tbuckley/cabot-search huggingface dataset:
Prediction of Long-Term Survival After Liver Transplantation for Familial Transthyretin Amyloidosis
Authors: Vincent Algalarrondo, Teresa Antonini, Marie Théaudin, Béatrice Ducot, Pierre Lozeron, Denis Chemla, Anouar Benmalek, Catherine Lacroix, Daniel Azoulay, Denis Castaing, Cécile Cauquil, François Rouzet, Sylvie Dinanian, Ludivine Eliahou, Dominique Le Guludec, Didier Samuel, Michel S. Slama, David Adams
Journal: Journal of the American College of Cardiology (2015)

Familial transthyretin amyloidosis (ATTR) is a rare, life-threatening, autosomal dominant disease involving mainly the heart and the peripheral nervous system due to a point mutation of the transthyretin ( TTR ) gene. By removing the main source of the mutated TTR , liver transplantation (LT) has
Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis
Authors: Shao-Ling Zhang, Yun-Wen Chen, Stella Tran, Isabelle Chenier, Marie-Josée Hébert, Julie R. Ingelfinger
Journal: Journal of the American Society of Nephrology (2007)

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.
PDGF receptor kinase inhibitors for the treatment of restenosis
Authors: A LEVITZKI
Journal: Cardiovascular Research (2004)

The clogging of arteries by neointima is a hallmark of atherosclerosis and of restenosis following balloon angioplasty. The realization in the 1980s that PDGF and its receptor play a key role in the onset of neointimal formation led us to develop PDGFR kinase inhibitors as antirestenosis agents. In this review, we describe the development of these inhibitors and their implementation as antirestenosis agents by localized delivery to the site of injury.
IMMUNOFLUORESCENT STUDIES OF HUMAN CELL CULTURES AND CHICK EMBRYOS INOCULATED WITH THE AMEBOID CELL-"LIPOVIRUS" COMPLEX
Authors: Chien Liu, Patricia Rodina
Journal: The Journal of Experimental Medicine (1966)

Tissue culture cells of human origin (HeLa, Lich, and AV(3)) were inoculated with the AL complex. By immunofluorescent staining, AL complex antigen was detectable in the cytoplasm of infected cells as punctate fluorescent granules during the early stage and as homogeneous fluorescence during the late stage of infection. By combining fluorescence and phase-contrast microscopy, many infected cells with cytoplasmic AL complex antigen were shown to have a normal nuclear morphology indistinguishable from uninfected cells. Initiation of AL complex infection was interpreted as occurring by transfer of transmissible factor(s) from cell to cell by contact and mutiplication of such factor(s) therein. Chick embryos were susceptible to AL complex infection following allantoic or amniotic inoculations. Antigen and infectious AL complex were demonstrable in the liver, brain, intestines, lungs, and embryonic membranes. Further investigations on AL complex and its relation to human disease are suggested.
Interstitial Lung Disease in Systemic Sclerosis
Authors: Nicole S. L. Goh, Sujal R. Desai, Srihari Veeraraghavan, David M. Hansell, Susan J. Copley, Toby M. Maher, Tamera J. Corte, Clare R. Sander, Jonathan Ratoff, Anand Devaraj, Gracijela Bozovic, Christopher P. Denton, Carol M. Black, Roland M. du Bois, Athol U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

