tbuckley/cabot-search huggingface dataset:
Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients
Authors: P. B. Jeppesen, E. L. Sanguinetti, A. Buchman, L. Howard, J. S. Scolapio, T. R. Ziegler, J. Gregory, Kelly A. Tappenden, J. Holst, P. B. Mortensen
Journal: Gut (2005)

<b>Background and aims:</b> Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity. <b>Methods:</b> Teduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with &lt;50% colon in continuity (dose 0.03 mg/kg/day), and five with ≥50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with ≥50% colon in continuity. <b>Results:</b> Pooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p&lt;0.001) and relative (+22 (16)%; p&lt;0.001) wet weight absorption, urine weight (+555 (485) g/day; p&lt;0.001), and urine sodium excretion (+53 (40) mmol/day; p&lt;0.001). Teduglutide decreased faecal wet weight (−711 (734) g/day; p = 0.001) and faecal energy excretion (−808 (1453) kJ/day (−193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice. <b>Conclusion:</b> Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.
SPIROCHÆTAL FINDINGS IN THE BRAINS OF PARETICS TREATED WITH MALARIA
Authors: Nicholas Kopeloff, Nathan Blackman
Journal: American Journal of Psychiatry (1933)

1. Spirochætes were found by the Jahnel method in the brains of 6 out of 39 malaria treated general paralytics. 2. Among the six positive findings degenerate forms of spirochaætes were encountered in more instances than normal forms. Three of these patients came to autopsy shortly after malarial inoculation (within six weeks). 3. Spirochætes were found by the Jahnel and Dieterle methods in 8 out of 10 general paralytics not treated with malaria and none were found in a normal brain. 4. Having thus established the validity of the technical procedure it may be stated that within the limitations of the material at hand it appears that (a) artificially induced malaria is likely to destroy spirochætes in the brains of general paralytics; or (b) that failing to destroy the spirochæta completely, this form of therapy alters the morphology of the Spiroæta pallida to such a degree as to render it degenerate in appearance.
C-Propeptides of Procollagens Iα1 and II that Differentially Accumulate in Enchondromas versus Chondrosarcomas Regulate Tumor Cell Survival and Migration
Authors: Jean-Baptiste Vincourt, Stéphanie Etienne, Justine Cottet, Camille Delaunay, Bantsimba Malanda, Frédéric Lionneton, François Sirveaux, Patrick Netter, François Plénat, Didier Mainard, Jean-Michel Vignaud, Jacques Magdalou
Journal: Cancer Research (2010)

Chondrogenic tumors that exhibit benign or malignant behaviors synthesize variable amounts of cartilage-like extracellular matrix. To define the regulators of these phenotypes, we performed a proteomic comparison of multiple human chondrogenic tumors, which revealed differential accumulation of the C-propeptides of procollagens Ialpha1 and II (PC1CP and PC2CP) in malignant versus benign tumors, respectively. Expression patterns of PC1CP correlated with levels of tumor vascularization, whereas expression patterns of PC2CP suggested its susceptibility to immobilization within the extracellular matrix. Prompted by these observations, we investigated the functions of recombinant PC1CP and PC2CP in the extracellular matrix in soluble or immobilized states. Each induced beta1 integrin-mediated chondrocyte adhesion by distinct domains and efficacies, suggesting that they initiated distinct signaling pathways. Indeed, immobilized PC2CP, but not PC1CP, induced apoptosis of primary chondrocytes and EAhy926 endothelial cells. In contrast, soluble PC1CP, but not PC2CP, induced the migration of EAhy926 cells and increased vascular endothelial growth factor (VEGF) and CXCR4 expression in chondrocytes. Soluble PC2CP also increased VEGF expression, but along with a more pronounced effect on CXCR4 and matrix metalloproteinase 13 expression. Our findings suggest that PC1CP favors angiogenesis and tumor progression, but that PC2CP acts in a more complex manner, exerting antitumor and antiangiogenic properties through apoptosis induction when immobilized, but progression and metastasis when soluble. In summary, the relative levels of PC1CP and PC2CP and their interactions within the extracellular matrix contribute to tumor progression, angiogenesis, and metastasis in chondrogenic tumors.
Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study
Authors: Sandrine Faivre, Eric Raymond, Eveline Boucher, Jean Douillard, Ho Y Lim, Jun S Kim, Magaly Zappa, Silvana Lanzalone, Xun Lin, Samuel DePrimo, Charles Harmon, Ana Ruiz-Garcia, Maria J Lechuga, Ann Lii Cheng
Journal: The Lancet Oncology (2009)
H syndrome: novel and recurrent mutations in <i>SLC29A3</i>
Authors: T.P. Priya, N. Philip, V. Molho-Pessach, T. Busa, A. Dalal, A. Zlotogorski
Journal: British Journal of Dermatology (2010)

