tbuckley/cabot-search huggingface dataset:
Age-related changes in glomerular volume and hydroxyproline content in rat and human.
Authors: P Cortes, X Zhao, F Dumler, B C Tilley, J Atherton
Journal: Journal of the American Society of Nephrology (1992)

Total 4-hydroxyproline content and volume were measured in the same sample of microdissected glomeruli obtained fro rat and human outer or inner cortex. Glomerular volume was determined by computer-assisted image analysis, and 4-hydroxyproline was measured by a highly sensitive gas-liquid chromatographic method. Results were expressed as weight of basement membrane material by comparison with the amount of 4-hydroxyproline in purified basement membrane/mesangial matrix preparations. Microanalyses were possible in samples containing as few as eight human glomeruli. Rat glomerular size increased sevenfold between 5 wk and 2 yr of age, with volume being consistently 36 to 45% greater in inner than in outer cortex glomeruli. Basement membrane material content per glomerulus markedly increased with age (12-fold); however, when expressed per unit volume, this change was greatly reduced (2-fold). Expressed per volume, inner and outer cortex glomerular content of basement membrane material was always similar, regardless of age. Therefore, a greater glomerular size, in itself, does not accelerate the rate of basement membrane material deposition. Glomerular size distributions (measured by skewness and kurtosis) did not change, indicating that, although glomerular volume increases with age, aging does not appear to cause the emergence of distinct glomerular populations within an age group. Basement membrane material accumulation is probably a generalized change. Human glomeruli increased sevenfold in size from infancy to adulthood and then declined during senescence. Contrary to that in the rat, glomerular basement membrane material content appeared to closely follow size changes, thus, varying little from infancy to senescence if expressed per unit of glomerular volume.
Diagnostic Value Of Serum Level Of Soluble CD14-Subtype In Febrile Neutropenia In Patients With Hematologic Disorders
Authors: Hideo Koh, Hirohisa Nakamae, Mizuki Aimoto, Takako Katayama, Asao Hirose, Mika Nakamae, Masayuki Hino
Journal: Blood (2013)
Serum markers to monitor response to zoledronic acid in patients with bone metastases from breast cancer.
Authors: L. Mercatali, T. Ibrahim, E. Sacanna, R. Ricci, E. Scarpi, F. Fabbri, P. Serra, C. Tison, D. Amadori
Journal: Journal of Clinical Oncology (2010)

1105 Background: Breast cancer is the most frequent tumor in women and 80% of patients with advanced disease have bone metastases (BM), which are responsible for high morbidity and reducedquality of life. Zoledronic acid (Zol), routinely used to treat patients with BM, inhibits bone resorption andhas antitumor and antiangiogenic properties. Methods: The present study evaluated serum levels of vascular endothelial growth factor (VEGF) and cross-linked N-telopeptide of type I collagen (NTX) in 31 consecutive patients at first diagnosis of bone metastases. All received the monthly standard Zol treatment and were monitored for about 9 months with 3-4 blood samples collected from each patient during that time. Results: The baseline VEGF median value of 298 pg/ml (25-1264) increased to 345 pg/ml(62-977)at 3 months and, after falling to 307 pg/ml (112-1307) at 6 months, rose again, reaching 411 pg/ml (172-1004) at 9 months. However, these differences were not statistically significant. In contrast, the baseline NTX median value of 16 nm BCE (range 3-45) significantly decreased at 3 (11 nm BCE, range 5-35) and 6 (10 nm BCE, range 5-21) months (p<0.001), and reduced even further (12 nm BCE, range 5-45), albeit not significantly, at 9 months. Conclusions: The present work shows that standard monthly treatment with zoledronic acid did not influence serum VEGF levels but significantly reduced serum NTX values by about 35% 3 and 6 months after treatment. The study is ongoing to validate these data in a larger series of patients. No significant financial relationships to disclose.
Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy
Authors: Bernt van den Blink, Marlous R. Dillingh, Leo C. Ginns, Lake D. Morrison, Matthijs Moerland, Marlies Wijsenbeek, Elizabeth G. Trehu, Brian J. Bartholmai, Jacobus Burggraaf
Journal: European Respiratory Journal (2016)

Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM-151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study. A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients. Subjects in three successive cohorts (1, 5, or 10 mg·kg −1 versus placebo) received intravenous study drug on days 1, 3, 5, 8 and 15, and were followed-up to day 57. PRM-151 was well tolerated at all dose levels, with no serious adverse reactions. Administration of PRM-151 resulted in two- to eight-fold dose-dependent increases in circulating pentraxin-2 levels. Forced vital capacity and 6-min walk test showed trends towards improvement in the combined PRM-151 dose groups. On high-resolution computed tomography scans, stable or improved lung volume unoccupied by interstitial lung abnormality was noted in some PRM-151 subjects compared to placebo subjects on day 57. The efficacy of PRM-151 in IPF remains to be investigated in dedicated future trials.
Deaths From Motor-Vehicle—Related Unintentional Carbon Monoxide Poisoning—Colorado, 1996, New Mexico, 1980-1995, and United States, 1979-1992
Journal: JAMA (1996)

This report describes the investigation of deaths associated with multiple motor-vehicle related carbon monoxide (CO) poisonings in Colorado on November 3, 1996; summarizes a review of such deaths in New Mexico during 1980-95; and presents geographic and seasonal patterns in national death rates for 1979-92. Findings indicate that deaths from motor-vehicle related unintentional CO poisonings increase during winter months and that death rates from CO poisoning in stationary motor vehicles are highest in states with colder average winter temperatures.
Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving
Authors: Mohsen Akbari, Ali Tamayol, Sara Bagherifard, Ludovic Serex, Pooria Mostafalu, Negar Faramarzi, Mohammad Hossein Mohammadi, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2016)

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted.
Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study
Authors: Maria-Elisabeth Goebeler, Stefan Knop, Andreas Viardot, Peter Kufer, Max S. Topp, Hermann Einsele, Richard Noppeney, Georg Hess, Stefan Kallert, Andreas Mackensen, Kathrin Rupertus, Lothar Kanz, Martin Libicher, Dirk Nagorsen, Gerhard Zugmaier, Matthias Klinger, Andreas Wolf, Brigitte Dorsch, Beate D. Quednau, Margit Schmidt, Jürgen Scheele, Patrick A. Baeuerle, Eugen Leo, Ralf C. Bargou
Journal: Journal of Clinical Oncology (2016)

Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome-negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m(2)/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.Between 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 μg/m(2)/day was established as the MTD. Thirty-four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 μg/m(2)/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 μg/m(2)/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B-cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days).In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 μg/m(2)/day. Single-agent blinatumomab showed antilymphoma activity.
Superiority of trimodality therapy to surgery alone in esophageal cancer: Results of CALGB 9781
Authors: J. E. Tepper, M. Krasna, D. Niedzwiecki, D. Hollis, C. Reed, R. Goldberg, T. Rich, K. Kiel, R. Mayer
Journal: Journal of Clinical Oncology (2006)

