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Search Results: 1 - 10 of 301645 matches for " Arthur J. Weiss "
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A Hypothesis Concerning the Effect of Schedule on the Pattern of 5-Fluorouracil Toxicity  [PDF]
Arthur J. Weiss
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.63028

The significant effect that scheduling has upon the severity and types of drug toxicity has been known for many years. Evidence is available demonstrating that the schedule chosen will substantially effect the relative distribution of drug to various target organs. It has been shown that a likely cause for this with doxorubicin is that the efficiency of the various enzyme complexes responsible for disposing of the drug can be affected by scheduling. We believe a similar process can explain the marked effect that scheduling has on the pattern of 5-fluorouracil toxicity and present both clinical and computer data to illustrate this.

Three Protocols Designed to Individualize and Maximize Anti-Cancer Drug Therapy  [PDF]
Arthur J. Weiss, Irwin L. Stoloff
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.612120
Abstract: The role that attaining maximum drug dosage intensity plays in many anti-cancer protocols is a major one, particularly in those protocols that attempt to totally eradicate the neoplasm. A classic approach to facilitate this process utilizes stem cell transplants as well as the use of hematopoetic growth factors. However, problems arise with both allogenic and autologous transplants as well as from the significant variability in drug tolerance between individual patients. With average fixed dose protocols, these problems substantially limit the ability to optimize drug dosage. We attempted to circumvent this difficulty by using low dose continuous infusional therapy of variable duration depending upon the patient’s response, together with simultaneous hematopoietic growth factor support. This paper presents our results with three drugs, doxorubicin, ifosphamide, and vinorelbine. With these protocols, we were able to individualize and optimize the amount of drug delivered to each patient, as well as to substantially increase the drug dosage intensity of each of these agents.
The Effect of Granulocyte Macrophage-Colony Stimulating Factor upon the Induction of Peripheral Blood Dendritic and Natural Killer Cells When Given Simultaneously with a Slow Continuous Doxorubicin Infusion  [PDF]
Arthur J. Weiss, Irwin L. Stoloff, Antonio C. Simoes
Journal of Cancer Therapy (JCT) , 2017, DOI: 10.4236/jct.2017.87054
Abstract: It has been demonstrated that it is safe to give Gm-Csf, together with Doxorubicin, by continuous intravenous infusion, thereby substantially increasing the amount of Doxorubicin administered to the average patient, and assuring that each patient receives an individually-determined safe and maximal amount of drug. It is known that Gm-Csf is a potent inducer of components that are major factors in an immunologic attack upon neoplasms. For that reason, we thought it would be worth evaluating in 4 patients’ surface markers of dendritic precursor cells, dendritic cells [DC], and natural killer [NK] cells during the infusion. While there was substantial variation in individual responses, all 4 patients receiving Gm-Csf developed persistent marked increases in cells with each of these markers. The significance of these findings will be discussed.
The Relation between the Initial Type of Schedule Used to Administer Doxorubicin and Long Term Doxorubicin Cardiotoxicity  [PDF]
Arthur J. Weiss, Irwin L. Stoloff, Antonio C. Simoes, Richard D. Lackman
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.512117
Abstract: Background: As more patients survive cancer chemotherapy, problems associated with the late complications of therapy have become increasingly apparent; late doxorubicin cardio-myopathy being one of the most pressing. The relationship between initial dose, schedule employed, and etiology are still not well defined. This study attempts to clarify some of these issues. Methods: Patients receiving large total doses of doxorubicin by schedules designed to minimize peak drug levels were monitored in regard to their cardiac status for up to 31 years following completion of doxorubicin therapy. A computer program predicting the amount of doxorubicin retained by the heart vs. schedules employed was devised with the predictions of the computer program being compared to the clinical findings. Results: 1365 patients receiving doses of doxorubicin greater than 610 mgm./M2 were monitored for up to 31 years following completion of such therapy. No patient developed unequivocal clinical and pathologic evidence of a doxorubicin related cardiomyopathy. Knowing that human cardio-myocytes contain enzymes capable of neutralizing doxorubicin, a computer program predicted that by increasing their efficiency, the schedules employed substantially l decreased the relative amount of drug retained by the heart, findings compatible with both animal experiments and clinical results. Conclusions: administration of doxorubicin by schedules in which peak plasma levels of drug were minimized resulted in marked decreases in both acute and long-term cardiac toxicity; believed to be due to potentiation of myocardial enzymes capable of inactivating the drug.
