tbuckley/cabot-search huggingface dataset:
Synergistic Suppression of Microtubule Dynamics by Discodermolide and Paclitaxel in Non-Small Cell Lung Carcinoma Cells
Authors: Stéphane Honore, Kathy Kamath, Diane Braguer, Susan Band Horwitz, Leslie Wilson, Claudette Briand, Mary Ann Jordan
Journal: Cancer Research (2004)

Abstract Discodermolide is a new microtubule-targeted antimitotic drug in Phase I clinical trials that, like paclitaxel, stabilizes microtubule dynamics and enhances microtubule polymer mass in vitro and in cells. Despite their apparently similar binding sites on microtubules, discodermolide acts synergistically with paclitaxel to inhibit proliferation of A549 human lung cancer cells (L. Martello et al., Clin. Cancer Res., 6: 1978–1987, 2000). To understand their synergy, we examined the effects of the two drugs singly and in combination in A549 cells and found that, surprisingly, their antiproliferative synergy is related to their ability to synergistically inhibit microtubule dynamic instability and mitosis. The combination of discodermolide and paclitaxel at their antiproliferative IC50s (7 nm for discodermolide and 2 nm for paclitaxel) altered all of the parameters of dynamic instability synergistically except the time-based rescue frequency. For example, together the drugs inhibited overall microtubule dynamicity by 71%, but each drug individually inhibited dynamicity by only 24%, giving a combination index (CI) of 0.23. Discodermolide and paclitaxel also synergistically blocked cell cycle progression at G2-M (41, 9.6, and 16% for both drugs together, for discodermolide alone, and for paclitaxel alone, respectively; CI = 0.59), and they synergistically enhanced apoptosis (CI = 0.85). Microtubules are unique receptors for drugs. The results suggest that ligands that bind to large numbers of binding sites on an individual microtubule can interact in a poorly understood manner to synergistically suppress microtubule dynamic instability and inhibit both mitosis and cell proliferation, with important consequences for combination clinical therapy with microtubule-targeted drugs.
Growing Plaque on the Foot
Authors: Bryan E. Anderson, Elizabeth Billingsley
Journal: New England Journal of Medicine (2005)

A 64-year-old woman presented to our clinic with a 20-year history of a slowly growing plaque on her left foot. This lesion had been pared and a biopsy reportedly performed in the past, but the patient's concomitant mental illness had made her very reluctant to undergo treatment. She ultimately sought treatment because of increasing pain and difficulty walking, as well as drainage and odor. On examination, a large, hyperkeratotic plaque with multiple horny projections was found. The central portion was friable, and after some debridement, an underlying abscess was discovered. An excisional biopsy revealed verrucous carcinoma. A radiograph revealed no . . .
Familial Hereditary Hemorrhagic Telangiectasia in the Negro
Authors: Steven O. Schwartz, Berthe E. Armstrong
Journal: New England Journal of Medicine (1948)

BECAUSE familial hereditary hemorrhagic telangiectasia in the Negro has not been previously described in the literature, it was believed that the following case deserved mention.A 48-year-old Negress first entered the Cook County Hospital on October 31, 1945, because of a nosebleed lasting 8 hours. She had had frequent epistaxes all her life, and 2 weeks before admission had noted vertigo, syncope and edema of the face and feet. The nosebleeds had occurred at intervals "as long as she could remember" but had been inconsequential until the menopause, at the age of 42. During the next 4 years they increased . . .
Spirochaetosis Icterohaemorrhagica in Norfolk
Authors: F. W. Burton-Fanning, A. J. Cleveland
Journal: BMJ (1926)

DURING thle last fifteeni moniths we lave seen four cases in Norfolk presenlting tlle clinical featur es cf spirocliaetosis icteirohaemorrh liagica.Tlhough the actual presence of tile spiroclhaete was olnly p)roved in one, tile symptoms anid course of the disease welre so similar and distinctive in all that we tliink we iav assuime the idlenltity of their affection.The organism is acknow-ledged to be elusi7e, and we liad 11o opportuniity fol aniimal inoculation.A closely studied series of eighteen cases in East Lotllian has been described by G. L. Gulland and G. Buchanan,' but in En-glanid wYe find the record of only one case, by Dr. Plhilip Manson-Balr.2The cardinal symptomls of the disease are so few and so constant as nlanifested by our patients that a br ief account of each will be given. CASE T.A man living in the outskirts of North Walsham, wlho had retired and occupied himself ill his gardeni, was in good healtl until December 9th, 1924.Oii that day he felt exhausted and uiiable to eat.For the next few days he remained ill bed oil accounit of this sense of prostrationi.
Malaria: an update on treatment of adults in non-endemic countries
Authors: Christopher J M Whitty, David Lalloo, Andrew Ustianowski
Journal: BMJ (2006)

