tbuckley/cabot-search huggingface dataset:
Potent Activity of a Novel Dimeric Heat Shock Protein 90 Inhibitor against Head and Neck Squamous Cell Carcinoma <i>In vitro</i> and <i>In vivo</i>
Authors: Xiaoying Yin, Hong Zhang, Francis Burrows, Lin Zhang, Carol G. Shores
Journal: Clinical Cancer Research (2005)

Abstract Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical testing. However, 17-AAG is difficult to formulate and displays weak activity against some tumors. A novel dimeric ansamycin, EC5, was evaluated for antitumor activity in eight head and neck squamous cell carcinoma (HNSCC) cell lines. Both 17-AAG and EC5 inhibited tumor cell proliferation effectively, but EC5 was more potent, with IC50 below 200 nmol/L in most cell lines tested, including several lines that were resistant to 17-AAG. The inability of 17-AAG to kill JHU12 cells was linked to a defect in retinoblastoma signaling and could be rescued by ectopic expression of p16INK4a. EC5 induced G1 growth arrest of tumor cells and apoptosis, with the degradation of client proteins including epidermal growth factor receptor, c-Raf-1, Akt, and Cdk4 and inhibition of Akt phosphorylation. In vivo, EC5 dramatically reduced the growth rate of established HNSCC xenografts in nude mice and decreased expression of epidermal growth factor receptor and Akt within the xenografts. These results suggest that this novel ansamycin-based Hsp90 inhibitor affects multiple pathways involved in tumor development and progression and may represent a new strategy for the treatment of HNSCC patients.
Zyxin Mediation of Stretch-Induced Gene Expression in Human Endothelial Cells
Authors: Agnieszka Wójtowicz, Sahana Suresh Babu, Li Li, Norbert Gretz, Markus Hecker, Marco Cattaruzza
Journal: Circulation Research (2010)

Rationale: Prolonged exposure to enhanced stretch, such as in hypertension, triggers endothelial dysfunction, a hallmark of pathological vascular remodeling processes. Despite its clinical relevance, little is known about stretch-induced gene expression in endothelial cells. Objective: Here, we have characterized a new stretch-inducible signaling pathway and the subsequent changes in endothelial gene expression in response to stretch. Methods and Results: Using human primary endothelial cells, we observed that the protein zyxin translocates from focal adhesions to the nucleus solely in response to stretch. There, it orchestrates complex changes in gene expression by interacting with a novel cis -acting element found in all zyxin-regulated genes analyzed so far. By way of DNA microarray pathway analyses, stretch-induced changes in endothelial cell gene expression were systematically explored, revealing that zyxin mainly regulates proinflammatory pathways. Conclusions: Stretch appears to be an important factor in the development of endothelial dysfunction with zyxin as a potential therapeutic target to interfere with these early changes in endothelial cell phenotype.
Pneumatic Tourniquet Electromyographic Changes
Authors: Ronald W. Rau
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The article by Weingarden et al, "Electromyographic Changes in Postmeniscectomy Patients: Role of the Pneumatic Tourniquet" (241:1248,1979), implicating the pneumatic tourniquet as a factor in causing postelectromyographic changes in patients who have had meniscectomy, is extremely misleading. As all orthopedic surgeons well know, virtually all patients who undergo meniscectomy and who have been suffering from discomfort and injury to the knee for more than several days have quadriceps wasting. Undoubtedly, a substantial number of these patients would have electromyographic (EMG) changes prior to meniscectomy. The article by Weingarden et al studied only postoperative patients and did not examine the same patients preoperatively. Had they done this, they might well have found notable changes before surgery that would certainly have made their implication of the pneumatic tourniquet tenuous. They also should have included preoperative and postoperative EMG studies in patients who underwent meniscectomy without the use of the
Effects of Angiotensin on the Heart and Coronary Circulation of the Dog Before and After Beta-adrenergic Blockade
Authors: G. Ross
Journal: Cardiovascular Research (1967)

