bluuebunny/crossref_metadata_2025_split huggingface dataset:
Creation and the Symbiosis of Science and Judaism
Authors: Samuelson Norbert M. 
Published: March 2003

It seems to me that the critical questions that science and natural philosophy raise for Jewish theology are the following: Does God evolve? Does the universe have or even need an interpretation, specifically with reference to the fact that most of the universe most of the time is uninhabitable, and there may be many more than one universe? Does the universe need a beginning? What is distinctive about human consciousness, intelligence, and ethics in the light of evidence for evolution from all of the life sciences? Finally, will both life and the universe end?These questions are not only modern. They contain all the primary issues that have dominated rabbinic thought. That agenda can be summarized in six topics: How should we model what we believe about (1) God, (2) the world, and (3) the human being; and how should we understand the relations between them, that is, between (4) God and the world (or, creation), (5) God and the human (or, revelation), and (6) the human and the world (or, redemption)? In this paper I focus on the fourth issue, creation. My answer is presented in detail in my Judaism and the Doctrine of Creation(Samuelson 1994). Here I shall summarize my conclusions there concerning science, Jewish texts, and the correlation between them.
Religion/Technology, Not Theology/Science, as the Defining Dichotomy
Authors: Roy Rustum 
Published: March 2003

Science and religion are incommensurable: one cannot use centimeters to measure volume. Science's proper cognate is theology. Science and theology are human activities that are basically conceptual (partly fallible) frameworks for explaining experience. Religion and technology, by contrast, involve and control or limit human practice and experience: they involve “sensate” reality—people and things. The study of the interaction of these four terms (or any two) must use the terms more precisely.Science as practiced today has become scientism, another theology. Technology is, without any doubt, the world's most powerful and fastest growing religion.Minor squabbles among theologies, including science, must continue, but it is the tensions between technology and the established religions that will define this century. Battles on three fronts are already clear: the environment, globalization, and economic gaps. But whole–person healing, the replacement for high–tech reductionist modern medicine, is the most significant, because it will undermine science, which has hitched its wagon to this falling star.The end of fundamental science is upon us, because it has been so successful. Science will be increasingly applications–driven, and it will be judged by results. Here, it has met its nemesis in wholeperson healing that incorporates integrative medicine. Scientists must now reconsider their role in society. It will not be easy to accept a humbler position. Moreover, the vague allusions to spirituality by scientists need a more authentic commitment to praxis in lifestyle.
Ligands for L-Selectin: Homing, Inflammation, and Beyond
Authors: Rosen Steven D. 
Published: March 2003

Understanding the molecular basis of lymphocyte homing to lymphoid organs was originally a problem of concern only to immunologists. With the discovery of l-selectin and its ligands, interested scientists have expanded to include glycobiologists, immunopathologists, cancer biologists, and developmental biologists. Going beyond its first discovered role in homing to lymph nodes, the l-selectin system is implicated in such diverse processes as inflammatory leukocyte trafficking in both acute and chronic settings, hematogenous metastasis of carcinoma cells, effector mechanisms for inflammatory demyelination of axons, and implantation of the early mammalian embryo. This review focuses on the ligands for l-selectin that are found on vascular endothelium, leukocytes, carcinoma cells, and at various extravascular sites. The discovery of selectins and their ligands has validated the long-predicted hypothesis that carbohydrate-directed cell adhesion is relevant in eukaryotic systems. Emphasis will be given to the carbohydrate and sulfation modifications of the ligands, which enable recognition by l-selectin.The rapid “homing” of labeled cells into the lymph nodes presumably had its basis in the special affinity of small lymphocytes for the endothelium of the postcapillary venules.     Gowans & Knight ( 1 )
Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules
Authors: Mackewicz Carl E. , Wang Baikun , Metkar Sunil , Richey Matthew , Froelich Christopher J. , Levy Jay A. 
Published: March 2003

