tbuckley/cabot-search huggingface dataset:
Whole-body resting and exercise-induced lipolysis in sarcopaenic patients with COPD
Authors: F. M. E. Franssen, H. P. Sauerwein, E. P. A. Rutten, E. F. M. Wouters, A. M. W. J. Schols
Journal: European Respiratory Journal (2008)

Impaired beta-adrenoceptor-mediated lipolysis has been reported in sarcopenic [corrected] chronic obstructive pulmonary disease (COPD) patients. This could play a role in the shift in body composition towards decreased fat-free mass (FFM) and relative maintenance of fat mass (FM). Lipolysis could be affected by chronic treatment with beta(2)-agonists or disease-related factors. Therefore, whole-body resting and exercise-induced lipolysis were investigated in sarcopenic [corrected] COPD patients with moderate disease severity. Seven sarcopenic [corrected] COPD patients (mean+/-sem forced expiratory volume in one second (FEV(1)) 53+/-5% of the predicted value; body mass index (BMI) 27.5+/-0.9 kg x m(-2)) and seven controls matched for age, sex and BMI were studied. In addition, six underweight COPD patients (FEV(1) 51+/-5% pred; BMI 20.6+/-0.7 kg x m(-2)) matched for disease severity were recruited. Lipolysis and plasma levels of catecholamines were assessed during infusion of [(2)H(5)]glycerol at rest and during submaximal cycling exercise. The proportional FM was comparable between sarcopenic [corrected] patients and controls, whereas the FFM index was significantly reduced in patients. At rest, the rate of appearance (R(a)) of glycerol (4.1+/-0.6 and 3.3+/-0.2 micromol x kg FFM(-1) x min(-1), respectively) did not differ significantly. In underweight patients, glycerol R(a) (4.3+/-0.5 micromol x kg FFM(-1) x min(-1)) was also comparable. End-of-exercise lipolytic rates did not differ significantly between groups. Glycerol R(a) was not related to FM. Resting adrenalin levels were significantly increased in underweight COPD patients and were related to resting lipolysis. Sarcopenia [corrected] in chronic obstructive pulmonary disease patients with moderate disease severity is not characterised by an abnormal lipolytic rate. Altered regulation of muscle protein turnover seems to be the trigger in the body compositional shift observed in these patients.
Patterns and Predictors of Amelioration of Genitourinary Toxicity After High-dose Intensity-modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Postradiotherapy Urinary Toxicity
Authors: Pirus Ghadjar, Andrew Jackson, Daniel E. Spratt, Jung Hun Oh, Per Munck af Rosenschöld, Marisa Kollmeier, Ellen Yorke, Margie Hunt, Joseph O. Deasy, Michael J. Zelefsky
Journal: European Urology (2013)
Molecular Evolution of the Ankyrin Gene Family
Authors: Xinjiang Cai, Yanhong Zhang
Journal: Molecular Biology and Evolution (2005)