Rapid intravenous injections of angiotensin increased systemic pressure and reduced coronary flow while cardiac output remained unchanged or reduced. After a few seconds cardiac output and coronary flow increased. After β-adrenergic blockade, angiotensin produced only a reduction in cardiac output and the coronary flow increase per unit rise of pressure was diminished. These studies provide further evidence indicating an intimate association between angiotensin and the sympathetico-adrenal axis.
Release of prostaglandin D<sub>2</sub> and leukotriene C<sub>4</sub> in response to hyperosmolar stimulation of mast cells
Authors: M. Gulliksson, L. Palmberg, G. Nilsson, S. Ahlstedt, M. Kumlin
Journal: Allergy (2006)

Background: Mannitol‐induced bronchoconstriction in subjects with exercise‐induced asthma is associated with increased urinary excretion of 9 α , 11 β ‐PGF 2 , a metabolite of prostaglandin D 2 (PGD 2 ) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD 2 and leukotriene C 4 (LTC 4 ) after osmotic challenge with mannitol in vitro . Methods: Cord blood‐derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD 2 , LTC 4 and histamine contents with enzyme immunoassays. Results: Significant release of de novo synthesized eicosanoids, predominantly PGD 2 [12 (8.8, 14) pmol/10 6 cells; median (25th, 75th percentile) but also LTC 4 (0.1 (0.08, 0.15) pmol/10 6 cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD 2 and LTC 4 , following immunological stimulation. Conclusion: The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.
A CASE OF ANDROGYNOUS PSEUDOHERMAPHRODISM
Authors: Frederick Christopher
Journal: JAMA (1924)

S. S., a high school student, aged 17, was first brought to me for a fracture of the clavicle. In the course of treatment for this injury, the mother informed me that the child had never menstruated, and requested that I investigate the cause of this trouble and suggest treatment. Examination showed the hymen to be perforate and the vagina of normal size, but no uterus could be palpated. This finding was confirmed by Dr. H. O. Jones, who saw the patient in consultation. The external genitalia were somewhat smaller than normal, and the growth of hair was perhaps less than usual. The patient was well developed; the shoulders were somewhat angular, but the breasts were very large and well developed. The patient had a quiet voice, and gave the impression of a most refined and retiring girl. The mother told me that when the child was less than 2
Ethics and Human Experimentation
Authors: David J. Rothman
Journal: New England Journal of Medicine (1987)

TWENTY-ONE years ago, in June 1966, Henry Beecher, Dorr Professor of Research in Anesthesia at Harvard Medical School, published in these pages an analysis of "Ethics and Clinical Research" and thereby accelerated the movement that brought human experimentation under rigorous federal and institutional control.1 Although Beecher was not the first to direct attention to abuses in human experimentation, and the National Institutes of Health was already formulating stricter rules, his presentation of 22 examples of investigators who endangered "the health or the life of their subjects" without informing them of the risks or obtaining their permission was a critical element . . .
Growth on Sabouraud's agar of dermatophytes obtained by conventional scraping and by stripping with vinyl tape
Authors: E. A. KNUDSEN
Journal: British Journal of Dermatology (1974)

In a preliminary investigation it was demonstrated that dermatophytes may grow from stratum corneum strippings placed direct on Sabouraud's dextrose agar. In the current study the results of such culture from stratum corneum strippings were compared with those of culture by the conventional technique. Out of 930 fungal tests, growth was obtained by both methods in eighty‐two cases. In thirty‐one cases growth of dermatophytes was obtained solely by the conventional technique and in eight cases solely by the tape method. Six species of dermatophytes were represented in the culture experiments This significant difference between the number of positive cultures is due to the strip technique being in some cases less suited for collecting scales, as there are no signs that the vinyl tape inhibits fungal growth. The strip technique is easy and practical, but as it yields less than the conventional technique, it is not suitable as a routine procedure.
Benign Tumors of the Duodenum
Authors: Harvey E. Knoernschild
Journal: JAMA (1962)

