RESUMEN

The transition to pulmonary respiration following birth requires rapid alterations in the structure of the mammalian cardiovascular system. One dramatic change that occurs is the closure and remodeling of the ductus arteriosus (DA), an arterial connection in the fetus that directs blood flow away from the pulmonary circulation. A role for prostaglandins in regulating the closure of this vessel has been supported by pharmacological and genetic studies. The production of prostaglandins is dependent on two cyclooxygenases (COX-1 and COX-2), which are encoded by separate genes. We report here that the absence of either or both COX isoforms in mice does not result in premature closure of the DA in utero. However, 35% of COX-2(-/-) mice die with a patent DA within 48 h of birth. In contrast, the absence of only the COX-1 isoform does not affect closure of the DA. The mortality (35%) and patent DA incidence due to absence of COX-2 is, however, significantly increased (79%) when one copy of the gene encoding COX-1 is also inactivated. Furthermore, 100% of the mice deficient in both isoforms die with a patent DA within 12 h of birth, indicating that in COX-2-deficient mice, the contribution of COX-1 to DA closure is gene dosage-dependent. Together, these data establish roles for COX-1, and especially for COX-2, in the transition of the cardiopulmonary circulation at birth.

Asunto(s)

Conducto Arterioso Permeable/genética , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Animales , Animales Recién Nacidos , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Muerte , Conducto Arterial/patología , Conducto Arterioso Permeable/epidemiología , Femenino , Impresión Genómica , Genotipo , Isoenzimas/deficiencia , Isoenzimas/genética , Masculino , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Ratones Noqueados , Prostaglandina-Endoperóxido Sintasas/deficiencia , Prostaglandina-Endoperóxido Sintasas/genética , Factores de Tiempo

RESUMEN

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the function of cyclooxygenases, COX-1 and COX-2, which catalyze the first step in the synthesis of inflammatory mediators (PGE2). We sought to understand the roles of cyclooxygenases and NSAIDs in T-cell development. Our data show no significant defects in T-cell development in fetal thymic organ cultures of mice disrupted in both or either COX genes or in mice disrupted in either EP-1 or EP-2 receptor genes. On the other hand, NSAIDs reproducibly caused thymocyte developmental defects. However, the specific effects of the COX-2 inhibitors were not correlated with their potency for inhibition of COX-2 activity. We focused on the NS-398 COX-2 inhibitor and showed that its effects could not be reversed by exogenous PGE2. Furthermore, NS-398 was inhibitory even when its target, COX-2, was absent. These data show that the T-cell developmental effects of NS-398 are COX-2 and PGE2 independent.

Asunto(s)

Antiinflamatorios no Esteroideos/toxicidad , Inhibidores de la Ciclooxigenasa/toxicidad , Dinoprostona/fisiología , Síndromes de Inmunodeficiencia/inducido químicamente , Isoenzimas/fisiología , Nitrobencenos/toxicidad , Prostaglandina-Endoperóxido Sintasas/fisiología , Sulfonamidas/toxicidad , Linfocitos T/patología , Timo/patología , Animales , Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/farmacología , Dinoprostona/farmacología , Indometacina/análogos & derivados , Indometacina/farmacología , Indometacina/toxicidad , Isoenzimas/antagonistas & inhibidores , Isoenzimas/deficiencia , Isoenzimas/genética , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , Nitrobencenos/farmacología , Técnicas de Cultivo de Órganos , Prostaglandina-Endoperóxido Sintasas/deficiencia , Prostaglandina-Endoperóxido Sintasas/genética , Receptores de Prostaglandina E/deficiencia , Receptores de Prostaglandina E/genética , Subtipo EP1 de Receptores de Prostaglandina E , Subtipo EP2 de Receptores de Prostaglandina E , Sulfonamidas/farmacología , Tiofenos/farmacología , Timo/embriología , Timo/inmunología

RESUMEN

The development of cyclooxygenase (COX) deficient mice has allowed investigation into the individual physiological roles of the COX-1 and COX-2 isoforms. In the following article, the phenotypes of the two Ptgs (genes coding for COX-1 and COX-2) knockouts are summarized, and recent studies to investigate the effects of COX deficiency on cancer susceptibility, inflammatory response, gastric ulceration, and female reproductive processes are discussed. Also, the development and potential uses of mice deficient in both COX isoforms and mice containing only a single copy of one isoform are discussed. Additionally, when the data permit, the effects of genetic ablation of COX activity are compared with those of pharmacological inhibition of COX activity by nonsteroidal anti-inflammatory drugs. The data suggest that prostaglandins derived via the individual COX isoforms have separate as well as common functions. However, for the maintenance of normal physiology, it appears that deficiency of COX-2 has more profound effects than deficiency of COX-1.

