tbuckley/cabot-search huggingface dataset:
Gene expression in nephrotoxic and ischemic acute renal failure.
Authors: R Safirstein
Journal: Journal of the American Society of Nephrology (1994)

The commitment to DNA synthesis by the kidney to recovery from ischemic and nephrotoxic acute renal failure is accompanied by a pattern of gene expression that bears a striking resemblance to that exhibited by growth factor-stimulated cells in culture. Prominent among them is the expression of the immediate early genes that code for transcriptional factors that are rapidly and briefly expressed well before the onset of DNA synthesis. Other genes are activated that code for small secreted peptides. These proteins have cytokine-like activity that may be involved in the recruitment and activation of other cells that serve the regenerative response in some way. The expression of several additional genes, which are relatively kidney specific and developmentally regulated, are actually reduced during renal failure, suggesting that the commitment to DNA synthesis by the kidney may require dedifferentiation. Many different cell types participate in the increased DNA synthesis provoked by ischemic and nephrotoxic damage, including tubule cells removed from the site of greatest injury, as well as those outside of the tubule compartment, suggesting that paracrine, autocrine, and juxtacrine factors support the growth-promoting process. A prominent site of altered gene expression during acute renal failure is the thick ascending limb, which undergoes both positive and negative changes in expression and which seems to be a prominent site of reaction to nephrotoxic stimuli at the molecular level. Studying the interaction between the regulatory sequences of a select group of genes with their transactivating factors and the transduction pathways that activate them should identify the initial growth-promoting signal and the subsequent steps leading to renal regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
Trichome Distribution in Arabidopsis thaliana and its Close Relative Arabidopsis lyrata: Molecular Analysis of the Candidate Gene GLABROUS1
Authors: M T Hauser, B Harr, C Schlötterer
Journal: Molecular Biology and Evolution (2001)

GLABROUS1 (GL1) belongs to the large family of MYB transcription factors and is known to play a central role in trichome initiation. We studied trichome distribution and the molecular variation of GL1 in 28 A. thaliana accessions. Trichome density on rosette leaves was highly variable among those accessions. On the molecular level, we detected substantial sequence variation in a 3-kb fragment which included the complete coding region of the GL1 locus (π = 0.01). Phylogenetic analysis of GL1 indicates the presence of two diverged clades among 28 accessions. Using ANOVA, we show that the phenotypic variation in trichome density cannot be explained by the sequence divergence between the two phylogenetic lineages. Sequence analysis of wild-type Arabidopsis thaliana and Arabidopsis lyrata accessions indicates that all amino acid substitutions are located outside of the conserved helix-turn-helix DNA-binding domains R2 and R3. Using plants of A. thaliana and A. lyrata with either naturally occurring or ethyl methane sulfonate–induced glabrous phenotypes, we demonstrate that the last 14 C-terminal amino acids of the GL1 gene have no major impact on the initiation of trichomes.
Evaluation and Treatment of Patients With Systemic Hypertension
Authors: Jay Garg, Adrian W. Messerli, George L. Bakris
Journal: Circulation (2002)

65-year-old man presented for evaluation of high blood pressure found on screening at a local health fair.History and physical examination did not show any signs or symptoms suggestive of a secondary cause, nor was there evidence of target end-organ damage except for grade 1 Keith-Wagener-Barker retinopathy.The patient denied taking any prescription or over-the-counter medications.Hypertension is the most common disease-specific reason Americans visit a physician.Despite the risks associated with an elevated blood pressure (BP), there is still woefully low achievement of recommended BP goals.From 1991 to 1994, only 27.4% of hypertensive Americans aged 18 to 74 years had a BP Ͻ140/90 mm Hg, the current stated goal for most people with hypertension, and in those with diabetes, less than half that number (11%) were controlled to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI (JNC VI) recommended goal of Ͻ130/85 mm Hg. 1 The present update will provide an overview of the evaluation and management of essential hypertension and help to guide clinicians in developing a management plan for a patient like the one described above.
Rescue of human RET gene expression by sodium butyrate: a novel powerful tool for molecular studies in Hirschsprung disease
Authors: P Griseri
Journal: Gut (2003)

