tbuckley/cabot-search huggingface dataset:
Waldenström macroglobulinemia: 2015 update on diagnosis, risk stratification, and management
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2015)

Disease Overview : Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis : Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification : Age, hemoglobin level, platelet count, β 2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Risk‐Adapted Therapy : Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or both). The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Management of Refractory Disease : Bortezomib, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials. Am. J. Hematol. 90:347–354, 2015. © 2015 Wiley Periodicals, Inc.
Effects of repeated exposure to 4 ppm nitrogen dioxide on bronchoalveolar lymphocyte subsets and macrophages in healthy men
Authors: T Sandstrom, R Helleday, L Bjermer, N Stjernberg
Journal: European Respiratory Journal (1992)

Following the basal descriptive studies of the bronchoalveolar inflammatory cell response induced by single exposure with nitrogen dioxide (NO2) in man, it was considered important to clarify the cell response to repeated exposure with NO2. This investigation was, therefore, undertaken with bronchoalveolar lavage (BAL) 3 weeks before and 24 h after six repeated exposures with 4 ppm NO2 (7 mg.m-3) in ten healthy volunteers. The exposures were performed during 20 min and every second day. Analysis of the recovered BAL fluid demonstrated that repeated exposures to NO2 caused a lung cell response different from that reported after a single exposure. Amounts of lavaged alveolar macrophages, B-cells, and natural killer (NK)-cells were decreased and the T-helper-inducer/cytotoxic-suppressor cell ratio was altered, but there was no lymphocytosis or mastocytosis as after single exposure. Lymphocyte numbers in peripheral blood were reduced after exposure. These results suggest that repeated exposure with NO2 adversely affects the immune defence. This could contribute to the increased susceptibility to airway infections reported to be associated with NO2 exposure.
ZAP‐70 Genotype Disrupts the Relationship Between Microbiota and Host, Leading to Spondyloarthritis and Ileitis in SKG Mice
Authors: Linda M. Rehaume, Stanislas Mondot, Daniel Aguirre de Cárcer, Jared Velasco, Helen Benham, Sumaira Z. Hasnain, Jaclyn Bowman, Merja Ruutu, Philip M. Hansbro, Michael A. McGuckin, Mark Morrison, Ranjeny Thomas
Journal: Arthritis & Rheumatology (2014)

The spondyloarthritides share genetic susceptibility, interleukin-23 (IL-23) dependence, and the involvement of microbiota. The aim of the current study was to elucidate how host genetics influence gut microbiota and the relationship between microbiota and organ inflammation in spondyloarthritides.BALB/c ZAP-70(W163C) -mutant (SKG) mice, Toll-like receptor 4 (TLR-4)-deficient SKG mice, and wild-type BALB/c mice were housed under specific pathogen-free conditions. SKG and wild-type BALB/c mice were maintained under germ-free conditions, and some of these mice were recolonized with altered Schaedler flora. All of the mice were injected intraperitoneally with microbial β-1,3-glucan (curdlan). Arthritis, spondylitis, and ileitis were assessed histologically. Microbiome composition was analyzed in serial fecal samples obtained from mice that were co-housed beginning at the time of weaning, using 454 pyrosequencing. Infiltrating cells and cytokines in the peritoneal cavity were measured by flow cytometry and enzyme-linked immunosorbent assay. Cytokine, endoplasmic reticulum (ER) stress marker, and tight junction protein transcription was measured by quantitative real-time polymerase chain reaction.Microbiota content and response to curdlan varied according to whether T cell receptor signal strength was normal or was impaired due to the ZAP-70(W163C) mutation. Curdlan triggered acute inflammation regardless of the presence of the SKG allele or microbiota. However, no or limited microbiota content attenuated the severity of arthritis. In contrast, ileal IL-23 expression, ER stress, lymph node IL-17A production, goblet cell loss, and ileitis development were microbiota-dependent. Ileitis but not arthritis was suppressed by microbiota transfer upon co-housing SKG mice with wild-type BALB/c mice, as well as by TLR-4 deficiency.The interaction between immunogenetic background and host microbiota leads to an IL-23-dependent loss of mucosal function, triggering ileitis in response to curdlan.
Megalin is an endocytic receptor for insulin.
Authors: R A Orlando, K Rader, F Authier, H Yamazaki, B I Posner, J J Bergeron, M G Farquhar
Journal: Journal of the American Society of Nephrology (1998)