4012 Background: CALGB 9781 was a prospective randomized Intergroup trial of trimodality therapy versus surgery alone for the treatment of stages 1–3 esophageal cancer. Methods: Five-hundred patients were targeted for enrollment with three years of follow-up planned. The primary endpoint was overall survival. All patents had EGD with biopsy, barium esophagogram and CT. Additional staging by EUS and/or thoracoscopy/laparoscopy was recommended. Patients were randomized to treatment with either surgery alone or cisplatin (100mg/m 2 ) and 5FU (1000 mg/m 2 /d × 4d) weeks 1 and 5 concurrent with radiation therapy (50.4 Gy- 1.8 Gy/fx over 5.6 weeks) followed by esophagectomy with lymph node dissection. Results: A total of 56 patients were entered on study between October 1997 and March 2000 when the trial was closed due to poor accrual. Thirty patients were randomized to trimodality therapy and 26 to surgery alone. Patient characteristics were similar between groups. Surgical staging was conducted in just over 50% of patients in both groups. The primary toxicities of Gr 3 or greater with preoperative therapy were hematopoietic (54%), and esophagitis/dysphagia (40%). There were 14 and 17 patients with surgical complications on the trimodality and surgery alone arms, respectively, with 2 post-surgical deaths (within 30 days), both on the surgery alone arm. Postoperative hospital stays were 11.5 and 10 days, respectively. Median follow-up is 6 years. An intent- to- treat analysis showed a median survival of 4.5 yrs vs 1.8 yrs in favor of trimodality therapy (log-rank p=0.02). A log rank test with stratifications by N stage, staging approach and histology demonstrated a p-value of 0.005. 5-year survival was 39% (95% CI [21%, 57%]) vs 16% (95% CI [5%, 33%]) in favor of trimodality therapy. Analysis of progression-free survival is underway. Conclusions: This randomized study demonstrates a long-term survival advantage with the use of chemoradiation therapy followed by surgery in the treatment of esophageal cancer. Although accrual was well below that planned, the observed survival difference is statistically significant and suggests that trimodality therapy is an appropriate standard of care for patients with this disease. No significant financial relationships to disclose.
First Results from the Phase I Dual Rectal Angiogenesis Mek Inhibition Radiotherapy (DreamTherapy) Trial in Locally Advanced Rectal Cancer
Authors: F.E. Marti Marti, A. Backen, A.G. Renehan, A. Jackson, P. Manoharan, O. Ataman, V. Misra, G.C. Jayson, C. Dive, M.P. Saunders
Journal: Annals of Oncology (2012)
Activation of procollagenase IV by cytochalasin D and concanavalin A in cultured rat mesangial cells
Authors: M Allenberg, T Weinstein, I Li, M Silverman
Journal: Journal of the American Society of Nephrology (1994)

The secretion and activation of procollagenase IV were studied in cultured rat mesangial cells. Under resting conditions, mesangial cells secrete predominantly a protein that, by gel zymography, exhibits gelatinase activity and also reacts with an anti-72-kd procollagenase IV antibody raised against a conserved region of the activation site of the enzyme. Cytochalasin D or concanavalin A treatment of mesangial cells causes disruption of actin stress fibers and results in the activation of procollagenase IV, yielding two lower molecular mass forms with gelatinase activity. Concanavalin A-induced actin filament disruption and procollagenase IV activation can be blocked by alpha-methyl-D-mannopyranoside but not by D(+)-galactose. Procollagenase IV as well as the activated forms all exhibit Ca2+ and Zn2+ dependency, characteristic of metalloproteinases. Mesangial cells in culture also secrete a specific tissue inhibitor of metalloproteinase, TIMP-2. Cytochalasin D treatment of mesangial cells reduces TIMP-2 expression. Cytochalasin D and concanavalin A both inhibited the serum-induced contraction of collagen gels embedded with mesangial cells. It was concluded that cytochalasin D-induced cytoskeletal disruption in mesangial cells may activate procollagenase IV by inhibiting TIMP-2 expression and that there is a concanavalin A-binding site on mesangial cells that is part of a transmembrane signaling system altering mesangial cell cytoskeletal organization and metalloproteinase secretion and activation.
The emerging influenza pandemic: estimating the case fatality ratio
Authors: N Wilson, M G Baker
Journal: Eurosurveillance (2009)

To determine appropriate influenza pandemic containment and mitigation measures, health authorities need to know the approximate case fatality ratio (CFR) for this new infection. We present four different methods for very provisionally estimating the plausible range of the CFR for symptomatic infection by this pandemic strain in developed countries. All of the methods produce substantially lower values (range 0.06% to 0.0004%) than a previously published estimate for Mexico (0.4%). As these results have many limitations, improved surveillance and serological surveys are needed in both developed and developing countries to produce more accurate estimates.
Rigid, Inflexible Approach Results in No Recommendation for Autism Screening
Authors: Jeremy Veenstra-VanderWeele, Kelly McGuire
Journal: JAMA Psychiatry (2016)

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Abstract 17576: Frequency, Timing and Co-Occurrence of Heart Failure Signs and Symptoms Among 50,625 Heart Failure Cases and Matched Controls in a Primary Care Population in the Months Preceding the Clinical Diagnosis of Heart Failure
Authors: Rajakrishnan Vijayakrishnan, Steven Steinhubl, Jimeng Sun, Roy Byrd, Zahra Daar, Adam Perer, Shahram Ebadollahi, Walter F Stewart
Journal: Circulation (2012)

