tbuckley/cabot-search huggingface dataset:
The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota
Authors: D. S Pardi, E. V Loftus, T. C Smyrk, P. P Kammer, W. J Tremaine, C. D Schleck, W S. Harmsen, A. R Zinsmeister, L J. Melton, W. J Sandborn
Journal: Gut (2006)

Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population.In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies).Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence.We identified 130 incident cases for an overall rate of 8.6 cases per 100,000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100,000 early in the study to 19.6 per 100,000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100,000 for collagenous colitis and 5.5 per 100,000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100,000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis).The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.
Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development.
Authors: A M Kruisbeek, R J Hodes, A Singer
Journal: The Journal of Experimental Medicine (1981)

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 wk after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. However, in the presence of interleukin-2 (I1-2), the the putative T helper cell product, CTL could be generated in vitro by thymocytes from recently reconstituted chimeras. Experiments with thymocytes from A leads to A X B and A X B leads to A chimeras revealed the following: (a) thymocytes from both types of chimeras were nonreactive to either A or B parental major-histocompatibility complex (MHC) determinants even though they were alloreactive to third-party stimulator cells; and (b) thymocytes from these chimeras were restricted to the recognition of TNP in association with MHC determinants syngeneic to the chimeric host. Thus, these experiments demonstrate that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the concept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentiation.
Is Soviet Psychiatric Training Relevant in America?
Authors: NANCY ROLLINS
Journal: American Journal of Psychiatry (1971)

There are three levels of medical workers in Soviet medicine; nurse, feldsher, and doctor, and there are advanced degrees for doctors. On the basis of this multiplicity of levels, the author suggests some adaptations for American child psychiatry: a child health worker, a middle medical worker, and two kinds of doctor-therapist; a specialist in child psychiatry and a Ph.D. in medical sciences trained for research and teaching. Other advantages of Soviet training that the author found were the required written reports and the stress on continuing education, with rewards for participation.
M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis
Authors: Yoshiaki Kubota, Keiyo Takubo, Takatsune Shimizu, Hiroaki Ohno, Kazuo Kishi, Masabumi Shibuya, Hideyuki Saya, Toshio Suda
Journal: The Journal of Experimental Medicine (2009)

Antiangiogenic therapy for the treatment of cancer and other neovascular diseases is desired to be selective for pathological angiogenesis and lymphangiogenesis. Macrophage colony-stimulating factor (M-CSF), a cytokine required for the differentiation of monocyte lineage cells, promotes the formation of high-density vessel networks in tumors and therefore possesses therapeutic potential as an M-CSF inhibitor. However, the physiological role of M-CSF in vascular and lymphatic development, as well as the precise mechanisms underlying the antiangiogenic effects of M-CSF inhibition, remains unclear. Moreover, therapeutic potential of M-CSF inhibition in other neovascular diseases has not yet been evaluated. We used osteopetrotic (op/op) mice to demonstrate that M-CSF deficiency reduces the abundance of LYVE-1+ and LYVE1− macrophages, resulting in defects in vascular and lymphatic development. In ischemic retinopathy, M-CSF was required for pathological neovascularization but was not required for the recovery of normal vasculature. In mouse osteosarcoma, M-CSF inhibition effectively suppressed tumor angiogenesis and lymphangiogenesis, and it disorganized extracellular matrices. In contrast to VEGF blockade, interruption of M-CSF inhibition did not promote rapid vascular regrowth. Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF–targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer.
Nurse-Based Management in Patients With Gestational Diabetes
Authors: Apolonia García-Patterson, Esther Martín, Justa Ubeda, Miguel A. María, Juan M. Adelantado, Gemma Ginovart, Alberto de Leiva, Rosa Corcoy
Journal: Diabetes Care (2003)

