tbuckley/cabot-search huggingface dataset:
Induction of rat facial nerve regeneration by functional collagen scaffolds
Authors: Jiani Cao, Zhifeng Xiao, Wei Jin, Bing Chen, Danqing Meng, Wenyong Ding, Sufang Han, Xiaoshan Hou, Tiansheng Zhu, Baoyu Yuan, Jing Wang, Weibang Liang, Jianwu Dai
Journal: Biomaterials (2012)
THE STAINING OF ANIMAL PARASITES
Authors: I. W. Hall
Journal: BMJ (1907)

ANIMAL PARASITES. LMARCH 9, 1907.jaws and much general muscular rigidity, and the patient was not fully convalescent till September 28th, two months and four days from the date of the accident.During the course of the illness the most prominent symptoms were rigidity of the muscles of the jaws, back, abdomen, and upper part of the thighs, accompanied by frequent clonic spasms at irregular intervals ; the muscles of the upper extremities were but little affected.Swallowing was accomplished with great difficulty, but fortunately the act of deglutition never failed completely.Tenacious mucus accumulated in the pharynx, causing much trouble and dis- tress.The bowels were constipated; urine passed without difficulty.Temperature varied-between 1010 and 1020, and on one occasion reached 1030.Pulse became very rapid, sometimes almost uncountable, and even when convalescence was fully established remained well over 80.From the third day and for seventeen subsequent days 20 c.cm. antitetanus serum were injected every twelve hours, till on August 20th the patient was able to open his mouth a little way, the spasms being also less frequent, so the dose of serum was reduced to 10 c.cm. twice in twenty-four hours; the
A Phase I Pharmacokinetic Study of HMN-214, a Novel Oral Stilbene Derivative with Polo-Like Kinase-1–Interacting Properties, in Patients with Advanced Solid Tumors
Authors: Linda L. Garland, Charles Taylor, Deborah L. Pilkington, Jan L. Cohen, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2006)

Abstract Purpose: HMN-214 is an oral prodrug of HMN-176, a stilbene derivative that interferes with the subcellular spatial location of polo-like kinase-1, a serine/threonine kinase that regulates critical mitotic events. We conducted a dose escalation study of HMN-214 in patients with advanced cancer to assess the safety profile and pharmacokinetics of HMN-214 and to establish the maximum tolerated dose. Experimental Design: Thirty-three patients were enrolled onto four dosing cohorts of HMN-214 from 3 to 9.9 mg/m2/d using a continuous 21-day dosing schedule every 28 days, with pharmacokinetic sampling during cycle 1. Results: A severe myalgia/bone pain syndrome and hyperglycemia were dose-limiting toxicities at 9.9 mg/m2/d. A dose reduction and separate enrollment by pretreatment status (lightly versus heavily pretreated) was undertaken, with one dose-limiting toxicity (grade 3 bone pain) at 8 mg/m2/d. The maximum tolerated dose was defined as 8 mg/m2/d for both treatment cohorts. Dose-proportional increases were observed in AUC but not Cmax. There was no accumulation of HMN-176, the metabolite of HMN-214, with repeated dosing. Seven of 29 patients had stable disease as best tumor response, including 6-month stable disease in a heavily pretreated breast cancer patient. A transient decline in carcinoembryonic antigen in a patient with colorectal cancer was noted. Conclusions: The maximum tolerated dose and recommended phase II dose of HMN-214 when administered on this schedule was 8 mg/m2/d regardless of pretreatment status. Further development of HMN-214 will focus on patient populations for which high expression of polo-like kinase-1 is seen (i.e., prostate and pancreatic cancer patients).
Metabolic Biotinylation of Recombinant Proteins in Mammalian Cells and in Mice
Authors: M.Brandon Parrott, Michael A. Barry
Journal: Molecular Therapy (2000)

