tbuckley/cabot-search huggingface dataset:
Effects of GLIADEL® wafer initial molecular weight on the erosion of wafer and release of BCNU
Authors: Wenbin Dang, Todd Daviau, Peter Ying, Yong Zhao, David Nowotnik, Charles S Clow, Betty Tyler, Henry Brem
Journal: Journal of Controlled Release (1996)

The GLIADEL® wafer is a polyanhydride implant used in the treatment of malignant glioma, in which the anticancer agent carmustine (BCNU) is incorporated into a copolymer matrix consisting of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20 to 80 molar ratio (p(CPP:SA, 20:80)). It is crucial to determine the relationship between the wafer's initial molecular weight and the erosion rate of polymer matrix and the subsequent release rate of drug substance BCNU. This study focuses on the effect of the initial molecular weight of GLIADEL® on polymer erosion and BCNU release from the polymer matrix. Wafer erosion in vitro was characterized by weight loss, molecular weight change and the appearance of water soluble CPP and SA in the incubation medium at 37°C. Wafer erosion and BCNU release were also investigated in the brains of normal rats. It was found that both the in vitro and in vivo erosion of wafer is independent of its initial molecular weight, which in this study ranged from 20 000–110 000 Da. The average molecular weight of the wafer was reduced to less than 10 000 Da after 10 h of incubation in phosphate buffered saline (37°C, pH 7.4) or after implantation in the brains of normal rats, despite the differences in initial wafer molecular weight. Furthermore, the release of carmustine (BCNU) from GLIADEL® is a combination of the diffusion of drug substance and the erosion of polymer matrix. The release rate of BCNU is also independent of initial wafer molecular weight.
A comparative study on ischaemia- or anoxia-induced impairment of myocytic structure and cardiac function in the isolated, isovolumicly-contracting, perfused rat heart
Authors: A VAN DER LAARSE, J C ALTONA, A C M ZOET, P OEMRAWSINGH, P R M VAN DIJKMAN
Journal: Cardiovascular Research (1984)

Impairment of contractile function and extent of release of several intracellular marker enzymes and DNA were studied in isolated perfused rat hearts after low-flow (0.16 ml . min-1) ischaemia followed by 2 h of reperfusion and after anoxia followed by 2 h of reoxygenation. After varying periods of ischaemia or anoxia, the hearts were analysed for cytoplasmic, lysosomal and mitochondrial enzymes, for nuclear DNA and for increase in heart weight (oedema formation). Recovery of contractile function, weight increase and release of lactate dehydrogenase (LDH), a cytoplasmic enzyme, were measured as a function of duration of ischaemia or anoxia. Myocardial enzyme activities and DNA content after varying periods of ischaemia or anoxia were compared with myocardial LDH activity. The study demonstrates that the ultimate extent of enzyme depletion after ischaemia + reperfusion differs significantly from that after anoxia + reoxygenation in respect of mitochondrial enzymes. For mitochondrial aspartate aminotransferase and monoamine oxidase ultimate depletion is 64 +/- 8% and 114 +/- 22%, respectively, for hearts after ischaemia + reperfusion, and 7 +/- 8% and 58 +/- 11%, respectively, for hearts after anoxia + reoxygenation. It is concluded that mitochondrial damage, as reflected by mitochondrial enzyme release from the heart, is less marked after anoxia + reoxygenation than after ischaemia + reperfusion at corresponding extent of LDH depletion.
Mixed chimerism and tolerance without whole body irradiation in a large animal model
Authors: Yasushi Fuchimoto, Christene A. Huang, Kazuhiko Yamada, Akira Shimizu, Hiroshi Kitamura, R.B. Colvin, Vincent Ferrara, Michael C. Murphy, Megan Sykes, Mary White-Scharf, David M. Neville, David H. Sachs
Journal: Journal of Clinical Investigation (2000)

