tbuckley/cabot-search huggingface dataset:
Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction
Authors: Michel de Lorgeril, Patricia Salen, Jean-Louis Martin, Isabelle Monjaud, Jacques Delaye, Nicole Mamelle
Journal: Circulation (1999)

Background —The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. Methods and Results —Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P =0.0001), as were CO 2 (27 events versus 90, P =0.0001) and CO 3 (95 events versus 180, P =0.0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count &gt;9×10 9 /L), female sex (adjusted risk ratios, 0.27 to 0.46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. Conclusions —The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.
Application of Economic Analysis to Diabetes and Diabetes Care
Authors: Ping Zhang, Michael M. Engelgau, Susan L. Norris, Edward W. Gregg, K. M. Venkat Narayan
Journal: Annals of Internal Medicine (2004)

Facing limited resources and increases in demand from competing programs, policymakers and health care providers seek guidance from economic studies on how to use health care resources wisely. Previous economic studies mainly focused on estimating the cost of diabetes and cost-effectiveness of different interventions. These studies found that diabetes is costly and that its cost will continue to increase; thus, more resources should be devoted to research aimed at finding effective means to prevent the disease and its complications. In addition, the cost-effectiveness of interventions varies greatly in terms of quality-adjusted life-years gained; therefore, efficient uses of resources should be an important consideration when interventions are prioritized. The need for economic studies will continue to grow because of increasing demand for limited resources from the growing number of interventions available. Future studies should be of better quality and broadened in areas of research.
Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis.
Authors: J L Brasier, E P Henske
Journal: Journal of Clinical Investigation (1997)

It is not known whether mutations in the PKD1 gene cause autosomal dominant polycystic kidney disease (PKD) by an activating (gain-of-function) or an inactivating (loss-of-function) model. We analyzed DNA from cyst epithelial cells for loss of heterozygosity (LOH) in the PKD1 region of chromosome 16p13 using microsatellite markers. 29 cysts from four patients were studied. Five cysts from three patients had chromosome 16p13 LOH. Four of the cysts had loss of two chromosome 16p13 markers that flank the PKD1 gene. In two patients, microsatellite analysis of family members was consistent with loss of the wild-type copy of PKD1 in the cysts. In the third patient, 16p13 LOH was detected in three separate cysts, all of which showed loss of the same alleles. Chromosome 3p21 LOH was detected in one cyst. No LOH was detected in four other genomic regions. These results demonstrate that some renal cyst epithelial cells exhibit clonal chromosomal abnormalities with loss of the wild-type copy of PKD1. This supports a loss-of-function model for autosomal dominant PKD, with a germline mutation inactivating one copy of PKD1 and somatic mutation or deletion inactivating the remaining wild-type copy.
Modelling and Dosimetry of Monoclonal Antibody 170H.82 in Breast Cancer
Authors: S A McQuarrle, A JB McEwan, L Golberg, K Golberg, G R Boniface, A A Noujalm
Journal: Clinical Nuclear Medicine (1994)

McQuarrle, S A; McEwan, A JB; Golberg, L; Golberg, K; Boniface, G R; Noujalm, A A Author Information
SOME ASPECTS OF THE METABOLISM OF 16-C14-ESTRONE IN NORMAL INDIVIDUALS*
Authors: Claude J. Migeon, Patricia E. Wall, Jean Bertrand
Journal: Journal of Clinical Investigation (1959)

Furthermore, in this study an attempt has been made to fractionate and determine the nature of the metabolites of estrone. METHODSExperimental subjects.The experimental subjects of this study were two normal males, A. D. and A. N., 32 and 30 years of age, respectively, and a normal 28 year old female (A.K) who had a regular 29 to 30 day menstrual cycle.This latter subject received the radio- active steroid 11 days after onset of the last menses.Purity of 16-C"-estrone.The 16-C14-estrone was pro-
Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development
Authors: Yoshiaki Ito, Takaaki Matsui, Akihide Kamiya, Taisei Kinoshita, Atsushi Miyajima
Journal: Hepatology (2000)

