David Zava

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Papers by David Zava

Perceived Stress, Psychosocial Stressors, and Behavioral Factors: Association With Inflammatory, Immune, and Neuroendocrine Biomarkers in a Cohort of Healthy Very Elderly Men and Women

Cleveland Clinic Journal of Medicine, Aug 1, 2011

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Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke

Frontiers in Human Neuroscience, Feb 21, 2017

This single-arm non-randomized pilot study explores an intervention to improve the health of flig... more This single-arm non-randomized pilot study explores an intervention to improve the health of flight attendants (FA) exposed to second-hand cigarette smoke prior to the smoking ban on commercial airlines. This group exhibits an unusual pattern of long-term pulmonary dysfunction. We report on Phase I of a two-phase clinical trial; the second Phase will be a randomized controlled trial testing digital delivery of the intervention. Subjects were recruited in the Northeastern US; testing and intervention were administered in 4 major cities. The intervention involved 12 h of training in Meditative Movement practices. Based on recent research on the effects of nicotine on fear learning, and the influence of the autonomic nervous system on immune function, our hypothesis was that this training would improve autonomic function and thus benefit a range of health measures. Primary outcomes were the 6-min walk test and blood levels of C-reactive protein. Pulmonary, cardiovascular, autonomic, and affective measures were also taken. Fourteen participants completed the training and posttesting. There was a 53% decrease in high sensitivity C-Reactive Protein (p ≤ 0.05), a 7% reduction in systolic blood pressure (p ≤ 0.05), a 13% increase in the 6-min walk test (p ≤ 0.005), and significant positive changes in several other outcomes. These results tend to confirm the hypothesized benefits of MM training for this population, and indicate that autonomic function may be important in the etiology and treatment of their symptoms. No adverse effects were reported. This trial is registered at ClinicalTrials.gov (), and is supported by a grant from the Flight Attendant Medical Research Institute (FAMRI).

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Neuroendocrine, Inflammatory, and Immune Biomarkers Associated With Body Composition, Depression, and Cognitive Impairment in Elderly Men and Women

Cleveland Clinic Journal of Medicine, Aug 1, 2011

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The Relationship Between Progesterone, Sleep, and LH and FSH Secretory Dynamics in Early Postmenarchal Girls

The Journal of Clinical Endocrinology and Metabolism, Jan 15, 2019

Context: During puberty, LH pulse frequency increases during sleep; in women, LH pulse frequency ... more Context: During puberty, LH pulse frequency increases during sleep; in women, LH pulse frequency slows during sleep in the early/middle follicular phase (FP) of the menstrual cycle. The origin and significance of this developmental transition are unknown. Objective: To determine the relationship between progesterone (P4) exposure, sleep-related slowing of LH pulses in the FP, and the intercycle FSH rise, which promotes folliculogenesis, in early postmenarchal girls. Methods: 23 girls (gynecologic age 0.4 to 3.5 years) underwent hormone measurements and pelvic ultrasounds during two consecutive cycles and one frequent blood sampling study with concurrent polysomnography during the FP. Results: Subjects demonstrated one of four patterns during cycle 1 that represent a continuum of P4 exposure: ovulatory cycles with normal or short luteal phase lengths or anovulatory cycles 6 follicle luteinization. Peak serum P4 and urine pregnanediol (Pd) in cycle 1 were inversely correlated with LH pulse frequency during sleep in the FP of cycle 2 (r = 20.5; P = 0.02 for both). The intercycle FSH rise and folliculogenesis in cycle 2 were maintained after anovulatory cycles without P4 or Pd exposure or nocturnal slowing of LH pulse frequency in the FP. Conclusions: During late puberty, rising P4 levels from follicle luteinization and ovulation may promote a slower LH pulse frequency during sleep in the FP. However, a normal FSH rise and follicle growth can occur in the absence of P4-associated slowing. These studies therefore suggest that an immature LH secretory pattern during sleep is unlikely to contribute to menstrual irregularity in the early postmenarchal years.

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Screening and characterization of estrogenic activity from a hydroxystilbene library

Chemistry & Biology, 1995

Compounds that either inhibit or induce an estrogen response in vi00 are important as potential d... more Compounds that either inhibit or induce an estrogen response in vi00 are important as potential drugs and biochemical tools. Non-steroidal stilbene analogs such as tamoxifen are known to function as both estrogen agonists and antagonists depending upon the analog structure. This family of compounds is amenable to parallel-manifold synthesis because stilbene analogs are easily synthesized using a single-step olefination reaction. Results: We have prepared a small 23-component hydroxystilbene library using a solid phase synthesis approach. The library was screened for estrogenic and antiestrogenic activity using a cell-based bioassay that measures estrogen receptor-mediated transcription of a reporter gene.Three of the analogs proved to have dose-dependent estrogenic activity with EC,, values between 5 uM and 15 /.&I. Further characterization of the hydroxystilbene-mediated estrogenic activity suggests that the agonist activity results from direct binding to the steroid site on the estrogen receptor with IC,, values of l-10 PM. The results of this study show that classic olefination chemistry can be adapted to a solid-phase format for parallel synthesis of analog libraries. Although yields varied for the individual analogs, sufficient quantity of pure material was obtained directly h-om the resin for structural characterization and biological evaluation. This study further validates solid-phase organic synthesis as a useful approach for rapid parallel-manifold library synthesis to augment both lead compound discovery and optimization.