<i>Every year people die from malaria in Britain and other industrialised countries. Most of these deaths are avoidable: they occur because a patient or doctor has underestimated the severity of the disease or has not considered the diagnosis early enough. This article provides the essential facts on treating malaria in adults in a non-endemic setting and is based on the best available evidence</i>
Changes in the biophysical properties and ultrastructure of lungs, and intrapulmonary fibrin deposition in experimental acute pancreatitis.
Authors: A R Berry, G C Davies, A M Millar, T V Taylor
Journal: Gut (1983)

Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.
Medical Device Bill
Authors: Mike Mitka
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Good Teacher
Authors: Jeffrey M. Drazen
Journal: New England Journal of Medicine (2006)

Earlier this year, I learned that my high school chemistry teacher had died. This was not surprising, since he had been my teacher in 1961. What was rather astounding was the outpouring of appreciation from his former students that followed. All of us mourned the passing of a man who had motivated us in a way that no previous instructor had been able to do, but each of us had thought that we alone had been so imprinted. This self-described “simple Kansas farmer” somehow knew how to leave a mark on his students for the rest of their lives.I . . .
Hematological Malignancies in Patients and Their Pets
Authors: Michael V. Viola
Journal: JAMA (1968)

Hematological malignancies are among the most commonly occurring neoplasms of domestic animals. The viral cause of lymphosarcoma in birds and cats is established and is suspected in a number of other species. Six patients with various hematological malignancies owned pets in which neoplasms developed. Five of the pets had lymphosarcoma and one had multiple myeloma. Because of the frequency of these malignancies in humans and lower animals it is most probable that the neoplasms co-occurred in patient and pet because of chance factors. Whether this is an epidemiologically significant relationship remains to be determined.
The Expression of Insulin-Like Growth Factor-1 Receptor (IGF-1R) in Early Breast Cancer.
Authors: M. Spears, C. Cunningham, J. Thomas, G. Kerr, W. Jack, F. Campbell, L. McKay, I. Kunkler, D. Cameron, U. Chetty, J. Bartlett
Journal: Cancer Research (2009)

Abstract Background: The insulin-like growth factor-1 receptor (IGF-1R) is expressed in normal breast epithelial cells and breast carcinomas. A number of studies have examined the over-expression of IGF-1R in breast cancer with the range of between 39% to 93%. However, many of these studies were carried out using ELISAs, radioimmunoassay with small patient cohorts. Phosphorylation of IGF-1R results in the activation of the MAPK and PI3K/Akt pathway. Activation of the PI3K/Akt pathway under the influence of IGF-1R plays an important role in maintaining the proliferation of breast cancer cells that are resistant to gefitnib, trastuzumab or chemoradiotherapy in vitro and in vivo. In the present study, we examined the expression of IGF-1R in early breast cancer and investigated the clinicopathological implications using immunohistochemistry and FISH.Methods: TMAs from a consecutive series (1981-98) of 1,812 women managed by wide local excision and postoperative radiotherapy (45Gy in 20-25 fractions) were collected following appropriate ethical review. Of 1686 cases stained, 198 received no adjuvant hormonal or chemotherapy, 1106 received tamoxifen only as adjuvant therapy and 144 received a combination of hormonal and chemotherapy. Median age at diagnosis was 56, 72% were post-menopausal, 23.9% node positive, median size was 1.5 cm. Samples were stained, using triplicate 0.6mm2 TMA cores for IGF-1R.Results: FISH for IGF1R gene amplification was successful in 343/408 cases (84%). Only 7 cases of IGF1R amplification were observed (2%). IGF1R expression was successfully evaluated in 1597 of 1686 (94.7%) cases. High levels of IGF-1R expression was weakly associated with tumour ER-a (correlation coefficient, 0.108; p=2.2 x 10-5) and PgR levels (correlation coefficient 0.162; p=1.86x10-10) and inversely correlated with EGFR expression (correlation coefficient -0.189; p=6.33x10-6). No association was noted between IGF1R expression and other molecular or clinical markers, such as tumour size. There was a trend for over-expression of IGF-1R to link with increased distant relapse free survival, particularly in ER positive breast cancers. This trend is time dependent, such that no difference in outcome is observed at 15 years.Conclusions: We have demonstrated in a large cohort of patients that IGF-1R gene amplification is a rare event, and over-expression is weakly associated with good prognostic features (ERa and PgR, lack of EGFR and better outcome). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2128.
Increased arterial expression of a glycosylated haptoglobin isoform after balloon dilation
Authors: M Smeets
Journal: Cardiovascular Research (2003)

