tbuckley/cabot-search huggingface dataset:
Human platelet activation by C3a and C3a des-arg.
Authors: M J Polley, R L Nachman
Journal: The Journal of Experimental Medicine (1983)

C3a liberated from C3 by treatment with C3 convertase (or by trypsin) induced aggregation of gel-filtered human platelets and stimulated serotonin release. At concentrations of 10(-10) M to 8 X 10(-12) M, C3a induced aggregation when added alone to platelets. However, at lower concentrations (2 X 10(-12) M) C3a did not aggregate platelets directly but exhibited highly significant synergism (two-way analysis of variance P less than 0.0001) with ADP in mediating platelet aggregation and release of serotonin. Removal of the C-terminus arginine from C3a abolished anaphylotoxin activity but did not affect the platelet-stimulating activity of the peptide. C3a and C3a des-arg were equally reactive in mediating platelet aggregation and release of serotonin. Further C3a and C3a des-arg exhibited synergism with ADP of equal significance in both aggregation and the release reaction. The concentrations of C3a required for the platelet-stimulating activity involve relatively small number of molecules per platelet (4,000-10,000 for the synergistic reaction with ADP). These data suggest the possibility of a C3a (C3a des-arg) receptor on human platelets. This premise is strengthened by the demonstration ultrastructurally of C3a on the platelet membrane subsequent to C3a stimulation.
<i>TP53</i> and <i>KRAS2</i> Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study
Authors: Emmanuelle Gormally, Paolo Vineis, Giuseppe Matullo, Fabrizio Veglia, Elodie Caboux, Emilie Le Roux, Marco Peluso, Seymour Garte, Simonetta Guarrera, Armelle Munnia, Luisa Airoldi, Herman Autrup, Christian Malaveille, Alison Dunning, Kim Overvad, Anne Tjønneland, Eiliv Lund, Françoise Clavel-Chapelon, Heiner Boeing, Antonia Trichopoulou, Domenico Palli, Vittorio Krogh, Rosario Tumino, Salvatore Panico, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Guillem Pera, Carmen Martinez, Miren Dorronsoro, Aurelio Barricarte, Carmen Navarro, José Ramón Quirós, Göran Hallmans, Nicholas E. Day, Timothy J. Key, Rodolfo Saracci, Rudolf Kaaks, Elio Riboli, Pierre Hainaut
Journal: Cancer Research (2006)

Abstract In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for &amp;gt;10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis. (Cancer Res 2006; 66(13): 6871-6)
Developmental changes of infant cries – the evolution of complex vocalizations
Authors: Kathleen Wermke, Angela D. Friederici
Journal: Behavioral and Brain Sciences (2004)

The signal functions of infant crying cannot be understood properly without due attention to their ontogenetic development. Based on our own research on the development of infant cries, we argue that the controversies in cry literature will not be solved by static models, but that progress will made only when considering ontogenetic changes in interpreting cry data.
Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis
Authors: Maria D Mayan, Raquel Gago-Fuentes, Paula Carpintero-Fernandez, Patricia Fernandez-Puente, Purificacion Filgueira-Fernandez, Noa Goyanes, Virginijus Valiunas, Peter R Brink, Gary S Goldberg, Francisco J Blanco
Journal: Annals of the Rheumatic Diseases (2013)

This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels.
Improved Glycemic Control in Intensively Treated Type 1 Diabetic Patients Using Blood Glucose Meters With Storage Capability and Computer-Assisted Analyses
Authors: Suzanne M Strowig, Philip Raskin
Journal: Diabetes Care (1998)

OBJECTIVE To determine the effect on glycemic control in intensively treated type 1 diabetic patients using a blood glucose meter with storage capability and computer-assisted analyses. RESEARCH DESIGN AND METHODS Glycemic control was assessed in 22 intensively treated adults with type 1 diabetes for 12 months while using a meter without memory, followed by 12 months while using a meter with memory. Log books were used to assist patients in managing aspects of the diabetes treatment plan during the first 12-month period, and computer-assisted analyses were used when the meter with memory was used. GHb levels were measured monthly throughout the 24 months of observation. RESULTS The mean GHb level averaged across all patients during the period of memory meter use (6.4%) was significantly lower than that during the period of meter use without memory (6.9%) (P = 0.0004). The change in GHb levels from each period-specific baseline level occurred at significantly different slopes (P = 0.046) when adjusted for baseline GHb level. In addition, the downward trend in GHb level was greater in those patients who increased the frequency of testing the most (r = −0.54, P = 0.01). CONCLUSIONS Use of a meter with memory in conjunction with computer-generated analyses of stored blood glucose test results can lead to improved glycemic control when used by a group of intensively treated adult diabetic patients. Improvement in glycemic control was related to frequency of blood glucose testing.
Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ)
Authors: E Piitulainen, S Eriksson
Journal: European Respiratory Journal (1999)

Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development. Highly variable rates of decline in lung function are reported in PiZZ individuals. The annual decline in forced expiratory volume in one second (FEV1; delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult PiZZ individuals included in the Swedish national AAT deficiency register. Delta FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current smokers after performing at least two spirometries during a follow-up time of 1 yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never-smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41 mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI 58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found between cigarette consumption and delta FEV1 in current smokers and exsmokers. In never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No sex differences were found in delta FEV1. In conclusion, among PiZZ individuals, the change in forced expiratory volume in one second is essentially the same in never-smokers and exsmokers. Smoking is associated with a dose-dependent increase in the change in forced expiratory volume in one second.
Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy
Authors: Erin E. Mueller, Abdul Momen, Stéphane Massé, Yu-Qing Zhou, Jie Liu, Peter H. Backx, R. Mark Henkelman, Kumaraswamy Nanthakumar, Duncan J. Stewart, Mansoor Husain
Journal: Cardiovascular Research (2010)

Binary transgenic (BT) mice with doxycycline (DOX)-suppressible cardiac-specific overexpression of endothelin-1 (ET-1) exhibit progressive heart failure (HF), QRS prolongation, and death following DOX withdrawal. However, the molecular basis and reversibility of the electrophysiological abnormalities in this model were not known. Here, we assess the mechanisms underlying ET-1-mediated electrical remodelling, and its role in HF.BT vs. non-BT littermate controls were withdrawn from DOX and serially studied with ultrasound biomicroscopy, octapolar catheters, multielectrode epicardial mapping, histopathology, western blot, immunohistochemistry, and qRT-PCR. Abnormalities in ventricular activation and -dV/dt were detected as early as 4 weeks after transgene activation, when the structure and function of the heart remained unaffected. By 8 weeks of ET-1 overexpression, biventricular systolic and diastolic dysfunction, myocardial fibrosis, and cardiomyocyte hypertrophy were observed. Intracardiac and epicardial electrograms revealed prolonged conduction and ventricular activation, reduced -dV/dt, and abnormal atrioventricular nodal function. Within 4 weeks of ET-1 induction, connexin 40 (Cx40) protein and Cx43 mRNA, protein, and phosphorylation levels were reduced by 36, 64, 93, and 69%, respectively; Na(v)1.5 mRNA and protein levels were reduced by 30 and 50%, respectively, as was Na(+) channel conductance. Importantly, the associated electrophysiological abnormalities at this time point were reversible upon suppression of ET-1 overexpression and completely prevented the development of structural and functional remodelling.ET-1-mediated electrical remodelling correlates with reduced Cx40, Cx43, and Na(v)1.5 expression and decreased Na(+) channel conductance and precedes HF. The sequence and reversibility of this phenotype suggest that a primary abnormality in electrical remodelling may contribute to the pathogenesis of HF.
The Proteasome Inhibitor Bortezomib Acts Independently of p53 and Induces Cell Death via Apoptosis and Mitotic Catastrophe in B-Cell Lymphoma Cell Lines
Authors: Sandra J. Strauss, Karen Higginbottom, Simone Jüliger, Lenushka Maharaj, Paul Allen, David Schenkein, T. Andrew Lister, Simon P. Joel
Journal: Cancer Research (2007)

Bortezomib is a proteasome inhibitor with proven efficacy in multiple myeloma and non-Hodgkin's lymphoma. This study reports the effects of bortezomib in B-cell lymphoma cell lines with differing sensitivity to bortezomib to investigate factors that influence sensitivity. Bortezomib induced a time- and concentration-dependent reduction in cell viability in five lymphoma cell lines, with EC(50) values ranging from 6 nmol/L (DHL-7 cells) to 25 nmol/L (DHL-4 cells) after 72 h. Bortezomib cytotoxicity was independent of p53 function, as all cell lines exhibited mutations by sequence analysis. The difference in sensitivity was not explained by proteasome or nuclear factor-kappaB (NF-kappaB) inhibition as these were similar in the most and least sensitive cells. NF-kappaB inhibition was less marked than that of a specific NF-kappaB inhibitor, Bay 11-7082. Cell cycle analysis showed a marked G(2)-arrested population in the least sensitive DHL-4 line only, an effect that was not present with Bay 11-7082 treatment. Conversely, in DHL-7 cells, bortezomib treatment resulted in cells moving into an aberrant mitosis, indicative of mitotic catastrophe that may contribute to increased sensitivity to bortezomib. These studies show that although bortezomib treatment had similar effects on apoptotic and NF-kappaB signaling pathways in these cell lines, different cell cycle effects were observed and induction of a further mechanism of cell death, mitotic catastrophe, was observed in the more sensitive cell line, which may provide some pointers to the difference in sensitivity between cell lines. An improved understanding of how DHL-7 cells abrogate the G(2)-M cell cycle checkpoint may help identify targets to increase the efficacy of bortezomib.
<i>De Novo</i> Design of a Tumor-Penetrating Peptide
Authors: Luca Alberici, Lise Roth, Kazuki N. Sugahara, Lilach Agemy, Venkata R. Kotamraju, Tambet Teesalu, Claudio Bordignon, Catia Traversari, Gian-Paolo Rizzardi, Erkki Ruoslahti
Journal: Cancer Research (2012)

