tbuckley/cabot-search huggingface dataset:
Abstract 220: Transcriptional Analysis Of Caveolin And Cavin In The Male And Female Ageing Mouse Heart Following Ischemic Stress
Authors: Can J Kiessling, Melissa Reichelt, John Headrick, Kevin Ashton
Journal: Circulation Research (2014)

Cardioprotection against infarction and dysfunction in the myocardium involves G-protein-coupled receptor signalling orchestrated by specialised membrane microdomains termed caveolae. The caveolin protein family consist of three subtypes: caveolin-1, −2 and −3 (Cav1-3) and are responsible for the formation of caveolae and hypothesized to orchestrate cardioprotective signalling. Caveolin-3 deficiency and overexpression has been shown to attenuate and restore cardioprotection, respectively. Recently, a family of four related proteins known as cavins (Cavin1-4) have been implicated as regulators of caveolae formation and function. The roles and expression distribution of the cavin family is currently unknown in cardiac tissue. In this study hearts were isolated from 8, 16, 32 and 48 week male and female mice and subjected to normoxic perfusion (80 min) or ischemic stress (20 min global ischemia, 60 min reperfusion). RT-qPCR was used to assess differential gene expression of caveolin and cavin subtypes across these ages in both sexes. Decreased post-ischemic pressure development and increased LDH release were observed in 32 and 48 week old relative to 8 week old male hearts hearts, indicative of age-related loss of ischemic tolerance. Females showed greater tolerance to ischemia at 32 and 48 week old hearts when compared to male counterparts. In normoxic male 48 week old hearts, Cav1,-2,-3 and Cavin1 were significantly repressed, whilst post-ischemic male 48 week old hearts demonstrated significant repression of Cav3 and Cavin1 only. Normoxic female hearts showed no significant changes in caveolin and cavin transcript expression over the aging time course. However, post-ischemic female 48 week old hearts showing significant down-regulation of Cav3 only. Taken together, alterations in caveolin and cavin expression may contribute to the age-related loss of ischemic tolerance and G-protein-coupled receptor-mediated protection in aging male and female mice hearts.
Phase II study of trimetrexate, fluorouracil, and leucovorin for advanced colorectal cancer.
Authors: C D Blanke, B Kasimis, P Schein, R Capizzi, M Kurman
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase II study to evaluate the response rate and toxicities of a trimetrexate, fluorouracil (5FU), and leucovorin regimen in patients with advanced incurable colorectal cancer. PATIENTS AND METHODS Thirty-six patients with unresectable or metastatic colorectal cancer who had not been treated for advanced disease received the following chemotherapy regimen weekly for six courses every 8 weeks: trimetrexate 110 mg/m2 intravenously (I.V.) on day 1, leucovorin 200 mg/m2 I.V. on day 2 (24 hours later), 5FU 500 mg/m2 on day 2 immediately following leucovorin, and oral leucovorin 15 mg every 6 hours for seven doses starting 6 hours after 5FU. Patients were treated until progression or unacceptable toxicity. RESULTS Thirty patients were assessable for response, and all 36 were assessable for toxicity. Two patients (7%) achieved a complete response (CR) and 13 (43%) a partial response (PR), for an overall response (OR) rate of 50% (95% confidence interval [CI], 32% to 68%). Analysis by intent to treat demonstrated a 42% OR rate (95% CI, 26% to 58%). At final analysis, 16 patients were alive. The median survival duration for the entire cohort was 53.4 weeks. Gastrointestinal toxicity was most common, with 21 patients (58%) having grade 3/4 diarrhea and 12 patients (34%) grade 3/4 nausea. Hematologic toxicity was generally low grade, although two patients died of sepsis. CONCLUSION The combination of trimetrexate with 5FU and leucovorin is active in metastatic colorectal cancer. Gastrointestinal toxicity with this regimen is most prominent, but is manageable.
Monte Carlo Investigation of a Model for Competing Risks
Authors: G. J. Atta, A. W. Kimball
Journal: JNCI Journal of the National Cancer Institute (1968)

