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1.
J Infect Dis ; 228(3): 299-310, 2023 08 11.
Article in English | MEDLINE | ID: mdl-36722147

ABSTRACT

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.


WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Pregnancy , Humans , Female , Infant , Infant, Newborn , Adolescent , Young Adult , Adult , Antibodies, Viral , Antibodies, Neutralizing , Mothers , Respiratory Syncytial Virus Infections/prevention & control , Viral Fusion Proteins , Placenta , Immunogenicity, Vaccine
2.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1535242

ABSTRACT

Objetivo: Describir la prevalencia del parto adolescente por cohorte a través de los años y su relación con factores sociodemográficos, en Panamá. Metodología: A partir de un análisis secundario de la "Encuesta nacional de salud sexual y reproductiva 2014-2015" de Panamá, utilizando cohortes por año de nacimiento (1966-1975, 1976-1985, 1986-1995 y 1996-2000), la relación enunciada se analizó mediante regresión logística. Se incluyeron 4795 adultas (20-49 años) y 821 adolescentes (15-19 años). Resultados: Se encontró un aumento en la prevalencia del parto adolescente entre cohortes, donde la prevalencia fue de 30,9 % en la cohorte mayor (1966-1975) y de 51,5 % en la cohorte de 1986-1995. En todas las cohortes, el parto adolescente estuvo asociado a la ruralidad (1966-1975, 42,3 % rural no indígena; 1976-1985, 56,6 % rural indígena; 1986-1995, 65,4 % rural no indígena y 58,2 % rural indígena). En todas las cohortes, el parto adolescente se relacionó con menor bienestar, encontrándose una prevalencia mayor que el 40 % en el quintil menor de riqueza en todas las cohortes. El parto adolescente se asoció a tener 4 o más hijos en las cohortes mayores (1966-1975 y 1976-1985), con prevalencias mayores que el 63 %. Conclusiones: La prevalencia del parto en adolescente en Panamá se ha mantenido en crecimiento. Las poblaciones rurales y de menor bienestar se han mantenido con mayor prevalencia de parto adolescente, indicando dónde enfocar las intervenciones preventivas.


Objective: To describe the prevalence of adolescent childbirth by cohort over time and its relationship with sociodemographic factors in Panama. Methodology: The analysis was conducted through logistic regression, based on a secondary analysis of the Panama "Encuesta nacional de salud sexual y reproductiva 2014- 2015" (2014-2015 National Survey on Sexual and Reproductive Health), using cohorts by year of birth (1966-1975, 1976-1985, 1986-1995, and 1996-2000). A total of 4795 adult women (20-49 years old) and 821 adolescent girls (15-19 years old) were included. Results: We found an increased prevalence of adolescent childbirth between cohorts, where prevalence was 30.9% in the older cohort (1966-1975) and 51.5% in the 1986- 1995 cohort. In all cohorts, adolescent childbirth was associated with rurality (1966-1975, 42.3% rural non Indigenous; 1976- 1985, 56.6% rural Indigenous; 1986-1995, 65.4% rural non Indigenous, and 58.2% rural Indigenous). Adolescent childbirth was also associated with lower well-being; across all cohorts, there was a prevalence of over 40% in the lowest wealth quintile. Adolescent childbirth was associated with having 4 or more children in the older cohorts (1966-1975 and 1976-1985), with a prevalence of over 63%. Conclusions: The prevalence of adolescent childbirth in Panama has continued to increase. Rural and lower well-being populations have continued to exhibit a higher prevalence of adolescent childbirth, which signals where to focus preventive interventions.


