tbuckley/cabot-search huggingface dataset:
Toso, a Cell Surface, Specific Regulator of Fas-Induced Apoptosis in T Cells
Authors: Yasumichi Hitoshi, James Lorens, Shin-Ichi Kitada, Joan Fisher, Mark LaBarge, Huijun Z Ring, Uta Francke, John C Reed, Shigemi Kinoshita, Garry P Nolan
Journal: Immunity (1998)

Fas is a surface receptor that can transmit signals for apoptosis. Using retroviral cDNA library–based functional cloning we identified a gene toso, that blocks Fas-mediated apoptosis. Toso expression was confined to lymphoid cells and was enhanced after cell-specific activation processes in T cells. Toso appeared limited to inhibition of apoptosis mediated by members of the TNF receptor family and was capable of inhibiting T cell self-killing induced by TCR activation processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition of caspase-8 processing, the most upstream caspase activity in Fas-mediated signaling, potentially through activation of cFLIP. Toso therefore serves as a novel regulator of Fas-mediated apoptosis and may act as a regulator of cell fate in T cells and other hematopoietic lineages.
α-Adrenergic Receptor–Stimulated Hypertrophy in Adult Rat Ventricular Myocytes Is Mediated via Thioredoxin-1–Sensitive Oxidative Modification of Thiols on Ras
Authors: Gabriela M. Kuster, David R. Pimentel, Takeshi Adachi, Yasuo Ido, Daniel A. Brenner, Richard A. Cohen, Ronglih Liao, Deborah A. Siwik, Wilson S. Colucci
Journal: Circulation (2005)

Background— α-Adrenergic receptor (αAR)–stimulated hypertrophy in adult rat ventricular myocytes is mediated by reactive oxygen species–dependent activation of the Ras-Raf-MEK1/2-ERK1/2 signaling pathway. Because Ras is known to have redox-sensitive cysteine residues, we tested the hypothesis that αAR-stimulated hypertrophic signaling is mediated via oxidative modification of Ras thiols. Methods and Results— The effect of αAR stimulation on the number of free thiols on Ras was measured with biotinylated iodoacetamide labeling. αAR stimulation caused a 48% decrease in biotinylated iodoacetamide–labeled Ras that was reversed by dithiothreitol (10 mmol/L), indicating a decrease in the availability of free thiols on Ras as a result of an oxidative posttranslational modification. This effect was abolished by adenoviral overexpression of thioredoxin-1 (TRX1) and potentiated by the TRX reductase inhibitor azelaic acid. Likewise, αAR-stimulated Ras activation was abolished by TRX1 overexpression and potentiated by azelaic acid. TRX1 overexpression inhibited the αAR-stimulated phosphorylation of MEK1/2, ERK1/2, and p90RSK and prevented cellular hypertrophy, sarcomere reorganization, and protein synthesis (versus β-galactosidase). Azelaic acid potentiated αAR-stimulated protein synthesis. Although TRX1 can directly reduce thiols, it also can scavenge ROS by increasing peroxidase activity. To examine this possibility, peroxidase activity was increased by transfection with catalase, and intracellular reactive oxygen species were measured with dichlorofluorescein diacetate fluorescence. Although catalase increased peroxidase activity ≈20-fold, TRX1 had no effect. Likewise, the αAR-stimulated increase in dichlorofluorescein diacetate fluorescence was abolished with catalase but retained with TRX1. Conclusions— αAR-stimulated hypertrophic signaling in adult rat ventricular myocytes is mediated via a TRX1-sensitive posttranslational oxidative modification of thiols on Ras.
Novel therapies in breast cancer: what is new from ASCO 2008
Authors: David Chu, Janice Lu
Journal: Journal of Hematology & Oncology (2008)

Breast cancer is the most common female cancer and the second most common cause of female cancer-related deaths in the United States. World-wide, more than one million women will be diagnosed with breast cancer annually. In 2007, more than 175,000 women were diagnosed with breast cancer in the United States. However, deaths due to breast cancer have decreased in the recent years in part because of improved screening techniques, surgical interventions, understanding of the pathogenesis of the disease, and utilization of traditional chemotherapies in a more efficacious manner. One of the more exciting areas of improvement in the treatment of breast cancer is the entrance of novel therapies now available to oncologists. In the field of cancer therapeutics, the area of targeted and biologic therapies has been progressing at a rapid rate, particularly in the treatment of breast cancer.Since the advent of imatinib for the successful treatment of chronic myelogenous leukemia in the 2001, clinicians have been searching for comparable therapies that could be as efficacious and as tolerable. In order for targeted therapies to be effective, the agent must be able to inhibit critical regulatory pathways which promote tumor cell growth and proliferation. The targets must be identifiable, quantifiable and capable of being interrupted.In the field of breast cancer, two advances in targeted therapy have led to great strides in the understanding and treatment of breast cancer, namely hormonal therapy for estrogen positive receptor breast cancer and antibodies directed towards the inhibition of human epidermal growth factor receptor (HER)2. These advances have revolutionized the understanding and the treatment strategies for breast cancer. Building upon these successes, a host of novel agents are currently being investigated and used in clinical trials that will hopefully prove to be as fruitful. This review will focus on novel therapies in the field of breast cancer with a focus on metastatic breast cancer (MBC) and updates from the recent annual ASCO meeting and contains a summary of the results.
NOTES ON THE PROBLEMS OF SUICIDE AND ESCAPE
Authors: LAWRENCE F. WOOLLEY, ARNOLD H. EICHERT
Journal: American Journal of Psychiatry (1941)

