tbuckley/cabot-search huggingface dataset:
Genetic control of immunoregulatory circuits. Genes linked to the Ig locus govern communication between regulatory T-cell sets.
Authors: D D Eardley, F W Shen, H Cantor, R K Gershon
Journal: The Journal of Experimental Medicine (1979)

Antigen-stimulated Ly1:Qa1+ cells induce a nonimmune set of T-acceptor cells (surface phenotype Ly123+Qa1+) to participate in the generation of specific suppressive activity. The experiments reported here were designed to test the possibility that the interaction between T-inducer and T-acceptor cells might be governed by genes linked to the Ig locus. We find that inducer:acceptor interactions occur only if the inducer and acceptor T-cell sets are obtained from donor that are identical at the Ig locus and are independent of the Ig locus expressed on the B cells used for assay of T-helper activity. In addition, experiments using inducer and acceptor T cells from the congenic recombinant BAB. 14 strain show that T-T interactions are not governed by Ig-CH genes, per se. These data indicate that T-inducer: T-acceptor interactions are governed by Ig-linked genes that may control expression of VH-like structures on T cells, or control expression of as yet unidentified cell-surface molecules.
ANTIGEN-SPECIFIC T-CELL FACTOR IN CELL COOPERATION: PHYSICAL PROPERTIES AND MAPPING IN THE LEFT-HAND (K) HALF OF <i>H</i>-2
Authors: A. J. Munro, M. J. Taussig, Rosalie Campbell, Heather Williams, Yvonne Lawson
Journal: The Journal of Experimental Medicine (1974)

Mouse thymus cells, educated to poly(tyrosyl,glutamyl)-polyDLalanyl--polylysyl [(T,G)-A--L], release an antigen-specific factor on brief culture in vitro. The factor cooperates with bone marrow cells in the antibody response to (T,G)-A--L in irradiated recipients. Its mol wt determined from Sephadex G100 chromatography is in the region of 50,000. The factor is removed by specific antigen-coated columns, but not by anti-immunoglobulin (anti-Fab, anti-µ, anti-Fv) adsorbents. The factor is removed by alloantisera directed against the H-2 haplotype of the strain in which it is produced. Moreover, only antisera with specificity for the K side of H-2 were successful in removing the factor activity.
Effects of nifedipine on systemic hydraulic vascular load in patients with hypertension
Authors: K.-C. Chang, K.-S. Hsieh, T.-S. Kuo, H. I Chen
Journal: Cardiovascular Research (1990)

Journal Article Effects of nifedipine on systemic hydraulic vascular load in patients with hypertension Get access Kuo-Chu Chang, Kuo-Chu Chang Correspondence to: Dr Chen Search for other works by this author on: Oxford Academic PubMed Google Scholar Kai-Shen Hsieh, Kai-Shen Hsieh Search for other works by this author on: Oxford Academic PubMed Google Scholar Te-Son Kuo, Te-Son Kuo Search for other works by this author on: Oxford Academic PubMed Google Scholar Hsing I Chen Hsing I Chen Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 9, September 1990, Pages 719–726, https://doi.org/10.1093/cvr/24.9.719 Published: 01 September 1990 Article history Received: 15 August 1989 Accepted: 01 May 1990 Published: 01 September 1990
<i>IRF5</i>polymorphism predicts prognosis in patients with systemic sclerosis
Authors: Roozbeh Sharif, Maureen D Mayes, Filemon K Tan, Olga Y Gorlova, Laura Kathleen Hummers, Ami A Shah, Daniel E Furst, Dinesh Khanna, Javier Martin, Lara Bossini-Castillo, Emilio B Gonzalez, Jun Ying, Hilda Torres Draeger, Sandeep K Agarwal, John D Reveille, Frank C Arnett, Fredrick M Wigley, Shervin Assassi
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> The first genome-wide association study (GWAS) of systemic sclerosis (SSc) demonstrated three non-major histocompatibility complex (MHC) susceptibility loci. The goal of this study was to investigate the impact of these gene variants on survival and severity of interstitial lung disease (ILD) in SSc. <h3>Methods</h3> The authors examined 1443 Caucasian SSc patients enrolled in the <b><i>G</i></b>enetics versus <b><i>E</i></b>nvironment <b><i>I</i></b>n <b><i>S</i></b>cleroderma <b><i>O</i></b>utcome <b><i>S</i></b>tudy (GENISOS) and Scleroderma Family Registry (n = 914 – discovery cohort) and The Johns Hopkins Scleroderma Cohort (n = 529 – replication cohort). Forced vital capacity (FVC)% predicted was used as a surrogate for ILD severity. Five single nucleotide polymorphisms, <i>IRF5</i> (rs10488631, rs12537284, rs4728142), <i>STAT4</i> (rs3821236), <i>CD247</i> (rs2056626) reached genome-wide significance in the SSc-GWAS and were examined in the current study. <h3>Results</h3> Overall, 15.5% of the patients had died over the follow-up period of 5.5 years. The <i>IRF5</i> rs4728142 minor allele was predictive of longer survival in the discovery cohort (p = 0.021) and in the independent replication cohort (p = 0.047) and combined group (HR: 0.75, 95% CI 0.62 to 0.90, p = 0.002). The association of this SNP with survival was independent of age at disease onset, disease type and autoantibody profile (anticentromere and antitopoisomerase antibodies). The minor allele frequency of <i>IRF5</i> rs4728142 was 49.4%. Moreover, <i>IRF5</i> rs4728142 minor allele correlated with higher FVC% predicted at enrolment (p = 0.019). Finally, the <i>IRF5</i> rs4728142 minor allele was associated with lower <i>IRF5</i> transcript expression in patients and controls (p = 0.016 and p = 0.034, respectively), suggesting that the <i>IRF5</i>, rs4728142 SNP, may be functionally relevant. <h3>Conclusion</h3> An SNP in the <i>IRF5</i> promoter region (rs4728142), associated with lower <i>IRF5</i> transcript levels, was predictive of longer survival and milder ILD in patients with SSc.
Coexistence of hypothyroidism with inflammatory arthritis is associated with cardiovascular disease in women
Authors: Hennie G Raterman, Mark M J Nielen, Mike J L Peters, Robert A Verheij, Michael T Nurmohamed, Francois G Schellevis
Journal: Annals of the Rheumatic Diseases (2012)

