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1.
Hum Biol ; 92(2): 63-80, 2021 02.
Article in English | MEDLINE | ID: mdl-33639638

ABSTRACT

Haplogroup Q originated in Eurasia around 30,000 years ago. It is present in Y-chromosomes from Asia and Europe at rather low frequencies. Since America is undoubtedly one of the continents where this haplogroup is highly represented, it has been defined as one of the founding haplogroups. Its M3 clade has been early described as the most frequent, with pan-American representation. However, it was also possible to find several other haplogroup Q clades at low frequencies. Numerous mutations have been described for haplogroup Q, allowing analysis of its variability and assignment of its geographic origin. We have analyzed 442 samples of unrelated men from Argentina and Paraguay belonging to haplogroup Q; here we report specifically on 27 Q (xM3) lineages. We tested 3 single-nucleotide polymorphisms (SNPs) by amplified product-length polymorphism (APLP) analysis, 3 SNPs for restriction fragment length polymorphism (RFLP) analysis, 15 SNPs by Sanger sequencing, and 17 short tandem repeats (STRs). Our approach allowed us to identify five subhaplogroups. Q-M3 and Q-CTS2730/Z780 are undoubtedly autochthonous lineages and represent the most frequent subhaplogroups, with significant representation in self-defined aboriginal populations, and their autochthonous status has been previously described. The aim of present work was to identify the continental origin of the remaining Q lineages. Thus, we analyzed the STR haplotypes for the samples and compared them with haplotypes described by other authors for the rest of the world. Even when haplogroup Q lineages have been extensively studied in America, some of them could have their origin in post-Columbian human migration from Europe and Middle East.


Subject(s)
Chromosomes, Human, Y , Genetics, Population , Americas , Argentina , Asia , Chromosomes, Human, Y/genetics , Europe , Haplotypes/genetics , Humans , Male , Microsatellite Repeats , Middle East , Paraguay , Phylogeny , Polymorphism, Single Nucleotide/genetics
2.
Rev. argent. radiol ; 84(2): 47-54, abr. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1125855

ABSTRACT

Resumen Objetivo: La osteoporosis es una condición de relevancia a nivel epidemiológico en Argentina, así como en el resto del mundo. Si bien actualmente la herramienta diagnóstica más relevante es la densitometría ósea, los análisis radiológicos pueden aportar información, principalmente en lo referente a la calidad ósea. En ese sentido, nos proponemos evaluar la estructura trabecular calcánea de una población local. Métodos: El material para dicho estudio consistió en 91 calcáneos de esqueletos pertenecientes a una muestra esqueletal. Fueron analizados individuos adultos, de ambos sexos, mediante imágenes radiográficas, a fin de clasificar su estructura trabecular de acuerdo al índice propuesto por Jhamaria y col., en una escala de V (normal) a I (osteoporosis severa). Resultados: Las prevalencias estimadas fueron de 23,1% de osteoporosis (fases I y II), 16,5% de borderline (fase III) y 48,4% se clasificó como estructura trabecular normal (fases IV y V). En relación a la edad de los individuos, se encontró una correlación significativa negativa entre ella y la pérdida trabecular (tau-b = -0,524, p = 0,00). No se encontraron diferencias significativas en cuanto a la afección dimórfica de la patología. Discusión: La relación entre envejecimiento y osteoporosis hallada es coincidente con estudios nacionales e internacionales que reconocen una disminución en la densidad mineral ósea (DMO) y una mala calidad ósea en individuos adultos mayores. La ausencia de afección dimórfica podría deberse a la edad promedio de la muestra, sumada a la posible resistencia de la estructura esponjosa del calcáneo a los cambios generados por el déficit estrogénico en las mujeres, característica de la osteoporosis tipo I. Conclusión: Creemos que es necesario revalorizar el análisis óseo por medio de radiografías, puesto que pueden ser de utilidad tanto en la clínica como en la investigación básica, debido a la mayor disponibilidad de equipos y a que posibilitan el análisis de otras propiedades del tejido óseo.