In interstitial lung disease complicating systemic sclerosis (SSc-ILD), the optimal prognostic use of baseline pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) is uncertain.To construct a readily applicable prognostic algorithm in SSc-ILD, integrating PFTs and HRCT.The prognostic value of baseline PFT and HRCT variables was quantified in patients with SSc-ILD (n = 215) against survival and serial PFT data.Increasingly extensive disease on HRCT was a powerful predictor of mortality (P < 0.0005), with an optimal extent threshold of 20%. In patients with HRCT extent of 10-30% (termed indeterminate disease), an FVC threshold of 70% was an adequate prognostic substitute. On the basis of these observations, SSc-ILD was staged as limited disease (minimal disease on HRCT or, in indeterminate cases, FVC >or= 70%) or extensive disease (severe disease on HRCT or, in indeterminate cases, FVC < 70%). This system (hazards ratio [HR], 3.46; 95% confidence interval [CI], 2.19-5.46; P < 0.0005) was more discriminatory than an HRCT threshold of 20% (HR, 2.48; 95% CI, 1.57-3.92; P < 0.0005) or an FVC threshold of 70% (HR, 2.11; 95% CI, 1.34-3.32; P = 0.001). The system was evaluated by four trainees and four practitioners, with minimal and severe disease on HRCT defined as clearly < 20% or clearly > 20%, respectively, and the use of an FVC threshold of 70% in indeterminate cases. The staging system was predictive of mortality for all scorers, with prognostic separation higher for practitioners (HR, 3.39-3.82) than trainees (HR, 1.87-2.60).An easily applicable limited/extensive staging system for SSc-ILD, based on combined evaluation with HRCT and PFTs, provides discriminatory prognostic information.
A Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment—A Systematic Review
Authors: Andrea M. Isidori, Jacques Buvat, Giovanni Corona, Irwin Goldstein, Emmanule A. Jannini, Andrea Lenzi, Hartmut Porst, Andrea Salonia, Abdulmaged M. Traish, Mario Maggi
Journal: European Urology (2013)
Role of Myocardial Neuronal Nitric Oxide Synthase–Derived Nitric Oxide in β-Adrenergic Hyporesponsiveness After Myocardial Infarction–Induced Heart Failure in Rat
Authors: Jennifer K. Bendall, Thibaud Damy, Philippe Ratajczak, Xavier Loyer, Virginie Monceau, Isabelle Marty, Paul Milliez, Estelle Robidel, Françoise Marotte, Jane-Lise Samuel, Christophe Heymes
Journal: Circulation (2004)

An emerging concept is that a neuronal isoform of nitric oxide synthase (NOS1) may regulate myocardial contractility. However, a role for NOS1-derived nitric oxide (NO) in heart failure (HF) has not been defined.Using a model of myocardial infarction-induced HF, we demonstrated that cardiac NOS1 expression and activity increased in HF rats (P<0.05 and P<0.001 versus shams, respectively). This was associated with translocation of NOS1 from the ryanodine receptor to the sarcolemma through interactions with caveolin-3 in HF hearts. With ex vivo and in vivo pressure-volume analysis, cardiac NOS1-derived NO was found to be negatively inotropic in shams but not HF hearts. Ventricular elastance (E(es)) was significantly reduced in HF rats (P<0.05), and tau, the time constant of left ventricular relaxation, was prolonged (both P<0.05). Acute NOS1 inhibition significantly increased E(es) by 33+/-3% and tau by 17+/-2% (P<0.05) in shams, although these effects were significantly attenuated in HF hearts. beta-Adrenergic stimulation induced a marked increase in systolic performance in sham hearts, with the responses being significantly blunted in HF hearts. E(es) increased by 163+/-42% (P<0.01) in sham hearts and 56+/-9% in HF hearts, and LV +dP/dt increased by 97+/-9% (P<0.01) in shams and 37+/-7% (P<0.05) in the HF group. Interestingly, preferential NOS1 inhibition enhanced the blunted responses of LV +dP/dt and E(es) to beta-adrenergic stimulation in HF rats but had no effect in shams.These results provide the first evidence that increased NOS1-derived NO production may play a role in the autocrine regulation of myocardial contractility in HF.
Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition
Authors: Yujie Tang, Sharareh Gholamin, Simone Schubert, Minde I Willardson, Alex Lee, Pratiti Bandopadhayay, Guillame Bergthold, Sabran Masoud, Brian Nguyen, Nujsaubnusi Vue, Brianna Balansay, Furong Yu, Sekyung Oh, Pamelyn Woo, Spenser Chen, Anitha Ponnuswami, Michelle Monje, Scott X Atwood, Ramon J Whitson, Siddhartha Mitra, Samuel H Cheshier, Jun Qi, Rameen Beroukhim, Jean Y Tang, Rob Wechsler-Reya, Anthony E Oro, Brian A Link, James E Bradner, Yoon-Jae Cho
Journal: Nature Medicine (2014)
High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival
Authors: Diane K. Birks, Andrew M. Donson, Purvi R. Patel, Christopher Dunham, Andrea Muscat, Elizabeth M. Algar, David M. Ashley, B. K. Kleinschmidt-DeMasters, Rajeev Vibhakar, Michael H. Handler, Nicholas K. Foreman
Journal: Neuro-Oncology (2011)