CRUVEILHIER REPORTED the first case of a benign tumor involving the duodenum in 1835. This was regarded as an unique medical curiosity until Rokitansky, in 1861, reviewed several cases from his extensive postmortem dissections and wrote a treatise describing the basic pathology and clinical symptoms. Since that time, numerous case reports of benign duodenal lesions have appeared in the literature. In a monumental piece of work River, Silverstein and Tope reviewed 1,399 benign small intestinal tumors reported in the literature. Their study included 211 benign duodenal tumors.  Within a recent 4-week period, 3 patients were admitted to our hospital for surgical excision of benign duodenal lesions. A subsequent review of the hospital case records for the past eight years disclosed an additional 4 operated cases and 8 nonoperated cases. In the 8 nonoperated cases the diagnosis was made by the characteristic roentgenologic appearance and confirmed by a follow-up of 3
Polysialic Acid Glycomimetic Promotes Functional Recovery and Plasticity After Spinal Cord Injury in Mice
Authors: Ali Mehanna, Igor Jakovcevski, Ayşe Acar, Meifang Xiao, Gabriele Loers, Geneviève Rougon, Andrey Irintchev, Melitta Schachner
Journal: Molecular Therapy (2009)

Regeneration after injury of the central nervous system is poor due to the abundance of molecules inhibiting axonal growth. Here we pursued to promote regeneration after thoracic spinal cord injury in young adult C57BL/6J mice using peptides which functionally mimic polysialic acid (PSA) and human natural killer cell-1 (HNK-1) glycan, carbohydrate epitopes known to promote neurite outgrowth in vitro. Subdural infusions were performed with an osmotic pump, over 2 weeks. When applied immediately after injury, the PSA mimetic and the combination of PSA and HNK-1 mimetics, but not the HNK-1 mimetic alone, improved functional recovery as assessed by locomotor rating and video-based motion analysis over a 6-week observation period. Better outcome in PSA mimetic-treated mice was associated with higher, as compared with control mice, numbers of cholinergic and glutamatergic terminals and monaminergic axons in the lumbar spinal cord, and better axonal myelination proximal to the injury site. In contrast to immediate post-traumatic application, the PSA mimetic treatment was ineffective when initiated 3 weeks after spinal cord injury. Our data suggest that PSA mimetic peptides can be efficient therapeutic tools improving, by augmenting plasticity, functional recovery when applied during the acute phase of spinal cord injury.
Behavioral and Emotional Disturbances in the Offspring of Depressed Parents with Anger Attacks
Authors: Jonathan E. Alpert, Timothy Petersen, Pamela A. Roffi, George I. Papakostas, Rachel Freed, Megan M. Smith, Andrew R. Spector, Andrew A. Nierenberg, Jerrold F. Rosenbaum, Maurizio Fava
Journal: Psychotherapy and Psychosomatics (2003)

To examine the emotional and behavioral characteristics of the offspring of depressed parents with and without anger attacks.Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist - Parent Report Version (CBCL) for each of their birth children (n = 58, age range 6-17 years). Unpaired t tests were used to evaluate the CBCL scale score differences between children of parents with and children of parents without anger attacks. Baseline demographics and clinical differences between the two groups of parents were also evaluated.Parents with anger attacks had a significantly younger age of onset of MDD. Offspring of depressed parents with anger attacks were found to have significantly lower social and school competency scale scores and higher scores for delinquency, attention problems, and aggressive behavior. In addition, this group was found to have a significantly higher total T score (a global measure of psychopathology).There are some important differences between offspring of depressed parents with and without anger attacks. This finding may be important in identifying and formulating intervention strategies for childhood problems in the offspring of depressed parents.
Twenty-seven Cases of Syphilitic Aneurysm of the Thoracic Aorta and its Branches
Authors: J. Borrie, S. G. Griffin
Journal: Thorax (1950)

