tbuckley/cabot-search huggingface dataset:
Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling
Authors: Toshinori Ueno, Ayumu Nakashima, Shigehiro Doi, Takeshi Kawamoto, Kiyomasa Honda, Yukio Yokoyama, Toshiki Doi, Yukihito Higashi, Noriaki Yorioka, Yukio Kato, Nobuoki Kohno, Takao Masaki
Journal: Kidney International (2013)

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have regenerative capability and exert paracrine actions on damaged tissues. Since peritoneal fibrosis is a serious complication of peritoneal dialysis, we tested whether MSCs suppress this using a chlorhexidine gluconate model in rats. Although MSCs isolated from green fluorescent protein-positive rats were detected for only 3 days following their injection, immunohistochemical staining showed that MSCs suppressed the expression of mesenchymal cells, their effects on the deposition of extracellular matrix proteins, and the infiltration of macrophages for 14 days. Moreover, MSCs reduced the functional impairment of the peritoneal membrane. Cocultures of MSCs and human peritoneal mesothelial cells using a Transwell system indicated that the beneficial effects of MSCs on the glucose-induced upregulation of transforming growth factor-β1(TGF-β1) and fibronectin mRNA expression in the human cells were likely due to paracrine actions. Preincubation in MSC-conditioned medium suppressed TGF-β1-induced epithelial-to-mesenchymal transition, α-smooth muscle actin, and the decrease in zonula occludens-1 in cultured human peritoneal mesothelial cells. Although bone morphogenic protein 7 was not detected, MSCs secreted hepatocyte growth factor and a neutralizing antibody to this inhibited TGF-β1 signaling. Thus, our findings imply that MSCs ameliorate experimental peritoneal fibrosis by suppressing inflammation and TGF-β1 signaling in a paracrine manner.
International Union of Pharmacology. XVII. Classification of Muscarinic Acetylcholine Receptors
Authors: M P Caulfield, N J Birdsall
Journal: Pharmacological Reviews (1998)

Actions of acetylcholine in the periphery are the result of activation of either the ionotropic nicotinic receptor or the metabotropic muscarinic receptor. In the mammalian central nervous system (CNS)c, both nicotinic and muscarinic receptor subtypes are present on neurons, although there is as yet
Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome
Authors: Saeed Shoaie, Pouyan Ghaffari, Petia Kovatcheva-Datchary, Adil Mardinoglu, Partho Sen, Estelle Pujos-Guillot, Tomas de Wouters, Catherine Juste, Salwa Rizkalla, Julien Chilloux, Lesley Hoyles, Jeremy K. Nicholson, Joel Dore, Marc E. Dumas, Karine Clement, Fredrik Bäckhed, Jens Nielsen
Journal: Cell Metabolism (2015)
Regression of polyvinylchloride polymer pneumoconiosis
Authors: N. W. White, R. I. Ehrlich
Journal: Thorax (1997)

A 35 year old man heavily exposed to polyvinylchloride (PVC) polymer dust developed dyspnoea and a mild restrictive lung disorder consistent with PVC pneumoconiosis. Clinical and radiological abnormalities cleared on removal from exposure, suggesting that in its early stages PVC pneumoconiosis is reversible.
A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents
Authors: Karen Dineen Wagner, Adelaide S Robb, Robert L Findling, Jianqing Jin, Marcelo M Gutierrez, William E Heydorn
Journal: American Journal of Psychiatry (2004)

Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression.An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28.The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group.In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated.
Protein Hydrolysate/Leucine Co-Ingestion Reduces the Prevalence of Hyperglycemia in Type 2 Diabetic Patients
Authors: Ralph J.F. Manders, Stephan F.E. Praet, Ruth C.R. Meex, René Koopman, André L. de Roos, Anton J.M. Wagenmakers, Wim H.M. Saris, Luc J.C. van Loon
Journal: Diabetes Care (2006)

Epidemiological surveys and preliminary intervention studies have shown that postprandial hyperglycemia is a direct and independent risk factor for the development of cardiovascular disease in type 2 diabetes (1–4). Moreover, it has been reported that postprandial spikes in blood glucose concentration are even more relevant to the onset of cardiovascular complications than merely elevated fasting blood glucose levels (5–7).

Protein hydrolysate/leucine coingestion could represent an effective nutritional intervention to stimulate postprandial insulin secretion, augment postprandial blood glucose disposal, and improve blood glucose homeostasis in type 2 diabetic patients (8–10). Though promising, the clinical relevance and applicability of such a nutritional intervention remains to be established.

