tbuckley/cabot-search huggingface dataset:
Translational Profiles of Medullary Myofibroblasts during Kidney Fibrosis
Authors: Ivica Grgic, A. Michaela Krautzberger, Andreas Hofmeister, Matthew Lalli, Derek P. DiRocco, Susanne V. Fleig, Jing Liu, Jeremy S. Duffield, Andrew P. McMahon, Bruce Aronow, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2014)

Myofibroblasts secrete matrix during chronic injury, and their ablation ameliorates fibrosis. Development of new biomarkers and therapies for CKD will be aided by a detailed analysis of myofibroblast gene expression during the early stages of fibrosis. However, dissociating myofibroblasts from fibrotic kidney is challenging. We therefore adapted translational ribosome affinity purification (TRAP) to isolate and profile mRNA from myofibroblasts and their precursors during kidney fibrosis. We generated and characterized a transgenic mouse expressing an enhanced green fluorescent protein (eGFP)-tagged L10a ribosomal subunit protein under control of the collagen1α1 promoter. We developed a one-step procedure for isolation of polysomal RNA from collagen1α1-eGFPL10a mice subject to unilateral ureteral obstruction and analyzed and validated the resulting transcriptional profiles. Pathway analysis revealed strong gene signatures for cell proliferation, migration, and shape change. Numerous novel genes and candidate biomarkers were upregulated during fibrosis, specifically in myofibroblasts, and we validated these results by quantitative PCR, in situ, and Western blot analysis. This study provides a comprehensive analysis of early myofibroblast gene expression during kidney fibrosis and introduces a new technique for cell-specific polysomal mRNA isolation in kidney injury models that is suited for RNA-sequencing technologies.
Venom-Related Transcripts from Bothrops jararaca Tissues Provide Novel Molecular Insights into the Production and Evolution of Snake Venom
Authors: Inácio L.M. Junqueira-de-Azevedo, Carolina Mancini Val Bastos, Paulo Lee Ho, Milene Schmidt Luna, Norma Yamanouye, Nicholas R. Casewell
Journal: Molecular Biology and Evolution (2014)

Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins.
Parity: An Ongoing Challenge and Research Opportunity
Authors: Dennis McCarty
Journal: American Journal of Psychiatry (2013)

Until recently, health plans typically imposed higher co-pays and limited benefits for treatment of mental health and substance abuse disorders.The co-pays and benefit restrictions discouraged unnecessary use of services and reduced the health plans' economic risks (1;2).After many years of seeking comprehensive reforms in these discriminatory policies, mental health and substance abuse advocates succeeded when Congress passed the Mental Health Parity and Addiction Equity Act of 2008.The legislation prohibits health plans that include behavioral health benefits from imposing greater quantitative limits (e.g., co-pays and limits on the amount of care) and more restrictive non-quantitative limits (e.g., pre-authorization) for mental health and substance abuse disorders relative to the benefits provided for general health care -parity.
Effects of 1α,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells
Authors: Wei-Lin W Wang, Namita Chatterjee, Sridar V Chittur, JoEllen Welsh, Martin P Tenniswood
Journal: Molecular Cancer (2011)

There is evidence from epidemiological and in vitro studies that the biological effects of testosterone (T) on cell cycle and survival are modulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer. To investigate the cross talk between androgen- and vitamin D-mediated intracellular signaling pathways, the individual and combined effects of T and 1,25(OH)2D3 on global gene expression in LNCaP prostate cancer cells were assessed.Stringent statistical analysis identifies a cohort of genes that lack one or both androgen response elements (AREs) or vitamin D response elements (VDREs) in their promoters, which are nevertheless differentially regulated by both steroids (either additively or synergistically). This suggests that mechanisms in addition to VDR- and AR-mediated transcription are responsible for the modulation of gene expression. Microarray analysis shows that fifteen miRNAs are also differentially regulated by 1,25(OH)2D3 and T. Among these miR-22, miR-29ab, miR-134, miR-1207-5p and miR-371-5p are up regulated, while miR-17 and miR-20a, members of the miR-17/92 cluster are down regulated. A number of genes implicated in cell cycle progression, lipid synthesis and accumulation and calcium homeostasis are among the mRNA targets of these miRNAs. Thus, in addition to their well characterized effects on transcription, mediated by either or both cognate nuclear receptors, 1,25(OH)2D3 and T regulate the steady state mRNA levels by modulating miRNA-mediated mRNA degradation, generating attenuation feedback loops that result in global changes in mRNA and protein levels. Changes in genes involved in calcium homeostasis may have specific clinical importance since the second messenger Ca2+ is known to modulate various cellular processes, including cell proliferation, cell death and cell motility, which affects prostate cancer tumor progression and responsiveness to therapy.These data indicate that these two hormones combine to drive a differentiated phenotype, and reinforce the idea that the age dependent decline in both hormones results in the de-differentiation of prostate tumor cells, which results in increased proliferation, motility and invasion common to aggressive tumors. These studies also reinforce the potential importance of miRNAs in prostate cancer progression and therapeutic outcomes.
Integration Patterns of HTLV-I Provirus in Relation to the Clinical Course of ATL: Frequent Clonal Change at Crisis From Indolent Disease
Authors: Kunihiro Tsukasaki, Hideki Tsushima, Masaomi Yamamura, Tomoko Hata, Ken Murata, Takahiro Maeda, Sunao Atogami, Hisashi Sohda, Saburo Momita, Shuichi Ideda, Sigeru Katamine, Yasuaki Yamada, Shimeru Kamihira, Masao Tomonaga
Journal: Blood (1997)
The “Effective” Pulmonary Collateral Blood Flow in Man1
Authors: A. P. Fishman, G. M. Turino, M. Brandfonbrener, A. Himmelstein
Journal: Journal of Clinical Investigation (1958)