Objetivo: Descrever a prevalência do parto adolescente por conjuntos estabelecidos por anos e sua relação com fatores sociodemográficos, em Panamá. Metodologia: A partir de uma análise secundária da "Enquete nacional de saúde sexual e reprodutiva 2014-2015" de Panamá, utilizando conjuntos por ano de nascimento (1966-1975, 1976-1985, 1986-1995 e 1996-2000), a relação enunciada foi analisada por meio de regressão logística. Incluíram-se 4795 adultas (29-49 anos) e 821 adolescentes (15-19 anos). Resultados: Achou-se um aumento na prevalência do parto adolescente entre conjuntos, onde a prevalência foi de 30,9% no conjunto mais velho (1966-1975) e de 51,5% no conjunto de 1986-1995. Em todos os conjuntos, o parto adolescente esteve associado à ruralidade (1966-1975, 42,3% rural não indígena; 1976-1985, 56,6% rural indígena; 1986-1995, 65,4% rural não indígena e 58C,2% rural indígena). Em todos os conjuntos, o parto adolescente relacionou-se com menor bem-estar, sendo achada uma prevalência maior ao 40% no quintil menor de riqueza em todos os conjuntos. O parto adolescente associou-se a ter 4 ou mais filhos nos conjuntos mais velhos (1966-1975 e 1976- 1985), com prevalências maiores ao 63%. Conclusões: A prevalência do parto em adolescentes em Panamá tem mantido seu crescimento. As populações rurais e com menor bem-estar mantêm a maior prevalência do parto adolescente, indicando onde enfocar as intervenções preventivas.

3.
Aging (Albany NY) ; 13(22): 24542-24559, 2021 11 29.
Article in English | MEDLINE | ID: mdl-34845112

ABSTRACT

Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.


Subject(s)
Cell Differentiation/physiology , Maternal Age , Mesenchymal Stem Cells/physiology , Placenta/cytology , Telomere Shortening/physiology , Adolescent , Adult , Cell Proliferation/physiology , Female , Humans , Pregnancy , Young Adult
4.
Rev. méd. Panamá ; 41(2): 2-7, oct. 2021.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1371917

ABSTRACT

Introducción. La Organización Mundial de la Salud reconoce que la violencia conyugal es una problemática que va más allá del ámbito familiar, afecta a todos los sectores de la sociedad convirtiéndose en un grave problema de salud pública y de derechos humanos. Objetivo: examinar la relación entre elementos del empoderamiento femenino y tipos de violencia conyugal. Métodos: con datos de la Encuesta Nacional de Salud Sexual y Reproductiva (2014-2015) se analizaron 3679 mujeres casadas/unidas. Se construyeron tres indicadores de empoderamiento como variable independiente, como variable dependiente se estudió la violencia física/sexual. Los datos fueron analizados con el programa SPSS utilizando descripciones de frecuencia, cruce de variables y pruebas de significancia estadística. Resultados: Aquellas mujeres que más justifican la violencia conyugal, son las que más sufren agresiones físicas como empujones y/o sacudidas (15%), las que no justifican la violencia por ninguna razón, solo 4.1% sufren ataques de este tipo (p=0.000). El 3.1% de las mujeres con menor participación en el hogar son las que menos agresiones sufren en comparación con las que toman más decisiones y sufren más agresiones (8.1%) (p< 0.000). El grado de participación en aspectos importantes de Salud Sexual y Reproductiva (SSR), muestra que aquellas que no tenían ningún tipo de intervención, padecen mayores agresiones de tipo sexual (7.3%), estas agresiones disminuyen cuando la mujer toma mayores decisiones en SSR (0.4%) (p=0.000). Conclusiones: Hay una asociación positiva entre una menor vivencia de violencia física/sexual con mayores niveles de autonomía en temas de SSR y Rechazo a la Violencia Conyugal. (provisto por Infomedic International)

