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Papers by Richard Hanna

The authors reconcile conflicting findings in the promotions literature regarding time restrictio... more The authors reconcile conflicting findings in the promotions literature regarding time restrictions. Using hypothetical and real coupons, the authors show that shorter time restrictions lower purchase intent by lowering deal evaluations while also increasing purchase intent by increasing consumers' sense of urgency. The authors also demonstrate that anticipated regret plays a more complex role in consumers' responses to promotions than previously believed.

The Faseb Journal, Apr 1, 2009

J Endocrinol, 2006

Recently, a unique family of membrane progestin receptors (mPRa, mPRb, and mPRg) was identified, ... more Recently, a unique family of membrane progestin receptors (mPRa, mPRb, and mPRg) was identified, which may be responsible for mediating rapid, nongenomic actions of progestins in a variety of target tissues. In this study, the mPRa and mPRb isoforms from zebrafish were shown to be rapidly and specifically activated by the maturation-inducing steroid (MIS) of this species, 4-pregnen-17,20b-diol-3-one (17,20b-DHP). The zebrafish mPRa and a previously uncharacterized mPRb isoform were stably expressed in nuclear progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231. Expression and surface localization of the receptors were verified by flow cytometry, biotin surface labeling, and Western blotting. Plasma membrane proteins from mPRa-or mPRb-transfected cells showed high affinity (mPRa, K d 7 nM; mPRb, K d 12 nM), saturable, displaceable, single-binding sites specific for 17,20b-DHP, whereas negligible specific 17,20b-DHP binding was observed in nontransfected cells. Progestin treatment caused significant activation of mitogen-activated protein kinase (MAPK) within 5 min in cells transfected with either of the receptors as measured by western blotting and flow cytometry. The rank order of the potencies of several progestins in activating MAPK via mPRa and mPRb was the same (17,20b,. Interestingly, the MIS in zebrafish, 17,20b-DHP, was also the most potent inhibitor, among the progestins tested, of adenylyl cyclase activity in cells transfected with either of the receptors. This progestin significantly decreased cAMP levels in both mPRa-and mPRb-transfected cells in a dose-responsive and timedependent manner. In addition, signaling of the zebrafish mPRa was blocked by pertussis toxin, implying activation of a G i protein, while sensitivity to pertussis or cholera toxin was not shown with mPRb-mediated signaling, possibly indicating that this receptor activates a different pertussis toxin-insensitive G protein. The results of this study suggest that zebrafish mPRa and mPRb signal similarly upon progestin binding resulting in rapid activation of MAPK and downregulation of adenylyl cyclase activity.

Ideas in Marketing: Finding the New and Polishing the Old, 2014

PloS one, 2013

Gammadelta (γδ) T lymphocytes respond quickly upon antigen encounter to produce a cytokine respon... more Gammadelta (γδ) T lymphocytes respond quickly upon antigen encounter to produce a cytokine response. In this study, we sought to understand how functions of γδ T cells are differentially regulated compared to αβ T cells. We found that cholesterol, an integral component of the plasma membrane and a regulator of TCR signaling, is increased in γδ T cells compared to αβ T cells, and modulates their function. Higher levels of activation markers, and increased lipid raft content in γδ cells suggest that γδ T cells are more activated. Cholesterol depletion effectively decreased lipid raft formation and activation of γδ T cells, indicating that increased cholesterol content contributes to the hyper-activated phenotype of γδ T cells, possibly through enhanced clustering of TCR signals in lipid rafts. TCR stimulation assays and western blotting revealed that instead of a lower TCR threshold, enhanced TCR signaling through ERK1/2 activation is likely the cause for high cholesterol-induced rapi...

