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1. It Didn’t Go Away: The Political and Social Determinants of COVID-19 Mortality Rates across Counties in the United States

Author

Simone Rambotti, Caroline Wolski, and Kathryn Freeman Anderson

Subjects
COVID-19, mortality, political polarization, social determinants of health, Specialties of internal medicine, RC581-951
Abstract

Research over the last several years has demonstrated a wide variety of inequalities in the COVID-19 pandemic by socio-demographic characteristics, place, and political and religious ideology. In this study, by combining several county-level data sources, we examine how the social conditions of counties across the United States relate to their differential COVID-19 mortality rates. We find that percent Black, percent Hispanic, and income inequality are all positively related to higher mortality rates at the county level. Moreover, the percentage of the population that voted for Trump in the 2020 election was a significant and substantively large predictor of higher mortality rates. We also include healthcare-related variables, but compared to the social circumstances of the pandemic, these effects are relatively small. These results indicate that the social conditions of areas are strong predictors of how counties have experienced the pandemic and where the greatest loss of life has occurred.

Published
2023
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3. Extreme and Inconsistent: A Case-Oriented Regression Analysis of Health, Inequality, and Poverty

Author

Simone Rambotti and Ronald L. Breiger

Subjects
Social Sciences, Sociology (General), HM401-1281
Abstract

A methodological paradox characterizes macro-comparative research: it routinely violates the assumptions underlying its dominant method, multiple regression analysis. Comparative researchers have substantive interest in cases, but cases are largely rendered invisible in regression analysis. Researchers seldom recognize the mismatch between the goals of macro-comparative research and the demands of regression methods, and sometimes they end up engaging in strenuous disputes over particular variable effects. A good example is the controversial relationship between income inequality and health. Here, the authors offer an innovative method that combines variable-oriented and case-oriented approaches by turning ordinary least squares regression models “inside out.” The authors estimate case-specific contributions to regression coefficient estimates. They reanalyze data on income inequality, poverty, and life expectancy across 20 affluent countries. Multiple model specifications are dependent primarily on two countries with values on the outcome that are extreme in magnitude and inconsistent with conventional theoretical expectations.

Published
2020
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5. A novel role for Tm7sf2 gene in regulating TNFα expression.

Author

Ilaria Bellezza, Rita Roberti, Leonardo Gatticchi, Rachele Del Sordo, Maria Grazia Rambotti, Maria Cristina Marchetti, Angelo Sidoni, and Alba Minelli

Subjects
Medicine, Science
Abstract

We have explored the role of Tm7sf2 gene, which codifies for 3β-hydroxysterol Δ14-reductase, an endoplasmic reticulum resident protein, in the sensitivity to endoplasmic reticulum stress and in the resulting inflammatory response. We used mouse embryonic fibroblasts, derived from Tm7sf2(+/+) and Tm7sf2(-/-) mice, to determine the in vitro effects of thapsigargin on NF-κB activation. Our results show that the Tm7sf2 gene controls the launch of the unfolded protein response and presides an anti-inflammatory loop thus its absence correlates with NF-κB activation and TNFα up-regulation. Our data also show that Tm7sf2 gene regulates liver X receptor activation and its absence inhibits LXR signalling. By expressing the hTm7sf2 gene in KO MEFs and observing a reduced NF-κB activation, we have confirmed that Tm7sf2 gene is linked to NF-κB activation. Finally we used genetically modified mice in an in vivo model of ER stress and of inflammation. Our results show a significant increase in renal TNFα expression after tunicamycin exposure and in the oedematogenic response in Tm7sf2(-/-) mice. In conclusion, we have shown that the Tm7sf2 gene, to date involved only in cholesterol biosynthesis, also controls an anti-inflammatory loop thereby confirming the existence of cross talk between metabolic pathways and inflammatory response.

Published
2013
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7. PACAP activated adenylate cyclase in human sweat glands. An ultracytochemical study

Author

MG Rambotti, S Simonetti, and A Spreca

Subjects
Biology (General), QH301-705.5
Abstract

The ultracytochemical localization of adenylate cyclase (AC) was studied after stimulation with pituitary adenylate cyclase activating peptide (PACAP) in human sweat glands. PACAP stimulated AC in both eccrine and apocrine glands. In the secretory cells, enzymatic activity was associated with membranes involved in the secretory mechanism. In both glands, the cells of the excretory duct and myoepithelial cells presented AC activity. These localizations of enzymatic activity suggest a role for PACAP in regulating glandular secretion.