5.
Rev. méd. Panamá ; 41(1): 2-13, ene. 2021.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1371898

ABSTRACT

Objetivo. Identificar la prevalencia y factores asociados al uso del condón en la última relación sexual con una pareja no conyugal no conviviente (PNCC) entre aquellos que mantuvieron relaciones con este tipo de parejas en los últimos 12 meses. Métodos. Análisis secundario de 3261 entrevistados con PNCC de la Encuesta Nacional de Salud Sexual y Reproductiva (ENASSER) 2015, utilizando regresión logística multivariada para identificar asociaciones entre características sociodemográficas, acceso a servicios, comportamiento, y violencia de pareja con el uso del condón. Resultados. El 54% de los entrevistados usó condón en la última relación sexual. El análisis ajustado muestra que los hombres (aOR=2.89; p<0.001) tienen mayores oportunidades de usar condón. Estas oportunidades disminuyen con la edad y aumentan con el bienestar: menor en el grupo de 25-49 (aOR=0.47; p<0.001) y 20-24 (aOR=0.51; p=0.019) en comparación con el grupo de 15-19 años, mayor en hogares con bienestar alto (aOR=2.48; p<0.001) y medio (aOR=1.83; p=0.034), viviendo en áreas no comarcales (aOR=1.74; p=0.026), con trabajadora sexual/casual/conocido (aOR=6.82; p<0.001), novio/novia (aOR=3.41; p<0.001) como última pareja sexual. En las mujeres, las oportunidades eran mayores si vivían en áreas no comarcales (aOR=2.95; p=0.021), con trabajadora sexual/casual/conocido como última pareja sexual (aOR=3.99; p=0.001); y baja con menor educación (noveno grado o menos) (aOR=0.55; p=0.031), y si sufrió violencia por parte de una pareja en los últimos 12 meses (aOR=0.43; p=0.027). Conclusiones. La prevalencia de uso del condón con PNCC fue baja. Los factores asociados fueron sexo, edad, residencia, bienestar, tipo de pareja y violencia reciente en las mujeres. (provisto por Infomedic International)

6.
Rev. centroam. obstet. ginecol ; 20(2): 31-38, abr.-jun. 2015. graf, tab
Article in Spanish | LILACS | ID: biblio-835840

ABSTRACT

Objetivo. Estudiar asociaciones entre tener una actitud negativa hacia la educación sexual a jóvenes, y factores socio-demográficos y conocimientos, actitudes y prácticas sobre salud sexual y reproductiva. Métodos. Se estudiaron 5676 mujeres y 2357 hombres de15 a 49 años con datos de la Encuesta Nacional sobre Salud Sexual y Reproductiva 2009. Se utilizó Chi cuadrado de Pearson y el Test de Wald en STATA/SE 13.1. Las frecuencias relativas se ponderaron por factores de expansión. Resultados. Mas mujeres (17.9%) que hombres (13.4%)no están a favor de la educación sexual a jóvenes (p=0.01), sin embargo, no hay diferencias según sexo en la oposicióna enseñar métodos de planificación familiar (22.7%). Seoponen a la educación sexual principalmente personas sineducación o sólo con educación primaria, pobres extremos, viviendo en áreas indígenas y rurales, pertenecientes apueblos originarios, que apoyan la violencia contra la mujery sin conocimiento comprensivo sobre VIH-SIDA. En los hombres, el no haber tenido relaciones sexuales se relacionacon una actitud negativa hacia la educación sexual a jóvenes, mientras que en las mujeres se relacionan la religión y las actitudes de aceptación de roles tradicionales de género. La edad y el estado civil no influyen en el apoyo a la educación sexual...


Objective. Studying associations between having a negativeattitude towards sex education to young people, and sociodemographic factors and knowledge, attitudes and practices on sexual and reproductive health Methods. Were studied 5676 women and 2357 men aged 15to 49 years using data from the National Survey on Sexual and Reproductive Health 2009. It was used Chi square test and the Wald test with STATA / SE 13.1. The relative frequencies were weighted by expansion factors. Results. More women (17.9%) than men (13.4%) are notin favor of sex education to youth (p = 0.01), however, nodifferences by sex in opposition to teach methods of family planning (22.7%). The opposition to sex education is mainly from uneducated people or only with primary education, living in extreme poverty, living in rural and indigenous areas, belonging to indigenous peoples, who support violence against women, and without comprehensive knowledge aboutHIV-AIDS. In men, not having sex is related to a negative attitude towards sex education to young, while in women religion and the attitudes of acceptance of traditional genderroles are related. Age and marital status did not influence support for sex education...


Subject(s)
Humans , Adolescent , Sex Education/methods , Panama , Reproductive Health/education
7.
Rev. centroam. obstet. ginecol ; 20(2): 40-46, abr.-jun. 2015. tab
Article in Spanish | LILACS | ID: biblio-835841

ABSTRACT

Objetivo. Identificar los factores que se relacionan a la iniciación sexual a temprana edad en las adolescentes panameñas. Métodos. Se estudiaron 1193 mujeres de 15 a 19 años con datos de la Encuesta Nacional sobre Salud Sexual y Reproductiva de 2009. Se utilizó la regresión de riesgos proporcionales de Cox en SPSS 20. Las frecuencias relativas se ponderaron por factores de expansión...