We have presented a study of suicide and escape emergencies occurring in the Sheppard and Enoch Pratt Hospital during the nine year period from 1930 to 1938 inclusive. During this period there has been a progressive fall not only in actual suicides and escapes but in the number of attempts as well as the number of persons engaging in those attempts. We find it impossible to attribute this change to either the general trend in the United States during the same period or to statistical data such as age, severity of illness of our patients, or the case load of patients per unit personnel over the period of time studied. A review of this period reveals changes in attitude toward these problems that appear to be more significant and which may be summed up as follows: 1. A recognition that every mentally ill person is a potential suicide or escape hazard. 2. That the best preventive of suicide or escape is a nursing personnel that is acutely aware of the hazards and methods involved. 3. That special precautions against suicide and escape may be so exaggerated as to bring about the attempt through suggestion. 4. A recognition of the fact that much of the discomfort of patients in mental hospitals arises from their sexual tensions in situations rigidly restricted to a homosexual environment. This can be relieved in part by increasing as far as possible the mixed sexuality of the milieu in which the patient finds himself. 5. A recognition that too great restriction of patients' activities for the purpose of preventing suicide or escape may so increase the patient's discomfort as to add to the urgency of his attempts. 6. That the assignment of a special nurse to a patient with a view to preventing suicide or escape is only justifiable when the drive exhibited by the patient is immediately active to a degree that renders this necessary and that such specials should be removed as soon as possible. 7. These attitudes should not interfere in any way with carrying out routine practical measures which remove or prevent the development of special hazards. 8. That the prevention of suicide is after all primarily a nursing problem and should be carried out by the nurses. To meet this responsibility it is necessary for them to have special instruction and grounding in the fundamental principles involved.
Lipid–Protein Interactions along the Slit Diaphragm of Podocytes
Authors: Bernhard Schermer, Thomas Benzing
Journal: Journal of the American Society of Nephrology (2009)

Podocytes are visceral epithelial cells supporting the function of the glomerular filter. Interdigitating foot processes of podocytes enwrap the glomerular capillaries and are connected by a highly specialized cell junction, the slit diaphragm. Signal transduction at the slit diaphragm is essential for the proper function of the kidney filtration barrier. The slit diaphragm constitutes a dynamic multiprotein signaling complex that contains structural proteins, receptors, signaling adaptors, ion channels, and scaffolding proteins. Function of some of these proteins requires cholesterol attached to the multiprotein complex. Recruitment of cholesterol is achieved through the PHB domain protein podocin, a member of a novel family of lipid-binding proteins that are conserved through evolution. The finding that cholesterol interaction regulates the activity of ion channels at the glomerular filtration barrier has important implications for renal physiology and pathophysiology.
Long-term follow-up of two cases of pulmonary varicosity.
Authors: T Shirakusa
Journal: Thorax (1978)

Before diagnosis by pulmonary angiography two cases of pulmonary varicosity, one in a young girl and the other in a middle-aged man, had been misdiagnosed as pulmonary tuberculosis. Both patients were asymptomatic and received no specific treatment. Six and four years later there was no radiological change in either patient. Previously reported cases are briefly reviewed.
Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit.
Authors: L Jayakody, M Senaratne, A Thomson, T Kappagoda
Journal: Circulation Research (1987)

The effect of feeding a diet supplemented with lipids and containing 2% cholesterol on the endothelium-dependent relaxation of rabbit aorta to acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2% cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2% cholesterol diet or a standard rabbit diet. The animals were anesthetized with pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2% cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of atherosclerosis in the aorta was assessed by Sudan Red staining, estimation of tissue cholesterol, and light and electron microscopy. The relaxation response to acetylcholine was measured in rings of the thoracic aorta following precontraction with norepinephrine (-6.0 log mol/l). The relaxation was significantly impaired in aortas from rabbits fed the 2% cholesterol diet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2% cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2% cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.
Measurements on the Elasticity and Damping of Isolated Aortic Strips of the Dog
Authors: RICHARD W. LAWTON
Journal: Circulation Research (1955)

