tbuckley/cabot-search huggingface dataset:
Central Pulse Pressure Is a Major Determinant of Ascending Aorta Dilation in Marfan Syndrome
Authors: Guillaume Jondeau, Pierre Boutouyrie, Patrick Lacolley, Brigitte Laloux, Olivier Dubourg, Jean-Pierre Bourdarias, Stéphane Laurent
Journal: Circulation (1999)

Background —In patients with Marfan syndrome (MFS), brachial pulse pressure (PP) has been recognized as a risk factor for aortic dilatation, leading to aortic dissection, the main cause of premature death. However, the relationships between aortic PP, aortic stiffness, and aortic root dilation have not been investigated. Our main objective was to determine whether central PP, which takes into account wave reflections and aortic stiffness, is a better determinant of ascending aorta diameter than brachial PP in MFS patients. Methods and Results —Twenty patients with confirmed MFS and 20 age- and sex-matched control subjects were included in this cross-sectional, noninvasive study. Elastic properties of the abdominal aorta and common carotid, common femoral, and radial arteries were calculated from the pulsatile changes in arterial diameter and pressure. The ascending aorta diameter, measured with conventional echocardiography, was 37% larger in MFS than in control subjects ( P &lt;0.001). Arterial distensibility was 38% lower in MFS than in control subjects at the site of the abdominal aorta ( P &lt;0.01) but not at other sites (common carotid, common femoral, and radial arteries). Independently of age and body surface area, ascending aorta diameter was positively correlated with carotid PP in MFS ( P &lt;0.01) and negatively in control subjects ( P &lt;0.01) but was not correlated with brachial PP and mean blood pressure. Conclusions —In patients with MFS, local PP, estimated from carotid PP, was a major determinant of ascending aorta diameter, whereas brachial PP was not. Increased arterial stiffness was confined to the aorta.
Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions
Authors: Alejandro Vazquez-Martin, Eugeni López-Bonetc, Sílvia Cufí, Cristina Oliveras-Ferraros, Sonia Del Barco, Begoña Martin-Castillo, Javier A. Menendez
Journal: Drug Resistance Updates (2011)
Abstract 621: High-dose gefitinib overcomes the resistance to gefitinib related to hepatocyte growth factor
Authors: Hiromi Kashihara, Eiki Ichihara, Saburo Takata, Kadoaki Ohashi, Toshio Kubo, Hiromasa Takeda, Masanori Fujii, Nagio Takigawa, Mitsune Tanimoto, Kunio Matsumoto, Katsuyuki Kiura
Journal: Cancer Research (2010)

Abstract Molecular targeted agents are being a mainstay in non-small cell lung cancer. Dramatic responses to the epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKI) are observed in advanced non-small cell lung cancer (NSCLC), especially with EGFR mutation. Different from cytotoxic agents, it remains unclear whether EGFR-TKI exerts its anti-tumor effect dose-dependently. Gefitinib could not show survival benefit in previously treated unselected patients with NSCLC in a randomized phase III trial, whereas erlotinib did. The difference is considered resulting from the fact that erlotinib was dosed at its maximum-tolerated dose (MTD), while gefitinib was dosed at about one third of its MTD. To investigate the dose-dependency of gefitinib in the cells harboring mutated EGFR, we compared two doses of gefitinib (15 or 50 mg/kg) using PC-9 (adenocarcinoma of lung) xenografts. Both doses of gefitinib reduced tumors. However, the tumors regrew in the low-dose group after several weeks of treatment, whereas did not in the high dose group. This result indicates that gefitinib might have the dose-dependency in the tumors harboring mutated EGFR. We resected tumors at 10 weeks after gefitinib treatment. The removed tumors did not acquired T790M mutation and MET amplification. Interestingly, the cells (PC-9/RX) that were derived from the xenograft tumors treated with low-dose gefitinib remained the sensitivity to gefitinib. Thus, we investigated hepatocyte growth factor (HGF) as the environmental factor. Tumor tissues treated with gefitinib were positively stained with anti-mouse HGF. Mouse HGF mRNA and protein expression in the tumor tissues treated with gefitinib were significantly high when compared to those treated with vehicle alone, and similar results were obtained by ELISA. We confirmed that mouse HGF induced resistance to gefitinib in an ex vivo experiment. To elucidate the role of HGF in vivo, PC-9 xenografts were treated with gefitinib in combination with rabbit anti-HGF antibody. The combination of gefitinib with anti-HGF antibody inhibited tumor growth partially compared with the low-dose gefitinib alone. Taken together, HGF might induce resistance to low-dose of gefitinib treatment in an in vivo xenograft model before the tumor cells themselves acquired the resistant genetic changes. In conclusion, higher-dose of gefitinib might prevent resistance to gefitinib related to HGF and produce longer response duration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 621.
Regulation of calcium channel expression in neonatal myocytes by catecholamines.
Authors: T Maki, E J Gruver, A J Davidoff, N Izzo, D Toupin, W Colucci, A R Marks, J D Marsh
Journal: Journal of Clinical Investigation (1996)

