tbuckley/cabot-search huggingface dataset:
Pressure-Diameter Relation of the Human Aorta
Authors: Christodoulos Stefanadis, Costas Stratos, Charalambos Vlachopoulos, Stelios Marakas, Harisios Boudoulas, Ioannis Kallikazaros, Eleftherios Tsiamis, Konstantinos Toutouzas, Lambros Sioros, Pavlos Toutouzas
Journal: Circulation (1995)

Background Pressure-diameter relation of the aorta provides important information about the elastic properties of the vessel. However, owing to methodological limitations, data regarding this relation are limited in conscious humans. In the present study, we assessed a new method for the direct estimation of the elastic properties of the aorta in conscious humans by simultaneous acquisition of instantaneous aortic pressure and diameter. Methods and Results With this method, instantaneous diameter of the thoracic aorta was acquired by a newly designed intravascular catheter developed in our institution that incorporates an ultrasonic displacement meter at its distal end. Instantaneous aortic pressure was acquired simultaneously at the same aortic level with a catheter-tip micromanometer. Aortic pressure-diameter loops were derived from computer analysis of data. After in vitro and animal testing, elastic properties of the aorta were investigated in coronary artery disease (CAD) patients (n=15) and compared with those of control subjects (n=10). Aortic distensibility was less in the CAD group than in the control group (1.73±0.33 versus 3.95±1.09×10 −6 ×cm 2 ×dyne −1 , P &lt;.001). Compared with control subjects, the mean value of the slope of the pressure-diameter loops was significantly greater in the CAD group (38.89±8.75 versus 19.62±5.46 mm Hg · mm −1 , P &lt;.001), whereas the mean value of the intercept was lower in this latter group of patients (−785.60±177.55 versus −313.43±126.41 mm Hg, P &lt;.001). An excellent correlation was found between the slope of pressure-diameter loop and age in the group of control subjects ( r =.827). Ninety-three percent of the patients with CAD had values above the upper 95% confidence limits of the control subjects ( P &lt;.001). In a third group of patients (n=16) in whom assessment of pulse wave velocity was also included in the study of the elastic properties of the aorta, pulse wave velocity had a strong inverse correlation with aortic distensibility ( r =−.95) and a strong positive correlation with the slope of the pressure-diameter loop ( r =.97). Conclusions This new method of determination of pressure-diameter of the aorta enables an accurate and reliable evaluation of the elastic properties of the aorta in conscious humans and may be useful for a profound study of human aorta mechanics.
Prevention of insulin-dependent diabetes mellitus in nonobese diabetic mice by immunogenic but not by tolerated peptides.
Authors: M Vaysburd, C Lock, H McDevitt
Journal: The Journal of Experimental Medicine (1995)

In the nonobese diabetic (NOD) mouse, susceptibility to insulin-dependent diabetes mellitus is in part controlled by a single expressed class II major histocompatibility complex (MHC) molecule, I-Ag7. This molecule probably exerts its control through the representation of a self-peptide, derived from an unknown beta cell antigen, leading to T cell activation and eventual islet destruction. In this paper, synthetic peptides have been used to compete for binding to the I-Ag7 molecule in an attempt to suppress the autoimmune response. The administration of an I-Ag7-binding immunogenic peptide, lambda repressor (cI) 12-26, in a water and oil emulsion (incomplete Freund's adjuvant) can prevent the transfer of IDDM into irradiated recipients by spleen cells from diabetic donors. Nonbinding, nonimmunogenic peptides have no effect in this situation. However, the immune response to the "blocking" peptide in these experiments was a complicating factor in interpreting the results. To establish that the effect was at the level of competition for MHC binding, two additional approaches were tried. First, tolerance was induced to the immunogenic peptide, cI 12-26, before using it to "block" disease. Tolerance abolished the effect on diabetes transfer. Second, an effort was made to identify peptides that were nonimmunogenic but that bound to I-Ag7. Such a peptide, mouse prostatic secretory glycoprotein precursor 63-76, had no effect on the incidence of transferred disease. We conclude that the "blocking" effects seen in initial experiments in the NOD mouse were not caused by blockade of MHC presentation, but by other unknown effects related to the immunogenicity of the "blocking" peptide.
Abstract B40: MiR-30c-2-3p participates in a regulatory feedback loop to inhibit the progression of chemoresistant ovarian cancer cells
Authors: Mandi Murph, Wei JIa, Molly Altman, Ha Nguyen
Journal: Clinical Cancer Research (2013)

