tbuckley/cabot-search huggingface dataset:
Sprint Training Increases Muscle Oxidative Metabolism During High-Intensity Exercise in Patients With Type 1 Diabetes
Authors: Alison R. Harmer, Donald J. Chisholm, Michael J. McKenna, Sandra K. Hunter, Patricia A. Ruell, Justine M. Naylor, Lyndal J. Maxwell, Jeff R. Flack
Journal: Diabetes Care (2008)

To investigate sprint-training effects on muscle metabolism during exercise in subjects with (type 1 diabetic group) and without (control group) type 1 diabetes.Eight subjects with type 1 diabetes and seven control subjects, matched for age, BMI, and maximum oxygen uptake (Vo(2peak)), undertook 7 weeks of sprint training. Pretraining, subjects cycled to exhaustion at 130% Vo(2peak). Posttraining subjects performed an identical test. Vastus lateralis biopsies at rest and immediately after exercise were assayed for metabolites, high-energy phosphates, and enzymes. Arterialized venous blood drawn at rest and after exercise was analyzed for lactate and [H(+)]. Respiratory measures were obtained on separate days during identical tests and during submaximal tests before and after training.Pretraining, maximal resting activities of hexokinase, citrate synthase, and pyruvate dehydrogenase did not differ between groups. Muscle lactate accumulation with exercise was higher in type 1 diabetic than nondiabetic subjects and corresponded to indexes of glycemia (A1C, fasting plasma glucose); however, glycogenolytic and glycolytic rates were similar. Posttraining, at rest, hexokinase activity increased in type 1 diabetic subjects; in both groups, citrate synthase activity increased and pyruvate dehydrogenase activity decreased; during submaximal exercise, fat oxidation was higher; and during intense exercise, peak ventilation and carbon dioxide output, plasma lactate and [H(+)], muscle lactate, glycogenolytic and glycolytic rates, and ATP degradation were lower in both groups.High-intensity exercise training was well tolerated, reduced metabolic destabilization (of lactate, H(+), glycogenolysis/glycolysis, and ATP) during intense exercise, and enhanced muscle oxidative metabolism in young adults with type 1 diabetes. The latter may have clinically important health benefits.
Inhaled corticosteroids in COPD: a case in favour
Authors: D. S. Postma, P. Calverley
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, which is characterised by reduced post-bronchodilator lung function in all patients 1. Although hyperresponsiveness and acute bronchodilator reversibility have been regarded as characteristics of asthma, it is now generally acknowledged that these clinical features are also present in COPD. Results as high as 39–66% for reversibility 2, dependent on the method of expression, and 60% for hyperresponsiveness, as measured with methacholine, have been reported. Patients generally show progressive lung function loss, accompanied by worsening respiratory symptoms and health status 1. These clinical features are associated with airway inflammation, i.e. bronchial infiltration of neutrophils, macrophages, lymphocytes, and mast cells 3–5. Smoking accelerates lung function loss and increases mortality in COPD, and smoking cessation has consistently been shown to improve these outcomes. Other risk factors for a worse prognosis include higher age, female sex, airway hyperresponsiveness, sputum production, underweight and frequent exacerbations 1. As well as smoking cessation, it is logical to investigate whether treatment that changes these risk factors and/or their underlying mechanisms can also change the long-term outcome of COPD.

Many studies have assessed the long-term benefits of available COPD treatments, such as inhaled corticosteroids (ICS), long-acting β2-agonists (LABA) and long-acting anticholinergics. As a result, current guidelines recommend treatment with ICS for patients with severe COPD and frequent exacerbations, in addition to long-acting bronchodilators for patients with moderate-to-severe COPD 1. Below we summarise evidence advising the use of ICS or ICS+LABA in COPD from double-blind studies with intermediate (1–2 yrs) and long-term (>2 years) follow-up.

