α1C subunit of and reduced Ca2+ influx through L-type Ca2+ channels, (ii) reduced expression of ryanodine receptors with increased phosphorylation at Ser2808, (iii) decreased activity of the Na+ / Ca2+ exchanger (at unaltered intracellular Na+ concentration), and (iv) increased SR Ca2+ load with reduced fractional release. These changes were associated with an increased propensity of SHR atrial myocytes to develop frequency-dependent, arrhythmogenic Ca2+ alternans.In SHR, hypertension induces early subcellular LA myocyte Ca2+ remodelling during compensated LV hypertrophy. In basal conditions, atrial myocyte CaTs are not changed. At increased stimulation frequency, however, SHR atrial myocytes become more prone to arrhythmogenic Ca2+ alternans, suggesting a link between hypertension, atrial Ca2+ homeostasis, and development of atrial tachyarrhythmias.
BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect
Authors: Andrew R Hallahan, Joel I Pritchard, Roshantha A S Chandraratna, Richard G Ellenbogen, J Russel Geyer, Ryan P Overland, Andrew D Strand, Stephen J Tapscott, James M Olson
Journal: Nature Medicine (2003)
Association of response endpoints with survival outcomes in multiple myeloma
Authors: S Lonial, K C Anderson
Journal: Leukemia (2013)

Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response.