Hypothyroidism and inflammatory arthritis tend to coexist, but data on this association are sparse. In terms of cardiovascular risk, this association may have clinical relevance as this coexistence may carry an additional cardiovascular risk. This study calculates, first, the prevalence of hypothyroidism in patients with inflammatory arthritis and, second, the cardiovascular disease (CVD) prevalence rate in patients with either hypothyroidism or inflammatory arthritis, or both.Data from the Netherlands Information Network of General Practice, a representative Dutch sample of 360,000 registered patients, were used. Prevalence rates of hypothyroidism were calculated, and multilevel logistic regression analyses were used to calculate CVD prevalence rates.Hypothyroidism prevalence was 6.5% in female patients with arthritis compared to 3.9% in controls (p<0.001). CVD prevalence was 4.3% in patients with hypothyroidism, 5.9% in patients with inflammatory arthritis, 14.3% in patients with hypothyroid inflammatory arthritis and 2.1% in controls. Adjusted CVD prevalence rates were 1.2 (95% CI 0.99 to 1.4) for hypothyroidism, 1.5 (95% CI 1.1 to 2.0) for inflammatory arthritis and 3.7 (95% CI 1.7 to 8.0) for hypothyroid inflammatory arthritis as compared with controls.These data raise awareness on the coexistence of hypothyroidism and inflammatory arthritis and emphasise the importance of cardiovascular risk management in these patients, particularly when hypothyroidism and inflammatory arthritis coexist.
Reduced Ciliary Polycystin-2 in Induced Pluripotent Stem Cells from Polycystic Kidney Disease Patients with PKD1 Mutations
Authors: Benjamin S. Freedman, Albert Q. Lam, Jamie L. Sundsbak, Rossella Iatrino, Xuefeng Su, Sarah J. Koon, Maoqing Wu, Laurence Daheron, Peter C. Harris, Jing Zhou, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2013)

Heterozygous mutations in PKD1 or PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively, cause autosomal dominant PKD (ADPKD), whereas mutations in PKHD1, which encodes fibrocystin/polyductin (FPC), cause autosomal recessive PKD (ARPKD). However, the relationship between these proteins and the pathogenesis of PKD remains unclear. To model PKD in human cells, we established induced pluripotent stem (iPS) cell lines from fibroblasts of three ADPKD and two ARPKD patients. Genetic sequencing revealed unique heterozygous mutations in PKD1 of the parental ADPKD fibroblasts but no pathogenic mutations in PKD2. Undifferentiated PKD iPS cells, control iPS cells, and embryonic stem cells elaborated primary cilia and expressed PC1, PC2, and FPC at similar levels, and PKD and control iPS cells exhibited comparable rates of proliferation, apoptosis, and ciliogenesis. However, ADPKD iPS cells as well as somatic epithelial cells and hepatoblasts/biliary precursors differentiated from these cells expressed lower levels of PC2 at the cilium. Additional sequencing confirmed the retention of PKD1 heterozygous mutations in iPS cell lines from two patients but identified possible loss of heterozygosity in iPS cell lines from one patient. Furthermore, ectopic expression of wild-type PC1 in ADPKD iPS-derived hepatoblasts rescued ciliary PC2 protein expression levels, and overexpression of PC1 but not a carboxy-terminal truncation mutant increased ciliary PC2 expression levels in mouse kidney cells. Taken together, these results suggest that PC1 regulates ciliary PC2 protein expression levels and support the use of PKD iPS cells for investigating disease pathophysiology.
Preventive Therapy of Tuberculosis
Authors: D L Brummer
Journal: Annual Review of Medicine (1974)