Ankyrins are membrane adaptor molecules that play important roles in coupling integral membrane proteins to the spectrin-based cytoskeleton network. Human mutations of ankyrin genes lead to severe genetic diseases such as fatal cardiac arrhythmias and hereditary spherocytosis. To elucidate the evolutionary history of ankyrins, we have identified novel ankyrin sequences in insect, fish, frog, chicken, dog, and chimpanzee genomes and explored the phylogenetic relationships of the ankyrin gene family. Our data demonstrate that duplication of ankyrin genes occurred at two different stages. The first duplication resulted from an independent evolution event specific in Arthropoda after its divergence from Chordata. Following the separation from Urochordata, expansion of ankyrins in vertebrates involved ancestral genome duplications. We did not find evidence of coordinated arrangements of gene families of ankyrin-associated membrane proteins on paralogous chromosomes. In addition, evolution of the 24 ANK-repeats strikingly correlated with the exon boundary sites of ankyrin genes, which might have occurred before its duplication in vertebrates. Such correlation is speculated to bring functional diversity and complexity. Moreover, based on the phylogenetic analysis of the ANK-repeat domain, we put forward a novel model for the putative primordial ankyrin that contains the fourth six–ANK-repeat subdomain and the spectrin-binding domain. These findings will provide guides for future studies concerning structure, function, evolutionary origins of ankyrins, and possibly other cytoskeletal proteins.
Complete Antitumor Protection by Perioperative Immunization with GM3/VSSP Vaccine in a Preclinical Mouse Melanoma Model
Authors: Mariano R. Gabri, Zaima Mazorra, Giselle V. Ripoll, Circe Mesa, Luis E. Fernandez, Daniel E. Gomez, Daniel F. Alonso
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The GM3/VSSP vaccine is composed of very small sized proteoliposomes resulting from the hydrophobic conjugation of GM3 ganglioside with membrane proteins from Neisseria meningitidis. Previously, we showed that preventive vaccination with GM3/VSSP induces a specific antitumor response and elicits the rejection of syngeneic GM3-positive melanoma cells in immunized mice. Our aim was to explore the antitumor properties of perioperative GM3/VSSP vaccination in a preclinical mouse model. Experimental Design: The highly metastatic B16F10 mouse melanoma was used to investigate perioperative vaccination with GM3/VSSP. The vaccine was administered i.m. in doses of 120 μg emulsified with the adjuvant Montanide ISA 51 at weekly or biweekly intervals, and s.c. tumors were excised 25 to 31 days after tumor cell implantation. The persistence of antitumor protection and dose dependency was also examined in preimmunized animals. To evaluate the immune performance of tumor-bearing and tumor-operated mice, ovoalbumin-specific delayed-type hypersensitivity, cytokine secretion, and cell proliferation responses were studied. Results: Surgical excision of B16F10 tumors improved survival, and perioperative immunization with four biweekly GM3/VSSP doses yielded survival for all animals (P = 0.04; log-rank test). Mice showed neither local recurrence nor lung metastasis at the end of the experiment. An impairment of CD4+ T-cell responses was observed in tumor-bearing animals measured as neoantigen-specific delayed-type hypersensitivity, with a significant recovery after surgery. A strong interleukin-4 secretion was induced in B16F10-operated mice, whereas IFN-γ remained unaffected. Conclusion: Preclinical evidence suggests that GM3/VSSP vaccine might have therapeutic potential to induce antitumor immunity in patients with minimal residual disease after surgery, thereby preventing or prolonging the time to recurrence.
Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study
Authors: E. Odding, H. A Valkenburg, D. Algra, F. A Vandenouweland, D. E Grobbee, A. Hofman
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function. <h3>METHODS</h3> During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis. <h3>RESULTS</h3> The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women). <h3>CONCLUSIONS</h3> Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability.
THE SIGNIFICANCE OF THE EPITHELIAL CELLS AND SAPROPHYTES IN SPUTUM
Authors: Morisuke Otani
Journal: The Journal of Experimental Medicine (1917)

1. Microscopical examination of sputum that has been washed with isotonic salt solution indicates its source. Sputum from above the vocal cords contains polygonal flat epithelial cells and numerous species of non-pathogenic microorganisms. Sputum from below the cords is clear of saprophytes, although it sometimes contains bronchoalveolar cuboidal cells. 2. The source of the sputum can be determined by the erythrocytes and the bacilli that are contained in it, and the site of the lesion can also be ascertained. 3. In every instance I found erythrocytes in the pulmonary sputum after severe pulmonary hemorrhage. 4. Six of the cases of laryngeal affection referred to in the presentpaper had had no subjective symptoms, but microscopical examination showed tubercle bacilli in the laryngeal sputum. All the six cases were examined by Dr. Tanaka and were found to have tuberculous lesions in the larynx. In the laryngeal sputum of most cases of laryngeal tuberculosis with symptoms, tubercle bacilli have been frequently demonstrated, while in some cases contaminated laryngeal sputum was obtained only after a long series of examinations. 5. Microscopical examination of the sputum plays a significant part in the diagnosis of tuberculosis.
Clinical utility of blood tests in elite athletes with short term fatigue * Commentary
Authors: K E Fallon
Journal: British Journal of Sports Medicine (2006)

