tbuckley/cabot-search huggingface dataset:
Ratio of myeloid and plasmacytoid dendritic cells and TH2 skew in CRS with nasal polyps
Authors: H. Kirsche, A. Niederführ, T. Deutschle, C. Fuchs, H. Riechelmann
Journal: Allergy (2009)

The role of myeloid and plasmacytoid dendritic cells and its consequences for the T(H)2 skew in chronic rhinosinusitis (CRS) with nasal polyps (CRSNP(+)) should be detailed.In 18 CRS patients without nasal polyps (CRSNP(-)), 35 CRSNP(+) patients and 22 patients with nasal structural abnormalities without rhinosinusitis (controls), dendritic cells (DC) were differentiated into myeloid (mDC) and plasmacytoid (pDC) subtypes using an antibody cocktail including CD1c (BDCA-1) and CD303 (BDCA-2) in peripheral blood mononuclear cells (PBMC) and single cell preparations of sinonasal mucosa by flow cytometry. Moreover, cells were analysed for expression of CD45, CD3, CD4, CXCR3 (T(H)1) and CCR4 (T(H)2) and IFN-gamma, IL-5, TGF-beta1, TGF-beta2, ECP and total IgE in nasal secretions were determined. As a possible confounder, Staphylococcus aureus in nasal lavages was detected.The tissue mDC/pDC-ratio was 1.7 (1.0-2.4) in controls, 3.0 (1.8-4.0) in CRSNP(-) and 0.8 (0.6-1.0) in CRSNP(+) (P < 0.01). In tissue samples, the T(H)1/T(H)2 ratio was 12.6 (6.4-16.0) in controls, 12.5 (6.9-21.2) in CRSNP(-) and 1.8 (1.3-3.6) in CRSNP(+) (median and interquartile range, P < 0.001). Less pronounced differences were found in PBMC. S. aureus detection rates or TGF-beta levels did not differ between patient groups and S. aureus detection had no influence on the parameters investigated.A significant T(H)2 skew in CRSNP(+) could be confirmed on the cellular level. It was driven by low myeloid dendritic cell numbers. The T(H)2 skew did not correlate with S. aureus detection. The data support the concept that CRSNP(+) and CRSNP(-) are pathophysiologically distinct.
Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles
Authors: Shufang Nie, Jia Zhang, Raul Martinez-Zaguilan, Souad Sennoune, Md Nazir Hossen, Alice H. Lichtenstein, Jun Cao, Gary E. Meyerrose, Ralph Paone, Suthipong Soontrapa, Zhaoyang Fan, Shu Wang
Journal: Journal of Controlled Release (2015)
Light and Electron Microscopy of Low and High Malignancy Sublines of a Rat Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N. A. Ratcliffe, A. E. Williams, H. Smith
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Light and Electron Microscopy of Low and High Malignancy Sublines of a Rat Tumor Get access N. A. Ratcliffe, N. A. Ratcliffe Department of Microbiology, University of Birmingham, Birmingham 15, England Search for other works by this author on: Oxford Academic PubMed Google Scholar A. E. Williams, A. E. Williams Department of Microbiology, University of Birmingham, Birmingham 15, England Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Smith H. Smith Department of Microbiology, University of Birmingham, Birmingham 15, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 2, February 1971, Pages 243–252, https://doi.org/10.1093/jnci/46.2.243 Published: 01 February 1971 Article history Received: 18 May 1970 Accepted: 16 October 1970 Published: 01 February 1971
Calcium acetate as a phosphorus binder in hemodialysis patients.
Authors: J A Delmez, C A Tindira, D W Windus, K Y Norwood, K S Giles, T L Nighswander, E Slatopolsky
Journal: Journal of the American Society of Nephrology (1992)