The RET gene encodes a tyrosine kinase receptor involved in different human neurocristopathies, such as specific neuroendocrine tumours and Hirschsprung disease (HSCR). Gene expression is developmentally regulated and the RET transcript is undetectable in most adult cells, including lymphocytes. The impossibility of performing functional studies on RET mRNA has to date limited the detection and characterisation of an indefinite proportion of gene anomalies that cannot be identified by conventional DNA genomic screening in HSCR cases.Development of a protocol suitable to activate RET expression in RET negative cell lines and therefore to investigate directly RET mRNA, extending the conventional gene mutation analysis to detection of splicing anomalies and impaired expression of the RET gene.The effect of sodium butyrate (NaB), a histone deacetylase inhibitor, on rescuing RET expression was tested by one round of reverse transcription- polymerase chain reaction from total RNA of treated lymphoblasts from both HSCR patients and control individuals.Analysis of RET expression was possible by NaB treatment of RET negative cells, such as lymphoblasts. This treatment allowed us to detect impaired RET expression as well as a splicing defect in two HSCR patients previously believed to be devoid of any gene abnormality.The full application of the proposed protocol in most of the unexplained HSCR cases will allow us to establish the precise role of RET not only in causing but also in predisposing to HSCR pathogenesis.
Attention Bias Modification Treatment for Pediatric Anxiety Disorders: A Randomized Controlled Trial
Authors: Sharon Eldar, Alan Apter, Daniel Lotan, Koraly Perez Edgar, Reut Naim, Nathan A. Fox, Daniel S. Pine, Yair Bar-Haim
Journal: American Journal of Psychiatry (2011)

While attention bias modification (ABM) is a promising novel treatment for anxiety disorders, clinical trial data remain restricted to adults. The authors examined whether ABM induces greater reductions in pediatric anxiety symptoms and symptom severity than multiple control training interventions.
Challenges to the Development of New Agents for Molecularly Defined Patient Subsets: Lessons From <i>BRCA1/2</i>-Associated Breast Cancer
Authors: Susan M. Domchek, Gillian Mitchell, Geoffrey J. Lindeman, Nadine M. Tung, Judith Balmaña, Steven J. Isakoff, Rita Schmutzler, M. William Audeh, Niklas Loman, Clare Scott, Michael Friedlander, Bella Kaufman, Judy E. Garber, Andrew Tutt, Mark E. Robson
Journal: Journal of Clinical Oncology (2011)

Susan M. Domchek, University of Pennsylvania School of Medicine, Philadelphia, PA Gillian Mitchell, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Geoffrey J. Lindeman, Walter and Eliza Hall Institute of Medical Research and Royal Melbourne Hospital, Melbourne, Victoria, Australia Nadine M. Tung, Beth Israel/Deaconess Medical Center, Boston, MA Judith Balmana, Vall d’Hebron University Hospital, Barcelona, Spain Steven J. Isakoff, Massachusetts General Hospital, Boston, MA Rita Schmutzler, University of Cologne, Cologne, Germany M. William Audeh, Cedars Sinai Medical Center, Los Angeles, CA Niklas Loman, Skane University Hospital, Malmo, Sweden Clare Scott, Walter and Eliza Hall Institute of Medical Research and Royal Melbourne Hospital, Melbourne, Victoria, Australia Michael Friedlander, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia Bella Kaufman, The Chaim Sheba Medical Center, Tel Aviv, Israel Judy E. Garber, Dana-Farber Cancer Institute, Boston, MA Andrew Tutt, Guy’s Hospital, King’s Health Partners Academic Health Sciences Centre, London, United Kingdom Mark E. Robson, Memorial Sloan-Kettering Cancer Center, New York, NY
Induction of pulmonary connective tissue growth factor in heart failure is associated with pulmonary parenchymal and vascular remodeling
Authors: M AHMED, E OIE, L VINGE, T VONLUEDER, T ATTRAMADAL, H ATTRAMADAL
Journal: Cardiovascular Research (2006)

