tbuckley/cabot-search huggingface dataset:
Role of endothelin B receptor in Th2-induced pulmonary vascular hyperresponsiveness
Authors: Christoph Tabeling, Carla R. González Calera, Thomas Tschernig, Matthisas W. Laschke, Berthold Hocher, Norbert Suttorp, Martin Witzenrath
Journal: European Respiratory Journal (2013)

Introduction: Inflammation is a major component in the pathogenesis of pulmonary arterial hypertension (PAH). Pulmonary Th2 inflammation induces morphological and functional changes which resemble those observed in PAH, including perivascular inflammation, pulmonary vascular hyperresponsiveness and pulmonary arterial remodeling. Endothelin receptor antagonists (ERA) are routinely used treatments for PAH. However, whether a combined inhibition of the endothelin A (ETA) and endothelin B (ETB) receptors or a selective inhibition of ETA is superior over the other is currently unknown.

Methods: ETB-deficient mice (ETB-/-) and corresponding wild-type mice (wt) were employed in pulmonary Th2 inflammation. After systemic sensitization, mice were repeatedly exposed to aerosolized ovalbumin. The effects of ETB-deficiency on pulmonary arterial resistance and pulmonary vascular responsiveness were studied in isolated perfused and ventilated lungs. Hearts were weighed for assessment of Fulton’s Index. The effects on perivascular inflammation and collagen deposition were analyzed via microscopy.

Results: Pulmonary arterial resistance, pulmonary vascular responsiveness and Fulton’s index were elevated in non-sensitized ETB-/- mice as compared to wt mice. After induction of pulmonary inflammation, ETB deficiency led to a greater increase in pulmonary vascular hyperresponsiveness. Histological analysis showed augmented perivascular inflammation and collagen deposition in ETB-/- mice.

Conclusion: This study provides evidence for protective effects of ETB on PAH-associated pulmonary vascular pathologies. Whether these ETB-related protective effects also play a role in selective ERA treatment needs further evaluation.
Occupational air pollutants - More hazardous for respiratory health than smoking? Report from the obstructive lung disease in northern Sweden studies
Authors: Ulf Hedlund, Linnea Hedman, Bo Lundbäck, Eva Rönmark
Journal: European Respiratory Journal (2012)

Background:  Both smoking and occupational air pollutants (OAP) are risk factors for impaired respiratory health. Comparisons of their effects and how they interact are scarce.   Aim:  To compare the effects of ever smoking and ever OAP on non-malignant respiratory disorders and to assess their interactions.   Material and methods:  In a population-based incidence study of asthmatic and bronchitic disorders in northern Sweden, 5896 subjects answered a postal questionnaire in 1996 and in 2006 (79% of the responders in 1996). Cumulative incidences were calculated. Risk factors were analyzed in multiple logistic regressions adjusted for possible confounders and the results are presented as odds ratios (OR). Ever/never smoking (S) and ever/never OAP were used as a combined variable with four categories or as dichotomous variables, respectively.   Result:  Cumulative incidences for 10 years were for S 0 /OAP 0  3.2 - 7.4, S 1 /OAP 0  3.3 - 9.5, S 0 /OAP 1  3.8 – 11.0, and for S 1 /OAP 1  7.1 – 15.0. Using a combined variable with S 0 /OAP 0  as the reference odds ratios were for S 1 /OAP 0  0.99 – 1.8 with some significant results, S 0 /OAP 1  1.0 – 2.2, with more significant results, and S 1 /OAP 1  1.4 – 3.4 with all results significant. Interactions between smoking and OAP were mostly multiplicative for both asthmatic and bronchitic disorders. Population attributable risks based on dichotomous variables were for smoking about 15%, for OAP about 20%, and for smoking and/or OAP about 25%.   Conclusion:  OAP were at least as strong a risk factor as smoking for impaired respiratory health. Both smoking and OAP ought to be considered as possible confounders.
Nephrotoxicity of the BRAF Inhibitors Vemurafenib and Dabrafenib
Authors: Kenar D. Jhaveri, Vipulbhai Sakhiya, Steven Fishbane
Journal: JAMA Oncology (2015)