Perfusion of one lung solely by systemic arterial blood 0. B. F 34 1.60 0 Status 11 years post ligation of left pulmonary artery A. B. M 71 1.65 + + Status 6 months post occlusion of left pulmonary ar- tery by bronchogenic carcinoma Perfusion of one lung by both mixed venous and systemic arterial blood J. S. M 42 1.69 + + Bronchogenic carcinoma of right upper lobe J. Mc.M 55 1.95 ++ Bronchogenic carcinoma of left upper lobe P. C. M 54 2.13 0 Bronchogenic carcinoma of right lower lobe J. C. M 54 1.71 0 Bronchiectatic and cystic changes in right middle and lower lobes, 10 years after Friedlander's pneumonia T. C. M 53 1.93 + + Bronchiectasis of right lower lobe J. G. M 27 1.57++++ Idiopathic clubbing of digits recognized in early childhood Perfusion of both lungs solely by systemic arterial blood J. W. F 24 1.55 + + + + Tetralogy of Fallot; atresia of pulmonary artery
Performance of A1C for the Classification and Prediction of Diabetes
Authors: Elizabeth Selvin, Michael W. Steffes, Edward Gregg, Frederick L. Brancati, Josef Coresh
Journal: Diabetes Care (2010)

OBJECTIVE Although A1C is now recommended to diagnose diabetes, its test performance for diagnosis and prognosis is uncertain. Our objective was to assess the test performance of A1C against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes. RESEARCH DESIGN AND METHODS We conducted population-based analyses of 12,485 participants in the Atherosclerosis Risk in Communities (ARIC) study and a subpopulation of 691 participants in the Third National Health and Nutrition Examination Survey (NHANES III) with repeat test results. RESULTS Against a single fasting glucose ≥126 mg/dl, the sensitivity and specificity of A1C ≥6.5% for detection of prevalent diabetes were 47 and 98%, respectively (area under the curve 0.892). Against repeated fasting glucose (3 years apart) ≥126 mg/dl, sensitivity improved to 67% and specificity remained high (97%) (AUC 0.936). Similar results were obtained in NHANES III against repeated fasting glucose 2 weeks apart. The accuracy of A1C was consistent across age, BMI, and race groups. For individuals with fasting glucose ≥126 mg/dl and A1C ≥6.5% at baseline, the 10-year risk of diagnosed diabetes was 88% compared with 55% among those individuals with fasting glucose ≥126 mg/dl and A1C 5.7–&amp;lt;6.5%. CONCLUSIONS A1C performs well as a diagnostic tool when diabetes definitions that most closely resemble those used in clinical practice are used as the “gold standard.” The high risk of diabetes among individuals with both elevated fasting glucose and A1C suggests a dual role for fasting glucose and A1C for prediction of diabetes.
Keratoconus Associated with Floppy Eyelld Syndrome
Authors: Eric D. Donnenfeld, Henry D. Perry, Richard P. Gibralter, Herbert J. Ingraham, Ira J. Udell
Journal: Ophthalmology (1991)

Floppy eyelid syndrome is a recently described entity, which characteristically involves overweight individuals. The characteristic findings are an upper lid that may be readily everted, tarsal laxity, and diffuse papillary conjunctival changes. The cause of floppy eyelid syndrome is believed to be a mechanical disorder due to the eversion of the lids while sleeping. The cause of keratoconus remains uncertain. There are strong proponents to a mechanical etiology for this disease. The authors report five cases of floppy eyelid syndrome with concomitant keratoconus. One patient with bilateral keratoconus had bilateral symmetric floppy eyelid syndrome. The other four patients had asymmetric keratoconus and floppy eyelid syndrome. In all four patients, the keratoconus was significantly worse in the eye with the more severe case of floppy eyelid syndrome. In addition, these four patients all gave a history of sleeping with their head facing predominantly on the side with the floppy eyelid syndrome and keratoconus. Two patients with keratoconus and floppy eyelid syndrome were able to undergo successful contact lens rehabilitation of their keratoconus after treatment of the floppy eyelid syndrome.
Intraocular Lens Implantation after Atopic Cataract Surgery Decreases Incidence of Postoperative Retinal Detachment
Authors: Makoto Inoue, Kei Shinoda, Susumu Ishida, Atsuro Uchida, Daijiro Kurosaka, Hiroshi Katsura, Kazuo Tsubota
Journal: Ophthalmology (2005)
SPONTANEOUS AMPUTATION IN UTERO OF THE RIGHT FOREARM
Authors: G. Greenwood
Journal: BMJ (1854)