Published
2010
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8. Enzyme-ultracytochemical study of adenylate and guanylate cyclases in normal and pathologic human nasal mucosa

Author

MG Rambotti, G Altissimi, and A Spreca

Subjects
Biology (General), QH301-705.5
Abstract

The ultracytochemical localization of adenylate cyclase (AC) and guanylate cyclase B (GC-B) and C (GC-C) activity was studied after stimulation with pituitary adenylate cyclase activating peptide, C-type natriuretic peptide and guanylin, respectively, in normal human respiratory nasal mucosa and mucosa of nasal polyps. To demonstrate these enzymatic activities, we employed enzyme-ultracytochemical methods for electron microscopy. Both normal and pathologic nasal mucosa contained AC, GC-B and GC-C activity. In the upper portion of respiratory epithelium, the enzymes were detected on ciliary and microvillar membranes. In ciliary membranes, GC-B was the predominant form expressed. In goblet cells and in glands of the lamina propria, enzymatic activities were localized mainly on plasma membranes and on membranes lining secretory granules. The results did not reveal any evident differences between the enzymatic activities in normal and pathological nasal mucosa and suggest complementary activities for these enzymes and their stimulators in the regulation of mucociliary transport and glandular secretion.

Published
2009
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22. COVID-19 and the Political Framing of China, Nationalism, and Borders in the U.S. and South Korean News Media

Author

Davis, Andrew P., Rambotti, Simone, Hill, Terrence D., Chung, Angie Y., Jo, Hyerim, Lee, Ji-won, and Yang, Fan

Abstract

Using an inductive framing analysis of news coverage, we examine how the most popular liberal and conservative news media in the United States and South Korea mobilize different nationalist narratives on China in responding to social, economic, and political upheavals during the early stages of the COVID-19 pandemic. We identify three major areas of political cleavage in both Korean and U.S. media discourse on nationalist identities vis-à-vis the construction of the national or racialized “Other.” This includes (1) imagined solidarity against China as an adversary; (2) political disputes over boundary-making; (3) and the construction of ethnonational belonging and exclusion. Our research underscores how intrastate and interstate shifts during periods of crisis can heighten political cleavages along racial and ethnic fault lines and complicate dominant frameworks of civic and ethnic nationalism in both countries.

Published
2021
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23. No Choice but to Be Essential: Expanding Dimensions of Precarity During COVID-19

Author

Davis, Andrew P., Rambotti, Simone, Hill, Terrence D., Loustaunau, Lola, Stepick, Lina, Scott, Ellen, Petrucci, Larissa, and Henifin, Miriam

Abstract

Under COVID-19, low-wage service sector workers found themselves as essential workers vulnerable to intensified precarity. Based on in-depth interviews with a sample of 52 low-wage service workers interviewed first in Summer 2019 and then in the last two weeks of April 2020, we argue that COVID-19 has created new and heightened dimensions of precarity for low-wage workers. They experience (1) moments of what we call precarious stability, in which an increase in hours and predictable schedules is accompanied by unpredictability in the tasks workers are assigned, (2) increased threats to bodily integrity, and (3) experiences of fear and anxiety as background conditions of work and intensified emotional labor. The impacts of COVID-19 on workers’ lives warrant an expanded conceptualization of precarity that captures the dynamic and shifting nature of precarious stability and must incorporate workers’ limited control over their bodily integrity and emotions as core components of precarious working conditions.

Published
2021
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24. The Nastiest Question: Does Population Mobility Vary by State Political Ideology during the Novel Coronavirus (COVID-19) Pandemic?

