tbuckley/cabot-search huggingface dataset:
Evaluation of bone marrow iron stores in anemia associated with chronic disease: A comparative study of serum and red cell ferritin
Authors: Edward P. Balaban, Richard G. Sheehan, Saba E. Demian, John V. Cox, Eugene P. Frenkel
Journal: American Journal of Hematology (1993)

The serum ferritin (SERFER) may be elevated and misleading in the setting of chronic disease (chronic inflammation, liver disease, and neoplasm). The red cell ferritin (RBCFER) may be more stable in clinical situations that affect the SERFER. We compared the ability of SERFER and RBCFER to assess iron stores in these settings. Iron stores were defined by bone marrow aspirate staining. We studied 120 anemic (Hb < 14 g/dl) male patients. Twenty-eight (23%) were iron deficient based on the absence of marrow iron. The SERFER correlation with marrow iron stores (r = 0.58; P < 0.001) was better than the RBCFER (r = 0.36; P < 0.001). Cutoff values for the diagnosis of iron deficiency were determined by chi-square analysis (SERFER < 70 ng/ml; RBCFER < or = 4 ag/RBC). The sensitivity for detecting iron deficiency with SERFER (0.60) was less than RBCFER (0.82). The specificity of SERFER (0.90) was slightly better than RBCFER (0.83). Neither difference reached statistical significance (P > 0.05). The positive predictive value between the two assays was the same (SERFER 0.65 vs. RBCFER 0.59). The combination of SERFER < 70 ng/ml with RBCFER < or = 4 ag/RBC was more specific (0.97) when compared with the SERFER alone (0.90) (P = 0.04). In addition, the potential of this combination to predict iron deficiency (0.82) was higher than that seen with either SERFER (0.65) or the RBCFER (0.59). Our findings show that the RBCFER as a single assay is not anymore accurate than the SERFER. However, we find that the RBCFER can effectively complement the SERFER to either predict iron depletion or confirm the presence of bone marrow iron.
Glandular and extraglandular expression of costimulatory molecules in patients with Sjogren's syndrome
Authors: R Matsumura
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren9s syndrome (SS). <h3>METHODS</h3> Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated. <h3>RESULTS</h3> In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon γ (IFNγ) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor α (TNFα), interleukin 1β (IL1β), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNγ consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFα, IL1β, IL2, and IL4 had no discernible effects. <h3>CONCLUSIONS</h3> Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNγ. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction.
A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins
Authors: T. Nishikawa, T. Nakajima, M. Moriguchi, M. Jo, S. Sekoguchi, M. Ishii, H. Takashima, T. Katagishi, H. Kimura, M. Minami, Y. Itoh, K. Kagawa, T. Okanoue
Journal: Journal of Hepatology (2005)
Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo
Authors: Le Sun, Weixiang Zhang, Xiaohong Liu, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The objective of this study was to prepare azithromycin (AZI) sustained-release products in order to allow for a high dose to be administered, reduce gastrointestinal side-effects and increase the compliance of patients. AZI sustained-release tablets with different release performance (F-I: T100% = 3 h and F-II: T100% = 8 h in pH 6.0 phosphate buffer) were successfully prepared by wet granulation. The in vitro release rate and drug release mechanism were studied. The release rate of F-I was affected by dissolution media with different pH, but not for F-II. Hixson–Crowell model was the best regression fitting model for F-I and F-II. Additionally, F-I and F-II both belonged to non-Fick diffusion. Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration. Compared with the reference, the Cmax of F-I and F-II were decreased, and the Tmax were prolonged, in that case which meet the requirement of sustained-release tablets. The relative bioavailability of F-I and F-II were 79.12% and 64.09%. T-test of AUC0–144, and AUC0–∞ for F-I and F-II indicated there was no significant difference between F-I and F-II. These mean that the extended release rate did not induce different pharmacokinetics in vivo.
Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study
Authors: B. Schultheis, G. Folprecht, J. Kuhlmann, R. Ehrenberg, U.T. Hacker, C.H. Köhne, M. Kornacker, O. Boix, J. Lettieri, J. Krauss, R. Fischer, S. Hamann, D. Strumberg, K.B. Mross
Journal: Annals of Oncology (2013)

BackgroundMetastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil, folinic acid, and oxaliplatin or irinotecan. The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective).Patients and methodsForty-five patients were treated every 2 weeks with 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h, folinic acid 400 mg/m2, and either oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. On days 4–10, patients received regorafenib 160 mg orally once daily.ResultsThe median duration of treatment was 108 (range 2–345 days). Treatment was stopped for adverse events or death (17 patients), disease progression (11 patients), and consent withdrawal or investigator decision (11 patients). Six patients remained on regorafenib at data cutoff (two without chemotherapy). Drug-related adverse events occurred in 44 patients [grade ≥3 in 32 patients: mostly neutropenia (17 patients) and leukopenia, hand–foot skin reaction, and hypophosphatemia (four patients each)]. Thirty-three patients achieved disease control (partial response or stable disease) for a median of 126 (range 42–281 days).ConclusionRegorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics.
Post-Transplantation Lymphoproliferative Disorder After Kidney Transplantation: Report of a Nationwide French Registry and the Development of a New Prognostic Score
Authors: Sophie Caillard, Raphael Porcher, François Provot, Jacques Dantal, Sylvain Choquet, Antoine Durrbach, Emmanuel Morelon, Valérie Moal, Benedicte Janbon, Eric Alamartine, Claire Pouteil Noble, Delphine Morel, Nassim Kamar, Matthias Buchler, Marie France Mamzer, Marie Noelle Peraldi, Christian Hiesse, Edith Renoult, Olivier Toupance, Jean Philippe Rerolle, Sylvie Delmas, Philippe Lang, Yvon Lebranchu, Anne Elisabeth Heng, Jean Michel Rebibou, Christiane Mousson, Denis Glotz, Joseph Rivalan, Antoine Thierry, Isabelle Etienne, Marie Christine Moal, Laetitia Albano, Jean François Subra, Nacera Ouali, Pierre François Westeel, Michel Delahousse, Robert Genin, Bruno Hurault de Ligny, Bruno Moulin
Journal: Journal of Clinical Oncology (2013)

Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years.A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses.Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high-risk recipients.This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.
Therapeutic Synergy between microRNA and siRNA in Ovarian Cancer Treatment
Authors: Masato Nishimura, Eun-Jung Jung, Maitri Y. Shah, Chunhua Lu, Riccardo Spizzo, Masayoshi Shimizu, Hee Dong Han, Cristina Ivan, Simona Rossi, Xinna Zhang, Milena S. Nicoloso, Sherry Y. Wu, Maria Ines Almeida, Justin Bottsford-Miller, Chad V. Pecot, Behrouz Zand, Koji Matsuo, Mian M. Shahzad, Nicholas B. Jennings, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K. Sood, George A. Calin
Journal: Cancer Discovery (2013)

Development of improved RNA interference-based strategies is of utmost clinical importance. Although siRNA-mediated silencing of EphA2, an ovarian cancer oncogene, results in reduction of tumor growth, we present evidence that additional inhibition of EphA2 by a microRNA (miRNA) further "boosts" its antitumor effects. We identified miR-520d-3p as a tumor suppressor upstream of EphA2, whose expression correlated with favorable outcomes in two independent patient cohorts comprising 647 patients. Restoration of miR-520d-3p prominently decreased EphA2 protein levels, and suppressed tumor growth and migration/invasion both in vitro and in vivo. Dual inhibition of EphA2 in vivo using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes loaded with miR-520d-3p and EphA2 siRNA showed synergistic antitumor efficiency and greater therapeutic efficacy than either monotherapy alone. This synergy is at least in part due to miR-520d-3p targeting EphB2, another Eph receptor. Our data emphasize the feasibility of combined miRNA-siRNA therapy, and will have broad implications for innovative gene silencing therapies for cancer and other diseases.This study addresses a new concept of RNA inhibition therapy by combining miRNA and siRNA in nanoliposomal particles to target oncogenic pathways altered in ovarian cancer. Combined targeting of the Eph pathway using EphA2-targeting siRNA and the tumor suppressor miR-520d-3p exhibits remarkable therapeutic synergy and enhanced tumor suppression in vitro and in vivo compared with either monotherapy alone.
INCREASED LEVELS OF APOPTOSIS AND P53 IN PARTIAL-THICKNESS SUPRASPINATUS TENDON TEARS
Authors: K Lundgreen, Ø Lian, A Scott, L Engebretsen
Journal: British Journal of Sports Medicine (2013)