The avidin–biotin system is a fundamental technology in biomedicine for immunolocalization, imaging, nucleic acid blotting, and protein labeling. While this technology is robust, it is limited by the fact that mammalian proteins must be expressed and purified prior to chemical biotinylation using cross-linking agents which modify proteins at random locations to heterogeneous levels and can inactivate protein function. To circumvent this limitation, we demonstrate the ability to metabolically biotinylate tagged proteins in mammalian cells and in mice using the endogenous biotinylation enzymes of the host. Endogenously biotinylated proteins were readily purified from mammalian cells using monomeric avidin and eluted under nondenaturing conditions using only biotin as the releasing agent. This technology should allow recombinant proteins and fragile protein complexes to be produced and purified from mammalian cells as well as from transgenic plants and animals. In addition, this technology may be particularly useful for cell-targeting applications in which proteins or viral gene therapy vectors can be biotinylated at genetically defined sites for combination with other targeting moieties complexed with avidin.
DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF NALOXONE ON MOTOR DEFICITS IN ACUTE CEREBROVASCULAR DISEASE
Authors: F. Perraro, G. Tosolini, F. Pertoldi, R. Sbrojavacca, A. Beorchia, A. Bulfoni, L.Del Fabbro, L. Grassi, A. Lestuzzi, V. Mione, V. Moretti, A. Moro
Journal: The Lancet (1984)
RNA-binding proteins to assess gene expression states of co-cultivated cells in response to tumor cells.
Authors: Luiz OF Penalva, Michael D Burdick, Simon M Lin, Hedwig Sutterluety, Jack D Keene
Journal: Molecular Cancer (2004)

Tumors and complex tissues consist of mixtures of communicating cells that differ significantly in their gene expression status. In order to understand how different cell types influence one another's gene expression, it will be necessary to monitor the mRNA profiles of each cell type independently and to dissect the mechanisms that regulate their gene expression outcomes.In order to approach these questions, we have used RNA-binding proteins such as ELAV/Hu, poly (A) binding protein (PABP) and cap-binding protein (eIF-4E) as reporters of gene expression. Here we demonstrate that the epitope-tagged RNA binding protein, PABP, expressed separately in tumor cells and endothelial cells can be used to discriminate their respective mRNA targets from mixtures of these cells without significant mRNA reassortment or exchange. Moreover, using this approach we identify a set of endothelial genes that respond to the presence of co-cultured breast tumor cells.RNA-binding proteins can be used as reporters to elucidate components of operational mRNA networks and operons involved in regulating cell-type specific gene expression in tissues and tumors.
TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas
Authors: O Defawe
Journal: Cardiovascular Research (2003)

Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or obstruction. These modifications have been ascribed to one or a group of proteases, their inhibitors or to the matrix macromolecules involved in the repair process without considering the extent of the observed variations.The mRNA steady-state level of a large spectrum of proteolytic enzymes (matrix metalloproteinases: MMP-1, -2, -3, -8, -9, -11, -12, -13, -14; urokinase plasminogen activator: u-PA), their physiological inhibitors (tissue inhibitors of MMPs: TIMP-1, -2, -3; plasminogen activator inhibitor: PAI-1) and that of structural matrix proteins (collagens type I and III, decorin, elastin, fibrillins 1 and 2) was determined by RT-PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture. The profile of expression was evaluated in AAA (n=7) and AOD (n=5) and compared to non-diseased abdominal (CAA, n=7) and thoracic aorta (CTA, n=5).The MMPs -8, -9, -12 and -13 mostly associated with inflammatory cells were not or barely detected in CAA and CTA while they were largely and similarly expressed in AAA and AOD. Expression of protease inhibitors or structural proteins were only slightly increased in both pathological conditions with the exception of elastin which was reduced. The main significant difference between AAA and AOD was a lower expression of TIMP-2 and PAI-1 in the aneurysmal lesions.The remodeling of the aortic wall in AAA and AOD involves gene activation of a large and similar spectrum of proteolytic enzymes while the expression of two physiological inhibitors, TIMP-2 and PAI-1, is significantly lower in AAA compared to AOD. The repair process in the aneurysmal disease seems similar to that of the occlusive disease.
Inhibition of matrix metalloproteinase-2 activity by propranolol in immunocompetent cells
Authors: Ftemeh Hajighasemi
Journal: European Respiratory Journal (2013)