Pulmonary remodeling is a well recognized consequence of heart failure (HF). However, the cellular and molecular mechanisms orchestrating the structural alterations of the lungs in HF are poorly understood. We have previously reported induction of the profibrotic peptide connective tissue growth factor (CTGF) in myocardial tissue of rats with HF, suggesting a role of CTGF during myocardial remodeling. The aim of the present study was to explore the potential role of CTGF in pulmonary remodeling in HF.Pulmonary tissue samples were obtained from rats with myocardial infarction (MI) subsequent to ligation of the left coronary artery. Real-time quantitative RT-PCR was employed to investigate mRNA levels. The cellular distribution of CTGF was analysed by immunohistochemistry.Seven days after induction of myocardial infarction (MI) and HF in rats we found 2.3-fold and 1.9-fold increase of pulmonary transforming growth factor-beta1 and procollagen alpha1(I) mRNA levels, respectively, and typical morphological characteristics of pulmonary remodeling including interstitial fibrosis and medial thickening of pulmonary arteries. Pulmonary CTGF mRNA levels were substantially elevated in HF rats compared to sham-operated rats (4-fold; P<0.05) and corresponded with similar increase (3-fold; P<0.05) of pulmonary CTGF protein contents. Immunohistochemical analysis revealed increased pulmonary anti-CTGF immunoreactivity in HF, with immunostaining predominantly localized to alveolar macrophages and interstitial fibroblasts. Isolated alveolar macrophages from HF rats demonstrated substantial induction of CTGF mRNA expression (16-fold; p<0.05). Interestingly, platelets caused robust induction of CTGF mRNA expression in alveolar macrophages upon co-culture in vitro.Pulmonary CTGF was substantially increased in parallel with pulmonary remodeling in rats with HF. Our data indicate that alveolar macrophages are a major source of increased pulmonary CTGF in HF and that CTGF may be a player in the profibrotic mechanisms associated with HF.
Terminal Differentiation of Epithelia from Trophectoderm to the Intercalated Cell
Authors: Qais Al-Awqati, Soundarapandian Vijayakumar, Jiro Takito
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The intercalated cells of the collecting tubules of mammalian kidneys were discovered by Haggege and Richet to change their morphology in response to a variety of physiologic stimuli related to changes in acid base status. Recent studies showed that the conversion of β to α intercalated cell under the influence of acidification of the medium is due to the deposition of hensin in the extracellular matrix of these cells and activation of a novel inductive signal transduction pathway. The conversion of β to α cells is shown to be a process of terminal differentiation. Hensin is secreted as a monomer, and activation of the cell induces two activities that convert it to a dimer by folding and into a fiber by bundling of the folded dimers by galectin 3. Only the fiber is functional. Hensin is expressed in most epithelial cells, and its staining pattern suggests that it might be involved in the terminal differentiation of most epithelia. There is loss of heterozygosity of hensin in a large number of epithelial and neural tumors, making it likely that it is a tumor suppressor gene. E-mail: qa1@columbia.edu
Intravenous atrial natriuretic peptide prevents left ventricular remodeling in patients with first anterior acute myocardial infarction
Authors: Masaru Hayashi, Takayoshi Tsutamoto, Atsuyuki Wada, Keiko Maeda, Naoko Mabuchi, Takashi Tsutsui, Hajime Horie, Masato Ohnishi, Masahiko Kinoshita
Journal: Journal of the American College of Cardiology (2001)
The overall structure of the multi-domain amyloid precursor protein
Authors: Ina Coburger, Sven O Dahms, Manuel E Than
Journal: Molecular Neurodegeneration (2013)

