tbuckley/cabot-search huggingface dataset:
Role of Acid Ceramidase in Resistance to FasL: Therapeutic Approaches Based on Acid Ceramidase Inhibitors and FasL Gene Therapy
Authors: Saeed Elojeimy, Xiang Liu, John C Mckillop, Ahmed M El-Zawahry, David H Holman, Jonathan Y Cheng, William D Meacham, Ayman EM Mahdy, Antonio F Saad, Lorianne S Turner, Joseph Cheng, Terrence A Day, Jian-Yun Dong, Alicja Bielawska, Yusuf A Hannun, James Scott Norris
Journal: Molecular Therapy (2007)

Head and neck squamous cell cancers (HNSCC) are particularly aggressive and are resistant to many forms of treatment. Ceramide metabolism has been shown to play an important role in cancer progression and cancer resistance to therapy in many tumor models, including HNSCC. Here, we study the role of the ceramide-metabolizing enzyme acid ceramidase (AC) in therapeutic responses in HNSCC. First, we show that AC is over-expressed in 70% of head and neck squamous cell tumors compared with normal tissues, suggesting that this enzyme may play an important role in facilitating HNSCC growth. Next, comparison of three HNSCC cell lines with low, medium, and high levels of AC reveals an inverse correlation between the levels of AC and their response to exogenous C-6-ceramide. Furthermore, over-expression of AC in SCC-1 cells increased resistance to Fas-induced cell killing. Conversely, down-regulation of AC using specific AC small interfering RNA (siRNA) sensitized the SCC-1 cancer cell line to Fas-induced apoptosis. Finally, we show that the AC inhibitor LCL 204 can sensitize HNSCC cell lines to Fas-induced apoptosis both in vitro and in a xenograft model in vivo, suggesting that the combination of FasL gene therapy and LCL 204 may become a new treatment option for advanced-stage head and neck cancer. Head and neck squamous cell cancers (HNSCC) are particularly aggressive and are resistant to many forms of treatment. Ceramide metabolism has been shown to play an important role in cancer progression and cancer resistance to therapy in many tumor models, including HNSCC. Here, we study the role of the ceramide-metabolizing enzyme acid ceramidase (AC) in therapeutic responses in HNSCC. First, we show that AC is over-expressed in 70% of head and neck squamous cell tumors compared with normal tissues, suggesting that this enzyme may play an important role in facilitating HNSCC growth. Next, comparison of three HNSCC cell lines with low, medium, and high levels of AC reveals an inverse correlation between the levels of AC and their response to exogenous C-6-ceramide. Furthermore, over-expression of AC in SCC-1 cells increased resistance to Fas-induced cell killing. Conversely, down-regulation of AC using specific AC small interfering RNA (siRNA) sensitized the SCC-1 cancer cell line to Fas-induced apoptosis. Finally, we show that the AC inhibitor LCL 204 can sensitize HNSCC cell lines to Fas-induced apoptosis both in vitro and in a xenograft model in vivo, suggesting that the combination of FasL gene therapy and LCL 204 may become a new treatment option for advanced-stage head and neck cancer.
Cefoxitin, a New Semi-synthetic Cephamycin: An In-vitro and In-vivo Comparison with Cephalothin
Authors: J. Kosmidis, J. M. T. Hamilton-Miller, J. N. G. Gilchrist, D. W. Kerry, W. Brumfitt
Journal: BMJ (1973)

The activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indole-producing Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by β-lactamases produced by Gram-negative organisms. Against Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood levels. Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.
The Limits of State Laws to Protect Genetic Information
Authors: G J Annas
Journal: New England Journal of Medicine (2001)

During the 2000 presidential campaign, Al Gore characterized the DNA code as a secret code like that of the Nazis. In his words, “with the completion of the Human Genome, we are on the verge of cracking another enemy's secret code. When we intercept and decipher the coded messages that cancer sends from cell to cell, we will turn the tide, and win the war against cancer.”1 Gore was expanding the metaphor of the war on cancer, and commandeering the DNA code in the service of that metaphor. At about the same time, then president Bill Clinton called the DNA . . .
What's the Beef?-Reply
Authors: Burdette C. Breidenstein
Journal: JAMA (1985)