Abstract Although many patients achieve a period of remission, serous epithelial ovarian carcinoma remains incurable because untreatable chemoresistant disease develops after first-line chemotherapy. The general lack of knowledge in understanding the molecular mechanisms that evolve in chemoresistance and the absence of ‘targetable’ molecules to exploit therapeutically is a major obstacle preventing an improvement in mortality. MicroRNAs (miRNAs) are naturally-produced, small noncoding RNA molecules that modulate gene transcription by fine-tuning messenger RNA (mRNA) expression and acting as mRNA co-repressors or co-activators. The mitogenic lipid, lysophosphatidic acid, and the epidermal growth factor mediate a significant increase in miR-30c-2-3p, which then participates in a regulatory feedback loop to inhibit viability, growth and proliferation of both chemo-sensitive and –resistant cells. Because a single miRNA can target hundreds of transcripts, we wanted to understand which mRNAs are targeted by miR-30c-2-3p and what is the extent of its ability to alter normal processes like survival, growth and proliferation through post-transcriptional modifications. In our study, we uncovered that miR-30c-2-3p targets the oncogene transcript for BCL9, which is a protein that promotes tumor progression, proliferation and metastasis. We hypothesize that the perpetuation of incessant, extracellular, mitogenic signaling overwhelms the anti-growth feedback loop mechanism supported by miR-30c-2-3p. Thus, the growth factor lysophosphatidic acid, which is abundantly present in ascites fluid, is a significant barrier to the successful treatment of chemoresistant ovarian tumors. Our data will demonstrate the effects of lysophosphatidic acid in both in vitro and in vivo models of ovarian cancer. Our long-term goal is to better understand the molecular mechanisms which evolve simultaneously with chemoresistance in ovarian tumor progression. Citation Format: Mandi Murph, Wei JIa, Molly Altman, Ha Nguyen. MiR-30c-2-3p participates in a regulatory feedback loop to inhibit the progression of chemoresistant ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B40.
<i>BRAF</i>V600E Mutation and Papillary Thyroid Cancer—In Reply
Authors: Mingzhao Xing
Journal: JAMA (2013)

In Reply I disagree with Dr Ciarrocchi and colleagues that BRAF V600E has no role in the aggressiveness of PTC because of its dependence on tumor behaviors, including local and distant metastases and invasion. It is clear that PTC would not cause patient death without aggressive tumor behaviors.

Our study demonstrated a strong synergism between BRAF V600E and aggressive clinicopathological behaviors, as reflected by the strong synergy indices and the fact that the association of mortality with BRAF V600E or clinicopathological behavior alone was only moderate but increased when the 2 were considered jointly. Thus, BRAF V600E does have a significant association with mortality, which likely occurs through promoting aggressive tumor behaviors and would be misleadingly lost using conventional multivariable models. Further efforts are needed to define how to specifically use the prognostic value of BRAF V600E clinically.

Some studies have not shown an association of BRAF V600E with aggressive behaviors of PTC. However, most have, as shown in large meta-analyses.1,2 Many factors could bias the conclusion about the prognostic value of BRAF V600E. For example, in a large study of 631 patients with PTC that failed to show an association of aggressiveness of PTC with BRAF V600E,3 many patients (41.5%) had only partial thyroidectomy, making thorough pathological characterization difficult. In addition, the majority of the patients in this study did not receive radioiodine ablation, potentially masking an effect of BRAF V600E on clinical outcomes given that BRAF mutation-negative PTC is more sensitive to radioiodine ablation.1,2

Ciarrocchi and colleagues' statement that a previous study4 showing no aggressive role of BRAF V600E in PTC confirms our study is incorrect. However, the 2 studies are not comparable; the former was a single institution study focused on a small number of highly selected cases and the latter was a large multicenter study of consecutive cases.