Background The amyloid precursor protein (APP) is a type I transmembrane protein that is expressed in a wide number of different cell types. Proteolytic processing by betaand gamma-secretases releases 38-43 amino acid long peptides, so called Ab amyloid peptides that accumulate within the plaques in the brain of Alzheimer s disease patients. Alternatively, initiation of the proteolysis cascade by alpha-secretase prevents the development of these toxic peptides [1,2]. In spite of intense research regarding the involvement of APP in Alzheimer s disease, The three-dimensional structure of the entire protein, its physiologic function and the regulation of its proteolytic processing remain, however, largely unclear to date [3].
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Inhibits TGF-β–Mediated Plasminogen Activator Inhibitor-1 Expression via Inhibition of Smad Pathway in Human Mesangial Cells
Authors: Keizo Kanasaki, Daisuke Koya, Toshiro Sugimoto, Motohide Isono, Atsunori Kashiwagi, Masakazu Haneda
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Recent large clinical trials indicate that angiotensin-converting enzyme inhibitors (ACE-I) attenuate the detrimental outcome of progressive renal disease. The hemoregulatory tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP, AcSDKP) is hydrolyzed by ACE, and plasma Ac-SDKP level is increased by fivefold after treatment with ACE-I. Ac-SDKP was found to ameliorate cardiac and renal fibrosis in hypertensive animal models. However, the molecular mechanisms by which Ac-SDKP mediates anti-fibrotic effects remain unclear. This study is an examination of the interaction between Ac-SDKP and transforming growth factor-β (TGF-β), one of the key cytokines in the progression of renal disease, in human mesangial cells. Ac-SDKP inhibited TGF-β1–induced plasminogen activator inhibitor-1 (PAI-1) and alpha2 (I) collagen mRNA. Ac-SDKP suppressed not only TGF-β1–induced Smad2 phosphorylation at Ser-465/467 in a dose-dependent manner, but also the nuclear accumulation of receptor-regulated Smads (R-Smad), Smad2 and Smad3. As expected, Ac-SDKP inhibited TGF-β–responsive Smad-dependent luciferase reporters, 3TP-luc and 4xSBE-luc. Immunofluorescence analysis revealed that the inhibitory Smad, Smad7, was exported to the cytoplasm from the nucleus by the treatment with Ac-SDKP. These findings provide novel evidence that Ac-SDKP inhibits TGF-β signal transduction through the suppression of R-Smad activation via nuclear export of Smad7, highlighting an alternative mechanism involved in the reno-protective efficacy of ACE-I. E-mail: [email protected]
Association of Different Adverse Life Events With Distinct Patterns of Depressive Symptoms
Authors: Matthew C Keller, Michael C Neale, Kenneth S Kendler
Journal: American Journal of Psychiatry (2007)

Objective: The authors sought to determine whether, in a general population sample, different categories of adverse life events were associated with different patterns of depressive symptoms. Method: A total of 4,856 individuals (53% female) who experienced depressive symptoms in the previous year were assessed in up to four waves over a maximum of 12 years. At each wave, participants reported the severity of 12 symptoms disaggregated from the nine DSM-III-R criteria for major depression and the self-identified cause of these symptoms, which were classified into nine categories of adverse life events. Results: The patterns of depressive symptoms associated with the nine categories of adverse life events differed significantly. Deaths of loved ones and romantic breakups were marked by high levels of sadness, anhedonia, appetite loss, and (for romantic breakups) guilt. Chronic stress and, to a lesser degree, failures were associated with fatigue and hypersomnia, but less so with sadness, anhedonia, and appetite loss. Those who reported that no adverse life events caused their dysphoric episodes reported fatigue, appetite gain, and thoughts of self-harm, but less sadness or trouble concentrating. These symptom patterns were found in a between-persons analysis of participants who had a single dysphoric episode, and they were replicated in an independent within-persons analysis of episode-specific symptom deviations among individuals with multiple episodes. Similar results were obtained when the sample was restricted to those meeting DSM-III-R diagnostic criteria for major depression. Conclusions: Depression is a pathoplastic syndrome. Different types of life events are related to different depressive symptom profiles. The results from the within-persons analysis suggest that these relationships are causal.
Postprandial serum C-peptide to plasma glucose concentration ratio correlates with oral glucose tolerance test- and glucose clamp-based disposition indexes
Authors: Yoko Okuno, Hisako Komada, Kazuhiko Sakaguchi, Tomoaki Nakamura, Naoko Hashimoto, Yushi Hirota, Wataru Ogawa, Susumu Seino
Journal: Metabolism (2013)
The Expanding Pharmacopoeia for Bipolar Disorder
Authors: Philip B. Mitchell, Gin S. Malhi
Journal: Annual Review of Medicine (2002)

