tbuckley/cabot-search huggingface dataset:
Treatment of Parkinson's Disease With Lergotrile Mesylate
Authors: Abraham Lieberman
Journal: JAMA (1977)

Lergotrile mesylate, an ergot alkaloid derivative and putative dopamine agonist, was effective in the majority of patients with Parkinson's disease who were showing signs of disease progression despite treatment with levodopa combined with a peripheral decarboxylase inhibitor (carbidopa). Among 20 patients completing a six-month trial, there was a significant (P less than .01) reduction in rigidity, tremor, bradykinesia, gait disturbance, and total score when lergotrile was added to levodopa plus carbidopa. Mean daily dose of lergotrile mesylate was 52 mg, and the mean daily dose of levodopa was reduced by 15%. Abnormal involuntary movements were decreased on addition of lergotrile and reduction in levodopa while mental changes and orthostatic hypotension were increased. Elevations in serum transaminase levels were noted in three patients. The ergot alkaloids promise to be an important new class of antiparkinsonian drugs.
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia
Authors: Marco Tartaglia, Charlotte M Niemeyer, Alessandra Fragale, Xiaoling Song, Jochen Buechner, Andreas Jung, Karel Hählen, Henrik Hasle, Jonathan D Licht, Bruce D Gelb
Journal: Nature Genetics (2003)
Abstract A9: The HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) inhibits vascular endothelial growth factor C-induced lymphangiogenesis
Authors: Hsuen-Tsen Cheng, Wen-Chun Hung
Journal: Clinical Cancer Research (2010)

Abstract The lymphatic system plays an important role in tissue fluid homeostasis, immune surveillance, and fat absorption and also is involved in various pathological situations. Recent studies showed that lymphangiogenesis is not only important for physiological regulations but also associated with the metastatic spread of cancer. The histone deacetylase (HDAC) inhibitor SAHA has been reported to inhibit tumor cell proliferation, induce apoptosis and reduce angiogenesis in different cancer types. In this study, prox1-overexpressing endothelial cell line EA.hy926-Prox1 with the characteristics of lymphatic endothelial is used to evaluate the anti-lymphangiogenic and anti-cancer activity of SAHA. SAHA at low concentrations inhibits growth of EA.hy926-Prox1 endothelial cells via induction of G2/M arrest. Multiple G2/M cell cycle regulators are changed by SAHA. At high concentrations, SAHA causes significant cell death. SAHA at non-cytotoxic concentrations prevents vascular endothelial growth factor C (VEGF-C)-stimulated sprouting and capillary-like structure of EA.hy926-Prox1 cells. In addition, we find that SAHA treatment can inhibit the expression and secretion of VEGF-C in breast cancer cells. Our results provide evidence that SAHA can inhibit lymphagiogenic through (A) regulating the proliferation, apoptosis, sprouting and tube formation in lypmphatic endothelial cells and (B) reducing the expression and secretion of VEGF-C in cancer cells. Thus, SAHA may function as a therapeutic agent for the treatment or prevention of tumor-induced lymphangiogensis. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A9.
TRANSFORMATION OF ADULT ALLOGENEIC SMALL LYMPHOCYTES AFTER TRANSFUSION INTO NEWBORN RATS
Authors: K. A. Porter, E. H. Cooper
Journal: The Journal of Experimental Medicine (1962)

