tbuckley/cabot-search huggingface dataset:
Molecular phylogeny and evolution of primate mitochondrial DNA.
Authors: K Hayasaka, T Gojobori, S Horai
Journal: Molecular Biology and Evolution (1988)

We determined nucleotide sequences of homologous 0.9-kb fragments of mitochondrial DNAs (mtDNAs) derived from four species of old-world monkeys, one species of new-world monkeys, and two species of prosimians. With these nucleotide sequences and homologous sequences for five species of hominoids, we constructed a phylogenetic tree for the four groups of primates. The phylogeny obtained is generally consistent with evolutionary trees constructed in previous studies. Our results also suggest that the rate of nucleotide substitution for mtDNAs in hominines (human, chimpanzee, and gorilla) may have slowed down compared with that for old-world monkeys. This evolutionary feature of mitochondrial genes is similar to one found in nuclear genes.
Autoantibodies to the Insulin Receptor
Authors: Jeffrey S. Flier, C. Ronald Kahn, David B. Jarrett, Jesse Roth
Journal: Journal of Clinical Investigation (1977)

The serum of some patients with insulin-resistant “diabetes” contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of 125I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins.
The Middle Ear in Cleft Palate Children Pre and Post Palatal Closure
Authors: R S Dhillon
Journal: Journal of the Royal Society of Medicine (1988)

A multicentre prospective trial was commenced in July 1984 to establish the incidence of otitis media with effusion (OME) in children born with a cleft of the palate. Additionally, the data recorded would allow an assessment of the effect of palatal closure on middle ear function. Prior to palatal closure, 97% of ears in a group of 50 patients had otitis media with effusion (OME). The insertion of a long-term ventilation tube provided a means of aeration of one ear with the non-ventilated ear acting as a control. Eighty percent of control ears had persistent OME during a 24-month follow-up period post palatal repair. It would seem that OME is universally present in children with a cleft palate prior to 4 months of age and this incidence is only marginally diminished by palatal surgery. The liaison between plastic surgical and ENT units should be even closer than before in order to manage these patients satisfactorily.
Abstract 3536: Aprotinin Blocks Leukocyte Extravasation into Tissues in Patients Undergoing Cardio-Thoracic Surgery with Cardiopulmonary Bypass
Authors: R C Landis, Betsy J Evans, Dorian O Haskard, Kenneth M Taylor
Journal: Circulation (2006)

Introduction Aprotinin (Trasylol), used clinically to reduce transfusion requirement and the inflammatory response to cardiopulmonary bypass (CPB), has been shown to attenuate leukocyte extravasati...
Assessment of daily activity in COPD
Authors: Ali Albarrati, Nichola Gale, Stephanie Enright, Iain Munnery, Margaret Munnaery, John Cockcroft, Dennis Shale
Journal: European Respiratory Journal (2013)

Background 

Patients with COPD have progressive loss of daily physical activity; however, its measurement is limited to research settings. A simple measure of physical activity in the elderly is the Timed Up and Go (TUG) test. We hypothesised that the TUG could provide an estimation of daily physical activity in COPD.

Method 

As part of the ARCADE study, daily physical activity was monitored for a week, using a multisensor armband (SenseWear Pro armband), in 49 patients and 29 comparators. Spirometry, body composition, six minute walk distance (6MWD) and TUG test were also determined.

Results 

Patients and comparators were similar in age, BMI and gender, but differed in number of steps, 6MWD and TUG (Table1). In patients, the number of steps related to TUG (r=-0.52, p=0.001), FEV1% (r=0.48, p=0.001), 6MWD (r=0.68, p=0.001). The total energy expenditure related to 6MWD in patients (r=0.42, p=0.004) and comparators (r=0.39, p=0.04), but only to TUG in patients (r=-0.37, p=0.01). In COPD, stepwise regression analysis, adjusted for age, gender and BMI showed that TUG test, and FEV1% explained 39% of the variance in number of steps and 57% of the variance in 6MWD.

Conclusion 

The TUG test is an integrated test of gait speed, balance and functional capacity which appears to predict daily physical activity in COPD. As a simple rapid test, the TUG test may be a useful indicator of daily physical performance in clinical practice.