Abstract Objective: Osteoporosis is an important condition in an epidemiologic level in Argentina as in the rest of the world. Even though nowadays the most relevant diagnostic technique is bone densitometry, radiological studies can provide useful information, mainly in relation to bone quality. For this purpose, we aim to evaluate the calcaneus trabecular structure in a contemporary local population. Methods: The sample for this study consisted of 91 calcaneus from skeletons belonging to the skeletal repository. Adult individuals from both sexes were analyzed, to classify their trabecular structure according to the index proposed by Jhamaria et al., on a scale of V (normal) to I (severe osteoporosis). Results: The estimated prevalence were 23,1% of osteoporosis (phase I and II), 16,5% of borderline (phase III) and 48,4% were classified as normal trabecular structure (phase IV and V). In relation to the age of the individuals, a significant negative correlation was found between the first and the trabecular loss (tau-b = -0.524, p = 0.00). No significant differences were found in relation to the sex prevalence of this pathology. Discussion: The association found between aging and osteoporosis matches with the results of national and international studies that recognize that a decrease in Bone Mineral Density (BMD) and a bad bone quality in older adults. Absence of differences between sexes in this condition could be due to age average of the sample, added to the possible resistance of the calcaneus spongy structure to changes generated by estrogen deficit in women, characteristic of osteoporosis type I. Conclusion: We believe that it is necessary to revalue bone analysis by radiographic means, since they can be of use both in clinic and in basic research, due to a greater equipment availability and because they allow the analysis of other properties of bone tissue.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Osteoporosis/diagnostic imaging , Calcaneus/diagnostic imaging , Cancellous Bone/diagnostic imaging , Bone and Bones , Radiography , Bone Density , Cross-Sectional Studies
3.
Clin Cancer Res ; 26(7): 1725-1735, 2020 04 01.
Article in English | MEDLINE | ID: mdl-31732522

ABSTRACT

PURPOSE: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies. EXPERIMENTAL DESIGN: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as "training set"; the remaining two thirds, constituting the "test set," were used for the prospective validation of the GS. RESULTS: In the melanoma training set, the expression level of eight Th1/IFNγ-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications. CONCLUSIONS: These findings provide evidence that expression of Th1/IFNγ genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Gene Expression Regulation, Neoplastic , Interferon-gamma/immunology , Melanoma/pathology , Th1 Cells/immunology , Tumor Microenvironment/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Interferon-gamma/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Melanoma/drug therapy , Melanoma/genetics , Prognosis , Prospective Studies , Survival Rate , Th1 Cells/metabolism , Transcriptome
4.
Forensic Sci Int Genet ; 34: 116-127, 2018 05.
Article in English | MEDLINE | ID: mdl-29459285

ABSTRACT

The turn-around time of urgent crime scene DNA samples is often far longer than desired by law enforcement. Crime scene DNA sample processing involves both complex and routine processing steps. Simplification and integration of the routine steps would dramatically improve turn-around time and reduce the risk of operator contamination. Routine DNA extraction and quantitation is readily available. However, PCR amplification and electrophoretic analysis remain largely manual. Rapid DNA Analysis is a hands-free "swab in - profile out" process which consists of automated DNA extraction, amplification, separation, detection, and allele calling without human intervention. RapidHIT® 200 and RapidHIT ID are rapid DNA systems developed by IntegenX (Pleasanton, CA) and validated for the use of buccal swabs. A new generation of the RapidHIT sample cartridge for RapidHIT ID has been designed and tested which allows the loading of extracted and quantified DNA. RapidHIT EXT sample cartridge allows a user to generate a forensic DNA profile from less than 250 pg of extracted and quantified DNA in less than 90 min with less than one-minute hands-on time. Once the sample is loaded in the RapidHIT EXT sample cartridge, a DNA profile is produced after amplification, detection and automated data analysis. We report on sensitivity, reproducibility, concordance, DNA mixtures and carryover for EXT sample cartridges pre-loaded with GlobalFiler® Express and AmpFLSTR® NGM SElect™ Express, (Thermo Fisher Scientific, Waltham, MA) STR chemistries. Purified and quantified DNA from mock crime scene samples were used to demonstrate the utility of these cartridges in an established forensic laboratory.


