tbuckley/cabot-search huggingface dataset:
A Functional Floxed Allele of Pkd1 that Can Be Conditionally Inactivated In Vivo
Authors: Klaus B. Piontek, David L. Huso, Alexander Grinberg, Lijuan Liu, Djahida Bedja, Haidan Zhao, Kathleen Gabrielson, Feng Qian, Changlin Mei, Heiner Westphal, Gregory G. Germino
Journal: Journal of the American Society of Nephrology (2004)

Gene targeting has been used to create a variety of lines of mice with <i>Pkd1</i> mutations that share many common features. Homozygous <i>Pkd1</i> mutants invariably develop pancreatic and renal cysts if they survive to day 15.5 post coitum and die in either the fetal or the perinatal period. In contrast, mice with heterozygous mutations of <i>Pkd1</i> are generally normal and have few if any renal cysts. These features have limited the utility of these models as tools to study the pathogenesis of cyst formation and the effect of various therapeutic interventions on disease progression. This report describes a new line of mice with a floxed allele of <i>Pkd1</i> (<i>Pkd1</i><sup><i>cond</i></sup>) that has an FRT-flanked neomycin cassette inserted into intron 1 and lox P sites inserted into intron 1 and intron 4. The <i>Pkd1</i><sup><i>cond</i></sup> allele is fully functional, and homozygotes are viable and healthy. It is shown that the lox P and FRT sites can be selectively induced to recombine to produce two new alleles, <i>Pkd1</i><sup><i>del2–4</i></sup> and <i>Pkd1</i><sup><i>cond-Δneo</i></sup>, by crossing to animals that express either the cre or FLPe recombinase, respectively. It is found that <i>Pkd1</i><sup><i>del2–4</i></sup> allele functions as a true null, whereas presence or absence of the neomycin gene has no functional effects. It also is shown that somatic loss of <i>Pkd1</i> results in renal and hepatic cysts. This new line of mice will be invaluable in the study of <i>Pkd1</i> biology and serve as a powerful new tool that can be used to study the pathogenesis of autosomal dominant polycystic kidney disease.
Endocrine signaling in ovarian surface epithelium and cancer
Authors: Peter C.K. Leung, Jung-Hye Choi
Journal: Human Reproduction Update (2006)

Ovarian cancer is the sixth most common cancer and the fifth leading cause of cancer-related death among women in developed countries. Greater than 85% of human ovarian cancer arises within the ovarian surface epithelium (OSE), with the remainder derived from granulosa cells or, rarely, stroma or germ cells. The pathophysiology of ovarian cancer is the least understood among all major human malignancies because of a poor understanding of the aetiological factors and mechanisms of ovarian cancer progression. There is increasing evidence suggesting that several key reproductive hormones, such as GnRH, gonadotrophins and sex steroids, regulate the growth of normal OSE and ovarian cancer cells. The objective of this review was to highlight the effects of these endocrine factors on ovarian cancer cell growth and to summarize the signalling mechanisms involved in normal human OSE and its neoplastic counterparts.
IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites
Authors: Alexandre Morrot, Julius C.R. Hafalla, Ian A. Cockburn, Luzia H. Carvalho, Fidel Zavala
Journal: The Journal of Experimental Medicine (2005)

IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite protein of Plasmodium yoelii develop a severely impaired memory response after priming with parasites. Memory CD8+ T cells lacking the IL-4R are unable to establish a stable population residing in nonlymphoid organs, although they develop normally in lymphoid organs. Because memory cells from nonlymphoid organs disappear shortly after immunization, the protective antiparasitic activity of this T cell response also is lost. These results demonstrate that IL-4/IL-4R interactions on CD8+ T cells play a critical role in modulating the development and tissue distribution of memory cells induced by parasite immunization. They also indicate that memory cells residing in nonlymphoid tissues are critical for protective immunity against malaria parasites.
Layers of mutualism with commensal bacteria protect us from intestinal inflammation
Authors: C Mueller
Journal: Gut (2006)

Mammals are highly adapted to their very high densities of non-pathogenic bacteria which inhabit the lower small intestine and colon. This is achieved by a series of functional and cellular layers that normally avoid the inflammatory consequences of immune activation by bacterial molecules. In this review we set out the layers of mucosal immune defence to show the many ways in which mutualism with the commensal flora can break down to trigger chronic intestinal inflammation in animal models and inflammatory bowel disease (IBD) in humans.