OBJECTIVE—To compare the rate of insulin treatment and perinatal outcome in women with gestational diabetes mellitus (GDM) under endocrinologist-based versus diabetes nurse-based metabolic management. RESEARCH DESIGN AND METHODS—In a retrospective analysis, maternal characteristics, rate of insulin treatment, and perinatal outcome of patients with GDM delivering between 1 January 1995 and 30 June 1997 (n = 244) receiving endocrinologist-based care were compared with those delivering between 1 July 1997 and 31 December 1999 (n = 283) who received diabetes nurse-based care. The diabetes nurse’s role was similar to that of an advanced practice nurse in the U.S. There were no changes in the metabolic goals and instruments or in obstetric and neonatal management. Quantitative data were compared with the Mann-Whitney U test and categorical data, with Fisher’s exact test. RESULTS—Maternal characteristics (age, BMI, family history of diabetes, prior glucose intolerance, gestational age, and blood glucose at diagnosis of GDM) did not differ between groups treated during the two periods. Rates of insulin treatment and perinatal outcome (hypertension, preterm delivery, cesarean section, low Apgar score, macrosomia, small- and large-for-gestational-age newborns, obstetric trauma, major malformations, hypoglycemia, hypocalcemia, polycythemia, jaundice, respiratory distress, and mortality) were also similar in both groups. CONCLUSIONS—Comparison of periods of endocrinologist-based and diabetes nurse-based metabolic management of women with GDM showed no differences in the rate of insulin treatment and perinatal outcome. This supports a more active role of nurses in the management of women with GDM.
Perineal Powder Use and Risk of Ovarian Cancer
Authors: S. C. Houghton, K. W. Reeves, S. E. Hankinson, L. Crawford, D. Lane, J. Wactawski-Wende, C. A. Thomson, J. K. Ockene, S. R. Sturgeon
Journal: JNCI Journal of the National Cancer Institute (2014)

Case-control studies have reported an increased risk of ovarian cancer among talc users; however, the only cohort study to date found no association except for an increase in serous invasive ovarian cancers. The purpose of this analysis was to assess perineal powder use and risk of ovarian cancer prospectively in the Women's Health Initiative Observational Study cohort. Perineal powder use was assessed at baseline by self-report regarding application to genitals, sanitary napkins, or diaphragms and duration of use. The primary outcome was self-reported ovarian cancer centrally adjudicated by physicians. Cox proportional hazard regression was used to estimate risk, adjusting for covariates, including person-time until diagnosis of ovarian cancer (n = 429), death, loss to follow-up, or September 17, 2012. All statistical tests were two-sided. Among 61576 postmenopausal women, followed for a mean of 12.4 years without a history of cancer or bilateral oophorectomy, 52.6% reported ever using perineal powder. Ever use of perineal powder (hazard ratio [HR] adj = 1.06, 95% confidence interval [CI] = 0.87 to 1.28) was not associated with risk of ovarian cancer compared with never use. Individually, ever use of powder on the genitals (HR adj = 1.12, 95% CI = 0.92 to 1.36), sanitary napkins (HR adj = 0.95, 95% CI = 0.76 to 1.20), or diaphragms (HR adj = 0.92, 95% CI = 0.68 to 1.23) was not associated with risk of ovarian cancer compared with never use, nor were there associations with increasing durations of use. Estimates did not differ when stratified by age or tubal ligation status. Based on our results, perineal powder use does not appear to influence ovarian cancer risk.
Adrenergic Nervous System in Heart Failure
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Walter J. Koch
Journal: Circulation Research (2013)

Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart.
Direct Observations In Vivo on the Role of Endothelial Selectins and α <sub>4</sub> Integrin in Cytokine-Induced Leukocyte-Endothelium Interactions in the Mouse Aorta
Authors: Einar E. Eriksson, Joachim Werr, Yancai Guo, Peter Thoren, Lennart Lindbom
Journal: Circulation Research (2000)