Subject(s)
DNA Fingerprinting/instrumentation , Microsatellite Repeats , DNA/analysis , DNA Fingerprinting/methods , Electrophoresis, Capillary , Female , Humans , Male , Polymerase Chain Reaction , Reproducibility of Results , Time Factors
5.
Forensic Sci Int Genet ; 28: 21-34, 2017 05.
Article in English | MEDLINE | ID: mdl-28135583

ABSTRACT

The RapidHIT® ID is a fully automated sample-to-answer system for short tandem repeat (STR)-based human identification. The RapidHIT ID has been optimized for use in decentralized environments and processes presumed single source DNA samples, generating Combined DNA Index System (CODIS)-compatible DNA profiles in less than 90min. The system is easy to use, requiring less than one minute of hands-on time. Profiles are reviewed using centralized linking software, RapidLINK™ (IntegenX, Pleasanton, CA), a software tool designed to collate DNA profiles from single or multiple RapidHIT ID systems at different geographic locations. The RapidHIT ID has been designed to employ GlobalFiler® Express and AmpFLSTR® NGMSElect™, Thermo Fisher Scientific (Waltham, MA) STR chemistries. The Developmental Validation studies were performed using GlobalFiler® Express with single source reference samples according to Scientific Working Group for DNA Analysis Methods guidelines. These results show that multiple RapidHIT ID systems networked with RapidLINK software form a highly reliable system for wide-scale deployment in locations such as police booking stations and border crossings enabling real-time testing of arrestees, potential human trafficking victims, and other instances where rapid turnaround is essential.


Subject(s)
DNA Fingerprinting , DNA/genetics , High-Throughput Nucleotide Sequencing/instrumentation , Microsatellite Repeats , Animals , Humans , Reproducibility of Results , Software , Species Specificity
6.
Rev. esp. med. legal ; 40(4): 133-138, oct.-dic. 2014.
Article in Spanish | IBECS | ID: ibc-127413

ABSTRACT

Introducción. Este trabajo tiene por objeto evaluar la aplicabilidad y precisión de 4 métodos para estimar la edad por el desarrollo de la dentición en el período posnatal temprano. Material y métodos. Para la realización de este estudio se seleccionó una muestra constituida por 25 individuos de ambos sexos, sin evidencias de enfermedades y con edades documentadas entre 0 y 6 meses posnatales. Se estimaron las edades dentales mediante la utilización de los trabajos de Moorrees et al. (1963a; b), Lunt y Law (1974), Ubelaker (1978) y AlQahtani et al. (2010) y se compararon las edades estimadas con la edad cronológica documentada para cada individuo de la muestra. Resultados. Los resultados mostraron que el método de Moorrees no es adecuado para el período de edad analizado dado no permitió estimar la edad del total de los individuos de la muestra y las edades estimadas presentan diferencias significativas con las edades cronológicas documentadas. Los métodos de Lunt y Law y Ubelaker son poco precisos y el método de AlQahtani es el que arrojó mayor exactitud respecto de la edad cronológica documentada. Conclusiones. A partir de los resultados se llegó a la conclusión de que los métodos gráficos son de muy fácil aplicación sin detrimento de la precisión que pueden conseguir en la estimación, y que el método de AlQahtani es el que presenta mayor precisión y exactitud en el rango etario analizado (AU)


Introduction. This work aims to assess the applicability, accuracy and precision of four methods for estimating age by tooth development in the early postnatal period. Material and methods. To perform this study a sample of 25 individuals of both sexes, with no evidence of pathology and documented ages from 0 to 6 postnatal months was selected. Dental ages were estimated using reference data from Moorrees et al. (1963), Lunt and Law (1974), Ubelaker (1978) and AlQahtani et al. (2010). Estimated and chronological documented ages were compared. Results. The results showed that the Moorrees et al. method is not suitable for the targeted age group as it was not possible to estimate the age of all individuals in the sample and the estimated ages had significant differences with documented chronological age. Lunt and Law and Ubelaker methods are vague and AlQahtani et al. method is more accurate. Conclusions. On the basis of the results it is concluded that graphical methods are easily applied without loss of accuracy and that the most accurate and precise method is by AlQahtani et al (AU)