Expression of the dihydropyridine (DHP) receptor (alpha 1 subunit of L-type calcium channel) in heart is regulated by differentiation and innervation and is altered in congestive heart failure. We examined the transmembrane signaling pathways by which norepinephrine regulates DHP receptor expression in cultured neonatal rat ventricular myocytes. Using a 1.3-kb rat cardiac DHP receptor probe, and Northern analysis quantified by laser densitometry, we found that norepinephrine exposure produced a 2.2-fold increase in DHP receptor mRNA levels at 2 h followed by a decline to 50% of control at 4-48 h (P < 0.02). The alpha-adrenergic agonist phenylephrine and a phorbol ester produced a decline in mRNA levels (8-48 h). The beta-adrenergic agonist isoproterenol and 8-bromo-cAMP produced a transient increase in mRNA levels. After 24 h of exposure to isoproterenol, 3H-(+)PN200-110 binding sites increased from 410 +/- 8 to 539 +/- 39 fmol/mg (P < 0.05). The number of functional calcium channels, estimated by whole-cell voltage clamp experiments, was also increased after 24 h of exposure to isoproterenol. Peak current density (recordings performed in absence of isoproterenol) increased from -10.8 +/- 0.8 (n = 23) to -13.9 +/- 1.0 pA/pF (n = 27) (P < 0.01). Other characteristics of the calcium current (voltage for peak current, activation, and inactivation) were unchanged. Exposure for 48 h to phenylephrine produced a significant decline in peak current density (P < 0.01). We conclude that beta -adrenergic transmembrane signaling increases DHP receptor mRNA and number of functional calcium channels and that alpha - adrenergic transmembrane signaling produces a reciprocal effect. Regulation of cardiac calcium channel expression by adrenergic pathways may have physiological and pathophysiological importance.
Correlation of Bioscintigraphy, Contrast Venography, and lodine-125 Fibrinogen Uptake Test
Authors: GERALD L. DeNARDO, SALLY J. DeNARDO, ROBERT F. CARRETTA, HUGO G. BOGREN, ANNE-LINE JANSHOLT, KENNETH A. KROHN, NEAL F. PEEK
Journal: Clinical Nuclear Medicine (1985)