Renal clearance is a major pathway for regulating the levels of insulin and other low molecular weight polypeptide hormones in the systemic circulation. Previous studies have shown that the reabsorption of insulin from the glomerular filtrate occurs by binding to as yet unidentified sites on the luminal surface of proximal tubule cells followed by endocytosis and degradation in lysosomes. In this study, an insulin binding site was identified in renal microvillar membranes by chemical cross-linking procedures. By immunoprecipitation it was demonstrated that this binding site is megalin, the large multiligand binding endocytic receptor that is abundantly expressed in clathrin-coated pits on the apical surface of proximal tubule cells. Moreover, using cytochemical procedures, it was also shown that megalin is able to internalize insulin into endocytic vesicles. In ligand blotting assays, megalin also bound several other low molecular weight polypeptides, including beta2-microglobulin, epidermal growth factor, prolactin, lysozyme, and cytochrome c. These data suggest that megalin may play a significant role as a renal reabsorption receptor for the uptake of insulin and other low molecular weight polypeptides from the glomerular filtrate.
Propagation of the Mammary Tumor Agent (Bittner Virus) in the Absence of Mammary Glands in Mice
Authors: Anna Dux, O. Mühlbock
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Propagation of the Mammary Tumor Agent (Bittner Virus) in the Absence of Mammary Glands in Mice Get access Anna Dux, Anna Dux Biological Department, Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar O. Mühlbock O. Mühlbock Biological Department, Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 6, June 1968, Pages 1309–1312, https://doi.org/10.1093/jnci/40.6.1309 Published: 01 June 1968 Article history Received: 13 February 1968 Accepted: 23 February 1968 Published: 01 June 1968
Phase II study of PHY906 plus capecitabine (CAP) in pts with gemcitabine-refractory pancreatic cancer (PC) and measurement of cytokines.
Authors: M. Saif, J. Li, L. Lamb, K. Kaley, S. Bussom, R. Carbone, K. Elligers, S. Krishnamoorthy, S. Liu, Y. C. Cheng
Journal: Journal of Clinical Oncology (2010)

e14540 Background: Oral CAP offers convenience as a palliative chemotherapeutic option, however, diarrhea and HFS may compromise its efficacy. Pts in USA cannot tolerate CAP 1,250 mg/m2 BID D1-14 without experiencing toxicities. PHY906, a traditional Chinese botanical formula has shown synergistic anti-tumor activity with CAP as well as cytoprotective anti-diarrheal effect in preclinical and phase I studies (ASCO 2007, 2008). These data provide a strong rationale for extending this combination into PC. Methods: PC pts with prior gemcitabine received CAP 1,500 mg/m2 BID D1-7 and PHY906 800 mg/m2 BID D1-4 q 2 wks. AEs were assessed per NCI CTCAE v3.0 and response per RECIST q 6 wks. Primary objective was OS and secondary aim to determine effect of PHY906 on cytokines and chemokines including IL-2, IL-4, IL-5, IL-6, IL-10, MCP-1, TNF-a, IFN-g, VEGF, FGF-B, GM-CSF, G-CSF using a cytometric bead array assay. Results: Twenty-five pts were enrolled: 25 received study drug (evaluable for safety); 23 received at least 1 cycle (evaluable for efficacy). Median age was 60yr (range 45-84), 10 F and 15 M, with a median ECOG PS of 1 (range 0-2). Predominant AEs included grade 3 diarrhea (n = 3), grade 3 fatigue (n = 3) and grade 3 HFS (n = 1). Among 23 pts, 2 achieved PR (9%), 10 had stable disease (43%) resulting in disease control rate of 52%. All intent-to-treat pts reached mPFS of 10 wks (r: 0.4-51) and mOS of 12 wks (r: 0.4-63). For 18 pts who received > = 2 cycles, mPFS was 13 wks and mOS 31 wks. 9-mth survival rate was 22%. Preliminary correlative studies showed that none of the cytokines except serum IL-6 was reversely correlated with survival. QOL data is currently under evaluation. Conclusions: This is the first clinical study to evaluate a botanical drug PHY906 plus CAP in PC. Our results suggest that PHY906 can increase therapeutic index of CAP by reducing diarrhea and HFS. This combination appears a safe and feasible salvage therapy after gemcitabine failure and warrants further investigation in a randomized study against CAP. Recent studies have indicated role of IL-6 in tumor progression and tumor cachexia, suggesting a need to investigate its relation to pathophysiology of PC and development of anti-IL-6 therapeutics. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PhytoCeutica PhytoCeutica Bayer, Bristol-Myers Squibb, Genentech, Novartis, Roche, sanofi-aventis Enzon, Merck, PhytoCeutica, Roche, Taiho Pharmaceutical
Epidermal Carcinogenesis by Carcinogen Followed by Various Concentrations of Croton Oil&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: J. V. Frei, A. C. Ritchie
Journal: JNCI Journal of the National Cancer Institute (1962)

