tbuckley/cabot-search huggingface dataset:
Pirfenidone and BIBF1120 regulate properties of myofibroblasts
Authors: Siri Lehtonen, Henna Karvonen, Elisa Lappi-Blanco, Raija Sormunen, Ulrika Zagai, Magnus Sköld, Riitta Kaarteenaho
Journal: European Respiratory Journal (2014)

Myofibroblast-type stromal cells are aggregated in fibroblast foci in idiopathic pulmonary fibrosis (IPF). Myofibroblasts produce most of the excess extracellular matrix protein (ECM) and also interact with epithelium in IPF having an essential role in the pathogenesis of the disease. We have previously characterized myofibroblasts from the patients with several types of interstitial lung diseases (Karvonen, H.M. et al. Lab Invest 2012;92:1270-1284).  The aim of this study was to evaluate the effect of pirfenidone and BIBF1120 (nintedanib), a triple kinase inhibitor, to the structural and functional properties of myofibroblasts of the patients with IPF.  Primary cells were collected from lung tissue and bronchoalveolar lavage samples from the patients with IPF. Cell lines containing of fibroblasts and myofibroblasts were exposed to pirfenidone and BIBF1120 with and without transforming growth factor beta (TGF-beta) induction, and characterized by gel contraction assay, Western blotting, electron (TEM) and immunoelectron microscopy (IEM).  Pirfenidone and BIBF1120 inhibited contraction of cells in collagen gel and decreased the amount of alpha smooth muscle actin (alpha-SMA), a marker of myofibroblasts, by Western blotting, which effects were more pronounced with TGF-beta induction. Amount of actin and alpha-SMA was decreased by pirfenidone and BIBF1120 exposition with TGF-beta induction in IEM and TEM.  We conclude that both pirfenidone and BIBF1120 affected to the amount of alpha-SMA in myofibroblasts, and moreover, to the collagen gel contraction capacity of the cells regulating both functional and structural phenotype of myofibroblasts.
CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer.
Authors: N Masuda, M Fukuoka, Y Kusunoki, K Matsui, N Takifuji, S Kudoh, S Negoro, M Nishioka, K Nakagawa, M Takada
Journal: Journal of Clinical Oncology (1992)

PURPOSE To evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS Sixteen patients with refractory or relapsed SCLC were entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival. RESULTS Seven patients (47%; 95% confidence limits for an overall response rate, 21.4% to 71.9%) responded to CPT-11 with a median duration of response of 58 days. The major toxicities were myelosuppression (predominantly leukopenia), diarrhea, and pulmonary toxicity. CONCLUSION CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC.
Genetic and Tumorigenic Characteristics of Cell Hybrids Formed In Vivo Between Injected Tumor Cells and Host Cells 2 3
Authors: Fa-Ten Kao, Judith A. Hartz
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Genetic and Tumorigenic Characteristics of Cell Hybrids Formed In Vivo Between Injected Tumor Cells and Host Cells Get access Fa-Ten Kao, Fa-Ten Kao 5 5Address reprint requests to Dr. Kao, Eleanor Roosevelt Institute for Cancer Research. Search for other works by this author on: Oxford Academic PubMed Google Scholar Judith A. Hartz Judith A. Hartz Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 409–413, https://doi.org/10.1093/jnci/59.2.409 Published: 01 August 1977 Article history Received: 05 November 1976 Accepted: 11 March 1977 Published: 01 August 1977
Prevalence of spondyloarthritis in Serbia: a EULAR endorsed study
Authors: Mirjana I Zlatkovic-Svenda, Roksanda M Stojanovic, Sandra B Sipetic-Grujicic, Marija M Radak-Perovic, Nemanja S Damjanov, Francis Guillemin
Journal: Annals of the Rheumatic Diseases (2015)

In order to determine the burden of inflammatory rheumatic diseases across Europe, the European League Against Rheumatism (EULAR) unique-methodology prevalence survey of rheumatoid arthritis (RA) and spondyloarthritis (SpA) was carried out in several European countries, including Serbia. Aiming to enable comparable results, it comprised a common two-stage approach: a detection phase (validated screening telephone questionnaire, primarily tested in France1 ,2) and a confirmation phase (according to a certified rheumatologist or, for previously non-diagnosed cases, a rheumatology examination).