Molecular and Cellular Endocrinology, 2011

Both membrane progestin receptors (mPRs) and the nuclear progestin receptor (nPR or Pgr) decode t... more Both membrane progestin receptors (mPRs) and the nuclear progestin receptor (nPR or Pgr) decode the non-genomic progestin signaling (NGPS) in vertebrates. However, the receptor for deciphering extracellular NGPS and initiating meiosis resumption in vertebrate oocytes is still contested hotly. We studied the roles of nPR and mPRs by determining their localization, changes of expression, and activation of NGPS during final oocyte maturation (FOM) in zebrafish. The nPR transcript and protein were expressed abundantly in follicular cells that were surrounding stage IV oocytes, but nPR transcript appeared absent within stage IV oocytes. The most significant daily changes of nPR transcript were observed in stage IV follicular cells, with the highest level observed just prior to ovulation. In contrast, the expressions of mPR␣ and mPR␤ transcripts and proteins were abundant and increased significantly in late stage denuded oocytes prior to oocyte maturation, consistent with the purported role of mPRs in interpreting NGPS. Moreover, over-expression of mPR␣ in follicle-enclosed oocytes significantly increased the activity of MAPK, the production of cyclin B protein, and the number of oocytes that underwent FOM without exogenous progestin, while over-expression of mPR␤ or nPR alone had no such effect. Intriguingly, significant acceleration of FOM was observed when follicle-enclosed oocytes were incubated with the maturation inducing steroid, 4-pregnen-17, 20␤-diol-3-one (DHP) following over-expression of nPR or mPR␣. Interestingly, this acceleration in oocyte maturation was observed approximately 1 h later in oocytes over-expressing nPR compared to those over-expressing mPR␣. Importantly, the acceleration of maturation in the nPR injected group was blocked by treatment with the transcription inhibitor actinomycin D, implying a requirement of the genomic signaling pathway, while the same treatment did not affect the accelerated rate of maturation in mPR˛injected oocytes. Taken together, these results imply that nPR and mPR␤ are unlikely receptors for inducing FOM, while mPR␣ is the long-sought-after nongenomic progestin receptor that deciphers extracellular NGPS to initiate meiosis resumption in follicle-enclosed zebrafish oocytes.

Journal of Personal Selling and Sales Management, 2010

Drawing on social learning theory, we examine how the perceived technological savvy of a salesper... more Drawing on social learning theory, we examine how the perceived technological savvy of a salesperson's manager, coworkers, and competitors affects sales technology usage behavior. Data were drawn from a major retail bank in Nigeria, Africa. Analyses of data from relationship managers confirm predictions that while perceived coworker savvy directly influences technology usage, the influence of managers' and competitors' perceived savvy is mediated. Perceived manager savvy influences usage by increasing feelings of monitoring and the level of perceived coworker savvy. Similarly, perceived competitor savvy influences usage by increasing perceived manager and coworker savvy. We also confirm that usage of sales technology has a positive influence on salesperson performance.

Journal of Endocrinology, 2006

Gynecologic Oncology, 2011

Gynecologic Oncology, 2011

The study aims to compare the difference in treatment and survival between White (W) and African ... more The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC). Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed. A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p<0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p=0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%,…

Gynecologic Oncology, 2011

To identify factors that increase the risk of neutropenic events in women with advanced ovarian c... more To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy. Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC]<500/mm(3)) and febrile neutropenia (FN; ANC<1000/mm(3) and temperature>38.1°C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression. Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area<2.0m(2) (p=0.03), body mass index (BMI)<30 kg/m(2) (p<0.01), Caucasian race (p<0.01), treatment on research protocols (p<0.01), non-carboplatin-containing regimens (p<0.01), and planned relative dose intensity (RDI)>85% of standard (p=0.02). Women over age 60 were more likely to develop FN (p=0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p<0.01), Caucasian race (HR 2.13; p=0.01), and planned RDI>85% (HR 1.69; p=0.05); predictors of FN were age>60 (HR 2.84; p=0.05) and non-carboplatin containing regimens (HR 4.06; p<0.01). While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

General and Comparative Endocrinology, 2009

A distinct family of membrane progestin receptors (mPRa, mPRb, and mPRc) that mediate rapid, nong... more A distinct family of membrane progestin receptors (mPRa, mPRb, and mPRc) that mediate rapid, nongenomic actions of progestins has been identified and characterized in several fish species as well as in frogs, rats, pigs, and humans. However, few studies to date have thoroughly examined tissue specific expression of mPR protein and transcripts in any model species. In the present study, the expression of both mPRa and mPRb in zebrafish was examined by RT-PCR, Western blotting and immunohistochemistry using mPR specific primers and antibodies. The proteins and mRNAs of mPRa and mPRb were colocalized in the major reproductive organs, including the ovary, testis, and pituitary. Both mPRa and mPRb were found in scattered cells in the pituitary for the first time. In the testis, immunostaining of mPRa was restricted to the sperm, while mPRb was found in spermatocytes and spermatogonia. In the ovary, both mPRa and mPRb were detected in denude oocytes and follicular layer cells. Furthermore, mPRa and mPRb proteins were localized at or near the oocyte membrane of maturationally competent stage IV oocytes in a probable location for mediating progestin-induced nongenomic signaling in oocytes.