Author

Davis, Andrew P., Rambotti, Simone, Hill, Terrence D., Hill, Terrence, Gonzalez, Kelsey E., and Davis, Andrew

Abstract

We consider the association between state political ideology and population mobility during the coronavirus (COVID-19) pandemic. We use first-party geo-behavioral data to estimate the average distance traveled by approximately 15,000,000 devices over 10 weeks (February 24, 2020 to April 27, 2020). Regression models with state clustered robust standard errors show lowershelter-in-place rates and highermobility scores in states with larger percentages of voters who supported Trump in the 2016 presidential election. We also find that shelter-in-place rates increased and mobility scores declined at slowerrates in states with greater Trump support. Shelter-in-place rates and average mobility scores were comparablein states governed by Republicans and Democrats. There was some evidence that shelter-in-place rates increased and average mobility scores declined at slowerrates in states governed by Republicans. Overall, states with more Trump voters are more resistant to public health recommendations and state stay-at-home orders during the coronavirus pandemic.

Published
2021
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26. Erratum

Author

Fanelli, C., Pampanelli, S., Epifano, L., Rambotti, A. M., Di Vincenzo, A., Modarelli, F., Ciofetta, M., Lepore, M., Annibale, B., Torlone, E., Perriello, G., De Feo, P., Santeusanio, F., Brunetti, P., and Bolli, G. B.

Published
1995
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29. IX Eular Workshop for Rheumatology Research: Molecular biology of autoantigens, autoantibodies and immunopeptides. Vienna, Austria, March 9–12, 1989