The Serbian SpA prevalence survey was conducted by 30 trained interviewers on urban population in four Serbian towns: Belgrade (north), and Cacak, Krusevac and Užice (south), by telephone (every 100th telephone number) from April to October 2008. The sample covered 36.5% of the total Serbian population with more than 99% Caucasians, mostly orthodox Serbs (83%), <4% Hungarians, Gypsies and Bosnians and a minority of other nationalities. Respondents were asked whether they have (or …
Patients Need More Help to Quit Smoking
Authors: Lynne Lamberg
Journal: JAMA (2004)

Stress during pregnancy can also create problems for the fetus, such as accelerated maturation, which can result in fewer cells in growing organs (Early Hum Dev. 2004;78:15-27). “We really don’t know what the longterm outcome of this is, nor do we identify those individuals in such a way that they can be followed,” said Hall. Another study indicates that a woman who is stressed during her pregnancy is at greater risk of bearing a child who will develop an anxiety disorder or behavioral problems (Child Dev. 2004; 75:1085-1097). Infection in a pregnant woman can have repercussions on the unborn fetus as well. Whether the mother is symptomatic or not, her body produces molecules called cytokines to suppress the infection, and these cytokines can cross the placenta and affect the fetus. Hall pointed to evidence of an association between some cases of cerebral palsy and proinflammatory cytokines, mainly in association with maternal chorioamnionitis (J Obstet Gynaecol Can. 2002;24: 705-709). “Twenty-five percent of cases of cerebral palsy are associated with low birth weight, and in many of these the mother had an infection,” she said. Detailed research on multigenerational data is needed to determine the long-term effects of the fetal environment on individuals. Much care must be taken to keep medical records intact as individuals move from physician to physician throughout life. Hall stressed the need to document family histories of premature births as well as pregnancy histories that include information on nutrition, smoking, and maternal diseases. “To understand adult health, we really need to take these things into consideration,” she said.
Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor.
Authors: E K Rowinsky, L B Grochow, C B Hendricks, D S Ettinger, A A Forastiere, L A Hurowitz, W P McGuire, S E Sartorius, B G Lubejko, S H Kaufmann
Journal: Journal of Clinical Oncology (1992)

PURPOSE A phase I and pharmacologic study was undertaken to determine the maximum-tolerated dose (MTD), describe the principal toxicities, and characterize the pharmacologic behavior of topotecan, which is a semisynthetic analog of camptothecin with broad preclinical antitumor activity and the first topoisomerase I-targeting agent to enter clinical development in the United States since studies of sodium camptothecin over 2 decades ago. PATIENTS AND METHODS Thirty-minute infusions of topotecan were administered daily for 5 consecutive days every 3 weeks to patients with advanced solid malignancies at doses ranging from 0.5 to 2.5 mg/m2/d. RESULTS At doses of 1.5 and 2.0 mg/m2, grade 3 and 4 neutropenia occurred in most courses; however, neutropenia was brief and rarely associated with fevers or treatment delays. Neutropenia was more severe in patients with extensive prior treatment than in minimally pretreated patients, but these differences were not substantial. At 2.5 mg/m2, topotecan induced profound and prolonged neutropenia that was frequently associated with fever and treatment delays in minimally pretreated patients. Topotecan also induced mild depressions in the hematocrit level in the majority of courses; however, precipitous drops requiring transfusional therapy occurred in 14% of courses and suggested a drug-induced hemolytic effect. Unlike sodium camptothecin, hemorrhagic cystitis was not observed. Thrombocytopenia, skin rash, diarrhea, and vomiting occurred infrequently and were modest in severity. Responses were observed in non-small-cell lung carcinoma and platinum-refractory ovarian carcinoma. Drug disposition in plasma was described by a biexponential model, with renal elimination accounting for 38.7% of drug disposition. Topotecan was rapidly hydrolyzed in vivo to a less active, open-ring form. CONCLUSIONS Neutropenia is the dose-limiting toxicity, and 1.5 mg/m2 is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/m2 if treatment is well tolerated. Non-small-cell lung and platinum-refractory ovarian carcinomas should be among those evaluated in phase II trials of topotecan.
A case of fallow deer allergy
Authors: T. Huwyler, B. Wüthrich
Journal: Allergy (1992)