The experimental data obtained on the viscoelastic behavior of isolated aortic strips of the dog consist of: (1) the resonant or natural frequency of forced or free longitudinal vibration; (2) the logarithmic decrement. From these data, static and dynamic moduli and the time constants for the specimens are computed. Variations of these values with frequency, temperature and elongation are presented. The experimental observations are not adequately explained by a simple mechanical analogue. An alternative explanation is offered based on studies of dynamic elasticity in high polymers.
Uptake of Tc-99m-PIPIDA in Pulmonary Metastases from a Hepatoma
Authors: Jack R. Cannon, Robert F. Long, Sanford V. Berens, Gerald E. Caplan
Journal: Clinical Nuclear Medicine (1980)

Metastatic pulmonary nodules from a well-differentiated hepatoma were well demonstrated by a Tc-99m-labeled hepatobiliary imaging agent. Uptake of this type of radionuclide by metastases from a primary hepatic malignancy has not previously been reported. Such radiopharmaceuticals may prove useful in the future as imaging agents for primary hepatobiliary tumors.
Risk Factors for Measles in a Vaccinated Population-Reply
Authors: Eric E. Mast
Journal: JAMA (1991)

<h3>In Reply. —</h3> We thank Dr Waters and Ms Cook for their interest in our report. Our study was designed to assess the independent effects of vaccination before the age of 15 months, time since vaccination, and vaccination before a change in the measles vaccine stabilizer in 1979 as risk factors for measles vaccine failure. Siblings of case patients were selected as controls to attempt to ensure that all case patients and controls were exposed to the measles virus. To investigate age as a risk factor, cases and controls were not age matched because, contrary to the statement by Dr Waters and Ms Cook, the etiologic role of a variable on which both cases and controls are matched cannot be evaluated.<sup>1</sup>As Dr Waters and Ms Cook note, case patients in our study were older than the controls. We also agree that crude measles attack rates can vary with
Changing Concepts in Psychosomatic Theory I. Historical Analysis
Authors: Chase Patterson Kimball
Journal: Psychotherapy and Psychosomatics (1979)

Psychosomatic medicine has utilized static, linear, two-dimensional models in attempting to identify a causative relationship between psychosocially conceptualized events and biologically conceptualized ones. This has led to inherent difficulties that are logistically unresolvable. For example, the different language systems lend themselves to overlap with the possibility of addressing themselves to describing manifestations of the same phenomenon from dissimilar conceptual orientations. The problem is further complicated by attempting to link these together in a temporal sequence suggesting a causal relationship. We have ignored both feedback processes in terms of a sequential process modifying a preceding one and the possibility that a reverse order of relationships might explain some processes. In our quest for specificity, we have ignored that disease states are not static ones any more than is life but change over time, suggesting that alterations will occur in the original relationships proposed among our different systems of conceptualization. Among the remedies suggested for a reordering of our thinking are: (a) a revision of linear unidirectional causative models to cyclical bidirectional models; (b) a reformulation of two-dimensional temporal linear relationships toward three-dimensional spherical ones which overlap in time; (c) the relating of these aspects not to each other but to a third factor, common to the three which remains to be identified; (d) the development of a language that bridges the psychological, social and biological.
Development and maintenance of renal hypertension in normal and guanethidine sympathectomized rats.
Authors: J R Douglas, E M Johnson, G R Marshall, J Heist, B K Hartman, P Needleman
Journal: Circulation Research (1975)

The sympathetic nervous system has been postulated to play a role in the maintenance of renal hypertension. Permanent peripheral sympathectomy was performed by treating newborn rats for 21 days with guanethidine. Sympathectomy was confirmed by (1) relative insensitivity to tyramine, (2) lack of responsiveness to renal nerve stimulation, and (3) absence of dopamine-beta-hydroxylase immunofluorescence in renal blood vessels. Placement of a clip on the left renal artery led to the development of two-kidney renal hypertension. No differences were observed between the two-kidney renal hypertensive normal and sympathectomized rats; both had elevated plasma renin activity and vasodepression with angiotensin antagonists which were maintained up to nine weeks. Furthermore, in normal rats chronic beta-adrenergic blockade with propranolol caused no change in the development of the two-kidney renal hypertension. Similarly, no differences were seen in blood pressure, plasma renin activity, or response to antagonists between the one-kidney renal hypertensive (clip plus contralateral nephrectomy) normal and sympathectomized rats. Both showed sustained low renin hypertension up to 12 weeks. The absence of the peripheral sympathetic nervous system did not affect the development or maintenance of hypertension in either model of hypertension.
THE EFFECT OF OPERATIVE INTERFERENCE WITH THE CERVICAL SYMPATHETIC NERVOUS SYSTEM UPON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF THE RABBIT
Authors: Louise Pearce, Chester M. Van Allen
Journal: The Journal of Experimental Medicine (1925)