To determine, in a population of elite athletes at their initial presentation with tiredness or fatigue, whether a set of haematological and biochemical investigations enhances the diagnostic process over and above the information gained from clinical history and examination.A sequential series of 50 elite athletes were studied at the initial consultation for a primary complaint of fatigue, tiredness, or a synonym thereof. A standardised clinical history, physical examination, and series of haematological and biochemical test were performed. The effects of the results of the blood tests on the diagnosis made after the clinical history and examination were examined.In only one case did the test results lead to an alteration in diagnosis. Physical examination did not provide any findings that would not have been suspected from the history, except for a number of incidental findings not relevant to the presenting symptom.In cases of short term fatigue in elite athletes, a thorough clinical history is mandatory. Physical examination is unlikely to reveal any findings not suspected from the history. Routine ordering of a panel of blood tests at the initial consultation should be discouraged. Unless specifically indicated by the history and examination, investigations are not required at the initial consultation.
A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK
Authors: F Drobniewski
Journal: Thorax (2002)

<b>Background:</b> This study aimed to describe the clinical, microbiological, molecular epidemiology and treatment of multidrug resistant tuberculosis (MDRTB) cases in the UK and to determine factors associated with survival. <b>Methods:</b> Ninety MDRTB cases were identified from 1 January 1996 to 30 June 1997; 69 were DNA fingerprinted. Date of diagnosis was determined and data were collated on key demographic factors, clinical, radiological and treatment details. Variables associated with survival were included in a Cox proportional hazards model. <b>Results:</b> Most of the patients (72.4%) were male, born outside the UK (57.1%), were sputum smear positive (82.2%), and had entered the UK more than 5 years previously (61.9%). Thirty eight of 78 cases (48.7%) had prior TB. Sufficient data on 82 patients were available for survival analysis; 20/27 (74.1%) known to be dead at the end of the observation period had died of tuberculosis. Median survival time overall was 1379 days (95% CI 1336 to 2515) or 3.78 (95% CI 3.66 to 6.89) years (858 days (95% CI 530 to 2515) in immunocompromised individuals (n=32) and 1554 (95% CI 1336 to 2066) days in immunocompetent cases (n=48)). Median survival in patients treated with three drugs to which the bacterium was susceptible on in vitro testing (n=62) was 2066 days (95% CI 1336 to 2515) or 5.66 years, whereas in those not so treated (n=13) survival was 599 days (95% CI 190 to 969) or 1.64 years. <b>Conclusions:</b> Immunocompromised status, failure to culture the bacterium in 30 days or to apply appropriate three drug treatment, and age were significant factors in mortality. An immunocompromised patient was nearly nine times more likely to die, while application of appropriate treatment reduced the risk (risk ratio 0.06). Increasing age was associated with increasing risk of death (risk ratio 2.079; 95% CI 1.269 to 3.402)—that is, for every 10 year increase in age the risk almost doubled. Overall survival was lower than that reported in previous studies.
Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness.
Authors: R Ventura-Clapier, V Veksler
Journal: Circulation Research (1994)

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)-ATP50 to 3.71 +/- 0.04 (P &lt; .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P &lt; .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P &lt; .001) and presence (5.44 +/- 0.02, P &lt; .001) of PCr. Conversely, Mg(2+)-ADP (250 mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P &lt; .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to &lt; 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal rigor tension developed to 143% of the control value; P(i) had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg(2+)-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.
Year in review in Intensive Care Medicine 2010: I. Acute renal failure, outcome, risk assessment and ICU performance, sepsis, neuro intensive care and experimentals
Authors: Massimo Antonelli, Elie Azoulay, Marc Bonten, Jean Chastre, Giuseppe Citerio, Giorgio Conti, Daniel De Backer, Herwig Gerlach, Goran Hedenstierna, Michael Joannidis, Duncan Macrae, Jordi Mancebo, Salvatore M. Maggiore, Alexandre Mebazaa, Jean-Charles Preiser, Jerôme Pugin, Jan Wernerman, Haibo Zhang
Journal: Intensive Care Medicine (2011)