Author

Fournier, C., Texier, B., Chiocchia, G., Boissier, M. C., Herbage, D., Brown, C. M. S., Zyberk, C. Plater, Maini, R. N., Palacios, A., Sieper, J., Heinegard, D., Panayi, G. S., Gentric, A., Mackenzie, L., Lydyard, P. M., Youinou, P., Menzel, E. J., Kaik, B., Sykulev, Yu. K., Guschin, A. Je., Vasiljev, V. I., Ostreiko, K. K., Yeronina, T. V., Tumanova, I. A., Moynier, M., Abderrazik, M., Combe, B., Rucheton, M., Brochier, J., Tuomi, T., Palosuo, T., Heliövaara, M., Aho, K., McHugh, N. J., James, I. E., Kallenberg, C. G. M., Tervaert, J. W. Cohen, Goldschmeding, R., Von Dem Borne, A. E. G. K. R., Bouanani, M., Piechaczyk, M., Pau, B., Bastide, M., Le Page, S., Williams, W., Parkhouse, D., Cambridge, G., Isenberg, D. A., Nimmegeers, J., De Keyser, F., Verbruggen, G., Veys, E. M., Walravens M. J. F., Verdeyen I., Vandepol B., Cortens W., Schatteman, L., Goethals, K., Wu, D. -H., Tavoni, A., Neri, R., Garzelli, C., Vitali, C., Bombardieri, S., Logar, D., Kveder, T., Dobovisek, J., Rozman, B., Menard, H. A., Boire, G., Lopez-Longo, F. J., Masson, Ch., Lapointe, S., Clair, E. W. St., Zerva, L., Moutsopoulos, H. M., Keene, J. D., Pisetsky, D. S., Van Dam, A. P., Cuypers, H. T. M., Winkel, I., Smeenk, R. J. T., Taylor, D., Valente, E., Foster, J. P., Williams, D. G., Stocks, M. R., Caporali, R., De Gennaro, F., Cerino, A., Cobianchi, F., Astaldi-Ricotti, G. C. B., Montecucco, C., Habets, W., Sillekens, P. T. G., Hoet, M. H., McAllister, G., Lerner, M. R., Van Venrooij, W. J., Habets, W. J., Van Der Kemp, A., De Jong, B., Scarpa, R., Pucino, A., Di Girolamo, C., della Valle, G., Larizza, G., Casiere, D., Oriente, P., Paimela, L., Palvimo, J., Kurki, P., Hassfeld, W., Steiner, G., Graninger, W., Smolen, J. S., Lopez-Longo, E. J., Larose, A., Hoet, R., Zewald, R., Smeenk, R., Brinkman, K., Van Den Brink, H., Westgeest, A., Huss, R., Krapf, E. F., Herrmann, M., Leitmann, W., Kalden, J. R., Merétey, K., Cebecauer, L., Böhm, U., Kozakova, D., Brózik, M., Temesvári, P., Nagy, L., Bozic, B., Stegnar, M., Vene, N., Peternel, P., Giuggioli, C., Monti, P., Rossi, G., Ferri, C., Chiellini, S., Baboonian, C., Venables, P. J. W., Roffe, L., Booth, J., Krapf, F., Abuljadayel, I., Ebringer, A., Cox, N. L., Brand, S. R., McIntosh, D. P., Bernstein, R. M., Van Den Broek, M. F., Van Bruggen, M. C. J., Smetsers, T., Kuyer, P., Van De Putte, L., Van Den Berg, W. B., Toivanen, A., Jalkanen, S., Lahesmaa-Rantala, R., Isomäki, O., Pekkola-Heino, K., Merilahti-Palo Saario, R., Von Essen, R., Isomäki, H., Granfors, K., Gaston, J. S. H., Life, P. F., Bailey, L., Bacon, P. A., Khalafpour, S., Wilson, C., Awad, J., Toivanen, P., Saario, R., Skurnik, M., Van Der Straeten, C., Mielants, H., Gazic, M., Hartung, K., Riedel, T., Stannat, S., Specker, Ch., Röther, E., Pirner, K., Schendel, D., Baur, M., Corvetta, A., Peter, H. H., Lakomek, H. J., Deicher, H., Andonopoulos, A. P., Papasteriades, C. A., Drosos, A. A., Dimou, G. S., Shattles, W., Venables, P., Charles, P. J., Markwick, J. R., Venables, P. J., Galeazzi, M., Lulli, P., Tuzi, T., Cappellacci, S., Morellini, M., Trabace, S., Cutrupi, F., Sorrentino, R., Botti, S., Iannicola, C., Costanzi, S., Tosi, R., Gospodinoff, A., Eliaou, J. F., Humbert, H., Balaguer, P., Nicolas, J. C., Sany, J., Clot, J., Sakkas, L. I., Bird, H., Welsh, K. I., Pitzalis, C., Kingsley, G., Haskard, D., Vischer, T. L., Bas, S., Werner-Favre, C., Wohlwend, D., Zubler, R. H., Afeltra, A., De Pita, O., Basso, P., Pietrucci, A., Ferri, G. M., Bonomo, L., Gerli, R., Cernetti, C., Bertotto, A., Agea, E., Arcangeli, C., Lanfrancone, L., Rambotti, P., Crupi, S., Baglioni, A., Spinozzi, F., Papazoglou, S., Skoumi, D., Athanasiou, P., Iliopoulos, A., Stavropoulou, A., Kontomerkos, T., Hendrich, G., Kuipers, J. G., Hammer, M., Schmidt, R. E., Manoussakis, M. N., Germandis, G., Zerva, L. V., Siouna-Fatourou, H. J., Katsikis, P. D., Mavridis, A., Toubert, A., Sadouk, M., de la Tour, B., Vaquero, C., Amor, B., Miossec, P., Naviliat, M., Cretien, I., Banchereau, J., Graninger, P., Aschauer, B., Sinski, A., Smolen, J., Krutmann, J., Kirnbauer, R., Köck, A., Schwarz, T., May, L. T., Sehgal, P. B., Luger, T. A., Field, M., Chu, C. Q., Feldmann, M., Wilbrink, B., Nietfeld, J. J., Helle, M., Boeije, L. C. M., Van Roy, J. L. A. M., Den Otter, W., Aarden, L. A., Huber-Bruning, O., Malejczyk, J., Urbanski, A., Malejczyk, M., Karbowski, A., Völker, W., Feige, U., Otter, W. Den, Malfait, A. M., Wieme, N., Gyselbrecht, L., Van de Loo, A. A. J., Van Lent, P. L. E. M., Haskard, D. O., Wellicome, S., Lanchbury, J., Thornhill, M., Krutmann, K., Gschnait, F., Yaron, M., Yaron, I., Dayer, J. -M., Bleiberg, I., Meyer, F. -A., Maury, C. P. J., Teppo, A. -M., Salo, E., Pelkonen, P., Malfait, A., Cochez, Ph., Gruschwitz, M., Müller, P. U., Wick, G., Madhok, R., Wilson, R., Frame, M., Thompson, J., Sturrock, R. D., Partsch, G., Matucci-Cerinic, M., Marabini, S., Jantsch, S., Neumüller, J., Eberl, R., van Beuningen, H. M., Arntz, O. J., Zlabinger, G. J., Steffen, C., Brand, H. S., Van Kampen, G. P. J., De Koning, M. H. M. T., Kiljan, E., Van Der Korst, J. K., Gemmell, C. G., Swaak, A. J. G., Van Rooyen, A., Hall, N. D., Woolf, A. D., Kantharia, B., Maymo, J., Blake, D. R., Goulding, N. J., Maddison, P. J., Munthe, E., Berntzen, H. B., Fagerhol, M., Mathieu, A., Pala, R., Contu, L., Cirillo, R., Garau, P., Nurchis, P., Viberti, G. C., Meyer, O., Zenklusen, C., Le Thi Huong Du, Z., Gaudouen, C., Mery, J. Ph., Ronco, P., Kahn, M. F., Rasmussen, N., Szpirt, W., Thomsen, B., Humbel, R. L., Ter Borg, E. J., Horst, G., Hummel, E., Limburg, P. C., Aeschilmann, A., Bourgeois, P., De Rooij, D. J., Van de Putte, L. B. A., Verbeek, L., Farinaro, C., Infranzi, E., Couret, M., Ackerman, C., De Vlam, K., Carapic, V., Carapic, D., Annefeld, M., Erne, B., Rosenwasser, L. J., Pazoles, C. J., Otterness, I. G., Hanson, D. C., McDonald, B., Loose, L. D., Dougados, M., Machold, K. P., Wiesenberg-Böttcher, I., Wanner, K., Pignat, W., Altmann, H., Tuschl, H., Bröll, H., Balestrieri, G., Tincani, A., Cattaneo, R., Bertoli, M. T., Martinelli, M., Allegro, F., Meroni, P. L., Balesini, G., Aichinger, G., Schlögl, E., Huber, Ch., Shoenfeld, Y., Fleishmaker, E., Mendlovic, S., Mozes, E., Blank, M., Talal, N., Hogervorst, E. J. M., Van Eden, W., Van Der Zee, R., Psychos, D., Dimou, G., Stefanaki-Nikou, S., Papadimitriou, C. S., Settas, L., Alexiou, P., Dimitriadis, G., Mataftsi, E., Soliou, E., Tourkantonis, A., Babic, M., Jeurissen, M. E. C., and Boerbooms, A. MTh