Mixed hematopoietic chimerism may provide a treatment for patients with nonmalignant hematologic diseases, and may tolerize patients to organ allografts without requiring chronic immunosuppression. However, the toxicity of the usual conditioning regimens has limited the clinical applicability of this approach. These regimens generally include some level of whole body irradiation (WBI), which is thought to facilitate engraftment either by making room for donor hematopoietic stem cells or by providing sufficient host immunosuppression to enable donor cells to engraft. Here, we have established mixed chimerism across both minor and major histocompatibility barriers in swine, by using high doses of peripheral blood stem cells in the absence of WBI. After mixed chimerism was established, swine leukocyte antigen–matched (SLA-matched) donor skin grafts were tolerated and maintained for a prolonged period, whereas third-party SLA-matched skin was rejected promptly. Donor-matched kidney allografts were also accepted without additional immunosuppression. Because of its low toxicity, this approach has potential for a wide range of clinical applications. Our data may indicate that niches for engrafting stem cells are filled by mass action and that WBI, which serves to empty some of these niches, can be omitted if the donor inoculum is sufficiently large and if adequate host T-cell depletion is achieved before transplant.
Beyond health care
Authors: K. Judge
Journal: BMJ (1994)

The aims of health policy ought not to be contentious. Topping the list should be a commitment to improve the length and quality of life of everyone and to minimise avoidable differences in health status among social groups. The corollaries of such goals include improving our understanding of the determinants of health and intervening in public policy to deliver the required outcomes. Unfortunately, no evidence exists that any political party in Britain has grasped the extent to which thinking must change. Debates about the financing, governance, and structure of the NHS remain as dominant as they are largely unconstructive. What is needed now is a radical change of direction away from tinkering with the organisation of health care towards developing new approaches to health policy.

The importance of this proposition is illustrated in a new book produced under the auspices of …
A Genetic Progression Model of BrafV600E-Induced Intestinal Tumorigenesis Reveals Targets for Therapeutic Intervention
Authors: Roland Rad, Juan Cadiñanos, Lena Rad, Ignacio Varela, Alexander Strong, Lydia Kriegl, Fernando Constantino-Casas, Stefan Eser, Maren Hieber, Barbara Seidler, Stacey Price, Mario F. Fraga, Vincenzo Calvanese, Gary Hoffman, Hannes Ponstingl, Günter Schneider, Kosuke Yusa, Carolyn Grove, Roland M. Schmid, Wei Wang, George Vassiliou, Thomas Kirchner, Ultan McDermott, Pentao Liu, Dieter Saur, Allan Bradley
Journal: Cancer Cell (2013)
[499] NOVEL 4-AZIDO-2-DEOXY-NUCLEOSIDE ANALOGS ARE POTENT INHIBITORS OF NS5B-DEPENDENT HCV REPLICATION
Authors: D.B. Smith, H. Ma, S. Le Pogam, V. Leveque, C. Brown, N.G. Johansson, G. Kalayanov, S. Eriksson, E. Usova, C. Sund, A. Winqvist, T. Maltseva, M. Smith, W.R. Jiang, N. Cammack, J.A. Martin, I. Najera, K. Klumpp
Journal: Journal of Hepatology (2007)
ASSESSMENT OF THE LEFT ATRIAL SUBSTRATE IN LONE ATRIAL FIBRILLATION: IMPLICATIONS FOR STAGING OF ATRIAL FIBRILLATION
Authors: Nathan Burgon, Troy J. Badger, Nazem W. Akoum, Gaston Vergara, Lori McMullan, Yaw A. Adjei-Poku, Thomas S. Haslam, Jeremy Fotheringham, Eugene G. Kholmovski, Rob S. MacLeod, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2010)
Hedgehog Signaling Drives Cellular Survival in Human Colon Carcinoma Cells
Authors: Tapati Mazumdar, Jennifer DeVecchio, Ting Shi, Janay Jones, Akwasi Agyeman, Janet A. Houghton
Journal: Cancer Research (2010)