Newborn rats of one inbred strain were given an intracardiac injection of adult thoracic duct lymphocytes from another inbred strain. It was found that although there was a direct relationship between the number of small lymphocytes injected and the incidence of fatal runt disease, there was no particular relationship between the large lymphocyte content of an inoculum and its runt-inducing potentiality. Using tritiated thymidine and an autoradiographic technique, the small lymphocytes in the inoculum were labelled and found to migrate in large numbers into the cortex of the lymph nodes and into the Peyer's patches of the host animal, and in smaller numbers into the white pulp of the spleen. Within 24 hours isotope, previously present in the DNA of small lymphocytes, appeared in a number of the large pyroninophilic cells which were a characteristic feature of the spleen and lymph nodes in this early phase of runt disease. When the large lymphocytes in the inoculum were labelled they were found to migrate to the red pulp of the spleen, medulla of the lymph nodes, and the Peyer's patches and the lamina propria of the small intestine. Later some labelled small lymphocytes appeared at these sites. These findings suggest that: (1) Some small lymphocytes are immunologically competent cells, and (2) After introduction into the circulation of a newborn rat, these same small lymphocytes are the first cells to react with the antigens of the host, and in the process they become transformed into large pyroninophilic cells capable of division. The large lymphocytes seem to play little part in this initiating of an immunological response, but do give rise to some small lymphocytes.
P332 DEVELOPMENT OF HUMAN HEPATIC HepaRG CELL-BASED LiverBioChip PROTOTYPES USING ELECTRON BEAM LITHOGRAPHY DIRECTED-NANOPATTERNING FOR HTS-COMPATIBLE PRE-CLINICAL DRUG EVALUATION APPLICATIONS
Authors: L.J. Nelson, C. LeBled, P. Treskes, M. Thompson, M. Navarro, J.N. Plevris, N. Gadegaard
Journal: Journal of Hepatology (2014)
Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes.
Authors: F Ahmad, J L Azevedo, R Cortright, G L Dohm, B J Goldstein
Journal: Journal of Clinical Investigation (1997)

Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase activity in the skeletal muscle particulate fraction and cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, and obese individuals with non-insulin-dependent diabetes. PTPase activities in subcellular fractions from the nondiabetic obese subjects were increased to 140-170% of the level in lean controls (P < 0.05). In contrast, PTPase activity in both fractions from the obese subjects with non-insulin-dependent diabetes was significantly decreased to 39% of the level in controls (P < 0.05). By immunoblot analysis, leukocyte antigen related (LAR) and protein-tyrosine phosphatase 1B had the greatest increase (threefold) in the particulate fraction from obese, nondiabetic subjects, and immunodepletion of this fraction using an affinity-purified antibody directed at the cytoplasmic domain of leukocyte antigen related normalized the PTPase activity when compared to the activity from control subjects. These findings provide further support for negative regulation of insulin action by specific PTPases in the pathogenesis of insulin resistance in human obesity, while other regulatory mechanisms may be operative in the diabetic state.
EPICARDIAL FAT VOLUME AND CONCURRENT PRESENCE OF BOTH MYOCARDIAL ISCHEMIA AND OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Ryo Nakazato, Damini Dey, Victor Cheng, Heidi Gransar, Piotr Slomka, Sean Hayes, Louise Thomson, John Friedman, James Min, Daniel Berman
Journal: Journal of the American College of Cardiology (2012)
Depressed Coronary Flow Reserve Is Associated With Decreased Myocardial Capillary Density in Patients With Heart Failure Due to Idiopathic Dilated Cardiomyopathy
Authors: Eleftheria P. Tsagalou, Maria Anastasiou-Nana, Emmanuel Agapitos, Apostolia Gika, Stavros G. Drakos, John V. Terrovitis, Argirios Ntalianis, John N. Nanas
Journal: Journal of the American College of Cardiology (2008)
Pericardial Fat and Echocardiographic Measures of Cardiac Abnormalities
Authors: Jiankang Liu, Caroline S. Fox, DeMarc A. Hickson, Warren L. May, Jingzhong Ding, J. Jeffery Carr, Herman A. Taylor
Journal: Diabetes Care (2011)

Pericardial adipose tissue (PAT), a regional fat depot adjacent to the myocardium, may mediate the complex relation between obesity and cardiac left ventricular (LV) abnormalities. We sought to evaluate the association of PAT with echocardiographic measures of LV abnormalities in the Jackson Heart Study (JHS).
Technique and Value of Aortography
Authors: R. E. Horton, E. M. Nanson
Journal: BMJ (1953)