Asunto(s)

Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Animales , Transformación Celular Neoplásica , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Femenino , Humanos , Inflamación/enzimología , Isoenzimas/deficiencia , Isoenzimas/genética , Proteínas de la Membrana , Ratones , Ratones Noqueados , Fenotipo , Prostaglandina-Endoperóxido Sintasas/deficiencia , Prostaglandina-Endoperóxido Sintasas/genética , Reproducción/fisiología , Úlcera Gástrica/enzimología

RESUMEN

Cyclooxygenase (COX)-1- and COX-2-deficient mice have unique physiological differences that have allowed investigation into the individual biological roles of the COX isoforms. In the following, the phenotypes of the two COX knockout mice are summarized, and recent studies to investigate the effects of COX deficiency on inflammatory responses and cancer susceptibility are discussed. The data suggest that both isoforms have important roles in the maintenance of physiological homeostasis and that such designations as house-keeping and/or response gene may not be entirely accurate. Furthermore, data from COX-deficient mice indicate that both isoforms can contribute to the inflammatory response and that both isoforms have significant roles in carcinogenesis.

Asunto(s)

Modelos Animales de Enfermedad , Inflamación/genética , Isoenzimas/genética , Ratones Noqueados , Neoplasias Experimentales/genética , Prostaglandina-Endoperóxido Sintasas/genética , Animales , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Predisposición Genética a la Enfermedad , Inflamación/etiología , Proteínas de la Membrana , Ratones , Neoplasias Experimentales/etiología

RESUMEN

CONTEXT: Maryland began a statewide firearm-related injury surveillance system in 1995. The system now focuses on firearm-related deaths; a system to monitor nonfatal injuries is being developed. The system is passive; it accesses, integrates, and analyzes data collected by Maryland's Office of the Chief Medical Examiner, Maryland State Police, and Division of Health Statistics. OBJECTIVE: To evaluate the surveillance system's ability to ascertain cases in the absence of a standard for the true number of cases. DESIGN: Link records of the same firearm-related death captured by the surveillance system's multiple data sources, comparing the rate of false positives and false negatives, and assessing errors in linkage variables. SETTING: Maryland, 1991-1994. PARTICIPANTS: All deaths occurring in the state of Maryland as a result of a firearm-related injury. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value. RESULTS: The system is extremely sensitive, detecting 99.61% of cases, and it has a very high positive predictive value, with 99.87% of the cases identified from medical examiner's office data being confirmed as actual cases. CONCLUSIONS: Maryland's database of information from the medical examiner's office is highly accurate for ascertaining firearm-related deaths that occur in the state. A unique identifier common across data sources would ease record linkage efforts, and improve the system's ability to monitor firearm-related deaths.

Asunto(s)

Vigilancia de la Población/métodos , Heridas por Arma de Fuego/mortalidad , Adolescente , Adulto , Sesgo , Recolección de Datos/métodos , Armas de Fuego/legislación & jurisprudencia , Armas de Fuego/estadística & datos numéricos , Humanos , Maryland/epidemiología , Registro Médico Coordinado , Evaluación de Programas y Proyectos de Salud , Sensibilidad y Especificidad , Heridas por Arma de Fuego/etiología , Heridas por Arma de Fuego/prevención & control

RESUMEN

OBJECTIVE: To investigate the neuromuscular activity of the gastrointestinal tract by antroduodenal manometry in women with endometriosis documented by laparoscopy, to assess the effects of diet and drug therapy on symptoms, and to assess the bacterial overgrowth that is commonly associated with these nerve diseases. DESIGN: Prospective, open-label study. SETTING: A clinical center for the care of women's health. PATIENT(S): Fifty women with endometriosis documented by laparoscopy and gastrointestinal tract symptoms characterized by chronic abdominal pain, nausea, vomiting, early satiety, bloating and distention, and altered bowel habits. INTERVENTION(S): Motility of the gastrointestinal tract was recorded and bacterial overgrowth was assessed. Treatment consisted of dietary changes, including reduction of glycemic carbohydrates, balancing with omega 9 oils, elimination of foods with caffeine and tyramine, and addition of omega 3 fatty acids, as well as drug therapy with clonazepam (0.25 mg 3 times per day). RESULT(S): All 50 women showed a characteristic motility change (ampulla of Vater-duodenal wall spasm, a seizure equivalent of the enteric nervous system). Forty of the women showed bacterial overgrowth. There was a significant reduction in the total symptom score after 8 weeks of treatment. CONCLUSION(S): This study suggests that endometriosis and gastrointestinal tract symptoms are a result of the dysfunction of hollow organs. Correction of the biochemical imbalance of the eicosanoid system and the hypersecretion of insulin that results from excessive intake of glycemic carbohydrates and lack of essential fatty acids significantly decreases symptoms in patients with endometriosis and associated neuromuscular disease of the gastrointestinal tract.