The immune system of the intestine is phylogenetically ancient, and its development appears to have preceded most other lymphoid structures, including the thymus.1 The intestinal mucosal immune system is also of immense size. Approximately 70% of all lymphocytes in the body are within the mucosal immune system and most of the antibody produced in healthy individuals is IgA, which is secreted across mucous membranes. Intestinal immunity must be finally balanced between the capacity for mounting protective immune responses to infectious agents and yet tolerate the enormous load of antigens and immunostimulatory molecules that constitute the commensal intestinal bacteria.

Commensal bacteria are present in vast numbers.2 The colon is colonised with approximately 1012 organisms/g intestinal contents, making us walking culture media because the bacteria outnumber our own cells! The benefits of commensal bacteria are well known: they help us digest cellulose and salvage energy, synthesise vitamin K, and fill up the microbiological niche that might otherwise be exploited by less benign microbes. Of course, commensals can become pathogens in the right setting, such as debilitated or immunocompromised patients, but on the whole it is impressive how well we coexist with our microbial passengers.

Our bodies have adapted in many ways to achieve this harmonious mutualism with our commensals. The evidence for this comes …
Treatment of central sleep apnoea in congestive heart failure with nasal ventilation
Authors: G N Willson, I Wilcox, A J Piper, W E Flynn, R R Grunstein, C E Sullivan
Journal: Thorax (1998)

Cheyne-Stokes respiration (CSR) is common in patients with congestive heart failure (CHF). 1 This characteristic crescendo-decrescendo pattern of breathing is often seen during sleep in patients with CHF and is a form of central sleep apnoea. 2 Disordered nocturnal breathing leads to oxygen desaturation, poor sleep quality, and altered sleep architecture. 3These features may lead to complaints of daytime somnolence, fatigue, insomnia, and many of the symptoms typical of sleep disordered breathing.It has been proposed that CSR during sleep in patients with heart failure is an indicator of a poor prognosis. 4 5The likely adverse eVects of CSR on daytime performance and myocardial function have resulted in the introduction and evaluation of a range of treatments aimed at reducing CSR.These include low flow oxygen, 6 theophylline, 7 and nasal continuous positive airways pressure (nCPAP). 8In one controlled study nCPAP was shown to improve both sleep quality and daytime myocardial function. 8Other groups have found nCPAP to be ineVective in controlling CSR. [9][10][11] Nocturnal nasal intermittent positive pressure ventilation (nIPPV) is the accepted treatment for patients with chronic respiratory failure due to hypoventilation during sleep. 12 13 We hypothesised that nIPPV may also eVectively treat central sleep apnoea in heart failure by controlling ventilation and carbon dioxide in patients whose disordered breathing has been linked to fluctuating carbon dioxide levels, relative hyperventilation, and hypocapnia. 14 15Nasal IPPV was administered in an attempt to mechanically ventilate the patient through the apnoeic portion of the Cheyne-Stokes cycle, thereby preventing fluctuations in carbon dioxide levels and consequently abolishing CSR.This study describes the use of nocturnal nIPPV in a group of patients with heart failure and Cheyne-Stokes respiration during sleep.The eVects of this therapy on respiratory disturbance and sleep quality following an in-hospital acclimatisation period are reported.We also report our experience with long term domiciliary therapy and its eVects on daytime left ventricular function in patients who remained compliant with treatment.
Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation
Authors: Giuseppe Esposito, Elena Capoccia, Fabio Turco, Ilaria Palumbo, Jie Lu, Antonio Steardo, Rosario Cuomo, Giovanni Sarnelli, Luca Steardo
Journal: Gut (2013)