Although aortography was introduced by Dos Santos et al. in 1929, it has never been a popular form of investigation in this country, and it is still considered by many to be a difficult and hazardous procedure of no clinical value.Recent developments in vascular surgery, however, have made aortography an absolutely essential investigation in certain cases.It is, in fact, neither difficult nor hazardous, and can be performed under sedation alone.The use of general or high spinal anaesthesia is unnecessary.
Alterations in thyroid hormone economy during acute infection with Diplococcus pneumoniae in the rhesus monkey
Authors: Kenneth A. Woeber, William A. Harrison
Journal: Journal of Clinical Investigation (1971)

In order to study the alterations in thyroid hormone economy that accompany an acute bacterial infection, rhesus monkeys were inoculated i.v. with a virulent Diplococcus pneumoniae culture containing approximately 10(8) organisms per dose. This was found to produce a well-defined febrile illness followed in most instances by spontaneous recovery, thereby permitting sequential observations to be made during progression from the healthy state through acute infection into convalescence. During the acute febrile period of the infection, the clearance of both exogenously labeled L-thyroxine (T(4)) and 3,3',5-triiodo-L-thyronine (T(3)) from their peripheral pools was accelerated. This alteration was often evident by 8 hr after inoculation with the virulent culture and could not be ascribed to a decrease in extracellular binding. Despite the accelerated hormonal clearance, the concentrations of both endogenously labeled thyroid hormone and stable T(4) in the sera of the surviving monkeys remained essentially unchanged or increased, indicating that hormonal secretion must have increased during this period. During the convalescent period, hormonal clearance was similar to preinfection control values. Leukocytes isolated from blood obtained 6 hr after inoculation with the virulent culture displayed enhanced T(4)-deiodinative activity.
PYELONEPHRITIS AND ITS RELATION TO NONGONORRHEAL URETHRITIS
Authors: B. C. CORBUS
Journal: JAMA (1927)

According to most textbooks on urology, infections of the urethra are considered somewhat as follows:   Gonorrheal.  Nongonorrheal.   The nongonorrheal infection is caused by:   Bacteria other than the gonococcus.  Chemical irritants.  Mechanical irritants.   Nongonorrheal urethritis is caused by bacteria conveyed to the urethra from without in or from within out. Simple nongonorrheal urethritis caused by chemical or mechanical irritants is transitory and disappears as soon as the cause is removed.  In view of the large number of exposures to nongonorrheal organisms to which the average urethra is subjected, infections from without in should be more common than from within out but they are not, because the urethra is more vulnerable to this class of infection and, in addition, the passage of the urine along the urethra has a tendency to wash the infection away.  Examination of the literature for the past ten years reveals little of importance with regard to the
Effect of etretinate on cyclosporin metabolism in vitro
Authors: I.R. WEBBBR, D.J. BACK
Journal: British Journal of Dermatology (1993)

