David Spiegel

Bio: David Spiegel is an academic researcher from Stanford University. The author has contributed to research in topics: Medicine & Breast cancer. The author has an hindex of 106, co-authored 733 publications receiving 46276 citations. Previous affiliations of David Spiegel include Tel Aviv University & University of Adelaide.

An Antibody-Recruiting Small Molecule That Targets HIV gp120

Abstract: HIV/AIDS is a global pandemic for which new treatment strategies are desperately needed. We have designed a novel small molecule, designated as ARM-H, that has the potential to interfere with HIV survival through two mechanisms: (1) by recruiting antibodies to gp120-expressing virus particles and infected human cells, thus enhancing their uptake and destruction by the human immune system, and (2) by binding the viral glycoprotein gp120, inhibiting its interaction with the human protein CD4 and preventing virus entry. Here we demonstrate that ARM-H is capable of simultaneously binding gp120, a component of the Env surface viral glycoprotein (found on the surface of both HIV and virus-infected cells) and anti-2,4-dinitrophenyl antibodies (already present in the human bloodstream). The ternary complex formed between the antibody, ARM-H, and gp120 is immunologically active and leads to the complement-mediated destruction of Env-expressing cells. Furthermore, ARM-H prevents virus entry into human T-cells and s...

Psychosocial intervention for lesbians with primary breast cancer.

Abstract: This study examined the effects of a Supportive-Expressive group therapy intervention offered to lesbians with early stage breast cancer. Twenty lesbians diagnosed with breast cancer in the previous 12-months were recruited and assessed at baseline, and at 3, 6, and 12 months after the group intervention. During the 12-week intervention, group members focused on the problems of a new diagnosis, coping with the illness and treatment, mood changes, coping responses and self-efficacy, improving relationships with family, friends and physicians, the impact of the illness on life, pain and sleep, and changes in body image and sexuality. A within-subject slopes analysis was conducted on data collected for each woman over the first year. As predicted, women reported reduced emotional distress, intrusiveness, and avoidance, and improved coping. There were significant changes in their social support, but in the unexpected direction. Instrumental support and informational support declined. However, conflict in family relations also declined, while trends were found towards more cohesiveness and expressiveness. Participants reported less pain and better sleep. There were no changes in body image, sexuality, or attitudes toward health-care providers. These results suggest that Supportive/Expressive group intervention appears to be helpful for lesbians with breast cancer.

Bioimpedance resistance ratios for the evaluation of dry weight in hemodialysis

Abstract: Material: Restoration of body water compartments to normal by ultrafiltration is a major goal of hemodialysis. Dry weight is the term used to define normal body water in dialysis patients, but it is limited, as it is based solely on clinical observations. Bioimpedance spectroscopy can accurately measure the resistance of body fluid compartments. The ratio of the resistances of the intracellular to extracellular water should reflect the relative volume of these compartments. As dialysis patients accumulate excess fluid in their extracellular compartment, this ratio may prove useful in the evaluation of dry weight. Methods: We measured the resistances of the intracellular and extracellular fluid compartments in normal subjects to define the normal ratio of the resistances of these compartments. Women had a slightly higher ratio than men (women: 2.41 ± 0.23 vs. men: 2.08 ± 0.23 vs. p < 0.0001). The ratios determined in the normal population were taken as the normal physiologic ratio and were used to define physiologic dry weight. We then compared dialysis patients both pre- and post-dialysis to this normal population. Results: We found that most patients (67%, n = 18) had an elevated ratio pre-dialysis suggesting excess extracellular fluid. Of the 38 treatments in which patients achieved their clinical dry weight, 19 (50%) had persistently elevated R i /R e ratios, suggesting they had not reached physiologic dry weight. Conclusion: These data suggest that many dialysis patients carry excess extracellular fluid post dialysis despite achieving their clinical dry weight. Furthermore, the resistance ratio derived from bioimpedance spectroscopy may be a useful clinical tool in determining dry weight.

An oligomer-based approach to skeletal diversity in small-molecule synthesis.

Abstract: Access to small molecules of widely varying molecular shapes has been identified as an enabling step in the discovery of biologically active materials. In this communication we introduce an approach to the systematic development of architecturally distinct chemical compounds based upon the assembly of reactive monomers into linear oligomers, each of which encodes a unique molecular framework under a common set of reaction conditions. Certain products of the initial chemical transformation (Ru-catalyzed metathesis reaction) encode additional skeletons upon treatment with a second common set of reagents (Diels−Alder dienophiles). Application of this oligomerization approach has led to the discovery of a previously unreported tandem ene-yne−yne metathesis−6π-electrocyclization−1,5-hydride migration that converts a linear substrate into a complex tricyclic 1,3-diene in a single step. Thus, the reported strategy might serve not only as a generator of skeletally diverse small molecules but also as a discovery p...

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The Benefits of Being Present: Mindfulness and Its Role in Psychological Well-Being

Abstract: Mindfulness is an attribute of consciousness long believed to promote well-being. This research provides a theoretical and empirical examination of the role of mindfulness in psychological well-being. The development and psychometric properties of the dispositional Mindful Attention Awareness Scale (MAAS) are described. Correlational, quasi-experimental, and laboratory studies then show that the MAAS measures a unique quality of consciousness that is related to a variety of well-being constructs, that differentiates mindfulness practitioners from others, and that is associated with enhanced selfawareness. An experience-sampling study shows that both dispositional and state mindfulness predict self-regulated behavior and positive emotional states. Finally, a clinical intervention study with cancer patients demonstrates that increases in mindfulness over time relate to declines in mood disturbance and stress. Many philosophical, spiritual, and psychological traditions emphasize the importance of the quality of consciousness for the maintenance and enhancement of well-being (Wilber, 2000). Despite this, it is easy to overlook the importance of consciousness in human well-being because almost everyone exercises its primary capacities, that is, attention and awareness. Indeed, the relation between qualities of consciousness and well-being has received little empirical attention. One attribute of consciousness that has been much-discussed in relation to well-being is mindfulness. The concept of mindfulness has roots in Buddhist and other contemplative traditions where conscious attention and awareness are actively cultivated. It is most commonly defined as the state of being attentive to and aware of what is taking place in the present. For example, Nyanaponika Thera (1972) called mindfulness “the clear and single-minded awareness of what actually happens to us and in us at the successive moments of perception” (p. 5). Hanh (1976) similarly defined mindfulness as “keeping one’s consciousness alive to the present reality” (p. 11). Recent research has shown that the enhancement of mindfulness through training facilitates a variety of well-being outcomes (e.g., Kabat-Zinn, 1990). To date, however, there has been little work examining this attribute as a naturally occurring characteristic. Recognizing that most everyone has the capacity to attend and to be aware, we nonetheless assume (a) that individuals differ in their propensity or willingness to be aware and to sustain attention to what is occurring in the present and (b) that this mindful capacity varies within persons, because it can be sharpened or dulled by a variety of factors. The intent of the present research is to reliably identify these inter- and intrapersonal variations in mindfulness, establish their relations to other relevant psychological constructs, and demonstrate their importance to a variety of forms of psychological well-being.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.