Objective. To identify the factors that were related to thesexual initiation to early age in the Panamanian adolescents.Methods. 1193 women of 15 to 19 years were studied with dataof the National Survey studied on Sexual and ReproductiveHealth of 2009. The regression of proportional risks of Cox inSPSS 20 was used. The relative frequencies were weighedby expansion factors...


Subject(s)
Humans , Adolescent , Adolescent , Sex Education/classification , Sex Education/methods , Reproductive Health
8.
Rev. centroam. obstet. ginecol ; 19(2): 41-47, abr.-jun. 2014. ilus
Article in Spanish | LILACS | ID: lil-734141

ABSTRACT

Objetivo. Identificar los determinantes de las necesidades insatisfechas de planificación familiar en las comarcas n gabe-Buglé y Emberá. Método. Se estudiaron 447 mujeres casadas o unidas y no embarazadas, de 15 a 49 años de las etnias n gabe,Buglé, Emberá y Wounaan, con datos de la Encuesta Nacional de Salud Sexual y Reproductiva 2009...


Subject(s)
Female , Family Development Planning , Indigenous Peoples , Health Services Needs and Demand/legislation & jurisprudence , Planning Techniques
9.
Rev. centroam. obstet. ginecol ; 18(1): 15-20, ene.-mar. 2013. ilus
Article in Spanish | LILACS | ID: lil-734062

ABSTRACT

Las mujeres indígenas en toda América Latina, incluyendo Panamá, presentan condiciones de inequidad en lo que se refiere a la salud sexual y reproductiva. La fecundidad elevada, el alto índice de embarazo adolescente, y la falta de una adecuada atención y asistencia a la salud materna, son evidencia de esto. Las altas tasas de mortalidad materna están relacionadas con falta de cobertura de los servicios de salud sexual y reproductiva...


Subject(s)
Humans , Maternal Welfare/ethnology , Health Inequities , Maternal Mortality/ethnology
10.
Int J Biochem Cell Biol ; 43(10): 1523-31, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21801849

ABSTRACT

Setleis Syndrome (OMIM ID: 227260) is a rare autosomal recessive disease characterized by abnormal facial development. Recently, we have reported that two nonsense mutations (c.486C>T [Q119X] and c.324C>T [Q65X]) of the basic helix-loop-helix (bHLH) transcription factor TWIST2 cause Setleis Syndrome. Here we show that periostin, a cell adhesion protein involved in connective tissue development and maintenance, is down-regulated in Setleis Syndrome patient fibroblast cells and that periostin positively responds to manipulations in TWIST2 levels, suggesting that TWIST2 is a transactivator of periostin. Functional analysis of the TWIST2 mutant form (Q119X) revealed that it maintains the ability to localize to the nucleus, forms homo and heterodimers with the ubiquitous bHLH protein E12, and binds to dsDNA. Reporter gene assays using deletion constructs of the human periostin promoter also reveal that TWIST2 can activate this gene more specifically than Twist1, while the Q119X mutant results in no significant transactivation. Chromatin immunoprecipitation assays show that both wild-type TWIST2 and the Q119X mutant bind the periostin promoter, however only wild-type TWIST2 is associated with higher levels of histone acetylation across the 5'-regulatory region of periostin. Taken together, these data suggest that the C-terminal domain of TWIST2, which is missing in the Q119X mutant form of TWIST2, is responsible for proper transactivation of the periostin gene. Improper regulation of periostin by the mutant form of TWIST2 could help explain some of the soft tissue abnormalities seen in these patients therefore providing a genotype-phenotype relationship for Setleis Syndrome.