AbstractIn HIV infection, CD8+ cells show cytotoxic and noncytotoxic anti-HIV activity. The latter function is mediated, at least in part, by a secreted antiviral protein, the CD8+ cell antiviral factor (CAF). Because antiviral effector molecules, such as perforin and granzymes, reside in the exocytic granules of CD8+ T cells, we examined the possibility that granules contain CAF-like activity. CD8+ cells from HIV-infected individuals showing strong CAF-mediated antiviral activity were induced to release their granule constituents into culture media. Within 1 hour of stimulation, high levels of granzyme B (a primary granule constituent) were found in the culture fluids of previously activated CD8+ cells. The same culture fluids contained no or very low amounts of CAF activity, as measured with HIV-infected CD4+ cells. Maximal levels of CAF activity were not observed until 5 or 7 days after stimulation, consistent with typical CAF production kinetics. In addition, extracts of granules purified from antiviral CD8+ cells did not show any CAF activity, whereas the cytoplasmic fraction of these cells showed substantial levels of antiviral activity. These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells. (Blood. 2003;102: 180-183)
Sorting of soluble TNF-receptor for granule storage in hematopoietic cells as a principle for targeting of selected proteins to inflamed sites
Authors: Gao Ying , Rosén Hanna , Johnsson Ellinor , Calafat Jero , Tapper Hans , Olsson Inge 
Published: March 2003

AbstractHematopoietic cells have secretory lysosomes that degranulate at the inflammatory site upon stimulation. We asked whether one could target exogenous proteins with a therapeutic potential to secretory lysosomes in hematopoietic cells. For this purpose, we expressed a soluble tumor necrosis factor (TNF) receptor form (sTNFR1) in hematopoietic cell lines. In order to accomplish targeting to secretory lysosomes, both endoplasmic reticulum (ER) retention and constitutive secretion have to be prevented. ER export was facilitated by addition of a transmembrane (tm) sequence, and constitutive secretion was overcome by incorporating a cytosolic sorting signal (Y) from CD63. This signal directed the resulting sTNFR1-tm-Y to secretory lysosomes. Confirmation of these results was provided by biosynthetic radiolabeling, subcellular fractionation, immunofluorescence microscopy, and immunoelectron microscopy. The tm-Y fragment was cleaved by proteolysis, resulting in generation of the membrane-free sTNFR1 in secretory lysosomes. Our results suggest a potential for using the storage organelles of hematopoietic cells as vehicles for targeting sites of inflammation with therapeutically active agents.
Multiparity induces priming to male-specific minor histocompatibility antigen, HY, in mice and humans
Authors: James Edward , Chai Jian-Guo , Dewchand Hamlata , Macchiarulo Eugenio , Dazzi Francesco , Simpson Elizabeth 
Published: March 2003

AbstractOne of the factors that increases the risk of graft-versus-host disease following allogeneic stem cell transplantation is the use of multiparous females as donors. Since minor histocompatibility (H) antigens are the main targets of graft-versus-host and graft-versus-leukemia responses, we tested the hypothesis that multiparity could prime minor H antigen—specific T cells. We examined the peripheral lymphoid populations of multiparous mice and humans for evidence of priming of CD8+ T-cytotoxic lymphocytes against peptide epitopes of the male-specific minor H antigen, HY. In contrast to naive females, multiparous females have measurable levels of circulating HY-specific tetramer-positive T lymphocytes, which can be readily expanded in vitro. These findings have implications for the in vitro generation of T-cell clones as reagents for immunotherapy for tumors following stem cell transplantation. (Blood. 2003; 102:388-393)
Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems
Authors: Gordon Susan M. , Buchwald Manuel 
Published: March 2003

AbstractFanconi anemia (FA) is an autosomal recessive syndrome characterized by progressive bone marrow failure and cancer predisposition. Eight FA complementation groups have been identified. The FANCA, FANCC, FANCE, FANCF, and FANCG proteins form a nuclear complex required for the monoubiquination of the FANCD2 protein. To investigate the architecture of the FA protein complex, the yeast 2-hybrid system was used to map contact points of the FANCA/FANCG, FANCC/FANCE, and FANCF/FANCG interactions. FANCG was shown to interact with both the amino-terminus of FANCA and the carboxyl-terminal region of FANCF. A FANCG mutant truncated at the carboxyl-terminus retained the ability to interact with FANCA. The interaction between FANCG and FANCF was ablated by a Leu71Pro mutant of FANCG. A central region of FANCE was sufficient for FANCC binding. A Leu554Pro mutant of FANCC failed to interact with FANCE. To further examine complex assembly, the yeast 3-hybrid system was used to investigate the ability of FANCG to act as a molecular bridge in mediating interaction between other FA proteins. FANCG was able to mediate interaction between FANCA and FANCF, as well as between monomers of FANCA. Direct interaction between FANCE and FANCD2 was also demonstrated in the yeast 2-hybrid system. This interaction involving an amino-terminal region of FANCD2 may provide a link between the FA protein complex and its downstream targets. (Blood. 2003;102:136-141)
Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence
Authors: Cavalieri Simona , Cazzaniga Sabrina , Geuna Massimo , Magnani Zulma , Bordignon Claudio , Naldini Luigi , Bonini Chiara 
Published: March 2003