In 40 patients believed to have deep venous thrombosis, bioscintigrams performed with 1-123 fibrinogen were available for comparison with either contrast venograms or 1-125 fibrinogen uptake tests. If either contrast venography or the fibrinogen uptake test was accepted as a standard for comparison, the accuracy of bioscintigraphic imaging was 90%. Most discrepancies between the procedures could be interpreted as due to heparin treatment, although bioscintigrams often were positive in patients treated with heparin for a short interval of time. Additionally, bioscintigrams provided information to distinguish venous thrombosis from other sources for local accumulation of radioactivity. Bioscintigraphy seems to be a promising noninvasive method for the detection of deep venous thrombosis of the lower extremities.
Reply to M. Ozsahin et al
Authors: Kåre G. Sunesen, Mette Nørgaard, Hanne Havsteen, Lilli Lundby, Steen Buntzen, Ole Thorlacius-Ussing, Søren Laurberg
Journal: Journal of Clinical Oncology (2011)

with radiotherapy intended as a preoperative procedure before abdominoperineal resection, were not included in our patient cohort.Therefore, excluding the patients with pretreatment colostomies, as suggested by Ozsahin et al, 1 would cause us to underestimate the actual number of patients needing a colostomy despite intended sphincter-sparing treatment.Finally, we observed in patients with local excision preceding radiotherapy a substantially higher risk of therapy-related colostomy despite slightly lower radiotherapy doses (mean dose, 61.6 v 63.1 Gy; P ϭ .007).However, our speculation that local excision should not be the primary therapeutic option was also based on other studies, which reported higher frequency of colostomy 14 or severe anorectal injury, 15 but no decrease in local failure in patients with local excision before radiotherapy or chemoradiotherapy. 15
Prevalence and distribution of melanocytic naevi on the scalp: a prospective study
Authors: V. De Giorgi, S. Sestini, M. Grazzini, A. Janowska, V. Boddi, T. Lotti
Journal: British Journal of Dermatology (2009)

Few studies have examined the incidence and characteristics of naevi on the scalp. Most studies of scalp naevi have been performed in children, whose incidence of scalp naevi is relatively high, at about 0.5-11.7% of the total body count of common naevi.To investigate the prevalence and distribution of scalp melanocytic naevi in patients of all ages. To our knowledge, ours is the first study to analyse in detail the relationships between melanocytic naevi on the scalp and total body naevi and total body atypical naevi.We conducted a prospective study of patients visiting the dermatology outpatient clinic at the University of Florence, for examinations unrelated to the presence of naevi or melanoma. The study enrolled 795 subjects (417 females; 52.4%), with a median age of 35 years (range 4-80).The number of melanocytic naevi on the scalp increased significantly (r = 0.2057, P = 0.0008) as the number of total body melanocytic naevi increased and a correlation was found between the number of clinically atypical total body naevi and the number of scalp naevi. Relatively few naevi (15.5%) were located at the frontal region compared with other regions of the scalp, although the frontal region is more exposed to ultraviolet (UV) rays. Compared with subjects without alopecia, whose hair shields the scalp from UV rays, subjects with androgenetic alopecia showed no significant increase in number of scalp naevi.Despite practical difficulties, early diagnostic screening for melanoma or screening during follow-up examination for previous melanoma should involve examination of the entire skin surface, scalp included.
Thomas Hodgkin: Morbid Anatomist and Social Activist
Authors: Ruben D. Rumbaut
Journal: JAMA (1994)

Outstanding minds are remembered with awe by posterity because of their inspiring creations. In contrast, an outstanding physician might go down in history with the ironic privilege of having his or her name given to a dreadful disease. That is the case with Thomas Hodgkin, the first person to describe the autopsy findings characteristic of one of the cruelest of illnesses. In his time, and for many decades thereafter, the diagnosis of Hodgkin's disease was the equivalent of a death sentence. His paper "On Some Morbid Appearances of the Absorbent Glands and Spleen" was read in England (January 10 and 24, 1832) before the Medical and Chirurgical Society. He considered the peculiar enlargement of the lymph nodes and the spleen as a separate entity from cancer, tuberculosis, and other already recognizable conditions: a primary disease, not some secondary response to an obscure inflammatory process. Thus, a disease that is now
A controlled study of hand function in nodal and erosive osteoarthritis.
Authors: M Pattrick, S Aldridge, E Hamilton, A Manhire, M Doherty
Journal: Annals of the Rheumatic Diseases (1989)