We report the case of a 25‐year‐oId housewife, a native of Mexico City, with rhinitis and asthma induced by exposure to fallow deer in an animal park close to her home. In the literature, we could find only one previous case. The patient presented a polyvalent IgE sensitization in prick skin tests and RAST to several animals’ dander and epithelia, but RAST inhibition experiments showed a cross‐reactivity only between fallow deer and horse allergen extracts.
Phenotypic Variability in Anchorage-Independent Growth by a Human Breast Tumor Cell Line&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M C Hancock, H S Smith
Journal: JNCI Journal of the National Cancer Institute (1984)

Possible mechanisms responsible for expression of anchorage independence were investigated with the use of the human breast carcinoma cell line Hs578T. This phenotype was not stable and most likely occurred via alterations in gene expression, causing secretion of growth factor (s). Colony-forming efficiency in methylcellulose was proportional to initial plating density at low passage number and increased with passage in culture. At high passages, there was less sensitivity to initial plating density, suggesting less dependence on surrounding cells for feeding effects. Clonal variants isolated in methylcellulose maintained a higher plating efficiency when kept in suspension, and removal of selective pressure resulted in the loss of the high level of expression upon subsequent challenge in suspension. In contrast to other systems, anchorage-dependent clones acquired the ability to grow in methylcellulose after only one passage in culture. This suggests that rapid variation at rates not typical of classical somatic mutation plays a role in expression of anchorage independence. Exposure to 5-azacytidine, which decreases methylation of DNA and may thereby activate gene transcription, increased the incidence of anchorage-independent growth 20 times; whereas treatment with 6-azacytidine had no effect. Unconcentrated medium conditioned by cells previously exposed to 5-azacytidine or by cells at high passage stimulated growth in suspension by as much as 10.9 times. The factor(s) present in this conditioned medium was stable to heat up to 63 degrees C for 30 minutes and was larger than 12,000-14,000 mol wt as determined by dialysis.
Outbreak in France of Neisseria meningitidis B:15:P1.12 belonging to sequence type 1403
Authors: C. Grodet, P.F. Dequin, S. Watt, P. Lanotte, C. de Gialluly, M.K. Taha, J.M. Alonso, R. Quentin, A. Goudeau, L. Mereghetti
Journal: Clinical Microbiology and Infection (2004)
Rigid bronchoscopy in adult population using total intravenous anaesthesia (TIVA) with spontaneous ventilation in Sabah, East Malaysia
Authors: Muhammad Redzwan S. Rashid Ali, Kunji Kannan Sivaraman Kannan, Arfian Ibrahim
Journal: European Respiratory Journal (2013)

BACKGROUND: We aim to document our experience in the use of diagnostic/therapeutic rigid bronchoscopy using Total Intravenous Anaesthesia(TIVA) with spontaneous ventilation without use of muscle paralyzing agents or inhalational anaesthesia in a tertiary center in Sabah, North Borneo, East Malaysia. METHODS: A retrospective study in all (n=90)patients that underwent elective diagnostic/interventional rigid bronchoscopy in our centre from 1st January 2012 -1st December 2012.RESULTS: Main indications for procedure were cough& abnormal CT findings(38.9%), smear negative tuberculosis( 17.8%) and incidental abnormal CT findings(15.6%). The mean induction dose given Fentanyl(50mcg) & Propofol(0-50 mcg) & maintenance by TCI(target controlled infusion) Propofol. Mean intraoperative duration=30.2 minutes & mean recovery room time= 37.9 minutes. Intraoperative complications were 46%(majority were reversible mild-moderate bleeding and transient hypoxia). 7% had postoperative complications. Biopsy yield was satisfactory= 67 % showing either granuloma, malignancy, abscess, atypical cells, interstitial pneumonitis and others.ANALYSIS done comparing patients ASA score, age and total bolus/maintenance of Fentanyl/Propofol in relation to intraoperative and postoperative complications, intraoperative time and recovery room time duration did not reach statistical significance.CONCLUSION:Rigid bronchoscopy using TIVA with spontaneous ventilation is safe, has a short intraoperative and post operative recovery time with acceptable complication rates. More studies are needed to compare TIVA against conventional inhalational anaesthesia in rigid bronchoscopy.
Didgeridoo may lower apnea hypopnea index through reducing parapharyngeal fat pads
Authors: Alexander Turk, Alice Zuercher, Fredi Zahn, Thomas Frauenfelder, Milo Puhan
Journal: European Respiratory Journal (2011)