It is now clear that regular anti-inflammatory treatment with ICS improves symptoms, health status and forced expiratory volume in 1 s (FEV1) while decreasing exacerbation rates 6–9. Withdrawing ICS (under protection of LABA) in …
Familial influence on tibiofemoral alignment
Authors: Abdurrahman Tufan, Ingrid Meulenbelt, Jessica Bijsterbosch, Herman M Kroon, Sita M A Bierma-Zeinstra, Rob G Nelissen, Margreet Kloppenburg
Journal: Annals of the Rheumatic Diseases (2009)

Background Tibiofemoral alignment has a role in knee osteoarthritis (OA), but which factors contribute to alignment is unknown. Objective To investigate familial aggregation of tibiofemoral alignment in participants of the GARP (Genetics ARthrosis and Progression) study. Methods The tibiofemoral anatomical angle on semiflexed knee radiographs was measured in sibling pairs (mean age 60 years, 81% women) with primary OA with multiple joint involvement. Radiographic OA was assessed according to the Kellgren–Lawrence (KL) method. Heritability estimates of the tibiofemoral angle were calculated by comparing twice the between-sibling variance with the total variance; adjustments were made for age, gender, body mass index, history of meniscectomy, lower limb fracture and in analyses including all knees, for KL score. Results 360 subjects representing 180 families were studied. The mean (SD) tibiofemoral angle of right and left knees in the probands was 182.7 (2.9)° and 182.8 (2.6)°, respectively; similar angles were measured in the siblings. Radiographic knee OA (KL score ≥2) was present in 27% of the knees. Stratified analyses in sib pairs with non-osteoarthritic right or left knees showed adjusted heritability estimates of the tibiofemoral angle of the right and left knees of 0.42 (95% CI 0.02 to 0.82) and 0.56 (95% CI 0.19 to 0.93). In addition, adjusted heritability estimates of the tibiofemoral angle in all right and left knees were calculated, being 0.48 (95% CI 0.18 to 0.78) and 0.50 (95% CI 0.21 to 0.79), respectively. Conclusion The alignment of the tibiofemoral joint is influenced by familial factors, implying that tibiofemoral malalignment may add to the genetic predisposition for knee OA development. These results need to be confirmed in other study populations.
Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer
Authors: Juan Valle, Harpreet Wasan, Daniel H. Palmer, David Cunningham, Alan Anthoney, Anthony Maraveyas, Srinivasan Madhusudan, Tim Iveson, Sharon Hughes, Stephen P. Pereira, Michael Roughton, John Bridgewater
Journal: New England Journal of Medicine (2010)

There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here.We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival.After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups.As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.)
Primary Health and Supportive Care Needs of Long-Term Cancer Survivors: A Questionnaire Survey
Authors: Siân E. Harrison, Eila K. Watson, Alison M. Ward, Nada F. Khan, Daniel Turner, Eike Adams, David Forman, Monica F. Roche, Peter W. Rose
Journal: Journal of Clinical Oncology (2011)

There are 1.2 million long-term cancer survivors in the United Kingdom. Existing research on the health and supportive care needs of these survivors is sparse and inconclusive. This study investigated health status, psychological morbidity, and supportive care needs in long-term cancer survivors in the United Kingdom.Five to 16 years after diagnosis, 1,275 eligible survivors of breast, colorectal, and prostate cancers were approached to participate in a questionnaire survey. The questionnaire explored health status (European Quality of Life-5 Dimensions), psychological morbidity (Hospital Anxiety and Depression Scale), and supportive care needs (Cancer Survivors' Unmet Needs Measure). Data were analyzed by type of cancer and time since diagnosis. Logistic regression was used to identify predictors of unmet supportive care needs.The response rate was 51.7% (659 survivors). Overall health status and levels of psychological morbidity were consistent with population norms. At least one unmet supportive care need was reported by 47.4% of survivors, but overall numbers of unmet needs were low (mean, 2.8; standard deviation, 4.8). The most frequently endorsed unmet need was for help to manage concerns about cancer recurrence. Trait anxiety (P < .001), nondischarged status (P < .01), dissatisfaction with discharge (P < .01), and receipt of hormonal therapy (P < .01) were predictive of unmet supportive care needs.The findings suggest a majority of long-term breast, colorectal, and prostate cancer survivors who have no signs of recurrence report good health and do not have psychological morbidity or large numbers of unmet supportive care needs. A minority of long-term survivors may benefit from ongoing support. The identification and support of those long-term survivors with ongoing needs is a key challenge for health care professionals.
Effect of Serotonin Receptor Antagonist on Phosphate Excretion
Authors: JENNIFER M. GROSS, THERESA J. BERNDT, FRANKLYN G. KNOX
Journal: Journal of the American Society of Nephrology (2000)