Hand function using a standardised test of activities of daily living was assessed in (a) 57 patients (53 female, four male; mean age 69 years) with established (that is, symptom onset greater than 10 years before) nodal generalised osteoarthritis (NGOA); (b) 10 patients (nine female, one male; mean age 70 years) with established erosive osteoarthritis (EOA); and (c) 52 matched controls (48 female, four male; mean age 71 years) with asymptomatic, clinically normal hands. Although significant differences between controls and patient groups were observed for individual tasks, only minor global impairment was seen, the worst function occurring in patients with EOA. There was no consistent correlation between tested aspects of hand function and extent of radiographic change assessed by summated graded score for separate osteoarthritic features in individual joints. In controls increasing age correlated with longer time to complete all tasks and weaker power grip; a similar, less pronounced correlation occurred in patients. Differences between controls and patients with NGOA were most apparent in younger subjects; in the elderly (greater than 80 years) hand function was essentially the same. This study shows good functional outcome for patients with NGOA, and suggests that the OA process is of little functional importance to the aging hand.
Developmental and hormonal regulation of glucocorticoid receptor messenger RNA in the rat.
Authors: J E Kalinyak, C A Griffin, R W Hamilton, J G Bradshaw, A J Perlman, A R Hoffman
Journal: Journal of Clinical Investigation (1989)

The biological action of glucocorticoids is dependent upon tissue-specific levels of the glucocorticoid receptor (GR). During stress, the hypothalamic-pituitary-adrenal axis is stimulated, and high levels of glucocorticoids circulate. This axis is modulated by negative feedback by glucocorticoids, which inhibit hypothalamic and pituitary hormone secretion and downregulate GR gene expression. To study the developmental tissue-specific regulation of the GR, we measured the relative concentration of GR mRNA in fetal, neonatal, adult, and aged rats and examined the effects of dexamethasone on GR gene expression. Three different tissue-specific developmental patterns of GR mRNA accumulation were found. In addition, there was an age-dependent tissue-specific pattern in the feedback regulation of GR mRNA by glucocorticoids. In the fetus and neonate, GR mRNA abundance was not regulated by circulating glucocorticoids. The adult pattern of glucocorticoid feedback inhibition of GR mRNA expression appeared between 2 and 7 d of life in liver, and after 7 but before 14 d of age in brain. The GR was biologically active in the 2-d-old neonate, however, since dexamethasone enhanced gene expression of angiotensinogen, which is another glucocorticoid responsive gene. These data demonstrate that the GR gene is regulated by both developmental and tissue-specific factors, and provide another molecular basis for ontogenic variations in the hypothalamic-pituitary-adrenal response to stress.
Ambulatory 23 hour recording of intraoesophageal pressures in normal volunteers: a propagation analysis from one proximal and two distal recording sites.
Authors: S Kruse-Andersen, L Wallin, T Madsen
Journal: Gut (1991)

pH data were obtained from one level and pressure data from three levels in the oesophagus over 23 hours in 24 healthy volunteers, followed by automatic propagation analysis of motility data and analysis of time with pH less than 4. Apart from periods of meal ingestion, isolated pressure complexes were found more frequently in the distal than in the proximal oesophagus. This was especially common in the recumbent position at night. Most contractions of the proximal oesophagus were propagating. In the distal oesophagus were propagating. In the distal oesophagus propagating pressure waves were more frequent during the day than during the night and most frequent during meals. The state of consciousness rather than body position per se is important in determining the frequency of simultaneous contractions in the distal oesophagus.
Capillary recruitment and pain relief on leg dependency in patients with severe lower limb ischemia.
Authors: D T Ubbink, M J Jacobs, D W Slaaf, G J Tangelder, R S Reneman
Journal: Circulation (1992)