The H syndrome (OMIM 612391) is a recently described autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature (low height), hyperglycaemia/diabetes mellitus, hallux valgus, and fixed flexion contractures of the toe and finger joints.1, 2 Histologically, there is an inflammatory infiltrate consisting mainly of histiocytes, later replaced by fibrosis of the deep dermis and subcutis.3 In total, 31 patients have been reported in the literature with the clinical phenotype characteristic of this syndrome.1–7
Stage Migration, Selection Bias, and Survival Associated With the Adoption of Positron Emission Tomography Among Medicare Beneficiaries With Non–Small-Cell Lung Cancer, 1998-2003
Authors: Michaela A. Dinan, Lesley H. Curtis, William R. Carpenter, Andrea K. Biddle, Amy P. Abernethy, Edward F. Patz, Kevin A. Schulman, Morris Weinberger
Journal: Journal of Clinical Oncology (2012)

Previous studies have linked the use of positron emission tomography (PET) with improved outcomes among patients with non-small-cell lung cancer (NSCLC). However, this association may be confounded by PET-induced stage migration and selection bias. We examined the association between PET use and overall survival among Medicare beneficiaries with NSCLC.Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) -Medicare data was used to characterize changes in overall survival, stage-specific survival, and stage distribution among Medicare beneficiaries with NSCLC between 1998 and 2003.A total of 97,007 patients with NSCLC diagnosed between 1998 and 2003 met the study criteria. Two-year and 4-year survival remained unchanged, despite widespread adoption of PET. The proportion of patients staged with advanced disease increased from 44% to 50%. Upstaging of disease was accompanied by stage-specific improved survival, with 2-year survival of stage IV disease increasing from 8% to 11% between 1998 and 2003. PET was more likely to be administered to patients with less advanced disease (stages I through IIIA) and greater overall survival.Overall survival among Medicare beneficiaries with NSCLC was unchanged between 1998 and 2003, despite widespread adoption of PET. The association between PET use and increased survival likely reflects an artifact of selection bias and consequent stage migration.
Effects of nitroprusside on myocardial blood flow and oxygen consumption in conscious lambs with an aortopulmonary left-to-right shunt.
Authors: G P Toorop, R Hardjowijono, M Dalinghaus, A M Gerding, J H Koers, W G Zijlstra, J R Kuipers
Journal: Circulation (1990)

We studied the effect of vasodilation on regional myocardial blood flow and oxygen consumption of the left ventricular free wall by infusing 10 micrograms/kg/min sodium nitroprusside into 7-week-old conscious lambs with and without aortopulmonary left-to-right shunts. Resting myocardial oxygen consumption in the 13 shunt lambs was significantly higher than in the nine control lambs (989 +/- 104 [+/- SEM] vs. 432 +/- 41 mumol/min/100 g left ventricle). This was achieved by a significantly higher left ventricular myocardial blood flow (294 +/- 33 vs. 143 +/- 16 ml/min/100 g left ventricle) because the arteriovenous oxygen concentration difference across the left ventricular free wall was similar in shunt and control lambs. Infusion of nitroprusside did not significantly change myocardial oxygen consumption and regional myocardial blood flows at 10 and 50 minutes after the onset of the infusion. This occurred despite a substantial drop in aortic and left atrial pressures and stroke volume, which decreases wall stress as well as external work of the left ventricle. Heart rate, however, increased significantly. We postulate that, during infusion of nitroprusside, the potential decrease in myocardial oxygen consumption due to a decrease in wall stress and external work of the left ventricle is neutralized by the consequences of the increased heart rate. In view of this and because of its hemodynamic effects, we do not consider sodium nitroprusside useful in the treatment of circulatory congestion in patients with left-to-right shunts, normal arterial pressures, and normal systemic blood flows.
Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program
Authors: Leigh Perreault, Steven E. Kahn, Costas A. Christophi, William C. Knowler, Richard F. Hamman
Journal: Diabetes Care (2009)