The purpose of this paper is to review the treatment of aortic aneurysms and to discuss a series of 27 cases.An aortic aneurysm in most instances is a progressive and ultimately fatal disease.Most body tissues are unable to withstand its steady encroachment.Pressure on the trachea or bronchus may produce obstructive and infective pul- monary lesions or even necrosis and perforation with sudden death.Natural cure may occur by clotting, especially in saccular aneurysms, but this is uncommon.Colt (1948) stated that 1,500 patients die of aneurysm each year in England and Wales, and that its frequency has not been lessened by arsenical drugs.Untreated patients with aneurysm have a poor expectation of life.Colt (1927) has shown that, at the age of 42 years, in a series of 37 cases, a quarter died four months from the time of the first symptom, half before seven months, another quarter before 16 months.Aneurysms of the transverse aorta are especially serious; out of 219 patients, one half died under 10 months and only a quarter lived more than 20 months.Blakemore (1945), who has studied aneurysms both from the points of view of pathology and haemodynamics, found that the blood, circulating under pres- sure through an unclotted saccular or fusiform aneurysm, created a total strain on the sac wall that varied with the square root of the surface area.Doubling the diameter of an aneurysm by growth increased the strain upon the sac by 100%.Thus, in rapidly growing aneurysms, there is a vicious circle of increased strain upon a sac of diminishing strength.On the other hand, he stated that once the contents of an aneurysm had clotted, the physical laws governing solids obtained, wherein the total strain is reduced from the aggregate pressure exerted on the entire sac wall to that exerted on the mouth of the aneurysm alone.As the nutrition and strength of the aneurysmal wall largely depend on collateral blood vessels from its neck, the more rapidly expanding aneurysms may outstrip their blood supply, with resulting areas of anaemic necrosis, and in certain situations rupture.HISTORICAL SURVEY WIRING There is no effective medical treatment for an established aneurysm.A patient suffering from this disease is doomed, unless the aneurysmal growth can be checked by clotting and organization of the contents.In 1864 this was first attempted on July 12,
Endothelial function is impaired and intina-media thickness of the common carotid arterial wall is increased in patients with β-thalassemia major
Authors: G. Hahalis, A. Kalogeropoulos, A. Chrysanthopoulou, E. Arvanitopoulou, A. Kourakli, A. Thomaidi, G. Terzis, C. Stathopoulos, D. Alexopoulos, A.S. Manolis
Journal: Journal of the American College of Cardiology (2002)
Hematopoietic differentiation activity of a recombinant human interleukin-6 (IL-6) isoform resulting from alternatively spliced deletion of the second exon
Authors: Daniel P. Kestler, Keith M. Goldstein, Sujata Agarwal, Joseph E. Fuhr, Richard Andrews, Robert E. Hall
Journal: American Journal of Hematology (1999)

We have previously identified and cloned an alternatively spliced form of human interleukin-6 mRNA lacking exon II, which encodes amino acid residues known to be important in gp130-mediated signal transduction pathways. We expressed and purified the recombinant protein (rIL6-alt) resulting from this alternatively spliced mRNA and now report the initial characterization of its biologic activities with comparison to full length IL6 (rIL6-full). rIL6-alt was found to have 104 to 105 fold less activity in proliferation assays with 7TD1 murine plasmacytoma cells and did not competitively inhibit the stimulatory activity of rIL6-full. In addition, like rIL6-full, rIL6-alt had antiproliferative activity toward M1 murine myeloblast cells and was 10–200-fold less active than rIL6-full. In contrast, in assays with human HL60 promyelocytic leukemia cells, rIL6-alt had greater antiproliferative activity than rIL6-full and more strongly upregulated phagocytosis as well as surface expression of the differentiation antigen CD11b. rIL6-full and rIL6-alt upregulated the level of lysozyme mRNA in HL60 cells approximately equally. These findings suggest that IL6-alt, which lacks amino acid residues encoded by the second exon of the gene, is not a natural inhibitor of IL6-full but may be relatively tissue specific and may play a role in modulation of hematopoietic cell growth and differentiation. Am. J. Hematol. 61:169–177, 1999. © 1999 Wiley-Liss, Inc.
SINGLE ISOTOPE-DOUBLE PHASE PARATHYROID SCINTIGRAPHY: UPTAKE PATTERNS OF TC-99M SESTAMIBI BY PARATHYROID ADENOMAS.
Authors: M. B. Tomas, G. Tronco, C. J. Palestro
Journal: Clinical Nuclear Medicine (1999)