Subject(s)
Humans , Male , Female , Statistics as Topic , Forensic Dentistry/legislation & jurisprudence , Forensic Dentistry/methods , Forensic Medicine , Forensic Anthropology/methods , Forensic Anthropology/trends , Age Distribution , Forensic Dentistry/organization & administration , Forensic Dentistry/standards , Forensic Medicine/organization & administration , Forensic Medicine/standards , Forensic Anthropology/organization & administration , Forensic Anthropology/standards
7.
Public Health Nutr ; 15(11): 2086-90, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22444072

ABSTRACT

OBJECTIVE: To compare estimates of underweight, stunting, wasting, overweight and obesity based on three growth charts. DESIGN: Cross-sectional study to estimate weight-for-age, length/height-for-age and weight-for-height comparing the 2006 WHO Child Growth Standards ('the WHO standards'), the 1977 National Center for Health Statistics (NCHS) international growth reference ('the NCHS reference') and the 1987 Argentine Pediatric Society Committee of Growth and Development reference ('the APS reference'). Cut-off points were defined as mean values ±2 s d. Epi-Info software version 6·0 (Centers for Disease Control and Prevention) was used for statistical evaluations (χ 2, P ≤ 0·05). SETTING: Greater La Plata conurbation, Buenos Aires, Argentina. SUBJECTS: A total of 2644 healthy, full-term children from 0 to 5 years of age. RESULTS: Prevalence of underweight was higher with the WHO standards than with the other references up to the first 6 months. For the rest of the ages, prevalence was lower with the WHO standards. Stunting prevalence was higher with the WHO standards at all ages. Prevalence of wasting was higher with the WHO standards compared with the NCHS reference up to the first 6 months and lower at 2-5 years of age. Overweight and obesity prevalences were higher with the WHO standards at all ages. CONCLUSIONS: The new WHO standards appear to be a solid and reliable tool for diagnosis and treatment of nutritional diseases, also being the only one built with infants fed according to WHO recommendations. Therefore, our results support the decision of the National Ministry of Health about the utilization of the new WHO standards to monitor the nutritional status of Argentinean children aged less than 5 years.


Subject(s)
Growth Disorders/epidemiology , Growth , Nutritional Status , Obesity/epidemiology , Thinness/epidemiology , Wasting Syndrome/epidemiology , World Health Organization , Age Factors , Argentina/epidemiology , Body Height , Body Weight , Child, Preschool , Female , Humans , Infant , Male , National Center for Health Statistics, U.S. , Overweight , Prevalence , Reference Values , Societies, Medical , United States
8.
Am J Phys Anthropol ; 140(3): 578-82, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19591214

ABSTRACT

We analyzed 21 paragroup Q* Y chromosomes from South American aboriginal and urban populations. Our aims were to evaluate the phylogenetic status, geographic distribution, and genetic diversity in these groups of chromosomes and compare the degree of genetic variation in relation to Q1a3a haplotypes. All Q* chromosomes from our series and five samples from North American Q* presented the derivate state for M346, that is present upstream to M3, and determined Q1a3* paragroup. We found a restrictive geographic distribution and low frequency of Q1a3* in South America. We assumed that this low frequency could be reflecting extreme drift effects. However, several estimates of gene diversity do not support the existence of a severe bottleneck. The mean haplotype diversity expected was similar to that for South American Q1a3* and Q1a3a (0.478 and 0.501, respectively). The analysis of previous reports from other research groups and this study shows the highest frequencies of Q* for the West Corner and the Grand Chaco regions of South America. At present, there is no information on whether the phylogenetic status of Q* paragoup described in previous reports is similar to that of Q1a3* paragroup though our results support this possibility.