The selective BRAF inhibitors vemurafenib and dabrafenib have shown significant improvement in patient survival compared with standard therapy in BRAF V600-mutant metastatic melanoma.We reviewed Food and Drug Administration Adverse Event Reporting System (FAERS) data for both agents for renal toxic effects. From July 2011 through June 2014, 132 cases of acute kidney injury in patients receiving vemurafenib therapy were reported. Renal injury was more common in men (85 men vs 47 women; P<.001). From April 2013 through June 2014, 13 cases of renal injury in patients receiving dabrafenib therapy were reported (12 men and 1 woman). Hypokalemia (6 cases in patients receiving vemurafenib and 2 cases in patients receiving dabrafenib) and hyponatremia (8 and 6 cases, respectively) were also reported.Vemurafenib seems to be more nephrotoxic than dabrafenib. This renal toxicity seems to be more prevalent among male patients with melanoma. On the basis of the few published case reports, the mode of injury seems to be tubular interstitial injury. Our findings suggest a need to monitor renal function and electrolyte levels in all patients who receive these drugs. Dermatologists, oncologists, and nephrologists need to be aware of this potential hazard.
Verapamil improves the outcome after cadaver renal transplantation.
Authors: I Dawidson, P Rooth, C Lu, A Sagalowsky, K Diller, B Palmer, P Peters, R Risser, Z Sandor, F Seney
Journal: Journal of the American Society of Nephrology (1991)

Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression and Role of Parathyroid Hormone-Related Protein in Human Renal Proximal Tubule Cells during Recovery from ATP Depletion
Authors: ADOLFO GARCÍA-OCAN[Combining Tilde]A, SUSAN C. GALBRAITH, SCOTT K. VAN WHY, KAI YANG, LINA GOLOVYAN, PAMELA DANN, RICHARD A. ZAGER, ANDREW F. STEWART, NORMAN J. SIEGEL, JOHN J. ORLOFF
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo , the role of PTHrP in the kidney is unknown. To study the effects of injury on PTHrP expression and its consequences in more detail, the immortalized human proximal tubule cell line HK-2 was used in an in vitro model of ATP depletion to mimic in vivo renal ischemic injury. These cells secrete PTHrP into conditioned medium and express the type I PTH/PTHrP receptor. Treatment of confluent HK-2 cells for 2 h with substrate-free, glucose-free medium containing the mitochondrial inhibitor antimycin A (1 μM) resulted in 75% depletion of cellular ATP. After an additional 2 h in glucose-containing medium, cellular ATP levels recovered to approximately 75% of baseline levels. PTHrP mRNA levels, as measured in RNase protection assays, peaked at 2 h into the recovery period (at four times baseline expression). The increase in PTHrP mRNA expression was correlated with an increase in PTHrP protein content in HK-2 cells at 2 to 6 h into the recovery period. Heat shock protein-70 mRNA expression was not detectable under baseline conditions but likewise peaked at 2 h into the recovery period. Treatment of HK-2 cells during the recovery period after injury with an anti-PTHrP(1-36) antibody (at a dilution of 1:250) resulted in significant reductions in cell number and uptake of [ 3 H]thymidine, compared with nonimmune serum at the same titer. Similar results were observed in uninjured HK-2 cells. It is concluded that this in vitro model of ATP depletion in a human proximal tubule cell line reproduces the pattern of gene expression previously observed in vivo in rat kidney after ischemic injury and that PTHrP plays a mitogenic role in the proliferative response after energy depletion.
Links between food manufacturers and Spanish health institutions are highlighted in report
Authors: Aser García Rada
Journal: BMJ (2015)

“Dangerous liaisons between the food industry and health institutions” have been highlighted in a report by VSF Global Food Justice, an organisation that aims to curb agribusiness and defend food sovereignty.1

The report, Confiad en Mi [Trust Me] , published on 21 July, described attempts by brands such as AB Sugar, Danone, Nestle, Coca-Cola, PepsiCo, Ferrero, Bimbo, Panrico, and Nutrexpa to link the image of unhealthy products to health by lobbying through medical societies, universities, the media, and other public and private organisations.

Its author, Ferran Garcia, denounced “the continuous and scandalous collaboration of public bodies with the food industry,” highlighting how this lobby has promoted or funded institutions to disseminate scientific research in line with the interests of the industry and distort messages about the effect of sugar and bad food habits.