Abstract —The molecular mechanisms underlying leukocyte recruitment in large arteries have been extensively studied using histological techniques on fixed tissues. However, there are no reports that address the dynamics of leukocyte recruitment in large arteries in vivo. We developed an intravital microscopy technique for direct observation of leukocyte-endothelium interactions in the mouse aorta. Circulating leukocytes were labeled intravasally with rhodamine 6G and microscopically visualized within the aorta, allowing direct analysis of leukocyte rolling and adhesion. In untreated vessels, leukocyte-endothelium interactions were virtually absent. However, local pretreatment with cytokines interleukin-1β and tumor necrosis factor-α induced clear-cut leukocyte rolling and adhesion, compatible with normal blood flow and wall shear rate. High shear decreased rolling leukocyte flux and increased leukocyte rolling velocity, thus decreasing the tendency for firm adhesion. Leukocyte rolling was almost abolished by an antibody blocking the function of P-selectin, whereas function-blocking antibodies against E-selectin and the α 4 -integrin subunit decreased rolling leukocyte flux to 51±34% (mean±SD) and 59±11% of the value before antibody treatment, respectively. In addition, inhibition of E-selectin function, but not of α 4 integrin, resulted in increased leukocyte rolling velocity (from 48±32 to 71±32 μm per second). Taken together, we introduce the first model for direct studies of leukocyte-endothelium interactions in a large artery in vivo and demonstrate cytokine-induced shear-sensitive leukocyte rolling that is critically dependent on P-selectin and modulated by E-selectin and α 4 integrin.
AngRem104, an Angiotensin II–Induced Novel Upregulated Gene in Human Mesangial Cells, Is Potentially Involved in the Regulation of Fibronectin Expression
Authors: Xiubin Liang, Hong Zhang, Anyu Zhou, Haiyan Wang
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Accumulation of extracellular matrix (ECM) in the glomerular mesangium is a common feature of many progressive renal diseases. Angiotensin II (AngII) plays important roles in the proliferation of glomerular mesangial cells (MC) as well as the synthesis of ECM such as fibronectin (FN) and collagens. However, the precise molecular signals responsible for these effects are unknown. To explore possible molecule mechanism of ECM accumulation related to AngII, suppression subtractive hybridization (SSH) was performed to screen and identify upregulated genes induced by AngII in cultured human MC. A novel gene, AngRem104 (GenBank accession number, AF367870), was isolated. The full-length cDNA of AngRem104 is 1690 bp, and it contains a 1041-bp open reading frame (ORF) encoding 347 amino acid residues with a predicted molecular mass of 37.2 kD. AngRem104 widely expressed in human heart, placenta, liver, muscle, kidney, and pancreas. Moreover, AngRem104 was found in human glomeruli and tubule by in situ hybridization. In human MC, the upregulation of AngRem104 induced by AngII was time-dependent, and it was dose-dependently blocked by AngII type 1 receptor antagonist (AT1RA), Losartan. The subcellular localization detected by AngRem104-pEGFP fusion protein revealed that AngRem104 was a nuclear protein. Interestingly, when AngRem104 was overexpressed by transfection of its sense construct, cDNA Microarray showed that two of the ECM-related genes, i.e., human mRNA for FN and integrin-β-1 (FN receptor), dramatically upregulated their expressions. Furthermore, AngRem104 could regulate the expression of FN induced by AngII, which were detected by RT-PCR and quantitative real-time PCR, when AngRem104 was overexpressed. It is concluded that AngRem104 is a novel human gene potentially involved in the regulation of FN induced by AngII in human MC. These findings may provide new insights into mechanisms of glomerular sclerosis associated with AngII. E-mail: [email protected]
The Ice Pack Test in the Differential Diagnosis of Myasthenic Diplopia
Authors: Klio I. Chatzistefanou, Tassos Kouris, Evangelos Iliakis, Georgios Piaditis, Georgios Tagaris, Nikolaos Katsikeris, Grigorios Kaltsas, Michael Apostolopoulos
Journal: Ophthalmology (2009)
ASAS/EULAR recommendations for the management of ankylosing spondylitis: the patient version
Authors: U Kiltz, D van der Heijde, H Mielants, E Feldtkeller, J Braun
Journal: Annals of the Rheumatic Diseases (2008)

Background: The ASAS/EULAR (Assessment of SpondyloArthritis International Society/European League Against Rheumatism) recommendations for the management of ankylosing spondylitis (AS) have been developed by rheumatologists for a target population of health professionals. Objective: To extend the cooperation between ASAS and EULAR by translating the recommendations into a language that can be easily understood by patients in order to further disseminate and evaluate the recommendations. Methods: In cooperation with patient organisations 18 patients with AS (17 European, one Canadian) were invited to attend a meeting in February 2008. As a starting point the original publication and a version created by Canadian patients with AS were used. To improve the understanding of potential problems, data on the evaluation of a recent German translation were presented. After intensive discussions the wording was adjusted and a vote was held on the new wording of the recommendations aiming for &gt;80% agreement on each sentence. Finally, patients were asked to indicate their level of agreement with the content of the recommendations. Results: Ten recommendations were successfully translated into a patient-understandable version. The original text was changed in most cases. In all but one case (recommendation No 4) there was broad agreement with the proposed translation. The overall agreement with the content of the recommendations was high: 8.7 (0.6). Conclusion: For the first time, EULAR recommendations were successfully converted into a patient-understandable language version by a large international group of patients in collaboration with rheumatologists. The evaluation showed broad agreement. Translations into different languages and further dissemination in individual countries will be performed.
Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass® composites
Authors: Superb K. Misra, Dirk Mohn, Tobias J. Brunner, Wendelin J. Stark, Sheryl E. Philip, Ipsita Roy, Vehid Salih, Jonathan C. Knowles, Aldo R. Boccaccini
Journal: Biomaterials (2008)
SKI-606 Decreases Growth and Motility of Colorectal Cancer Cells by Preventing pp60(c-Src)–Dependent Tyrosine Phosphorylation of β-Catenin and Its Nuclear Signaling
Authors: Addolorata Maria Luce Coluccia, Daniela Benati, Hafedh Dekhil, Annamaria De Filippo, Cathy Lan, Carlo Gambacorti-Passerini
Journal: Cancer Research (2006)