Scientific Abstracts And Posters From The 44Th Annual Meeting Of The Southwestern Chapter Of The Society Of Nuclear Medicine, And From The 12Th Northeastern Regional Scientific Meeting Of The New England And New York Chapters Of The Society Of Nuclear Medicine
Erratum: Corrigendum: Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases
Authors: P M Reeves, B Bommarius, S Lebeis, S McNulty, J Christensen, A Swimm, A Chahroudi, R Chavan, M B Feinberg, D Veach, W Bornmann, M Sherman, D Kalman
Journal: Nature Medicine (2005)
Refractory Postpartum Anemia Due to Vitamin B_6 Deficiency
Authors: Allen J. Orehek
Journal: Annals of Internal Medicine (1997)

Letters15 May 1997Refractory Postpartum Anemia Due to Vitamin B6 DeficiencyAllen J. Orehek, MD and Chad D. Kollas, MDAllen J. Orehek, MDGeisinger Medical Center, Danville, PA 17822Search for more papers by this author and Chad D. Kollas, MDGeisinger Medical Center, Danville, PA 17822Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-10-199705150-00038 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:An 18-year-old woman presented with fever, chills, back pain, lightheadedness on standing, and weakness. Six weeks earlier, she had given birth to a full-term infant by spontaneous vaginal delivery complicated by uterine atony and anemia, presumed to have been caused by blood loss. She began receiving iron supplementation. Her medical history included only a spinal fusion for scoliosis. On presentation, the blood pressure was 133/66 mm Hg, body temperature was 39 °C, pulse was 140 beats/min, and respiratory rate was 32 breaths/min. The patient appeared weak and pale. Cardiac examination revealed tachycardia with a II/VI systolic murmur. ...References1. Bender DA. Novel functions of vitamin B6. Proc Nutr Soc. 1994; 53:625-30. Google Scholar2. Sauberlich HE. Beyond deficiencies: new views on the function and health effects of vitamins. Ann N Y Acad Sci. 1992; 669:125-9. Google Scholar3. Vitamin deficiencies in excess. In: Nelson WE, ed. Nelson's Textbook of Pediatrics. 15th ed. Philadelphia: WB Saunders; 1995:177. Google Scholar4. Jacobson MD, et al. Vitamin B6 pyridoxine therapy for carpal tunnel syndrome. Carpal and Cuboidal Tunnel Surgery. 1996; 12:253-8. Google Scholar5. Conningham FG, ed. Williams Obstetrics. 19th ed. Norwalk, CT: Appleton and Lange; 1993; 1174. Google Scholar Author, Article, and Disclosure InformationAffiliations: Geisinger Medical Center, Danville, PA 17822 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByVitamin B6 15 May 1997Volume 126, Issue 10Page: 834-835KeywordsAnemiaAttentionBloodHemoglobinPyridoxineReticulocytesSpinal fusionSystolic ejection murmurTachycardiaTemperature Issue Published: 15 May 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
A Clinical Lecture on Appendicitis and its Surgical Treatment: Delivered at the Western Infirmary, Glasgow
Authors: J. C. Renton
Journal: BMJ (1901)

You have already had an opportunity of seeing various forms of appendicitis and the operations for their relief.I will now try to make clear to you the points of importance tobe borne in mind in treating such cases.For clinical convenience, inflammatory affections of the appendix vermiformis may be divided into three forms: I. Catarrhal, with no distinct lump or swelling around the appendix.2. Appendicitis with a swelling which may entirely disap- pear, either by absorption or the formation of a local abscess, which may require an operation or may burst into one of the viscera, such as the bowel or bladder, or more seriously into the free abdominal cavity.3. Acute perforative appendicitis, which leads to general peritonitis and the formation of abscess in the general peritoneal cavity.
Are activity promotion interventions based on the transtheoretical model effective? A critical review
Authors: J Adams, M White
Journal: British Journal of Sports Medicine (2003)

The health benefits of physical activity are well documented yet 70% of adults remain sedentary. It has been suggested that inverventions based on the transtheoretical model of behaviour change (TTM) may be useful in promoting physical activity. Published work on the effectiveness of such inteventions is therefore critically reviewed. Although there is evidence that TTM based activity promotion interventions are effective in promoting activity adoption, initial results on longer term adherence are disappointing.