View this table:

Clinical characteristics of patients and comparators
TLR9 ligation in pancreatic stellate cells promotes tumorigenesis
Authors: Constantinos P. Zambirinis, Elliot Levie, Susanna Nguy, Antonina Avanzi, Rocky Barilla, Yijie Xu, Lena Seifert, Donnele Daley, Stephanie H. Greco, Michael Deutsch, Saikiran Jonnadula, Alejandro Torres-Hernandez, Daniel Tippens, Smruti Pushalkar, Andrew Eisenthal, Deepak Saxena, Jiyoung Ahn, Cristina Hajdu, Dannielle D. Engle, David Tuveson, George Miller
Journal: The Journal of Experimental Medicine (2015)

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis.
Clinical features of four children with pulmonary alveolar proteinosis
Authors: Nagehan Emiralioglu, Ebru Yalçin, Deniz Dogru Ersöz, Ugur Özçelik, Aydin Erden, Peter Lohse, Matthias Griese, Nural Kiper
Journal: European Respiratory Journal (2014)

Background:Pulmonary alveolar proteinosis(PAP)is a rare respiratory disease characterized by accumulation of phospholipids and surfactant proteins within the alveolarlumen.The clinical course is variable ranging from spontaneous improvement to respiratory insufficiency.Removal of the lipoproteinic material by whole lung lavage(WLL) can be an effective treatment for severe cases.  Cases:Here we present the clinical,radiological and pathological features of four children with PAP.All presented with cough,dyspnea was diagnosed at ages of six months,four,six and fourteen years.Chest X-ray and CT showed diffuse homogenous patterns of groundglass opacity.Crazy  appearance was observed in two of the patients.Clinical diagnosis was made by demonstrating PASpositive material in bronchoalveolar lavage.Mutational analysis demonstrated GMCSFRαsubunit deficiency in two subjects investigated.One patient had a homozygous deletion of exons2-13of theCSF2RA gene,the other patient had a homozygous G→A donor splice site mutation at position +1relativeto the exon12/intron12 border.Bilateral partial lung lavage was done after the diagnosis.One patient died dueto respiratory insufficiency at age of 13months.Two of the patients need yearly lung lavage.The child with ΔEx2-13 needs lung lavage nearly every two months.  Conclusion:PAP is a rare disease in children which can progress to fatal respiratory insufficiency.Bilateral infiltrates are typically present on chest radiograph and high-resolution computed tomography reveals diffuse ground-glass opacities,characteristic crazy paving pattern.By WLL, progression of the disease maybe inhibited in some patients or in others the disease may progresses to chronic respiratory failure.
Optimal cut-off point of exhaled carbon monoxide to validate self-reported smoking status in healthy adults
Authors: Juliana Zabatiero, Demétria Kovelis, Mahara Proença, Karina Furlanetto, Leandro Mantoani, Ercy Ramos, Fábio Pitta
Journal: European Respiratory Journal (2011)

Background:  There is no current consensus regarding the optimal cut-off point of exhaled carbon monoxide (CO) to distinguish smokers from nonsmokers.   Objectives:  To assess the accuracy of an exhaled carbon monoxide cut-off point in order to distinguish actual smokers from nonsmokers among apparently healthy adults.   Methods:  We studied 50 current smokers (20 male; 47±12 years; BMI: 26±4 kg/m 2 ), with normal lung function (FEV 1 /FVC: 81±6; FEV 1 : 84±18%pred) who self-reported their smoking status and habits; and 31 paired non-smokers (11 male; 44±11 years; BMI: 26±4 kg/m 2 ; FEV 1 /FVC: 83±6; FEV 1 : 102±11%pred). All subjects were submitted to CO assessment (in the group of smokers, after a mean of 10±1.2 hours of cigarette abstinence), using a portable CO monitor (MicroCO®).   Results:  Median [interquartile range] levels of CO in the group of smokers and non-smokers were 10 [7-17] and 3 [2-4], respectively. The 6ppm cut-off point suggested by the manufacturer generated a 77% sensitivity and 100% specificity; however a 4.5ppm cut-off point generated the highest combined sensitivity (90%) and specificity (90%). The ROC analysis indicated that the CO monitor provided high diagnostic accuracy to distinguish smokers from nonsmokers [area under the curve = 0.979 p   Conclusions:  Using a portable CO monitor, a 4.5ppm cut-off point seems more accurate than the cut-off point suggested by the manufacturer in order to distinguish smokers from nonsmokers among apparently healthy adults.
Confidential voluntary scheme has been set up in Britain
Authors: R M Brown
Journal: BMJ (1996)

