tbuckley/cabot-search huggingface dataset:
Dopamine regulates phosphate uptake by opossum kidney cells through multiple counter-regulatory receptors.
Authors: E D Lederer, S S Sohi, K R McLeish
Journal: Journal of the American Society of Nephrology (1998)

The purpose of this study was to determine the mechanisms of dopamine regulation of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate uptake into OK cell monolayers by 14.4 +/- 1.8%. The effect of dopamine was transient, as phosphate uptake returned toward control level by 3 h despite the continued presence of dopamine. Pretreatment with pertussis toxin increased dopamine inhibition of phosphate uptake to 25 +/- 3%, increased the duration of the dopamine effect to at least 3 h, and enhanced cAMP generation. In an OK cell clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit phosphate uptake, but pharmacologic inhibition of protein kinase A activation did not prevent dopamine inhibition of phosphate uptake. A DA1 receptor agonist inhibited phosphate uptake more potently than dopamine (29.5 +/- 1.1%) or a DA2 receptor agonist (7.9 +/- 2%). However, both DA1 and DA2 receptor antagonists completely blocked dopamine inhibition of phosphate uptake. DA1, but not the DA2, antagonists blocked dopamine-stimulated cAMP generation. Treatment with alpha-adrenergic receptor antagonists potentiated dopamine inhibition of phosphate uptake to the same extent as pertussis toxin and was not additive with pertussis toxin. It is concluded that dopamine inhibits phosphate uptake through DA1 and DA2 receptor stimulation by cAMP-dependent and -independent pathways and activates a pertussis toxin-sensitive counter-regulatory pathway that attenuates this response through alpha-adrenergic receptor stimulation.
An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment.
Authors: Hans Gelderblom, David Pérol, Christine Chevreau, Martin HN Tattersall, Silvia Stacchiotti, Paolo Giovanni Casali, Claire Cropet, Sophie Piperno-Neumann, Axel Le Cesne, Antoine Italiano, Virginia Ferraresi, Florence Duffaud, Nicolas Penel, Palma Dileo, François Bertucci, Andrew Bassim Hassan, Judith R. Kroep, Severine Denizot-Guillemaut, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2013)

10516 Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare pathological entity affecting the synovium in young adults. This neoplastic disease is driven by a t(1;2) translocation resulting in the fusion of COL6A3 and M-CSF genes. Nilotinib has inhibitory properties on M-CSF receptor pathway which could be of therapeutic interest in patient (pts) with non resectable PVNS. Methods: In this open-label international, multicentric, non-randomized, phase II study the primary objective is to evaluate the efficacy of nilotinib treatment (800 mg/day) in pts with progressive or relapsing PVNS not amenable to surgery or in whom surgery would be mutilating, as measured by the 12-week progression-free rate (12-w PFR) validated by an independent committee. Using a Bayesian design with a futility stopping rule and a maximum sample size set to 50 evaluable pts, interim analyses (IA) were planned after the inclusion of 10 and then every 5 pts. Results: From December 2010 to September 2012, 56 pts with progressive disease were enrolled by 17 institutions from Europe and Australia. Successive previous IA led to positive results in favour of the study continuation. 47 pts (median age 37 y (range: 18-74), 51% of males) were evaluable at the time of the last IA, with a median follow-up of 11.2 months (range: 0.6-12.7). Median time since diagnosis was 2.5 years (range: 0.02-26). Primary tumour was mainly located on knee (25 pts, 53%), hip (6 pts, 13%), ankle (6 pts, 13%). 4 pts had already received imatinib, 76% of pts had undergone a previous surgery. The 12-w PFR was 93.6% (95%CI, 82.5%-98.7%), without any OR. PR were observed later (2 at w-24 and 1 at w-48). Nilotinib was well tolerated, with only 4 pts experiencing grade 3 adverse events (anorexia: 1 pt; prurit: 1 pt; diarrhea: 1 pt; hepatic failure: 1 pt). 8 pts (17%) had a dose reduction and/or temporary discontinuation of nilotinib due to toxicity. Final results will be further presented. Conclusions: Nilotinib treatment induces disease stabilisation in a large proportion of PVNS patients with non resectable disease or in whom resection would be mutilating. Clinical trial information: NCT01261429.
Magnetic Nanoparticles Labeled Mesenchymal Stem Cells: A Pragmatic Solution toward Targeted Cancer Theranostics
Authors: Abhalaxmi Singh, Sumeet Jain, Shantibhusan Senapati, Rama Shanker Verma, Sanjeeb K. Sahoo
Journal: Advanced Healthcare Materials (2015)