<h3>Objective</h3> Enteric glia activation has been reported to amplify intestinal inflammation via the enteroglial-specific S100B protein. This neurotrophin promotes macrophage recruitment in the mucosa, amplify colonic inflammation and interacts with toll-like receptors (TLR). Molecules inhibiting S100B-driven enteric activation might mitigate the course of ulcerative colitis (UC). This study aims to investigate the effects of palmitoylethanolammide (PEA), a drug able to counteract astroglial activation in the central nervous system, on intestinal inflammation, in humans and mice. <h3>Design</h3> Mouse models of dextran sodium sulphate (DSS)-induced colitis, colonic biopsies deriving from UC patients and primary cultures of mouse and human enteric glial cells (EGC), have been used to assess the effects of PEA, alone or in the presence of specific PPARα or PPARγ antagonists, on: macroscopic signs of UC (DAI score, colon length, spleen weight, macrophages/neutrophils infiltration); the expression and release of proinflammatory markers typical of UC; TLR pathway in EGCs. <h3>Results</h3> PEA treatment improves all macroscopic signs of UC and decreases the expression and release of all the proinflammatory markers tested. PEA anti-inflammatory effects are mediated by the selective targeting of the S100B/TLR4 axis on ECG, causing a downstream inhibition of nuclear factor kappa B (NF-kB)-dependent inflammation. Antagonists at PPARα, but not PPARγ, abolished PEA effects, in mice and in humans. <h3>Conclusions</h3> Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC.
Reduction of Visceral Fat Is Associated With Decrease in the Number of Metabolic Risk Factors in Japanese Men
Authors: Yukiyoshi Okauchi, Hitoshi Nishizawa, Tohru Funahashi, Tomoko Ogawa, Midori Noguchi, Miwa Ryo, Shinji Kihara, Hiromi Iwahashi, Kazuya Yamagata, Tadashi Nakamura, Iichiro Shimomura, Yuji Matsuzawa
Journal: Diabetes Care (2007)

Visceral fat accumulation is associated with the development of metabolic disorders such as glucose intolerance, dyslipidemia, hypertension, and atherosclerotic cardiovascular diseases (1–8). However, the relationship between reduction of visceral fat and decrease in the number of metabolic risk factors has not been defined in the general population. Recently, we developed a new technique, the abdominal bioelectrical impedance analysis (BIA), to evaluate visceral fat area (VFA) (9). The aim of this study was to investigate whether reduction of visceral fat, estimated by the BIA, is associated with a decrease in the number of metabolic risk factors.

The study group comprised 2,336 Japanese men (aged mean ± SD 48.0 ± 10.5 years, BMI 24.2 ± 2.9 kg/m2), who were employees of Amagasaki City Office, an urban area, and had undergone annual health check-ups in both 2004 and 2005. After the health check-up, the medical staff provided risk factor–oriented, rather than obesity-oriented, health promotion programs to select individuals with visceral fat accumulation and multiple risk factors, with the aim of encouraging a scientific understanding of the spectrum of metabolic syndrome from visceral fat accumulation to atherosclerotic cardiovascular diseases. In this study, we used VFA estimated by the BIA, which was shown to correlate significantly with VFA determined by computed tomography (9). The measurement of VFA by BIA complied with the Guidelines of the Ethical Committees of …
A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE)
Authors: Marcelo Silva, Jorge Poo, Frank Wagner, Mary Jackson, David Cutler, Michael Grace, Ronald Bordens, Connie Cullen, Joann Harvey, Mark Laughlin
Journal: Journal of Hepatology (2006)
Some Circulatory Effects of Thoracotomy and Intermittent Positive Pressure Respiration in Dogs
Authors: JAMES K. FINLAYSON, MILTON N. LURIA, PAUL N. YU
Journal: Circulation Research (1961)