Acute renal injuryAcute renal failure (or acute kidney injury, AKI) is an important issue in critical care because, as was demonstrated in the past, the patients' prognosis is dependent on the disturbed renal function.In 2010, four interesting reviews were presented dealing with general, but also with some specific issues of AKI in critically ill patients: One of the utmost important topics in this context is the question if and how AKI may be prevented in patients at risk for
Clinical efficacy of anti-pneumococcal vaccination in patients with COPD
Authors: I Alfageme
Journal: Thorax (2005)

<b>Background:</b> A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD). <b>Methods:</b> A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20–1454). <b>Results:</b> There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI −24 to 54; p = 0.333). In the subgroup aged &lt;65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second &lt;40%) it was 48% (95% CI −7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01). <b>Conclusions:</b> PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.
Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP
Authors: Francois G. Gervais, Rani P.G. Cruz, Anne Chateauneuf, Stephen Gale, Nicole Sawyer, Francois Nantel, Kathleen M. Metters, Gary P. O'Neill
Journal: Journal of Allergy and Clinical Immunology (2001)
Phylogeography and Ethnogenesis of Aboriginal Southeast Asians
Authors: Catherine Hill, Pedro Soares, Maru Mormina, Vincent Macaulay, William Meehan, James Blackburn, Douglas Clarke, Joseph Maripa Raja, Patimah Ismail, David Bulbeck, Stephen Oppenheimer, Martin Richards
Journal: Molecular Biology and Evolution (2006)

Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula ∼4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia.
Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes
Authors: Céline Dubuquoy, Céline Robichon, Françoise Lasnier, Clotilde Langlois, Isabelle Dugail, Fabienne Foufelle, Jean Girard, Anne-Françoise Burnol, Catherine Postic, Marthe Moldes
Journal: Journal of Hepatology (2010)
Smoking Is Related to Albuminuria and Abnormal Renal Function in Nondiabetic Persons
Authors: Sara-Joan Pinto-Sietsma
Journal: Annals of Internal Medicine (2000)

Background: Smoking induces albuminuria and accelerates progression to renal failure in persons with diabetes, but little is known about the relation between smoking and renal function in nondiabetic persons. Objective: To investigate whether smoking is related to albuminuria and abnormal renal function in nondiabetic persons. Design: Cross-sectional study. Setting: Groningen, The Netherlands. Participants: 7476 participants in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study. Measurements: Microalbuminuria and high normal albuminuria were defined as urinary albumin excretion of 30 to 300 mg/24 h and 15 to 30 mg/24 h, respectively. Elevated or decreased glomerular filtration rate (GFR) was defined as a creatinine clearance that exceeded or was less than two times the standard deviation of the mean value in nondiabetic, nonsmoking participants who had an albumin excretion of 0 to 15 mg/24 h, adjusted for age and sex. Results: Current smokers had a higher median albumin excretion than nonsmokers and were more likely to have microalbuminuria and high normal albuminuria with elevated or decreased GFR. After adjustment for several potential confounding factors, persons who smoked 20 or fewer cigarettes/d and persons who smoked more than 20 cigarettes/d, respectively, showed a dose-dependent association between smoking and high normal albuminuria (relative risk, 1.33 [95% CI, 1.10 to 1.61] and 1.98 [CI, 1.49 to 2.64]), microalbuminuria (relative risk, 1.92 [CI, 1.54 to 2.39] and 2.15 [CI, 1.52 to 3.03]), elevated GFR (relative risk, 1.82 [CI, 1.31 to 2.53] and 1.84 [CI, 1.12 to 3.02]), and decreased GFR (relative risk, 1.53 [CI, 1.04 to 2.24] and 1.83 [CI, 1.05 to 3.20]), respectively. Quitting smoking was associated only with microalbuminuria. Conclusions: Smoking is associated with albuminuria and abnormal renal function. However, these associations are less pronounced or absent in former smokers.