The study by Sancisi et al4 selected patients with distant metastases who only had well-differentiated primary cancer; cases of PTC with distant metastases and high-grade disease or poorly differentiated or undifferentiated components were excluded. This biased case selection misrepresents the real metastatic behaviors of PTC, in which cases with high-grade disease or aggressive pathological components tend to metastasize distantly. This exclusion criterion is problematic, particularly when the role of BRAF V600E is studied because the BRAF mutation promotes dedifferentiation of PTC.5

It is also unclear whether the control patients were matched with respect to factors that may potentially affect BRAF V600E. For example, only the mean age of patients and the mean and range of the follow-up time were provided, without detailed informationonpatientagedistributionandthechronologicaltime of recruitment. This is an important issue because BRAF V600E displays a lower prevalence in younger vs older patients and in patients treated earlier compared with more recently.6
Pulmonary and Articular Sporotrichosis
Authors: Doris S. Serstock
Journal: JAMA (1975)

Two rare forms of sporotrichosis were seen in one hospital within a two-year period. One, a case of primary sporotrichosis of the lung, represents the eighth case on record, to our knowledge. The other, a case of articular sporotrichosis, is not as rare, but is still uncommon manifestation of the disease. The problems in management of these two patients are of interest because of the challenge of conventional concepts of therapy.
Hypokalaemia, Metabolic Alkalosis, and Hypernatraemia due to "Massive" Sodium Penicillin Therapy
Authors: F. P. Brunner, P. G. Frick
Journal: BMJ (1968)

Hypokalaemia and metabolic alkalosis were seen in three patients and additionally hypernatraemia in two patients treated with 100 mega units of sodium penicillin G for subacute bacterial endocarditis. The hypernatraemia was probably due to the administration of insufficient fluid, while urinary potassium loss was an important factor in producing hypokalaemia and metabolic alkalosis after. Penicillin may promote urinary potassium excretion by acting as a non-reabsorbable anion.Potassium depletion during treatment with massive doses of sodium penicillin G may be prevented by concurrently administering potassium-sparing diuretics or by using the potassium salt of penicillin.
Resection of a Giant Neuroblastoma Misdiagnosed as Atypical Mediastinal Carcinoid
Authors: Eleftherios Chalvatzoulis, Jeremias Wohlschlaeger, Thomas Hager, Danjouma Cheufou, Wilfried Eberhardt, Georgios Stamatis, Stefan Welter
Journal: Journal of Thoracic Oncology (2013)
Changes in neuroendocrine elements in bronchial mucosa in chronic lung disease in adults.
Authors: M Pilmane, A Luts, F Sundler
Journal: Thorax (1995)

<h3>Abstract</h3> Demographers were among the first to emphasize the importance of age in explaining the spread and impact on mortality of COVID-19. Yet, the relationship between age and COVID-19 is not fully understood. This study aims to answer the following questions: Do COVID-19 deaths follow the Gompertz force of mortality? How does the relationship between age and COVID-19 mortality compare with other major causes of death? Does this relationship vary between countries? Using US vital Statistics, COVID-19 mortality doubling time is compared with 68 major cause of death categories. COVID-19 fatality is similarly compared across 33 countries using COVerAGE-DB, a harmonized dataset of confirmed COVID-19 cases and deaths. Several findings are supported by the evidence. First, COVID-19 mortality increasing exponentially with age at a rate near the median of aging-related causes of death, as well as pneumonia and influenza. Second, COVID-19 mortality levels in the US are currently 4 to 8 times higher than pneumonia and influenza across the adult age range. Third, the relationship between COVID-19 fatality and age varies considerably across high-income countries. Fourth, these regularities can be utilized for indirect estimation of COVID-19 deaths by age. In conclusion, the relationship between COVID-19 mortality and age resembles the population rate of aging. Between-country variation in the Gompertz slope of COVID-19 fatality may point to differences in underlying population health, standards of clinical care, and data quality.
Genetic Analysis of Vertebrate Sensory Hair Cell Mechanosensation: the Zebrafish Circler Mutants
Authors: Teresa Nicolson, Alfons Rüsch, Rainer W Friedrich, Michael Granato, Johann Peter Ruppersberg, Christiane Nüsslein-Volhard
Journal: Neuron (1998)