In Reply.—  I do not believe  are as easily misled as Liebman and Tolins suggest. The JAMA advertisement in question presents hard data on the amounts of dietary cholesterol provided by several foods. Dietary cholesterol has been the subject of extensive speculation in the medical and nutritional literature. It is  reasonable assumption  your readers are both interested in the data and capable of interpreting them accurately. Liebman and Tolins' concern  all but the most nutritionally aware physicians somehow will infer from the data presented in the ad that beef has miraculously been transformed into any food other than  which the ad describes is misplaced.  Furthermore, the letter from Liebman and Tolins shows clear bias and scientifically unsupportable use of data. Its authors state  a hefty 48% of the fat in beef is saturated but neglect to point out  32% of the fat in
Identification of marker genes including RUNX3 (AML2) that discriminate between different myeloproliferative neoplasms and normal individuals
Authors: C I Müller, Q T Luong, L-Y Shih, L C Jones, J C Desmond, N Kawamata, O Tcherniantchouk, Q Liu, K Ito, M Osato, Y Ito, A Tefferi, S de Vos, H P Koeffler
Journal: Leukemia (2008)
Substrate Overlap between Mrp4 and Abcg2/Bcrp Affects Purine Analogue Drug Cytotoxicity and Tissue Distribution
Authors: Kazumasa Takenaka, Jessica A. Morgan, George L. Scheffer, Masashi Adachi, Clinton F. Stewart, Daxi Sun, Markos Leggas, Karin F.K. Ejendal, Christine A. Hrycyna, John D. Schuetz
Journal: Cancer Research (2007)

Abstract The use of probe substrates and combinations of ATP-binding cassette (ABC) transporter knockout (KO) animals may facilitate the identification of common substrates between apparently unrelated ABC transporters. An unexpectedly low concentration of the purine nucleotide analogue, 9-(2-(phosphonomethoxy)ethyl)-adenine (PMEA), and up-regulation of Abcg2 in some tissues of the Mrp4 KO mouse prompted us to evaluate the possibility that Abcg2 might transport purine-derived drugs. Abcg2 transported and conferred resistance to PMEA. Moreover, a specific Abcg2 inhibitor, fumitremorgin C, both increased PMEA accumulation and reversed Abcg2-mediated PMEA resistance. We developed Mrp4 and Abcg2 double KO mice and used both single KOs of Abcg2 and Mrp4 mice to assess the role of these transporters in vivo. Abcg2 contributed to PMEA accumulation in a variety of tissues, but in some tissues, this contribution was only revealed by the concurrent absence of Mrp4. Abcg2 also transported and conferred resistance to additional purine analogues, such as the antineoplastic, 2-chloro-2′-deoxyadenosine (cladribine) and puromycin, a protein synthesis inhibitor that is often used as a dominant selectable marker. Purine analogues interact with ABCG2 by a site distinct from the prazosin binding site as shown by their inability to displace the substrate analogue and photoaffinity tag [125I]iodoarylazidoprazosin. These studies show that Abcg2, like Mrp4, transports and confers resistance to purine nucleoside analogues and suggest that these two transporters work in parallel to affect drug cytotoxicity and tissue distribution. This new knowledge will facilitate an understanding of how Abcg2 and Mrp4, separately and in combination, protect against purine analogue host toxicity as well as resistance to chemotherapy. [Cancer Res 2007;67(14):6965–72]
Right Lower Lobe Mass
Authors: Stanley P. Bohrer
Journal: JAMA (1963)

Dr. Stanley P. Bohrer: A 22-year-old professional prize fighter entered the emergency ward of the Massachusetts General Hospital with a history of sharp right upper quadrant pain that had continued for 36 hours. He denied recent trauma. Eight hours after its onset the pain began to radiate into his right chest and with deep inspiration radiated to his right shoulder. At this time severe hiccoughs developed as well as a low-grade fever. Prior to this illness he had been in good health. A chest x-ray film taken 7 years prior to this admission was reported as negative. His father died at age 54 of tuberculosis. On admission he was tachypneic, breathing 32 times per minute. His blood pressure and pulse were normal. His temperature was 101 F ( 38.33 C ). He had slight right upper quadrant tenderness. Initially, his chest was reported as clear. Later, a consultant reported some dullness at the right lung base. His breathing was very shallow and he complained of pain with
Neutrophil function after exposure to polychlorinated biphenyls in vitro.
Authors: P E Ganey, J E Sirois, M Denison, J P Robinson, R A Roth
Journal: Environmental Health Perspectives (1993)