Background:  Our aim was to assess changes in anatomical structures of the upper airways in patients with obstructive sleep apnea syndrome (OSAS) undergoing didgeridoo training to understand the mechanisms by which this treatments exhibits its beneficial effects.   Methods:  We included patients over 18 years of age with newly diagnosed OSAS and an AHI between 15-45/hour. We excluded patients with central sleep apnea, need for CPAP therapy, planned weight reduction intervention, high alcohol inatke and adiposity. Patients received didgeridoo lessons and practiced for 4 months. To measure compliance a device attached inside the didgeridoo continuously monitored temperature and pressure. Before and after treatment patients underwent polysomnography and MRI imaging for soft-tissue volumetric measurements.   Results:  In 10 patients included so far (median age 52 years, BMI 27 kg/m 2 ) the median AHI decreased from 31 to 19/hour and Epworth sleepiness score from 12 to 10. Figure 1 shows very strong associations between the extent of playing digeridoo and a decrease in AHI (r= -0.85) and in the volume of parapharyngeal fat pads (r= -0.90) but a moderate association only with decrease in daytime sleepiness (r= -0.34).  A decrease in AHI was strongly associated with a decrease in the volume of parapharyngeal fat pads (r=0.70).   Conclusion:  The data strongly suggest that didgeridoo playing decreases the AHI by downsizing parapharyngeal fat pads.
As Americans, We Should Get This Right
Authors: N. Sydney Moise
Journal: Circulation (1999)

In their recent study, Frolkis and colleagues 1 attempt to determine by chart review how often patients with acute myocardial infarction are counseled to quit smoking and encouraged to exercise.They acknowledge that if no such counseling nor encouragement is documented in the chart, the study assumes none was done.Certainly a patient hospitalized with an acute infarction is unusually likely to be amenable to the idea of quitting smoking and ought to be so encouraged.But many patients are still not interested in quitting.In those cases, most doctors probably do not document a fruitless attempt at counseling in the chart.Why commemorate a waste of breath with a waste of ink? Frolkis and colleagues suggest doing the documentation if only to placate chart reviewers and defense lawyers.Physician time and patience are finite resources.Suggesting that a patient quit smoking and getting the brush-off from that patient is a bit trying.Having in addition to write in a chart, "Counseled patient to quit smoking, but compliance doubtful," is considerably more trying on a doctor's patience.Furthermore, a cursory comment about smoking and lifestyle changes, made mainly to justify a chart entry that "covers" the doctor, is very unlikely to leave a patient with any useful motivation.The idea that "If it's not documented in the chart, it wasn't done," speaks volumes about anyone who subscribes to it.
Individual dynamic of inflammatory markers as indicators of COPD treatment effectiveness
Authors: L. Konopkina, Bogdana Basina
Journal: European Respiratory Journal (2014)

Aim:  to determine the role of initial and dynamic levels of different inflammatory markers as indicators of COPD treatment.   Methods:  50 patients with verified stable COPD, divided into 2 groups (gr): gr1 – 23 patients with COPD GOLD II (age – 60,4±0,94 years, men – 21 (96,8%), women – 2 (8,3%)), gr 2 – 27 patients with COPD GOLD III-IV (age – 66,5±0,71 years, men – 24 (88,8%), women – 3 (11,2%)). General analysis, plasma levels of C-reactive protein (C-RP), fibrinogen, matrix metalloproteinase (MMP) -2 and 9, hyaluronic acid on visit 1 (before correction of basic treatment), on visit 2 – after 12 month of regular basic treatment, statistic analysis. Control group was 26 healthy people (age – 58,9±11,5, men – 18 (69,3%), women – 8 (30,7%)).   Results:  are present in table 1.   Conclusions:  1) some patients with COPD even of I and II stages in stable phase, but during inadequate treatment, has activation of systemic inflammation with increased plasma levels of C-RP, fibrinogen, MMP-2 and MMP-9, hyaluronic acid; 2) during adequate basic treatment levels of markers of systemic inflammation gradually normalized, while the fastest reagent is the CRP, more slowly and gradually react markers such as MMP-9 and hyaluronic acid, MMP-2.
Release of a Cytotoxic Factor by Macrophages Stimulated With Adjuvant-Active Peptidoglycans
Authors: F Vacheron, M Guenounou, H Zinbi, C Nauciel
Journal: JNCI Journal of the National Cancer Institute (1986)