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Estrogen and Progestin Receptors in Meningiomas

Clinical Neuropharmacology, Dec 1, 1984

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Human Breast Cancer: Androgen Action Mediated by Estrogen Receptor

Science, Feb 17, 1978

Each copy of any part of a JSTOR transmission must contain the same copyright notice that appears... more Each copy of any part of a JSTOR transmission must contain the same copyright notice that appears on the screen or printed page of such transmission. JSTOR is an independent not-for-profit organization dedicated to and preserving a digital archive of scholarly journals. For more information regarding JSTOR, please contact

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Estrogen Receptor Translocation and Replenishment by the Antiestrogen Tamoxifen

Endocrinology, Oct 1, 1977

ABSTRACT

Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture

Environmental Health Perspectives, Apr 1, 1997

Key words: xenoestrogens, phytoestrogens, endogenous estrogens, synthetic estrogens, breast cance... more Key words: xenoestrogens, phytoestrogens, endogenous estrogens, synthetic estrogens, breast cancer, reproduction (4,5) have contested the notion that trace levels of petrochemicals to which humans are inadvertently exposed act as endocrine dis- ruptors or increase the incidence of cancer. This counterargument suggests that xeno- estrogen levels to which humans are exposed daily are trivial relative to the daily exposure to natural phytoestrogens found abundantly in common foods consumed by humans. Many estrogen mimics are produced by plants and by the petrochemical and

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Androgen Receptor Assay with [<sup>3</sup>H]Methyltrienolone (R1881) in the Presence of Progesterone Receptors*

Endocrinology, Apr 1, 1979

The synthetic radiolabeled androgen methyltrienolone-17βhiydroxy-17α-methyl-estra-4,9,ll-trien-3-... more The synthetic radiolabeled androgen methyltrienolone-17βhiydroxy-17α-methyl-estra-4,9,ll-trien-3-one (R1881) is superior to the native ligand 5α-dihydrotestosterone (DHT) in the measurement of androgen receptor (AR), especially in tissues where radiolabeled DHT binds with high affinity to plasma proteins in addition to receptor or is rapidly metabolized to inactive derivatives. However, R1881 also binds progesterone receptor (PgR), as shown by its ability to complete for [3]-promestone-17α,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020) binding to 8S PgR on sucrose density gradients, resulting in an overestimation of AR if PgR is present. Therefore, we have devised a method by which PgR binding of R1881 can be blocked without interfering with AR binding. The glucocorticoid triamcinolone acetonide (TA) was found to bind PgR (competition for 8S [3]R5020 binding) but not AR (no competition for 8S [3H]DHT binding). In cytosols containing both receptors, a 500-fold excess of unlabeled TA was sufficient ...

RF15 | PMON304 Utilizing LC-MS/MS for the clinical quantitation of testosterone using dried blood spot and how it compare to serum

Journal of the Endocrine Society, Nov 1, 2022

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Receptors and breast cancer: Do we know it all?

Journal of Steroid Biochemistry, May 1, 1978

ABSTRACT The use of cytoplasmic estrogen receptor to predict endocrine responsiveness in breast c... more ABSTRACT The use of cytoplasmic estrogen receptor to predict endocrine responsiveness in breast cancer patients is now well established. It is our contention that this pertinent clinical application is only the first of many contributions from receptor studies to the clinic. Efforts are now underway to examine the distribution of receptors within tumor cells, and in particular the significance of receptors in tumor nuclei in the absence of hormone. Also, the demonstration of a direct stimulation of progesterone receptor synthesis by estradiol in cultured breast tumor cells now permits a careful dissection of the complete estrogen response system which should provide clues to the mechanism of antiestrogen action in causing tumor regression. Finally, it is now evident that pharmacologic effects of steroids in breast cancer may be mediated through different pathways than expected from studies of normal physiology.