Asunto(s)

Endometriosis/fisiopatología , Enfermedades Gastrointestinales/fisiopatología , Motilidad Gastrointestinal/fisiología , Enfermedades Neuromusculares/fisiopatología , Adulto , Clonazepam/uso terapéutico , Dieta , Endometriosis/dietoterapia , Endometriosis/tratamiento farmacológico , Ácidos Grasos Omega-3/metabolismo , Femenino , Agonistas del GABA/uso terapéutico , Enfermedades Gastrointestinales/dietoterapia , Enfermedades Gastrointestinales/tratamiento farmacológico , Motilidad Gastrointestinal/efectos de los fármacos , Humanos , Hidrógeno , Laparoscopía , Manometría , Complejo Mioeléctrico Migratorio/fisiología , Enfermedades Neuromusculares/dietoterapia , Enfermedades Neuromusculares/tratamiento farmacológico , Receptores de GABA-A/efectos de los fármacos , Receptores de GABA-A/fisiología

RESUMEN

Surprisingly, disruption of the COX-1 gene resulted in generally healthy mice. This is in spite of the fact that prostaglandin levels in the tissues examined were reduced by greater than 99%. The results obtained to date with the COX-1 deficient mice indicate that some of the physiological roles previously attributed to COX-1 may not be entirely correct. Ongoing studies with the COX deficient mice are aimed at better defining the physiological roles of the cyclooxygenases and concomitantly the mechanisms by which NSAIDs cause their biological effects.

Asunto(s)

Isoenzimas/genética , Ratones/genética , Prostaglandina-Endoperóxido Sintasas/genética , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/toxicidad , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/genética , Ciclooxigenasa 1 , Inhibidores de la Ciclooxigenasa/uso terapéutico , Inhibidores de la Ciclooxigenasa/toxicidad , Femenino , Marcación de Gen , Genes , Genotipo , Inflamación/tratamiento farmacológico , Isoenzimas/fisiología , Masculino , Proteínas de la Membrana , Ratones Noqueados , Ratones Mutantes , Prostaglandina-Endoperóxido Sintasas/fisiología , Reproducción/fisiología , Úlcera Gástrica/inducido químicamente

RESUMEN

We have developed derivatives of mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cells that stably express high levels of murine prostaglandin synthase-1 or -2 (PGHS-1 or -2). The cDNAs were transferred using retroviral vectors and the resulting G418-resistant clones were analyzed for prostaglandin E2 (PGE2) production. Specific expression was confirmed by Western and Northern analyses. Enzyme activities, protein, and message levels peaked 1 (10T1/2) or 2 (AS52) days after seeding but decreased as cells became density arrested. Upon subculturing, enzyme activities returned to their initial high levels. With 10 microM exogenous arachidonic acid (AA) as the substrate, PGHS-1 activities were approximately 3- to 5-fold higher than PGHS-2 activities. Conversely, when exogenous AA was left out of the medium and only endogenous AA was available as substrate, enzyme activities were lower; but PGHS-2 activities were 5-fold (10T1/2) or 1.5-fold (AS52) higher than PGHS-1 activities. Following phorbol ester treatment to stimulate endogenous AA release, PGHS-2 activities increased over time and by 6 hours, were 4-fold (10T1/2) or 2-fold (AS52) higher than PGHS-1 activities. However, when calcium ionophore A23187 was used to stimulate endogenous AA release, maximum PGHS activities occurred within 30 min of treatment; PGHS-1 activities were equal to (10T1/2) or 2-fold higher (AS52) than PGHS-2 activities. Because these cell lines allow us to measure specific PGHS activity in intact cells, we were able to demonstrate that the relative activities of the two PGHS isozymes depend on the source of AA (exogenous versus endogenous) or biochemical stimulus used to mobilize endogenous AA (A23187 versus phorbol ester). These data suggest that PGHS-1 and PGHS-2 preferentially utilize different pools of AA and may be modulated through different stimulus-initiated pathways.