In the anesthetized dog, thoracotomy and intermittent positive-atmospheric pressure (I.P.-A.P.) respiration produce a marked arid sustained fall in cardiac output. Evidence suggests that most of the fall is due to thora cotomy, and the I.P.-A.P. respiration at levels sufficient to maintain adequate ventilation plays a relatively minor part. Thoracotorny also results in considerable reduction of all compartments of the central blood volume, presumably due to loss of the distending ef fect of negative intrapleural pressure on the heart aiid great vessels. There was a consistent rise in pulmonary vascular resistance which was not significantly affected by the adminis tration of hexamethonium or phentolamine. It is suggested that humoral or neurogenic factors play a minor role in producing the in creased resistance.
Regular exercise did not modify significantly superoxide dismutase activity in adolescents with Down's syndrome
Authors: F J Ordoñez, M Rosety, M Rosety-Rodriguez
Journal: British Journal of Sports Medicine (2006)

Superoxide dismutase (SOD) overexpression in people with Down's syndrome negatively modifies the equilibrium SOD/glutathione peroxidase+catalase, which may ultimately lead to an increased hydroxyl radical formation.To assess the influence of regular exercise on erythrocyte SOD activity to determine the ability of exercise to attenuate increased oxidative damage.Thirty one male adolescents with Down's syndrome (mean (SD) age 16.3 (1.1) years) performed a 12 week training programme (three days a week), consisting of a warm up, exercise at a work intensity of 60-75% of peak heart rate (the latter calculated from 194.5 - (0.56 x age)), and a cool down period. The reduction of cytochrome c at 550 nm was used to monitor SOD activity in the supernatant of erythrocyte haemolysates.Mean (SD) SOD activity in non-exercised adolescents with Down's syndrome was 679.0 (82) U/g haemoglobin (95% confidence interval 642.2 to 715.8). After the 12 week training programme, it had increased to 706.8 (91) U/g haemoglobin (95% confidence interval 663.9 to 749.8). This increase was not significant (p = 0.099).Regular exercise did not significantly increase SOD activity and consequently did not affect the unbalanced equilibrium SOD/glutathione peroxidase+catalase observed in patients with Down's syndrome. Further studies are required to assess the behaviour of other antioxidant enzymes included in this pathway in order to highlight potential benefits of regular exercise in redox metabolism of patients with Down's syndrome.
Chymase inhibition suppresses high-cholesterol diet-induced lipid accumulation in the hamster aorta
Authors: Y Uehara
Journal: Cardiovascular Research (2002)

Objective: The role of chymase (a mast cell-derived angiotensin II-forming serine proteinase) in aortic lipid deposition was investigated using an orally active, non-peptide chymase inhibitor, SUN-C8257. Methods: Male golden Syrian hamsters, 8 weeks old, were fed with a standard rodent meal supplemented with or without 0.5% cholesterol and 10% coconut oil for 12 weeks. The hamsters fed high cholesterol diet were further separated into two groups treated with or without SUN-C8257 for 12 weeks. The aortic lipid deposition was visualized by Oil red O staining and planimetrically measured. Immunohistochemical staining for angiotensin II (Ang II) of the aortic root region was performed. Aortic Ang II-forming activity was measured using Ang I as a substrate. Plasma total-, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol and triglyceride were quantified by enzymatic methods. Plasma Ang I and Ang II were measured by radioimmunoassay. Results: After 12 weeks of high cholesterol diet, aortic chymase activity in the untreated group increased significantly and showed a positive correlation with plasma total- and LDL-cholesterol. This group of hamsters developed marked lipid deposits in the aortic intima. However, treatment with SUN-C8257 significantly suppressed aortic lipid deposition without changing body weight, blood pressure, plasma LDL-cholesterol and Ang II levels. The level of the adventitial Ang II-immunoreactivity was markedly inhibited in the group treated with SUN-C8257. Conclusion: Our results suggest that arterial chymase may participate in the acceleration of lipid deposition in arterial walls exposed to high plasma cholesterol and that inhibition of arterial chymase may retard the progression of atherosclerosis.
Severe inflammatory defect and reduced viability in CD18 and E-selectin double-mutant mice
Authors: S.B. Forlow, E.J. White, S.C. Barlow, S.H. Feldman, H. Lu, G.J. Bagby, A.L. Beaudet, D.C. Bullard, K. Ley
Journal: Journal of Clinical Investigation (2000)