In the present study, we applied continuous glucose monitoring to assess the impact of protein hydrolysate/leucine coingestion with each main meal as a nutritional intervention strategy to improve daily glycemic control in long-standing type 2 diabetic patients.

Eleven long-standing type 2 diabetic patients (aged 58 ± 1 years, BMI 28 ± 1 kg/m2, HbA1c 7.4 ± 0.3%) and 11 matched healthy control subjects (aged 59 ± 2 years, BMI 28 ± 1 kg/m2, HbA1c 5.5 ± 0.1%) participated in this study. All subjects were screened for type 2 diabetes according to American Diabetes Association guidelines (11). Type 2 diabetic patients …
Physiological Risk Factors for Severe High-Altitude Illness
Authors: Jean-Paul Richalet, Philippe Larmignat, Eric Poitrine, Murielle Letournel, Florence Canouï-Poitrine
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness.To assess, in a large cohort of subjects, the association between physiological parameters and the risk of altitude illness and their discrimination ability in a risk prediction model.A total of 1,326 persons went through a hypoxic exercise test before a sojourn above 4,000 m. They were then monitored up at high altitude and classified as suffering from severe high-altitude illness (SHAI) or not. Analysis was stratified according to acetazolamide use.Severe acute mountain sickness occurred in 314 (23.7%), high-altitude pulmonary edema in 22 (1.7%), and high-altitude cerebral edema in 13 (0.98%) patients. Among nonacetazolamide users (n = 917), main factors independently associated with SHAI were previous history of SHAI (adjusted odds ratios [aOR], 12.82; 95% confidence interval [CI], 6.95-23.66; P < 0.001), ascent greater than 400 m/day (aOR, 5.89; 95% CI, 3.78-9.16; P < 0.001), history of migraine (aOR, 2.28; 95% CI, 1.28-4.07; P = 0.005), ventilatory response to hypoxia at exercise less than 0.78 L/minute/kg (aOR, 6.68; 95% CI, 3.83-11.63; P < 0.001), and desaturation at exercise in hypoxia equal to or greater than 22% (aOR, 2.50; 95% CI, 1.52-4.11; P < 0.001). The last two parameters improved substantially the discrimination ability of the multivariate prediction model (C-statistic rose from 0.81 to 0.88; P < 0.001). Preventive use of acetazolamide reduced the relative risk of SHAI by 44%.In a large population of altitude visitors, chemosensitivity parameters (high desaturation and low ventilatory response to hypoxia at exercise) were independent predictors of severe high-altitude illness. They improved the discrimination ability of a risk prediction model.
Nonlinear Exercise Training in Advanced Chronic Obstructive Pulmonary Disease Is Superior to Traditional Exercise Training. A Randomized Trial
Authors: Peter Klijn, Anton van Keimpema, Monique Legemaat, Rik Gosselink, Henk van Stel
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The optimal exercise training intensity and strategy for individualized exercise training in chronic obstructive pulmonary disease (COPD) is not clear.This study compares the effects of nonlinear periodized exercise (NLPE) training used in athletes to traditional endurance and progressive resistance (EPR) training in patients with severe COPD.A total of 110 patients with severe COPD (FEV1 32% predicted) were randomized to EPR or NLPE. Exercise training was performed three times per week for 10 weeks. The primary outcomes were cycling endurance time and health-related quality of life using the Chronic Respiratory Questionnaire. The difference in change between EPR and NLPE was assessed using linear mixed-effects modeling.NLPE resulted in significantly greater improvements in cycling endurance time compared with EPR. The difference in change was +300.6 seconds (95% confidence interval [CI] = 197.2-404.2 s; P < 0.001). NLPE also resulted in significantly greater improvements in all domains of the Chronic Respiratory Questionnaire compared with EPR, ranging from +0.48 (95% CI = 0.19-0.78) for the domain, emotions, to +0.96 (95% CI = 0.57-1.35) for dyspnea.NLPE results in greater improvements in cycle endurance and health-related quality of life in patients with severe COPD than traditional training methods. Clinical trial registered with www.trialregister.nl (The Netherlands Trial Register; NTR 1045).
Role of atrial electrophysiology and autonomic nervous system in patients with supraventricular tachycardia and paroxysmal atrial fibrillation
Authors: Yi-Jen Chen, Shih-Ann Chen, Ching-Tai Tai, Zu-Chin Wen, An-Ning Feng, Yu-An Ding, Mau-Song Chang
Journal: Journal of the American College of Cardiology (1998)
Acetaldehyde substoichiometrically inhibits bovine neurotubulin polymerization.
Authors: S L Smith, R B Jennett, M F Sorrell, D J Tuma
Journal: Journal of Clinical Investigation (1989)