Aberrant activation of Hedgehog (HH) signaling is implicated in many human cancers. Classical HH signaling is characterized by Smoothened (Smo)-dependent activation of Gli1 and Gli2, which transcriptionally regulate target genes. A small molecule inhibitor of Gli1 and Gli2, GANT61, was used to block HH signaling in human colon carcinoma cell lines that express HH signaling components. GANT61 administration induced robust cytotoxicity in 5 of 6 cell lines and moderate cytotoxicity in the remaining 1 cell line. In comparison, the classical Smo inhibitor, cyclopamine, induced modest cytotoxicity. Further, GANT61 treatment abolished the clonogenicity of all six human colon carcinoma cell lines. Analysis of the molecular mechanisms of GANT61-induced cytotoxicity in HT29 cells showed increased Fas expression and decreased expression of PDGFRα, which also regulates Fas. Furthermore, DR5 expression was increased whereas Bcl-2 (direct target of Gli2) was downregulated following GANT61 treatment. Suppression of Gli1 by shRNA mimicked the changes in gene expression observed in GANT61-treated cells. Overexpression of dominant-negative FADD (to abrogate Fas/DR5-mediated death receptor signaling) and/or Bcl-2 (to block mitochondria-mediated apoptosis) partially rescued GANT61-induced cytotoxicity in HT29 cells. Thus, activated GLI genes repress DR5 and Fas expressions while upregulating Bcl-2 and PDGFRα expressions to inhibit Fas and facilitate cell survival. Collectively, these results highlight the importance of Gli activation downstream of Smo as a therapeutic target in models of human colon carcinoma.
Nocturnal Angina Pectoris
Authors: Fritz Brunn
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The answer by George Griffith, MD, to the question, "Nocturnal Angina Pectoris" (<i>JAMA</i><b>197</b>:519, 1966), appears excellent as far as it concerns the prevention of such attacks through avoidance of food and fluid intake in the evening and positioning of the bed during the night. As supportive measures may be added digitalization, salt-free diet, and diuretics. By avoiding pulmonary congestion this regime may improve oxygenation of the myocardium. In Dr. Griffith's contribution I missed reference to therapy during an actual attack of nocturnal angina pectoris. It was our practice to let the patient first sit up on the edge of his bed. Then he was directed to take a tablet of glyceryl trinitrate sublingually, to stand up, and even to take a few steps in his bedroom. This, of course, is in contrast to the rule that during an attack of angina pectoris<i>after effort</i>the
Hyposensitization.
Authors: A. B. Frostad, Ø Grimmer, L. Sandvik, K. Aas
Journal: Allergy (1980)

Most extracts used in hyposensitization (immunotherapy) are complex and ill‐denned mixtures of a large number of non‐antigenic and antigenic components, only a few of the latter being of significance for allergy and allergen specific immunotherapy. A new purified and well‐characterized allergen preparation from timothy pollen is now available, and it has been shown to be superior to the corresponding crude aqueous extract in the diagnosis of IgE‐mediated human allergy to timothy pollen. This paper describes the results of hyposensitization for 2 years, with the purified preparation and the crude extract compared. The changes in in vivo and in vitro tests Following this treatment in 40 patients with allergic rhinitis due to grass pollen are reported. Both patient groups showed a significant decrease in clinical symptom scores when compared with a control group during the grass pollen season. For all groups the symptom scores correlated well with atmospheric pollen counts. Nasal challenge tests showed a significant increase in nasal tolerance to timothy pollen after 2 years of treatment, but nasal tolerance was unchanged in the control group. Nasal function as a criterion for evaluating the effect of specific hyposensitization is discussed. Serum concentrations of timothy pollen‐specific IgE antibodies showed a significant decrease for the group treated with the purified preparation and a slighter and non‐significant reduction for the other treated group. There was no significant change in total serum IgE levels. The results indicate that the purified preparation is preferable to the crude aqueous extract in hyposensitization.
Single-Dose Antibiotic Treatment of Asymptomatic Gonorrhea in Hospitalized Women
Authors: David W. Johnson, Paul A. Kvale, Virgilio L. Afable, Shannon D. Stewart, Charles W. Halverson, King K. Holmes
Journal: New England Journal of Medicine (1970)