OBJECTIVE Participants in the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS) or metformin had a significantly reduced incidence of diabetes compared with those randomized to placebo, yet most were still at risk because they had pre-diabetes. We explored the effect of baseline characteristics, weight change, ILS, and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation (NGR) defined by American Diabetes Association criteria. RESEARCH DESIGN AND METHODS The DPP was a prospective randomized trial. Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up. RESULTS Lower baseline fasting (hazard ratio 1.52, P &amp;lt; 0.01) and 2-h (1.24, P &amp;lt; 0.01) glucose predicted regression to NGR, as did younger age (1.07, P &amp;lt; 0.01) and greater insulin secretion (1.09, P = 0.04). ILS (2.05, P &amp;lt; 0.01) and weight loss (1.34, P &amp;lt; 0.01) had significant and independent effects on regression. A nonsignificant trend for regression was also observed for metformin (1.25, P = 0.06), male sex (1.17, P = 0.08), and insulin sensitivity (1.07, P = 0.09). In those entering the study with both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), male sex and insulin sensitivity predicted regression to isolated IFG, whereas ILS, metformin, female sex, and greater insulin secretion predicted regression to isolated IGT. CONCLUSIONS Insulin secretion, and other biologic processes retained with younger age, are key in restoring NGR in people with pre-diabetes. However, NGR may also be attained through weight loss and additional aspects of ILS.
Human syngamosis: the first case in Korea
Authors: H. Y. Kim, S. M. Lee, J. E. Joo, M. J. Na, M. H. Ahn, D. Y. Min
Journal: Thorax (1998)

Parasites of the genus<i>Mammomonogamus</i> affect the respiratory tract of domestic mammals but have only rarely been reported in humans. In this case report the diagnosis of human syngamosis is described following bronchoscopic examination of a patient whose initial symptoms were simply of community acquired pneumonia. The patient had a persistent and productive cough with intermittent fever during 10 days of observation. After bronchoscopic extraction of the parasites and treatment with albendazole he recovered fully. This is one of the first recognised cases of human syngamosis in Korea.
Functional isotypes are not encoded by the constant region genes of the beta subunit of the T cell receptor for antigen/major histocompatibility complex.
Authors: H D Royer, A Bensussan, O Acuto, E L Reinherz
Journal: The Journal of Experimental Medicine (1984)

Human T cell clones and a cDNA probe specific for constant regions of the beta subunit of the antigen/major histocompatibility complex (MHC) receptor, TiC beta 1 and TiC beta 2, were employed to determine whether these genes were differentially used by functional classes of T lymphocytes. DNA from 10 interleukin-2-dependent T cell clones including class I and class II MHC-specific cytotoxic T lymphocytes (n = 6), T4+ inducer T lymphocytes (n = 2), and T8+ suppressor T lymphocytes (n = 2) showed rearrangement of the TiC beta 1 gene on Southern blot analysis with or without deletion of the other TiC beta 1 allele. In contrast, TiC beta 2 always remained in germline configuration. Moreover, the finding that one additional suppressor clone deleted both TiC beta 1 alleles, maintained a germline TiC beta 2 configuration, and yet actively transcribed TiC beta 2 message suggested that TiC beta 2 is not a pseudogene. Rather, it appeared to be used less frequently than the TiC beta 1 gene and in the absence of detectable DNA rearrangements. Together, these results demonstrate that the functional repertoire (or isotype) of a given subclass of T cells is not encoded within the Ti beta genes.
Concepts versus conceptions (again)
Authors: Georges Rey
Journal: Behavioral and Brain Sciences (2010)