The molecular basis of sensory hair cell mechanotransduction is largely unknown. In order to identify genes that are essential for mechanosensory hair cell function, we characterized a group of recently isolated zebrafish motility mutants. These mutants are defective in balance and swim in circles but have no obvious morphological defects. We examined the mutants using calcium imaging of acoustic-vibrational and tactile escape responses, high resolution microscopy of sensory neuroepithelia in live larvae, and recordings of extracellular hair cell potentials (microphonics). Based on the analyses, we have identified several classes of genes. Mutations in sputnik and mariner affect hair bundle integrity. Mutant astronaut and cosmonaut hair cells have relatively normal microphonics and thus appear to affect events downstream of mechanotransduction. Mutant orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli. The microphonics of lateral line hair cells of orbiter, mercury, and gemini larvae are absent or strongly reduced. Therefore, these genes may encode components of the transduction apparatus.
Of Genes and Men: The Alternative View of Sex Differences in Cystic Fibrosis
Authors: Marc Creus, Wolfgang Vogel, Heinz Zoller
Journal: Diabetes Care (2006)

quent (depending on the severity of the retinopathy) (3).Our data relate to patients Ͻ20 years old and cannot be generalized to the adult population.Stefa ´nsson states that in Iceland, no patient progressed from "no retinopathy" to "vision-threatening retinopathy" within 2 years.However, since collecting the original data (1990 -2002), we have been informed of two former patients who had rapid progression from level 31 and level 45 retinopathy to blindness in Ͻ2 years.These patients were 21 and 23 years old when blindness occurred (therefore outside of our study group), and both had significant risk factors for retinopathy (persistently high HbA 1c and diabetes duration 17 years).Stefa ´nsson describes a decrease in legal blindness due to retinopathy in the Icelandic population.Although this may be due to improved management of retinopathy, it may also indicate a reduction in retinopathy due to intensive insulin therapy.This would be in keeping with the trend in our population, in which the incidence of retinopathy has decreased over the last decade from 49 to 24% in patients of 8 years' diabetes duration (4).However, despite the declining incidence of retinopathy in our population, adolescents should be advised of the serious and real risk of blindness due to diabetic retinopathy.Indeed, blindness occurred in the two patients mentioned above in 2003 and 2004.
Abstract A31: Comparison of direct sequencing and peptide nucleic acid clamping of EGFR gene in patients with non-small cell lung cancer.
Authors: Young-Chul Kim, Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Bo-Ram Lee, Jin-Yeong Yu, Min-Ki Lee
Journal: Clinical Cancer Research (2014)

Abstract Background: Direct sequencing is considered as a gold standard for the detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC), but low sensitivity is a problem. The aim of this study is to prove higher detection rate of EGFR mutation with peptide nucleic acid (PNA) clamping compared to direct sequencing. Methods: This is a single arm, open label, prospective, observational study for patients with stage IIIB, IV or relapsed NSCLC. A sample size of 140 pairs will have 90% power to detect a difference in proportions of 0.1 when the proportion of discordant pairs is expected to be 0.16 and the method of analysis is a McNemar's test of equality of paired proportions with a 0.05 one-sided significance level and 20% drop out rate. Tumor DNA samples were obtained from paraffin block or cytology specimen. Both direct sequencing and PNA clamping for EGFR gene in exon 18, 19, 20 and 21 were performed. Results: Of 138 paired test sets, 24 mutations of EGFR gene were detected by direct sequencing (17.4%) and 45 mutations were detected by PNA clamping (32.6%). The difference of detection rate between two methods was 15.2% (95% Confidence Interval: 8.7-17.8%, p&amp;lt;0.001). After treatment with EGFR-tyrosine kinase inhibitors, 20 of 26 response evaluable patients with EGFR mutation by PNA clamping showed partial responses (PR, 76.9%). And 8 among 13 patients with EGFR mutation by direct sequencing showed PR (61.5%). Conclusion: This study proved that PNA clamping has significantly higher detection rate of EGFR mutation compared with direct sequencing. (ClinicalTrials.gov number, NCT01767974) Citation Format: Young-Chul Kim, Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Bo-Ram Lee, Jin-Yeong Yu, Min-Ki Lee. Comparison of direct sequencing and peptide nucleic acid clamping of EGFR gene in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A31.
Catatonia: A disorder of motivation and movement
Authors: Gregory Fricchione
Journal: Behavioral and Brain Sciences (2002)