Single-dose treatment of asymptomatic gonorrhea was studied in 396 Filipino women hospitalized to prevent reinfections. Endocervical cultures were obtained for six days after treatment to detect failures. Failure rates of 13 to 44 per cent were seen with varying doses of a parenteral penicillin G preparation given without probenecid. No failures occurred in 80 patients given 6,000,000 units of parenteral penicillin G with probenecid, or in 108 patients given 3.5 g of ampicillin orally with or without probenecid. These two regimens with probenecid and another with tetracycline were then compared in a prospective program of treatment. After one year, resistance of isolates of Neisseria gonorrhoeae to penicillin and ampicillin was unchanged, but over one third of isolates became resistant to 2 μg per milliliter of tetracycline. The use of penicillin G or of ampicillin, in association with probenecid, is recommended for treatment of women who are infected but have neither acute perineal discomfort nor the complications of pelvic inflammatory disease.
Warning Patients About Alcohol Abuse-Reply
Authors: Diana Chapman Walsh
Journal: JAMA (1992)

<h3>In Reply.</h3> —The letter from Volk et al is very much in the spirit of our article. In the context of a study conducted for altogether different purposes, we found a somewhat serendipitous blend of bad and good news: many physicians missed the drinking problems of seriously impaired patients who were ultimately identified on the job, but when they did issue a warning, it seemed to have an enduring positive effect. This points to a need for greater attention to effective strategies for earlier detection in clinical settings, whether they be the kinds of screens discussed by Volk et al or other approaches. We need carefully designed clinical trials to test alternative vehicles for enabling physicians to intervene earlier and more effectively when their patients are beginning to experience trouble with alcohol.
Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)?
Authors: R L Melnick
Journal: Environmental Health Perspectives (2001)

Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology Program as a possible or reasonably anticipated human carcinogen because it induces dose-related increases in liver tumors in both sexes of rats and mice. Recently, the suggestion has been advanced that DEHP should be considered unlikely to be a human carcinogen because it is claimed that the carcinogenic effects of this agent in rodents are due to peroxisome proliferation and that humans are nonresponsive to this process. An IARC working group recently downgraded DEHP to
A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia
Authors: M. Tariq, N. Wasif, W. Ahmad
Journal: British Journal of Dermatology (2007)

Journal Article A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia Get access M. Tariq, M. Tariq Department of Biochemistry, Faculty of Biological Sciences, Quaid‐i‐Azam University, Islamabad, Pakistan Search for other works by this author on: Oxford Academic Google Scholar N. Wasif, N. Wasif Department of Biochemistry, Faculty of Biological Sciences, Quaid‐i‐Azam University, Islamabad, Pakistan Search for other works by this author on: Oxford Academic Google Scholar W. Ahmad W. Ahmad Department of Biochemistry, Faculty of Biological Sciences, Quaid‐i‐Azam University, Islamabad, Pakistan Correspondence: Wasim Ahmad. E‐mail: wahmad@qau.edu.pk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 1, 1 July 2007, Pages 207–209, https://doi.org/10.1111/j.1365-2133.2007.07949.x Published: 01 July 2007
Doctor's Orders-Reply
Authors: Robert M. Veatch
Journal: JAMA (1986)

<h3>In Reply.—</h3> I am grateful that Drs Grattan, Peterson, and Blakley took the time to think about the term "doctor's orders" and to respond. I am also grateful that in at least two of their letters they demonstrated clearly that they grasped the two main points of the editorial: (1) that physicians should not think of instructions written in charts or transmitted to other health professionals as "orders" they themselves are giving but rather as instructions transmitted on behalf of the patient, and (2) that even when thought of as instructions from the patient, the term "order" is excessively harsh. Dr Grattan's formulation seems to me to be essentially correct. Patients should formulate treatment plans for such crucial decisions as cardiopulmonary resuscitation and other forms of resuscitation, taking into account the recommendations of any persons they trust, including their physician, priest, friends, and family. The physician is the appropriate person
ADDRESS ON THE PRESENT STATUS AND FUTURE TENDENCIES OF THE MEDICAL PROFESSION IN THE UNITED STATES, DELIVERED AT THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF MEDICAL EDITORS IN CLEVELAND, JUNE 5, 1883,
Authors: N. S. Davis
Journal: JAMA (1883)