Abstract Poor penetration of antitumor drugs into the extravascular tumor tissue is often a major factor limiting the efficacy of cancer treatments. Our group has recently described a strategy to enhance tumor penetration of chemotherapeutic drugs through use of iRGD peptide (CRGDK/RGPDC). This peptide comprises two sequence motifs: RGD, which binds to αvβ3/5 integrins on tumor endothelia and tumor cells, and a cryptic CendR motif (R/KXXR/K-OH). Once integrin binding has brought iRGD to the tumor, the peptide is proteolytically cleaved to expose the cryptic CendR motif. The truncated peptide loses affinity for its primary receptor and binds to neuropilin-1, activating a tissue penetration pathway that delivers the peptide along with attached or co-administered payload into the tumor mass. Here, we describe the design of a new tumor-penetrating peptide based on the current knowledge of homing sequences and internalizing receptors. The tumor-homing motif in the new peptide is the NGR sequence, which binds to endothelial CD13. The NGR sequence was placed in the context of a CendR motif (RNGR), and this sequence was embedded in the iRGD framework. The resulting peptide (CRNGRGPDC, iNGR) homed to tumor vessels and penetrated into tumor tissue more effectively than the standard NGR peptide. iNGR induced greater tumor penetration of coupled nanoparticles and co-administered compounds than NGR. Doxorubicin given together with iNGR was significantly more efficacious than the drug alone. These results show that a tumor-specific, tissue-penetrating peptide can be constructed from known sequence elements. This principle may be useful in designing tissue-penetrating peptides for other diseases. Cancer Res; 73(2); 804–12. ©2012 AACR.
Pneumomediastinum after sneezing
Authors: R Souza, C Figueiredo, A J Rocha
Journal: Thorax (2009)

Pneumomediastinum after sneezingA previously healthy 37-year-old man with an upper airway viral infection presented with a progressive onset of neck pain with odinophagia and pretracheal tenderness after repetitive sneezing efforts.Upon examination, cervical subcutaneous emphysema was the only finding.The chest radiograph confirmed the presence of pneumomediastinum.Cervical and chest CT scans performed during a Valsalva manoeuvre identified bilateral laryngoceles with a rupture in the left one and perilaryngeal air extending to the subcarinal level (fig 1).Laryngoceles are dilations of the laryngeal saccule, usually unilateral, more commonly found in men and classified into internal, external or mixed (about 50% of cases). 1 The aetiology of laryngoceles is still unknown; they may be related to congenital defects or anatomical variations, but a causal association with activities related to an increase in airway pressure such as playing brass instruments has also been advocated.Owing to the transient increase in airway pressure, sneezing might act as a trigger for the development of pneumomediastinum, 2 especially in patients with structural abnormalities such as the presence of laryngoceles, as in our case.
USE OF WHOLE PROTEIN SUPPLEMENT AS AN ADJUNCT IN INSULIN COMA THERAPY
Authors: JOHN D. DEMOTT
Journal: American Journal of Psychiatry (1955)

A study with the use of a whole protein supplement and dextrose solution administered orally or by intubation as an adjunct in interruption of insulin coma was conducted to determine if this procedure was more efficacious in reducing the frequency and severity of delayed adverse reactions than the administration of a 50% dextrose solution alone for interruption. Results of study indicate that delayed adverse reactions were reduced approximately by one-half with the whole protein supplement procedure. There is not much difference in the amount of intravenous medications required in either procedure, both in the insulin department or on the wards, because of patients' refusal or inability to eat lunch. The patients themselves greatly preferred the whole protein supplement to the dextrose solution and it seemed to satisfy their hunger. Also, much less vomiting was noted in patients receiving the whole protein supplement.
Effect of thrombosis on complement activation and neutrophil degranulation during in vitro hemodialysis.
Authors: A K Cheung, B Faezi-Jenkin, J K Leypoldt
Journal: Journal of the American Society of Nephrology (1994)