Molecular profiling of tumors has proven to be a valuable tool for identification of prognostic and diagnostic subgroups in medulloblastomas, glioblastomas, and other cancers. However, the molecular landscape of atypical teratoid/rhabdoid tumors (AT/RTs) remains largely unexplored. To address this issue, we used microarrays to measure the gene expression profiles of 18 AT/RTs and performed unsupervised hierarchical clustering to determine molecularly similar subgroups. Four major subgroups (clusters) were identified. These did not conform to sex, tumor location, or presence of monosomy 22. Clusters showed distinct gene signatures and differences in enriched biological processes, including elevated expression of some genes associated with choroid plexus lineage in cluster 4. In addition, survival differed significantly by cluster, with shortest survival (mean, 4.7 months) in both clusters 3 and 4, compared with clusters 1 and 2 (mean, 28.1 months). Analysis showed that multiple bone morphogenetic protein (BMP) pathway genes were upregulated in the short survival clusters, with BMP4 showing the most significant upregulation (270-fold). Thus, high expression of BMP pathway genes was negatively associated with survival in this dataset. Our study indicates that molecular subgroups exist in AT/RTs and that molecular profiling of these comparatively rare tumors may be of diagnostic, prognostic, and therapeutic value.
Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype
Authors: Manish Pareek, Jason Evans, John Innes, Grace Smith, Suzie Hingley-Wilson, Kathryn E Lougheed, Saranya Sridhar, Martin Dedicoat, Peter Hawkey, Ajit Lalvani
Journal: Thorax (2012)

<h3>Background</h3> Emerging evidence suggests that <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) lineage and host ethnicity can determine tuberculosis (TB) clinical disease patterns but their relative importance and interaction are unknown. <h3>Methods</h3> We evaluated prospectively collected TB surveillance and <i>Mtb</i> strain typing data in an ethnically heterogeneous UK population. Lineage assignment was denoted using 15-loci mycobacterial interspersed repetitive units containing variable numbers of tandem repeats (MIRU-VNTR) and MIRU-VNTRplus. Geographical and ethnic associations of the six global <i>Mtb</i> lineages were identified and the influence of lineage and demographic factors on clinical phenotype were assessed using multivariate logistic regression. <h3>Results</h3> Data were available for 1070 individuals with active TB which was pulmonary only, extrapulmonary only and concurrent pulmonary–extrapulmonary in 52.1%, 36.9% and 11.0% respectively. The most prevalent lineages were Euro-American (43.7%), East African Indian (30.2%), Indo-Oceanic (13.6%) and East Asian (12.2%) and were geo-ethnically restricted with, for example, Indian subcontinent ethnicity inversely associated with Euro-American lineage (OR 0.23; 95% CI 0.14 to 0.39) and positively associated with the East African-Indian lineage (OR 4.04; 95% CI 2.19 to 7.45). Disease phenotype was most strongly associated with ethnicity (OR for extrathoracic disease 21.14 (95% CI 6.08 to 73.48) for Indian subcontinent and 14.05 (3.97 to 49.65) for Afro-Caribbean), after adjusting for lineage. With East Asian lineage as the reference category, the Euro-American (OR 0.54; 95% CI 0.32 to 0.91) and East-African Indian (OR 0.50; 95% CI 0.29 to 0.86) lineages were negatively associated with extrathoracic disease, compared with pulmonary disease, after adjusting for ethnicity. <h3>Conclusions</h3> Ethnicity is a powerful determinant of clinical TB phenotype independently of mycobacterial lineage and the role of ethnicity-associated factors in pathogenesis warrants investigation.
Slow breathing reduces sympathoexcitation in COPD
Authors: T. Raupach, F. Bahr, P. Herrmann, L. Luethje, K. Heusser, G. Hasenfuß, L. Bernardi, S. Andreas
Journal: European Respiratory Journal (2008)