Abstract Inhibition of deregulated protein tyrosine kinases represents an attractive strategy for controlling cancer growth. However, target specificity is an essential aim of this strategy. In this report, pp60(c-Src) kinase and β-catenin were found physically associated and constitutively activated on tyrosine residues in human colorectal cancer cells. The use of specific small-interfering RNAs (siRNA) validated pp60(c-Src) as the major kinase responsible for β-catenin tyrosine phosphorylation in colorectal cancer. Src-dependent activation of β-catenin was prevented by SKI-606, a novel Src family kinase inhibitor, which also abrogated β-catenin nuclear function by impairing its binding to the TCF4 transcription factor and its trans-activating ability in colorectal cancer cells. These effects were seemingly specific, as cyclin D1, a crucial β-catenin/TCF4 target gene, was also down-regulated by SKI-606 in a dose-dependent manner accounting, at least in part, for the reduced growth (IC50, 1.5-2.4 μmol/L) and clonogenic potential of colorectal cancer cells. Protein levels of β-catenin remained substantially unchanged by SKI-606, which promoted instead a cytosolic/membranous retention of β-catenin as judged by immunoblotting analysis of cytosolic/nuclear extracts and cell immunofluorescence staining. The SKI-606-mediated relocalization of β-catenin increased its binding affinity to E-cadherin and adhesion of colorectal cancer cells, with ensuing reduced motility in a wound healing assay. Interestingly, the siRNA-driven knockdown of β-catenin removed the effect of SKI-606 on cell-to-cell adhesion, which was associated with prolonged stability of E-cadherin protein in a pulse-chase experiment. Thus, our results show that SKI-606 operates a switch between the transcriptional and adhesive function of β-catenin by inhibiting its pp60(c-Src)–dependent tyrosine phosphorylation; this could constitute a new therapeutic target in colorectal cancer. (Cancer Res 2006; 66(4): 2279-86)
Role of the area postrema in the modulation of the baroreflex control of heart rate by angiotensin II.
Authors: S Matsukawa, I A Reid
Journal: Circulation Research (1990)

During angiotensin II (Ang II)-induced elevation of arterial pressure, there is an attenuation of the baroreflex control of heart rate (HR), but the site of this action of Ang II on the baroreflex is not known. To investigate the role of the area postrema, the effects of Ang II on arterial pressure and HR and on the baroreflex control of HR were compared in intact and area postrema-lesioned conscious rabbits. In intact rabbits, infusion of Ang II (2.5-100 ng/kg/min) produced dose-related increases in mean arterial pressure (MAP); the largest dose increased MAP by 32 +/- 3 mm Hg. HR decreased only at the highest dose of Ang II (21 +/- 6 beats/min). In lesioned rabbits, the increase in MAP was reduced (23 +/- 2 mm Hg, p less than 0.05) while the decrease in HR was enhanced (50 +/- 8 beats/min, p less than 0.01). The pressor and HR responses to infusion of phenylephrine (PE) (2-20 micrograms/kg/min) were not different between the two groups. In intact rabbits, the slope of the relation between HR and MAP during Ang II infusion was less than that during PE infusion; in lesioned rabbits, the slopes were not significantly different. Responses to bolus injections of Ang II and PE in intact and lesioned rabbits were similar to those obtained in the infusion study. In another series of experiments, cardiac baroreflex responses with or without background infusion of Ang II were obtained by increasing blood pressure with graded infusions of PE (2-20 micrograms/kg/min). In intact rabbits, infusion of Ang II at 10 ng/kg/min shifted the baroreflex to a higher pressure level (resetting) without changing its slope (sensitivity). Background infusion of PE caused comparable increases in blood pressure, but the subsequent baroreflex response was identical to the response without background PE. In lesioned rabbits, background infusion of Ang II did not change the slope, nor did it reset the baroreflex. The effects of Ang II on baroreflex responses during nitroprusside infusions (2-20 micrograms/kg/min) in intact and lesioned rabbits were the same as those observed during the PE infusions. These findings indicate that the attenuation of the baroreflex control of HR by Ang II results from resetting of the cardiac baroreflex and suggest that this effect is mediated via the area postrema.