tbuckley/cabot-search huggingface dataset:
Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models
Authors: Federica Pisati, Marzia Belicchi, Francesco Acerbi, Chiara Marchesi, Carlo Giussani, Manuela Gavina, Sophie Javerzat, Martin Hagedorn, Giorgio Carrabba, Valeria Lucini, Sergio Maria Gaini, Nereo Bresolin, Lorenzo Bello, Andreas Bikfalvi, Yvan Torrente
Journal: Cancer Research (2007)

Abstract Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-β1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation. [Cancer Res 2007;67(7):3054–63]
Insulin response to carbohydrate ingestion after gastric surgery with special reference to hypoglycaemia
Authors: A. J. Cameron, J. P. Ellis, J. I. McGill, L. P. Le Quesne
Journal: Gut (1969)

Factors responsible for spontaneous hypoglycaemia were investigated in 23 gastrectomy patients and two patients with vagotomy and pyloroplasty. Plasma insulin and capillary blood glucose levels were followed after giving 175 ml of 50% glucose orally. In gastrectomy patients a significant correlation was found between the height of the peak blood glucose and insulin levels for the same individual. Patients with high peak glucose and insulin levels were significantly more likely to develop hypoglycaemia later in the test. These findings are compatible with the suggestion that the major factor predisposing to hypoglycaemia is a faster than average rate of emptying of the gastric remnant, but this does not explain all the results. In two cases, hypoglycaemia followed an abnormally large insulin response to oral glucose. The results of insulin injection tests in 14 patients do not exclude the further possibility that in some cases hypoglycaemia is due to excessive insulin sensitivity.
The influence of propanolol on portosystemic shunting
Authors: Jorge J. Gumucio, Laurence M. Blendis
Journal: Hepatology (1991)

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg · kg −1 d −1 , starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 ± 0.40 mm Hg) was significantly lower ( P &lt; 0.001) in the propranolol-treated animals (7.9 ± 0.80 mm Hg). Portal-systemic shunting was decreased by 79%, from 12.2 ± 3.34% in controls to 2.5 ± 0.99% in the propranolol group ( P &lt; 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 ± 0.73 ml/min; n = 6) compared with controls (4.00 ± 0.34 ml/min; n = 8; P &lt; 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.
Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves high-density lipoprotein cholesterol antioxidative capacity in rheumatoid arthritis patients
Authors: C Popa, L J H van Tits, P Barrera, H L M Lemmers, F H J van den Hoogen, P L C M van Riel, T R D J Radstake, M G Netea, M Roest, A F H Stalenhoef
Journal: Annals of the Rheumatic Diseases (2008)

Objective: High-density lipoprotein (HDL) antiatherogenic functions seem to be diminished during inflammatory conditions such as rheumatoid arthritis (RA). The aim of this study was to investigate the effects of tumour necrosis factor (TNF) inhibition on the antioxidative capacity of HDL in RA. Methods: Plasma lipids and paraoxonase (PON-1) activity were investigated in 45 RA patients, before and during 6 months of anti-TNF therapy. In addition, HDL was isolated and tested for its ability to inhibit copper-induced oxidation of low-density lipoprotein in vitro. Results: Plasma HDL concentrations did not change considerably after 6 months of therapy. However, stable increases of PON-1 activities were observed throughout the same period (p<0.03). The increases were more obvious when related to HDL or apolipoprotein AI concentrations. HDL total antioxidative capacity significantly improved 6 months after the initiation of anti-TNF therapy (p = 0.015). The initial improvement of PON-1 activity paralleled a decrease in the inflammatory status, whereas specific TNF blockade was likely to be responsible for the long-term effects. Conclusions: Anti-TNF therapy with infliximab has beneficial effects on lipids through changes in HDL antioxidative capacity, which might be clinically relevant and contribute to the reported protective effect of anti-TNF on cardiovascular morbidity in RA. This emphasises the importance of HDL antiatherogenic capacity for cardiovascular risk in chronic inflammatory conditions.
Thromboglobulin and platelet factor 4 in bronchoalveolar lavage fluid of patients with systemic sclerosis
Authors: O Kowal-Bielecka
Journal: Annals of the Rheumatic Diseases (2004)

To evaluate concentrations of the platelet activation markers beta thromboglobulin (BTG) and platelet factor 4 (PF4) in bronchoalveolar lavage fluid (BALF) from patients with systemic sclerosis with and without scleroderma interstitial lung disease (SLD).BTG and PF-4 were measured by enzyme immunoassay in BALF from 37 patients with systemic sclerosis. Controls were 10 healthy subjects. BALF was collected during routine bronchoscopy from the right middle lobe. SLD was diagnosed by high resolution computed tomography of the lungs.BTG was detected in 11 of the patients with systemic sclerosis (29.7%) and PF4 was found in eight (21.6%). Mean (SD) concentrations of BTG and PF4 in BALF from patients with detectable levels of these platelet activation markers were 106.9 (69.8) and 35.2 (17.4) IU/ml, respectively. The BTG:PF4 ratio was more than 2:1, indicating in vivo release. Both markers were found exclusively in patients with SLD. SLD patients with detectable platelet activation markers had a significantly shorter disease duration than those with undetectable BTG/PF4.The study provides evidence that activation of blood platelets takes place within the lungs of patients with SLD and may contribute to the development of lung fibrosis.
Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial
Authors: L. Silvestri, H.K.F. van Saene, M. Milanese, F. Fontana, D. Gregori, L. Oblach, N. Piacente, M. Blazic
Journal: European Respiratory Journal (2004)