Subject(s)
Cell Adhesion Molecules/genetics , Focal Dermal Hypoplasia/genetics , Helix-Loop-Helix Motifs , Repressor Proteins/metabolism , Skin Diseases/genetics , Transcriptional Activation , Twist-Related Protein 1/metabolism , Cells, Cultured , Codon, Nonsense/genetics , Ectodermal Dysplasia , Fibroblasts/metabolism , Focal Dermal Hypoplasia/metabolism , Focal Facial Dermal Dysplasias , Humans , Protein Multimerization , Repressor Proteins/chemistry , Repressor Proteins/genetics , Skin Diseases/metabolism , Twist-Related Protein 1/chemistry , Twist-Related Protein 1/genetics
11.
Biochemistry ; 48(22): 4881-94, 2009 Jun 09.
Article in English | MEDLINE | ID: mdl-19368335

ABSTRACT

Hemoglobin I (HbI) from the clam Lucina pectinata is an intriguing hemeprotein that binds and transports H(2)S to sulfide-oxidizing chemoautotrophic bacteria to maintain a symbiotic relationship and to protect the mollusk from H(2)S toxicity. Single point mutations at E7, B10, and E11 were introduced into the HbI heme pocket to define the reactivity of sulfide with hemeproteins. The functional and structural properties of mutant and wild-type recombinant proteins were first evaluated using the well-known ferrous CO and O(2) derivatives. The effects of these mutations on the ferric environment were then studied in the metaquo and hydrogen sulfide derivatives. The results obtained with the ferrous HbI mutants show that all the E7 substitutions and the PheB10Tyr mutation influence directly CO and O(2) binding and stability while the B10 and E11 substitutions induce distal structural rearrangements that affect ligand entry and escape indirectly. For the metaquo-GlnE7His, -PheB10Val, -PheB10Leu, and -E11 variants, two individual distal structures are suggested, one of which is associated with H-bonding interactions between the E7 residues and the bound water. Similar H-bonding interactions are invoked for these HbI-H(2)S mutant derivatives and the rHbI, altering in turn sulfide reactivity within these protein samples. This is evident in the resonance Raman spectra of these HbI-H(2)S complexes, which show reduction of heme iron as judged by the appearance of the nu(4) oxidation state marker at 1356 cm(-1), indicative of heme-Fe(II) species. This reduction process depends strongly on distal mutations showing faster reduction for those HbI mutants exhibiting the strongest H-bonding interactions. Overall, the results presented here show that (a) H(2)S association is regulated by external kinetic barriers, (b) H(2)S release is controlled by two competing reactions involving simple sulfide dissociation and heme reduction, (c) at high H(2)S concentrations, reduction of the ferric center dominates, and (d) reduction of the heme is also enhanced in those HbI mutants having polar distal environments.


Subject(s)
Hemeproteins/metabolism , Hemoglobins/metabolism , Hydrogen Sulfide/antagonists & inhibitors , Hydrogen Sulfide/metabolism , Amino Acid Substitution/genetics , Animals , Binding, Competitive/genetics , Bivalvia , Dose-Response Relationship, Drug , Electron Transport/genetics , Ferrous Compounds/chemistry , Ferrous Compounds/metabolism , Heme/chemistry , Heme/metabolism , Hemeproteins/chemistry , Hemeproteins/genetics , Hemoglobins/chemistry , Hemoglobins/genetics , Hydrogen Sulfide/toxicity , Protein Binding/genetics , Spectrum Analysis, Raman , Stereoisomerism , Structure-Activity Relationship
12.
Am J Pathol ; 171(3): 1023-36, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17675579

ABSTRACT

Notch functions as an oncogene or tumor inhibitor in various cancers, and decreases in Notch2 expression are associated with increasing grade of human breast cancer. We constitutively activated Notch signaling with intracellular domain (ICD) expression in the human adenocarcinoma line MDA-MB-231. Notch2 signaling increased apoptosis, whereas Notch4ICD (int3) significantly increased cell proliferation and growth. Cells with activated Notch2 or Notch4 were injected into nu/nu mice for analysis of in vivo tumor xenograft phenotype. Tumor growth was significantly altered depending on the receptor activated. Notch2ICD potently suppressed tumor take and growth, leading to a 60% decrease in tumors and significantly smaller, necrotic tumors. Despite this, Notch2ICD tumors were highly vascularized, although the vessels were smaller and comprised a more immature network compared with Notch4ICD tumors. Notch4ICD tumors were highly aggressive and well vascularized, indicating a role for Notch4 signaling in the promotion of the malignant phenotype in addition to its transforming ability. Although both NotchICD groups expressed angiogenic factors, Notch4ICD had selective vascular endothelial growth factor-D in both tumor and host stroma, suggesting a differential regulation of cytokines that may impact vascular recruitment and autocrine tumor signaling. Our results demonstrate that Notch2 signaling is a potent inhibitory signal in human breast cancer xenografts.