Haptoglobin is a novel cell migration factor that is expressed in arteries after sustained flow changes and involved in arterial restructuring. Arterial restructuring is the major determinant of arterial shrinkage after balloon dilation. Although the function of extrahepatic haptoglobin expression is not yet understood, local haptoglobin expression may provide the tissue with functionally different haptoglobin due to post-translational modifications. We hypothesized that haptoglobin expression is increased during arterial restructuring after balloon dilation and compared glycosylation patterns between arterial and liver haptoglobin.Arterial haptoglobin expression was studied in rabbits at 0, 2, 7, 14 and 28 days after balloon dilation (n=36) using real-time polymerase chain reaction, Western blotting and in situ hybridization. Two-dimensional gel electrophoresis and lectin affinity blotting were used to identify liver and arterial haptoglobin glycoforms.Arterial haptoglobin mRNA (5.7-fold, P=0.01) and protein levels (1.4-fold, P=0.01) were increased after balloon dilation whereas liver haptoglobin expression remained constant. Haptoglobin was expressed in the adventitia of balloon dilated rabbit arteries, which was confirmed in human atherosclerotic arteries. Comparison between liver and arterial haptoglobin demonstrated the expression of artery-specific haptoglobin glycoforms.This study demonstrates that arterial haptoglobin expression is increased early after balloon dilation whereas liver haptoglobin expression does not change. Furthermore, arterial haptoglobin consists of an unique set of glycoforms compared to haptoglobin produced in the liver.
Genetic defects in PRC2 components other than EZH2 are not common in myeloid malignancies
Authors: Leonie I. Kroeze, Gorica Nikoloski, Pedro da Silva-Coelho, Patricia van Hoogen, Ellen Stevens-Linders, Roland P. Kuiper, Susanne Schnittger, Torsten Haferlach, Heike L. Pahl, Bert A. van der Reijden, Joop H. Jansen
Journal: Blood (2012)
D5-01: Prognostic significance of molecular markers and clinical factors in stage ib non-small cell lung cancer (NSCLC): a laboratory companion study to CALGB 9633
Authors: Stephen L. Graziano, Lin Gu, Xiaofei F. Wang, Arthur H. Tatum, Robin T. Vollmer, Gary M. Strauss, Robert A. Kratzke, Mark R. Green, Everett E. Vokes
Journal: Journal of Thoracic Oncology (2007)
Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome.
Authors: K Ladefoged, K C Christensen, J Hegnhoj, S Jarnum
Journal: Gut (1989)

The effect of a long acting somatostatin analogue SMS 201-995 on stomal effluents in patients with severe short bowel syndrome was investigated in a double blind placebo controlled balance study. Six patients, five with Crohn9s disease and one with radiation enteropathy were studied. Five patients had a jejunostomy and one an ileostomy. The patients had a normal food intake, but because of severe malabsorption had received home parenteral nutrition for several years. Faecal mass was reduced (p less than 0.005) and intestinal net sodium absorption was increased (p less than 0.005) by intravenous infusion of SMS 25 micrograms/h. Net absorption of potassium, calcium, magnesium phosphate, zinc, nitrogen and fat was not influenced. Subcutaneous injections of 50 micrograms SMS every 12 hours had a similar effect on net intestinal absorption of sodium and water. Four patients continued with a five to six months open follow up study when subcutaneous SMS in the same dose was administered by the patients at home. The effect on faecal sodium loss persisted, but in one patient faecal mass gradually increased and finally exceeded pretreatment values. SMS may decrease net absorption of water and sodium following reduced secretion of digestive juices rather than by increasing absorptive capacity. SMS may be useful as an antidiarrhoeal drug in patients with high output jejuno- or ileostomies, but in patients who need permanent parenteral nutrition the effect is too small to significantly alter management.
Sublingual Pyramidal Lobe Complications of Subtotal Thyroidectomy for Graves?? Disease
Authors: JOSHUA L. STERNBERG
Journal: Clinical Nuclear Medicine (1986)

A potential complication of subtotal thyroidectomy where a large pyramidal lobe is present is described. The pyramidal lobe normally is immobilized inferiorly by its attachment to the thyroidal isthmus. When the isthmus is removed and the pyramidal lobe is left in situ during subtotal thyroidectomy its superior attachments will allow the pyramidal lobe to become situated sublingually. This may produce gagging and nausea. To avoid the complication, it is recommended that the pyramidal lobe be removed during subtotal thyroidectomy. If the patient also is thyrotoxic, I-131 can be used to treat this complication successfully.
Effect of Hematocrit on Venous Return
Authors: ARTHUR C. GUYTON, TRAVIS Q. RICHARDSON
Journal: Circulation Research (1961)