We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)-6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown. To address this issue, we expressed signal molecules by a retroviral expression vector in primary fetal hepatic cells and investigated a signaling pathway essential for OSM-mediated hepatic development. Expression of a dominant-negative form of STAT3 (DeltaSTAT3), but not DeltaSTAT5, suppressed differentiated phenotypes of hepatocytes induced by OSM. On the other hand, dominant-negative forms of Ras (RasN17) and SHP-2(C463A) rather augmented the expression of hepatic differentiation markers, suggesting that the Ras pathway negatively regulates hepatic development. Consistently, expression of a constitutively activated form of Ras (RasV12) inhibited cellular responses to OSM. Our results indicate that STAT3 is an essential signaling component for OSM-induced hepatic development, while activation of Ras appears to negatively regulate this process. Thus, retrovirus-mediated gene transfer is an effective means to analyze function of a gene in primary fetal hepatic culture.
CARNARVONSHIRE AND ANGLESEY INFIRMARY: SURGICAL CASES
Authors: H. R. Hughes
Journal: BMJ (1856)

up into the throa; he also complained of severe pain in th leg; he also ated that he had two similar attcks in thO previous night, which he had not mentioned before.A little brandy was given, and, in a short time, he appeared to be quite recovered.About an hour afterwards, another summons came, saying the man was dying.All the symptoms of the former attack had returned, with the addition of twitching of all the faial muscles, and insensibility.The inhalation of chloro- form, to a very small extent, again relieved him, but not so perfectly as before, the pain in the jaws and twitching of the face remaining.He could not put out his tongue steadily, nor speak distinctly, and had a difficulty in swallowing.His pulse was quick, and face flushed.A poultice was ordered to the leg and foot, a line of caustic was pencilled round the leg, above the inflamed parts, and two rops of chloroform in camphor mixture ordered to be taken every two hours.At 11 P.x. had had several other paroxysms; the twitch-
Doctor with an accent
Authors: G. Farah
Journal: BMJ (2014)

“So, where is this lovely accent from?” the nice old lady inquires as I am examining her diabetic foot ulcer. I’m used to this question by now, and once I would have responded by smiling and asking the patient to guess.

Over the years, patients and colleagues have struggled to work out where I’m from. I put them out of their misery after two or three wrong guesses. I used to be amused and a little annoyed that very few people …
Abstract 2804: Radiosensitization by the Dual PI3K/mTOR inhibitor NVP-BEZ235
Authors: George J. Cerniglia, Jayashree Karar, Constantinos Koumenis, Amit Maity
Journal: Cancer Research (2012)

Abstract The PI3K/Akt pathway has been implicated in cancer progression and in the survival of cancer cells following DNA damage induced by radiation. Hence, we chose to study the radiosensitizing ability of the Novartis compound, NVP-BEZ235, a dual PI3K/mTOR inhibitor. Clonogenic cell survival assays following ionizing radiation, cell cycle analysis, immunofluorescence for γ-H2AX foci, and Western blotting were performed using standard protocols.Treatment of SQ20B head and neck squamous cell carcinoma cells and U251 glioblastoma cells with NVP-BEZ235 led to a decrease in phosphorylation of Akt at serine 473 and of S6 and 4E-BP1, both of which are downstream markers of mTOR activation. Pre-treatment with the drug (25-50 nM) led to radiosensitization of these cell lines with a dose enhancement ratio (DER) ranging from 1.32 - 1.72. Knockdown of Akt1, p110alpha, or mTOR in these cell lines, also resulted in radiosensitization, but not to the same extent as with NVP-BEZ235. Of note, treatment with rapamycin led to minimal radiosensitization of these cells. Reduced survival with NVP-BEZ235 does not result from cell cycle redistribution during the treatment intervals tested, although combining NVP-BEZ235 with radiation enhances the G2/M delay seen after radiation. We examined how cells died after radiation and found no suggestion of increased apoptosis or necrosis. We did find evidence of increased conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, suggestive of autophagy. In split course experiments, in which cells were either irradiated with a single dose of radiation or with two half-doses separated by time, as the interval between doses increased, so did clonogenic survival. This increase in survival was abolished by pre-treatment with NVP-BEZ235, suggesting that the drug interfered with DNA damage repair. This was confirmed by assessing levels of gamma-H2AX after ionizing radiation. Initial post-radiation levels of gamma-H2AX foci were similar in NVP-BEZ235-pretreated and control cells; however, the resolution of these foci was significantly delayed in the BEZ235-treated cells. We then examined DNA-PKcs, a protein important for DNA damage repair, and found that the drug abrogated the increased phosphorylation normally seen after radiation. These results indicate that NVP-BEZ235 is a potent radiosensitizer of HNC cells in vitro. As siRNA against either p110alpha or mTOR leads to radiosensization, both of these targets of NVP-BEZ235 may be critical mediators of its to radiosensitizing ability; however, a second mechanism involved, may be via delayed repair of DNA damage following radiation, via interference of DNA-PKcs phosphorylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2804. doi:1538-7445.AM2012-2804
Current Concepts of Leukemia and Lymphoma: Etiology, Pathogenesis, and Therapy
Authors: COSTAN W. BERARD
Journal: Annals of Internal Medicine (1976)