A random sample of N animals from an infinite population was observed until all animals in the sample had died. At death, the cause of death was recorded. The observation period was divided into n intervals, not necessarily of equal length, and the number of animals dying from each cause of death was calculated for each time interval. It was desired to estimate the mortality probabilities in a population in which one cause of death had been eliminated. The estimation was to be performed with a sample from a population in which all causes of death were operating. It was based on an estimation procedure developed by Kimball (Bull Int Stat Inst 36: 193–204, 1958). To provide some information on the small sample properties of the estimates, a large-scale random-sampling experiment was designed and carried out. This empirical study based on a population exposed to four distinct risks reflected favorably on the estimation procedure. The sampling distributions of two estimates were approximately normal, while the third was positively skewed. The biases in the estimates of the mortality probabilities were negligible. The distributions of the variance estimates approximated a chi-square distribution, as would be expected.
B cell signature contributes to the prediction of RA development in patients with arthralgia
Authors: Joyce Lübbers, Saskia Vosslamber, Lotte A van de Stadt, Marian van Beers-Tas, John G Wesseling, B Mary E von Blomberg, Birgit I Witte, Hetty J Bontkes, Dirkjan van Schaardenburg, Cornelis L Verweij
Journal: Annals of the Rheumatic Diseases (2015)

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman’s space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After &gt;9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman’s capsule and expressed the activation marker CD44 <i>de novo</i>. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents.
Platelet Enhancement of Tumor Cell Adhesion to Subendothelial Matrix: Role of Platelet Cytoskeleton and Platelet Membrane&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D G Menter, B F Sloane, B W Steinert, J Onoda, R Craig, C Harkins, J D Taylor, K V Honn
Journal: JNCI Journal of the National Cancer Institute (1987)

Platelet involvement during tumor cell adhesion to subendothelial matrix was examined in vitro. Platelets were subjected to thrombin stimulation and mechanical lysis and examined for their effects on tumor cell adhesion. These treatments altered the platelet ultrastructure and cytoskeletal integrity. Untreated washed rat platelets (WRP) exhibited extensive adhesion to and spreading on substrates and substantially enhanced tumor cell adhesion to the same substrates (i.e., 250% greater than tumor cells without platelets). Thrombin prestimulation of platelets limited platelet adhesion and spreading and platelet facilitation of tumor cell adhesion. Complete mechanical lysis disrupted both the platelet membrane and the cytoskeleton and eliminated the ability of platelets to adhere or to enhance tumor cell adhesion. Partially lysed platelets resembled membrane ghosts and facilitated tumor cell adhesion by a mechanism independent of spreading and cytoskeletal rearrangement. Fractionation studies indicated that platelet cytoskeletal components played a role in the adhesion process. Pretreatment of WRP with cytochalasin A or B dose dependently inhibited microfilament-mediated platelet spreading and platelet-enhanced tumor cell adhesion. Colchicine and vinblastine induced microtubule depolymerization, but they had no observable effect on platelet spreading or platelet-enhanced tumor cell adhesion. It was concluded that platelet-enhanced tumor cell adhesion to subendothelial matrix depends on an intact platelet cytoskeleton and on a platelet membrane component(s) and is mediated by surface contact between platelets and tumor cells. Furthermore, platelet-mediated tumor cell adhesion to subendothelial matrix may involve two mechanisms: one dependent on, and one independent of, platelet spreading and cytoskeletal rearrangement.
Impact of experience and education in treatment of adult respiratory distress syndrome (ARDS) using extracorporeal membrane oxygenation (ECMO)
Authors: Go Woon Kim, Sang Bum Hong, Yoounsuck Koh, Chae Man Lim, Jin Won Huh
Journal: European Respiratory Journal (2012)

Background:

Extracorporeal membrane oxygenation (ECMO) is a form of long-term cardiopulmonary bypass and recently have been used to treat adults with respiratory or cardiac failure despite maximal medical therapy. ECMO is a high risk procedure with 25% of mortality rate.

The previous a few studies showed that improving equipment and increased experience to manage ECMO are important to patient survival and improving results.

ECMO training program is important in solving significant, life-threatening problems that can occur during ECMO application.

Our aims in this study are to show our experience of ECMO management and reduction in mortality rate according to an accumulation of experience and knowledge.

Methods : A nonrandomized restrospective study was performed.

Results :

In 2009-2011, ECMO was applied to 82 patients. Veno-venous and veno-arterial ECMO was 63.4% and 36.6%, respectively. ECMO was applied to 47 patients in 2009∼2010 and 35 patients in 2011. The most common cause of ECMO application was pulmonary problem.

The most common complication of ECMO was bleeding and the most common cause of death was pneumonia. 41.5% of patients was weaned off the ECMO.

Intensive care unit mortality was higher on 2009∼2010 than on 2011 (89.4% vs 57.1%, OR 6.3, CI 2.008-19.771, p<0.001). Hospital mortality was higher on 2009∼2010 than on 2011 (89.4% vs 57.1%, OR 6.3, CI 2.008-19.771, p<0.001) and 28-day mortality was higher on 2009∼2010 than on 2011 (72.3% vs 45.7%, OR 3.106, CI 1.235-7.812, p<0.014).

