tbuckley/cabot-search huggingface dataset:
Collagen–platelet interaction: Gly-Pro-Hyp is uniquely specific for platelet Gp VI and mediates platelet activation by collagen
Authors: C Knight
Journal: Cardiovascular Research (1999)

Peptides consisting of a repeat Gly-Pro-Hyp sequence are potent platelet agonists. The aim of this study was: (1) to examine the specificity of this sequence for platelet activation; (2) to confirm its recognition by platelet glycoprotein VI; and (3) to assess with suitable peptides the relative importance of glycoprotein VI and integrin alpha 2 beta 1 in platelet activation by collagen.Peptides were synthesized by standard Fmoc chemistry and tested for their ability to support adhesion of human platelets and HT 1080 cells, induce platelet aggregation, bind integrin alpha 2 subunit A-domain and to cause tyrosine phosphorylation of platelet proteins.(1) Peptides consisting of a repeat Gly-Pro-Pro, Gly-Pro-Ala or Gly-Pro-Arg sequence exhibited little if any platelet-reactivity. (2) The platelet-reactive peptide consisting of a repeating Gly-Pro-Hyp sequence failed to induce tyrosine phosphorylation in glycoprotein VI-deficient platelets. Platelet adhesion to this peptide was inhibited by intact anti-glycoprotein VI antibody and its Fab fragment. The latter inhibited aggregation by the peptide and fibres of both collagens I and III. (3) A peptide containing a 15-mer alpha 2 beta 1-binding sequence in a repeat Gly-Pro-Pro structure supported alpha 2 beta 1-mediated platelet and HT 1080 cell adhesion and bound alpha 2 A-domain, but failed to activate platelets or to induce tyrosine phosphorylation. Conversely, a peptide containing this sequence but with an essential Glu replaced by Ala and inserted in a repeat Gly-Pro-Hyp structure did not recognize alpha 2 beta 1, but was highly platelet activatory.Platelet activation by collagen involves the highly-specific recognition of the Gly-Pro-Hyp sequence by platelet glycoprotein VI. Recognition of alpha 2 beta 1 is insufficient to cause activation. Interaction between collagen and glycoprotein VI is unique since Gly-Pro-Hyp is common in collagens but occurs rarely in other proteins, and glycoprotein VI may be expressed solely by platelets. This sequence could provide a basis for a highly-specific anti-thrombotic reagent to control thrombosis associated with plaque rupture.
Abstract 1639: Targeting the p38 MAPK pathway inhibits irinotecan resistance in colon adenocarcinoma
Authors: Salomé Paillas, Florence Boissiere, Frederic Bibeau, Caroline Mollevi, Annick Causse, Vincent Denis, Nadia Vezzio-Vié, Imade Ait-Arsa, Philippe Pourquier, Pierre Martineau, Maguy Del Rio, Céline Gongora
Journal: Cancer Research (2011)

Abstract Despite recent advances in the treatment of colon cancer, tumor resistance is a frequent cause of chemotherapy failure. To better elucidate the molecular mechanisms involved in resistance to irinotecan (and its active metabolite SN38), we established SN38-resistant clones derived from the colon adenocarcinoma HCT-116 and SW48 cell lines. These clones show various levels (6 to 60 fold) of resistance to SN-38 and display enhanced levels of activated MAPK p38 as compared to the corresponding parental cells. Because four different isoforms of p38 have been described, we then studied the effect of p38 overexpression or downregulation of each isoform on cell sensivity to SN38 and found that both alpha and beta isoforms are involved in the development of resistance to SN38. In this line, we show that cell treatment with SB202190, which specifically inhibits p38 alpha and beta, enhanced the cytotoxic activity of SN38, but not of 5-FU or oxaliplatin. Moreover, p38 inhibition sensitized tumor cells derived from both SN38-sensitive and -resistant HCT116 cells to irinotecan treatment in xenograft models. Finally, we detected less phosphorylated p38 in primary colon cancer of patients sensitive to irinotecan-based treatment, compared to non-responder patients. This indicates that enhanced level of expression of phosphorylated p38 could predict the absence of clinical response to irinotecan. Altogether, our results show for the first time that the p38 MAPK pathway is involved in irinotecan sensitivity and suggest that phosphorylated p38 expression level could be used as a marker of clinical resistance to irinotecan. They further suggest that targeting the p38 pathway may be a potential strategy to overcome resistance to irinotecan-based chemotherapies in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1639. doi:10.1158/1538-7445.AM2011-1639
Comparative evaluation of hepatitis C virus RNA quantitation by branched DNA, NASBA, and monitor assays
Authors: Françoise Lunel, Pascale Cresta, Damien Vitour, Christopher Payan, Bruno Dumont, Lionel Frangeul, Dorothée Reboul, Christine Brault, Jean-Charles Piette, Jean-Marie Huraux
Journal: Hepatology (1999)