Gentlemen:—I have promised to occupy your attention on this occasion, in considering the present status, and future tendencies of the medical profession in the United States. There is probably no more difficult problem than that involved in the question, as to the real status and tendencies of the times in which we live; and especially in reference to communities or classes of communities of which we constitute a part. An intelligent mind furnished with all the facts of the past history of a people, or of a profession, does not find it difficult to trace the various influences and measures which have contributed to their development and progress up to a given period in the past. But our minds are so liable to be influenced by such part of the events transpiring in the present as are most nearly related to our own interests, that we find great difficulty in
Estrogen and Tamoxifen Metabolites Protect Smooth Muscle Cell Membrane Phospholipids Against Peroxidation and Inhibit Cell Growth
Authors: Raghvendra K. Dubey, Yulia Y. Tyurina, Vladimir A. Tyurin, Delbert G. Gillespie, Robert A. Branch, Edwin K. Jackson, Valerian E. Kagan
Journal: Circulation Research (1999)

The goal of this study was to test the hypothesis that antioxidant estrogens, by a mechanism independent of the estrogen receptor, protect phospholipids residing in the plasma membrane of vascular smooth muscle cells from peroxidation and peroxidation-induced cell growth and migration. Peroxidation of membrane phospholipids was assessed by HPLC analysis of phospholipids extracted from rat aortic vascular smooth muscle cells prelabeled with cis-parinaric acid (a fatty acid that is susceptible to peroxidation, which quenches its fluorescent properties). Incubation of cells for 2 hours with the peroxyl radical donor 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN) caused peroxidation of all measured membrane phospholipids. This effect was attenuated by pretreating cells for 15 minutes with 50 to 5000 ng/mL of 2-hydroxyestradiol (strong antioxidant but weak estrogen-receptor ligand) or 4-hydroxytamoxifen (strong antioxidant and potent estrogen-receptor ligand), but not by estrone or droloxifene (both weak antioxidants but potent estrogen-receptor ligands). Moreover, pretreatment of cells for 20 hours with physiological concentrations (0.3 ng/mL) of 2-hydroxyestradiol or pharmacologically relevant concentrations of 4-hydroxytamoxifen (40 ng/mL) also decreased AMVN-induced phospholipid peroxidation. Both 2-hydroxyestradiol and 4-hydroxytamoxifen were as effective as 2,2,5, 7,8-pentamethyl-6-hydrochromane (an antioxidant homolog of vitamin E) in attenuating AMVN-induced peroxidation of membrane phospholipids. Also, physiological concentrations of 2-hydroxyestradiol, but not estrone, and pharmacologically relevant concentrations of 4-hydroxytamoxifen attenuated AMVM-induced DNA synthesis, cell proliferation, and cell migration. These studies demonstrate in vascular smooth muscle cells that antioxidant estrogens via a non-estrogen receptor-dependent mechanism attenuate peroxidation of membrane phospholipids and peroxidation-induced cell growth and migration.
Throwing injuries of the shoulder.
Authors: S Copeland
Journal: British Journal of Sports Medicine (1993)

A review of the mechanism of throwing is presented and split into the different phases. The presentation and history is often more important than the clinical signs which may only be present after repetitive throwing activity. The pathological relationship between instability and impingement is discussed. Arthroscopy has been found to be extremely helpful in extending knowledge of pathological anatomy as well as defining diagnosis and aiding treatment.
Japanese Psychoanalysis and the Ajase Complex (Kosawa)
Authors: Keigo Okonogi
Journal: Psychotherapy and Psychosomatics (1979)

In 1932, <i>Kosawa</i> visited <i>Freud</i> at 19 Berggasse, and submitted to him a paper entitled: 'Two kinds of guilt feelings, the Ajase complex. In his paper, <i>Kosawa</i> expounded his theory of the Ajase complex, rooted in Buddhist thought. He discussed the psychological peculiarity of the Japanese as evidenced by the acceptance of oral dependency toward the mother, the repression of the resentment at the mother and 'guilt feeling over being forgiven' and a need to make restitution for harboring this evil intent. This type of guilt feeling is quite different from the guilt feeling as a fear of punishment which Freud embodied in his theory of the Oedipus complex.
Loss of the Par3 Polarity Protein Promotes Breast Tumorigenesis and Metastasis
Authors: Luke Martin McCaffrey, JoAnne Montalbano, Constantina Mihai, Ian G. Macara
Journal: Cancer Cell (2012)

Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras61L expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer.