tbuckley/cabot-search huggingface dataset:
Cell Therapy of Peripheral Arterial Disease
Authors: Zankhana Raval, Douglas W. Losordo
Journal: Circulation Research (2013)

The age-adjusted prevalence of peripheral arterial disease in the US population was estimated to approach 12% in 1985, and as the population ages, the overall population having peripheral arterial disease is predicted to rise. The clinical consequences of occlusive peripheral arterial disease include intermittent claudication, that is, pain with walking, and critical limb ischemia (CLI), which includes pain at rest and loss of tissue integrity in the distal limbs, which may ultimately lead to amputation of a portion of the lower extremity. The risk factors for CLI are similar to those linked to coronary artery disease and include advanced age, smoking, diabetes mellitus, hyperlipidemia, and hypertension. The worldwide incidence of CLI was estimated to be 500 to 1000 cases per million people per year in 1991. The prognosis is poor for CLI subjects with advanced limb disease. One study of &gt;400 such subjects in the United Kingdom found that 25% required amputation and 20% (including some subjects who had required amputation) died within 1 year. In the United States, ≈280 lower-limb amputations for ischemic disease are performed per million people each year. The first objective in treating CLI is to increase blood circulation to the affected limb. Theoretically, increased blood flow could be achieved by increasing the number of vessels that supply the ischemic tissue with blood. The use of pharmacological agents to induce new blood vessel growth for the treatment or prevention of pathological clinical conditions has been called therapeutic angiogenesis. Since the identification of the endothelial progenitor cell in 1997 by Asahara and Isner, the field of cell-based therapies for peripheral arterial disease has been in a state of continuous evolution. Here, we review the current state of that field.
Hypertensive Crisis With Bilateral Bullous Retinal Detachment
Authors: Linda L. Stropes
Journal: JAMA (1977)

MALIGNANT hypertension develops in approximately 1% of patients with essential hypertension. Patients may have a variety of signs and symptoms related to neurologic, cardiac, renal, or gastrointestinal systems. Presentation of malignant hypertension as near total blindness with bilateral bullous retinal detachments is exceedingly rare, but this case underscores that all physicians, regardless of specialty, must take blood pressure measurements in all patients regardless of their complaints. <h3>Report of a Case</h3> In a 19-year-old man, blurred vision developed three weeks prior to admission to the hospital. He was seen by an ophthalmologist who diagnosed optic neuritis and prescribed prednisone, 20 mg every other day. His vision transiently improved, but then deteriorated to the point where he could differentiate only light from dark. He was referred to Indiana University Medical Center for further examination. He had a blood pressure reading of 300/170 mm Hg, and the visual acuity was impairedbilaterally so that
Dose-dependency of massage-like compressive loading on recovery of active muscle properties following eccentric exercise: rabbit study with clinical relevance
Authors: Caroline Haas, Timothy A Butterfield, Yi Zhao, Xiaoli Zhang, David Jarjoura, Thomas M Best
Journal: British Journal of Sports Medicine (2012)