Several studies have shown a relationship between pretreatment hepatitis C virus (HCV) viral load and the response to interferon (IFN) therapy, creating a need for quantitative HCV–RNA assays. Here, we compared three commercial methods: nucleic acid sequence-based amplification NASBA (Organon), branched DNA 2.0 (bDNA) (Chiron), and Monitor (Roche), with reverse–transcription polymerase chain reaction (RT–PCR) as the reference. We assessed sensitivity and reproducibility on a well–characterized panel of sera (EUROHEP), a Chimp Rodney plasma pool, and samples from IFN–treated and –untreated patients with chronic hepatitis C caused by different HCV genotypes. The reproducibility of the NASBA and bDNA methods was slightly better than that of Monitor, especially for genotypes 2 and 4. NASBA had the highest sensitivity (99% vs. 94% and 88% with Monitor and bDNA, respectively), especially for the follow–up of patients on IFN. NASBA gave the highest HCV–RNA concentrations, which were approximately 10–fold more than with the bDNA assay and 100–fold more than with the Monitor kit. The linearity, tested on the chimp Rodney plasma pool, was better with bDNA for high viral load than with NASBA and Monitor, although for low concentration of HCV RNA, bDNA was negative. Pretreatment viral load was lower in patients who had a sustained virological response to IFN, although the bDNA method was not sensitive enough to quantify all pretreatment samples. This study indicates that gene amplification methods (NASBA or Monitor) have better sensitivity than bDNA assays for quantification of HCV RNA in patients with chronic HCV infection, although the bDNA and NASBA methods are more likely to quantify all genotypes. Prospective studies are needed to demonstrate the usefulness of quantitative assays for the follow–up of patients with chronic hepatitis C
Statewide Study of Chloramphenicol Therapy and Fatal Aplastic Anemia
Authors: Ralph O. Wallerstein
Journal: JAMA (1969)

Fatal aplastic anemia is a rare disorder, occurring in two per million population each year. Death usually follows overwhelming infection or hemorrhage, or both. The course from onset of anemia to death is often only a few months. Fatal aplastic anemia appeared to be 13 times more frequent after the use of chloramphenicol. Anemia may not appear until the second or even third course of chloramphenicol therapy, and it is not related to dosage.
Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus.
Authors: K Tanaka, H Nakazawa, K Okada, K Umezawa, N Fukuyama, Y Koga
Journal: Journal of Clinical Investigation (1997)

4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite.
Corneal Topography of Excimer Laser Photorefractive Keratectomy Using a 6-mm Beam Diameter
Authors: Peter S. Hersh, Shetal I. Shah, Marc Michelson, John Owen, Michael Gordon, Roger Steinert, Carmen Puliafito, Helen Wu, Michael Raizman, Jay Pepose, Daniel Durrie, Timothy Cavanaugh, John Hunkeler
Journal: Ophthalmology (1997)
Survival After Out-of-Hospital Cardiac Arrest in Relation to Age and Early Identification of Patients With Minimal Chance of Long-Term Survival
Authors: Mads Wissenberg, Fredrik Folke, Carolina Malta Hansen, Freddy K. Lippert, Kristian Kragholm, Bjarke Risgaard, Shahzleen Rajan, Lena Karlsson, Kathrine Bach Søndergaard, Steen M. Hansen, Rikke Normark Mortensen, Peter Weeke, Erika Frischknecht Christensen, Søren L. Nielsen, Gunnar H. Gislason, Lars Køber, Christian Torp-Pedersen
Journal: Circulation (2015)