Subject(s)
Chromosomes, Human, Y , Genetic Variation , Geography , Indians, South American/genetics , Genetic Drift , Haplotypes , Humans , Phylogeny , South America
9.
Nutr Res ; 29(1): 35-40, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19185775

ABSTRACT

The relationship between protein-energy malnutrition and genetic damage has been studied in human beings and laboratory animals, but results are still conflicting. The aim of the present study was to assess the induction of structural chromosomal aberrations in peripheral blood lymphocytes of children with primary protein-energy malnutrition. A case-control study was performed. Samples were obtained from 25 primary malnourished infants (mean age, 22 months; range, 1-66 months). The control group consisted of 25 eutrophic children from the same population who were matched 1:1 by age and sex. Anthropometric and clinic evaluations were performed to assess nutritional condition. Before blood collection, we interviewed each individual's parent to complete a semi-structural survey specifying age, dietary habits, viral or bacterial diseases; previous exposure to diagnostic x-rays; and use of therapeutic drugs. After 48 hours, 100 cultured lymphocytes were analyzed per patient. Statistical analysis was performed using the Epi Dat 3.0 program (P < or = .05). The chromosomal aberration frequency was nearly 7 times higher in malnourished infants than in controls (14.61% vs 2.2%, respectively). This difference was statistically significant (P < .001) and may be explained by the occurrence of achromatic lesions, breaks, and telomeric associations. DNA damage could be attributed to several factors: severe deficiency of essential nutrients (ie zinc, iron, and vitamin A) required in the synthesis of DNA maintenance factors; deterioration of repair mechanisms allowing the persistence of an unusually high number of structural chromosomal aberrations; and/or the absence of specific factors needed to protect the cell against oxidative DNA damage.


Subject(s)
Chromosome Aberrations/statistics & numerical data , DNA Damage , Protein-Energy Malnutrition/complications , Argentina , Case-Control Studies , Child, Preschool , Chromosome Aberrations/chemically induced , DNA/ultrastructure , Data Collection , Female , Humans , Infant , Lymphocytes/ultrastructure , Male , Mutagens/adverse effects , Protein-Energy Malnutrition/genetics
10.
Arch. latinoam. nutr ; 58(4): 330-335, dic. 2008. graf, tab
Article in Spanish | LILACS | ID: lil-588723

ABSTRACT

La evaluación de la situación nutricional de los niños, depende en gran medida de las curvas de crecimiento utilizadas. El objetivo de esta investigación es comparar las prevalencias de sobrepeso y obesidad estimadas con tres referencias internacionales en una población de niños, a través del Índice de Masa Corporal. Se incluyeron 737 niños/as nacidos de término sanos, de 2 a 5 años (estudio transversal). La Participación fue voluntaria y consentida. Se estableció el Índice de Masa Corporal (kg/m²). Las técnicas de medición se basaron en guías nacionales. Las referencias utilizadas fueron: 1. Centers for Disease Control and Prevention (CDC) (>Pc85: sobrepeso; > Pc95: obesidad); 2. International Obesity Task Force (IOTF) (valores límites sexo-edad específicos) y 3. Organización Mundial de la Salud (OMS) (+2 desvíos estándar: sobrepeso; >+3: obesidad). Los resultados fueron evaluados estadísticamente mediante el programa Epi Info 6.0 (χ², p < 0,05 por ciento). La prevalencia de niños con sobrepeso estimada con la referencia del CDC es 1,1 veces mayor que la de IOTF y 2,33 veces la de OMS y la de IOTF es 2,1 veces la de OMS (p= 0,00001). La prevalencia de niños con obesidad estimada con la referencia del CDC es 5,4 veces la de IOTF y 23,9 veces la de OMS, mientras que la de IOTF es 4,4 veces la de OMS (p= 0,0000001). Las prevalencias de sobrepeso y obesidad, difieren substancialmente de acuerdo a la referencia y valores límite utilizados. No existiendo aún un criterio único, cada una de las referencias debe utilizarse con precaución.