Antigen receptor signaling in the rheumatic diseases
Julie Zikherman, Arthur Weiss
Arthritis Research & Therapy , 2009, DOI: 10.1186/ar2528
Abstract: The classic concept of autoimmune disease rests upon the notion that the adaptive immune system generates inappropriate antigen-specific responses to self epitopes which in turn drive disease. Indeed, the presence of autoantibodies is one of the most characteristic features of the rheumatic diseases. Since the canonical definition of the adaptive immune response relates to the ability of somatic recombination to produce an enormous range of antigen receptors on lymphocytes, it follows that antigen receptor signal transduction ought to play a role in autoimmune diseases. The T-cell antigen receptor (TCR)-beta chain was cloned in 1983, and the subsequent decade saw the discovery of the signal transduction pathway downstream of the TCR [1]. Parallel discoveries for B-cell antigen receptor (BCR) signaling followed. Not only antigen receptors themselves but the complex machinery that elaborates the cellular response to antigen have been implicated in the rheumatic diseases. The past decade has seen evidence confirm this view from a range of sources, including engineered and spontaneous mouse models, primary lymphocytes from patients, as well as human genetics. Here, we provide a selective overview of some of these advances and propose some general principles that tie these observations together.TCR signal transduction is initiated following interaction of the TCR αβ chains with peptide antigen bound to major histocompatibility complex (MHC) class I or II molecules. The signal is transmitted to a complex network of kinases, phosphatases, and adaptors (Figure 1). The TCR αβ chains lack any ability to transmit signals on their own and depend on CD3 (ε, δ, and γ) and ζ chains that contain varying numbers of immunoreceptor tyrosine-based activating motifs (ITAMs). The dual tyrosines of ITAMs are phosphorylated by the Src family kinases (SFKs), which, in T cells, are Lck and Fyn. Dually phosphorylated ITAMs, in turn, form docking sites for the tandem SH2 domains of Syk family
Some Non-Unimodal Level Algebras
Arthur Jay Weiss
Mathematics , 2007,
Abstract: In 2005, building on his own recent work and that of F. Zanello, A. Iarrobino discovered some constructions that, he conjectured, would yield level algebras with non-unimodal Hilbert functions. This thesis provides proofs of non-unimodality for Iarrobino's level algebras, as well as for other level algebras that the author has constructed along similar lines. The key technical contribution is to extend some results published by Iarrobino in 1984. Iarrobino's results provide insight into some naturally arising vector subspaces of the vector space R_d of forms of fixed degree in a polynomial ring in several variables. In this thesis, the problem is approached by combinatorial methods and results similar to Iarrobino's are proved for a different class of vector subspaces of R_d. The combinatorial methods involve the definition of a new class of matrices called L-Matrices, which have useful properties that are inherited by their submatrices. A particular class of square L-Matrices, associated with some specialized partially ordered sets having interesting combinatorial properties, is identified. For this class of L-Matrices, necessary and sufficient conditions are given that they be nonsingular. Several larger questions are discussed whose answers are incrementally improved by the knowledge that the new non-unimodal level algebras exist.
