tbuckley/cabot-search huggingface dataset:
Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat
Authors: John Buerkert, Daniel Martin, David Trigg, Eric Simon
Journal: Journal of Clinical Investigation (1983)

Papillary and surface micropuncture were used to study the handling of ammonium and the formation of net acid by surface nephrons, deep nephrons, and the terminal segment of collecting duct (CD) after renal mass was reduced by two-thirds. Net acid excretion by the remnant kidney (RK) was significantly reduced, averaging 794±81 neq/min (SE) compared with 1,220±105 neq/min after sham operation (P < 0.001), due to a decrease in ammonium excretion (494±54 vs. 871±79 nmol/min in controls, P < 0.001). Urinary pH and titratable acid excretion were not different in the two groups of animals. After RK formation, ammonium delivery to the end of the proximal tubule increased nearly threefold and averaged 66.2±5.6 compared with 18.4±2.9 pmol/min in controls, (P < 0.001). This greater delivery of ammonium was primarily due to renal tubule entry rather than to changes in the filtered load and was only partially related to the differences in flow rate. Ammonium processing by deep nephrons was profoundly affected by a reduction in renal mass. Although absolute delivery of ammonium was greater to the bend of Henle's loop (BHL), the difference could be accounted for on the basis of an increase in nephron size. Thus, fractional delivery (FDNH+4) to this site was not different for the two groups of animals, averaging 1,567±180% in controls and 1,400±181% in the group with the RK. Hydrogen secretion in the proximal segments of deep and surface nephrons did not increase in proportion to the decrease in renal mass and as a consequence bicarbonate delivery to the end of the proximal tubule of surface nephrons and to the BHL of deep nephrons was increased.
HLJ1, a novel invasion/metastasis suppressor, regulates nucleophosmin translocation and function
Authors: Tzu-Pei Chang, Sung-Liang Yu, Sheg-Yi Lin, Pan-Chyr Yang, Jeremy J.w. Chen
Journal: Cancer Research (2006)

2487   Lung cancer has become the most common cause of cancer deaths in the world. Similar to other malignant tumors, undesirable prognosis for patients with lung cancer has been attributed to the development of metastasis. By using a microarray and invasion/metastasis cell line model in a previous study, we have identified and characterized a novel suppressor candidate HLJ1 (Human Liver DnaJ-like protein) that may play an important role in tumor growth and metastasis. HLJ1, a member of Hsp40 family (DnaJ-like Heat Shock Protein) was isolated from human liver cDNA library first. In this study, the results of co-immunoprecipitation showed that HLJ1, Hsc70 (Hsp70 family), and nucleophosmin (NPM/B23) could interact with each other to form a multi-protein complex. NPM is a phosphoprotein and involved in nucleolar assembly, centrosome duplication, cell cycle progression, and ribosome assembly and transport. Dissociation/reassociation of NPM with centrosomes in a cell cycle stage-specific manner may be controlled by phosphorylation. The complex immunoprecipitated from cell extracts was treated with phosphatase or RNase A, the results suggested that the interaction is dependent on phosphorylation and RNA-binding activity. Using mammalian two-hybrid assay, we have identified the major interaction domain between HLJ1 and NPM, including J domain of HLJ1 and HoD/NBD domain of NPM. The HoD, N-terminal homo-oligomerization domain, is required for formation of NPM dimmer and hexamers that is important for nucleus translocation. Western blot analyses also showed that HLJ1 overexpression could affect NPM translocation and decrease the nucleus level of NPM. Furthermore, immunofluorescent staining was performed to indicate the sub-cellular location of protein interaction and deduce the putative mechanisms in cell cycle progression. Our results also showed that overexrpesssion of NPM could enhance cell invasion and migration. We concluded that HLJ1 can interact with Hsc70 and NPM respectively, which is dependent on phosphorylation and RNA-binding activity; and further, HLJ1 may inhibit NPM oligomerization and prevent NPM in cytoplasm from translocating into nucleus to inhibit cancer cell invasion and migration. NPM plays a role in the regulation of nucleolar function for cellular growth, differentiation, and apoptosis. It is important to identify and investigate a novel molecular mechanism about HLJ1-NPM interaction because they could potentially provide a new insight to understand the pathway of metastasis regulation and may be the new target molecule for anti-cancer therapy in the future.
Impact of climate change on ozone induced mortality in Europe
Authors: Bertil Forsberg, Hans Orru, Christofer Åström, Camilla Andersson, Kristie Ebi, Joakim Langner
Journal: European Respiratory Journal (2011)