Introduction:  Matrix metalloproteinases (MMPs) are a large group of proteases degredate the extracellular matrix proteins and have a major role in inflammation. Matrix metalloproteinase-2 (MMP-2) belongs to MMPs family plays an important role in some inflammatory mediated respiratory disorders such as chronic obstructive pulmonary disease (COPD) and asthma. Propranolol (a non selective beta-adrenergic blocker) has been widely used for treatment of several cardiovascular complications such as arterial hypertension and arrhythmias. Anti-inflammatory effects of propranolol have also been reported.   Objectives:  In this study the effect of propranolol on MMP-2 activity in human peripheral blood mononuclear cells (PBMCs) has been investigated in vitro.   Methods:  Human PBMCs were cultured in complete RPMI medium. The cells at logarhytmic growth phase were stimulated with phytoheamagglutinin (PHA) (at optimal concentration) and then incubated with different concentrations of propranolol (4 ×10 -7  - 4 ×10 -4  M) for 48 hours. The gelatinolytic activity of MMP-2 in cell culture supernatants was tested by zymography.   Results:  Propranolol significantly decreased the MMP-2 activity in PHA-stimulated human PBMCs dose-dependently compared to untreated control cells.   Conclusion:  According to the results of the present study propranolol down-regulates the MMP-2 activity in human PBMCs. Thus the anti-inflammatory effects of propranolol may be in part due to its inhibitory effects on MMP-2 activity. Therefore propranolol along with its long-term usage in cardiac problems might be a useful tool in planning of therapeutic approaches for inflammatory-based disorders such as COPD and asthma.
Transcription Factor 7-Like 2 (<i>TCF7L2</i>) Polymorphism and Hyperglycemia in an Adult Italian Population-Based Cohort
Authors: Roberto Gambino, Simona Bo, Luigi Gentile, Giovanni Musso, Gianfranco Pagano, Paolo Cavallo-Perin, Maurizio Cassader
Journal: Diabetes Care (2009)

OBJECTIVE To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control. RESEARCH DESIGN AND METHODS Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort. RESULTS At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for β-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35–3.20] and 3.56 [2.11–5.98] in CT and TT genotypes, respectively). CONCLUSIONS The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.
Predictors of recovery of ovarian function during aromatase inhibitor therapy
Authors: N.L. Henry, R. Xia, M. Banerjee, C. Gersch, D. McConnell, D. Giacherio, A.F. Schott, M. Pearlman, V. Stearns, A.H. Partridge, D.F. Hayes
Journal: Annals of Oncology (2013)
Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function.
Authors: D L Eizirik, G S Korbutt, C Hellerström
Journal: Journal of Clinical Investigation (1992)

The aim of the present study was to clarify whether prolonged in vitro exposure of human pancreatic islets to high glucose concentrations impairs the function of these cells. For this purpose, islets isolated from adult cadaveric organ donors were cultured for seven days in RPMI 1640 medium supplemented with 10% fetal calf serum and containing either 5.6, 11, or 28 mM glucose. There was no glucose-induced decrease in islet DNA content or signs of morphological damage. However, islets cultured at 11 or 28 mM glucose showed a 45 or 60% decrease in insulin content, as compared to islets cultured at 5.6 mM glucose. Moreover, when such islets were submitted to a 60-min stimulation with a low (1.7 mM) followed by a high (16.7 mM) concentration of glucose, the islets cultured at 5.6 mM glucose showed a higher insulin response to glucose than those of the two other groups. Islets cultured at the two higher glucose concentrations showed increased rates of insulin release in the presence of low glucose, and a failure to enhance further the release in response to an elevated glucose level. Islets cultured at 28 mM glucose showed an absolute decrease in insulin release after stimulation with 16.7 mM glucose, as compared to islets cultured at 5.6 mM glucose. The rates of glucose oxidation, proinsulin biosynthesis, and total protein biosynthesis were similar in islets cultured at 5.6 or 11 mM glucose, but they were decreased in islets cultured at 28 mM glucose. These combined results suggest that lasting exposure to high glucose concentrations impairs the function of human pancreatic islets.
Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway
Authors: Rafael Cubas, Sheng Zhang, Min Li, Changyi Chen, Qizhi Yao
Journal: Molecular Cancer (2010)