Subject(s)
Apoptosis/physiology , Breast Neoplasms , Neoplasm Transplantation , Receptor, Notch2/metabolism , Signal Transduction/physiology , Transplantation, Heterologous , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Mice , Mice, Nude , Oligonucleotide Array Sequence Analysis , Phenotype , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Receptor, Notch2/genetics , Receptor, Notch4 , Receptors, Notch/genetics , Receptors, Notch/metabolism , Transplantation, Heterologous/pathology , Transplantation, Heterologous/physiology
13.
Biochim Biophys Acta ; 1764(4): 758-65, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16380302

ABSTRACT

Lucina pectinata hemoglobin I (HbI), which is a ferric sulfide-reactive hemeprotein, contains a distal pocket characterized by the presence of GlnE7 and PheB10. To elucidate the structural-functional properties of HbI, oxygen binding kinetics and FTIR studies with recombinant HbI (rHbI) and a set of mutants were conducted using CO and CN- as sensors of the hemeprotein environment. Three nuCO modes were observed for rHbI at 1936 cm(-1) (A3, closed conformer) 1950 cm(-1) (A1,2, closed conformer) and 1960 cm(-1) (A0, open conformer). These nuCO were affected by substitution of GlnE7 and PheB10 in the CO complexes. The contribution of GlnE7 is demonstrated when this residue is replaced with Asn, Val or His. For instance, decreasing the positive electrostatic environment with GlnE7Val, causes an increase of 65% in the population of A0 and the disappearance and 55% reduction of the population of the A1,2 and A3 respectively. The contribution of PheB10 to the stabilization of ligands is also observed in the Leu and Tyr mutants. The PheB10Leu mutation produced an 8% decrease in the population of the A3 conformer while that of the A1,2 configuration increased by 30%. This suggests that GlnE7 and PheB10 contribute to the A3 conformer stabilizing the CO in a closed configuration. With CN- as probe no substantial differences in the nuCN was observed upon substitution of GlnE7 by Val while a slight down shift in the nuCN from 2120 cm(-1) to 2117 cm(-1) was observed in the PheB10Leu mutant. This implies that in HbICN GlnE7 moves away from the binding site while PheB10 remains in the vicinity of the bound CN-. Here, a mechanism in which the flexibility of the distal protein matrix coupled with hemeporphyrin movement toward a different configuration is suggested as an important process in the H2S transport and delivery in hemoglobin I.


Subject(s)
Bivalvia/chemistry , Heme/chemistry , Hemoglobins/chemistry , Ligands , Amino Acid Sequence , Animals , Carbon Monoxide/chemistry , Cyanides/chemistry , Ferric Compounds , Ferrous Compounds , Hemoglobins/genetics , Kinetics , Oxygen/chemistry , Protein Structure, Tertiary , Spectroscopy, Fourier Transform Infrared
14.
Biochim Biophys Acta ; 1747(2): 195-203, 2005 Mar 14.
Article in English | MEDLINE | ID: mdl-15698954

ABSTRACT

The distal pocket of hemoglobin II (HbII) from Lucina pectinata is characterized by the presence of a GlnE7 and a TyrB10. To elucidate the functional properties of HbII, biophysical studies were conducted on HbII and a HbI PheB10Tyr site-directed mutant. The pH titration data at neutral conditions showed visible bands at 486, 541, 577 and 605 nm for both proteins. This suggests the possible existence of a conformational equilibrium between an open and closed configuration due to the interactions of the TyrB10, ligand, and heme iron. The kinetic behavior for the reaction of both ferric proteins with H2O2 indicates that the rate for the formation of the ferryl intermediates species varies with pH, suggesting that the reaction is strongly dependent on the conformational states. At basic pH values, the barrier for the reaction increases as the tyrosine adopts a closed conformation and the ferric hydroxyl replaces the met-aquo species. The existence of these conformers is further supported by resonance Raman (RR) data, which indicate that in a neutral environment, the ferric HbII species is present as a possible mixture of coordination and spin states, with values at 1558 and 1580 cm(-1) for the nu2 marker, and 1479, 1492, and 1503 cm(-1) for the nu3 mode. Moreover, the presence of the A3 and A(o) conformers at 1924 and 1964 cm(-1) in the HbII-CO infrared spectra confirms the existence of an open and closed conformation due to the orientation of the TyrB10 with respect to the heme active center.