Much interest is currently centered on the use of calcium acetate as a phosphorus binder in patients with renal failure. Therefore, this compound in subjects previously stable on calcium carbonate and undergoing high-efficiency hemodialysis with a dialysate calcium of 2.5 mEq/L was evaluated. Twenty subjects were switched from generic calcium carbonate to a single calcium carbonate preparation for a period of 2 months. This was followed by a phase (1 month) in which calcium acetate was substituted for calcium carbonate at a dose containing half the amount of elemental calcium. Subjects then continued calcium acetate for 6 months. It was found that calcium acetate allowed comparable control of immunoreactive parathyroid hormone, calcium, and phosphorus levels compared with calcium carbonate. This occurred with half the amount of elemental calcium ingested in the form of calcium acetate (349 +/- 25 versus 699 +/- 75 mmol/day; P less than 0.001). With this lower dose, the overall incidence of hypercalcemia was the same with each formulation. In the eight subjects concurrently receiving i.v. calcitriol, the incidence of hypercalcemia was significantly higher during the first month of calcium acetate compared with that in those not receiving this compound (P less than 0.05). Of those four subjects receiving the high dose of calcitriol (2 micrograms thrice weekly), all required either reduction in the dose or discontinuation of the drug. Thus, mineral metabolism could be controlled adequately with calcium acetate despite using half as much elemental calcium compared with calcium carbonate. This, however, did not result in a lower incidence of hypercalcemia, particularly in those receiving i.v. calcitriol.
Late Effects of Treatment in Survivors of Childhood Acute Myeloid Leukemia
Authors: Wing Leung, Melissa M. Hudson, Donald K. Strickland, Sean Phipps, Deo K. Srivastava, Raul C. Ribeiro, Jeffrey E. Rubnitz, John T. Sandlund, Larry E. Kun, Laura C. Bowman, Bassem I. Razzouk, Prasad Mathew, Patricia Shearer, William E. Evans, Ching-Hon Pui
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: Of 77 survivors (median follow-up duration, 16.7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. RESULTS: Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. CONCLUSION: Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.
Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion
Authors: Gang Chen, Chul-Kyu Park, Rou-Gang Xie, Ru-Rong Ji
Journal: Journal of Clinical Investigation (2015)

Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia, for several weeks in murine chronic constriction injury (CCI) and spared nerve injury models. Moreover, i.t. BMSCs reduced CCI-induced spontaneous pain and axonal injury of dorsal root ganglion (DRG) neurons and inhibited CCI-evoked neuroinflammation in DRGs and spinal cord tissues. BMSCs secreted TGF-β1 into the cerebrospinal fluid, and neutralization of TGF-β1, but not IL-10, reversed the analgesic effect of BMSCs. Conversely, i.t. administration of TGF-β1 potently inhibited neuropathic pain. TGF-β1 acted as a powerful neuromodulator and rapidly (within minutes) suppressed CCI-evoked spinal synaptic plasticity and DRG neuronal hyperexcitability via TGF-β receptor 1–mediated noncanonical signaling. Finally, nerve injury upregulated CXCL12 in lumbar L4–L6 DRGs, and this upregulation caused migration of i.t.-injected BMSCs to DRGs through the CXCL12 receptor CXCR4, which was expressed on BMSCs. BMSCs that migrated from the injection site survived at the border of DRGs for more than 2 months. Our findings support a paracrine mechanism by which i.t. BMSCs target CXCL12-producing DRGs to elicit neuroprotection and sustained neuropathic pain relief via TGF-β1 secretion.
The indices of body composition (IBC) in chronic obstructive pulmonary disease (COPD)
Authors: Aliaksandr Makarevich, Sviatlana Lemesheuskaya, Natalja Vasieljeva
Journal: European Respiratory Journal (2011)