Abstract Background Trop2 is a cell-surface glycoprotein overexpressed by a variety of epithelial carcinomas with reported low to restricted expression in normal tissues. Expression of Trop2 has been associated with increased tumor aggressiveness, metastasis and decreased patient survival, but the signaling mechanisms mediated by Trop2 are still unknown. Here, we studied the effects murine Trop2 (mTrop2) exerted on tumor cellular functions and some of the signaling mechanisms activated by this oncogene. Results mTrop2 expression significantly increased tumor cell proliferation at low serum concentration, migration, foci formation and anchorage-independent growth. These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27. The activation of ERK was also observed in human pancreatic ductal epithelial cells and colorectal adenocarcinoma cells overexpressing human Trop2. Conclusions These findings demonstrate some of the pathogenic effects mediated by mTrop2 expression on cancer cells and the importance of targeting this cell surface glycoprotein. This study also provides the first indication of a molecular signaling pathway activated by Trop2 which has important implications for cancer cell growth and survival.
Faecal fat excretion after truncal, selective, and highly selective vagotomy for duodenal ulcer
Authors: J. P. Edwards, P. J. Lyndon, R. B. Smith, D. Johnston
Journal: Gut (1974)

Faecal fat excretion was measured on a metabolic ward in 16 patients with duodenal ulcer before operation, and in patients who were in good health more than one year after truncal vagotomy and pyloroplasty (n = 11), bilateral selective vagotomy and pyloroplasty (n = 9), or highly selective vagotomy without a drainage procedure (HSV, n = 12). Excretion of faecal fat was significantly greater (p &lt; 0·01) in patients after both truncal and selective vagotomy with drainage than in patients before operation. Fat excretion in HSV patients was little different from that of preoperative patients. If steatorrhoea is defined as a faecal fat output of more than 6 g per day, one of 16 preoperative patients with duodenal ulcer (6%) had steatorrhoea, one of 12 HSV patients (8%) had steatorrhoea, one of nine patients after selective vagotomy and pyloroplasty (11%) had steatorrhoea but five of 11 patients after truncal vagotomy and pyloroplasty (45%) had steatorrhoea.
Pressure-activated cation channel in intact rat endocardial endothelium
Authors: R Köhler
Journal: Cardiovascular Research (1998)

Objective: The endocardial endothelium (EE) regulates myocardial performance in response to humoral and mechanical stimuli. In vascular endothelium mechanosensitive ion channels (MSC) act as mechanosensors for hemodynamic changes. In the present study we examined whether MSC are present in intact EE of rat papillary muscle segments and characteristics of MSC are altered in experimental hypertension. Methods: MSC were investigated by the use of standard patch-clamp technique. For a comparative study, ion channel characteristics were determined in EE of two-kidney-one-clip rats and sham-operated controls. Results: We identified a new class of MSC with a mean conductance of 21.8±4.4 (s.d.) pS for K+ and Na+ and of 4.1±1.5 pS for Ca2+. Channel activity was initiated by positive pipette pressure and blocked by negative pipette pressure. Channel open probability (Po) was characterized by its pressure sensitivity. Po increased from 0.06 at 10 mmHg to 0.37 and 0.55 at 20 mmHg and 30 mmHg, respectively. Gadolinium (20 μM), a blocker of MSC, completely inhibited channel activity. In some experiments activation of this pressure-activated channel (PAC) was followed by the opening of a Ca2+-dependent non-selective cation channel (NSC). This indicates that Ca2+ influx through PAC may be sufficient to increase intracellular Ca2+ concentration and thereby to activate neighboring NSC. In renovascular hypertension (2K1C), channel density of PAC was significantly increased compared to sham-operated controls. Channel density of NSC was not changed in 2K1C compared to sham-operated controls. Conclusion: A novel type of Ca2+ permeable MSC in intact EE of rat ventricular papillary muscle was identified, which is regulated by membrane pressure. PAC might be implicated in EE mechanotransduction by inducing an intracellular Ca2+ signal. Up-regulation of PAC density in EE from 2K1C might contribute to an altered mechanotransduction in hypertension.
Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells
Authors: Shizuko Sei, Jodie K Mussio, Quan-en Yang, Kunio Nagashima, Ralph E Parchment, Matthew C Coffey, Robert H Shoemaker, Joseph E Tomaszewski
Journal: Molecular Cancer (2009)

Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC). ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell lines examined, with the 50% effective dose, defined as the initial virus dose to achieve 50% cell killing after 48 hours of infection, ranging from 1.46 ± 0.12 ~2.68 ± 0.25 (mean ± SD) log10 pfu/cell. Chou-Talalay analysis of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine demonstrated strong synergistic effects on cell killing, but only in cell lines that were sensitive to these compounds. In contrast, the combination of ReoT3D and paclitaxel was invariably synergistic in all cell lines tested, regardless of their levels of sensitivity to either agent. Treatment of NSCLC cell lines with the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose) polymerase cleavage and caspase activity compared to single therapy, indicating enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated with the ReoT3D-paclitaxel combination showed increased proportions of mitotic and apoptotic cells, and a more pronounced level of caspase-3 activation was demonstrated in mitotically arrested cells. These data suggest that the oncolytic activity of ReoT3D can be potentiated by taxanes and other chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively achieves synergy through accelerated apoptosis triggered by prolonged mitotic arrest.
Dermoscopic pattern in facial trichilemmomas: Red iris-like structure
Authors: Celia Horcajada-Reales, José Antonio Avilés-Izquierdo, Cristina Ciudad-Blanco, Elena Conde-Montero, Verónica Parra-Blanco, Pablo Lázaro-Ochaita, Ricardo Suárez-Fernández
Journal: Journal of the American Academy of Dermatology (2014)
The Influence of CKD on Colonic Microbial Metabolism
Authors: Ruben Poesen, Karen Windey, Ellen Neven, Dirk Kuypers, Vicky De Preter, Patrick Augustijns, Patrick D’Haese, Pieter Evenepoel, Kristin Verbeke, Björn Meijers
Journal: Journal of the American Society of Nephrology (2015)

There is increasing interest in the colonic microbiota as a relevant source of uremic retention solutes accumulating in CKD. Renal disease can also profoundly affect the colonic microenvironment and has been associated with a distinct colonic microbial composition. However, the influence of CKD on the colonic microbial metabolism is largely unknown. Therefore, we studied fecal metabolite profiles of hemodialysis patients and healthy controls using a gas chromatography-mass spectrometry method. We observed a clear discrimination between both groups, with 81 fecal volatile organic compounds detected at significantly different levels in hemodialysis patients and healthy controls. To further explore the differential impact of renal function loss per se versus the effect of dietary and other CKD-related factors, we also compared fecal metabolite profiles between patients on hemodialysis and household contacts on the same diet, which revealed a close resemblance. In contrast, significant differences were noted between the fecal samples of rats 6 weeks after 5/6th nephrectomy and those of sham-operated rats, still suggesting an independent influence of renal function loss. Thus, CKD associates with a distinct colonic microbial metabolism, although the effect of renal function loss per se in humans may be inferior to the effects of dietary and other CKD-related factors. The potential beneficial effect of therapeutics targeting colonic microbiota in patients with CKD remains to be examined.
Abdominal Pain Caused by Diabetic Radiculopathy
Authors: GEORGE F. LONGSTRETH
Journal: Annals of Internal Medicine (1977)

In diabetes mellitus, pain and weakness in a lower extremity can result from lumbosacral radiculopathy. However, abdominal pain caused by a similar type of thoracic nerve root disease is not generally recognized. Four diabetic patients with abdominal pain were studied. In none of the patients was the actual cause—radiculopathy—suspected until after extensive negative diagnostic investigation, which frequently included invasive procedures. Their clinical features were suggestive of malignant disease. Electromyographic examination revealed the correct diagnosis, and all four of the patients had a spontaneous and complete recovery.