Subject(s)
Heme/chemistry , Hemoglobins/chemistry , Mollusca/metabolism , Tyrosine/chemistry , Animals , Heme/metabolism , Hemoglobins/genetics , Hydrogen Peroxide/pharmacology , Hydrogen-Ion Concentration , Iron/chemistry , Kinetics , Ligands , Models, Chemical , Mutation , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Tyrosine/metabolism
15.
Panama; s.n; 2005. 80 p. ilus.
Non-conventional in Spanish | LILACS | ID: lil-426968

ABSTRACT

Presenta el estudio de algunos mitos y prácticas sexuales de 1269 estudiantes adolescentes entre 14 y 19 años, con una media de edad de 16 años, de colegios públicos y privados pertenecientes a la provincia de Panamá. Se encontró que más de la cuarta parte de la población tenía mitos en diferentes áreas como : menstruación, masturbación, métodos anticonceptivos y relaciones sexuales. Al evaluar sus conocimientos se encontró que sólo un 4 porciento maneja la terminología correcta de los órganos reproductores esternos e internos del hombre y la mujer. Un 19 porciento conocía y manejaba el concepto días fértiles. Un 74 porciento había escuchado hablar alguna vez de algún método anticonceptivo y un 75 porciento poseían la definición correcta de ciertas palabras claves como : Ovulación, mestruación, orgasmo, entre otros. El 39 porciento de estos estudiantes ya habían iniciado vida sexual activa y un 48 porciento de ellos, habían iniciado antes de los 15 años de edad, El 57 porciento utilizó alguna vez métodos anticonceptivos. Un 12 porciento reportó haber estado enbarazada o haber enbarazado a alguien. Este estudio sugiere que los mitos y las crencias populares pueden influir en la conducta sexual de los adolescentes. El conocimiento de estos mitos es de gran utilidad al momento de implementar programas de educación sexual en las escuelas de Panamá


Subject(s)
Adolescent , Sexuality
16.
Protein Expr Purif ; 38(2): 184-95, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15555934

ABSTRACT

Hemoglobin I (HbI) from Lucina pectinata is a monomeric protein composed of 143 amino acids with high sulfide affinity. Its unique heme pocket contains three residues not commonly found in vertebrate globins: Phe 29 (B10), Gln 64 (E7), and Phe 68 (E11), which are thought to be important for high affinity for hydrogen sulfide. Recombinant HbI (rHbI) and several site-directed mutants were cloned and expressed in Escherichia coli yielding high amounts of protein. The highest rHbI protein yield was obtained when the HbI cDNA was cloned into the pET28 (a+) expression vector, transformed into BLi5 cells, the induction performed with 1 mM IPTG at 30 degrees C and TB medium was supplemented with 30 microg/mL hemin chloride and 1% glucose. The highest yield obtained of HbI was 32 mg/L of culture using Fernbach flasks. UV/Visible spectral analysis showed that rHbI binds heme and ESI-MS shows that its molecular weight corresponds to the expected size. Kinetic studies with H2S confirmed that rHbI and HbI have identical binding properties, where the kON for the clam's Hb is 2.73x10(4)M-1s-1 and for rHbI is 2.43x10(4)M-1s-1.