Survival after out-of-hospital cardiac arrest has increased during the last decade in Denmark. We aimed to study the impact of age on changes in survival and whether it was possible to identify patients with minimal chance of 30-day survival.Using data from the nationwide Danish Cardiac Arrest Registry (2001─2011), we identified 21 480 patients ≥18 years old with a presumed cardiac-caused out-of-hospital cardiac arrest for which resuscitation was attempted. Patients were divided into 3 preselected age-groups: working-age patients 18 to 65 years of age (33.7%), early senior patients 66 to 80 years of age (41.5%), and late senior patients >80 years of age (24.8%). Characteristics in working-age patients, early senior patients, and late senior patients were as follows: witnessed arrest in 53.8%, 51.1%, and 52.1%; bystander cardiopulmonary resuscitation in 44.7%, 30.3%, and 23.4%; and prehospital shock from a defibrillator in 54.7%, 45.0%, and 33.8% (all P<0.05). Between 2001 and 2011, return of spontaneous circulation on hospital arrival increased: working-age patients, from 12.1% to 34.6%; early senior patients, from 6.4% to 21.5%; and late senior patients, from 4.0% to 15.0% (all P<0.001). Furthermore, 30-day survival increased: working-age patients, 5.8% to 22.0% (P<0.001); and early senior patients, 2.7% to 8.4% (P<0.001), whereas late senior patients experienced only a minor increase (1.5% to 2.0%; P=0.01). Overall, 3 of 9499 patients achieved 30-day survival if they met 2 criteria: had not achieved return of spontaneous circulation on hospital arrival and had not received a prehospital shock from a defibrillator.All age groups experienced a large temporal increase in survival on hospital arrival, but the increase in 30-day survival was most prominent in the young. With the use of only 2 criteria, it was possible to identify patients with a minimal chance of 30-day survival.
High Circulating Retinol-Binding Protein 4 Is Associated With Elevated Liver Fat but Not With Total, Subcutaneous, Visceral, or Intramyocellular Fat in Humans
Authors: Norbert Stefan, Anita M. Hennige, Harald Staiger, Jürgen Machann, Fritz Schick, Erwin Schleicher, Andreas Fritsche, Hans-Ulrich Häring
Journal: Diabetes Care (2007)

Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured circulating RBP4 in 75 healthy subjects and used state-of-the-art measurements of body fat distribution.Total body, visceral, and subcutaneous abdominal fat were determined by magnetic resonance tomography and liver fat and intramyocellular fat by localized proton magnetic resonance spectroscopy. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp and, together with insulin clearance, estimated from the oral glucose tolerance test (OGTT).Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r = -0.33, P = 0.005; OGTT: r = -0.36, P = 0.002) and positively with parameters in the fasting state as insulin levels (r = 0.35, P = 0.003) and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.004). In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r = -0.25, P = 0.04). Circulating RBP4 was not associated with total body, visceral, or subcutaneous abdominal fat (all P > or = 0.29). Plasma RBP4 levels were also not associated with intramyocellular fat or circulating adiponectin or leptin. In contrast, plasma RBP4 levels correlated positively with liver fat in cross-sectional (r = 0.27, P = 0.03) and longitudinal (r = 0.37, P = 0.04) analyses.Circulating RBP4 is not associated with the amount of fat in the classical depots or in the ectopic depots in muscle. However, it correlates positively with liver fat. Furthermore, metabolic parameters support the close relationship between circulating RBP4 with liver fat and, presumably, hepatic insulin resistance.
Letter by Hnid and Chtioui Regarding Article, “Clinical Events as a Function of Proton Pump Inhibitor Use, Clopidogrel Use, and Cytochrome P450 2C19 Genotype in a Large Nationwide Cohort of Acute Myocardial Infarction: Results From the French Registry of Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) Registry”
Authors: Karim Hnid, Mamoun Chtioui
Journal: Circulation (2011)
CpG Island Methylator Phenotype Association with Elevated Serum α-Fetoprotein Level in Hepatocellular Carcinoma
Authors: Changsong Zhang, Zhengyou Li, Yue Cheng, Fengqi Jia, Rong Li, Mengchao Wu, Ke Li, Lixin Wei
Journal: Clinical Cancer Research (2007)

Abstract Purpose: CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumor-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC). Experimental Design: We examined the promoter methylation status of nine genes in 50 HCCs, 50 paired nontumor tissues, and 6 normal liver tissues by methylation-specific PCR. CIMP+ was defined as having five genes that are concordantly methylated. Results: The frequency of promoter methylation of nine genes in 50 HCCs varied from 10% in P53 to 94% in c-Myc. The methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and nontumor tissues (P &amp;lt; 0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent in HCC than in nontumor tissues (70% and 12%, P &amp;lt; 0.001). There is a significant association between CIMP and methylation of P14, P15, P16, ER, RSAAF1A, and WT1 (P &amp;lt; 0.05) and serum α-fetoprotein (AFP) level (P = 0.017). CIMP+ was more frequent in HCC with AFP ≥ 30 μg/L than those with AFP &amp;lt; 30 μg/L (P = 0.005). In addition, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (P &amp;lt; 0.05). Conclusions: Positive correlation of CIMP and AFP levels in HCC suggests that CIMP can serve as a molecular marker of late-stage HCC development.
AMBLYOPIA FROM SUPPRESSION, CONGENITAL IMPERFECTION OR DISUSE: WHICH OR ALL?
Authors: LEARTUS CONNOR
Journal: JAMA (1898)