The evaluation of child nutritional status is highly dependent on the growth charts used. The aim of this study was to compare different references assessing overweight and obesity in children population, through the Body Mass Index. A total of 737 healthy children born at term, aged 2-5 years, were included (cross-sectional study). The participation was voluntary and consent. Body Mass Index (kg/m²) was estimated. The measurements techniques were based on national guidelines. We compared three references: (1) Centers for Disease Control and Prevention (CDC) (>Pc85: overweight; >Pc95: obesity; (2) International Obesity Task Force (IOTF) (sex-age-specific body mass index cut-offs); (3) World Health Organization (WHO) (+2 standard deviation: overweight; +3: obesity). The Epi Info 6.0 software was used to the statistical evaluation ((χ2, p≤ , 05 percent). The prevalence of overweight was 1,1 and 2,33 times higher in CDC application respect to the IOTF and the WHO references respectively. The prevalence of overweight was 2,1 times higher in IOTF application respect to the WHO references (p=, 00001). The prevalence of obesity was 5,4 and 23,9 times higher in CDC application respect to the IOTF and the WHO references respectively. The prevalence of obesity was 4,4 times higher in IOTF application respect to the WHO references (p=, 0000001). The prevalence of overweight and obesity, calculated through the BMI, differs substantially according to the reference and cut-off points used. In the absence of even a single criterion, each of the references should be used with care.


Subject(s)
Humans , Male , Female , Child, Preschool , Anthropometry/methods , Body Mass Index , Body Weight , Obesity , Child Nutrition Sciences , Pediatrics
11.
Arch Latinoam Nutr ; 58(4): 330-5, 2008 Dec.
Article in Spanish | MEDLINE | ID: mdl-19368292

ABSTRACT

The evaluation of child nutritional status is highly dependent on the growth charts used. The aim of this study was to compare different references assessing overweight and obesity in children population, through the Body Mass Index. A total of 737 healthy children born at term, aged 2-5 years, were included (cross-sectional study). The participation was voluntary and consent. Body Mass Index (kg/m2) was estimated. The measurements techniques were based on national guidelines. We compared three references: (1) Centers for Disease Control and Prevention (CDC) (> Pc85: overweight; > Pc95: obesity; (2) International Obesity Task Force (IOTF) (sex-age-specific body mass index cut-offs); (3) World Health Organization (WHO) (+2 standard deviation: overweight; +3: obesity). The Epi Info 6.0 software was used to the statistical evaluation (chi2, p < or = .05%). The prevalence of overweight was 1.1 and 2.33 times higher in CDC application respect to the IOTF and the WHO references respectively. The prevalence of overweight was 2.1 times higher in IOTF application respect to the WHO references (p = .00001). The prevalence of obesity was 5.4 and 23.9 times higher in CDC application respect to the IOTF and the WHO references respectively. The prevalence of obesity was 4.4 times higher in IOTF application respect to the WHO references (p = .0000001). The prevalence of overweight and obesity, calculated through the BMI, differs substantially according to the reference and cut-off points used. In the absence of even a single criterion, each of the references should be used with care.


Subject(s)
Body Mass Index , Obesity/diagnosis , Obesity/epidemiology , Argentina/epidemiology , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Nutritional Status/physiology , Overweight/epidemiology , Prevalence , Reference Standards , Reference Values
12.
Exp Cell Res ; 306(1): 128-41, 2005 May 15.
Article in English | MEDLINE | ID: mdl-15878339