Background Optimal strategies for massage and its use in athletes have not been conclusively demonstrated. Purpose/study design Effects of varying duration, frequency and magnitude of massage-like compressive loading (MLL) on recovery of skeletal muscle active properties (torque angle (T-Θ) relationship) following exercise-induced muscle injury were studied. Methods Twenty-four New Zealand White rabbits were surgically instrumented with bilateral peroneal nerve cuffs for stimulation of hindlimb tibialis anterior muscles. Following a bout of eccentric exercise (EEX), rabbits were randomly assigned to a MLL protocol of 0.25 or 0.5 Hz at 5 or 10 N for 15 or 30 min. T-Θ was obtained for 21 tibiotarsal joint angles pre- and post-EEX and post 4 consecutive days of MLL. Muscle wet weight and H&amp;E sections were obtained following final treatments. Results EEX produced an average 61.8%±2.1 decrease in peak isometric torque output. Differences in torque recovery were found between magnitudes (5 and 10 N; p=0.004, n=12) and frequencies (0.25 and 0.5 Hz; p=0.012, n=12), but no difference for durations (15 and 30 min) with the 0.5 Hz, 10 N, 15 min protocol showing greatest recovery 4 days post-EEX. MLL muscle (n=12) wet weight was 3.22±0.18 g, while no MLL tissue (n=9) weighed 3.74±0.22 g (p=0.029). Histological analysis showed a difference in torn fibres between low-parameter and high-parameter MLL (6.5±1.04 vs 0.5±0.29 per 0.59 mm 2 , p=0.005). Conclusions Results showed a dose-response effect for magnitude and frequency of MLL on recovery of active muscle properties following EEX. Future studies will investigate underlying biological mechanisms for this enhanced recovery of muscle function.
JAK–STAT pathway activation in COPD
Authors: Liang Yew-Booth, Mark A. Birrell, Ming Sum Lau, Katie Baker, Victoria Jones, Iain Kilty, Maria G. Belvisi
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung, most commonly resulting from cigarette smoke exposure, characterised by a largely irreversible and progressive airflow limitation [1, 2]. Currently, there are no disease-modifying therapies to prevent the relentless disease progression in patients with COPD. As a consequence, COPD is associated with high mortality and increasing prevalence worldwide [2]. Therefore, significant research effort has been directed to understanding the mechanism by which cigarette smoke exposure leads to the inflammation seen in COPD in the hope of discovering novel, effective anti-inflammatory therapies to tackle underlying pathogenic mechanisms. Cytokines are thought to be critical orchestrators of the persistent inflammation seen in several inflammatory diseases, including COPD. Many of these cytokines signal through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway and/or are produced as a result of JAK–STAT pathway signalling [3]. Thus, currently, there is considerable interest in developing JAK–STAT inhibitors as a potential treatment for COPD. However, there are no published studies that have comprehensively investigated the activation of all the STAT family members in tissue from COPD patients. Therefore, the aim of our study was to determine the extent of JAK–STAT pathway activation by detecting the presence of phosphorylated STAT proteins 1–6 in lung tissue from nonsmokers, healthy smokers and COPD patients (from transplant surgery) by Western blotting and immunohistochemistry (IHC). The hope was that this would provide important information regarding the role of the JAK–STAT pathway in COPD, which may in turn be useful in the development of novel treatments for COPD. JAK–STAT pathway activation in the lung of COPD patients <http://ow.ly/KTwCB>
Ventricular Diastolic Suction at Normal Arterial Pressures
Authors: GERHARD A. BRECHER, ABBOTT T. KISSEN
Journal: Circulation Research (1958)

It has been shown previously that an empty ventricle can suck in a small amount of fluid during diastole, but the question of whether a normal ventricle does so was not answered. In the present experiments it was demonstrated that even a ventricle with a more nearly normal endsystolic residual volume draws blood into its cavity and that this ventricular vis a fronte is augmented by the action of epinephrine.
All that wheezes is not asthma: the value of curves
Authors: Leigh M Seccombe, Liam Polley, Peter G Rogers, Alvin J Ing
Journal: Thorax (2011)