▪ Abstract Over the past decade, the number of treatments available for bipolar disorder has undergone an extraordinary expansion. In that period, valproate and olanzapine have received regulatory approval in the United States for the acute treatment of mania, and carbamazepine has been indicated for this condition in many other countries. In addition to those agents, a number of other anticonvulsants (in particular lamotrigine, gabapentin, and topiramate) are in trials, as are the atypical antipsychotics clozapine and risperidone, and other novel compounds. This article critically reviews the evidence from controlled trials of these proposed “mood stabilizers,” highlighting the strengths and limitations of the data for each compound. A major challenge to the field is the capacity to prove the prophylactic properties of agents for which effectiveness in acute mania and/or bipolar depression has been demonstrated. Finally, as the mechanisms of agents such as lithium are now becoming apparent, and the possibility of understanding the molecular defects underpinning the condition is no longer highly fanciful, the prospect of targeted therapies is considered feasible by both academia and the pharmaceutical industry.
Variation in Prevalence of Gestational Diabetes Mellitus Among Hospital Discharges for Obstetric Delivery Across 23 States in the United States
Authors: Barbara H. Bardenheier, Anne Elixhauser, Giuseppina Imperatore, Heather M. Devlin, Elena V. Kuklina, Linda S. Geiss, Adolfo Correa
Journal: Diabetes Care (2012)

To examine variability in diagnosed gestational diabetes mellitus (GDM) prevalence at delivery by race/ethnicity and state.We used data from the Healthcare Cost and Utilization Project State Inpatient Databases for 23 states of the United States with available race/ethnicity data for 2008 to examine age-adjusted and race-adjusted rates of GDM by state. We used multilevel analysis to examine factors that explain the variability in GDM between states.Age-adjusted and race-adjusted GDM rates (per 100 deliveries) varied widely between states, ranging from 3.47 in Utah to 7.15 in Rhode Island. Eighty-six percent of the variability in GDM between states was explained as follows: 14.7% by age; 11.8% by race/ethnicity; 5.9% by insurance; and 2.9% by interaction between race/ethnicity and insurance at the individual level; 17.6% by hospital level factors; 27.4% by the proportion of obese women in the state; 4.3% by the proportion of Hispanic women aged 15-44 years in the state; and 1.5% by the proportion of white non-Hispanic women aged 15-44 years in the state.Our results suggest that GDM rates differ by state, with this variation attributable to differences in obesity at the population level (or "at the state level"), age, race/ethnicity, hospital, and insurance.
Pathogen-specific T Regulatory 1 Cells Induced in the Respiratory Tract by a Bacterial Molecule that Stimulates Interleukin 10 Production by Dendritic Cells
Authors: Peter McGuirk, Chantelle McCann, Kingston H.G. Mills
Journal: The Journal of Experimental Medicine (2002)

Antigen-specific T helper type 1 (Th1) cells mediate protective immunity against a range of infectious diseases, including that caused by Bordetella pertussis. Distinct T cell subtypes that secrete interleukin (IL)-10 or tumor growth factor (TGF)-β are considered to play a role in the maintenance of self-tolerance. However, the antigens recognized by these regulatory T cells in vivo have not been defined. Here we provide the first demonstration of pathogen-specific T regulatory type 1 (Tr1) cells at the clonal level and demonstrate that these cells are induced at a mucosal surface during an infection where local Th1 responses are suppressed. Tr1 clones specific for filamentous hemagglutinin (FHA) and pertactin were generated from the lungs of mice during acute infection with B. pertussis. The Tr1 clones expressed T1/ST2 and CC chemokine receptor 5, secreted high levels of IL-10, but not IL-4 or interferon (IFN)-γ, and suppressed Th1 responses against B. pertussis or an unrelated pathogen. Furthermore, FHA inhibited IL-12 and stimulated IL-10 production by dendritic cells (DCs), and these DCs directed naive T cells into the regulatory subtype. The induction of Tr1 cells after interaction of a pathogen-derived molecule with cells of the innate immune system represents a novel strategy exploited by an infectious pathogen to subvert protective immune responses in vivo.
Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis
Authors: Bettina Heidecker, Michelle M. Kittleson, Edward K. Kasper, Ilan S. Wittstein, Hunter C. Champion, Stuart D. Russell, Ralph H. Hruban, E. Rene Rodriguez, Kenneth L. Baughman, Joshua M. Hare
Journal: Circulation (2011)

Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures.Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy.Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.