Published
1989
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31. Income Inequality and Chronic Health Conditions: A Multilevel Analysis of the U.S. States

Author

Anderson, Kathryn Freeman, Bjorklund, Eric, and Rambotti, Simone

Abstract

ABSTRACTRecently, scholarly work has examined the effect of rising income inequality on health outcomes. However, this work is somewhat inconclusive. The mechanisms that could produce such an association are still being sorted out. Much of this work focuses on mortality outcomes with little attention to how this process operates for actual health conditions, including chronic health problems—arguably the main public health concerns of the developed world. In a series of multilevel binary logistic regression models using data from the 2005 and 2007 Behavioral Risk Factor Surveillance System, we examine the association between state-level income inequality, poverty, and social welfare measures on spending and policy to examine the association between these factors for three chronic health outcomes: diabetes, hypertension, and coronary heart disease. We find that income inequality is conditionally positively related only to the diagnosis of diabetes and hypertension, and only in 2007. However, absolute poverty is related to the outcome across all three dependent variables. Certain social welfare measures attenuate the effects of both income inequality and absolute poverty, suggesting that some policies reduce this association.

Published
2019
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32. Artrite reumatoide

Author

Larizza, P., Rambotti, P., and Capodicasa, Enrico

Published
1993

33. [Immunotherapy in allergic diseases. Evaluation of short-term efficacy of aluminum hydroxide-absorbed slow-release preparations]

Author

Spinozzi, Fabrizio, Cimignoli, E, Broccucci, L, Gerli, Roberto, Cernetti, C, and Rambotti, P.

Subjects
Adult, Male, Rhinitis, Allergic, Perennial, Adolescent, Rhinitis, Allergic, Seasonal, Aluminum Hydroxide, Allergens, Middle Aged, Asthma, Immunoglobulin A, Desensitization, Immunologic, Immunoglobulin G, Respiratory Hypersensitivity, Humans, Female, Prospective Studies, Skin Tests
Abstract

Clinical and immunological changes after immunotherapy (ITS) for respiratory allergy were evaluated in 29 subjects during a one year follow up period. No adverse effects were noted with alum-absorbed allergen extracts. However, only patients receiving ITS for grass pollens demonstrated clinical improvement and blocking IgG increase as compared with those with multiple allergen sensitivity.