Patients suffering from severe lower limb ischemia may experience pain relief on leg dependency despite the fact that dependency normally results in arteriolar vasoconstriction. To clarify this possible paradox, skin microcirculation of the limb was investigated in 75 patients with different stages of lower limb ischemia and in 12 asymptomatic subjects.Using nailfold capillary video microscopy, red blood cell-perfused capillary density and diameter and red blood cell velocity were assessed in supine and sitting positions. Capillary density increased by changing from the supine to the sitting position, especially in patients with limb-threatening ischemia (showing a 4.5-fold increase versus a 1.5-fold increase in asymptomatic subjects). In subjects without or with mild ischemia, capillary perfusion was two to four times lower in the sitting than in the supine position. In patients with limb-threatening ischemia, perfusion was strongly reduced, being slightly higher in the sitting position. Patients with relief of pain while sitting did not always have a higher capillary perfusion but did have a higher capillary density in the sitting position.The arteriolar postural vasoconstrictive mechanism at the nutritive level is still intact in subjects without or with mild ischemia but not in patients with severe ischemia. Capillary recruitment rather than disturbed arteriolar vasoconstriction could explain why patients with severe leg ischemia prefer leg dependency.
THE WHITMAN OPERATION FOR TALIPES CALCANEUS PARALYTICUS
Authors: JOHN PRENTISS LORD
Journal: JAMA (1913)

During the last year I have done the Whitman operation twenty times on eighteen patients, and the immediate results have been so gratifying that I am most enthusiastic in indorsement of the operation. At a clinic given before the American Orthopedic Association in New York, May, 1912, I was privileged to witness the performance of the operation by its author. Prior to this time its full technic had not been sufficiently comprehended to justify its adoption. But my indifferent results had stimulated my special interest. The results in very numerous cases there exhibited were convincing. A personal communication from Professor Whitman states that few, besides himself, do the operation in New York. It is my observation that too few surgeons employ this method of radical relief, and I, therefore, desire to aid the cause of its popularization through the report of the results of my experience. The operation has a wider
From the Museum: the Art of Thinking. Part Eleven: Composition
Authors: Tom Kotsimbos
Journal: European Respiratory Journal (2014)

Reciprocal Accords is a delightfully balanced large format composition painted by Kandinsky in the final synthesising phase of his art. In it there is a striking accord between two strongly coloured, multi-composite geometric forms finely anchored on their tips as they project outwards from a background of three distinctly softened panes of colour that elegantly defines them and the surrounding space. Assemblages of linear, curved and circular forms are either attached to the two dominants or float freely between them in clusters of pulsing energy that is equally reminiscent of the music of nature, our cellular biology and a socially connected life. Biomorphic abstraction has come to the fore on a background of "inner necessity" as Kandinsky remains consumed by his inner world right to the end. The resonating agreement between "eye and soul" is now matched by the romantic coupling of new life emerging from chaos. In a penultimate symphonic burst of creative synthesis, Kandinsky's unique expressive use of form and colour once again becomes original signal amongst what for him was the artistic noise of the time.
Generation of Induced Pluripotent Stem Cells with High Efficiency from Human Umbilical Cord Blood Mononuclear Cells
Authors: Juan Wang, Qi Gu, Jie Hao, Donghui Bai, Lei Liu, Xiaoyang Zhao, Zhonghua Liu, Liu Wang, Qi Zhou
Journal: Genomics Proteomics & Bioinformatics (2013)

Abstract Human induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine. Generating iPSCs from immunologically immature newborn umbilical cord blood mononuclear cells (UCBMCs) is of great significance. Here we report generation of human iPSCs with great efficiency from UCBMCs using a dox-inducible lentiviral system carrying four Yamanaka factors. We generated these cells by optimizing the existing iPSC induction protocol. The UCBMC-derived iPSCs (UCB-iPSCs) have characteristics that are identical to pluripotent human embryonic stem cells (hESCs). This study highlights the use of UCBMCs to generate highly functional human iPSCs that could accelerate the development of cell-based regenerative therapy for patients suffering from various diseases.