Polychlorinated biphenyls (PCBs) are known to be immunotoxic, yet the effects on neutrophil (PMN) function are not well characterized. We incubated PMNs isolated from rat peritoneum with a mixture of PCB congeners, Aroclor 1242, in the absence or presence of either phorbol myristate acetate (PMA) to stimulate generation of superoxide anion (O2-) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) to induce degranulation (measured as release of beta-glucuronidase). Aroclor 1242 alone stimulated O2- production at a concentration of 10 micrograms/ml. Significant cytotoxicity was not observed under these conditions. This concentration of Aroclor 1242 also increased O2- generation in PMNs activated with 20 ng PMA/ml. In the presence of a concentration of PMA (2 ng/ml) that by itself did not stimulate production of O2-, 1 microgram Aroclor 1242/ml caused significant generation of O2-, indicating synergy between Aroclor 1242 and PMA. Aroclor 1242 caused release of beta-glucuronidase from quiescent PMNs; however, in PMNs stimulated with fMLP to undergo degranulation, Aroclor 1242 inhibited release of beta-glucuronidase. The effects of two PCB congeners, one that binds to the Ah receptor (3,3', 4,4'-tetrachlorobiphenyl) and one that has little affinity for this receptor (2,2', 4,4'-tetrachlorobiphenyl) were examined. 3,3', 4,4'-Tetrachlorobiphenyl had no effect on PMN function in vitro, whereas 2,2', 4,4'-tetrachlorobiphenyl had effects similar to those observed with Aroclor 1242. These results indicate that PCBs affect PMN function in vitro in a complex manner, stimulating or inhibiting function under different conditions. These effects are apparently not mediated through the Ah receptor.
Closing the chapter on Maharishi Ayur-Veda
Authors: D. Chopra
Journal: JAMA (1992)

To the Editor.  —With the October 2, 1991, publication of your attack against Maharishi Ayur-Veda, 1  JAMA's readers have been presented with two diametrically opposed views of our activities:   In the May 22/29, 1991, article co-authored by me, 2 Maharishi Ayur-Veda is portrayed as a serious attempt to bring a respected system of traditional Indian medicine to the West.  This effort is backed by credentialed physicians who wish to explore a viable health care alternative. No outlandish claims are made for the efficacy of Maharishi Ayur-Veda. We present sound scientific research to support our hope that promising new therapies are being uncovered.   In stark contrast, JAMA's subsequent attack portrays a cult that uses deceptive practices to further its dubious ends. I and my colleagues are made out to be quacks and unprincipled agents of a conspiracy to infiltrate prestigious journals with our superstitious nonsense. It is further alleged that our approach
Radiotherapy plus chemotherapy is best for breast cancer
Authors: J. Wise
Journal: BMJ (1997)

Women with breast cancer who are treated with adjuvant chemotherapy survive significantly longer if they also receive radiation treatment, according to the 15 year results from two prospective, randomised controlled trials.

The two trials from Denmark and Canada examined whether the addition of radiation treatment to the chest wall and regional lymph nodes increased survival in premenopausal women who underwent modified radical mastectomy and received adjuvant chemotherapy. The results of both trials are strongly positive. The Danish trial shows an overall survival of 54% at 10 years in the …
Access to Care and the Evolution of Corporate, for-Profit Medicine
Authors: Donald O. Nutter
Journal: New England Journal of Medicine (1984)

Access to health care was the centerpiece of federal health policy and legislation in the 1960s and 1970s. Government programs designed to improve access focused on health-manpower shortages and maldistribution, the development of public, rural, and urban ambulatory-care centers, and the health-insurance gap for the aged and the poor. The major defects in these efforts appear to have been a failure to consider a comprehensive approach to financing health care and a lack of long-range planning concerning the supply of and need for manpower. Consequently, in the 1980s the public and private sectors are preoccupied with cost containment and an . . .
Application of Polaroid Film for Bronchoscopic Photography
Authors: T. Okamoto, S. Horie, K. Shimada, M. Okita, H. Katsuki
Journal: Endoscopy (1974)

Polaroid films were applied to bronchoscopic photography. Pictures in color and black & white were taken by a Polaroid camera on the market attaching an adaptor to the bronchoscope. The fact that Polaroid films are quickly developed makes them valuable for recording and evaluating routine bronchoscopic examinations. Some pictures taken by Polaroid films are presented.
COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR PREDICTION OF PERCUTANEOUS CORONARY INTERVENTION IN CHRONIC TOTAL OCCLUSION: THE CT-RECTOR MULTICENTER REGISTRY
Authors: Maksymilian P. Opolski, Stephan Achenbach, Annika Schuhbaeck, Andreas Rolf, Johannes Rixe, Cezary Kepka, Adam Witkowski, Holger Nef, Helge Möllmann, Christian Hamm
Journal: Journal of the American College of Cardiology (2014)
Relationship of Blood Thromboxane-B2 (TxB2) With Lipid Peroxides and Effect of Vitamin E and Placebo Supplementation on TxB2 and Lipid Peroxide Levels in Type 1 Diabetic Patients
Authors: Sushil K Jain, K Stephan Krueger, Robert McVie, John J Jaramillo, Melissa Palmer, Tiney Smith
Journal: Diabetes Care (1998)