Published
1991

34. Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody

Author

Bertotto, A, Gerli, Roberto, Lanfrancone, L, Crupi, S, Arcangeli, C, Cernetti, C, Spinozzi, Fabrizio, and Rambotti, P.

Subjects
Antigens, Differentiation, T-Lymphocyte, CD3 Complex, T-Lymphocytes, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, Gene Expression, Receptors, Interleukin-2, In Vitro Techniques, Fetal Blood, Lymphocyte Activation, Solubility, Humans, Interleukin-2, Tetradecanoylphorbol Acetate, RNA, Messenger, Calcimycin, Interleukin-1
Abstract

Despite the fact that the percentage of circulating CD3-positive cells is similar in cord and adult blood, the proliferative response induced by anti-CD3 monoclonal antibody (mAb) was impaired in the majority of human cord peripheral blood mononuclear cell (PBMC) samples we tested. The cell proliferative defect was associated with low interleukin 2 (IL 2) gene expression and scant IL 2 production. However, interleukin 2 receptor was fully expressed at both the mRNA and protein levels. Such a finding is consistent with the observation that exogenous recombinant IL 2 is able to boost the anti-CD3-mediated response of cord PBMC. Furthermore, when anti-CD3 and phorbol myristate acetate (PMA) were added together, they exerted a very marked synergistic effect on both the proliferation of, and IL 2 production by, cord PBMC. The addition of allogeneic antigen presenting cells plus soluble anti-CD3 or Sepharose-coupled anti-CD3 mAb to the cord T cell cultures had no significant effect on proliferation, whereas both elicited good mitogenesis of adult T cells. Moreover, addition of exogenous recombinant interleukin 1 to anti-CD3-stimulated T cells failed to trigger any proliferation in either adult or cord samples. Since the combination of PMA and calcium ionophore A23187 is effective in triggering optimal proliferation of cord T cells, the defect would seem to be associated with a failure in transmembrane transduction of the activation signals provided by the anti-CD3 stimulus for the cord T cell.

Published
1990

37. The tricyclic antidepressant amitriptyline is cytotoxic to HTB114 human leiomyosarcoma and induces p75NTR-dependent apoptosis

Author

Pula, Grazia, Pistilli, Alessandra, Montagnoli, Claudia, Stabile, Anna M., Rambotti, Maria G., and Rende, Mario

Abstract

Nerve growth factor (NGF) receptors, TrKA and p75NTR, are being investigated in cancer therapy. Our previous data show that, in HTB114 uterine leiomyosarcoma cells, p75NTR-dependent apoptosis is inducible by cytotoxic drugs and can suppress nerve growth factor-dependent growth. Although amitriptyline can kill cancer cells and bind TrKAB, its effects on p75NTR-dependent apoptosis are unknown. The aim of this paper was to evaluate the antineoplastic potential of amitriptyline, and the role of p75NTR-dependent apoptosis in the chemoresistant uterine HTB114 leiomyosarcoma. Using proliferation assays and fluorescence-activated cell sorting analysis, we found that amitriptyline caused a marked reduction in HTB114 cell viability, associated with the parallel upregulation of p75NTRexpression. This converted the TrKA-proliferating cells into TrKAp75NTR, leading to downregulation of TrKA-prosurvival signaling (AKT) and activation of p75NTR-dependent apoptosis (through caspase-3). Overall, we provide novel evidence that HTB114 uterine leiomyosarcoma cells are highly sensitive to amitriptyline, supporting the role of p75NTR-dependent apoptosis as a novel cytotoxic mechanism of this drug and of p75NTRas an inducible stress receptor and a novel target in clinical oncology.