Introduction The role of apoptosis in the progression of rotator cuff tendinopathy is poorly understood. The primary aim of this study was to quantify the amount of apoptosis in supraspinatus tendons presenting partial-thickness tears and matched intact subscapularis tendons. Methods 9 partially torn supraspinatus tendons and matched intact subscapularis tendons were biopsied and compared to 10 reference subscapularis tendon samples. Immunohistochemistry was used to assess apoptotic cells (activated caspase-3; Asp175), proliferation (Ki67) and p53 (M7001), a key protein involved in regulating cell death. The Bonar scale was used to evaluate tendon degeneration. Results The partially torn supraspinatus tendons and matched subscapularis tendons demonstrated a significant increase in the density of apoptotic cells and p53 expression. The Bonar score revealed significant tendon degeneration in the partially torn supraspinatus tendon compared to both matched and reference subscapularis tendon. The number of proliferating tendon cells was higher in the partially torn supraspinatus than in the matched or reference subscapularis tendons. Discussion The presence of increased apoptosis and p53 in partial-thickness tears of the supraspinatus tendon is accompanied by features of both degeneration as well as ongoing repair. Apoptosis may be a relatively early feature in the continuum of rotator cuff tendinopathy.
Exacerbations in cystic fibrosis: 4 {middle dot} Non-cystic fibrosis bronchiectasis
Authors: A B Chang, D Bilton
Journal: Thorax (2008)

Bronchiectasis unrelated to cystic fibrosis (CF) is increasingly recognised as an important and major primary respiratory disease in developing countries. In affluent countries, bronchiectasis is also increasingly recognised in subsections of communities (such as indigenous peoples) as well as a co-existent disease/co-morbidity and disease modifier in respiratory diseases such as chronic obstructive pulmonary disease. The epidemiology, pathogenesis, prevention and management of exacerbations of non-CF bronchiectasis are reviewed. There are few data on all aspects of exacerbations in bronchiectasis. Some of the management issues are common to non-CF and CF bronchiectasis, but it would be unwise to extrapolate from CF studies to non-CF bronchiectasis. In some situations this may be harmful.
Patient-controlled analgesia. Does a concurrent opioid infusion improve pain management after surgery?
Authors: R. K. Parker
Journal: JAMA (1991)

--To assess the influence of a continuous (basal) morphine infusion as part of a patient-controlled analgesia (PCA) system on the postoperative analgesic requirement and on recovery parameters following abdominal hysterectomy.--Single-center, randomized, controlled protocol.--University medical center.--A total of 230 adult women were randomly assigned to receive no morphine infusion (control group) or a continuous 0.5-, 1.0-, or 2.0-mg/h morphine infusion. Each patient was able to self-administer supplemental intravenous bolus doses of morphine (1 to 2 mg) using a PCA infuser.--Use of the PCA device, opioid-related side effects, recovery times, and the patients' assessment of pain and sedation on linear visual analog scales were recorded during the 72-hour study period. Follow-up questionnaires were completed by the patients and their health care professionals to assess the overall adequacy of PCA therapy.--Patients who received the 2-mg/h morphine infusions received significantly more opioid medication 9 to 72 hours after their operation than those who received no infusion (control group). The presence of a continuous morphine infusion of 0.5 to 2 mg/h did not significantly decrease the number of patient demands or supplemental bolus doses administered compared with the control group. Overall, 168 (84%) of the 199 patients who completed the 72-hour study were able to achieve adequate analgesia without requiring changes in the PCA regimen or experiencing major side effects. Recovery times and outcome variables were similar in all four groups.--The routine use of a continuous opioid infusion in combination with a standard PCA regimen does not improve pain management compared with PCA alone after abdominal hysterectomy.
<i>FBXO31</i> Is the Chromosome 16q24.3 Senescence Gene, a Candidate Breast Tumor Suppressor, and a Component of an SCF Complex
Authors: Raman Kumar, Paul M. Neilsen, Joanne Crawford, Ross McKirdy, Jaclyn Lee, Jason A. Powell, Zarqa Saif, Julie M. Martin, Marc Lombaerts, Cees J. Cornelisse, Anne-Marie Cleton-Jansen, David F. Callen
Journal: Cancer Research (2005)