Biology of Reproduction, 2010

The zebrafish nuclear progestin receptor (nPR; official symbol PGR) was identified and characteri... more The zebrafish nuclear progestin receptor (nPR; official symbol PGR) was identified and characterized to better understand its role in regulating reproduction in this well-established teleost model. A full-length cDNA was identified that encoded a 617amino acid residue protein with high homology to PGRs in other vertebrates, and contained five domains characteristic of nuclear steroid receptors. In contrast to the multiplicity of steroid receptors often found in euteleosts and attributed to probable genome duplication, only a single locus encoding the full-length zebrafish pgr was identified. Cytosolic proteins from pgr-transfected cells showed a high affinity (K d ¼ 2 nM), saturable, single-binding site specific for a native progestin in euteleosts, 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). Both 17,20beta-DHP and progesterone were potent inducers of transcriptional activity in cells transiently transfected with pgr in a dual luciferase reporter assay, whereas androgens and estrogens had little potency. The pgr transcript and protein were abundant in the ovaries, testis, and brain and were scarce or undetectable in the intestine, muscle, and gills. Further analyses indicate that Pgr was expressed robustly in the preoptic region of the hypothalamus in the brain; proliferating spermatogonia and early spermatocytes in the testis; and in follicular cells and earlystage oocytes (stages I and II), with very low levels within maturationally competent late-stage oocytes (IV) in the ovary. The localization of Pgr suggests that it mediates progestin regulation of reproductive signaling in the brain, early germ cell proliferation in testis, and ovarian follicular functions, but not final oocyte or sperm maturation. hypothalamus, nuclear progestin receptor, oocyte, ovarian follicle, ovary, pgr, PR, progesterone, progesterone receptor, testis, zebrafish

Advances in Consumer …, 2006

The authors reconcile conflicting findings in the promotions literature regarding time restrictio... more The authors reconcile conflicting findings in the promotions literature regarding time restrictions. Using hypothetical and real coupons, the authors show that shorter time restrictions lower purchase intent by lowering deal evaluations while also increasing purchase intent by increasing consumers' sense of urgency. The authors also demonstrate that anticipated regret plays a more complex role in consumers' responses to promotions than previously believed.

The Journal of Immunology, May 1, 2014

Nature immunology, Jan 2, 2015

The molecular mechanisms that link the sympathetic stress response and inflammation remain obscur... more The molecular mechanisms that link the sympathetic stress response and inflammation remain obscure. Here we found that the transcription factor Nr4a1 regulated the production of norepinephrine (NE) in macrophages and thereby limited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Lack of Nr4a1 in myeloid cells led to enhanced NE production, accelerated infiltration of leukocytes into the central nervous system (CNS) and disease exacerbation in vivo. In contrast, myeloid-specific deletion of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, protected mice against EAE. Furthermore, we found that Nr4a1 repressed autocrine NE production in macrophages by recruiting the corepressor CoREST to the Th promoter. Our data reveal a new role for macrophages in neuroinflammation and identify Nr4a1 as a key regulator of catecholamine production by macrophages.

Science (New York, N.Y.), Jan 22, 2015

The immune system plays an important role in regulating tumor growth and metastasis. For example,... more The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical "patrolling" monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient patrolling monocytes into Nr4a1-deficient mice prevented tumor invasion in lung. Patrolling monocytes established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature and promoted natural killer cell recruitment and activation. Thus, patrolling monocytes contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.

Scientific Reports, 2015

Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue m... more Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset.

Arteriosclerosis, thrombosis, and vascular biology, Jan 2, 2015

Nonclassical patrolling monocytes are characterized by their unique ability to actively patrol th... more Nonclassical patrolling monocytes are characterized by their unique ability to actively patrol the vascular endothelium under homeostatic and inflammatory conditions. Patrolling monocyte subsets (CX3CR1(high)Ly6C(-) in mouse and CX3CR1(high)CD14(dim)CD16(+) in humans) are distinct from the classical monocyte subsets (CCR2(high)Ly6C(+) in mouse and CCR2(high)CD14(+)CD16(-) in humans) and exhibit unique functions in the vasculature and inflammatory disease. Patrolling monocytes function in several disease settings to remove damaged cells and debris from the vasculature and have been associated with wound healing and the resolution of inflammation in damaged tissues. This review highlights the unique functions of these patrolling monocytes in the vasculature and during inflammation.