Machery neglects the crucial role of concepts in psychological explanation, as well as the efforts of numerous "externalists" of the last 40 years to provide an account of that role. He rightly calls attention to the wide variation in people's epistemic relations to concepts - people's conceptions of things - but fails to appreciate how externalist and kindred proposals offer the needed stability in concepts themselves that underlies that variation.
Vascular Endothelial Growth Factor-B Promotes In Vivo Angiogenesis
Authors: Jean-Sébastien Silvestre, Radia Tamarat, Teni G. Ebrahimian, Aude Le-Roux, Michel Clergue, Florence Emmanuel, Micheline Duriez, Bertrand Schwartz, Didier Branellec, Bernard I. Lévy
Journal: Circulation Research (2003)

Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B 167 or with rhVEGF-A 165 . After 14 days, cell ingrowth in the Matrigel plug was increased by 2.0- and 2.5-fold in rhVEGF-B 167 –treated and rhVEGF-A 165 –treated mice, respectively ( P &lt;0.01), in association with a raise in phospho-Akt/Akt (1.8-fold, P &lt;0.01) and endothelial NO synthase (eNOS) (1.80- and 1.60-fold, respectively; P &lt;0.05) protein levels measured by Western blot. VEGF-B–induced cell ingrowth was impaired by treatment with NOS inhibitor ( N G -nitro- l -arginine methyl ester; L-NAME, 10 mg/kg per day). Treatment with neutralizing antibody directed against the VEGF-B receptor VEGF-R1 (anti-VEGFR1, 10 μg) completely abrogated VEGF-B–related effects. Proangiogenic effect of VEGF-B was confirmed in a mouse model of surgically induced hindlimb ischemia. Plasmids containing human form of VEGF-A (phVEGF-A 165 ) or VEGF-B (phVEGF-B 167 or phVEGF-B 186 ) were administered by in vivo electrotransfer. Angiographic score at day 28 showed significant improvement in ischemic/nonischemic leg ratio by 1.4- and 1.5-fold in mice treated with phVEGF-B 167 and phVEGF-B 186 , respectively ( P &lt;0.05). Laser Doppler perfusion data also evidenced a 1.5-fold increase in phVEGF-B 167 –treated and phVEGF-B 186 –treated mice ( P &lt;0.05). Such an effect was associated with an upregulation of phospho-Akt/Akt and eNOS protein levels in the ischemic legs and was hampered by treatment with anti-VEGFR1. This study demonstrates for the first time that VEGF-B, in part through its receptor VEGF-R1, promotes angiogenesis in association with an activation of Akt and eNOS-related pathways.
Oxygen therapy during exacerbations of chronic obstructive pulmonary disease
Authors: A.G.N. Agustí, M. Carrera, F. Barbé, A Muñoz, B Togores
Journal: European Respiratory Journal (1999)

Venturi masks (VMs) and nasal prongs (NPs) are widely used to treat acute respiratory failure (ARF) in chronic obstructive pulmonary disease (COPD). In this study, these devices were compared in terms of their potentiality to worsen respiratory acidosis and their capacity to maintain adequate (&gt; 90%) arterial oxygenation (Sa,O2) through time (approximately 24 h). In a randomized cross-over study, 18 consecutive COPD patients who required hospitalization because of ARF were studied. After determining baseline arterial blood gas levels (on room air), patients were randomized to receive oxygen therapy through a VM or NPs at the lowest possible inspiratory oxygen fraction that resulted in an initial Sa,O2 of &gt; or = 90%. Arterial blood gas levels were measured again 30 min later (on O2), and Sa,O2 recorded using a computer during the subsequent approximately 24 h. Patients were then crossed-over to receive O2 therapy by means of the alternative device (NPs or VM), and the same measurements obtained again in the same order. It was observed that both the VM and NPs improved arterial oxygen tension (p&lt;0.0001) to the same extent (p=NS), without any significant effect upon arterial carbon dioxide tension or pH. However, despite this adequate initial oxygenation, Sa,O2 was &lt; 90% for 3.7+/-3.8 h using the VM and for 5.4+/-5.9 h using NPs (p&lt;0.05). Regression analysis showed that the degree of arterial hypoxaemia (p&lt;0.05) and arterial hypercapnia (p&lt;0.05) present before starting O2 therapy and, particularly, the initial Sa,O2 achieved after initiation of O2 therapy (p&lt;0.0001) enabled the time (in h) that patients would be poorly oxygenated (Sa,O2 &lt; 90%) on follow-up to be predicted. These findings suggest that, in order to maintain an adequate (&gt; 90%) level of arterial oxygenation in patients with chronic obstructive pulmonary disease and moderate acute respiratory failure: 1) the initial arterial oxygen saturation on oxygen should be maximized whenever possible by increasing the inspiratory oxygen fraction; 2) this strategy seems feasible because neither the VM nor NPs worsen respiratory acidosis significantly; and 3) the Venturi mask (better than nasal prongs) should be recommended.
Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms
Authors: Alun Jones, Rajdeep Deb, Evelyn Torsney, Franklyn Howe, Mathew Dunkley, Yanosha Gnaneswaran, David Gaze, Hosaam Nasr, Ian M. Loftus, Mathew M. Thompson, Gillian W. Cockerill
Journal: Circulation (2009)