Background:  Ozone is a highly oxidative pollutant, associated with respiratory morbidity and mortality. All else being equal, ground-level ozone will increase as temperatures increase with climate change.   Aim:  As a part of the Climate-TRAP project we used emission scenarios, models and epidemiological data to assess ozone-related health impacts under a changing climate.   Methods:  European ozone concentrations were modelled at a grid size of 50x50 km using MATCH-RCA3. Projections from two climate models, ECHAM4 and HADLEY, were used, assuming greenhouse gas emission scenarios A2 and A1B. Four periods were compared: the baseline period was defined as 1961–1990, the current situation as 1990–2009, nearer future as 2021–2050 and further future as 2041–2060. The impact on mortality (short-term effect) was calculated for exposures above a daily maximum 8-hour concentrations of 70 μgm-3. We use a European-wide exposure-response function with country-specific baseline mortality.   Results:  Comparing the current situation with the baseline period, the largest increase in ozone-associated mortality due to climate change (∼4%) occurred in Belgium, Ireland, Netherlands and UK. Comparing the baseline period and the further future, the increase is projected to be biggest in Belgium, France, Spain and Portugal (10–14%) and the effect will be stronger for the A2 scenario. However, in Nordic and Baltic countries there will be a decrease in ozone-related mortality of the same magnitude.   Discussion:  The current study suggests that projected effects of climate change on ozone levels could differentially influence mortality and morbidity across Europe.
Letrozole or anastrozole for the treatment of hormone-positive breast cancer: A clinical comparison using indirect statistical techniques.
Authors: S. Kaura, G. Dranitsaris
Journal: Journal of Clinical Oncology (2010)

e16519 Background: Letrozole (LET) and anastrozole (ANA) are more effective than tamoxifen (TAM) in preventing disease recurrence in postmenopausal women with early stage breast cancer. Recent data from BIG 1-98 study also suggests that LET may improve overall survival (Regan SABCS, 2009), a finding that has not been demonstrated with ANA. Notwithstanding, there are no data available from head to head randomized phase III trials comparing the statistical noninferiority between LET and ANA. In the absence of such data, an indirect statistical comparison between LET and ANA was performed. Such an analysis is feasible in this case because TAM was the common comparator in both trials and patients had similar baseline characteristics. Methods: Data in terms of early distant recurrences, disease-free survival (DFS) and overall survival (OS) were extracted from the BIG 1-98 and ATAC trials. After a median follow up of 74 months, the hazard ratio (HR) for OS based on an inverse probability censoring weighted (IPCW) analysis for LET was 0.83 (95%CI 0.71-0.97, p < 0.05). From ATAC after a follow up of 68 months, the HR was 0.97 (95%CI: 0.85-1.12, p = 0.70). An indirect statistical comparison between LET and ANA was then performed on early distant recurrences, DFS and OS using the method of Bucher et al. (1997), which maintains in part the benefits of randomization on the effect size. Results: There was little difference between the two drugs with respect to DFS (HR = 0.98; 95%CI: 0.83 to 1.15). However, the analysis did identify a substantial risk reduction for early distant recurrences between 2 to 2.5 years with LET (RR = 0.75; 95%CI: 0.52-1.07) over ANA. This translated to a trend for improved OS with LET (HR = 0.86; 95%CI: 0.70-1.05). Conclusions: Keeping in mind the caveats associated with cross trial comparisons, this indirect statistical comparison suggests that LET may be more effective than ANA in reducing early distant recurrences and mortality at 5 years. It is possible that the reduction in early distant metastases with LET is responsible for the later improvement in OS. Ongoing trials (FACE, MA.27) comparing the aromatase inhibitors should help us confirm the potential survival benefit with LET. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Nighttime symptoms and reduced quality of life among COPD patients
Authors: Michelle Mocarski, Cynthia Caracta, Stavros Tourkodimitris, Esther Garcia Gil, Juliana Setyawan
Journal: European Respiratory Journal (2012)

INTRODUCTION:

Little is known about the impact of COPD symptoms at night on patients' quality of life.