completely in the majority of cases, whereas occasionally they may regress with scarring constituted by linear opacities and bronchiectasis. 2 The posttreatment extensive cystic change was also considered to be rare.
P207 Obstructive sleep apnoea in patients undergoing bariatric surgery--a London teaching hospital experience
Authors: C. J. Jolley, S. Zimmerman, S. Shah, N. Davison, S. Singh
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Obstructive sleep apnoea (OSA) is common in patients scheduled for bariatric surgery and increases the likelihood of peri-operative adverse events. We aimed to describe the prevalence of OSA and risk profile of patients referred for pre-bariatric assessment locally. <h3>Methods</h3> A retrospective observational study of patients referred to the sleep clinic for assessment before bariatric surgery between June 2008 and February 2010. Clinical and anthropometric data were collected from the hospital notes and sleep studies. Patient-reported STOP BANG model scores were recorded or derived retrospectively from clinical data. Non-parametric statistics were used due to non-normally distributed data. <h3>Results</h3> 140/164 patients referred were seen in clinic. Referral rates increased from 2/month to 15/month in February 2010. The median (range) age was 46.5 (18–68) years, 71% female, weight 135.5 (87.4–180 kg), BMI 48.4 (35.3–84.5) kg/m<sup>2</sup>), and median ESS was 11 (0–24). STOP BANG scores were reported or could be calculated in 84 patients, in whom the median score was 5/8 (2–8). When incomplete STOP BANG scores were included, 124/130 scored &gt;2. 53% were non-smokers, 15% current smokers and were 37% ex-smokers. Comorbidities included: diabetes/IGT 70%, hypertension 50%, hypercholesterolaemia 39%, ACS/heart failure 9%, CVA 2%, COPD 3%, asthma 19%, and hypothyroidism 19%. Sleep studies were requested for 129 patients, completed in 116 patients. 114 were technically adequate for AHI and 106 for pulse oximetry. The median total AHI was 10.5 (0–111.2)/h, ODI 20.8 (0.2–145.2)/h, and mean SpO<sub>2</sub> 93.4 (78.3–98.6)%. 27% had AHI ≥5/h, 12% ≥15/h and 25% ≥30/h. Correlations between sleep study outcomes and clinical data are shown in Abstract P207 Table 1. Using STOP BANG &gt;2 to screen for AHI ≥5 had a sensitivity and specificity of 99.0% (95% CI 92.4 to 100%) and 5.6% (0.7–18.7%), respectively. <h3>Conclusions</h3> Referral rates for sleep studies pre-bariatric surgery have risen exponentially over the past 20 months, and 37% of patients studied had at least moderate OSA, presenting a burden for sleep services and CPAP provision. 35% of patients studied had no evidence of OSA. Although a sensitive test, STOP BANG alone did not reliably identify these lower-risk patients.
<scp>I</scp>g<scp>E</scp> detection to α/β/γ‐gliadin and its clinical relevance in wheat‐dependent exercise‐induced anaphylaxis
Authors: S. C. Hofmann, J. Fischer, C. Eriksson, O. Bengtsson Gref, T. Biedermann, T. Jakob
Journal: Allergy (2012)

Abstract Wheat‐dependent exercise‐induced anaphylaxis ( WDEIA ) is characterized by anaphylactic reactions after wheat ingestion and physical exercise. I g E antibodies to recombinant ω 5 ‐gliadin are detectable in a majority of WDEIA patients, but other wheat allergens may also play a role in elicitation of WDEIA . Here, we performed a comprehensive analysis of I g E reactivity to different wheat proteins in 17 patients with confirmed WDEIA by Immuno CAP research prototypes and a semi‐quantitative microarray immunoassay with α/β/γ‐gliadin, high‐molecular‐weight ( HMW ) glutenin, alpha‐amylase inhibitor ( AAI ) dimer, and wheat lipid transfer protein ( LTP ). By I mmuno CAP , I g E to recombinant ω 5 ‐gliadin was detectable in 14/17 patients (82%), to α/β/γ‐gliadin in 82% including the three patients lacking IgE to ω 5 ‐gliadin, and to HMW glutenin in 59%. The microarray revealed specifically γ‐gliadin as the second most important allergen. These results demonstrate the additional diagnostic value of α/β‐ and γ‐gliadin in particular in ω 5 ‐gliadin‐negative patients in the diagnosis of WDEIA .
Podocyte p53 Limits the Severity of Experimental Alport Syndrome
Authors: Ryosuke Fukuda, Mary Ann Suico, Yukari Kai, Kohei Omachi, Keishi Motomura, Tomoaki Koga, Yoshihiro Komohara, Kosuke Koyama, Tsubasa Yokota, Manabu Taura, Tsuyoshi Shuto, Hirofumi Kai
Journal: Journal of the American Society of Nephrology (2015)