Asunto(s)

Ácido Araquidónico/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/metabolismo , Animales , Células CHO , Línea Celular , Cricetinae , ADN Complementario/genética , Estabilidad de Enzimas , Expresión Génica , Ratones , Retroviridae/genética

RESUMEN

BALB/c mouse keratinocytes (BALB/MK) are nontumorigenic epithelial cells which are dependent on mouse epidermal growth factor (EGF) for maintaining proliferation in culture. In BALB/MK the oxygenation of both arachidonic acid and linoleic acid was dependent on EGF. EGF stimulated the formation of prostaglandin E2 and prostaglandin F2 alpha from arachidonic acid and 9- and 13-hydroxyoctadecadienoic acid (HODE) from linoleic acid. Analysis of the linoleic acid metabolites determined the ratio of 9-HODE to 13-HODE was approximately 6 to 4, and the 9-HODE was the (R) enantiomer, consistent with metabolism by prostaglandin G/H synthase (PGHS). The formation of these linoleic acid metabolites was sensitive to indomethacin, a PGHS inhibitor. EGF induced the expression of PGHS-2 mRNA after 30 min, which peaked after 1 h, and remained expressed for at least 24 h after the addition of EGF. A less significant increase in the expression of PGHS-1 mRNA occurred 4 h after EGF stimulation. Immunoblot analysis did not detect expression of PGHS-1 protein. However, PGHS-2 protein expression was increased 2 h after EGF exposure and was dependent on EGF. PGHS-2 protein was not transiently expressed as reported with other cell types, but was continually expressed in proliferating cells maintained with EGF at a subconfluent density. Indomethacin significantly attenuated EGF-dependent mitogenesis and cell proliferation. These results suggest that PGHS-2 activity contributes to the proliferative response of BALB/MK to EGF.

Asunto(s)

Factor de Crecimiento Epidérmico/farmacología , Isoenzimas/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/enzimología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Animales , Ácido Araquidónico/metabolismo , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Dexametasona/farmacología , Dinoprostona/biosíntesis , Indometacina/farmacología , Insulina/farmacología , Isoenzimas/genética , Queratinocitos/citología , Ácido Linoleico , Ácidos Linoleicos/metabolismo , Ratones , Ratones Endogámicos BALB C , Prostaglandina-Endoperóxido Sintasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate "housekeeping" functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 (Ptgs2). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop severe nephropathy and are susceptible to peritonitis.

Asunto(s)

Vectores Genéticos/genética , Riñón/patología , Prostaglandina-Endoperóxido Sintasas/genética , Animales , Ácido Araquidónico/farmacología , Bacteriófago lambda/genética , Secuencia de Bases , Dinoprostona/biosíntesis , Femenino , Genotipo , Homocigoto , Riñón/enzimología , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Mortalidad , Otitis Externa/inducido químicamente , Peritoneo/patología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Acetato de Tetradecanoilforbol/farmacología

RESUMEN

Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2.

Asunto(s)

Antiinflamatorios no Esteroideos/efectos adversos , Ácido Araquidónico/efectos adversos , Gastritis/genética , Vectores Genéticos/genética , Indometacina/farmacología , Prostaglandina-Endoperóxido Sintasas/genética , Úlcera Gástrica/genética , Animales , Northern Blotting , Western Blotting , Clonación Molecular , Dinoprostona/biosíntesis , Femenino , Gastritis/inducido químicamente , Homocigoto , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación/fisiología , Otitis Externa/inducido químicamente , Fenotipo , Plásmidos/genética , Agregación Plaquetaria/fisiología , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , Úlcera Gástrica/inducido químicamente