Cyclosporin (CyA) is an effective treatment for psoriasis, including cases unresponsive to other therapies. The major side-effect of CyA treatment is dose-related nephrotoxicity. Combinations of CyA and etretinate (Et) have been tested with a view to reducing CyA dose requirements, and therefore minimizing adverse effects. We have studied the effect of Et on the cytochrome P-450-mediated metabolism of CyA. Microsomes prepared from histologically normal human (obtained from four cadaver kidney transplant donors; all male; age range 21-56) were incubated with CyA and various concentrations of Et. Metabolism was quantified by high-performance liquid chromatography with radiometric detection, and metabolites tentatively identified from the retention times of authentic standards. After 30 min incubation of CyA and microsomal protein at 37 degrees C, 10.1 +/- 3.0% (mean +/- SD) 3H-CyA was converted to the monohydroxylated metabolites M1 and M17, and 3.3 +/- 0.8% to the N-demethylated metabolite M21. At an Et concentration of 100 microM inhibition of CyA hydroxylase and N-demethylase was < 20%. This study indicates that there is no metabolic interaction between CyA and Et in vitro; it is likely that the two drugs are metabolized by different P-450 isoenzymes.
Corruption of the Fas Pathway Delays the Pulmonary Clearance of Murine Osteosarcoma Cells, Enhances Their Metastatic Potential, and Reduces the Effect of Aerosol Gemcitabine
Authors: Nancy Gordon, Nadezhda V. Koshkina, Shu-Fang Jia, Chand Khanna, Arnulfo Mendoza, Laura L. Worth, Eugenie S. Kleinerman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Pulmonary metastases continue to be a significant problem in osteosarcoma. Apoptosis dysfunction is known to influence tumor development. Fas (CD95, APO-1)/FasL is one of the most extensively studied apoptotic pathways. Because FasL is constitutively expressed in the lung, cells that express Fas should be eliminated by lung endothelium. Cells with low or no cell surface Fas expression may be able to evade this innate defense mechanism. The purpose of these studies was to evaluate Fas expression in osteosarcoma lung metastases and the effect of gemcitabine on Fas expression and tumor growth. Experimental Design and Results: Using the K7M2 murine osteosarcoma model, Fas expression was quantified using immunohistochemistry. High levels of Fas were present in primary tumors, but no Fas expression was present in actively growing lung metastases. Blocking the Fas pathway using Fas-associated death domain dominant-negative delayed tumor cell clearance from the lung and increased metastatic potential. Treatment of mice with aerosol gemcitabine resulted in increased Fas expression and subsequent tumor regression. Conclusions: We conclude that corruption of the Fas pathway is critical to the ability of osteosarcoma cells to grow in the lung. Agents such as gemcitabine that up-regulate cell surface Fas expression may therefore be effective in treating osteosarcoma lung metastases. These data also suggest that an additional mechanism by which gemcitabine induces regression of osteosarcoma lung metastases is mediated by enhancing the sensitivity of the tumor cells to the constitutive FasL in the lung.
Timing of Breast Cancer Excision during the Menstrual Cycle Influences Duration of Disease-free Survival
Authors: Ruby T. Senie, Paul Peter Rosen, Philip Rhodes, Martin L. Lesser
Journal: Annals of Internal Medicine (1991)

Objective: To study disease-free survival at 10 years in relation to timing of breast tumor excision during the menstrual cycle. Design: A prospective study of consecutively treated patients with primary breast cancer. Setting: Memorial Sloan-Kettering Cancer Center, New York. Patients: Two hundred and eighty-three premenopausal patients treated by mastectomy and axillary dissection. Main Results: When the tumor was excised during the follicular phase, approximated by setting the putative day of ovulation on day 14 after the onset of last menses, a higher recurrence risk (43%) was observed compared with excision later in the menstrual cycle (29%, P = 0.02). The rate peaked among patients treated between days 7 and 14 and was lowest between days 20 and 30. Multivariate analysis using the Cox regression model to control for tumor size, nodal status, estrogen receptor status, adjuvant chemotherapy, and family history indicated that the hazard rate of breast cancer recurrence after excision during the follicular phase was 1.53 (95% Cl, 1.02 to 2.29). Stratification by nodal status indicated that the effect of phase was statistically significant only among patients with positive nodes (hazard ratio, 2.10; Cl, 1.19 to 3.70). Conclusions: Our results support the hypothesis that the risk for recurrence may be affected by the hormonal milieu of the menstrual cycle; these findings must be confirmed, however, by a prospective study in which cycle phase at time of tumor excision is biochemically documented.
Environmental contaminants as etiologic factors for diabetes.
Authors: M P Longnecker, J L Daniels
Journal: Environmental Health Perspectives (2001)

For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes. In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk. Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study.
Biochemical screening for Down's syndrome.
Authors: M Connor
Journal: BMJ (1993)