The cellular change (phenotypic) leading to leukemia may involve a disorder of leukocyte maturation, but the etiologic molecular change (genotypic) remains unknown. We present evidence here that human leukemic cells contain type-C viral information and consider the possible significance of this observation in the context of a working hypothesis. We reexamine reticuloendothelial neoplasms in the light of newer immunologic, cytochemical, and ultrastructural methods for identifying cells of the T-lymphocytic, B-lymphocytic, and monocyte-macrophage systems. Use of these methods has led to a challenging concept of malignant lymphomas as neoplasms of various anatomic and functional compartments of the immune system. Functional studies, although still in their inception, have already provided provocative clues in the etiology and pathophysiology of these disorders. Advances in laboratory research have been paralled by dramatic changes in clinical oncology, as evidenced by trends in the treatment of acute lymphocytic leukemia, acute myelogenous leukemia, Hodgkin's disease, and diffuse histiocytic lymphoma.
Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study
Authors: Toshio Watanabe, Satoshi Sugimori, Natsuhiko Kameda, Hirohisa Machida, Hirotoshi Okazaki, Tetsuya Tanigawa, Kenji Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Nobuhide Oshitani, Kazuhide Higuchi, Tetsuo Arakawa
Journal: Clinical Gastroenterology and Hepatology (2008)
Current views in HTLV-I-associated adult T-cell leukemia/lymphoma
Authors: Christophe Nicot
Journal: American Journal of Hematology (2005)

Epidemiological studies have demonstrated that the relative percentage of malignant lymphoid proliferations varies widely according to geographical location and ethnic populations. HTLV-I is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and is also associated with cutaneous T-cell lymphoma (CTCL). However, a definite role of HTLV-I in mycosis fungoides (MF) and/or Sezary syndrome (SS) remains controversial. While most HTLV-I-infected individuals remain asymptomatic carriers, 1–5% will develop ATLL, an invariably fatal expansion of virus-infected CD4+ T cells. This low incidence and the long latency period preceding occurrence of the disease suggest that additional factors are involved in development of ATLL. In this review, diagnosis, clinical features, and molecular pathogenesis of HTLV-I are discussed. Am. J. Hematol. 78:232–239, 2005. © 2005 Wiley-Liss, Inc.
Clinical Maternal-Fetal Nutrition
Authors: Frank R. Witter
Journal: JAMA (1994)

This concise, three-author text is an excellent introduction to the topic of nutrition in pregnancy. It begins with a unique chapter on the historical basis of maternal nutritional recommendations. This chapter clearly traces the evolution of nutritional recommendations during pregnancy.  In the next three chapters, the authors discuss the nutritional basis for reproductive health and evaluate how anthropometric and sociodemographic characteristics can influence the outcome of pregnancy. Following this, prenatal diet, calcium, and iron metabolism are covered in detail with clear recommendations for nutritional intake.  The authors then discuss the adverse effects of smoking and alcohol on pregnancy. The smoker's modified nutritional needs are highlighted, and nutritional methods of minimizing the adverse effects of smoking are put forth. Therapeutic nutrition for common conditions seen during pregnancy is discussed in chapters on diabetes mellitus, meternalfetal ketonuria, and multiple gestation. These chapters contain a fund of practical information written in an easily
Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor Exacerbate Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Amir Haghighat, Daiana Weiss, Matthew K. Whalin, D. Patrick Cowan, W. Robert Taylor
Journal: Circulation (2007)

Recent studies have suggested a potential contribution of bone marrow-derived progenitor cells to vascular repair. Preliminary clinical studies have explored the possibility that mobilization of progenitor cells with granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can affect vascular repair. However, it is not known whether the short-term administration of G-CSF or GM-CSF exerts beneficial effects on atherosclerosis.Apolipoprotein E-deficient mice were treated with either GM-CSF or G-CSF at a dose of 10 microg x kg(-1) x d(-1) s.c. administered daily for 5 days per week on alternating weeks for a total of 20 doses over an 8-week treatment period. We found that in animals maintained on a high-fat diet, both G-CSF and GM-CSF actually demonstrated an increase in atherosclerotic lesion extent. The increase in atherosclerotic extent was not associated with an increase in either inflammatory cells or expression of proinflammatory genes. Interestingly, adventitial vascularity significantly increased, suggesting a mechanistic role for vasa vasorum neovascularization.These findings demonstrate that in this animal model of atherosclerosis, not only did administration of G-CSF or GM-CSF fail to demonstrate any beneficial therapeutic effect, but both resulted in a worsening of atherosclerosis.
Lumps in the Breast
Authors: I. Burn, T. J. Deeley
Journal: BMJ (1966)