Subject(s)
Escherichia coli/genetics , Hemoglobins , Hydrogen Sulfide/chemistry , Amino Acid Sequence , Animals , Bivalvia/metabolism , Cloning, Molecular , Gene Expression Regulation, Bacterial , Genetic Vectors/genetics , Hemoglobins/biosynthesis , Hemoglobins/genetics , Hemoglobins/isolation & purification , Kinetics , Molecular Sequence Data , Mutagenesis, Site-Directed/genetics , Protein Binding , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Temperature
17.
Protein J ; 23(4): 239-45, 2004 May.
Article in English | MEDLINE | ID: mdl-15214494

ABSTRACT

The clam Lucina pectinata inhabits the sulfide-rich west coast of the island of Puerto Rico. It contains three different hemoglobins. Hemoglobin I (HbI), which is monomeric at all concentrations, carries H2S in its ferric state. Overexpression of recombinant HbI from Lucina pectinata in BL21STAR(DE3) Escherichia coli cells was performed in the presence of delta-aminolevulinic acid (delta-ALA). Purification of the protein was achieved using FPLC anion exchange and size exclusion chromatography. Functional characterization of the recombinant holo-protein was assessed by detection of the protein heme O2, CO, and H2S derivatives by UV-Vis spectroscopy, with Soret maxima at 416, 421, and 425 nm, respectively. The results indicated that the recombinant HbI binds H2S and forms a heme sulfide complex like the HbI wild-type hemoglobin. Kinetic measurements were performed to determine the H2S affinity of the recombinant HbI. The H2S dissociation and association rate constants were 0.055 x 10(-3)s(-1) and 0.068 x 10(5) M(-1)s(-1), respectively. The H2S affinity constant of the recombinant HbI (0.124 x 10(9) M(-1)) is eightfold lower than that of the native clam HbI reported earlier. This effect is attributed mostly to the first of two missense mutations [Met 61 (E4)-->Val 61 and Ile101 (FG4)-->Val 101] and additional amino acids present in our construct as demonstrated by measurements of the association rate with a new construct lacking most of the additional residues and the missense mutations. The elimination of these residues restores the similarity between the expressed and wild-type hemoglobins, as evidenced by H2S association kinetics. A pH dependence on the H2S association rate was also contributing to the overall affinity constant and was taken into account in the measurements of the functional properties of the new HbI construct.


Subject(s)
Bivalvia/metabolism , Escherichia coli/genetics , Hemoglobins/chemistry , Hemoglobins/genetics , Amino Acid Sequence , Amino Acid Substitution , Aminolevulinic Acid/pharmacology , Animals , Cloning, Molecular , Escherichia coli/metabolism , Heme/chemistry , Heme/metabolism , Hemoglobins/metabolism , Hydrogen Sulfide/chemistry , Molecular Sequence Data , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Alignment
18.
Panamá; s.n; 2003. 15 p. tab.
Non-conventional in Spanish | LILACS | ID: lil-471956

ABSTRACT

Informa que anualmente millones de jóvenes mujeres en todo el mundo, buscan poner fin aembarazos que no han sido planeados y deseados, por medio de abortos realizados encondiciones de riesgo.Métodos : Estudio descriptivo, comparativo, con intervención educativa. La muestra fueron100 jóvenes: 75 con aborto espontáneos y 25 con aborto provocados. Los datos se obtuvieronde una entrevista directa, utilizando un cuestionario pre codificado.Resultados : La edad media de las pacientes fue de 19 años ; el mayor nivel educativo se concentró en la secundaria incompleta. El 55% de las mujeres estaban en unión libre y el 76% profesaban el catolicismo. El inicio de vida sexual se presentó antes de los 15 años; más del 50% tuvieron 2 ó más parejas sexuales


Subject(s)
Abortion, Induced , Abortion, Spontaneous , Panama
19.
Panamá; s.n; 2002. 14 p. graf.
Non-conventional in Spanish | LILACS | ID: lil-471953

ABSTRACT

Informa que la adolescencia es un período crucial donde ocurren muchos cambios importantes. En esta etapa hay un cambio dramático en los niveles hormonales que se reflejan en un aumento en el deseo y la actividad sexual (1). Hoy día el adolescente inicia su vida sexual a edades muy tempranas. En este estudio quisimos indagar los conocimientos, actitudes y practicas sexuales de un grupo de adolescentes panameñas. Se captaron un total 150 adolescentes que acudían a la clínica de planificación familiar del Centro de Investigación en Reproducción Humana. La información se recopiló a través de un cuestionario pre- codificado.


Subject(s)
Adolescent , Attitude , Knowledge , Panama
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