The Framingham heart failure (HF) signs and symptoms are ubiquitous among primary care patients, leading to challenges in distinguishing a presentation attributable to HF versus other causes. A bet...
Gefitinib (IRESSA) sensitive lung cancer cell lines show constitutive phosphorylation of Akt
Authors: Rintaro Noro, Akihiko Gemma, Seiji Kosaihira, Yuji Minegishi, Tetsuya Okano, Masahiro Seike, Yutaka Kokubo, Akinobu Yoshimura, Shoji Kudoh
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3793 

Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, there were gefitinib-sensitive and long stable-disease-defined tumors which had not grown for a long time without EGFR gene mutation. To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression level of molecules within the PI3K-Akt and Ras/MEK/Erk pathways in 23 lung cancer cell lines and examined the sensitivity of these cell lines to gefitinib. From this, we identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate sensitivity, and 14 resistant lines. Only PC9 displayed an EGFR gene mutation. Eight out of the nine lines showing highly and intermediate sensitivity had constitutive Akt phosphorylation, while only three out of the 14 resistant lines displayed this characteristic ( P =0.0016). Constitutive phosphorylated EGFR was statistically significant in sensitive cells by the Chi-square test ( P =0.0319). Furthermore, the ratio of phosphor-Akt/total Akt in intermediate sensitive cells was higher than that observed in resistant cells ( P =0.003). Akt and EGFR phosphorylation were partially inhibited by gefitinib in all sensitive cell lines.These results suggest that Akt may play a key signaling role in gefitinib sensitivity, especially in intermediate-sensitive cells. Further studies should focus on the clinical markers of constitutive Akt activation, including Akt phosphorylation, EGFR phosphorylation, and the EGFR family. .
Assessing quality of care from the patients' and parent's perspective in three paediatric asthma settings; a randomised controlled study in children with stable asthma
Authors: Maarten Kuethe, Herman Sixma, Anja Vaessen-Verberne, Judith Booy, Wim van Aalderen
Journal: European Respiratory Journal (2011)

Aim:  To explore quality of care (QoC) as perceived by children with asthma and their parents in a randomized controlled study. Treatment, either by general practitioners (GP), paediatricians (PP) or asthma nurses (AN).   Methods:  Children (6-16 yrs) with stable asthma were recruited from hospital practice (n=62) and from general practice (n=45). Subjects were allocated to three follow up arms (GP, PP, AN). At baseline and after 1 and 2 years, QoC was measured, by parents completing the QUOTE-CNSLD-questionnaire. By factor-analysis an adapted version was derived. Children also completed a 5-item Likert scale, independently and if needed assisted by the research nurse.   Results:   The QoC dimensions of the adapted QUOTE-CNSLD-questionnaire resemble the original scales.  At baseline the asthma specific quality and the child specific quality were significantly better in subjects recruited from hospital-, compared to primary care (p   Conclusions:  The adapted QUOTE-CNSLD-questionnaire is applicable in a paediatric population.  Two dimensions measured significant differences between children recruited from hospital care and from primary care at baseline. No difference during follow-up indicates that from a quality prospective a specialized asthma nurse is cost effective.
A Search for Avian Leukosis Virus and Antiviral Activity in the Blood of Leukemic and Nonleukemic Adults and Children&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J J Solomon, H G Purchase
Journal: JNCI Journal of the National Cancer Institute (1969)

Serum or plasma from leukemic and nonleukemic humans was tested with subgroup A and B virus for anti-Rous sarcoma virus (RSV) activity and for the presence of avian leukosis virus. Nonspecific factors in human blood gave spurious results in tissue culture but not on membranes of embryonated eggs, when attempts were made to study antibody content. There was no evidence of avian leukosis virus. Thus, when residual virus was assayed in chick embryo cells, 17 of 353 samples inhibited subgroup A Bryan standard (BS) RSV and 23 of 26 inhibited both Schmidt-Ruppin RSV-2 and Harris RSV of subgroup B. However, no inhibition was obtained on retests of positive samples when residual virus was assayed on the chorioallantoic membrane. These data indicate the presence of nonspecific anti-RSV activity in some human leukemic and nonleukemic sera or plasmas and the absence of an etiologic relationship between avian and human leukemia.