AbstractGene transfer into T lymphocytes is currently being tested for the treatment of lymphohematologic disorders. We previously showed that suicide gene transfer into donor lymphocytes infused to treat leukemic relapse after allogeneic hematopoietic stem cell transplantation allowed control of graft-versus-host disease. However, the T-cell receptor (TCR) activation and sustained proliferation required for retroviral vector transduction may impair the half-life and immune competence of transduced cells and reduce graft-versus-leukemia activity. Thus, we tested lentiviral vectors (LVs) and stimulation with cytokines involved in antigen-independent T-cell homeostasis, such as interleukin 7 (IL-7), IL-2, and IL-15. Late-generation LVs transduced efficiently nonproliferating T cells that had progressed from G0 to the G1 phase of the cell cycle on cytokine treatment. Importantly, IL-2 and IL-7, but not IL-15, stimulation preserved physiologic CD4/CD8 and naive-memory ratios in transduced cells with only minor induction of some activation markers. Functional analysis of immune response to cytomegalovirus (CMV) showed that, although CMV-specific T cells were preserved by all conditions of transduction, proliferation and specific killing of autologous cells presenting a CMV epitope were higher for IL-2 and IL-7 than for IL-15. Thus, LV transduction of IL-2 or IL-7 prestimulated cells overcomes the limitations of retroviral vectors and may significantly improve the efficacy of T-cell–based gene therapy.
Randomized Trial of Tamoxifen Versus Tamoxifen Plus Aminoglutethimide as Adjuvant Treatment in Postmenopausal Breast Cancer Patients With Hormone Receptor-Positive Disease: Austrian Breast and Colorectal Cancer Study Group Trial 6
Authors: Schmid Marianne , Jakesz Raimund , Samonigg Hellmut , Kubista Ernst , Gnant Michael , Menzel Christian , Seifert Michael , Haider Karin , Taucher Susanne , Mlineritsch Brigitte , Steindorfer Peter , Kwasny Werner , Stierer Michael , Tausch Christoph , Fridrik Michael , Wette Viktor , Steger Günther , Hausmaninger Hubert 
Published: March 2003

Purpose: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor–positive, early-stage breast cancer. Patients and Methods: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. Results: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P = .89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P = .74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P = .0001). Conclusion: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.
Quantitation of GD2 Synthase mRNA by Real-Time Reverse Transcriptase Polymerase Chain Reaction: Clinical Utility in Evaluating Adjuvant Therapy in Neuroblastoma
Authors: Cheung Irene Y. , Lo Piccolo M. Serena , Kushner Brian H. , Kramer Kim , Cheung Nai-Kong V. 
Published: March 2003

Purpose: Minimal residual disease (MRD) is one of the final hurdles to cancer cure. Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy. Patients and Methods: Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of GD2 synthase (β1,4-N-acetylgalactosaminyltransferase, EC 2.4.1.92 ) mRNA, we evaluated MRD response to anti-GD2 monoclonal antibody 3F8 adjuvant therapy, namely, one cycle of radioimmunotherapy using iodine-131 (131I)-3F8 plus one cycle of unlabeled 3F8 in 45 stage 4 neuroblastoma patients (newly diagnosed or without prior relapse) on the N7 protocol at Memorial Sloan-Kettering Cancer Center. The prognostic effect of MRD in their bone marrows before and after this phase of adjuvant therapy on progression-free survival (PFS) and overall survival (OS) was also analyzed. Results: Before 3F8 treatment, 24 of 45 patients were in complete remission (CR), 12 were in very good partial remission (VGPR), and nine were in partial remission (PR), according to criteria from International Neuroblastoma Staging System plus 131I-3F8 scan; 71% had detectable tumor cells in marrow by real-time RT-PCR. Of the 32 positive patients, 20 became negative after therapy, with a 63% efficacy. When patients were stratified by CR/VGPR versus PR, GD2 synthase positivity was prognostic when detected before 3F8-targeted therapy (PFS, P = .045 and OS, P = .010). Persistent marker positivity was also predictive of PFS (P = .035) and OS (P = .027). Patients who succumbed to the disease had transcript levels four times higher than those who remain alive. Conclusion: GD2 synthase mRNA is a useful surrogate marker for evaluating adjuvant treatment efficacy in neuroblastoma with prognostic potential.
Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer
Authors: Henderson I. Craig , Berry Donald A. , Demetri George D. , Cirrincione Constance T. , Goldstein Lori J. , Martino Silvana , Ingle James N. , Cooper M. Robert , Hayes Daniel F. , Tkaczuk Katherine H. , Fleming Gini , Holland James F. , Duggan David B. , Carpenter John T. , Frei Emil , Schilsky Richard L. , Wood William C. , Muss Hyman B. , Norton Larry 
Published: March 2003