Neurohumoral activation has been shown to be present in hypoxic patients with chronic obstructive pulmonary disease (COPD). The aims of the present study were to investigate whether there is sympathetic activation in COPD patients in the absence of hypoxia and whether slow breathing has an impact on sympathoexcitation and baroreflex sensitivity. Efferent muscle sympathetic nerve activity, blood pressure, cardiac frequency and respiratory movements were continuously measured in 15 COPD patients and 15 healthy control subjects. Baroreflex sensitivity was analysed by autoregressive spectral analysis and the alpha-angle method. At baseline, sympathetic nerve activity was significantly elevated in COPD patients and baroreflex sensitivity was decreased (5.0±0.6 versus 8.9±0.8 ms·mmHg −1 ). Breathing at a rate of 6 breaths·min −1 caused sympathetic activity to drop significantly in COPD patients (from 61.3±4.6 to 53.0±4.3 bursts per 100 heartbeats) but not in control subjects (39.2±3.2 versus 37.5±3.3 bursts per 100 heartbeats). In both groups, slow breathing significantly enhanced baroreflex sensitivity. In conclusion, sympathovagal imbalance is present in normoxic chronic obstructive pulmonary disease patients. The possibility of modifying these changes by slow breathing may help to better understand and influence this systemic disease.
Cysts of the Tonsils, Nose, Larynx, and Ear
Authors: P. McBride
Journal: BMJ (1892)

Usually it does not give rise to any definite phenomena.'Wilson Fox1 says: " The symptoms of this condition are few and doubtful until subcutaneous emphysema is produced.Sudden and rapid increase of dyspncea, with augmented clearness of the percussion note, have been observed in some cases; but the auscultatory signs are not significant."Walsh quotes a case of phthisis in which, after profuse h2emorrhage, a percussionresonance likethat ofpneumothorax occurred atboth sides of the back of the chest, the cause of which was made clear in a few hours by the appearance of subcutaneous emphysema.The occurrence of pneumothoraK from rupture of the pleura in interlobular emphysema (as in Case i) is said by WIertz to be more common than the forcing of the air through the root of the lung and the mediastinum into the subcu- taneous connective tissue.The production of subcutaneous emphysema is an accident almost limited to early childhood.Of 25 cases collected by Roger, 20 occurred in children; and of these instances of "general emphysema in children," as Roger calls them, 6 occurred under the age of 2 years, 10 be- ween 3 and 4, and only 4 between 10 and 15.My own patient was 11 years old.It is not easy to account for the interlobular emphysema in the second case which I have described.The causes of this condition may be grouped under two heads:1. Violent strain upon healthy lungs, as in the case of croup.2. Normal or abnormal strain upon diseased lung tissue, as in the instances of abscess, acute tuberculosis, and pulmo- nary hsemorrhage before mentioned.
Posttransplant Administration of Cyclophosphamide and Donor Lymphocyte Infusion Induces Potent Antitumor Immunity to Solid Tumor
Authors: Masatoshi Eto, Yoriyuki Kamiryo, Ario Takeuchi, Masahiko Harano, Katsunori Tatsugami, Mamoru Harada, Keijiro Kiyoshima, Masumitsu Hamaguchi, Takanori Teshima, Masazumi Tsuneyoshi, Yasunobu Yoshikai, Seiji Naito
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Nonmyeloablative allogeneic stem cell transplantation (SCT) has been increasingly used for the treatment of hematologic and solid malignancies, and mature donor T cells are considered to be the main effectors of the graft-versus-tumor (GVT) activity. However, the association between degree of donor chimerism and intensity of GVT effects has not been fully elucidated. We recently proposed a unique nonmyeloablative cell therapy using posttransplant cyclophosphamide and donor lymphocyte infusion, by which a significant antitumor effect against murine renal cell carcinoma, RENCA, was induced, although the level of mixed chimerism was relatively low. In this study, we attempted to clarify a role of chimerism for in vivo antitumor effects on GVT effects in radiation-associated nonmyeloablative SCT. Experimental Design: We assessed antitumor effects on RENCA tumors and the degree of donor chimerism after several doses of irradiation followed by allogeneic SCT and compared the results with those of cyclophosphamide-based cell therapy. Results: Allogeneic SCT following sublethal irradiation (6 Gy) induced almost complete donor chimerism, whereas cyclophosphamide-based cell therapy produced low levels of donor chimerism. Nonetheless, GVT activity was much more potent in cyclophosphamide-based cell therapy than irradiation-conditioned SCT. Furthermore, cyclophosphamide-conditioned SCT induced more potent immune reconstitution with less severe graft-versus-host disease than irradiation-conditioned SCT. Conclusions: Our results indicate that a high level of chimerism is not essential for the in vivo antitumor effect of nonmyeloablative allogeneic cell therapy against solid tumor and that the recovery of peripheral lymphocytes after the initial immunosuppression might be a critical event for the elicitation of in vivo antitumor effects of that treatment modality.
Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects.
Authors: S Wieshammer, F S Keck, A C Schauffelen, H von Beauvais, H Seibold, V Hombach
Journal: Thorax (1990)