EDITOR,—Ruth Chambers and Richard Maxwell mention counselling services to help sick doctors.1 Canada has had a scheme for years to help chemically dependent doctors. Last November, while at a conference in York on addiction in doctors and dentists, I heard about the physicians support programme in Ontario from Dr Graeme Cunningham, the coordinator. This uses doctors who have recovered from dependence on alcohol and other drugs.

The authors of the editorial state that only 3% of sick …
STUDIES ON DIGITALIS IN AMBULATORY CARDIAC PATIENTS
Authors: Harry Gold, Arthur C. Degraff
Journal: Journal of Clinical Investigation (1929)

A study of the rate of elimination of digitalis in normal animals in terms of persistence of action was published by one of us (1) in 1923.The curves invariably show that after a single large injection, elimi- nation is very rapid at first and then slower, i.e., as the quantity of * (II-a) able to carry on slightly diminished physical activity; (II-b) able to carry on greatly diminished physical activity; (III) symptoms of heart failure at rest.
Systematic review of shorter 2-3 months regimens for treatment of latent tuberculosis
Authors: Carlos Acuna-Villaorduna, July Lau-Deza, Jorge Mora
Journal: European Respiratory Journal (2013)

Background : Latent tuberculosis treatment with 6-12 months of isoniazid is difficult to implement. Shorter regimens could achieve similar efficacy with acceptable side effects and better completion rates.   Objectives:  To evaluate the efficacy of three shorter regimens to treat latent tuberculosis.   Methods : We searched the following databases: Medline, Embase, OVID, Cochrane central register, clinical trials.gov, Conference paper index, the Cambridge scientific and the database of the International Union against Tuberculosis and Lung Diseases.  We selected randomized control trials that evaluated: rifapentine plus isoniazid, isoniazid plus rifampicin or rifampicin plus pyrazinamide for 2-3 months. The comparator was isoniazid for 6-12 months.  Data from each study were extracted and risk of bias was assessed. The number of pulmonary tuberculosis cases and the total population was obtained. The primary outcome was development of active pulmonary tuberculosis. A pooled risk ratio with 95% confidence intervals was calculated. Non inferiority and equivalence margins were defined.   Results:  We identified 16 trials evaluating 19 regimens. Shorter regimens were non inferior than standard isoniazid (pooled RR: 0.99 95% CI: 0.79-1.24). The effect was similar among each treatment regimen. Shorter regimens had a non significant increase in the side effects risk (pooled RR: 1.27 95% CI: 0.95-1.70) and better completion rates (pooled RR: 1.11 95% CI: 1.06-1.16). Side effects risk was increased for the rifampicin and pyrazinamide regimen (pooled RR: 1.90 95% CI: 1.47-2.44).   Conclusions:  Shorter regimens of 2-3 months are non inferior to standard isoniazid and have a better proportion of therapy completion.
Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan.
Authors: R Perez-Soler, B S Glisson, J S Lee, F V Fossella, W K Murphy, D M Shin, W K Hong
Journal: Journal of Clinical Oncology (1996)