Coagulation proteins are known to affect the complement system and neutrophils. To assess the influence of thrombosis on complement and neutrophils during hemodialysis, whole human blood obtained from normal donors and anticoagulated with either 0.8 or 2.0 U/mL of heparin was recirculated for 4 h through cellulose acetate hollow fibers in vitro. Plasma fibrinopeptide A (FPA) levels were measured to assess thrombosis, whereas the activation of the complement system was evaluated at various stages by determining plasma C3a(desArg), C5a(desArg), and SC5b-9 concentrations. The activation of circulating neutrophils was assessed by quantitation of the extracellular release of the intragranular proteins elastase and lactoferrin. Thrombosis was observed when 0.8 U/mL of heparin was used, as indicated by a 36-fold increase in (FPA) levels at 240 min of recirculation and occasional grossly visible blood clots. In contrast, no increase in FPA or clot formation was observed with 2.0 U/mL of heparin. The higher dose of heparin was also associated with a lesser increase in plasma C3a(desArg) and C5a(desArg) concentrations, an observation that is compatible with either an inhibitory effect of heparin or a stimulatory effect of coagulation on the complement system. Plasma elastase or lactoferrin concentrations increased during hemodialysis but were not dependent on heparin dosage at any time. It was concluded that anticoagulation with higher heparin concentration inhibits complement activation in the hemodialysis circuit, but it does not affect neutrophil degranulation.
On Cardiovascular Sound
Authors: VICTOR A. MCKUSICK, GEORGE N. WEBB, J. O'NEAL HUMPHRIES, JAMES A. REID
Journal: Circulation (1955)

Spectral phonocardiography, an adaptation of the method of sound spectrography devised at the Bell Telephone Laboratories, differs from conventional oscillographic phonocardiography principally in the fact that frequency spectrum is displayed as well as the dimensions of time and intensity. The display of frequency spectrum is responsible for three advantages of the method: (1) Quality, or timbre, is given physical definition, (2) resolution in the time dimension is improved, and a (3) a better display of the wide dynamic range of cardiovascular sound is attained. This method can do, or can be made to do, all the ear can, and can probably emulate the performance of the ear because 1) it is not wed to a particular frequency-intensity response curve, 2) it suffers from no "psychoacoustic" impediments, 3) it provides better resolution in the time dimension, and 4) it produces permanent, quantifiable records. Discussed here are selected features of mitral valve disease, aortic valve disease, gallops, systolic clicks, and extracardiac sounds. In general, intensity and peak frequency (or frequency range) vary in a parallel manner in sound of cardiovascular origin. Artefacts due to noncardiovascular ambient noise and to electrical interference can be identified and disregarded in the heart sound analysis.
Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy
Authors: F Parente
Journal: Gut (2004)

BACKGROUND/ AIM: Although ultrasound (US) has proved to be useful in intestinal diseases, barium enteroclysis (BE) remains the gold standard technique for assessing patients with small bowel Crohn's disease (CD). The ingestion of anechoic non-absorbable solutions has been recently proposed in order to distend intestinal loops and improve small bowel visualisation. The authors' aim was to evaluate the accuracy of oral contrast US in finding CD lesions, assessing their extent within the bowel, and detecting luminal complications, compared with BE and ileocolonoscopy.102 consecutive patients with proven CD, having undergone complete x ray and endoscopic evaluation, were enrolled in the study. Each US examination, before and after the ingestion of a polyethylene glycol (PEG) solution (500-800 ml), was performed independently by two sonographers unaware of the results of other diagnostic procedures. The accuracy of conventional and contrast enhanced US in detecting CD lesions and luminal complications, as well as the extent of bowel involvement, were determined. Interobserver agreement between sonographers with both US techniques was also estimated.After oral contrast, satisfactory distension of the intestinal lumen was obtained in all patients, with a mean time to reach the terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The correlation coefficient between US and x ray extent of ileal disease was r1 = 0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2 p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89% for contrast US. Overall interobserver agreement for bowel wall thickness and disease location within the small bowel was already good before but significantly improved after PEG ingestion.Oral contrast bowel US is comparable with BE in defining anatomic location and extension of CD and superior to conventional US in detecting luminal complications, as well as reducing interobserver variability between sonographers. It may be therefore regarded as the first imaging procedure in the diagnostic work up and follow up of small intestine CD.