The authors reconcile conflicting findings in the promotions literature regarding time restrictio... more The authors reconcile conflicting findings in the promotions literature regarding time restrictions. Using hypothetical and real coupons, the authors show that shorter time restrictions lower purchase intent by lowering deal evaluations while also increasing purchase intent by increasing consumers' sense of urgency. The authors also demonstrate that anticipated regret plays a more complex role in consumers' responses to promotions than previously believed.

The Faseb Journal, Apr 1, 2009

J Endocrinol, 2006

Recently, a unique family of membrane progestin receptors (mPRa, mPRb, and mPRg) was identified, ... more Recently, a unique family of membrane progestin receptors (mPRa, mPRb, and mPRg) was identified, which may be responsible for mediating rapid, nongenomic actions of progestins in a variety of target tissues. In this study, the mPRa and mPRb isoforms from zebrafish were shown to be rapidly and specifically activated by the maturation-inducing steroid (MIS) of this species, 4-pregnen-17,20b-diol-3-one (17,20b-DHP). The zebrafish mPRa and a previously uncharacterized mPRb isoform were stably expressed in nuclear progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231. Expression and surface localization of the receptors were verified by flow cytometry, biotin surface labeling, and Western blotting. Plasma membrane proteins from mPRa-or mPRb-transfected cells showed high affinity (mPRa, K d 7 nM; mPRb, K d 12 nM), saturable, displaceable, single-binding sites specific for 17,20b-DHP, whereas negligible specific 17,20b-DHP binding was observed in nontransfected cells. Progestin treatment caused significant activation of mitogen-activated protein kinase (MAPK) within 5 min in cells transfected with either of the receptors as measured by western blotting and flow cytometry. The rank order of the potencies of several progestins in activating MAPK via mPRa and mPRb was the same (17,20b,. Interestingly, the MIS in zebrafish, 17,20b-DHP, was also the most potent inhibitor, among the progestins tested, of adenylyl cyclase activity in cells transfected with either of the receptors. This progestin significantly decreased cAMP levels in both mPRa-and mPRb-transfected cells in a dose-responsive and timedependent manner. In addition, signaling of the zebrafish mPRa was blocked by pertussis toxin, implying activation of a G i protein, while sensitivity to pertussis or cholera toxin was not shown with mPRb-mediated signaling, possibly indicating that this receptor activates a different pertussis toxin-insensitive G protein. The results of this study suggest that zebrafish mPRa and mPRb signal similarly upon progestin binding resulting in rapid activation of MAPK and downregulation of adenylyl cyclase activity.

Ideas in Marketing: Finding the New and Polishing the Old, 2014

PloS one, 2013

Gammadelta (γδ) T lymphocytes respond quickly upon antigen encounter to produce a cytokine respon... more Gammadelta (γδ) T lymphocytes respond quickly upon antigen encounter to produce a cytokine response. In this study, we sought to understand how functions of γδ T cells are differentially regulated compared to αβ T cells. We found that cholesterol, an integral component of the plasma membrane and a regulator of TCR signaling, is increased in γδ T cells compared to αβ T cells, and modulates their function. Higher levels of activation markers, and increased lipid raft content in γδ cells suggest that γδ T cells are more activated. Cholesterol depletion effectively decreased lipid raft formation and activation of γδ T cells, indicating that increased cholesterol content contributes to the hyper-activated phenotype of γδ T cells, possibly through enhanced clustering of TCR signals in lipid rafts. TCR stimulation assays and western blotting revealed that instead of a lower TCR threshold, enhanced TCR signaling through ERK1/2 activation is likely the cause for high cholesterol-induced rapi...