Bacterial peptidoglycans (PG) possess various immunomodulating activities, including the ability to inhibit the growth of some experimental tumors. We report here that PG induce the release by mouse (DBA/2 and C3H/HeJ) peritoneal macrophages of a cytotoxic factor (CF) that is active on L-929 cells and a 3-methylcholanthrene-induced tumor cell line but inactive on normal fibroblasts. Only the adjuvant-active PG (extracted from Bacillus megaterium and Staphylococcus aureus) were good inducers of the CF, whereas the adjuvant inactive PG (extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) exhibited only weak activity. The CF was released within 2 hours of contact with PG either in serum-free or serum-containing media. The CF was inhibited neither by serum nor by the protease inhibitors that have been tested. It was stable for 30 minutes at 56 degrees C but inactivated after being heated for 10 minutes at 80 degrees C. After gel filtration, a single peak of activity at 80-90 kilodaltons was found. Chromatofocusing showed that the isoelectric point of the CF was 4.8.
Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses
Authors: D. Wallach, M.-D. Vignon-Pennamen
Journal: British Journal of Dermatology (2015)

Pyoderma gangrenosum, a dramatic ulcerative skin disease, and Sweet syndrome, a papular dermatosis, were described independently. It was subsequently shown that they share many characteristics, including clinical overlap and the frequent association with multisystemic disorders. The group of the neutrophilic dermatoses encompasses these two dermatoses, as well as other conditions having in common an aseptic neutrophilic infiltrate predominating in the epidermis and/or the dermis and/or the subcutis. Some patients also experience neutrophilic infiltrates in other organs, defining the neutrophilic disease. Recent research suggests that the neutrophilic dermatoses could be considered as the cutaneous expression of the autoinflammation, an aberrant hyperproduction of interleukin‐1. Autoinflammation is responsible for monogenic diseases, and is also involved in the mechanism of many polygenic conditions, including the neutrophilic dermatoses.
The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity
Authors: Jonathan J Miner, Brian P Daniels, Bimmi Shrestha, Jose L Proenca-Modena, Erin D Lew, Helen M Lazear, Matthew J Gorman, Greg Lemke, Robyn S Klein, Michael S Diamond
Journal: Nature Medicine (2015)
Adaptive Changes in Spontaneously Transformed Balb/3T3 Cells During Tumor Formation and Subsequent Cultivation&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: H Rubin
Journal: JNCI Journal of the National Cancer Institute (1984)

Cells from a clone of Balb/3T3 cells, which underwent spontaneous morphologic transformation and consistently had a high colony-forming efficiency when suspended in agar [colony-forming efficiency in agar (CFEag)], also formed primitive, pleomorphic sarcomas when inoculated into N:NIH(S)II-nu/nu mice. Cells cultured from 1 of the tumors had only 10% of the CFEag of those used to initiate the tumor but drifted back to the original high level during the first 2 months in culture. Twelve clones of the tumor cells differed widely from one another in CFEag in each of seven successive assays over a 10-week period, although the difference was most pronounced in the first assay. The CFEag for some of the clones fluctuated greatly in successive assays. Two of the clones usually scored lower than the others, and their average CFEag for the seven assays was significantly lower than that of the others. The ability of cells from a second tumor to form colonies in agar also increased with successive passaging. All clones from the second tumor increased in CFEag to a similar extent as the parental population in the same time period, suggesting the increase was the result of adaptation rather than selection of preexisting variants. A tumor produced from a different subpopulation of transformed cells yielded cells with the same CFEag as the input cells. Thus some populations of transformed cells change some of their characteristics when passaged in animals and again when passaged in culture.