OBJECTIVE To study the effect of vitamin E supplementation on platelet hyperaggregability in type 1 diabetic patients. RESEARCH DESIGN AND METHODS Written informed consent according to the Institutional Review Board on Human Experimentation guidelines was obtained from diabetic patients (n = 29) and their age-matched normal siblings (n = 21) to participate in this study. Diabetic patients were supplemented with DL-α-tocopherol (vitamin E) capsule (orally, 100 IU/day) or placebo for 3 months in a double-blind clinical trial. Alternate diabetic patients were assigned to vitamin E or placebo during regular visits to the clinic. Fasting blood was collected from each diabetic patient before the start and after the vitamin E or placebo supplementation. Platelet aggregability was assessed by competitive enzyme-linked immunosorbent assay of the blood TxB2 (a stable thromboxane metabolite). Plasma vitamin E and MDA (malondialdehyde, a product of lipid peroxidation) was assessed by high-performance liquid chromatography. Data were analyzed statistically on 12 diabetic patients on vitamin E and 12 on placebo supplementation. RESULTS Diabetic patients (n = 29) had 62% higher (P &amp;lt; 0.05) levels of TxB2 and 15% higher levels (P &amp;lt; 0.05) of MDA in comparison to normal subjects (n = 21). Plasma TxB2 levels had a significant correlation with MDA levels (r = 0.45, P &amp;lt; 0.02) but not with the HbA1 (r = −0.08), glucose (r = −0.13), duration of diabetes (r = −0.04), or age (r = 0.12) of diabetic patients. Vitamin E supplementation lowered MDA levels by 30% (P &amp;lt; 0.04), TxB2 levels by 51% (P &amp;lt; 0.03), and triglyceride levels by 22% (P &amp;lt; 0.04) in diabetic patients. There were no differences in these parameters before versus after placebo supplementation. CONCLUSIONS The elevated blood level of TxB2 (hyperaggregability of platelets) is significantly related to the level of lipid peroxidation products (oxidative stress) in type 1 diabetic patients. Supplementation of modest doses of vitamin E (100 IU/day) significantly lowers blood TxB2 and lipid peroxidation products levels in type 1 diabetic patients.
Flaujeac trait. Deficiency of human plasma kininogen.
Authors: K D Wuepper, D R Miller, M J Lacombe
Journal: Journal of Clinical Investigation (1975)

Flaujeac trait plasma resembled Hageman trait or Fletcher trait, in that the intrinsic coagulation pathway, plasma fibinolytic pathway, kinin-forming system, permeability factor of dilution (PF/dil) phenomenon were abnormal. The defect in each assay was reconstituted by afactor separable from Hageman factor or Fletcher factor. This substance was an alpha-globulin with an approximate mol wt of 170,000. Flaujeac plasma did not release a kinin upon incubation with kallikrein and was deficient in total kininogen antigen. Antiserum to kininogen inhibited the activity of the factor in solution. Flaufeac factor was identified as a kininogen of high molecular weight (HMW-kininogen). The mean total kininogen antigen in four children of the proposita was 51% (range 34-62%) of normal. A functional coagulation assay of HMW-kininogen in the children was 34% (range 23-55%). The results were consistent with autosomal recessive inheritance. The plasma pathways of intrinsic coagulation, fibrinolysis, kinin formation, and PF/dil generation are dependent upon HMW-kininogen. We believe this is the first demonstration of biological function for a kininogen apart from its role as a substrate for kallikreins.
At the New York Academy of Medicine
Authors: Richard Bronson
Journal: Annals of Internal Medicine (2010)