PURPOSE This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with small-cell lung cancer (SCLC) refractory to etoposide. PATIENTS AND METHODS Refractoriness to etoposide was defined as lack of response to etoposide-containing frontline therapy, or progression during or within 3 months of the last dose of etoposide-containing frontline or second-line therapy. Other eligibility criteria were presence of measurable disease, Zubrod scale performance status (PS) &lt; or = 2, &lt; or = two prior chemotherapy regimens, and adequate renal and liver function. TPT was administered at a dose of 1.25 mg/m2/d for 5 days over 30 minutes every 21 days. RESULTS Thirty-two patients were registered, of whom 28 are fully assessable. All patients had been treated with frontline etoposide and cisplatin. Three patients (11%) achieved a partial remission (PR) (durations, 7, 8, and 19 weeks) and two (7%) achieved a minor response; five patients (17%) had stable disease and 18 (65%) had progressive disease. One of the three patients who achieved a PR had failed to respond to frontline cisplatin and etoposide. The overall median survival duration was 20 weeks. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 70% and 31% of courses administered, respectively. No grade 3 to 4 non-hematological toxicities were observed. Grade 1 or 2 nonhematological toxicities (in percentage of patients) consisted of nausea (41%, 8%) and vomiting (25%, 11%), and alopecia (100%). CONCLUSION TPT at the dose and schedule used has modest antitumor activity in SCLC patients refractory to etoposide and cisplatin, which indicates that clinical resistance to the topoisomerase II poison etoposide does not confer cross-sensitivity to the topoisomerase I poison TPT. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.
Antimicrobial susceptibility to levofloxacin and other antibacterial agents among common respiratory pathogens—a Brazilian perspective from the GLOBAL Surveillance Initiative 2001–2002
Authors: C. Mendes, C.R.V. Kiffer, R.S. Blosser-Middleton, M.E. Jones, J.A. Karlowsky, A. Barth, F. Rossi, S. Andrade, H.S. Sader, C. Thornsberry, D.F. Sahm
Journal: Clinical Microbiology and Infection (2004)
Abstract #5379: Biodistribution of cisplatin-loaded magnetic iron oxide nanoparticles in nude mice bearing human head and neck cancer
Authors: Xianghong Peng, Yiqing Wang, Dong-Hai Huang, Hui Mao, Yongqiang Wang, Zuo Chen, Shuming Nie, Dong Shin
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo . Anticancer drugs can be loaded onto IO nanoparticles to improve the therapeutic efficiency of anticancer agents. We have developed poly(ethylene glycol) (PEG)-coated IO nanoparticles (10 nm in core size) to deliver cisplatin (DDP), a chemotherapy drug that is widely used to treat various types of cancers. The loading efficiency of cisplatin in the IO nanoparticles was around 90%, as measured by inductively-coupled plasma mass spectroscopy (ICP-MS) analysis. In vitro cellular uptake experiments indicated that IO-DDP could be taken up by head and neck cancer (HNC) cell lines Tu686 and Tu212. A cell proliferation assay indicated that cisplatin encapsulated in the IO-DDP could be released after 24 hrs and had the same cytotoxicity to the cancer cells as free cisplatin at 96 hrs. In addition, the nanoparticles showed prolonged circulation time (T1/2= 2 hrs). We labeled the IO nanoparticles with the near infrared (NIR) molecule Cy5, enabling both MR and NIR imaging of this IO nanoparticle. Tail vein injection of Cy5.5-IO-DDP nanoparticles in nude mice bearing subcutaneous HNC tumors led to about 2-fold accumulation of the DDP and IO nanoparticles in tumors. Our results demonstrated that systemic delivery of the IO-DDP nanoparticles led to greater accumulation of IO-DDP compared with free DDP in the xenograft HNC tumor. Current efforts focus on the antitumor efficiency of IO-DDP nanoparticles in tumor-bearing mice. (Supported by grants from 5 P50 CA128613 - SPORE in Head & Neck Cancer, U54CA119338-CCNE).

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5379.
Behaviour problems are underdocumented
Authors: H. Cameron
Journal: BMJ (1996)

EDITOR,—By applying American guidelines on neuroleptic use within nursing home facilities, Alice McGrath and Graham Jackson have deemed the prescription of these drugs for Glasgow nursing home residents to be potentially inappropriate in most cases.1 Their interpretation of the findings may be incorrect.