t:of L bm of oer dim; it was found in S ca t t, 26 with on tion; or 79 per cet.n tuberele existed, and in 131 per cent. of dis oter than tubescuois.GatgDe of tubrular cavities oecurred in 6 c l, and a gangrenous odour was observed in 2 other.Eworrhygic dotJ were less frequent in tuberculous than in non-tuberculous cases, in the respective ratios of 1.5 per at.d 3.8 per cent.Pneumothorax took place 19 times, or i 5.5 per cent. of the cases of vomica; 11 times in the right, and 8 times in the left side: thus reversing the experience of Louis, who found it on the left side in 7 out of 8 eases.
Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor.
Authors: S J Konturek, T Brzozowski, I Piastucki, A Dembinski, T Radecki, A Dembinska-Kiec, A Zmuda, H Gregory
Journal: Gut (1981)

This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats. Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa. The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis. This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa.
Increased frequency of T cell receptor V alpha 12.1 expression on CD8+ T cells: evidence that V alpha participates in shaping the peripheral T cell repertoire.
Authors: H DerSimonian, H Band, M B Brenner
Journal: The Journal of Experimental Medicine (1991)

The T cell receptor repertoire has a potential for vast diversity. However, this diversity is limited by the fact that the majority of thymocytes die as the repertoire is shaped by positive and negative selection events during development. Such thymic selection affecting TCR V beta gene segment usage has been demonstrated in the mouse. However, similar data has not been forthcoming in man, and little is known about the role of the TCR alpha chain in antigen/major histocompatibility complex (MHC) recognition in any species. Here, we used a monoclonal antibody recognizing the TCR V alpha 12.1 gene product to assess the expression of this gene in the peripheral blood of man. In most individuals tested, the percentage of cells expressing V alpha 12.1 was significantly higher in CD8+ T cells than in CD4+ T cells. That the V alpha gene product itself was responsible for this increased expression in CD8+ T cells was underscored by the lack of substantial skewing of V beta usage in the V alpha 12.1-bearing T cells. Moreover, the skewed expression of V alpha 12.1 was already present at birth, indicating that it was likely to be due to a developmental process rather than the result of exposure to environmental antigens. Based on the established role for CD8 in binding to class I MHC molecules, we suggest that increased expression of V alpha 12.1 on CD8+ T cells points to a role for TCR's using V alpha 12.1 in class I MHC/Ag recognition. These results indicate that V alpha gene usage in the peripheral blood of man is not random, and they support a role for V alpha as a participant in the self-MHC recognition process that shapes the TCR repertoire.
Defective DNA Repair in Cells With Human T-Cell Leukemia/Bovine Leukemia Viruses: Role of tax Gene
Authors: S. M. Philpott, G. C. Buehring
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Human T-cell leukemia virus (HTLV)/bovine leukemia virus (BLV) group retroviruses, which cause hematopoietic cancers, encode a unique protein, Tax, involved in the transformation of infected cells. Our purpose was to determine whether the mechanism by which Tax protein induces transformation in HTLV- or BLV-infected cells involves DNA damage. METHODS: We used a micronucleus assay to measure chromosomal damage and alkali denaturation analysis to test host-cell DNA integrity in cells infected with HTLV, BLV, or simian T-lymphotropic virus or in cells transfected with the tax gene of HTLV or BLV. Controls included uninfected cells and cells infected with other oncogenic retroviruses or oncogenic DNA viruses. We used a plasmid reactivation assay to examine whether the damage might be due to the inhibition of DNA repair. To ascertain which of several repair pathways might be inhibited, chemical methods were used to selectively introduce lesions repaired by specific pathways into the reporter plasmid. RESULTS: The presence of Tax was associated with DNA damage. HTLV- or BLV-infected or tax-transfected cells showed normal ability to repair damage induced by deoxyribonuclease I or psoralen but markedly decreased ability to repair damage induced by UV light, quercetin, or hydrogen peroxide. CONCLUSIONS: These data suggest that the DNA repair pathway most inhibited by Tax is base-excision repair of oxidative damage. To our knowledge, this is the first report demonstrating inhibition of DNA repair by any retrovirus and suggests that this inhibition of DNA repair may contribute to the mechanism of cell transformation by the HTLV/BLV group of viruses.
Prometheus's Vulture and the Stem-Cell Promise
Authors: Nadia Rosenthal
Journal: New England Journal of Medicine (2003)

Embryonic stem cells have been the focus of intense study over the past two decades. Embryonic stem cells originate from undetermined early embryos, with no possible history of differentiation, whereas the provenance of adult stem cells found in mature tissues is far less well understood. The possibility that a population of reserve stem cells, perhaps set aside during gestation, might be coerced into renewed regenerative service later in life holds great promise. This review considers the status of stem-cell research.
Nasal versus full face mask for noninvasive ventilation in chronic respiratory failure
Authors: P. Wijkstra
Journal: European Respiratory Journal (2004)

To the Editor: 

I read with interest the study by Willson et al. 1 published recently in the European Respiratory Journal . The paper was focused on interfaces, which are one of the most important issues in treating patients with chronic respiratory failure. The study was set up to compare nasal mask (NM) with full face mask (FFM) ventilation, in terms of sleep quality, gas exchange and tolerability. In addition, the authors …
Lymphoedema of the limbs as an extra-articular feature of rheumatoid arthritis.
Authors: J E Dacre, D L Scott, E C Huskisson
Journal: Annals of the Rheumatic Diseases (1990)

Seven patients with lymphoedema of the hands and arms, an unusual extra-articular feature of rheumatoid arthritis, are described. In all cases the lymphoedema persisted throughout follow up--in one case for more than five years--and was resistant to treatment with slow acting drugs, steroids, or cytotoxic agents. There was no correlation with severity of disease. It is concluded that the lymphoedema in these patients may be associated with reduced numbers of lymphatic vessels; increased capillary permeability or abnormal fibrinolysis may also be contributory factors. Conservative management of such patients is recommended.
Validity of a Single-Factor Model Underlying the Metabolic Syndrome in Children
Authors: Vicente Martínez-Vizcaíno, Montserrat Solera Martínez, Fernando Salcedo Aguilar, Sandra Serrano Martínez, Ricardo Franquelo Gutiérrez, Mairena Sánchez López, Pablo Moya Martínez, Fernando Rodríguez-Artalejo
Journal: Diabetes Care (2010)

OBJECTIVE We used confirmatory factor analysis to test whether a single factor might explain the clustering of the metabolic syndrome (MS) components in children. RESEARCH DESIGN AND METHODS We studied 1,020 children aged 10–13 years from 20 schools in Cuenca, Spain. The single-factor model included: waist circumference (WC), fasting insulin, triglyceride to HDL cholesterol ratio (Triglyl/HDL-C), and mean arterial pressure (MAP). The standardized scores of the four variables in the model were used to develop a continuous MS index. RESULTS Factor loadings were 0.67 for WC, 0.68 for fasting insulin, 0.57 for Triglyl/HDL-C, and 0.37 for MAP. The single-factor model also showed a good fit to the data. As compared with Adult Treatment Panel III criteria, the MS index showed strong validity in the diagnosis of MS (area under the receiver operating characteristic curve = 0.98, 95% CI 0.96–0.99). CONCLUSIONS A single underlying factor has acceptable validity to represent MS in children.
The role of lactate in the exercise-induced human growth hormone response: evidence from McArdle disease
Authors: R J Godfrey, G P Whyte, J Buckley, R Quinlivan
Journal: British Journal of Sports Medicine (2008)

Purpose: Increased blood lactate concentration has been suggested as a primary stimulus for the exercise-induced growth hormone response (EIGR). Patients with McArdle disease are unable to produce lactate in response to exercise and thus offer a unique model to assess the role of lactate in the EIGR. Accordingly, McArdle’s patients were exercised to test the hypothesis that lactate is a major stimulus of the EIGR. Methods: 11 patients with McArdle disease (3 male, 8 female; age: 35.5 (SD 13.9) years, height: 166 (8) cm, body mass: 75.2 (13.1) kg) were recruited for the study. The patients walked initially at 0.42 m/s, increasing by 0.14 m/s per 3 min stage. Exercise was terminated when participants completed 3 minutes at 1.80 m/s or when a Borg CR10 pain scale rating of “4” was reached. Stages were separated by 60 s for capillary blood sampling for analysis of hGH and blood lactate concentration. Results: McArdle’s patients’ blood lactate levels remained at resting levels (0.3–1.2 mmol/l) as exercise intensity increased. Nine out of 11 participants failed to demonstrate an EIGR obtaining hGH values below the clinical definition of a response (&gt;3 μg/l). Conclusion: The absence of an EIGR in nine out of 11 participants suggests that lactate could play a major role in the EIGR in humans.