Mesenchymal stem cells (MSCs) have gained much interest to be used as targeting vehicle in cancer therapy due to the intrinsic tumor-homing behavior associated with them. In this scenario, superparamagnetic nanoparticles are emerging as an ideal probe for noninvasive cell tracking for different stem cell applications. In the study, it is demonstrated that the formulated aqueous dispersible glyceryl monooleate coated magnetic nanoparticles (MNPs) can act as a better labeling and efficient tracking agent without affecting the inherent properties of MSCs. The MNPs-MSCs facilitate the stem cell tracking by magnetic resonance imaging at a very low cell number having high T2 relaxivity and potentiates the use of MNPs-MSCs as a prospective diagnostic tool. Most importantly, the homing of MNPs-MSCs toward inflammation site, subcutaneous prostate tumor (small as well as large tumor), and in orthotopic prostate tumor suggests the clinical relevance of the system. In addition, intraperitoneal delivery of MNPs-MSCs shows enhanced tumor accumulation and less sequestration in liver as revealed by in vivo imaging and histological studies. The results here demonstrate that MNPs-MSCs may prove as a better targeted delivery agent for early diagnosis of tumors even of smaller size.
Dietary Fat and Mammary Cancer. I. Promoting Effects of Different Dietary Fats on &lt;italic&gt;N&lt;/italic&gt;-Nitrosomethylurea-Induced Rat Mammary Tumorigenesis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;4&lt;/xref&gt;
Authors: L A Cohen, D O Thompson, Y Maeura, K Choi, M E Blank, D P Rose
Journal: JNCI Journal of the National Cancer Institute (1986)

The promoting effects of diets varying both in type and amount of fat on N-nitrosomethylurea [(NMU) CAS: 684-93-5]-induced mammary tumorigenesis were assessed in female inbred F344 rats. Two seed oils (safflower and corn) and two fruit oils (olive and coconut), varying widely in their diene, monoene, and saturated fatty acid ratios, were fed in the casein-based AIN-76A diets at 23% [high-fat (HF) diet] and 5% [low-fat (LF) diet] by weight, with the exception of coconut oil which was fed only at 23%. The predominant fatty acid in safflower and corn oils was linoleic acid (82 and 56%, respectively), while the predominant fatty acids in olive and coconut oils were oleic (79%) and myristic (54%), respectively. The test diets were fed beginning 2 days after administration of NMU and continued until termination of the experiment at 22 weeks post NMU administration. Analysis of tumor incidence, latency, and multiplicity data obtained from the 7 experimental groups indicated that animals fed the HF safflower and corn oil diets exhibited enhanced mammary tumor yields when compared to animals fed HF olive or coconut oil diets or their LF counterparts. Since weight gains and total caloric intake were similar in all 4 HF groups, the results of this study indicate that the tumor-promoting properties of HF diets are more of a function of differences in fatty acid composition than of fat content per se or of total caloric intake.
The new NHS: commentaries on the white paper: From specialist services to special groups (Challenging times for specialist services)
Authors: C. Bunch
Journal: BMJ (1998)

The white paper focuses to a large extent on dismantling the internal market and the development of primary care. The provision of specialist services—which investigate and treat the bulk of serious ill health—get scant mention, despite their accounting for about £1.4 billion of NHS expenditure annually.1

In an almost throw away line, the white paper insists that “everyone with suspected cancer will be able to see a specialist within two weeks of their GP deciding they need to be seen urgently and requesting an appointment.” It is not difficult to understand why cancer has been singled out for this treatment. It is a common and greatly feared disease. Much work has been done around the country following the Calman-Hine report2 to set standards for cancer care, define protocols and guidelines, develop multidisciplinary teams, and identify …
Effect of Carcinogen Release Rate on the Incidence of Preneoplastic and Neoplastic Lesions of the Respiratory Tract Epithelium in Rats<xref ref-type="fn" rid="fn2">2</xref><xref ref-type="fn" rid="fn3">3</xref>
Authors: M Shiba, A J Klein-Szanto, A C Marchok, B C Pal, P Nettesheim
Journal: JNCI Journal of the National Cancer Institute (1982)

Inbred F34 rat tracheal transplants were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) delivered at different release rates for intraluminal pellets made of various matrices to study the effect of carcinogen dose rate on the induction of lesions in the epithelium. These matrices were beeswax, beeswax-stearyl alcohol, and beeswax-cholesterol. In addition, DMBA absorbed onto carbon particles was dispersed in beeswax-stearyl alcohol. The fastest release was obtained from beeswax pellets from which 99% of the carcinogen (198 micrograms) was released in 4 weeks, and the slowest release was from DMBA absorbed on carbon at a ratio of 1:9 from which only 56% (113 micrograms) was released in 16 weeks. Morphometry of histologic sections showed marked differences in the percentage of luminal surface covered by dysplastic-neoplastic epithelium (i.e., 7.5% in the tracheas exposed to the fastest releasing pellets and 46.3% in the tracheas exposed to the slowest releasing pellets). An inverse linear correlation was found between the cumulative amount of DMBA relased from the different pellet matrices of 2 weeks and the incidence of dysplastic plus neoplastic lesions of tracheal epithelium at 16 weeks. The results indicate that lower doses of carcinogen delivered slowly are more effective in producing dysplastic plus neoplastic lesions than hgher doses delivered rapidly.
Increased circulating endothelial microparticles in COPD
Authors: Jéssica García, Roberto Del Pozo, Nuria Coll, Cristina Bonjoch, Isabel Crespo, Melina Musri, Olga Tura, Victor Ivo Peinado, Joan Albert Barberà
Journal: European Respiratory Journal (2013)