Georg Northoff employs a comparison with Parkinson's disease in an effort to tease apart the underlying pathophysiology of psychogenic catatonia. Northoff's extensive treatment of the subject is abetted by his own research as well as the research of others. Nevertheless, a number of points concerning basal ganglia/thalamocortical processing need to be raised, some adding support to his hypothesis and others detracting from it.
Incontinentia pigmenti: eosinophil chemotactic activity of the crusted scales in the vesiculobullous stage
Authors: H. TAKEMATSU, T. TERUI, W. TORINUKI, H. TAGAMI
Journal: British Journal of Dermatology (1986)

To investigate the mechanisms underlying eosinophil infiltration into the epidermis in incontinentia pigmenti (IP), we studied the eosinophil chemotactic activity in extracts of the crusted scales from three patients with IP in the vesiculobullous stage. Eosinophil ehemotactic activity was detected in the eluates from a Sephadex G‐75 chromatography column between the vitamin B12 and phenol red markers. The chemotactic activity was heat‐stable and resistant to enzyme digestion, and recovered after ether extraction at low pH. Leukotriene B4 (LTB4) was demonstrated in the fractions with high eosinophil chemotactic activity. These findings suggest that LTB4 plays an important role in the accumulation of eosinophils within the epidermis in IP, in the vesiculobullous stage. Blood eosinophilia, however, may not be induced by the eosinophil chemotactic factors in the scales.
Bioactive Supramolecular Peptide Nanofibers for Regenerative Medicine
Authors: Elif Arslan, I. Ceren Garip, Gulcihan Gulseren, Ayse B. Tekinay, Mustafa O. Guler
Journal: Advanced Healthcare Materials (2014)

Recent advances in understanding of cell-matrix interactions and the role of the extracellular matrix (ECM) in regulation of cellular behavior have created new perspectives for regenerative medicine. Supramolecular peptide nanofiber systems have been used as synthetic scaffolds in regenerative medicine applications due to their tailorable properties and ability to mimic ECM proteins. Through designed bioactive epitopes, peptide nanofiber systems provide biomolecular recognition sites that can trigger specific interactions with cell surface receptors. The present Review covers structural and biochemical properties of the self-assembled peptide nanofibers for tissue regeneration, and highlights studies that investigate the ability of ECM mimetic peptides to alter cellular behavior including cell adhesion, proliferation, and/or differentiation.
Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells
Authors: Gerty Schreibelt, Daniel Benitez-Ribas, Danita Schuurhuis, Annechien J. A. Lambeck, Maaike van Hout-Kuijer, Niels Schaft, Cornelis J. A. Punt, Carl G. Figdor, Gosse J. Adema, I. Jolanda M. de Vries
Journal: Blood (2010)
Independence of Blood Pressure and Aldosterone Secretion
Authors: E.A. Espiner, J.R. Tucci, P.I. Jagger, D.P. Lauler
Journal: New England Journal of Medicine (1967)

THAT essential hypertension may be associated with increased secretion of aldosterone, especially during an accelerated or malignant phase, is now well established.1 , 2 Reduction of the blood pressure has been reported in some of these cases to restore aldosterone secretion to normal,3 4 5 suggesting that the associated aldosteronism is secondary to some element of the elevated pressure itself. Since it is often difficult to separate such cases from aldosterone-producing tumors of the adrenal cortex, it has been suggested that a trial with antihypertensive, therapy be undertaken in patients suspected of having primary aldosteronism before surgical exploration is carried out.5 This presupposes that . . .