Since different writers use the term "amblyopia ex anopsia" to express radically diverse ideas, it is needful to define its meaning in this discussion. Negatively it is not applied to a dulness of vision induced either by an organic lesion, which can be objectively seen with the ophthalmoscope or otherwise; nor by exclusion of light from the retina, in part or whole, during long periods; nor by defective refraction or disturbed muscular equilibrium of either ciliary, rectus or oblique muscles. Positively it is applied to that dulness of vision which attends the inability of the brain to recognize impressions sent it from the retina. As to the nature and causes of the dulled vision, we have three widely differing views. The first contends that the brain actively inhibits the visual center from receiving impressions, until it loses its receptive power in whole or part; the second says that the brain
Classification of Newly Diagnosed Diabetic Patients as Insulin-Requiring or Non—Insulin-Requiring Based on Clinical and Biochemical Variables
Authors: Ole Hother-Nielsen, Ole Faber, Niels Schwartz Sørensen, Henning Beck-Nielsen
Journal: Diabetes Care (1988)

In a prospective study of 41 consecutively referred newly diagnosed diabetic patients, we evaluated the predictive value of fasting and glucagon-stimulated C-peptide values, ketonuria, age, and body weight in the classification of subjects as insulin-requiring (IR) or non-insulin-requiring (NIR). The patients were followed up for ≥12 mo and classified as NIR if adequate glycemic control could be achieved without insulin (i.e., fasting plasma glucose &amp;lt; 8 mM and no glycosuria). Patients who needed insulin to obtain this status were classified as IR. We found that all subjects with plasma C-peptide values &amp;gt;0.60 nM 6 min after intravenous glucagon were NIR, whereas all IR subjects together with 3 NIR subjects had C-peptide values below this limit. All NIR subjects but 1 had fasting C-peptide values &amp;gt; 0.30 nM, and all IR subjects but 1 had C-peptide values below this limit. Seventy-five percent of the subjects could be correctly classified by use of age and percent desirable body weight. Thus, all subjects &amp;gt; 40 yr old and &amp;gt;100% ideal body weight were NIR, and all subjects below both these limits were IR. Ketonuria was found in 10 of 12 IR subjects and in 10 of 29 NIR subjects. We conclude that 1) 75% of the subjects could be correctly classified by use of age and percent desirable body weight only and 2) C-peptide measurements are useful in the classification of newly diagnosed diabetes, whereas presence of ketonuria is of limited value.
Ethics, the Constitution, and the Dying Process
Authors: Lawrence O. Gostin
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Preparation of berberine hydrochloride long-circulating liposomes by ionophore A23187-mediated ZnSO4 gradient method
Authors: Xiang Luo, Jing Li, Ligang Guo, Xiaobo Cheng, Ting Zhang, Yihui Deng
Journal: Asian Journal of Pharmaceutical Sciences (2013)

The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters, and investigate the influence of different factors on the encapsulation efficiency. Berberine hydrochloride liposomes were prepared in response to a transmembrane ion gradient that was established by ionophore A23187. Free and liposomal drug were separated by cation exchange resin, and then the amount of intraliposomal berberine hydrochloride was determined by UV spectrophotometry. The optimized encapsulation efficiency of berberine hydrochloride liposomes was 94.3% ± 2.1% when the drug-to-lipid ratio was 1:20, and the mean diameter was 146.9 nm ± 3.2 nm. As a result, the ionophore A23187-mediated ZnSO4 gradient method was suitable for the preparation of berberine hydrochloride liposomes that we could get the desired encapsulation efficiency and drug loading.
Pioglitazone in chronic hepatitis C not responding to pegylated interferon-α and ribavirin
Authors: Kathrin Overbeck, Daniel Genné, Alain Golay, Francesco Negro
Journal: Journal of Hepatology (2008)

Insulin resistance reduces the response to interferon alfa-based therapy of chronic hepatitis C patients. It has been speculated that improvement of insulin sensitivity might increase the chances of responding to treatment of such individuals.We started a multicenter clinical trial of retreatment of chronic hepatitis C patients, who had failed to respond to the pegylated interferon alfa/ribavirin combination, with a triple therapy consisting in these same antivirals plus an insulin-sensitizer (pioglitazone) (The INSPIRED-HCV study).None of the first five patients fulfilling the inclusion criteria and included in the trial achieved a satisfactory virological response after 12 weeks of retreatment, despite the fact that in at least three of them the insulin resistance score improved. As a result, the study was terminated.Different schedules are warranted to improve insulin sensitivity prior to attempting retreatment of chronic hepatitis C patients with insulin resistance.