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for &gt;72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6‐h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus , is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus .
Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review
Authors: Veronique Peiffer, Spencer J. Sherwin, Peter D. Weinberg
Journal: Cardiovascular Research (2013)

Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data. We performed a systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterize the distribution of disease, and they have been compared with a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis.
Pulmonary Function of the Transplanted Human Lung
Authors: K D Dawkins, S W Jamieson
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis
Authors: D Ponce de Leon
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. <b>Objectives:</b> To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. <b>Methods:</b> 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD &lt;5 mm. <b>Results:</b> There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 <i>v</i> 11.5 mm, p&lt;0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p&lt;0.01), a response not influenced by disease activity or duration of disease in the patients with RA. <b>Conclusion:</b> A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.
Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study
Authors: Axel Bauer, Jan W Kantelhardt, Petra Barthel, Raphael Schneider, Timo Mäkikallio, Kurt Ulm, Katerina Hnatkova, Albert Schömig, Heikki Huikuri, Armin Bunde, Marek Malik, Georg Schmidt
Journal: The Lancet (2006)
DNA sequence comparisons of the human, mouse, and rabbit immunoglobulin kappa gene.
Authors: S Karlin, G Ghandour, D E Foulser
Journal: Molecular Biology and Evolution (1985)

A comparative analysis between human, mouse, and rabbit immunoglobulin (Ig) kappa-gene DNA sequences is presented. New formulas for determining the expected length and variance of the longest block identity (a succession of matching nucleotides) between multiple random sequences are given and are used to establish statistical criteria for ascertaining the significance of block identities shared in r out of s sequences. The statistically significant block identities within and between the Ig-kappa-gene sequences are ascertained, and alignment maps based on these similarities are constructed. The human and rabbit sequences (especially in the noncoding regions) and the human and mouse sequences (on the coding regions) show a similarity much stronger than that between the mouse and rabbit sequences. The existence of several highly significant shared oligonucleotides occurring in alignment with each other or with respect to the J- and C-gene segments suggests a configuration of multiple control sites. Discussion and interpretations of the form and distribution of the block identities are given.
DNA POLYMORPHISM OF HUMAN PORPHOBILINOGEN DEAMINASE GENE IN ACUTE INTERMITTENT PORPHYRIA
Authors: D.H. Llewellyn, N.A. Kalsheker, P.R. Harrison, C. Picat, P.H. Romeo, G.H. Elder, O.W.M. Marsh, B. Grandchamp, Y. Nordmann, M. Goossens
Journal: The Lancet (1987)
Measurement of Fibrinopeptide A in Human Blood
Authors: H. L. Nossel, I. Yudelman, R. E. Canfield, V. P. Butler, K. Spanondis, G. D. Wilner, G. D. Qureshi
Journal: Journal of Clinical Investigation (1974)

Since thrombin cleaves fibrinopeptides A (FPA) and B from the NH2-terminal end of the fibrinogen molecule, measurement of fibrinopeptide levels in plasma may provide a direct index of thrombin action. Recently a radioimmunoassay for FPA has been developed, and in the present paper, we describe the application of this assay to the measurement of FPA levels in clinical blood samples. Since fibrinogen cross-reacts with antibodies to FPA, dialysis was used to extract the peptide from plasma. In vitro generation of FPA was prevented by removing the fibrinogen from the plasma by precipitation with ethanol before dialysis. The processing technique permitted recovery of 75% of FPA added to blood in vitro. Evidence that the immunoreactivity measured in plasma is due to FPA was provided by the results of experiments in which two antisera to FPA with different specificities showed comparable results and addition of thrombin caused no change in immunoreactivity. In contrast, extracts of streptokinasetreated plasma showed a five-fold increase in activity when treated with thrombin and markedly different immunoreactivity with the two antisera.
Interleukin 4 (IL-4) or IL-7 Prevents the Death of Resting T Cells: Stat6 Is Probably Not Required for the Effect of IL-4
Authors: Anthony Vella, T. Kent Teague, James Ihle, John Kappler, Philippa Marrack
Journal: The Journal of Experimental Medicine (1997)