RESUMEN

BACKGROUND: Whether restricting access to handguns will reduce firearm-related homicides and suicides is currently a matter of intense debate. In 1976 the District of Columbia adopted a law that banned the purchase, sale, transfer, or possession of handguns by civilians. We evaluated the effect of implementing this law on the frequency of homicides and suicides. METHODS: Homicides and suicides committed from 1968 through 1987 were classified according to place of occurrence (within the District of Columbia or in adjacent metropolitan areas where the law did not apply), cause (homicide or suicide), mechanism of death (firearms or other means), and time of occurrence (before or after the implementation of the law). The number of suicides and homicides was calculated for each month during the study period, and differences between the mean monthly totals before and after the law went into effect were estimated. RESULTS: In Washington, D.C., the adoption of the gun-licensing law coincided with an abrupt decline in homicides by firearms (a reduction of 3.3 per month, or 25 percent) and suicides by firearms (reduction, 0.6 per month, or 23 percent). No similar reductions were observed in the number of homicides or suicides committed by other means, nor were there similar reductions in the adjacent metropolitan areas in Maryland and Virginia. There were also no increases in homicides or suicides by other methods, as would be expected if equally lethal means were substituted for handguns. CONCLUSIONS: Restrictive licensing of handguns was associated with a prompt decline in homicides and suicides by firearms in the District of Columbia. No such decline was observed for homicides or suicides in which guns were not used, and no decline was seen in adjacent metropolitan areas where restrictive licensing did not apply. Our data suggest that restrictions on access to guns in the District of Columbia prevented an average of 47 deaths each year after the law was implemented.

Asunto(s)

Armas de Fuego/legislación & jurisprudencia , Homicidio/estadística & datos numéricos , Concesión de Licencias/legislación & jurisprudencia , Suicidio/estadística & datos numéricos , Causas de Muerte , District of Columbia/epidemiología , Estudios Longitudinales , Maryland/epidemiología , Virginia/epidemiología

Asunto(s)

Adolescente , Armas de Fuego/legislación & jurisprudencia , Grupos Minoritarios , Violencia , Adulto , Estudios de Evaluación como Asunto , Humanos , Masculino , Estados Unidos/epidemiología

RESUMEN

BACKGROUND: In November 1986, a Detroit, Michigan city ordinance requiring mandatory jail sentences for illegally carrying a firearm in public was passed to preserve "the public peace, health, safety, and welfare of the people." METHODS: We conducted a set of interrupted time-series analyses to evaluate the impact of the law on the incidence of homicides, hypothesizing that the ordinance, by its nature, would affect only firearm homicides and homicides committed outside (e.g., on the street). RESULTS: The incidence of homicide in general increased after the law was passed, but the increases in non-firearm homicides and homicides committed inside (e.g., in a home) were either statistically significant or approached statistical significance (p = .006 and p = .070, respectively), whereas changes in the incidence of firearm homicides and homicides committed outside were not statistically significant (p = .238 and p = .418, respectively). We also determined that the ordinance was essentially unenforced, apparently because of a critical shortage of jail space. CONCLUSIONS: Our findings are consistent with a model in which the ordinance had a dampening effect on firearm homicides occurring in public in Detroit. The apparent preventive effect evident in the time series analyses may have been due to publicity about the ordinance, whereas the small nature of the effect may have been due to the lack of enforcement.

Asunto(s)

Armas de Fuego/legislación & jurisprudencia , Homicidio/prevención & control , Homicidio/tendencias , Humanos , Michigan

Asunto(s)

Crimen , Homicidio , Adulto , Estudios Transversales , Humanos , Robo , Estados Unidos

Asunto(s)

Homicidio , Problemas Sociales/tendencias , Violencia , Estudios Transversales , Humanos , Estados Unidos

RESUMEN

The most widely used source of nationwide data on homicide in the United States is the Supplementary Homicide Report (SHR) data compiled by the FBI as part of its Uniform Crime Reporting System. This paper describes a study of the reliability of robbery-murder classifications by the SHR for Baltimore, Maryland during 1983. The research is exploratory, but indicates a high level of inconsistency in the data. Of the 42 cases that were classified as robbery murders by the SHR or the replication study, only 20 were classified that way in both studies. The high level of unreliability can be attributed to three major problems: (1) the SHR codes are mutually exclusive, but many homicides could be placed in several of the categories; (2) there are few systematic rules for classifying ambiguously motivated homicides; and (3) the SHR placed too many cases in the "unknown" category. It appears that the reliability of the coding could be increased substantially with relatively minor changes in the procedures currently used.

Asunto(s)

Homicidio/clasificación , Robo/clasificación , Violencia , Baltimore , Homicidio/legislación & jurisprudencia , Humanos , Reproducibilidad de los Resultados

Asunto(s)

Fertilidad , Modelos Teóricos , Densidad de Población , Adolescente , Adulto , Chicago , Femenino , Humanos , Masculino

Asunto(s)

Cultura , Homicidio , Humanos , Proyectos de Investigación , Factores Socioeconómicos , Estados Unidos , Violencia