Alport syndrome (AS) is one of the most common types of inherited nephritis caused by mutation in one of the glomerular basement membrane components. AS is characterized by proteinuria at early stage of the disease and glomerular hyperplastic phenotype and renal fibrosis at late stage. Here, we show that global deficiency of tumor suppressor p53 significantly accelerated AS progression in X-linked AS mice and decreased the lifespan of these mice. p53 protein expression was detected in 21-week-old wild-type mice but not in age-matched AS mice. Expression of proinflammatory cytokines and profibrotic genes was higher in p53(+/-) AS mice than in p53(+/+) AS mice. In vitro experiments revealed that p53 modulates podocyte migration and positively regulates the expression of podocyte-specific genes. We established podocyte-specific p53 (pod-p53)-deficient AS mice, and determined that pod-p53 deficiency enhanced the AS-induced renal dysfunction, foot process effacement, and alteration of gene-expression pattern in glomeruli. These results reveal a protective role of p53 in the progression of AS and in maintaining glomerular homeostasis by modulating the hyperplastic phenotype of podocytes in AS.
Evolutionary-new centromeres preferentially emerge within gene deserts
Authors: Mariana Lomiento, Zhaoshi Jiang, Pietro D'Addabbo, Evan E Eichler, Mariano Rocchi
Journal: Genome biology (2008)

Abstract Background Evolutionary-new centromeres (ENCs) result from the seeding of a centromere at an ectopic location along the chromosome during evolution. The novel centromere rapidly acquires the complex structure typical of eukaryote centromeres. This phenomenon has played an important role in shaping primate karyotypes. A recent study on the evolutionary-new centromere of macaque chromosome 4 (human 6) showed that the evolutionary-new centromere domain was deeply restructured, following the seeding, with respect to the corresponding human region assumed as ancestral. It was also demonstrated that the region was devoid of genes. We hypothesized that these two observations were not merely coincidental and that the absence of genes in the seeding area constituted a crucial condition for the evolutionary-new centromere fixation in the population. Results To test our hypothesis, we characterized 14 evolutionary-new centromeres selected according to conservative criteria. Using different experimental approaches, we assessed the extent of genomic restructuring. We then determined the gene density in the ancestral domain where each evolutionary-new centromere was seeded. Conclusions Our study suggests that restructuring of the seeding regions is an intrinsic property of novel evolutionary centromeres that could be regarded as potentially detrimental to the normal functioning of genes embedded in the region. The absence of genes, which was found to be of high statistical significance, appeared as a unique favorable scenario permissive of evolutionary-new centromere fixation in the population.
Influence of variants of Fc receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor therapy in rheumatoid arthritis
Authors: J D Canete, B Suarez, M V Hernandez, R Sanmarti, I Rego, R Celis, C Moll, J A Pinto, F J Blanco, F Lozano
Journal: Annals of the Rheumatic Diseases (2008)

Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed.A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed.At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses.The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.
Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study.
Authors: S J Gallacher, J A Fenner, K Anderson, F M Bryden, S W Banham, F C Logue, R A Cowan, I T Boyle
Journal: Thorax (1992)

Bisphosphonates have been shown to be effective agents in the treatment of postmenopausal osteoporosis. Because corticosteroid associated osteoporosis is often associated with increased bone turnover, the effect of intermittent intravenous infusions of pamidronate on this condition has been investigated.Seventeen patients (five male) with chronic corticosteroid dependent lung disease (15 asthma, two sarcoidosis) were treated with infusions of 30 mg pamidronate once every three months for one year. These patients had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary hydroxyproline: creatinine ratio at the same time as densitometry and radiography were performed.Pretreatment density of L2-4 and the neck of the femur was significantly lower in these patients compared with a cohort of 100 age and sex matched controls (L2-4 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary hydroxyproline:creatinine ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in L2-4 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur.Intermittent infusions of intravenous pamidronate would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced osteoporosis associated with chronic lung disease. Longer term controlled studies are indicated.
Generation of Kidney Cancer-Specific Antitumor Immune Responses Using Peripheral Blood Monocytes Transduced With a Recombinant Adenovirus Encoding Carbonic Anhydrase 9
Authors: Hideki Mukouyama, Nicolette K. Janzen, Jose M. Hernandez, John S. Lam, Randy Caliliw, Allen Y. Wang, Robert A. Figlin, Arie S. Belldegrun, Gang Zeng
Journal: Clinical Cancer Research (2004)