Abstract. To determine whether endogenous intrarenal 5-hydroxytryptamine affects phosphate excretion, the serotonin receptor antagonist methiothepin (20 μg/kg, +6 μg/kg per h) was infused into the renal interstitium of rats fed a normal phosphate diet (0.7% phosphate [Pi]) in the presence of endogenous parathyroid hormone (PTH). Renal interstitial infusion of methiothepin significantly increased fractional phosphate excretion (FE Pi ) from 23 ± 4 to 30 ± 4% ( n = 8, P &lt; 0.05). To determine whether serotonin modulates the phosphaturic response to PTH during conditions of dietary phosphate excess or deprivation, rats were fed either a high (1.8% Pi, HPD) or low (0.07% Pi, LPD) phosphate diet, and methiothepin (100 μg/kg, +30 μg/kg per h) or saline vehicle was infused intravenously before and during PTH infusion (33 U/kg, +1 U/kg per min). Methiothepin infusion significantly increased FE Pi in thyroparathyroidectomized rats fed a HPD from 25 ± 4 to 32 ± 4% ( n = 9, P &lt; 0.05), and the subsequent administration of PTH further increased the FE Pi to 64 ± 3% ( P &lt; 0.05). The increase in FE Pi during PTH infusion was similar in the absence (Δ27 ± 5%, n = 7) and presence (Δ33 ± 6%) of methiothepin, P &gt; 0.05. In thyroparathyroidectomized rats fed a LPD, methiothepin infusion did not increase phosphate excretion (0.8 ± 0.4 to 1.3 ± 0.9%, n = 7, P &gt; 0.05). However, the increase in FE Pi during PTH infusion was significantly greater in the presence of methiothepin (1.3 ± 0.9 to 20.0 ± 4.0%, Δ18.7 ± 3.5%) than in the vehicle-infused rats (0.5 ± 0.2 to 8.8 ± 1.1%, Δ8.3 ± 1.2%; n = 8, P &lt; 0.05). In conclusion, these observations suggest that endogenous intrarenal serotonin enhances phosphate reabsorption in phosphate-replete rats, and attenuates the phosphaturic response to PTH in phosphate-deprived rats.
Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling
Authors: Meng-Ju Wu, Chia-Ing Jan, Yeou-Guang Tsay, Yau-Hua Yu, Chih-Yang Huang, Shu-Chun Lin, Chung-Ji Liu, Yu-Syuan Chen, Jeng-Fan Lo, Cheng-Chia Yu
Journal: Molecular Cancer (2010)

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated.Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+) exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN.In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.
Respiratory health and dust levels in cottonseed mills.
Authors: R N Jones, J Carr, H Glindmeyer, J Diem, H Weill
Journal: Thorax (1977)

Four cottonseed mills in the southern United States contained high levels of total and respirable dust. A survey of 172 workers showed low prevalences of byssinosis (2-3%) and chronic bronchitis (4%). Mean baseline (out of dust) lung function values were normal. Mean functional declines over the working shift were present on Monday and absent on Friday, indicating an acute bronchoconstrictor response. Despite limitations in translating measured dust levels into estimates of individual exposures, the overall dose-response relationship seems to differ from that found in the cotton textile industry.
Attenuation of ischaemia reperfusion injury by human thioredoxin.
Authors: T Fukuse, T Hirata, H Yokomise, S Hasegawa, K Inui, A Mitsui, T Hirakawa, S Hitomi, J Yodoi, H Wada
Journal: Thorax (1995)

Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury.Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed.In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls.These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.
Androgen-Sensitive Hypertension Associates with Upregulated Vascular CYP4A12–20-HETE Synthase
Authors: Cheng-Chia Wu, Shaojun Mei, Jennifer Cheng, Yan Ding, Adam Weidenhammer, Victor Garcia, Fan Zhang, Katherine Gotlinger, Vijaya L. Manthati, John R. Falck, Jorge H. Capdevila, Michal L. Schwartzman
Journal: Journal of the American Society of Nephrology (2013)