Background— Development and rupture of aortic aneurysms involve a combination of complex biological processes. Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, has been shown to have a broad spectrum of effects in vivo. The hypothesis that rosiglitazone would reduce aneurysm expansion or rupture was tested in the angiotensin II (Ang II)-induced hypercholesterolemic mouse model. Methods and Results— Apolipoprotein E-deficient mice, 12 months of age, were allocated to 4 groups. Three groups were infused with Ang II (1 μg · min −1 · kg −1 ), and the fourth was infused with saline. Rosiglitazone was given 1 week before infusion and 1 week after infusion. At day 28, aortic size was measured, and tissues were collected for analyses. Both pretreatment and posttreatment with rosiglitazone inhibited the occurrence of fatal rupture (11 of 30 versus 0 of 30 versus 0 of 15; P =0.0013) and reduced maximal dilatation of the aorta (4.6±0.13 versus 2.4±0.48 versus 2.15±0.46 mm 2 ; P &lt;0.0001). Blood glucose, total cholesterol, body weight, and atherosclerosis did not differ between groups. Pretreatment with rosiglitazone inhibited the Ang II-induced expression of angiotensin type 1a Ang II receptor while having no effect on the angiotensin type 2 Ang II receptor, in addition to reducing Ang II-induced expression of E-selectin, tumor necrosis factor-α, and interleukin-6. Conclusions— Pretreatment or posttreatment with RGZ reduced aortic expansion and rupture in this mouse model. Reduction of lesions in animals pretreated with rosiglitazone is concomitant with decreased expression of inflammatory mediators. Further studies are needed to elucidate the precise mechanism.
CD8α2 CD11b+ Dendritic Cells Present Exogenous Virus-like Particles to CD8+ T Cells and Subsequently Express CD8α and CD205 Molecules
Authors: Gabriel Morón, Paloma Rueda, Ignacio Casal, Claude Leclerc
Journal: The Journal of Experimental Medicine (2002)

Recombinant porcine parvovirus virus-like particles (PPV-VLPs) are particulate exogenous antigens that induce a strong, specific cytotoxic T lymphocyte (CTL) response in the absence of adjuvant. In the present report, we demonstrate in vivo that dendritic cells (DCs) present PPV-VLPs to CD8+ T cells after intracellular processing. PPV-VLPs are captured by DCs with a high efficacy, which results in the delivery of these exogenous antigens to 50% of the whole spleen DC population. In vivo, a few hours after injection, PPV-VLPs are presented exclusively to CD8+ T cells by CD8α− DCs, whereas 15 hours later they are presented mainly by CD8α+ DCs. After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8α and CD205 and the loss of CD4 molecules on their surface. The failure to detect mRNA coding for CD8α in CD11b+ DCs suggests that CD8α expression by these cells is not due to de novo synthesis. In recombination-activating gene knockout mice (Rag−/−), CD11b+ DCs did not express CD8α and PPV-VLPs presentation by CD8α+ DCs was severely diminished. These results indicate that both CD8α− and CD8α+ DCs play an important role in the induction of CTL responses by exogenous antigens, such as VLP.