The effect of the removal of the complete cervical sympathetic nervous system, of both superior and of both inferior cervical ganglia, and of a small portion of the cervical sympathetic nerve in the rabbit was studied in relation to the character of a malignant disease induced by a transplantable neoplasm. It was found that the general character of the disease which developed in the operated groups of animals was more severe than that of a similar sized control group. Comparisons of the mortality rate in the several groups, of the animal inddence of metastases, the number of metastatic foci, and the distribution of these secondary growths all showed this to be the case. There appeared, furthermore, to be differences in malignancy among the operated groups themselves. The most severe disease occurred in the group in which a portion of the sympathetic nerve only was removed (sympathotomy); that in the complete sympathectomy and superior sympathectomy groups was slightly less malignant; and that in the inferior group was much less so. These results have been interpreted as due to a less effective animal resistance, the mechanism of which has been interfered with in some way by the interference with the sympathetic nerves. The reasons for the difference in malignancy exhibited by the several operated groups are undetermined. A tentative explanation is suggested upon the basis of coordinating, favorable or deleterious functions subserved by the cervical sympathetic nervous system.
Paraquat and Adrenal Cortical Necrosis
Authors: A. H. Nagi
Journal: BMJ (1970)

article on corneal disease (4 April, p. 33) states that surgical removal of a pterygium has a recurrence rate of some 50%.This, of course, used to be true.Mr. Cairns seems to be unaware of the fact that the use of eye drops consisting of a 1/2,000 solution of triethylene thiophosphoramide (Thio-Tepa) reduces the recurrence rate to less than 1 %1 .The drops are used every three hours during the waking period for six to eight weeks.The solution keeps its activity for at least two weeks if stored in a refrigerator and gives better results and none of the complications that can occur with beta-radiation therapy.-Iam, etc.,
Transplanted organs from women more likely to be rejected
Authors: R. Dobson
Journal: BMJ (2002)

Patients who receive organs from female donors are more likely to reject the transplant than those who have organs from a male donor, according to the results of a new large study. Mortality was also found to be higher among this group.

Researchers at the University of Heidelberg in Germany who analysed a worldwide database of more than 124 000 kidney transplants, 25 000 heart transplants and 16 000 …
Improvements Needed in Management of Temporomandibular Joint Disorders
Authors: Tracy Hampton
Journal: JAMA (2008)

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An “Opting In” Paradigm for Kidney Transplantation
Authors: David Steinberg
Journal: The American Journal of Bioethics (2004)

Almost 60,000 people in the United States with end stage renal disease are waiting for a kidney transplant. Because of the scarcity of organs from deceased donors live kidney donors have become a critical source of organs; in 2001, for the first time in recent decades, the number of live kidney donors exceeded the number of deceased donors. The paradigm used to justify putting live kidney donors at risk includes the low risk to the donor, the favorable risk-benefit ratio, the psychological benefits to the donor, altruism, and autonomy coupled with informed consent; because each of these arguments is flawed we need to lessen our dependence on live kidney donors and increase the number of organs retrieved from deceased donors. An "opting in" paradigm would reward people who agree to donate their kidneys after they die with allocation preference should they need a kidney while they are alive. An "opting in" program should increase the number of kidneys available for transplantation and eliminate the morally troubling problem of "organ takers" who would accept a kidney if they needed one but have made no provision to be an organ donor themselves. People who "opt in" would preferentially get an organ should they need one at the minimal cost of donating their kidneys when they have no use for them; it is a form of organ insurance a rational person should find extremely attractive. An "opting in" paradigm would simulate the reciprocal altruism observed in nature that sociobiologists believe enhances group survival. Although the allocation of organs based on factors other than need might be morally troubling, an "opting in" paradigm compares favorably with other methods of obtaining more organs and accepting the status quo of extreme organ scarcity. Although an "opting in" policy would be based on enlightened self-interest, by demonstrating the utilitarian value of mutual assistance, it would promote the attitude that self-interest sometimes requires the perception that we are all part of a common humanity.
FLAVONOID ADMINISTRATION IMPROVES ARTERIAL WALL PROPERTIES IN HEALTHY SMOKERS
Authors: Eleni Kokkou, Gerasimos Siasos, Dimitris Tousoulis, Evangelos Oikonomou, Maria Eleni Kollia, Alexios Verveniotis, Stamatios Kioufis, Nikolaos Gouliopoulos, Marina Zaromitidou, Panagiotis Tourikis, Konstantinos Zisimos, Georgios Marinos, Athanasios Papavassiliou, Christodoulos I Stefanadis
Journal: Journal of the American College of Cardiology (2013)