ABSTRACT

B7-H4 protein is expressed on the surface of a variety of immune cells and functions as a negative regulator of T cell responses. We independently identified B7-H4 (DD-O110) through a genomic effort to discover genes upregulated in tumors and here we describe a new functional role for B7-H4 protein in cancer. We show that B7-H4 mRNA and protein are overexpressed in human serous ovarian cancers and breast cancers with relatively little or no expression in normal tissues. B7-H4 protein is extensively glycosylated and displayed on the surface of tumor cells and we provide the first demonstration of a direct role for B7-H4 in promoting malignant transformation of epithelial cells. Overexpression of B7-H4 in a human ovarian cancer cell line with little endogenous B7-H4 expression increased tumor formation in SCID mice. Whereas overexpression of B7-H4 protected epithelial cells from anoikis, siRNA-mediated knockdown of B7-H4 mRNA and protein expression in a breast cancer cell line increased caspase activity and apoptosis. The restricted normal tissue distribution of B7-H4, its overexpression in a majority of breast and ovarian cancers and functional activity in transformation validate this cell surface protein as a new target for therapeutic intervention. A therapeutic antibody strategy aimed at B7-H4 could offer an exciting opportunity to inhibit the growth and progression of human ovarian and breast cancers.


Subject(s)
B7-1 Antigen/genetics , Breast Neoplasms/pathology , Epithelial Cells/pathology , Gene Expression Regulation, Neoplastic/genetics , Ovarian Neoplasms/pathology , Animals , Apoptosis/genetics , Apoptosis/physiology , B7-1 Antigen/metabolism , Blotting, Western , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Membrane/chemistry , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , DNA, Complementary/genetics , Epithelial Cells/metabolism , Female , Glycosylation , Humans , Immunohistochemistry , Membrane Glycoproteins/analysis , Mice , Mice, SCID , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , RNA, Small Interfering/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transfection , V-Set Domain-Containing T-Cell Activation Inhibitor 1 , Xenograft Model Antitumor Assays/methods
13.
Ludovica pediátr ; 6(2): 43-50, ago. 2004. tab
Article in Spanish | LILACS | ID: lil-421987

ABSTRACT

Objetivos: algunos autores encontraron una relación entre la Malnutrición Proteico Energética (MPE) y elaumento de la frecuencia de Aberraciones Cromosómicas Estructurales (ACE) en niños menores de 5 años.El objetivo del siguiente trabajo es analizar la incidencia de ACE en una población de niños del partido de La Plata que presentan MPE. Material y Métodos: se tomó una muestra de 30 niños de 1 a 60 meses de edad cronológica, 15 controles sanos y 15 diagnosticados como MPE primarios a través de una evaluación antropométrica y clínica. Se aplicó una encuesta semiestructurada en la que se tuvieron en cuenta peso al nacimiento, variables antropométricas, alimentación, enfermedades virales, y/o infecciosas y exposición a agentes potencialmente genotóxicos. Se realizaron cultivos de sangre periférica y se analizó la frecuencia de ACE en 100 células por individuo. Los resultados obtenidos fueron sometidos a evaluación estadística utilizando el programa Epi Info 6.0. Resultados: la diferencia en la frecuencia global de ACE entre ambas muestras resultó significativa. Al tratar cada tipo de aberración en forma independiente se encontraron diferencias significativas para gaps y fracturas de mono e isocromátidas, cromosomas dicéntricos, fragmentos y asociaciones telométricas. No se encontraron diferencias significativas respecto a la exposición de los niños a agentes potencialmente genotóxicos tales como medicamentos, radiaciones, pesticidas y desechos industriales. Conclusiones: la MPE es capaz de inducir daño genotóxico, este efecto podria explicarse por la distorsión del ambiente químico interno o bien por la disminución de la acción de los mecanismos de reparación del ADN como consecuencia del déficit proteico


Subject(s)
Humans , Child , Chromosome Aberrations , Protein-Energy Malnutrition/classification
14.
Ludovica pediátr ; 6(2): 43-50, ago. 2004. tab
Article in Spanish | BINACIS | ID: bin-123623