Although the mechanism underlying the effect of androgen on BP and cardiovascular disease is not well understood, recent studies suggest that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a primary cytochrome P450 4 (Cyp4)-derived eicosanoid, may mediate androgen-induced hypertension. Here, treatment of normotensive mice with 5α-dihydrotestosterone increased BP and induced both Cyp4a12 expression and 20-HETE levels in preglomerular microvessels. Administration of a 20-HETE antagonist prevented and reversed the effects of dihydrotestosterone on BP. Cyp4a14(-/-) mice, which exhibit androgen-sensitive hypertension in the male mice, produced increased levels of vascular 20-HETE; furthermore, administration of a 20-HETE antagonist normalized BP. To examine whether androgen-independent increases in 20-HETE are sufficient to cause hypertension, we studied Cyp4a12-transgenic mice, which express the CYP4A12-20-HETE synthase under the control of a doxycycline-sensitive promoter. Administration of doxycycline increased BP by 40%, and administration of a 20-HETE antagonist prevented this increase. Levels of CYP4A12 and 20-HETE in preglomerular microvessels of doxycycline-treated transgenic mice approximately doubled, correlating with increased 20-HETE-dependent sensitivity to phenylephrine-mediated vasoconstriction and with decreased acetylcholine-mediated vasodilation in the renal microvasculature. We observed a similar contribution of 20-HETE to myogenic tone in the mesenteric microvasculature. Taken together, these results suggest that 20-HETE both mediates androgen-induced hypertension and can cause hypertension independent of androgen.
THE ROLE OF IMMUNOGENICITY IN THE INDUCTION OF TOLERANCE WITH CONJUGATES OF ARSANILIC ACID
Authors: Clelia Collotti, Sidney Leskowitz
Journal: The Journal of Experimental Medicine (1970)

A number of azobenzenearsonate (ABA) conjugates have been prepared and tested for ability to react with antibody, to sensitize for hapten-specific delayed hypersensitivity and to induce hapten-specific unresponsiveness. All conjugates tested by in vitro or in vivo methods show a capacity to react with preformed antibody. Conjugates of L-amino acid polymers are immunogenic and induce tolerance. Conjugates of D-amino acid polymers or conjugates with high density of ABA groups are nonimmunogenic and fail to induce tolerance. Since paired D- and L-polymer conjugates react comparably with preformed antibody but differ markedly in tolerance induction, it is argued that combination with an antibody-like receptor molecule on the surface of an immune-competent cell is not a sufficient condition for tolerance. The lack of effectiveness of sterically crowded conjugates as well as D-polymer conjugates argues for a preliminary biologic "processing" of antigen necessary for induction of immunity or tolerance. Such a processing event might well involve enzymatic attack on the antigen.
1066 INHIBITION OF TISSUE INHIBITOR OF METALLOPROTEINASE-1 BY RECOMBINANT ADENO-ASSOCIATED VIRUSES CARRYING SIRNA PREVENTS LIVER FIBROSIS IN RATS
Authors: M. Cong, P. Wang, T. Liu, Y. Bai, J. Jia, J. Chen, H. You
Journal: Journal of Hepatology (2011)
Jarvik 2000 Heart
Authors: Stephen Westaby, Takahiro Katsumata, Remi Houel, Rhys Evans, David Pigott, O. H. Frazier, Robert Jarvik
Journal: Circulation (1998)

Background —Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose. Methods and Results —The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft. Conclusions —The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.
Effect on lymph node status of triple levelling and immunohistochemistry with CAM 5.2 on node negative colorectal carcinomas.
Authors: A G Nicholson, C G Marks, M G Cook
Journal: Gut (1994)

Several papers have recently assessed whether immunohistochemistry increases the accuracy of staging in node negative colorectal carcinomas, by showing micrometastases. The results have been contradictory. In this paper 542 nodes which were negative for tumour on routine sectioning, were stained with CAM 5.2. In addition, the tissue was levelled three times, this technique being more economical, to see if either or both techniques increased the pick up of micrometastases. Six nodes showed positive staining of occasional cells in the subcapsular and paracortical sinuses, but these were cytologically benign on review and were not thought to represent metastatic tumour. Triple levelling did not show any additional micrometastases.