Published
2013
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38. Antiproliferative and Proapoptotic Effects of the TrK-inhibitor GW441756 in Human Myosarcomas and Prostatic Carcinoma

Author

M. Stabile, Anna, Montagnoli, Claudia, Pistilli, Alessandra, Grazia Rambotti, Maria, Pula, Grazia, and Rende, Mario

Abstract

Neurotrophins (NTs) and their receptors, TrKs and p75NTR, have been shown to regulate proliferation and apoptosis of neoplastic cells. Pharmacological TrK blockade is considered a valuable target in cancer therapy, and several TrK inhibitors are under investigation. However, only a few of them have reached the stage of clinical development. Myosarcomas are aggressive cancers, which secrete NGF and respond poorly to available chemotherapies. Our previous work has shown that these cancers, characterized by autocrine activation of TrKA by NGF, which promotes cancer growth and survival, are highly susceptible to TrK blockade, both in vitro and in vivo. The same pattern has also been described in prostatic carcinoma. The present report characterizes for the first time the anti-proliferative and pro-apoptotic effects of the oxindole TrK inhibitor GW441756, in a panel of human myosarcomas and prostatic adenocarcinoma cell lines. Furthermore, we provide novel evidence that, in myosarcomas, characterized by a high-TrK/low-p75NTR phenotype, GW441756 upregulates p75NTR receptor expression, leading to apoptosis via caspase-3 activation. Altogether, our data expand the knowledge of the anti-neoplastic and pro-apoptotic mechanisms of GW441756, and of TrK inhibitors in general, lending further support to the therapeutic potential of TrK blockade in clinical oncology.

Published
2013

39. Reduced number of natural killer cells in patients with pathological hyperprolactinemia.

Author

Gerli, G., Rambotti, P., Nicoletti, I., Orland, S., Migliorati, G., and Riccardi, C.

Subjects
*KILLER cells, *IMMUNOCOMPETENT cells, *HYPERPROLACTINEMIA, *METABOLIC disorders, *CELL physiology, *LYMPHOCYTES
Abstract

natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemia female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemia patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemia patients, as compared to normal controls and bromocriptine-treated subjects, correlated well with the decreased NK activity. Finally, 'in vitro' incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man. [ABSTRACT FROM AUTHOR]

Published
1986

47. Analysis of CD4-positive T cell subpopulation in sarcoidosis.

Author

Gerli, R., Darwish, S., Broccucci, L., Minotti, V., Spinozzi, F., Cernetti, C., Bertotto, A., Rambotti, P., and P. Rambotti

Subjects
IMMUNOFLUORESCENCE, SARCOIDOSIS, BRONCHOALVEOLAR lavage, BLOOD, MONOCLONAL antibodies, T cells
Abstract

Double-labelling immunofluorescence analysis within the CD4+ cell subset was carried out in 27 bronchoalveolar lavage fluids and 11 peripheral blood samples of sarcoidosis patients with anti-TQI, anti-2H4 and anti-4B4 monoclonal antibodies. Helper/inducer CD4+TQI- /4B4+ cells were strongly increased in the lung and slightly, but significantly, decreased in the blood of sarcoidosis patients with respect to normal controls. No differences were found in the number of both lung and blood CD4+2H4+ cells between sarcoidosis patients and controls. The findings are further evidence for a compartmentalization of T cell subsets in sarcoidosis. [ABSTRACT FROM AUTHOR]

Published
1988

48. Electron Microscopic Cytochemistry of Adenylyl Cyclase Activity in Mouse Spermatozoa

Author

Liguori, Lavinia, Rambotti, Maria Grazia, Bellezza, Ilaria, and Minelli, Alba

Abstract

We investigated adenylyl cyclase activity of mouse spermatozoa by electron microscopic cytochemistry. Subcellular localization of enzyme activity was determined in the presence and absence of bicarbonate ions. Results confirm the existence in sperm of a bicarbonate-regulated adenylyl cyclase, which suggests microdomain signaling. (J Histochem Cytochem 52:833–836, 2004)

Published
2004
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49. Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule

Author

Gerli, Roberto, Bertotto, A, Crupi, S, Arcangeli, C, Marinelli, I, Spinozzi, F, Cernetti, C, Angelella, P, and Rambotti, P.

Subjects
Antigens, Differentiation, T-Lymphocyte, CD3 Complex, T-Lymphocytes, Immunology, CD2 Antigens, Receptors, Antigen, T-Cell, Antibodies, Monoclonal, Antigen-Presenting Cells, Receptors, Interleukin-2, Fetal Blood, Lymphocyte Activation, Humans, Interleukin-2, Immunology and Allergy, Calcium, Phytohemagglutinins, Receptors, Immunologic, Interleukin-1
Abstract

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.

Published
1989

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