Although much is known about the activation, proliferation, and function of CD4+ T cells, little is known about how they survive as resting T cells in animals. Resting T cells have a half-life in animals of more than a week; however, when they are removed from animals and placed in tissue culture their half-life falls to ∼24 h. In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7). They may do this in part by maintaining levels of survival-promoting proteins such as Bcl-2 in the cells, because the levels of Bcl-2 and Bcl-Xl in resting T cells fall rapidly after the cells are isolated from animals, and are maintained by culture in IL-4. Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4– dependent T cell survival. Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner. These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.
The cascade of HIV care in British Columbia, Canada, 1996–2011: a population-based retrospective cohort study
Authors: Bohdan Nosyk, Julio S G Montaner, Guillaume Colley, Viviane D Lima, Keith Chan, Katherine Heath, Benita Yip, Hasina Samji, Mark Gilbert, Rolando Barrios, Réka Gustafson, Robert S Hogg
Journal: The Lancet Infectious Diseases (2013)
IFN-λ receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-λ3 genotype and with nonresponsiveness to IFN-α therapies
Authors: Francois H.T. Duong, Gaia Trincucci, Tujana Boldanova, Diego Calabrese, Benedetta Campana, Ilona Krol, Sarah C. Durand, Laura Heydmann, Mirjam B. Zeisel, Thomas F. Baumert, Markus H. Heim
Journal: The Journal of Experimental Medicine (2014)

The molecular mechanisms that link IFN-λ3 genotypes to differential induction of interferon (IFN)-stimulated genes (ISGs) in the liver of patients with chronic hepatitis C (CHC) are not known. We measured the expression of IFN-λ and of the specific IFN-λ receptor chain (IFN-λR1) in 122 liver biopsies of patients with CHC and 53 control samples. The IFN-λ3 genotype was not associated with differential expression of IFN-λ, but rather IFN-λR1. In a series of 30 primary human hepatocyte (PHH) samples, IFN-λR1 expression was low but could be induced with IFN-α. IFN-α–induced IFN-λR1 expression was significantly stronger in PHHs carrying the minor IFN-λ3 allele. The analysis of liver biopsies of patients with CHC revealed a strong association of high IFN-λR1 expression with elevated ISG expression, with IFN-λ3 minor alleles, and with nonresponse to pegylated IFN-α and ribavirin. The findings provide a missing link between the IFN-λ3 genotype and the associated phenotype of treatment nonresponse.
Periadventitial Adipose Tissue Plays a Critical Role in Vascular Remodeling
Authors: Minoru Takaoka, Daisuke Nagata, Shinji Kihara, Iichiro Shimomura, Yu Kimura, Yasuhiko Tabata, Yoshihiko Saito, Ryozo Nagai, Masataka Sata
Journal: Circulation Research (2009)

Rationale : Obesity is associated with a high incidence of cardiovascular complications. However, the molecular link between obesity and vascular disease is not fully understood. Most previous studies have focused on the association between cardiovascular disease and accumulation of visceral fat. Periadventitial fat is distributed ubiquitously around arteries throughout the body. Objective : Here, we investigated the impact of obesity on inflammation in the periadventitial adipose tissue and on lesion formation after vascular injury. Methods and Results : High-fat, high-sucrose feeding induced inflammatory changes and decreased adiponectin expression in the periadventitial adipose tissue, which was associated with enhanced neointima formation after endovascular injury. Removal of periadventitial fat markedly enhanced neointima formation after injury, which was attenuated by transplantation of subcutaneous adipose tissue from mice fed on regular chow. Adiponectin-deficient mice showed markedly enhanced lesion formation, which was reversed by local delivery, but not systemic administration, of recombinant adiponectin to the periadventitial area. The conditioned medium from subcutaneous fat attenuated increased cell number of smooth muscle cells in response to platelet derived growth factor-BB. Conclusions : Our findings suggest that periadventitial fat may protect against neointimal formation after angioplasty under physiological conditions and that inflammatory changes in the periadventitial fat may have a direct role in the pathogenesis of vascular disease accelerated by obesity.
Bankrolling Stem-Cell Research with California Dollars
Authors: Keith R. Yamamoto
Journal: New England Journal of Medicine (2004)

“The only possible source for adequate support of our medical schools and medical research is the taxing power of the Federal Government. Such a program must assure complete freedom for the institutions and the individual scientists in developing and conducting their research work.” These powerful assertions of responsibility — public funding of research at the national level and scientific prioritization by independent investigators — from U.S. Surgeon General Thomas Parran in 1945 presaged the peer-review, extramural grant-in-aid program that was established the following year within the National Institutes of Health (NIH). Of the 59 Nobel Prizes in Physiology or Medicine . . .
Beta-Cell Replacement for Type I Diabetes
Authors: Peter G. Stock, Jeffrey A. Bluestone
Journal: Annual Review of Medicine (2004)

The ability to achieve insulin independence with either solid-organ pancreas or islet transplantation has increased the number of patients seeking beta-cell replacement as an alternative to insulin therapy. Despite dramatic improvements in the ability to achieve insulin independence following solid-organ pancreas transplantation, the secondary complications of long-standing diabetes are frequently irreversible by the time surgical intervention is justified based on the risk of this procedure. Pancreatic islet transplantation provides a safer and less invasive alternative for beta-cell replacement that could be justified earlier in the course of diabetes to prevent the development of secondary complications. Recent advances in the technology of islet isolation, as well as the ability to prevent the alloimmune and recurrent autoimmune response following islet transplantation with immunosuppressive regimens that are not toxic to beta cells, have rekindled an interest in this field. Widespread application of islet transplantation will depend on further improvements in selective immunosuppression, development of immunologic tolerance, and finding new sources of beta cells.