The aim:  To analyze of IBC at different stages of COPD as well as the relationships between the IBC, lung function and smoking status.   Material and methods:  Bone mineral content (BMC), Fat mass (FM) and Lean mass (FFM, excluding BMC) were detected by dual-energy X-ray absorptionmetry. FM, FFM and BMC were expressed as the ratio to height squared to obtain indices FMI, FFMI and BMCI respectively. The pts (aged 40-69 yrs) were divided into 3 groups according to COPD severity. The 1st group was made of 14 men (GOLD I stage; mean age 55 yrs; FEV 1  78%; BMI 27 kg/m 2 , smokers 68%, packs/yrs smoking index 20); the 2nd included 43 men (GOLD II stage; mean age 57; FEV 1  63%; BMI 28 kg/m 2 , smokers 80%, packs/yrs 21); the 3rd - 20 men (GOLD III stage; mean age 60; FEV 1  41%; BMI 24 kg/m 2 , smokers 84%, packs/yrs 28). The control group was formed of 15 healthy men (mean age 56 yrs, mean BMI 26 kg/m 2 , smokers 66%, packs/yrs 20).   Results:  The FFMI value was decreased during COPD progression (from 21,3 kg/m 2  in the 1st group to 17,7 kg/m 2  in the 3rd group; p 1  (r=0,4). The BMCI value in 1st group and the control was similar (1,06 kg/m 2 ) and it was significantly higher than in 2nd and 3rd groups (1,01 and 0,89 kg/m 2  respectively). Pts of 3rd group had a lower FMI as compare with the pts of 1st and 2nd groups (4,25 vs. 8,28 and 9,72 respectively; p   Conclusions:  The dynamics of IBC changes can probably reflect COPD progression.
Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model
Authors: Sook In Chung, Hyuk Moon, Hye-Lim Ju, Kyung Joo Cho, Do Young Kim, Kwang-Hyub Han, Jung Woo Eun, Suk Woo Nam, Silvia Ribback, Frank Dombrowski, Diego F. Calvisi, Simon Weonsang Ro
Journal: Journal of Hepatology (2015)
Abstract 3512: MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
Authors: Nora Hipp, Lisa Christner, Thomas Wirth, Wolfgang Mueller-Klieser, Stefan Walenta, Evelin Schröck, Klaus-Michael Debatin, Christian Beltinger
Journal: Cancer Research (2014)

Abstract The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and HIF1α-linked vascular remodeling. This cooperation between MYCN and survivin may be important in the genesis of several cancers. Citation Format: Nora Hipp, Lisa Christner, Thomas Wirth, Wolfgang Mueller-Klieser, Stefan Walenta, Evelin Schröck, Klaus-Michael Debatin, Christian Beltinger. MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3512. doi:10.1158/1538-7445.AM2014-3512
Lapdesf 1 a Compound Hybrid of Hydroxyrea and Thalidomide Increases Gamma Globin Expression in the Human CD34+ Cultures and Reduces Chemotactic Activity in Neutrophils
Authors: Sheley Gambero, Carolina Lanaro, Flavia Rubia Pallis, Carla Fernanda Franco-Penteado, Lidia Moreira Lima, Jean Leandro Santos, Chung Man Chin, Fernando Ferreira Costa
Journal: Blood (2011)
Maternal Midpregnancy Glucose Levels and Risk of Congenital Heart Disease in Offspring
Authors: James R. Priest, Wei Yang, Gerald Reaven, Joshua W. Knowles, Gary M. Shaw
Journal: JAMA Pediatrics (2015)

There is a well-described association between maternal diabetes mellitus and risk of congenital heart disease (CHD) in offspring. Although the clinical diagnoses of type 2 diabetes or gestational diabetes are strong risk factors for CHD, subclinical abnormalities of glucose and insulin metabolism are common within the general population and could also confer risk for CHD. We hypothesize that continuous measures of blood analytes related to maternal diabetes are related to odds of cardiac malformations.
Longitudinal effects of a multidisciplinary programme of pulmonary rehabilitation for patients with chronic obstructive pulmonary disease in primary health care
Authors: Ann-Britt Zakrisson, Kersti Theander, Terese Anerös
Journal: European Respiratory Journal (2013)

Longitudinal effects of a multidisciplinary programme of pulmonary rehabilitation for patients with chronic obstructive pulmonary disease in primary health care
Adherence to asthma treatment: Can it be improved in general practice?
Authors: Maja Bornemann, Vibeke Backer
Journal: European Respiratory Journal (2012)

Background

Good treatment adherence is pivotal in maintaining well-controlled asthma, along with the right diagnosis and the right treatment.

Aim

In a GP setting, we aimed to study changes in adherence to asthma treatment among asthmatic patients when using a systematic asthma consultation guide based on the Global Initiative of Asthma guidelines.

Methods

The study comprised 2148 patients aged 18-79 years with doctor-diagnosed asthma from 130 clinics across Denmark. When managing the patients, the clinics were instructed to follow a consultation guide based on the principles of the GINA guidelines. This included evaluation of symptoms, treatment, adherence, lung function, and a scheduled follow-up appointment based on the level of asthma control. Adherence and use of medication were determined using a questionnaire as part of the consultation with a trained asthma nurse.