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
Quality of Life in Good Prognosis Patients With Metastatic Germ Cell Cancer: A Prospective Study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20)
Authors: Fosså Sophie D. , de Wit Ronald , Roberts J. Trevor , Wilkinson Peter M. , de Mulder Pieter H.M. , Mead Graham M. , Cook Pat , de Prijck Linda , Stenning Sally , Aaronson Neil K. , Bottomley Andrew , Collette Laurence 
Published: March 2003

Purpose: To describe global quality of life (GLQL) in patients with metastatic testicular cancer (TC) treated with four different schedules of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (four v three cycles given over 5 v 3 days). Patients and Methods: Quality-of-life data were prospectively collected in 666 patients with metastatic TC entered into the European Organization for Research and Treatment of Cancer (EORTC) Trial 30941/United Kingdom Medical Research Council Trial TE20, using the EORTC Quality-of-Life Questionnaire C30 and a TC module. Data were analyzed by a mixed effects model and by evaluation of clinically relevant changes at 2 years. Results: The pattern of GLQL changes was similar in the four groups. Two years after chemotherapy, 36% of patients displayed improved GLQL as compared with baseline, whereas GLQL had deteriorated in 13%. At 3 months, patients receiving the 3-day regimen experienced increased gastrointestinal (GI) toxicity more than those receiving the 5-day regimen, with the difference reaching the level of clinical relevance (≥ 10-point change) if four cycles were given. The 3-day schedule increased the 2-year risk of tinnitus, with clinical relevance demonstrated after four cycles. Long-term peripheral neuropathy and Raynaud-like phenomena were not associated with the number of cycles or days per cycle. At 2 years, Raynaud-like phenomena, tinnitus, or reduced hearing were reported by 21% to 26% of the patients. Conclusion: Because of the excess of acute GI toxicity and the increased risk of tinnitus after the 3-day regimen, we recommend the 5-day regimen if four cycles of BEP are planned. If only three cycles are to be given, then the 3-day regimen is acceptable, even given the increased risk of nausea/vomiting at 3 months.
Maternal Preoccupation and Parenting as Predictors of Emotional and Behavioral Problems in Children of Women With Breast Cancer
Authors: Sigal John J. , Perry J. Christopher , Robbins James M. , Gagné Marie-Anik , Nassif Edgard 
Published: March 2003

Purpose: To test the hypothesis that differences between sicker and not-so-sick women in their preoccupation with their illness and parenting behavior can explain why some investigators find that children of breast cancer patients fare better than controls and other investigators find the reverse. Patients and Methods: Forty-two women with metastasized breast cancer (sicker mothers) and 45 women with a first occurrence of nonmetastasized breast cancer (not-so-sick mothers) rated the degree of their preoccupation with the disease, their parenting behavior, mood, and social supports and the emotional and behavioral symptoms in one of their children. Their 12- to 18-year-old children rated their mothers’ parenting behavior, their own emotional and behavioral symptoms, and their self-esteem. Results: Sicker mothers reported relatively less preoccupation. They, and their children, reported less poor parenting and fewer externalizing symptoms in the children. Regression analyses revealed further differences between the groups. Conclusion: Less preoccupation with their illness and less poor parenting behavior by sicker mothers may explain why their children seem to fare better then those of not-so-sick mothers. Formulations concerning families of breast cancer patients should include consideration of the effect of the mothers’ perception of the severity of their illness.