Steroid Receptors in Breast Tumors—Current Status

Elsevier eBooks, 1978

Publisher Summary This chapter reviews the role of several hormones and their receptors in breast... more Publisher Summary This chapter reviews the role of several hormones and their receptors in breast cancer tissues and examines mechanisms of control. Breast cancer is often hormone-responsive because growth or regression of tumors can often be modulated by appropriate endocrine manipulations. Estrogen and progesterone appear to be the major hormones involved in the regulation of breast tumor growth. The inference that each hormone acts independently through its receptor to control tumor growth is belied by the current studies showing that certain hormones are capable of regulating the receptor sites, metabolism, or nuclear translocation of others. This may begin to explain the complex hormonal interactions and the requirements of normal and neoplastic breast tissues. Considerable progress has, thus, been made in understanding the basis for success of various ablative therapies. Many of the studies on hormone-dependent breast carcinoma employ animal models, particularly carcinogen-induced rat mammary tumors, which regress after endocrine ablative surgery. The chapter discusses the relevance of these animal models to the clinical problem of human breast cancer. It illustrates the physiological principles of hormone action in breast cancer tissue so that an appreciation of the mechanism of endocrine-induced breast tumor regression will develop. Such an understanding should lead to a more rational approach for selecting or rejecting endocrine therapy for advanced breast cancer patients.

Biological Expression of Steroid Hormone Receptors in Primary Meningioma Cells in Monolayer Culture

Clinical Neuropharmacology, Dec 1, 1984

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Reliability of steroid hormone receptor assays: an international study

European Journal of Cancer and Clinical Oncology, Mar 1, 1983

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Human Breast Cancer: Biologically Active Estrogen Receptor in the Absence of Estrogen?

Science, May 6, 1977

The human breast cancer cell line MCF-7 does not require estrogen for growth, but paradoxically i... more The human breast cancer cell line MCF-7 does not require estrogen for growth, but paradoxically its growth is inhibited by antiestrogens. Our results show that, unlike normal target cells, MCF-7 cells carry most of their estrogen receptors in their nuclei even when these receptors are not charged with estrogens. The receptors for androgen and for progesterone, on the other hand, are localized in the cytoplasm as usual. Therefore, it is possible that the growth of these abnormal cells is stimulated by estrogen receptor in spite of the absence of the hormone and that the binding of antiestrogen molecules antagonize this stimulation.

Estrogen and progesterone receptors in meningiomas in relation to clinical and pathologic features

Surgical Neurology, Jul 1, 1983

ABSTRACT

Sexual steroid hormone receptor assays in human astrocytomas

Surgical Neurology, Sep 1, 1983

293 Internal Quality Control of Routine Human Breast Cancer Estrogen and Progesterone Receptor Assays

Journal of Steroid Biochemistry, 1983

Sex Hormone Metabolism and Threatened Abortion

Medical Science Monitor, Oct 23, 2017

The aim of this study was to evaluate changes in sex hormone metabolism in patients with threaten... more The aim of this study was to evaluate changes in sex hormone metabolism in patients with threatened miscarriage. We recruited 73 women in early pregnancy (6-8 weeks of gestation) and divided them into the following 2 groups based on whether they had vaginal bleeding: group A (n=34), the threatened abortion group; and group B (n=39), the normal pregnancy group. Human chorionic gonadotrophin (hCG), estradiol (E 2 ), progesterone (P 4 ), and testosterone (T) serum levels were tested and sex hormone metabolites in the urine were detected using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). As the control, data for sex hormones and their metabolites were obtained in normal women of childbearing age without pregnancy (group C: n=23). E 2 and T serum levels were lower in women with threatened miscarriage (group A). Estrone (E 1 ), E 2 , estriol (E 3 ), 16a-hydroxyestrone (16a-OHE 1 ), 4-methoxyestrone (4-MeOE 1 ), 2-hydroxyestradiol (2-OHE 2 ), and 4-methoxyestradiol (4-MeOE 2 ) levels were significantly lower in group A (P=0.001, 0.003, 0.009, 0.001, 0.012, 0.032, and 0.047, respectively.). Urine levels of dehydroepiandrosterone (DHEA), androstenedione (A 2 ), and the metabolite of (A 2 ) were also significantly lower in group A (P=0.007, 0.009, and 0.011, respectively). The 2-OHE

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Perceived Stress, Psychosocial Stressors, and Behavioral Factors: Association With Inflammatory, Immune, and Neuroendocrine Biomarkers in a Cohort of Healthy Very Elderly Men and Women

Cleveland Clinic Journal of Medicine, Aug 1, 2011

Download

Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke

Frontiers in Human Neuroscience, Feb 21, 2017

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Neuroendocrine, Inflammatory, and Immune Biomarkers Associated With Body Composition, Depression, and Cognitive Impairment in Elderly Men and Women

Cleveland Clinic Journal of Medicine, Aug 1, 2011

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The Relationship Between Progesterone, Sleep, and LH and FSH Secretory Dynamics in Early Postmenarchal Girls

The Journal of Clinical Endocrinology and Metabolism, Jan 15, 2019