Molecular and Cellular Endocrinology, 2011

Both membrane progestin receptors (mPRs) and the nuclear progestin receptor (nPR or Pgr) decode t... more Both membrane progestin receptors (mPRs) and the nuclear progestin receptor (nPR or Pgr) decode the non-genomic progestin signaling (NGPS) in vertebrates. However, the receptor for deciphering extracellular NGPS and initiating meiosis resumption in vertebrate oocytes is still contested hotly. We studied the roles of nPR and mPRs by determining their localization, changes of expression, and activation of NGPS during final oocyte maturation (FOM) in zebrafish. The nPR transcript and protein were expressed abundantly in follicular cells that were surrounding stage IV oocytes, but nPR transcript appeared absent within stage IV oocytes. The most significant daily changes of nPR transcript were observed in stage IV follicular cells, with the highest level observed just prior to ovulation. In contrast, the expressions of mPR␣ and mPR␤ transcripts and proteins were abundant and increased significantly in late stage denuded oocytes prior to oocyte maturation, consistent with the purported role of mPRs in interpreting NGPS. Moreover, over-expression of mPR␣ in follicle-enclosed oocytes significantly increased the activity of MAPK, the production of cyclin B protein, and the number of oocytes that underwent FOM without exogenous progestin, while over-expression of mPR␤ or nPR alone had no such effect. Intriguingly, significant acceleration of FOM was observed when follicle-enclosed oocytes were incubated with the maturation inducing steroid, 4-pregnen-17, 20␤-diol-3-one (DHP) following over-expression of nPR or mPR␣. Interestingly, this acceleration in oocyte maturation was observed approximately 1 h later in oocytes over-expressing nPR compared to those over-expressing mPR␣. Importantly, the acceleration of maturation in the nPR injected group was blocked by treatment with the transcription inhibitor actinomycin D, implying a requirement of the genomic signaling pathway, while the same treatment did not affect the accelerated rate of maturation in mPR˛injected oocytes. Taken together, these results imply that nPR and mPR␤ are unlikely receptors for inducing FOM, while mPR␣ is the long-sought-after nongenomic progestin receptor that deciphers extracellular NGPS to initiate meiosis resumption in follicle-enclosed zebrafish oocytes.

Journal of Personal Selling and Sales Management, 2010

Drawing on social learning theory, we examine how the perceived technological savvy of a salesper... more Drawing on social learning theory, we examine how the perceived technological savvy of a salesperson's manager, coworkers, and competitors affects sales technology usage behavior. Data were drawn from a major retail bank in Nigeria, Africa. Analyses of data from relationship managers confirm predictions that while perceived coworker savvy directly influences technology usage, the influence of managers' and competitors' perceived savvy is mediated. Perceived manager savvy influences usage by increasing feelings of monitoring and the level of perceived coworker savvy. Similarly, perceived competitor savvy influences usage by increasing perceived manager and coworker savvy. We also confirm that usage of sales technology has a positive influence on salesperson performance.

Journal of Endocrinology, 2006

Gynecologic Oncology, 2011

Gynecologic Oncology, 2011

The study aims to compare the difference in treatment and survival between White (W) and African ... more The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC). Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed. A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p<0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p=0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%,…

Gynecologic Oncology, 2011

To identify factors that increase the risk of neutropenic events in women with advanced ovarian c... more To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy. Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC]<500/mm(3)) and febrile neutropenia (FN; ANC<1000/mm(3) and temperature>38.1°C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression. Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area<2.0m(2) (p=0.03), body mass index (BMI)<30 kg/m(2) (p<0.01), Caucasian race (p<0.01), treatment on research protocols (p<0.01), non-carboplatin-containing regimens (p<0.01), and planned relative dose intensity (RDI)>85% of standard (p=0.02). Women over age 60 were more likely to develop FN (p=0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p<0.01), Caucasian race (HR 2.13; p=0.01), and planned RDI>85% (HR 1.69; p=0.05); predictors of FN were age>60 (HR 2.84; p=0.05) and non-carboplatin containing regimens (HR 4.06; p<0.01). While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

General and Comparative Endocrinology, 2009

A distinct family of membrane progestin receptors (mPRa, mPRb, and mPRc) that mediate rapid, nong... more A distinct family of membrane progestin receptors (mPRa, mPRb, and mPRc) that mediate rapid, nongenomic actions of progestins has been identified and characterized in several fish species as well as in frogs, rats, pigs, and humans. However, few studies to date have thoroughly examined tissue specific expression of mPR protein and transcripts in any model species. In the present study, the expression of both mPRa and mPRb in zebrafish was examined by RT-PCR, Western blotting and immunohistochemistry using mPR specific primers and antibodies. The proteins and mRNAs of mPRa and mPRb were colocalized in the major reproductive organs, including the ovary, testis, and pituitary. Both mPRa and mPRb were found in scattered cells in the pituitary for the first time. In the testis, immunostaining of mPRa was restricted to the sperm, while mPRb was found in spermatocytes and spermatogonia. In the ovary, both mPRa and mPRb were detected in denude oocytes and follicular layer cells. Furthermore, mPRa and mPRb proteins were localized at or near the oocyte membrane of maturationally competent stage IV oocytes in a probable location for mediating progestin-induced nongenomic signaling in oocytes.