The rationale for pre-race aspirin to protect susceptible runners from sudden cardiac death during marathons: Deconstructing the Pheidippides conundrum  [PDF]
Arthur J. Siegel
World Journal of Cardiovascular Diseases (WJCD) , 2013, DOI: 10.4236/wjcd.2013.35A003
Abstract: Objectives: While endurance exercise such as training for marathons is cardioprotective, cardiac arrests and sudden death occur in previously healthy runners during races predominantly in middle-aged males due to atherosclerotic heart disease. Recent evidence related to this problem is reviewed herein including epidemiologic studies and findings related to acute cardiac risk in asymptomatic middle-aged male runners during races. Method: Literature review related to the above. Findings: The risks of cardiac arrest and sudden death were 1 in 57,002 and 1 in 171,005 respectively in runners with a mean age of 49.7 years among 1,710,052 participants in marathons in the United States since 1980. Atherosclerotic heart disease was the cause of death in over 90% of cases in two retrospective studies and a greater than two-fold increase in cardiac arrests was observed in middle-aged men in the latter half of a 10-year prospective registry beginning in the year 2000. Asymptomatic middle-aged male runners showed elevated biomarkers of inflammation such as interleukin-6, C-reactive protein together with procoagulant effects including in vivo platelet activation, indicating susceptibility to atherothrombosis. Conclusions: Antithrombotic prophylaxis is evidence-based by validated clinical paradigms to prevent cardiac arrest and sudden death in susceptibile marathon runners at high risk for atherothrombosis during races.

Preventing Sudden Cardiac Death during Marathons with Pre-Race Aspirin  [PDF]
Arthur J. Siegel
World Journal of Cardiovascular Diseases (WJCD) , 2015, DOI: 10.4236/wjcd.2015.58024
Abstract: Objectives: Prevention of sudden cardiac death is the number one clinical priority in sports cardiology. While the overall cardiovascular risk of long distance running is acknowledged as low, the frequency of cardiac arrests and sudden death has increased in middle-aged males during marathons since the year 2000. An evidence-based strategy for protecting susceptible runners from these acute cardiac events during races is considered based on identification of the underlying cause. Method: Review of articles in Pub Med on adverse cardiac events during marathons. Findings: Recent epidemiological studies have identified an increasing frequency of cardiac arrest in middle-aged males during marathons since the year 2000 with atherosclerotic heart disease as the main cause of sudden cardiac death. Same-aged asymptomatic middle-aged male physician-runners showed a post-race polymorphonuclear leukocytosis with sequential increases in interleukin-6 and C-reactive protein as a likely consequence of rhabdomyolysis after “hitting the wall”. Increased fibrinogen, von Willebrand factor and D-dimer with in vivo platelet activation indicated a concurrent hemostatic imbalance with pro-coagulant effects. Cardiac troponins I and T and NT-pro-B-type natriuretic peptide were elevated after races as additionally predictive of acute cardiac events in asymptomatic persons. Conclusions: High short-term risk for acute cardiac events in asymptomatic middle-aged male runners is shown by stratification of validated biomarkers, which may render non-obstructive coronary atherosclerotic plaques vulnerable to rupture during marathons. Pre-race aspirin usage is prudent to reduce these events mediated by atherothrombosis based on conclusive evidence for prevention of first acute myocardial infarctions in same-aged healthy male physicians. Prospective studies are needed to determine the efficacy of pre-race low-dose aspirin for curtailing the increasing frequency of race-related cardiac arrest and sudden death in susceptible runners.
An AAD Model of Point Particle and the Pauli Equation
J. Weiss
Physics , 2000,
Abstract: The classical relativistic linear AAD interaction, introduced by the author, leads in the case of weak coupling to a pointlike particle capable to be sub- mitted to quantization via Feynman's path integrals along the line adequate to the requirements of the Pauli equation. In the discussed nonrelativistic case of the model the concept of spin is considered within early Feynman's ideas.
A Linear-confined Particle and the Dirac Equation
J. Weiss
Physics , 2000,
Abstract: The model of a classical particle with the weak linear AAD potential is subjected to path integral quantization. The light cone constraints and peculiar properies of its internal variables permit to use in calculations commutative dynamics and apply path integrals for a matrix form of the transition amplitude. Quantization leads to description of a Dirac particle.
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