Conclusion :

According to an accumulation of experience and knowledge, mortality was reduced in 2011 compared to 2009-2010.
IL-10 and IL-1ra mediates OVA-induced Th2 airway allergic response at short and long-term
Authors: Ronaldo Aparecido Silva, Francine Maria Almeida, Clarice Rosa Olivo, Beatriz Mangueira Saraiva, Adenir Perini, Milton Arruda Martins, Celso Ricardo Fernandes Carvalho
Journal: European Respiratory Journal (2013)

Aerobic training (AT) decreases airway allergic inflammation in sensitized mice; however the anti-inflammatory mechanisms are poorly known. Aim: Evaluate the mechanisms involved during an AT in asthma animal model.Method: 160 Balb/c mice were divided in 4 groups (n=24 each): Control (CT), AT, Ovalbumin (OVA), OVA+AT. OVA groups were sensitized with i.p. OVA+Al(OH)-3 and OVA-inhalations that continued during AT. AT begun after chronic airway inflammation, and it was performed at 50% maximal exercise capacity (60 min/session; 5xweek) and it was performed for 1, 3, 7, 15 or 30 days. After those periods, mice were euthanized and then analyzed the eosinophil counting (BALF), expression of IL-4, IL-5, NF-kB, IL-10, IL-1ra, Eotaxin, RANTES and ICAM-1 by immunohistochemistry in tissue lung slices. Results: OVA-induced an increase in eosinophil migration and the expression of Th2 cytokines, NF-kB, Eotaxin, RANTES and ICAM-1 over time (*p
Where shall we send our Paper?
Authors: Tim Albert
Journal: Journal of the Royal Society of Medicine (2001)

I applaud Dr Herxheimer's attempt to encourage authors to make a rational decision about where to send their scientific papers (October 2001, JRSM, p. 515). It will certainly be an improvement on the present method which (according to accounts given on our courses) is based on the principle of starting with the journal with the highest impact factor, and then working down. However, I am not sure that Herxheimer's model is the answer. He encourages authors to decide on the basis of where they want to publish; surely a more sensible solution is to decide, using all the available evidence, which journal is most likely to accept the article. Getting a paper published is essentially a sales activity, and the most effective sales people are those who consider the needs of the market rather than their own.
Lead Time Gained by Diagnostic Screening for Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: George B. Hutchison, Sam Shapiro
Journal: JNCI Journal of the National Cancer Institute (1968)

Preliminary findings of a clinical trial of screening for breast cancer have been used to estimate descriptive parameters of preclinical disease. The average duration of preclinical disease, measured from first recognition on mammography or physical examination to diagnosis as clinical cancer in absence of special screening, is estimated to be 20 months. Since cases detected at screening are not all detected at the earliest possible moment, the average lead time gained at a single screening will often be less than the average duration of preclinical disease. If the population were completely homogeneous with respect to the natural course of preclinical disease, the lead time would be exactly half the duration of preclinical disease, or 10 months. In a heterogeneous population it would exceed 10, increasing in proportion to the variance of the natural duration of preclinical disease. Incidence of clinical breast cancer in the unscreened control group of this study is 1.6 per 1,000 per year as compared with corresponding incidences of 1.2–1.4 reported by others. The incidence of preclinical disease estimated from the early results of the present study is 2.2. This comparatively high rate may be due to selection bias or to nonspecificity or insensitivity of the screening procedure. The preliminary data suggest that selection bias is the chief distorting factor.
Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching
Authors: Satoshi Kubo, Shingo Nakayamada, Kazuhisa Nakano, Shintaro Hirata, Shunsuke Fukuyo, Ippei Miyagawa, Kentaro Hanami, Kazuyoshi Saito, Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> To compare the clinical outcomes at 1 year after the treatment with either abatacept or tocilizumab in patients with rheumatoid arthritis in routine clinical practice. <h3>Methods</h3> To overcome potential bias in allocation to treatment with abatacept or tocilizumab, a propensity score based on multiple baseline characteristics variables was calculated and 102 of 194 patients treated with abatacept and 102 of 273 patients treated with tocilizumab were statistically extracted. Clinical outcomes were assessed. <h3>Results</h3> The baseline characteristics were statistically comparable. At week 52, 72%/69% of patients (abatacept/tocilizumab) were still receiving treatment. The Simplified Disease Activity Index (SDAI) decreased from 28.7/27.7 at baseline to 14.0/12.5 at week 52 with abatacept/tocilizumab, respectively. At week 52, the remission rates for abatacept/tocilizumab were 18%/20%, respectively. No statistical difference in clinical efficacy between abatacept and tocilizumab was seen. Moreover, a subanalysis showed that abatacept and tocilizumab had similar effectiveness with or without methotrexate. However, prognostic factors at baseline contributing to the Clinical Disease Activity Index at week 52 were different between the two groups by multiple regression analysis. A higher rheumatoid factor (RF) titre and lower SDAI at baseline were associated with lower SDAI at week 52 in patients treated with abatacept, whereas patients receiving tocilizumab with a lower Health Assessment Questionnaire Disability Index and who were biologics-naïve at baseline had a lower SDAI at week 52. <h3>Conclusions</h3> We compared patients treated with abatacept or tocilizumab after statistical adjustment by propensity score matching. Clinical efficacies, including SDAI, were comparable in both treatment groups. However, the predictive factors were different: abatacept appears to benefit patients with higher RF titres, and early induction of tocilizumab is an important factor for good clinical efficacy.
Response of Transplanted AKR Leukemia to Combination Therapy With Amphotericin Band 1,3-Bis(2-chloroethyl)-1-nitrosourea: Dose and Schedule Dependency2
Authors: Gerald Medoff, Fred Valeriote, Julia Ryan, Sandra Tolen
Journal: JNCI Journal of the National Cancer Institute (1977)