Abstract A BAC located in the 16q24.3 breast cancer loss of heterozygosity region was previously shown to restore cellular senescence when transferred into breast tumor cell lines. We have shown that FBXO31, although located just distal to this BAC, can induce cellular senescence in the breast cancer cell line MCF-7 and is the likely candidate senescence gene. FBXO31 has properties consistent with a tumor suppressor, because ectopic expression of FBXO31 in two breast cancer cell lines inhibited colony growth on plastic and inhibited cell proliferation in the MCF-7 cell line. In addition, compared with the relative expression in normal breast, levels of FBXO31 were down-regulated in breast tumor cell lines and primary tumors. FBXO31 was cell cycle regulated in the breast cell lines MCF-10A and SKBR3 with maximal expression from late G2 to early G1 phase. Ectopic expression of FBXO31 in the breast cancer cell line MDA-MB-468 resulted in the accumulation of cells at the G1 phase of the cell cycle. FBXO31 contains an F-box domain and is associated with the proteins Skp1, Roc-1, and Cullin-1, suggesting that FBXO31 is a component of a SCF ubiquitination complex. We propose that FBXO31 functions as a tumor suppressor by generating SCFFBXO31 complexes that target particular substrates, critical for the normal execution of the cell cycle, for ubiquitination and subsequent degradation. (Cancer Res 2005; 65(24): 11304-313)
Stereotactic Body Radiation Therapy: Scope of the Literature
Authors: Kelley Tipton, Jason H. Launders, Rohit Inamdar, Curtis Miyamoto, Karen Schoelles
Journal: Annals of Internal Medicine (2011)

Stereotactic body radiation therapy (SBRT) is derived from the techniques of stereotactic radiosurgery used to treat lesions in the brain and spine. It combines multiple finely collimated radiation beams and stereotaxy to deliver a high dose of radiation to an extracranial target in the body in a single dose or a few fractions. This review provides a broad overview of the current state of SBRT for solid malignant tumors. Reviewers identified a total of 124 relevant studies. To our knowledge, no published comparative studies address the relative effectiveness and safety of SBRT versus other forms of external-beam radiation therapy. Stereotactic body radiation therapy seems to be widely diffused as a treatment of various types of cancer, although most studies have focused only on its use for treating thoracic tumors. Comparative studies are needed to provide evidence that the theoretical advantages of SBRT over other radiation therapies actually occur in the clinical setting; this area is currently being studied in only 1 small trial.
Dynamic usage of transcription start sites within core promoters
Authors: Hideya Kawaji, Martin C Frith, Shintaro Katayama, Albin Sandelin, Chikatoshi Kai, Jun Kawai, Piero Carninci, Yoshihide Hayashizaki
Journal: Genome biology (2006)

Abstract Background Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level, based on large-scale sequencing of transcript 5' ends. Results In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites is associated with CpG islands, broad and multimodal promoter structures, and imprinting. Conclusion Our results reveal a new level of biologic complexity within promoters - fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic transcriptional regulation.
Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with severe Moya Moya disease
Authors: S. Meyer, L. Zanardo, W.E. Kaminski, P. Horn, G. Schmitz, U. Hohenleutner, W.A. Herrmann, M. Landthaler, T. Vogt
Journal: British Journal of Dermatology (2005)

A 2‐year‐old girl with Moya Moya disease who had relapsing cerebrovascular strokes presented with loose skin folds, 'chicken' skin appearance and perforating elastosis serpiginosa‐like lesions in the genitocrural region. Histologically, calcified material perforating the epidermis and adjacent short curled and mineralized elastic fibres suggested a variant of pseudoxanthoma elasticum (PXE). As PXE is known to be caused by various mutations in the transmembrane transporter ABCC6 gene, we hypothesized that a novel ABCC6 mutation may underlie this unique combination of PXE and elastopathic vascular damage. Therefore, the complete ABCC6 coding region of the patient and her parents was screened for genetic alterations. No bona fide disease‐causing mutation of ABCC6 could be found in the child and in her parents. However, two novel allelic amino acid substitutions (Arg1273Lys and Glu1293Lys; exon 27) were found in the girl and her father, localized in close proximity to the region that codes for the functionally critical second nucleotide‐binding fold of ABCC6. Although a causal involvement of these amino acid substitutions could not be proven based on this study, both heterozygote substitutions may possibly have interacted with other undetected recessive maternal ABCC6 changes in the child. To the best of our knowledge, this is the first report of an association between early‐onset PXE and severe Moya Moya syndrome possibly related to ABCC6 changes.