Acetaldehyde is known to form covalent adducts with tubulin and to inhibit microtubule formation. Available evidence indicates that lysine residues are prominently involved in adduct formation. Previous work has shown that lysines on tubulin can be divided into two general classes based upon their reactivity toward acetaldehyde; those of normal reactivity ("bulk" lysines) and a highly reactive lysine (HRL) located on the alpha-polypeptide subunit. We took advantage of the fact that the HRL is unreactive when tubulin is in the microtubule form to differentiate the effects of bulk from HRL adducts on tubulin polymerization. Under conditions where both bulk lysines and HRL formed adducts, 0.2 mol acetaldehyde/mol tubulin caused complete inhibition of polymerization. When we modified bulk lysines, but not HRL, tubulin polymerized essentially normally. Finally, when we first blocked bulk lysines on microtubules (HRL unreactive) using unlabeled acetaldehyde and then measured the amount of [14C]acetaldehyde adduct formed with tubulin after depolymerization (HRL reactive), 0.08 mol acetaldehyde/mol tubulin resulted in completely impaired polymerization. These data show that microtubule formation is very sensitive to even small mole fractions of acetaldehyde-modified tubulin (especially with HRL) and further suggest that small amounts of acetaldehyde adduct could be damaging to cytoskeleton function in the cell.
Identifying genes that regulate bone remodeling as potential therapeutic targets
Authors: Stephen M. Krane
Journal: The Journal of Experimental Medicine (2005)

Bone remodeling, a coupled process involving bone resorption and formation, is initiated by mechanical signals and is controlled by local and systemic factors that regulate osteoblast and osteoclast differentiation and function. An excess of resorption over formation leads to the bone loss and increased propensity to fracture that is characteristic of osteoporosis. A newly described inhibitor of osteoblast differentiation, Ciz, interferes with bone morphogenic protein signaling. As a consequence, Ciz-deficient mice develop increased bone mass.
Multi-Institutional Study of Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis After Allogeneic Bone Marrow Transplantation Using Myeloablative Busulfan and Fludarabine Conditioning
Authors: Christopher G. Kanakry, Paul V. O'Donnell, Terry Furlong, Marcos J. de Lima, Wei Wei, Marta Medeot, Marco Mielcarek, Richard E. Champlin, Richard J. Jones, Peter F. Thall, Borje S. Andersson, Leo Luznik
Journal: Journal of Clinical Oncology (2014)

Purpose The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Patients and Methods Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. Results The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). Conclusion This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors.
Breast Cancer Stem Cells: Something Out of Notching?
Authors: Hannah Harrison, Gillian Farnie, Keith R. Brennan, Robert B. Clarke
Journal: Cancer Research (2010)

We and others have established that the developmental Notch receptor signaling pathway is active in breast cancer cell lines, as well as in preinvasive and invasive primary samples. Recently, a role for Notch in regulating the hierarchy of stem and progenitor cells in both normal and cancer epithelium has been elucidated. Because inhibiting the Notch receptor signaling pathway is a possible future breast cancer therapy, here, we review the expression and activity of the different ligands and receptors and summarize the various ways in which the pathway's activity can be inhibited, and the likely effects of inhibition on different tumor cell subpopulations.
A Transposable Element-Mediated Gene Divergence that Directly Produces a Novel Type Bovine Bcnt Protein Including the Endonuclease Domain of RTE-1
Authors: S. Iwashita
Journal: Molecular Biology and Evolution (2003)