METHODS:

In a 12-week, Phase III trial of twice-daily aclidinium (ACCORD I), COPD patients completed an electronic diary each morning for 2 weeks before baseline. Diaries included questions on presence and severity of nighttime symptoms and sleep quality. Health status and dyspnea were assessed via SGRQ and BDI. Post hoc analyses were performed to study the relationship between nighttime COPD symptoms and other symptomatic and health status measures. Nighttime symptoms were defined 2 ways: 1) ≥3 nights sleep disturbance during baseline week and 2) ≥3 nights coughing, wheezing, and/or breathlessness during baseline week. Data from the week before baseline for patients with >3 days of diary entries were analyzed via T-test and Chi-square.

RESULTS:

The analyses included 535 of 561 randomized patients. Patients with nighttime symptoms had significantly worse health status, as seen in SGRQ Total and domain scores, vs patients without (p<0.0001 for all, both definitions). A significantly higher percentage of patients with nighttime symptoms reported sleep disturbance on SGRQ vs those without (p<0.0001 both definitions). Patients with nighttime symptoms were more breathless (BDI domains, focal scores p<0.002, both definitions), had longer time to sleep onset, lower sleep quality, more awakenings, difficulty falling back to sleep, less total sleep, and were less rested in the AM (all p<0.02, both definitions) vs those with no symptoms.

CONCLUSIONS:

COPD nighttime symptoms are associated with impaired health status, breathlessness, and poor sleep. Clinicians should consider COPD nighttime symptoms when prescribing treatment.
The efficacy of CPAP and oral appliances in moderate obstructive sleep apnoea, used as CBO guideline states
Authors: L. Visscher, M.G.J. Brusse-Keizer, M.M.M. Eijsvogel
Journal: European Respiratory Journal (2014)

In obstructive sleep apnea syndrome (OSAS) continuous positive airway pressure (CPAP) is considered in most guidelines as the reference treatment for OSAS, and mandibular repositioning appliance (MRA) as alternative therapy in patients with CPAP-failure. The Dutch OSAS guideline of 2009 states that, CPAP is the preferred treatment in severe (AHI >30) OSAS but MRA and CPAP have the same efficacy in moderate (AHI 15-30) OSAS. This statement has, however, never been evaluated in clinical practice.  This study is a retrospective observational non-inferiority study. The 1-year treatment success (AHI   In 2011 31 MRA and 123 CPAP treatments where started in patients with moderate OSAS in our Dutch hospital. The OR of treatment success of CPAP versus MRA is 0.45 with a 95% CI of 0.137 to 1.45. Since this upper limit is below the inferiority threshold of 3.27, MRA is non-inferior to CPAP.  The 1-year efficacy of MRA is non-inferior to CPAP therapy in patients with moderate OSAS. The recommendation in the Dutch National OSAS guideline, to choose between MRA and CPAP in moderate OSAS, seems to be valid.
Assessment of Bisphosphonates Use As Adjuvant Therapy in Breast Cancer
Authors: F.M. Abu-Taleb, H.M. El-Zawahry, Z.K. Zekri, R.M.M. Gaafar, N.M.A. Al Lahloubi, N. Zakhari, O. Elfarargy, A. Abdel Raheem Alnagar
Journal: Annals of Oncology (2014)
The<i>Snark</i>and the Skin
Authors: Jennifer C. Aronica, Scott A. Norton
Journal: JAMA Dermatology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia
Authors: C-C Chen, J-Y You, J-P Gau, C-E Huang, Y-Y Chen, Y-H Tsai, H-J Chou, J Lung, M-H Yang
Journal: Blood Cancer Journal (2015)

Abstract Epithelial–mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1 , an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1 , and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1 . AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1 -overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.
A cognitive model of hallucinations
Authors: M J Horowitz
Journal: American Journal of Psychiatry (1975)

Hallucinations occur in a wide variety of altered states of consciousnes and are an important symptom in various psychiatric syndromes. Several psychological and biological theories of their origin have offered, ranging from the concept of wish fulfillment, to the hypothesis of an electorchemical release of the perceptual system, to denials that hallucinatory phenomena exist. No explanation has completely satisfied clinicans, probably because the word "hallucination" labels a complex set of phenomena. The author accepts this complexity and offers a conceptual analysis of four key dimensions of the halucinatory experience in an attempt to clarify the gamut of experiences that may be called hallucinations.
Orf-induced pemphigoid with antilaminin-332 antibodies
Authors: R.R. van den Bos, T. Middelburg, P. van Biezen, A.A. van der Eijk, H.H. Pas, G.F.H. Diercks
Journal: British Journal of Dermatology (2012)