Papillomas were induced in the skin of the mouse by a single application of 7,12-dimethylbenz[a]anthracene followed by repeated applications of croton oil. When the concentration of croton oil was altered, the yield of papillomas was changed, but not the period during which they appeared. A similar result was found when the concentration of the carcinogen was varied, but the croton oil treatment was kept constant. It is considered that in experiments of this sort, croton oil does not necessarily make all the cells changed by the initial application of carcinogen visible as papillomas.
Nitric oxide-releasing polysaccharide derivative exhibits 8-log reduction against Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus
Authors: Adoracion Pegalajar-Jurado, Kathryn A. Wold, Jessica M. Joslin, Bella H. Neufeld, Kristin A. Arabea, Lucas A. Suazo, Stephen L. McDaniel, Richard A. Bowen, Melissa M. Reynolds
Journal: Journal of Controlled Release (2015)
Interdigital dermatitis: sentinel skin damage in hairdressers
Authors: H.J. Schwanitz, W. Uter
Journal: British Journal of Dermatology (2000)

Journal Article Interdigital dermatitis: sentinel skin damage in hairdressers Get access H.J. Schwanitz, H.J. Schwanitz Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstraße 115, D‐49069 Osnabrück, Germany Search for other works by this author on: Oxford Academic Google Scholar W. Uter W. Uter Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstraße 115, D‐49069 Osnabrück, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 1011–1012, https://doi.org/10.1046/j.1365-2133.2000.03487.x Published: 01 May 2000
CA 19–9 as a predictor of response and survival in patients with pancreatic cancer treated with gemcitabine and cisplatin based chemotherapy
Authors: L. K. Heilbrun, A. Khanna, R. Venkatramanamoorthy, A. F. Shields, P. A. Philip, M. M. Zalupski, B. F. El-Rayes
Journal: Journal of Clinical Oncology (2007)