Rationale: COPD is associated with alterations of pulmonary circulation. Endothelial microparticles (EMPs) are   Aim: To assess the number of circulating EMPs in COPD patients, compared with control subjects, and assess if several indices of COPD severity are related with differences in circulating EMP counts.  Methods: Circulating EMPs were determined in 31 control subjects and 57 COPD patients. EMPs were determined by flow citometry in platelet-free plasma (PFP) according to the expression of membrane-specific antigens: CD31+CD42b-AnnexinV+ for the apoptotic phenotype and CD31+CD42b-CD62E+ for the activated phenotype. In COPD patients we assessed differences in EMP counts related to FEV1, DLCO, gas trapping, PaO2 and the presence of pulmonary hypertension (PH).  Results: The number of circulating EMPs was increased in COPD patients compared with control subjects (median, 504 (IQR, 295-779) vs 340 (250-495) EMPs/μl PFP; p  Conclusion: COPD is associated with an increased number of circulating EMPs, presumably originated by an apoptotic mechanism. The severity of COPD does not seem to influence the number of circulating EMPs.  Supported by FIS PS09/00536.
Molecular and clinical characterization of plasmid-mediated AmpC β-lactamase-producing Escherichia coli bacteraemia: a comparison with extended-spectrum β-lactamase-producing and non-resistant E. coli bacteraemia
Authors: Y. Matsumura, M. Nagao, M. Iguchi, T. Yagi, T. Komori, N. Fujita, M. Yamamoto, A. Matsushima, S. Takakura, S. Ichiyama
Journal: Clinical Microbiology and Infection (2012)
Thoracic mechanics in COPD patients before and after pulmonary rehabilitation
Authors: Alina Croitoru, Diana Ionita, Carmen Stroescu, Lucia Marinescu, Stefan Dumitrache-Rujinski, Cornelia Tudose, Claudia Toma, Dragos Bumbacea, Dana Anghelescu, Miron Bogdan
Journal: European Respiratory Journal (2011)

Background:  Patients with COPD have severe breathlessness induced by the increased mechanical work of respiratory muscles in relation to dynamic hyperinflation. Pulmonary rehabilitation programs have been shown to relieve dyspneea, but the mechanism by which they succeed remains controversial.   Aim:  To evaluate the effect of pulmonary rehabilitation on thoracic mechanics.   Method:  The association between thoracic hyperinflation measured by plethysmography (functional residual capacity FRC, residual volume RV), respiratory muscle strength (maximal inspiratory pressure MIP, maximal expiratory pressure MEP) and dyspnoea scores (MRC scale) were analyzed in patients with stable COPD before and after pulmonary rehabilitation (outpatient program, 2 months, 3 sessions/week, including daily respiratory muscle training).   Results:  Twenty patients with COPD stage II-IV GOLD were included. Thoracic hyperinflation was present in all cases: mean FRC 164.9% of the predicted value and RV 209.2% before the rehabilitation program. Mean MIP was 69.6% and mean MEP 105.3%. The severity of dyspnoea before the pulmonary rehabilitation was negatively associated with inspiratory muscle strength (r -0.68) and hyperinflation (r -0.45). Hyperinflation decreased at the end of the rehabilitation program (mean RV decreased with 15.1% and mean FRC with 9.2%), mean MIP increased with 14.3% and the mean dyspnoea score decreased from 3.5 to 2.2.   Conclusion:  Pulmonary rehabilitation optimized thoracic mechanics in our patients by reducing thoracic hyperinflation and increasing the effectiveness of inspiratory muscles work.
Coagulation and inflammation in scrub typhus and murine typhus—a prospective comparative study from Laos
Authors: D H Paris, V Chansamouth, P Nawtaisong, E C Löwenberg, R Phetsouvanh, S D Blacksell, S J Lee, A M Dondorp, T van der Poll, P N Newton, M Levi, N P J Day
Journal: Clinical Microbiology and Infection (2011)