Ad Libitum6 July 2010At the New York Academy of MedicineRichard Bronson, MDRichard Bronson, MDFrom Stony Brook, NY 11794.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-1-201007060-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For Vernon IngramFather of molecular medicine,mentor to me,you were to lectureon the hemoglobinopathies,and I traveled by subwayafter a Bellevue shift,on call every other night,to hear you speak; you who taught methe foundation of good science—knowing what came before,reporting with accuracy, thinkingwhat next could be done.The Hall packed with notables,I in my white coat and pantssat at the back.I heard your first words.Awakened by a janitorto an empty hall near midnight,I thought of the people next to mewho must have thought“Let him sleep,”smiling to themselves.Richard Bronson, MDStony Brook, NY 11794 Author, Article, and Disclosure InformationAffiliations: From Stony Brook, NY 11794.Current Author Address: Richard Bronson, MD, Department of Obstetrics and Gynecology, Stony Brook University Medical Center, HSC T9-080, Stony Brook, NY 11794. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 July 2010Volume 153, Issue 1Page: 68KeywordsHemoglobinopathiesObstetrics and gynecologySleep ePublished: 6 July 2010 Issue Published: 6 July 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Narrative Review: Hyperkyphosis in Older Persons
Authors: Deborah M. Kado
Journal: Annals of Internal Medicine (2007)

Hyperkyphosis is a widely recognized yet largely ignored condition. Although there are no uniform diagnostic criteria for hyperkyphosis, current studies estimate its prevalence among older adults at 20% to 40%. The causes and consequences of hyperkyphosis are not well understood. Some physicians think that fractures cause hyperkyphosis and that management strategies should focus solely on diagnosis and treatment for osteoporosis. Recent studies, however, demonstrate that many older adults who are most affected by hyperkyphosis do not have vertebral fractures. Hyperkyphosis may be independently associated with an increased risk for adverse health outcomes, including impaired pulmonary function, decreased physical function capabilities, and future fractures. With the growing older population, we now need research that leads to a deeper understanding of the causes, consequences, and treatment of this common condition.
Abstract P4-01-07: Endoplasmic Reticulum-Associated Calcium Regulates Resistance of the Anti-Apoptotic Protein Bcl-2 to Taxol-Induced Apoptosis in Breast Cancer Cells
Authors: Z Pan, L Gollahon
Journal: Cancer Research (2010)

Abstract Background: The unique anti-apoptotic function of Bcl-2 results in cellular resistance to many chemotherapeutic agents used in solid tumor treatments. However, there is a controversy regarding the relationship between Bcl-2 resistance and the mechanism of action for Taxol, an anticancer agent commonly used in breast cancer treatment. Although previous studies showed both Bcl-2 and Taxol may have effects on calcium homeostasis independently, no studies have addressed whether calcium is the keystone in the relationship between Bcl-2 resistance and Taxol action. Objective: Since most internal calcium is stored in the endoplasmic reticulum (ER), this study focused on the role of ER calcium changes in Bcl-2-activated resistance to Taxol-induced apoptosis. The ER calcium channel IP3R and its relationship with Bcl-2 and Taxol were investigated in order to clarify the mechanism underlying calcium regulation. Methods and Materials: For this study, MDA-MB-468, a Bcl-2 negative breast carcinoma cell line, its Bcl-2 stable transfectant and MCF-7, a Bcl-2 positive breast carcinoma cell line were used. The dynamic calcium changes induced by Taxol in these cells were determined by measuring free cytosolic calcium fluctuations using Fluo4-AM and ER calcium changes by the calcium cameleon, D1ER. Taxol-induced apoptosis was measured using the Annexin V-FITC assay. The calcium interfering agents BAPTA-AM and 2-APB were applied to evaluate whether Taxol-induced calcium changes were related to this apoptotic event. Western blot was used to detect changes induced by Taxol treatment in Bcl-2 and IP3R protein levels. Results: Taxol induced a rapid ER calcium release followed by a gradual ER calcium depletion in both Bcl-2 positive and negative cell lines, indicating that ER calcium store provides a direct target for Taxol, independently of Bcl-2 expression. Interfering with these calcium changes inhibited the Taxol-induced apoptosis, suggesting ER calcium release promotes Taxol-induced apoptosis. Our results also showed that Bcl-2 inhibited the basal ER calcium release. Taxol stimulated ER calcium release and thus attenuated Bcl-2-initiated resistance to apoptosis. Relevance: This research addressed the question of whether ER calcium changes play a critical or marginal role in mediating resistance of Bcl-2 to Taxol-induced apoptosis. Elucidating the role of calcium in this process will not only help to clarify the mechanism of drug resistance associated with Bcl-2, but also aid in more effective application of Taxol in breast cancer treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-01-07.