Ruminant Bcnt protein with a molecular mass of 97 kDa (designated p97Bcnt) includes a region derived from the endonuclease domain of a retrotransposable element RTE-1. Human and mouse Bcnt proteins lack the corresponding region but have a highly conserved 82-amino acid region at the C-terminus that is not present in p97Bcnt. By screening a bovine BAC library, we found two more bcnt-related genes: human-type bcnt (h-type bcnt) and its processed pseudogene. Whereas the pseudogene is localized on chromosome 26, both bcntp97 and the h-type bcnt genes are found on bovine chromosome 18, a synteny region of human chromosome 16 on which human BCNT is localized. Complete nucleotide sequencing of the BAC clone reveals that the bcntp97 and h-type bcnt genes are located just 6 kb apart in a tandem manner. The two h-type bcnt and bcntp97genes are active at both the transcriptional level and the protein level. H-type bovine Bcnt is more like human BCNT than p97Bcnt, when compared at their N-terminal regions. However, phylogenetic analysis using the N-terminal region of the bcnt gene family revealed that the duplication of bovine genes occurred within the bovine lineage with significantly accelerated substitution in bcntp97. This acceleration was not ascribed definitely to positive selection. After duplication, one of the bovine bcnt genes recruited the endonuclease domain of an intronic RTE-1 repeat accompanied by the accelerated substitution at the 5'-ORF, resulting in creation of a novel type of Bcnt protein in bovine.
Fertility in Women With Type 1 Diabetes
Authors: Junmei Miao Jonasson, Kerstin Brismar, Pär Sparén, Mats Lambe, Olof Nyrén, Claes-Göran Östenson, Weimin Ye
Journal: Diabetes Care (2007)

The purpose of this study was to assess fertility in women with type 1 diabetes and the risk of congenital malformations in their offspring.This was a register-based cohort study in Sweden. All 5,978 women hospitalized for type 1 diabetes at age <or=16 years identified in the Swedish Inpatient Register during 1965-2004 were followed until the end of 2004 through linkage to nationwide registers. A standardized fertility ratio (SFR), the ratio of observed to expected number of live births, with 95% CIs, was used to express the relative fertility rate. The proportion of newborns with congenital malformations was compared with that of the general population.We observed 4,013 live births (SFR 0.80 [95% CI 0.77-0.82]). The SFRs for those who had retinopathy, nephropathy, neuropathy, or cardiovascular complications were 0.63, 0.54, 0.50, and 0.34, respectively. Stratified analyses by year of first hospitalization showed that the reduced fertility was confined to women first hospitalized before 1985, but the presence of complications was associated with subfertility in all calendar-year strata. The proportions of newborns with congenital malformations decreased from 11.7% during 1973-1984 to 6.9% during 1995-2004 but were consistently higher than the corresponding figures for the general population.Women with type 1 diabetes have reduced fertility, but it appears that normalization has occurred among women with uncomplicated disease and an onset in the past 20 years. Our results suggest that the stricter metabolic control exercised in the past 20 years may have helped prevent subfertility. However, although the risk of congenital malformations has decreased, it is still higher than that for the general population.
Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity
Authors: Tae Heung Kang, Kyung Hee Noh, Jin Hee Kim, Hyun Cheol Bae, Ken Y. Lin, Archana Monie, Sara I. Pai, Chien-Fu Hung, T.-C. Wu, Tae Woo Kim
Journal: Cancer Research (2010)

Abstract Tumor immune escape is a major obstacle in cancer immunotherapy, but the mechanisms involved remain poorly understood. We have previously developed an immune evasion tumor model using an in vivo immune selection strategy and revealed Akt-mediated immune resistance to antitumor immunity induced by various cancer immunotherapeutic agents. In the current study, we used microarray gene analysis to identify an Akt-activating candidate molecule overexpressed in immune-resistant tumors compared with parental tumors. X-linked lymphocyte-regulated protein pM1 (XLR) gene was the most upregulated in immune-resistant tumors compared with parental tumor cells. Furthermore, the retroviral transduction of XLR in parental tumor cells led to activation of Akt, resulting in upregulation of antiapoptotic proteins and the induction of immune resistance phenotype in parental tumor cells. In addition, we found that transduction of parental tumor cells with other homologous genes from the mouse XLR family, such as synaptonemal complex protein 3 (SCP3) and XLR-related, meiosis-regulated protein (XMR) and its human counterpart of SCP3 (hSCP3), also led to activation of Akt, resulting in the upregulation of antiapoptotic proteins and induction of immune resistance phenotype. Importantly, characterization of a panel of human cervical cancers revealed relatively higher expression levels of hSCP3 in human cervical cancer tissue compared with normal cervical tissue. Thus, our data indicate that ectopic expression of XLR and its homologues in tumor cells represents a potentially important mechanism for tumor immune evasion and serves as a promising molecular target for cancer immunotherapy. Cancer Res; 70(8); 3062–70. ©2010 AACR.