Scrub typhus (caused by Orientia tsutsugamushi) and murine typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub typhus, 55 murine typhus, and 11 typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in typhus patients; however, the activation patterns differed significantly between scrub and murine typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub typhus than in those with murine typhus. In patients with murine typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both typhus patient groups. This is the first study demonstrating that, in scrub typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.
Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli
Authors: William J. Housley, Salvador D. Fernandez, Kenneth Vera, Sasidhar R. Murikinati, Jaime Grutzendler, Nicole Cuerdon, Laura Glick, Phillip L. De Jager, Mitja Mitrovic, Chris Cotsapas, David A. Hafler
Journal: Science Translational Medicine (2015)

Genetic variants associated with multiple sclerosis result in increased NFκB signaling in CD4 T cells and a decreased threshold for activation.
Predominance of two M-types among erythromycin-resistant group A Streptococci from Greek children
Authors: L. Zachariadou, J. Papaparaskevas, I. Paraskakis, A. Efstratiou, A. Pangalis, N.J. Legakis, P.T. Tassios
Journal: Clinical Microbiology and Infection (2003)
Behavior of Skin Allografts in Backcross Progeny of Tolerant Males&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: David Steinmuller
Journal: JNCI Journal of the National Cancer Institute (1967)

Guttmann and co-workers reported an exceptionally high incidence of takes of allogeneic tumor and skin grafts in backcross progeny of an immunologically tolerant C3H male mouse. This finding was interpreted as evidence of a male germplasm-transmitted alteration of histocompatibility. An attempt was made to confirm this observation in a nearly identical experimental system. Five C3H males, made tolerant to varying degrees by the neonatal inoculation of strain A cells, were mated to normal (A × C3H)F1 females. The resulting backcross progeny were challenged with (A × C3H)F1 skin grafts. Neither the offspring of two highly tolerant sires, nor those of a partially tolerant sire, nor the offspring of two marginally tolerant sires showed any unusual incidence of tesf-graft acceptance. Moreover, no significant correlation was found between the distribution of rejection times of the allografts and the state of tolerance of the fathers in the backcross. It is concluded that the transmission of acquired immunologic tolerance from male parent to offspring, if it occurs at all, is not a general phenomenon.
Abstract 1639: Relationship between Overnight Rostral Fluid Shift and Sleep Apnea in Heart Failure
Authors: Dai Yumino, Stefania Redolfi, Pimon Ruttanaumpawan, Mao-Chang Su, Brian Yau, Jennifer Lam, T D Bradley
Journal: Circulation (2008)

Sleep apnea is commoner in heart failure (HF) patients, a fluid retaining state, than in those without HF. In HF patients, fluid displaced from the legs while recumbent could accumulate in the neck...
Anticancer Agents and Antitrypanosomiasis Activity in Mice2
Authors: Kenneth E. Kinnamon, Edgar A. Steck, Dora S. Rane
Journal: JNCI Journal of the National Cancer Institute (1980)

Of 303 compounds (66 active against cancer and 237 inactive against cancer) obtained from the Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 25 were found to be active against Trypanosoma rhodesiense infections of ICR/Ha Swiss mice. Fifteen of these 25 compounds also had anticancer properties. The percentage of anticancer compounds found to have antitrypanosomiasis properties was 22.7. This percentage compares with 6% antitrypanosomiasis compounds among compounds selectecd by other methods.
Abstract 339: High Prevalence of Coronary Artery Calcification in Asymptomatic First-Degree Relatives of Patients With Known Coronary Artery Disease, Despite Overall Young Age and Low Framingham Risk Score
Authors: Idean Marvasty, Zhen Qian, Renee LeStrange, Nancy Flockhart, Gustavo Vazquez, Sarah Rinehart, Joseph Miller, Szilard Voros
Journal: Circulation (2009)
Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report
Authors: Gaetano Bacci, Stefano Ferrari, Franco Bertoni, Pietro Ruggieri, Piero Picci, Alessandra Longhi, Roberto Casadei, Nicola Fabbri, Cristiana Forni, Michela Versari, Mario Campanacci
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years. PATIENTS AND METHODS: Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs. RESULTS: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered. CONCLUSION: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.
Radio: Signs of Life
Authors: I. McClure
Journal: BMJ (2001)

BBC Radio 4, Wednesdays at 9 pm, 5 to 19 December

Each of the three programmes in this short series of drama documentaries explores a different medical condition. The voices of patients and their doctors—the documentary part—are interwoven with a radio drama. These voiceovers serve as a commentary on the drama, which in turn serves as a metaphor for the pathology, the symptoms, and their emotional impact. A tall order, for a 30 minute programme. Did it work? The short answer (at least with the first two programmes made available for review) is no. Yet the series still provided moments of dramatic power.

The first programme, “The Drowning,” dealt with cystic fibrosis. In the drama, …