“There are no good or bad foods, but healthy or unhealthy lifestyles” is a common message among these institutions. For example, the Institute of Studies on Sugar and Beet (IEDAR), created in collaboration with sugar manufacturers, has received grants from the government while claiming “insufficient …
Etiology of Human Breast Cancer: A Review2
Authors: Brian MacMahon, Philip Cole, James Brown
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Etiology of Human Breast Cancer: A Review Get access Brian MacMahon, M.D., Brian MacMahon, M.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip Cole, M.D., Philip Cole, M.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar James Brown, Ph.D. James Brown, Ph.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 21–42, https://doi.org/10.1093/jnci/50.1.21 Published: 01 January 1973 Article history Received: 04 August 1972 Accepted: 14 August 1972 Published: 01 January 1973
Karyotype and Sex of Primary Testicular Teratomas in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Leroy C. Stevens, Merrill C. Bunker
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Karyotype and Sex of Primary Testicular Teratomas in Mice Get access Leroy C. Stevens, Leroy C. Stevens The Jackson Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Merrill C. Bunker Merrill C. Bunker The Jackson Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 1, July 1964, Pages 65–78, https://doi.org/10.1093/jnci/33.1.65 Published: 01 July 1964 Article history Received: 17 December 1963 Published: 01 July 1964
A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy
Authors: R Bain, R Rohde, L G Hunsicker, J McGill, S Kobrin, E J Lewis
Journal: Journal of the American Society of Nephrology (1992)

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroid resistant asthma: what is the clinical definition?
Authors: AJ Woolcock
Journal: European Respiratory Journal (1993)

Asthma is usually a steroid responsive disease. A few patients respond poorly to these drugs, and others need such high doses to control the disease that side-effects become a serious problem. The term steroid resistant asthma is used for both groups. In some patients, factors may be operating to make the asthma worse and, thus, to increase the requirement for steroids. In order to make a clinical diagnosis of steroid resistant asthma, it is therefore necessary to investigate the factors that could be operating to prevent a "normal" response to steroids. These factors include wrong diagnosis, insufficient steroid reaching the airway mucosa, continuing exposure to sensitizing agents, unrecognized aggravating agents, excessive use of beta-agonist aerosols, and failure to undertake regular management according to a strict management plan. Using a strict clinical definition of steroid resistant asthma leads to better investigation and treatment of individual patients, allows steroids to be stopped when they are not indicated, allows other anti-inflammatory drugs to be used with confidence, and provides a well-defined group of patients for further research relating to the mechanisms of action of steroids.
Health-Related Quality of Life in Survivors of Wilms’ Tumor and Advanced Neuroblastoma: A Cross-Sectional Study
Authors: Ronald D. Barr, Dawn Chalmers, Sonja De Pauw, William Furlong, Sheila Weitzman, David Feeny
Journal: Journal of Clinical Oncology (2000)

In pediatric oncology, Wilms' tumor and advanced neuroblastoma represent opposite ends of the spectra of survival probability and therapeutic intensity. Consequently, it was envisaged that survivors of Wilms' tumor would enjoy better health status and health-related quality of life (HRQL) than survivors of advanced neuroblastoma.Health status questionnaires were sent to the parents of all eligible children and to the children themselves if they were > or = 8 years of age. Responses were received from 84% of 93 eligible families. Responses were converted by established algorithms into levels of two multiattribute health status classification systems known as Health Utilities Index Mark 2 and Mark 3. These systems are linked to measures of preference, in the form of multiattribute utility functions, which provide scores of morbidity for single-attribute levels and of global HRQL for comprehensive health states.A greater burden of morbidity was identified in the survivors of advanced neuroblastoma than in survivors of Wilms' tumor based on the assessments of the parents of these children. In particular, survivors of advanced neuroblastoma exhibited deficits in hearing and speech. It is possible that this morbidity burden reflects the prevalent use of platinum compounds (causing ototoxicity) in this group. Within parent-child dyads there was a high level of percentage agreement on responses in all attributes except cognition.Extension of this study to a larger sample size of patients will provide clarification of these observations.
Effects of cardiomegaly on regional chest wall volume in patients with chronic Chagas cardiomyopathy
Authors: Joao Danyell Silva, Daniella Brandao, Jasiel Nascimento, Larissa Carvalho, Wilson Oliveira Junior, Raquel Britto, Guilherme Fregonezi, Andrea Aliverti, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2011)