Journal Article Orf‐induced pemphigoid with antilaminin‐332 antibodies Get access R.R. van den Bos, R.R. van den Bos Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar T. Middelburg, T. Middelburg Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar P. van Biezen, P. van Biezen Internal Medicine Search for other works by this author on: Oxford Academic Google Scholar A.A. van der Eijk, A.A. van der Eijk Virology, Erasmus Medical Centre Rotterdam, Burg S Jacobsplein S1, 3105, CA Rotterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar H.H. Pas, H.H. Pas Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar G.F.H. Diercks G.F.H. Diercks Departments of DermatologyPathology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands E‐mail: r.vandenbos@erasmusmc.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 4, 1 October 2012, Pages 956–958, https://doi.org/10.1111/j.1365-2133.2012.11005.x Published: 01 October 2012
Survivorship: Sleep Disorders, Version 1.2014
Authors: Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian, Deborah Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments.
Cytology sample from EBUS-TBNA for multi-gene analysis in non-small-cell lung cancer (NSCLC)
Authors: Carmen Centeno Clemente, Jose Sanz-Santos, Felipe Andreo, Enric Carcereny, Teresa Moran, Eva Castellà, Mariona Llatjòs, Ana María Muñoz-Mármol, José Luis Ramírez, Rafael Rosell, Juan Ruiz-Manzano
Journal: European Respiratory Journal (2014)

BACKGROUND  Identification of distinct oncogenic driver mutations is routinely used to guide clinical care in NSCLC patients (p). Tumor tissue availability is one of the major challenges for NSCLC genotyping. Cytology samples from EBUS-TBNA are one of the main sources of tumor tissue in NSCLC.  METHODS  We aimed to prospectively asses the utility of cytology samples from EBUS-TBNA for molecular characterization of NSCLC p. NSCLC p with stage IIIA, IIIB and IV were included; smoker p with squamous histology excluded. Molecular analyses for EGFR, KRAS, ALK, ROS1, BRAF and HER2 were performed sequentially. DNA sequencing for EGFR, KRAS, BRAF and HER2 was performed, and FISH for ALK and ROS1; both were analyzed by Molecular Biology Laboratory and Pathology Department, respectively.  RESULTS  From January 2013, 21 p were included (16 male, median age 63). 63 lymph nodes and 2 lung masses were analyzed and diagnosed malignant in 41%. Most frequently punctured lymph node stations were 4R, 4L, 7 and 11L. Cytology sample was sufficient in 71.4% (15/21) to perform sequential molecular analysis, either complete or until molecular alteration was detected. EGFR mutational status was possible in 21/21(100%) p, with 2 positive results (9.5%). KRAS mutations were tested in 20/20 (100%), with 3 positive results (15%). ALK rearrangements were tested in 16/19 (84.2%), with 1 positive (1/16[6.3%]). ROS1 was analyzed in 14/18 (77.8%) with no rearrangements found. No mutations found in HER2 and BRAF in 12/16(75%) and in 13/17 (76.5%), respectively.  CONCLUSIONS  Cytology samples from EBUS-TBNA are a suitable source of material for complete molecular genotyping in NSCLC p.  Sponsored by Menarini and AEER award A. Castella.
Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer
Authors: Christopher D. Corso, Charles E. Rutter, Henry S. Park, Nataniel H. Lester-Coll, Anthony W. Kim, Lynn D. Wilson, Zain A. Husain, Rogerio C. Lilenbaum, James B. Yu, Roy H. Decker
Journal: Journal of Clinical Oncology (2015)

To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database.Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching.A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01).In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach.
Treatment of Cigarette Smoking with Short-Term High-Dosage Corticotrophin Therapy: Preliminary Communication
Authors: Stephen Bourne
Journal: Journal of the Royal Society of Medicine (1985)

Uncontrolled studies have indicated that the smoker's "life' can be simulated clinically by short-term, high-dosage corticotrophin therapy. Following such treatment, smokers previously prevented by the withdrawal syndrome from giving up smoking were able to do so easily. All 10 patients reported here were still not smoking after seven months.