Results

At the date of analysis 706 patients had attended both baseline and follow-up visit. At baseline visit 542 (76.8%) patients were classified as having high adherence and 94 (13.3%) as having low adherence. Of the 94 who had low adherence at the baseline visit, 83 (88.3%) changed to high adherence at follow-up visit (p<0.001). Fewer patients (n=15 (2.8%)) of those who had high adherence at the baseline visit had changed to low adherence at the follow-up visit (P<0.001). Of those who after asthma education at baseline visit had changed from low to high adherence a better disease control was found at the follow-up visit (p<0.001).

Conclusion

The overall treatment adherence improved significantly when a systematic asthma management approach was introduced and applied by dedicated health care staff.
Phase I Trial of 40-kd Branched Pegylated Interferon Alfa-2a for Patients With Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Ashok Rakhit, Michelle Ginsberg, Karen Rittweger, Jacqueline Vuky, Richard Yu, Scott Fettner, Leon Hooftman
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNα2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNα2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled onto cohorts of three or six patients. PEG-IFN was administered on a weekly basis by subcutaneous injection. The dose was escalated from 180 μg/wk to a maximum of 540 μg/wk in 90-μg increments. Serial venous blood samples were drawn to assess concentrations of PEG-IFN and two immunologic surrogates, neopterin and 2′-5′ oligoadenylate synthetase (OAS). RESULTS: The maximum-tolerated dose was determined as 540 μg/wk, because two patients experienced dose-limiting toxicity within 28 days of starting treatment. One developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue. Six patients were treated at 450 μg/wk without dose-limiting toxicity. Over the course of treatment, the side-effect profile was mostly mild to moderate in intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and decreased appetite. Five patients (19%) achieved a partial response. The mean maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180 μg/wk to 540 μg/wk. Serum concentration of PEG-IFN was sustained at close to peak during the dosing interval, and steady-state was achieved in approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were induced at all doses with a sustained concentration profile similar to PEG-IFN. CONCLUSION: PEG-IFN is a modified form of IFNα2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 μg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNα and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNα.
Panobinostat for the Treatment of Multiple Myeloma
Authors: Jacob P. Laubach, Philippe Moreau, Jesús F. San-Miguel, Paul G. Richardson
Journal: Clinical Cancer Research (2015)

Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received ≥2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression-free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma.
Monitoring of antituberculous drugs adverse events during the treatment of multidrug-resistant pulmonary tuberculosis
Authors: Maryna Dziusmikeyeva, Aksana Zalutskaya, Aliaksandr Skrahin, Aleh Prasmyzki, Varvara Solodovnikova, Alena Skrahina
Journal: European Respiratory Journal (2011)

Setting:  The known determinants of drug-resistance development are non-compliance with prescribed treatment. Clinical management of multidrug-resistant tuberculosis (MDR-TB) requires lengthy multidrug regimens that often cause adverse events. Interruptions in treatment may result from the adverse events.   Design:  We retrospectively reviewed medical records of 220 patients with MDR-TB who received individualized treatment in accordance with the recommendations of the WHO. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome.   Results:  One or more adverse events were observed in all patients in the study. With an average of one patient receiving treatment, noted 10.4 episodes of adverse events. The most commonly reported events were nausea and vomiting (61%), dizziness (56%), abdominal pain (39%), arthralgia (31%), ototoxicity (19%) and dermatological effects (19%), psychiatric disorders (8%), hepatitis (4%) and renal failure (3%). These events led the clinicians to change in drug dose or withdraw one or more drugs from the treatment regimen temporarily or permanently.   Conclusion:  Antituberculous drugs adverse events and connected with them treatment interruptions are observed more often in treatment of MDR-TB. MDR-TB patients who are female, older or have severe TB disease should be closely monitored for treatment-related adverse events. Obtained data allow to predict possible adverse events of MDR-TB chemotherapy, to provide the availability of medications necessary for adverse events reduction, including emergency cases.
Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine
Authors: Aiden Haghikia, Stefanie Jörg, Alexander Duscha, Johannes Berg, Arndt Manzel, Anne Waschbisch, Anna Hammer, De-Hyung Lee, Caroline May, Nicola Wilck, Andras Balogh, Annika I. Ostermann, Nils Helge Schebb, Denis A. Akkad, Diana A. Grohme, Markus Kleinewietfeld, Stefan Kempa, Jan Thöne, Seray Demir, Dominik N. Müller, Ralf Gold, Ralf A. Linker
Journal: Immunity (2015)