CD18-deficient mice (CD18–/– mice) have a severe leukocyte recruitment defect in some organs, and no detectable defect in other models. Mice lacking E-selectin (CD62E–/– mice) have either no defect or a mild defect of neutrophil infiltration, depending on the model. CD18–/–CD62E–/–, but not CD18–/–CD62P–/–, mice generated by crossbreeding failed to thrive, reaching a maximum body weight of 10–15 grams. To explore the mechanisms underlying reduced viability, we investigated lethally irradiated CD62E–/– mice that were reconstituted with CD18–/– bone marrow. These mice, but not single-mutant controls, showed tenfold-increased rolling velocities in a TNF-α–induced model of inflammation. Leukocyte adhesion efficiency in CD18–/–CD62E–/– mice was reduced by 95%, and hematopoiesis was drastically altered, including severe bone marrow and blood neutrophilia and elevated G-CSF and GM-CSF levels. The greatly reduced viability of CD18–/–CD62E–/– mice appears to result from an inability to mount an adequate inflammatory response. Our data show that cooperation between E-selectin and CD18 integrins is necessary for neutrophil recruitment and that alternative adhesion pathways cannot compensate for the loss of these molecules.
Advanced Hodgkin’s Disease: ABVD Is Better, Yet Is Not Good Enough!
Authors: Volker Diehl
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.11.072 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12586791 Advanced Hodgkin's Disease: ABVD Is Better, Yet Is Not Good Enough! Volker DiehlxVolker DiehlSearch for articles by this author Show More University of Cologne, Cologne, Germany https://doi.org/10.1200/JCO.2003.11.072 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Clinical Diabetic Neuropathy
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2005)

This is the first in a series of articles on presentations at the American Diabetes Association Annual Meeting, San Diego, California, 10–14 June 2005.

A number of presentations at the American Diabetes Association (ADA) Annual Meeting discussed aspects of diabetic neuropathy. At a joint European Association for the Study of Diabetes/ADA Symposium, Rury Holman (Oxford, U.K.) reminded the audience that the U.K. Prospective Diabetes Study (UKPDS) included >5,000 individuals with newly diagnosed diabetes, followed from 1977 to 1991. Trial results were reported in 1998, with 30-year follow-up in progress to further understand the natural history of type 2 diabetes. Holman summarized clinical characteristics of diabetic neuropathy in the UKPDS population. Vibration sensory threshold was measured with a bioesthesiometer, with a cutoff of 25 V; erectile dysfunction (ED) and foot sensation were assessed by history; ankle and knee tendon reflexes, basal heart rate, and lying and standing blood pressure were determined on examination; and the shortest electrocardiographic RR interval, near the 15th heartbeat after standing from resting, and the longest, around the 30th heartbeat, were measured to give information about autonomic neuropathy. A total of 3,867 individuals had been randomized to conventional versus intensive glucose control from the time of diagnosis of type 2 diabetes, with an HbA1c (A1C) difference of 0.9% between the two groups over 9 years. At 12 years, there were modest although significant differences, with absence of ankle tendon reflexes in 37 vs. 35%, absence of knee reflexes in 12 vs. 11%, and a basal heart rate of 74 vs. 70 bpm. There was a trend to lower risk of sensory neuropathy with better glycemic control. Treatment allocation in the UKPDS blood pressure substudy had no effect on neuropathy.

In an observational analysis of neuropathy progression in 4,867 people, an elevated threshold for bioesthesiometer perception was …