The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.
Structural correlates of electrical remodeling in ventricular hypertrophy
Authors: H Reddy
Journal: Cardiovascular Research (2003)

Time for primary review 26 days. 

See article by Peschar et al. [2] (pages 510–517) in this issue. 

Ventricular remodeling is an adaptive change in cardiac chamber structure and function in response to volume and/or pressure overload. In the last few years, it became clear that this process also involves the electrical system of the ventricular chambers. Electrical remodeling associated with left ventricular hypertrophy and heart failure causes an increased frequency of ventricular ectopy and a high risk of cardiac arrest. The degree of electrical remodeling and arrhythmic risk is not directly proportional to the severity of left ventricular (LV) dysfunction. For example, in the VHeFT study (Veterans Administration Heart Failure Trial), the risk of sudden cardiac death was greater in patients with modest LV dysfunction [1]. It has been shown that there is a temporal relationship between the progression of structural and electrical remodeling of the left ventricle in response to various pressure and volume overload states. Concurrent regression of structural and electrical remodeling in pressure overload hypertrophy is seen, but there seems to be a dissociation in these processes in certain types of volume overload hypertrophy (Fig. 1). Such an interesting dissociation is shown in this issue of Cardiovascular Research by Peschar et al. [2]. The findings of this paper underscore the independent nature of electrical remodeling in volume overload hypertrophy in contrast to pressure overload hypertrophy. … 

*Corresponding author. 318 McHaney Hall, University of Missouri Hospital, 1 Hospital Drive, Columbia, MO, USA. Fax: +1-573-884-7743.
"Opportunist" mycobacterial infections
Authors: P D O DAVIES
Journal: Thorax (2000)

Opportunist" mycobacterial infectionsWe were greatly impressed by the Joint Tuberculosis Committee guidelines on the management of opportunist mycobacterial infections. 1 We do, however, wonder why the word "opportunist" has been used to describe the mycobacteria, other than the M tuberculosis complex, that cause human disease.All mycobacteria causing disease, even the M tuberculosis complex, are opportunists.Thus, the latter are often spoken of as causing opportunist disease in HIV positive persons.Since the causative role of these other mycobacteria in human disease was established in the middle of the 20th century, a wide range of collective nouns has been applied to them-atypical, anonymous, MOTT (mycobacteria other than tuberculosis), nontuberculous, and tuberculoid-as well as opportunist.The distinguishing feature of almost all mycobacteria other than members of the M tuberculosis complex is that they live freely in the environment.For this reason the expression "environmental mycobacteria" has been in widespread use in recent years.May we suggest that, for uniformity, this expression should be universally adopted.