Carbonic anhydrase 9 (CA9) is the most promising molecular marker described for renal cell carcinoma (RCC) to date. We investigated whether transduction of monocytes from peripheral blood with adenovirus encoding the CA9 gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer cells expressing CA9. The ability to consistently generate a T-cell response is an important step toward the development of a CA9-specific RCC vaccine.AdV-CA9 was generated using the AdEasy system. AdV-CA9-transduced peripheral blood mononuclear cell (PBMC)-derived monocytes were used to raise CTLs from autologous peripheral blood lymphocytes (PBLs). The ability of CTLs to lyse targets expressing CA9 was assessed by (51)Cr-release.Monocytes were efficiently transduced with AdV-CA9. In five of six experiments, AdV-CA9-transduced monocytes were able to induce a population of CTLs from bulk PBLs. CTLs were capable of lysing autologous, but not allogeneic monocytes expressing CA9. Furthermore, CTLs were able to lyse autologous RCC tumor cells expressing CA9. The ability of CTLs to lyse relevant targets was blocked by anti-CD3, anti-CD8, and anti-MHC class I antibodies demonstrating a MHC class I restricted response.These results suggest that PBMC-derived monocytes transduced with AdV-CA9 can generate RCC-specific MHC class I restricted CTLs capable of lysing CA9-expressing cancer cells. Transduction of PBMC-derived monocytes with adenovirus provides a simple and effective alternative to the use of dendritic cells for the induction of antigen-specific CTL.
Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease
Authors: H. Milburn, N. Ashman, P. Davies, S. Doffman, F. Drobniewski, S. Khoo, P. Ormerod, M. Ostermann, C. Snelson
Journal: Thorax (2010)

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of <i>Mycobacterium tuberculosis</i> infection and disease in patients with all grades of renal impairment.
Physical working capacity and mile run performance in adolescent boys.
Authors: J. Watkins, B. G. Ewing
Journal: British Journal of Sports Medicine (1983)

The degree of generality between the endurance characteristics of the one mile run and PWC170 tests was examined with a group of fifteen year old boys who performed both tests once a week for three weeks. A significant improvement in performance of both tests was found between trials 1 and 2, which was sustained between trials 2 and 3. These results suggest that norm scales regarding performance in both tests should be based on the average of at least two trials following a practice trial. The results of the present study also suggest that when average scores are used, rather than single scores, the amount of generality between the endurance characteristics of the one mile run and PWC170 test is high enough to allow physical working capacity to be predicted fairly accurately from performance in the one mile run.
Oestrogen-like effect of tamoxifen on vaginal epithelium.
Authors: E Ferrazzi, G Cartei, R Mattarazzo, M Fiorentino
Journal: BMJ (1977)

30-40 mg tamoxifen were administered orally in 86 postmenopausal women with late breast malignancy who were found to be resistant to standard endocrine and chemotherapy 2 months previous to this treatment. Vaginal smears were taken before and after 30-45 days treatment. A zero pyknotic index was seen before treatment. After tamoxifen, the index regularly increased to values between 10-30% reaching 50% in 4 cases and 80% in 1. Smears became atrophic within 2 months of withdrawal of treatment. 32% of the patients responded, showing an objective tumor regression. It is unclear whether the tumor is reacting to tamoxifen as if it were an estrogen.