No data are provided on the extent of behaviour problems among the patients studied. Previous research in similar settings suggests that a high prevalence of behaviour problems can be anticipated.2 3 Neuroleptic use may seem inappropriate in many cases because the …
Gene modulation and severity of lung disease in cystic fibrosis
Authors: A Pillai
Journal: Thorax (2008)

Progressive lung disease is an important cause of mortality and morbidity in patients with cystic fibrosis (CF). The severity and progression of lung disease, which has a poor correlation with CF transmembrane conductance regulator (CFTR) genotype, is thought to be modulated by secondary genetic factors known as CF modifiers. Mannose binding lectin 2 (MBL2) and transforming growth factor β1 (TGFβ1) genes are among …
Abstract 442: <i>RASA1</i> alteration promotes melanoma tumorigenesis
Authors: Hyeran Sung, Li Ding, Krishna L. Kanchi, Jane L. Messina, Vernon K. Sondak, Mulé J. James, Richard K. Wilson, Jeffrey S. Weber, Minjung Kim
Journal: Cancer Research (2014)

Abstract Melanoma shows frequent Ras-Raf-MAPK pathway activation via frequent mutations in NRAS and BRAF. Novel mutations in other components of this pathway such as MEK1, MEK2, MAP3K5, and MAP3K9 have been reported recently by high-throughput sequencing efforts. In addition, NF1 (neurofibromatosis type 1), one of the Ras GTPase activating proteins (RasGAPs), has been shown to be mutated or suppressed in melanoma. However, importance of other RasGAPs has not been addressed in melanoma. To obtain a comprehensive view of melanoma genomes, we conducted whole genome sequencing (WGS) of 15 metastatic melanomas and matched normal PBMC genomes from 13 melanoma patients. All melanoma genomes from these 13 patients contained at least one mutation in genes of Ras-Raf-MAPK pathway (MAPK1, MAP3K1, MAP4K2, MAP3K14, NRAS, and BRAF). Our whole genome analyses also identified two novel somatic missense mutations (p.Tyr472His and p.Leu481Phe) in or around the PH domain in RASA1 gene. RASA1 (RAS p21 protein activator (GTPase activating protein) 1, also called as p120RasGAP) is a GTPase activation protein that negatively regulates Ras by catalyzing the hydrolysis of active Ras-GTP to inactive Ras-GDP. In this study, we addressed possible roles of RASA1 in melanoma tumorigenesis. To determine RASA1 level in melanocytic lesions, immunohistochemical analysis of RASA1 on human melanoma tissue microarray (TMA) containing nevi (n=34), primary melanomas (n=63), lymph node metastasis (n=35), and distal metastasis (n=29) was performed. This analysis has shown the inverse correlation of RASA1 expression to melanoma progression. Functionally, ectopic expression of RASA1 mutant increased soft-agar colony formation and tumor growth while that of wild-type RASA1 decreased. shRNA-mediated knock down of RASA1 promoted soft-agar colony formation and invasion of melanocytes and melanoma cells with BRAF mutation as a consequence of the elevated Ras activity. Here, we established the functional significance of novel somatic missense mutations in RASA1 identified in our WGS study. Collectively, these data implicated that RASA1 inactivation by loss of expression and/or mutation may promote melanoma tumorigenesis. Citation Format: Hyeran Sung, Li Ding, Krishna L. Kanchi, Jane L. Messina, Vernon K. Sondak, Mulé J. James, Richard K. Wilson, Jeffrey S. Weber, Minjung Kim. RASA1 alteration promotes melanoma tumorigenesis. [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 442. doi:10.1158/1538-7445.AM2014-442
The Countess Margaret of Henneberg and Her 365 Children
Authors: J Bondeson, Arie Molenkamp
Journal: Journal of the Royal Society of Medicine (1996)

According to an oBScure medieval legend, the Countess Margaret of Henneberg, a notable Dutch noblewoman, gave birth to 365 children in the year 1276. The haughty Countess had insulted a poor beggar woman carrying twins, since she believed that a pair of twins must have different fathers, and that their mother must be an adultress. She was punished by God, and gave birth to 365 minute children on Good Friday, 1276. The Countess died shortly after, together with her offspring, in the village of Loosduinen near The Hague. The Countess and her numerous brood were frequently described in historical and obstetrical works. To this day, a memorial tablet and two basins, representing those in which the 365 children were baptized, are to be seen in the church of Loosduinen.