15094 Background: Radiologic evaluation of the efficacy of chemotherapy (CT) regimens in pancreatic cancer is complicated by the retroperitoneal location and the desmoplastic nature of the tumor. The aim of this study was to evaluate the role of baseline CA 19–9 and the decrease in CA 19–9 after one cycle of CT as predictors of response, time to progression (TTP) , and overall survival (OS). Methods: We conducted 3 consecutive phase II trials evaluating gemcitabine and cisplatin based CT between 1997 and 2004. A retrospective chart review of the 111 patients yielded demographic data, best response status, TTP, OS, and CA19–9 levels. Response by CA 19–9 (R-CA19–9) was defined as a decrease of = 50% in CA 19–9 after the completion of the first cycle of chemotherapy. Results: The median age was 59 years with 60% males. Median performance status (PS) was 1. No significant difference was observed across the three trials with respect to age, sex, or PS. Baseline CA19–9 was known for 102 patients, and was dichotomized near the median as: &lt; 1,000; and = 1,000 ng/mL. Lower baseline CA19–9 levels were not associated with higher radiologic response (RR) rate (p = 0.82): 22%, and 19%, respectively. Lower baseline CA19–9 was associated with longer OS, (p = 0.0057), as shown in a recent UK study. Median OS was 9.2, and 6.1 months, respectively. Similar results were observed for TTP, with p = 0.0146, and median TTP of 6.4 and 4.2 months, respectively. The change in CA19–9 from baseline to the end of treatment cycle 1 was available for 68 patients. The patients with R-CA19- 9 had a higher RR rate (29%) than did the other patients (24%), but not significantly so (p = 0.7495). The patients with R-CA19–9 had longer OS (median 8.7 vs 7.1 months) and longer TTP (median 7.1 vs 5.4 months), but not significantly so (p &gt; 0.73 for each endpoint). Conclusions: Lower baseline CA19–9 (but not R-CA19–9 after treatment cycle 1) was positively associated with OS and TTP prognosis in our patient population. A 50% decrease in CA19–9 after the first cycle of chemotherapy was not a useful predictor of response, TTP, or OS. No significant financial relationships to disclose.
Outcome and Reproductive Function After Chemotherapy for Ovarian Dysgerminoma
Authors: Molly Brewer, David M. Gershenson, Cynthia E. Herzog, Michele Follen Mitchell, Elvio G. Silva, J. Taylor Wharton
Journal: Journal of Clinical Oncology (1999)

To review the outcome for all patients with ovarian dysgerminoma treated at the M.D. Anderson Cancer Center who received bleomycin, etoposide, and cisplatin (BEP) and to assess the menstrual and reproductive function of those who received conservative treatment.Clinical information was abstracted from the medical record. Patients completed a detailed questionnaire about menstrual and reproductive function; those who did not return the questionnaire were interviewed by telephone.Twenty-six patients were identified as having been treated with BEP chemotherapy for pure ovarian dysgerminoma from January 1984 to January 1998. Their median age was 19.5 years (range, 7 to 32 years). Sixteen patients underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy. At a median follow-up time of 89 months, 25 (96%) of the 26 patients remained continuously disease-free. One patient apparently developed a second primary dysgerminoma in her remaining ovary after BEP and was clinically disease-free after further treatment. Of the 16 patients who underwent fertility-sparing surgery, one was lost to follow-up when she was pregnant, and one was still premenarchal. Of the remaining 14 patients, 10 (71%) maintained their normal menstrual function during and after chemotherapy, and 13 (93%) had returned to their prechemotherapy menstrual pattern at the time of the questionnaire. Five pregnancies have occurred thus far, and two patients have had difficulty conceiving.Most patients with metastatic dysgerminoma can expect cure with maintenance of normal reproductive function when treated with conservative surgery and BEP chemotherapy.
Relationship between carotid wall thickness and multiple severity parameters in COPD patients
Authors: Ovidiu Fira-Mladinescu, Rodica Dan, Cristian Oancea, Alexandru Crisan, Emanuela Tudorache, Lucian Petrescu, Voicu Tudorache
Journal: European Respiratory Journal (2014)

Background: Although several large cohort studies have already shown an association between chronic airflow limitation and subclinical carotid atherosclerosis, the underlying mechanisms for this relationship are still unclear.

Aim: To investigate the possible connections between the carotid intima-media thickness (cIMT) as an atherosclerosis hallmark, and the pulmonary and extrapulmonary effects of COPD.

Methods: In a cross-sectional study, 109 patients with stable COPD underwent spirometry together with determination of maximal respiratory pressure (MIP and MEP), blood sampling, chest radiogram, carotid ultrasonography, six-minute walk test (6MWT), dynamometry, and bioelectrical impedance analysis for body composition.

Results: In all stages of COPD the mean values of cIMT were greater than 0.92 mm, the optimal predictive cutoff value for the presence of atheromatous plaques, according to our ROC curve analysis. Even though we have found significant differences in cIMT values related to the severity of COPD (1.03±0.14 in GOLD 2, vs. 1.07±0.17 in GOLD 3, and vs. 0.95±0.18 in GOLD 4; p=0.04), we did not find a direct correlation with FEV1 ( r =0.02, p=0.84) and post-hoc analysis showed a more significant carotid wall thickness in early stages (p<0.05). We also have found a significant correlation between cIMT with the muscular dysfunction profile (MIP: r =-0.28, p<0.01; hand grip force: r =-0.31, p<0.01; 6MWT distance: r =-0.28, p<0.01), and with the body composition parameters (fat body weight r= 0.32, p=0.001).