Evidence exists, however, that once a medical technology is available its use becomes established regardless of broader social considerations.7If preconceptional sex selection was to become available one option would be to limit it, initially at least, to licensed centres.This would allow detailed research not only on the safety and reliability of the technique but also on the gamut of psychological, social, and demographic consequences.Without this research we cannot judge whether individual benefits of influencing the sex of our progeny will outweigh adverse social consequences.Preconceptional sex selection has been condemned as an example of positive eugenics-that is, an attempt to improve (as defined by the perpetrator) the inborn qualities of the human race.8It differs, however, from past eugenic episodes in not being perpetrated by a state.But does an absence of state intervention in such matters make it acceptable for people to select genetic characteristics of their unborn children?This is a key question that now confronts us as the fruits of analysis of the human genome reach the clinic and the marketplace.
Sjogren's Syndrome
Authors: G. R. V. Hughes, K. Whaley
Journal: BMJ (1972)

Sjögren's syndrome is a common accompaniment of rheumatoid arthritis and other connective-tissue diseases as well as several diseases thought to have an immunological basis. Despite the wide spectrum of clinical features and serological abnormalities the condition is, if anything, underdiagnosed. A clinical subgroup of patients with Sjögren's syndrome can be distinguished by their pronounced hypergammaglobulinaemia, widespread and prominent immunological abnormalities, severe salivary gland swelling, and mild or absent arthritis. It is in this group that lymphoma development has been a complication.
Arsenamide Treatment of Filariasis Due to W. bancrofti and A. perstans
Authors: J. A. McFadzean, F. Hawking
Journal: BMJ (1954)

ACUTE GASTRO-DUODENAL HAEMORRHAGE tant features are early complete replacement of the lost blood in all patients, and emergency surgical operation in selected cases.Employment of this method led to a halving of the mortality rate at Christchurch Hospital.The results in a series of 93 admissions compare favourably with those reported in the literature.We acknowledge with gratitude the help of Mr. J. T. Murray, hospital biochemist, who standardized and supervised the bloodvolume estimations and made many important contributions to our work; and of Drs. A. F. Burry and A. V. Kurta, who assisted throughout the course of these investigations.
998 SERUM TRIGLYCERIDE LEVEL AS A METABOLIC RISK FACTOR WAS INDEPENDENTLY ASSOCIATED WITH SERUM AMINOTRANSFERASE LEVEL IN NONALCOHOLIC FATTY LIVER DISEASE PATIENTS WITH CENTRAL OBESITY
Authors: E. Ishibashi, Y. Eguchi, T. Mizuta, Y. Kitajima, N. Oza, S. Nakashita, A. Matsunobu, H. Takahashi, Y. Kawaguchi, I. Ozaki, R. Iwakiri, T. Eguchi, N. Ono, K. Fujimoto
Journal: Journal of Hepatology (2009)
Radiotherapeutic Principles and Viewpoints
Authors: Isadore Lampe
Journal: JAMA (1971)

Squamous cell carcinoma is an important and common cancer of the oral cavity and the lower lip. Although variable degrees of differentiation do occur, the predominant histopathological finding is in the direction of a moderate to a well-differeniated tumor. On the lower lip, in the oral cavity (in which the common location is the oral portion of the tongue), the floor of the mouth, and the lower gingiva (mandible), the squamous cell carcinoma is a radioresponsive and radiocurable neoplasm. The therapeutic armamentarium currently available for attack on these lesions is diverse; it includes radiations uniquely advantageous for obtaining control of these tumors. They range from low-voltage x-ray suitable for superficial lip carcinomas, to orthovoltage radiation for advanced lip lesions and per oral techniques, to supervoltage radiation; the latter minimizes acute and chronic cutaneous radiation reactions and, significantly, relatively spares the bone tissues. In addition, low-intensity radium needles or radioactive substitutes