ABSTRACT

Objetivos: algunos autores encontraron una relación entre la Malnutrición Proteico Energética (MPE) y el aumento de frecuencia de Aberraciones Cromosómaticas Estructurales (ACE) en niños menores de 5 años. El objetivo del siguiente trabajo es analizar la incidencia de ACE en una población de niños del partido d La Plata que presentan MPE. Material y Métodos: se tomó una muestra de 30 niños de 1 a 60 meses de edad cronológica, 15 controles sanos y 15 diagnosticados como MPE primarios a través de una evaluación antropométrica y clínica. Se aplicó una encuesta semiestructurada en la que se tuvieron en cuenta peso al nacimiento, variables antropométricas, alimentación, enfermedades virales y/o infecciosas y exposición a agentes potencialmente genotóxico. Se realizaron cultivos de sangre periférica y se analizó la frecuencia de ACE en 100 células por individuo. Los resultados obtenidos fueron sometidos a evaluación estadística utilizando el programa Epi Info 6.0


Subject(s)
Chromosome Aberrations
15.
Ludovica pediátr ; 6(2): 43-50, ago. 2004. tab
Article in Spanish | BINACIS | ID: bin-123609

ABSTRACT

Objetivos: algunos autores encontraron una relación entre la Malnutrición Proteico Energética (MPE) y elaumento de la frecuencia de Aberraciones Cromosómicas Estructurales (ACE) en niños menores de 5 años.El objetivo del siguiente trabajo es analizar la incidencia de ACE en una población de niños del partido de La Plata que presentan MPE. Material y Métodos: se tomó una muestra de 30 niños de 1 a 60 meses de edad cronológica, 15 controles sanos y 15 diagnosticados como MPE primarios a través de una evaluación antropométrica y clínica. Se aplicó una encuesta semiestructurada en la que se tuvieron en cuenta peso al nacimiento, variables antropométricas, alimentación, enfermedades virales, y/o infecciosas y exposición a agentes potencialmente genotóxicos. Se realizaron cultivos de sangre periférica y se analizó la frecuencia de ACE en 100 células por individuo. Los resultados obtenidos fueron sometidos a evaluación estadística utilizando el programa Epi Info 6.0. Resultados: la diferencia en la frecuencia global de ACE entre ambas muestras resultó significativa. Al tratar cada tipo de aberración en forma independiente se encontraron diferencias significativas para gaps y fracturas de mono e isocromátidas, cromosomas dicéntricos, fragmentos y asociaciones telométricas. No se encontraron diferencias significativas respecto a la exposición de los niños a agentes potencialmente genotóxicos tales como medicamentos, radiaciones, pesticidas y desechos industriales. Conclusiones: la MPE es capaz de inducir daño genotóxico, este efecto podria explicarse por la distorsión del ambiente químico interno o bien por la disminución de la acción de los mecanismos de reparación del ADN como consecuencia del déficit proteico


Subject(s)
Humans , Child , Protein-Energy Malnutrition/classification , Chromosome Aberrations
16.
Acta amaz ; 34(2): 155-163, 2004. ilus, mapas
Article in Spanish | LILACS | ID: lil-394094

ABSTRACT

A arqueologia da Amazônia boliviana ou das "Terras Baixas" compreende um imenso território que mostra, a luz da informação disponível, significativas descontinuidades espaço-temporais. A identificação nesta área de sociedades constituindo "cacicados da floresta tropical" a partir de critérios baseados em preconceitos, requer a reavaliação da pré-história regional do ponto de vista causal. A arqueologia beniana (de Llanos de Mojos) é conhecida, fundamentalmente, a partir das escavações de Erland Nordenskiöld, que sem dúvida estabeleceu as bases conceituais existentes atualmente. Entre os anos de 1977 e 1981 uma missão do Museu de La Plata (Argentina), sob a direção de B. Dougherty, e em estreita colaboração com o Instituto de Arqueologia de La Paz (Bolívia) e com o Amazonian Ecosystem Research (EUA), conduziu pesquisas sistemáticas considerando variados itens antropológicos e produzindo numerosas datações de radiocarbono. Estas contribuições ajudaram a esclarecer, mas não a simplificar o panorama pré-hispânico regional, tão importante na temática arqueológica sul-americana. Complementa este artigo uma exaustiva lista de bibliografias que facilita o acesso ao conhecimento sobre este grande território.


Subject(s)
Archaeology , Bolivia , Secure Landfill
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