Heart failure is commonly related to changes in breathing pattern in order to evaluate the specific effects of cardiomegaly on chest wall function in Chronic Chagas Cardiomyopathy (CCC) we studied 12 CCC patients with cardiomegaly ejection fraction (EF) of left ventricle  2 ) and 5 CCC patients without cardiomegaly (EF > 45; 68.8±6.83 years; 32.92±7.69 kg/m 2 ). Maximal inspiratory pressure (MIP) and chest wall volume by Opto-Electronic Plethysmography (OEP) were measured. OEP data were acquired during quite breathing (QB) and inspiratory loaded breathes (ILB) with threshold set at 50% of MIP.  During QB, patients with cardiomegaly showed lower percentage contributions to tidal volume of both pulmonary rib cage (VRCp%) (p=0.01) and abdominal rib cage (VRCa%) (p=0,02) compared to patients without cardiomegaly. During ILB, VRCa% (p=0.03), end-inspiratory (p=0.03) and end-expiratory (p=0.04) volumes of abdominal rib cage volume were reduced compared to patients without cardiomegaly. In conclusion, increased heart size within thoracic cavity affects chest wall function in the rib cage compartments. The lower rib cage displacement is affected especially during inspiratory efforts. This mechanical constraint leads to a restrictive breathing pattern, which is related to high elastic load to both inspiration and expiration.
Relationships Between Body Mass Index, Fat Mass, Muscle Mass, and Musculoskeletal Pain in Community Residents
Authors: Jong Jin Yoo, Nam Han Cho, Seung Hun Lim, Hyun Ah Kim
Journal: Arthritis & Rheumatology (2014)

To evaluate the relationships between fat mass, muscle mass, fat:muscle mass ratio, metabolic syndrome, and musculoskeletal pain in community residents.In the Korean Health and Genome Study, 1,530 participants (mean ± SD age 60.8 ± 8.60 years) completed pain questionnaires and underwent dual x-ray absorptiometry to calculate body composition. Pain was categorized according to the number of pain regions, such that widespread pain, defined as pain above the waist, below the waist, on both sides of the body, and in the axial region, represented the most severe pain. Metabolic syndrome was defined using the International Diabetes Federation 2005 recommendations, and the association between metabolic syndrome and pain was evaluated by dividing the population into 4 groups, according to the presence/absence of metabolic syndrome and of high body mass index (BMI).Total fat mass and fat:muscle mass ratio were significantly and positively associated with musculoskeletal pain among female subjects only. Compared to the lowest quartile of fat:muscle mass ratio, the odds ratios for widespread pain among subjects in other quartiles were significantly increased after adjustment for confounders. Widespread pain was more prevalent among subjects with metabolic syndrome whether their BMI was high or normal, especially among female subjects.Increased fat mass and fat:muscle mass ratio were significantly associated with musculoskeletal pain among women. Widespread pain was significantly associated with a high fat:muscle mass ratio after adjustment for confounders. Understanding the relationship between fat mass and pain may provide insights into preventative measures and therapeutic strategies for musculoskeletal pain.
Low-dose atrial natriuretic factor and furosemide in experimental acute congestive heart failure.
Authors: D L Fett, P G Cavero, J C Burnett
Journal: Journal of the American Society of Nephrology (1993)

This study was designed to address three objectives in an experimental model of acute congestive heart failure (CHF) in the dog produced by rapid ventricular pacing. The first objective was to characterize cardiorenal and humoral responses before and during 2 h of acute CHF. The second objective was to determine the modulating action of iv furosemide upon these biologic responses to acute CHF, testing the hypothesis that furosemide-mediated natriuresis is associated with activation of the renin-angiotensin-aldosterone system (RAAS) compared with the control group. The third objective was to determine the modulating action of continuous low-dose atrial natriuretic factor (ANF) administration during acute CHF upon these biologic responses, testing the hypothesis that exogenous low-dose ANF would prevent activation of the RAAS and enhance the natriuretic action of furosemide. In the control group (Group 1; N = 6), plasma ANF increased after the onset of CHF; GFR and sodium excretion were maintained without activation of this RAAS despite arterial hypotension. In Group 2 (N = 6), furosemide in acute CHF increased sodium excretion but in association with a decrease in GFR and activation of the RAAS. Low-dose exogenous ANF and furosemide (Group 3; N = 6) in acute CHF were associated with a maintenance of GFR, no activation of the RAAS, and potentiation of furosemide-induced natriuresis. In summary, these studies demonstrate that furosemide potently increases sodium excretion in acute CHF, but with a decrease in GFR and activation of the RAAS. Low-dose ANF in acute CHF with furosemide maintains GFR, attenuates activation of the RAAS, and potentiates natriuresis.