Cloned CD4 T cells of the Th2 type make IL-4 and related cytokines upon receptor cross-linking, whereas cloned CD4 T cells of the Th1 type make IL-2, IFN-gamma, and TNF-beta. These two types of CD4 T cell are also reported to use distinct mechanisms of signal transduction. It has been reported that Th1 cells flux Ca2+ upon receptor cross-linking, whereas Th2 cells do not. We have noted that when cloned Th2 cells are exposed to high levels (20 U/ml) of IL-2, they show an altered phenotype. Such cells are much more sensitive to activation by certain antireceptor antibodies, they flux calcium upon receptor ligation without additional cross-linking with anti-Ig antibodies, and they make much larger amounts of IL-4. In addition, the organization of their TCR is altered, with increased levels of the TCR-eta chain and an increase in the extent of association of CD4 with CD3 and CD45, changes similar to those found in Th1 cells. These results suggest that there is no fundamental difference in the signal transduction apparatus of Th1 and Th2 cells; rather, the IL-2 made by Th1 cells may create similar phenotypic changes in these cells and thus create the impression of altered signal transduction mechanisms. These results do show that exposure to high levels of IL-2 can profoundly affect signal transduction in T cells. Furthermore, we found that the Ca2+ signal caused by CD3 antibodies seemed to differ in character from that caused by TCR antibodies suggesting that the use of CD3 antibodies is not always a good model for activation through the TCR.
Involuntary Movement Disorders
Authors: Oscar Sugar
Journal: JAMA (1970)

Encompassed in this well-printed and beautifully illustrated volume are the up-to-date views of the most prolific operator and writer in American neurosurgery. They are based on studies of more than 10,000 patients with dyskinesia; 6,800 surgical procedures have been carried out in more than 5,500 patients. Most have been for unilateral or bilateral parkinsonism, but significant numbers have been done for intention tremor, dystonia, hemiballismus, and hemichorea. A few patients have had multiple tics, torticollis, and athetosis. Numerous case histories are provided to support Cooper's concepts, with figures drawn from cinematographic analyses of the moving patient, or with series of frames from actual moving pictures. Some patients have been followed up as long as 15 years; a number of autopsies have permitted verification of the site and extent of the lesions which have (and some of which have not) led to improvement of the movement disorder. There seems now to
Risk Evaluation for Coronary Artery Disease in Patients With Impaired Glucose Tolerance After a Successful Coronary Intervention
Authors: Mitsuaki Horigome, Naoya Hattori, Hiroki Kasai, Miki Horigome, Shumpei Sakurai, Kazuhiro Oguchi, Uichi Ikeda
Journal: Clinical Nuclear Medicine (2011)

Patients with coronary artery disease (CAD) often have risk factors that may influence endothelial function. The purpose of this study was to evaluate the endothelial function and its association with coronary risk factors after percutaneous coronary intervention (PCI).A total of 14 patients with impaired glucose tolerance and CAD underwent positron emission tomography with N-13 ammonia to measure myocardial blood flow (MBF) at rest and during a cold pressor test (CPT), to estimate endothelial function as a percent increase (%increase) of MBF. The results were compared among normal segments (normal), reperfused segments with PCI (PCI), and nonculprit CAD segments without PCI (non-PCI). Correlations between the %increase and major risk factors were also investigated.CPT induced significant increase in MBF in all groups. The %increase of normal, non-PCI, and PCI groups were 33% ± 22%, 21% ± 23%, and 26% ± 23%, respectively. Comparison with risk factors demonstrated significant correlations only in the non-PCI group. Specifically, there were negative correlations between %increase and fasting blood sugar (r = -0.64, P < 0.05), hemoglobin A1c (r = -0.74, P < 0.05), total cholesterol (r = -0.87, P < 0.05), triglyceride (r = -0.71, P < 0.05), and low-density lipoprotein cholesterol (r = -0.92, P < 0.005), respectively.Although impaired glucose tolerance patients with a PCI-treated coronary stenosis showed preserved response to CPT, the %increase negatively correlated with risk factors in the non-PCI segments. Therefore, coronary risk factors may affect CAD lesions in PCI-treated patients.
Facial Perception Of the Blind
Authors: John Mandola
Journal: JAMA (1967)

To the Editor:—  Dr. J. Dana Darnley's answer to the question of facial perception of the blind (197: 738, 1966) is excellent as far as it goes, and he is correct in noting that there are no references in standard texts of neurology and ophthalmology.  However, there are several studies on this subject found in psychological and other journals. Some of these studies are concerned directly with facial perception:  Perhaps your readers would be interested in these references.