The thinking in the United States prior to the mid-1950s, as discussed by Ferebee (I), was that asymptomatic primary tuberculosis in children is a benign process, and indeed a healed primary tuberculous lesion was considered to grant a certain immu­ nity against subsequent infection. Antimicrobial therapy was considered necessary only for a small group whose primary infection caused clinical illness. In an even smaller group the complications of infection such as miliary or meningeal tuberculo­ sis would require heroic therapy. While on the children's chest service at Bellevue Hospital. Lincoln noted that no children receiving a regimen including isoniazid developed tuberculous meningitis as compared to children treated with regimens not containing isoniazid. It was apparently at her suggestion to the United States Public Health Service that the original controlled studies on a cooperative basis were undertaken (2, 3).
Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients
Authors: Eric Lawitz, Maribel Rodriguez-Torres, Andrew J. Muir, Tara L. Kieffer, Lindsay McNair, Ariya Khunvichai, John G. McHutchison
Journal: Journal of Hepatology (2008)
Mutations in the Ras–Raf Axis Underlie the Prognostic Value of CD133 in Colorectal Cancer
Authors: Kristel Kemper, Miranda Versloot, Katherine Cameron, Selçuk Colak, Felipe de Sousa e Melo, Joan H. de Jong, Joanne Bleackley, Louis Vermeulen, Rogier Versteeg, Jan Koster, Jan Paul Medema
Journal: Clinical Cancer Research (2012)

Abstract Purpose: High expression of cancer stem cell (CSC) marker CD133 has been used as a predictor for prognosis in colorectal cancer (CRC), suggesting that enumeration of CSCs, using CD133, is predictive for disease progression. However, we showed recently that both CD133 mRNA and protein are not downregulated during differentiation of colon CSCs, pointing to an alternative reason for the prognostic value of CD133. We therefore set out to delineate the relation between CD133 expression and prognosis. Experimental Design: A CRC patient series was studied for expression of CD133 and other CSC markers by microarray and quantitative PCR analysis. In addition, several common mutations were analyzed to determine the relation with CD133 expression. Results: CD133 mRNA expression predicted relapse-free survival in our patient series, whereas several other CSC markers could not. Moreover, no correlation was found between expression of other CSC markers and CD133. Interestingly, high CD133 expression was related to mutations in K-Ras and B-Raf, and inhibition of mutant K-Ras or downstream mitogen-activated protein kinase kinase (MEK) signaling decreases CD133 expression. In addition, an activated K-Ras gene expression signature could predict CD133 expression in our patient set as well as data sets of other tumor types. Conclusion: CD133 expression is upregulated in CRC tumors that have a hyperactivated Ras–Raf–MEK–ERK pathway and is therefore related to mutations in K-Ras or B-Raf. As mutations in either gene have been related to poor prognosis, we conclude that CD133 expression is not indicative for CSC numbers but rather related to the mutation or activity status of the Ras–Raf pathway. Clin Cancer Res; 18(11); 3132–41. ©2012 AACR.
The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time
Authors: James A. Shaver, Frank W. Kroetz, James J. Leonard, H. W. Paley
Journal: Journal of Clinical Investigation (1968)

The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity but lacking significant inotropic effect, was administered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial pacing, and there was no significant change in cardiac output. During methoxamine infusion, when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time increased as mean arterial pressure increased. There was a highly significant correlation between the increase in mean systolic blood pressure and the prolongation of left ventricular ejection time (r = 0.870). In one subject, an increase in mean systolic pressure of 75 mm Hg prolonged left ventricular ejection time 55 msec, producing paradoxical splitting of the second heart sound. The prolongation of left ventricular ejection time during infusion was not blocked by the prior intravenous administration of atropine sulfate or propranolol hydrochloride, thus ruling out both vagal inhibition of the left ventricle and reflex withdrawal of sympathetic tone as its cause. In three subjects, left ventricular end diastolic pressure was measured and found to be significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume in the presence of an increased pressure load by the Frank Starling mechanism. This study concludes that arterial pressure must be included as a prime determinant of left ventricular ejection time along with stroke volume, heart rate, and inotropic state in intact man.
Functional Disturbances Within Frontostriatal Circuits Across Multiple Childhood Psychopathologies
Authors: Rachel Marsh, Tiago V. Maia, Bradley S. Peterson
Journal: American Journal of Psychiatry (2009)

Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies.
Tumor necrosis factor alpha induces adhesion molecule expression on human fetal astrocytes.
Authors: A A Hurwitz, W D Lyman, M P Guida, T M Calderon, J W Berman
Journal: The Journal of Experimental Medicine (1992)

Leukocyte adhesion molecules on endothelial cells of the blood-brain barrier may participate in the entry of leukocytes into the central nervous system. Because astrocytes are also a component of the blood-brain barrier and have been associated with inflammation, we studied the ability of astrocytes to express leukocyte adhesion molecules using Northern blot and immunocytochemical techniques. Astrocytes treated with the proinflammatory cytokine tumor necrosis factor alpha (TNF) expressed messenger RNA for the adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, as well as their corresponding proteins. In addition, TNF-treated astrocytes expressed a monocyte adhesion protein identified by our laboratory, recognized by the monoclonal antibody IG9. These results indicate that under inflammatory conditions in the central nervous system, such as multiple sclerosis and acquired immune deficiency syndrome, astrocyte expression of adhesion molecules may facilitate the migration of leukocytes and contribute to the disease process.
Use of mass spectrometry to identify clinical Fusarium isolates
Authors: C. Marinach-Patrice, A. Lethuillier, A. Marly, J.-Y. Brossas, J. Gené, F. Symoens, A. Datry, J. Guarro, D. Mazier, C. Hennequin
Journal: Clinical Microbiology and Infection (2009)
Contribution of Macromolecular Structure to the Retention of Low-Density Lipoprotein at Arterial Branch Points
Authors: Gina P. Kwon, Jamie L. Schroeder, Marcelo J. Amar, Alan T. Remaley, Robert S. Balaban
Journal: Circulation (2008)

Extracellular deposition of low-density lipoprotein (LDL) in the arterial wall is an essential early step in atherosclerosis. This process preferentially occurs at arterial branch points, reflecting a regional variation in lipoprotein-arterial wall interactions. In this study, we characterized the submicron microstructure of arterial wall collagen and elastin to evaluate its potential role in regional LDL deposition.With 2-photon microscopy, we used the intrinsic optical properties of collagen and elastin to determine the arterial wall macromolecular microstructure in fresh porcine and murine arteries. This optical approach generated unique nondestructive en face 3-dimensional views of the wall. The collagen/elastin microstructure was found to vary with the topology of the arterial bed. A nearly confluent elastin surface layer was present throughout but was missing at atherosclerosis-susceptible branch points, exposing dense collagen-proteoglycan complexes. In LDL binding studies, this luminal elastin layer limited LDL penetration, whereas its absence at the branches resulted in extensive LDL binding. Furthermore, LDL colocalized with proteoglycans with a sigmoidal dose dependence (inflection point, approximately 130 mg LDL/dL). Ionic strength and competing anions studies were consistent with the initial interaction of LDL with proteoglycans to be electrostatic in nature.This optical sectioning approach provided a robust 3-dimensional collagen/elastin microstructure of the arterial wall in fresh samples. At atherosclerosis-susceptible vascular branch points, the absence of a luminal elastin barrier and the presence of a dense collagen/proteoglycan matrix contribute to increased retention of LDL.
Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?
Authors: E J Schoon
Journal: Gut (2001)

A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.
Additional review of Mohs slides to optimize Mohs micrographic surgery
Authors: C.B. van Lee, B. Graafland, S. Koljenović, H.A.M. Neumann, K. Nasserinejad, T.E.C. Nijsten, R.R. van den Bos, K. Munte
Journal: British Journal of Dermatology (2015)

One significant risk factor for recurrence after Mohs surgery is misinterpretation of slides.To determine how often pathologists detected incompletely excised basal cell carcinoma (BCC) on Mohs slides and to determine risk factors for incompletely excised BCCs.This retrospective study included 1653 BCCs treated with Mohs surgery in a university hospital between 2007 and 2011. For routine quality assurance, all slides were additionally reviewed by a pathologist within 1 week of the procedure. For this study, all cases that had divergent interpretations were re-evaluated by a Mohs surgeon and a pathologist. Mixed-effects logistic regression models with Mohs surgeon effects as random effects were used to determine risk factors for incompletely excised BCC.Incompletely excised BCCs were detected in 31 cases (2%), in which defects > 20 mm in diameter were an independent risk factor (odds ratio 3.58, 95% confidence interval 1.55-8.28). Other studied variables (i.e. aggressive subtype, previously treated BCC, location on nose and > 2 Mohs stages) did not affect the risk of incompletely excised BCCs.The additional review of Mohs slides might increase accurate interpretation, especially in large BCCs.