In 18 dogs, the major factors besides blood hematocrit that are known to affect venous return were exactly controlled, while the hematocrit itself was varied from 9.5 up to 65. In general, the changes in venous return in these experiments were approximately the reciprocal of the changes in blood viscosity, as estimated from standard blood viscosity curves. An interesting sidelight of these studies was the fact that the minute volume of red blood cells transported by the arterial blood to the tissues, as calculated by multiplying the hematocrit times the venous return, reached a maximum at a hematocrit of 40. The minute volume of red blood cells fell drastically in anemia because of decreased hematocrit and in polycythemia because of greatly reduced venous return.
Deposition of eosinophil-granule major basic protein and expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the mucosa of the small intestine in infants with cow’s milk–sensitive enteropathy
Authors: Hai Lee Chung, Jin Bok Hwang, Young Dae Kwon, Min Ho Park, Won Jeong Shin, Jae Bok Park
Journal: Journal of Allergy and Clinical Immunology (1999)
Abstract 4002: Epigenetic control of a checkpoint for miRNA tolerance
Authors: Qunfang Li, Michael A. Tainsky
Journal: Cancer Research (2011)

Abstract The interferon (IFN) pathway controls the cellular response to viral infection and double-stranded RNA. We have found that this pathway provides a novel checkpoint for enhanced expression of miRNAs. The IFN pathway is abrogated in fibroblasts from Li-Fraumeni Syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Interferon stimulated genes (ISGs) were down-regulated by epigenetic silencing during immortalization and some of these same ISGs were activated by replicative senescence. Bisulfite sequencing of the promoter regions of IFN-regulatory transcription factors (IRF5 and IRF7) revealed that IRF7 but not IRF5 was epigenetically silenced by methylation of CpG islands in immortal LFS cells. The re-activation of ISGs by those transcription factors is sufficient to inhibit cell proliferation and induce a senescence-related phenotype in immortal LFS cells. Similar epigenetic silencing of IRF7 also results in disruption of IFN pathway in ∼30% lung cancer cells and primary tissues. Examination of innate immunity status in normal bronchial epithelial cell line Beas2B, its ras transformed derivative BVK cells and tumor-generating clones reveals increasing loss of functional IFN pathway as cells become more cancerous. Furthermore, microarray profiling of differentially expressed microRNAs (miRNAs) in LFS cell lines revealed most miRNAs were up-regulated in IFN-pathway-defective MDAH087-10 fibroblasts compared to MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of ISGs in MDAH087-N cells resulting in significant cell death and reduced cell growth. In addition, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to altered activation of the IFN pathway. Dicer-overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicer transfected MDAH087-10 cells. The higher miRNA tolerance in immortal LFS fibroblasts with a disrupted IFN pathway indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA up-regulation to occur in early carcinogenesis. This IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation by epigenetic silencing leads to cellular immortalization and early events in tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4002. doi:10.1158/1538-7445.AM2011-4002
Genes can't be patented, rules Supreme Court
Authors: M. McCarthy
Journal: BMJ (2013)

In a unanimous decision the US Supreme Court ruled on 13 June that naturally occurring DNA segments cannot be patented because they are products of nature and not an act of invention.

For the past 30 years it has been standard practice for the US Patent Office to issue patents on human genes. The decision would seem to overturn that practice.

In the same decision, however, the Supreme Court found that another important tool of biotechnology, complementary DNA, could be patented because these molecules are not naturally occurring.

The case involved a challenge to the patent …
Natural killer T cell dysfunction in CD39-null mice protects against concanavalin A-induced hepatitis
Authors: Guido Beldi, Yan Wu, Yara Banz, Michael Nowak, Lindsay Miller, Keiichi Enjyoji, Arvand Haschemi, Gennady G. Yegutkin, Daniel Candinas, Mark Exley, Simon C. Robson
Journal: Hepatology (2008)

Concanavalin A (Con A)-induced injury is an established natural killer T (NKT) cell-mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A-stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses. Levels of extracellular nucleotides are in turn closely regulated by ectonucleotidases, such as CD39/NTPDase1. Effects of extracellular nucleotides and CD39 on NKT cell activation and upon hepatic inflammation have been largely unexplored to date. Here, we show that NKT cells express both CD39 and CD73/ecto-5'-nucleotidase and can therefore generate adenosine from extracellular nucleotides, whereas natural killer cells do not express CD73. In vivo, mice null for CD39 are protected from Con A-induced liver injury and show substantively lower serum levels of interleukin-4 and interferon-gamma when compared with matched wild-type mice. Numbers of hepatic NKT cells are significantly decreased in CD39 null mice after Con A administration. Hepatic NKT cells express most P2X and P2Y receptors; exceptions include P2X3 and P2Y11. Heightened levels of apoptosis of CD39 null NKT cells in vivo and in vitro appear to be driven by unimpeded activation of the P2X7 receptor.CD39 and CD73 are novel phenotypic markers of NKT cells. In turn, CD39 expression [corrected] modulates nucleotide-mediated cytokine production by, and limits apoptosis of, hepatic NKT cells. Deletion of CD39 is protective in [corrected] Con A-induced hepatitis. This study illustrates a [corrected] role for purinergic signaling in NKT-mediated mechanisms that result in liver immune injury.