Biology of Reproduction, 2010

The zebrafish nuclear progestin receptor (nPR; official symbol PGR) was identified and characteri... more The zebrafish nuclear progestin receptor (nPR; official symbol PGR) was identified and characterized to better understand its role in regulating reproduction in this well-established teleost model. A full-length cDNA was identified that encoded a 617amino acid residue protein with high homology to PGRs in other vertebrates, and contained five domains characteristic of nuclear steroid receptors. In contrast to the multiplicity of steroid receptors often found in euteleosts and attributed to probable genome duplication, only a single locus encoding the full-length zebrafish pgr was identified. Cytosolic proteins from pgr-transfected cells showed a high affinity (K d ¼ 2 nM), saturable, single-binding site specific for a native progestin in euteleosts, 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). Both 17,20beta-DHP and progesterone were potent inducers of transcriptional activity in cells transiently transfected with pgr in a dual luciferase reporter assay, whereas androgens and estrogens had little potency. The pgr transcript and protein were abundant in the ovaries, testis, and brain and were scarce or undetectable in the intestine, muscle, and gills. Further analyses indicate that Pgr was expressed robustly in the preoptic region of the hypothalamus in the brain; proliferating spermatogonia and early spermatocytes in the testis; and in follicular cells and earlystage oocytes (stages I and II), with very low levels within maturationally competent late-stage oocytes (IV) in the ovary. The localization of Pgr suggests that it mediates progestin regulation of reproductive signaling in the brain, early germ cell proliferation in testis, and ovarian follicular functions, but not final oocyte or sperm maturation. hypothalamus, nuclear progestin receptor, oocyte, ovarian follicle, ovary, pgr, PR, progesterone, progesterone receptor, testis, zebrafish

Advances in Consumer …, 2006

The authors reconcile conflicting findings in the promotions literature regarding time restrictio... more The authors reconcile conflicting findings in the promotions literature regarding time restrictions. Using hypothetical and real coupons, the authors show that shorter time restrictions lower purchase intent by lowering deal evaluations while also increasing purchase intent by increasing consumers' sense of urgency. The authors also demonstrate that anticipated regret plays a more complex role in consumers' responses to promotions than previously believed.

The Journal of Immunology, May 1, 2014

Nature immunology, Jan 2, 2015

The molecular mechanisms that link the sympathetic stress response and inflammation remain obscur... more The molecular mechanisms that link the sympathetic stress response and inflammation remain obscure. Here we found that the transcription factor Nr4a1 regulated the production of norepinephrine (NE) in macrophages and thereby limited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Lack of Nr4a1 in myeloid cells led to enhanced NE production, accelerated infiltration of leukocytes into the central nervous system (CNS) and disease exacerbation in vivo. In contrast, myeloid-specific deletion of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, protected mice against EAE. Furthermore, we found that Nr4a1 repressed autocrine NE production in macrophages by recruiting the corepressor CoREST to the Th promoter. Our data reveal a new role for macrophages in neuroinflammation and identify Nr4a1 as a key regulator of catecholamine production by macrophages.

Science (New York, N.Y.), Jan 22, 2015

The immune system plays an important role in regulating tumor growth and metastasis. For example,... more The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical "patrolling" monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient patrolling monocytes into Nr4a1-deficient mice prevented tumor invasion in lung. Patrolling monocytes established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature and promoted natural killer cell recruitment and activation. Thus, patrolling monocytes contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.

Scientific Reports, 2015

Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue m... more Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset.

Arteriosclerosis, thrombosis, and vascular biology, Jan 2, 2015

Nonclassical patrolling monocytes are characterized by their unique ability to actively patrol th... more Nonclassical patrolling monocytes are characterized by their unique ability to actively patrol the vascular endothelium under homeostatic and inflammatory conditions. Patrolling monocyte subsets (CX3CR1(high)Ly6C(-) in mouse and CX3CR1(high)CD14(dim)CD16(+) in humans) are distinct from the classical monocyte subsets (CCR2(high)Ly6C(+) in mouse and CCR2(high)CD14(+)CD16(-) in humans) and exhibit unique functions in the vasculature and inflammatory disease. Patrolling monocytes function in several disease settings to remove damaged cells and debris from the vasculature and have been associated with wound healing and the resolution of inflammation in damaged tissues. This review highlights the unique functions of these patrolling monocytes in the vasculature and during inflammation.