A number of different amphotericin B (AmB)-1,3-bis(2-chloroethyl)-1-nitrosourea (BCN U) treatment regimens were evaluated with our model of transplantable AKR leukemia. We found that dose levels and treatment schedules were critical in determining the number of survivors. A 4-day treatment regimen of 0.5 mg AmB/mouse on days 1, 2, 3, and 4 and 0.2 mg BCNU/mouse on day 4 was found to be the most effective and has been chosen as our standard regimen. The efficacy of the treatment regimen depended on the presence of a large tumor burden, and the response was abolished when the mice were preirradiated or treated with the immunosuppressive agent, cyclophosphamide. These results, as well as others which we discuss, supported our notion that AmB affected host immune response to the tumor.
Addressing the burden of mental, neurological, and substance use disorders: key messages from Disease Control Priorities, 3rd edition
Authors: Vikram Patel, Dan Chisholm, Rachana Parikh, Fiona J Charlson, Louisa Degenhardt, Tarun Dua, Alize J Ferrari, Steve Hyman, Ramanan Laxminarayan, Carol Levin, Crick Lund, María Elena Medina Mora, Inge Petersen, James Scott, Rahul Shidhaye, Lakshmi Vijayakumar, Graham Thornicroft, Harvey Whiteford
Journal: The Lancet (2015)
Hippocampal Volume in Adolescent-Onset Alcohol Use Disorders
Authors: Michael D. De Bellis, Duncan B. Clark, Sue R. Beers, Paul H. Soloff, Amy M. Boring, Julie Hall, Adam Kersh, Matcheri S. Keshavan
Journal: American Journal of Psychiatry (2000)

Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects.Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness.Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups.In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.
Pregnancy and pulmonary arterial hypertension (PAH)
Authors: Gisela Meyer, Fernanda Spilimbergo, Bruna Cardoso, Marcia Puchalski, Gabriela Roncato, Katya Rigatto, Ernesto Guedes
Journal: European Respiratory Journal (2013)

Introduction:  Although not recommended, pregnancy in PAH can occur. Despite modern treatments, pregnancy and PAH is associated with around 50% maternal mortality. There is no consensus to the PAH management in the pregnancy setting.  Objective:  To present the occurrence of pregnancy and PAH.  Methods:  Medical charts were reviewed including hemodynamic data and medical evolution reports of the pregnant patients associated with PAH, followed at our center.  Results:  Twelve patients (mean age = 27 years old) and 19 pregnancies were followed, in wich 6 had PAH associated with Congenital Heart Disease and 6 Idiopathic PAH. Five progressed to spontaneous abortion in the 6th, 16th, 24th and 24th week, and one abortion without embryo. There was 1 case of legal abortion and the remainder (13 cases) had a good prognosis, with 5 normal deliveries and 7 caesarean sections. Only 1 case of pregnancy complicated by disseminated intravascular coagulation in the third trimester of pregnancy and was resolved without sequelae. Six patients started the symptoms of PAH during pregnancy. After pregnancy, all the patients continued to be followed, there were not cases of death and all babies were born healthy.  Conclusion:  There were no maternal deaths. Although not recommended, pregnancy in PAH can occur. We need to establish the better approach management to these patients.