Conclusions: The atherosclerotic changes are present from the early stages of COPD, being in a closer relationship with the muscular dysfunction, rather than with the airflow obstruction.
Spirometry quality assessment performed by general practitioners in frame of the RESPECT study
Authors: Marina Pokhaznikiva, Elena Andreeva, Anatoly Lebedev, Olga Kuznetsova, Jean-Marie Degryse
Journal: European Respiratory Journal (2014)

Background:   Obstructive lung diseases remain one of the major public health problems in Russia due to a high prevalence of smoking. There is a consensus about the underestimation of the prevalence of chronic obstructive pulmonary disease (COPD) and a definite need for early screening on the primary care level. General practitioners (GPs) are usually the first to examine patients with asthma and COPD and still do not perform office spirometry.   Aim:  to assess the quality of GPs9 spirometry after the e-learning education course.   Methods:   The e-learning educational course was created as a part of the RESPECT project which aims to estimate the COPD prevalence in two Russian regions of the North-West. This three week course contains instructional videos with clinical cases, progress tests and literature for future reference. A one day face-to-face session (for each region) makes it possible to improve the practical skills of using a portable spirometer (Spirobank). Spirogram quality assessment was performed according to ATS/ERS criteria.   Results:   Altogether 33 investigators (from 10 centers in St. Petersburg and 5 centers in Arkhangelsk) were involved in this course. Totally 3020 spirogramms were performed (93.5% of them were acceptable with ATS/ERS 1 and 2 levels). 82% of all acceptable spirogramms were given reversibility tests. The main errors were: expiration less than 6 seconds (54% of all performed spirograms) and the artefacts (non-maximal effort throughout the test, the glottis closure and others, altogether - 4.7%).   Conclusion:   The RESPECT investigators were able to can carry out spirometry with acceptable quality.
Evaluation of highly sensitive PNA-LNA PCR clamp method for EGFR L858R mutation detection in lung adenocarcinoma patients
Authors: Michal Skronski, Tomoaki Tanaka, Adam Szpechcinski, Renata Langfort, Tadeusz Orlowski, Koichi Hagiwara, Joanna Chorostowska-Wynimko
Journal: European Respiratory Journal (2011)

Objective:  Direct sequencing is widely accepted method for EGFR mutation identification, but has limited sensitivity. It often requires additional procedures, like microdissection, to enrich the sample in cancer cells, when their content in tissue specimen is less than 50%. PNA-LNA PCR clamping represents allele-specific approach to gene analysis and demonstrates potent accuracy and ability to detect mutant alleles even if present in low fraction of cells.   Method:  79 DNA samples isolated from fresh-frozen and FFPE tissues, which mutation status was formerly confirmed by sequencing, were analyzed by PNA-LNA PCR clamping for EGFR point mutation L858R in exon 21.   Results:  L858R mutation was detected in 8/79 (10%) samples by direct sequencing, whereas in 12/79 (15%) samples by PNA-LNA PCR clamping. All mutant-positive samples by sequencing were correctly determined by PNA-LNA PCR clamp. The remaining 4 L858R mutant-positive samples were recognized as wild type by sequencing. Two of them contained only 5% and 20% of cancer cells, respectively. Surprisingly, in the other two samples PNA-LNA PCR clamping method detected only low levels of EGFR mutant allele, despite the cancer cell contents were high (100% and 80%).   Conclusions:  PNA-LNA PCR clamp technique enables sensitive and reliable detection of EGFR mutant allele in specimens with cancer cell content insufficient for direct sequencing or genetically heterogenous. Regarding its extremely high sensitivity, PNA-LNA PCR clamping should be validated thoroughly prior implementation into EGFR diagnostic routine to prevent overdiagnosis.