CD105 expression in cancer-associated fibroblasts: a biomarker for bone metastasis in early invasive ductal breast cancer patients.

Introduction: Bone metastasis is one of the causes that mainly decrease survival in patients with advanced breast cancer. Therefore, it is essential to find prognostic markers for the occurrence of this type of metastasis during the early stage of the disease. Currently, cancer-associated fibroblasts, which represent 80% of the fibroblasts present in the tumor microenvironment, are an interesting target for studying new biomarkers and developing alternative therapies. This study evaluated the prognostic significance of the CD105 expression in cancer-associated fibroblasts in early breast cancer patients. Methods: Immunohistochemistry was used to assess CD105 expression in invasive ductal breast carcinomas (n = 342), analyzing its association with clinical and pathological characteristics. Results: High CD105 expression in cancer-associated fibroblasts was associated with an increased risk of metastatic occurrence (p = 0.0003), particularly bone metastasis (p = 0.0005). Furthermore, high CD105 expression was associated with shorter metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0002, 0.0006, and 0.0002, respectively). CD105 expression also constituted an independent prognostic factor for metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0003, 0.0006, and 0.0001, respectively). Discussion: The high CD105 expression in cancer-associated fibroblasts is an independent prognostic marker for bone metastasis in early breast cancer patients. Therefore, the evaluation of CD105(+) CAFs could be crucial to stratify BCPs based on their individual risk profile for the development of BM, enhancing treatment strategies and outcomes.

CD1a- and CD83-positive dendritic cells as prognostic markers of metastasis development in early breast cancer patients.

PURPOSE: Dendritic cells (DCs) are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response in different types of cancer. However, the prognostic significance of the accumulation of these cells in human early breast tumors is not totally clear. The aim of this study is to evaluate the prognostic relevance of CD1a( +) and CD83( +) dendritic cells in early breast cancer patients. METHODS: We conducted immunohistochemical assays to determine the number of stromal CD1a( +) and CD83( +) DCs in primary tumors from early invasive ductal breast cancer patients, and analyzed their association with clinico-pathological characteristics. RESULTS: Patients with high CD1a( +) DC number had lower risk of bone metastatic occurrence, as well as, longer disease-free survival (DFS), bone metastasis-free survival (BMFS) and overall survival (OS). Moreover, CD1a( +) DC number was an independent prognostic factor for BMFS and OS. In contrast, we found that patients with high number of CD83( +) DCs had lower risk of mix (bone and visceral)-metastatic occurrence. Likewise, these patients presented better prognosis with longer DFS, mix-MFS and OS. Furthermore, CD83( +) DC number was an independent prognostic factor for DFS and OS. CONCLUSION: The quantification of the stromal infiltration of DCs expressing CD1a or CD83 in early invasive breast cancer patients serves to indicate the prognostic risk of developing metastasis in a specific site.

Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway.

Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3/contactin+/NG2+ cells, which correlated with an increase in F3/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.

Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

UNLABELLED: Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. AIM: The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. METHODS: 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. RESULTS: High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). CONCLUSION: Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer.

CD105 expression on CD34-negative spindle-shaped stromal cells of primary tumor is an unfavorable prognostic marker in early breast cancer patients.

Several studies have confirmed that the breast tumor microenvironment drives cancer progression and metastatic development. The aim of our research was to investigate the prognostic significance of the breast tumor microenvironment in untreated early breast cancer patients. Therefore, we analyzed the association of the expression of α-SMA, FSP, CD105 and CD146 in CD34-negative spindle-shaped stromal cells, not associated with the vasculature, in primary breast tumors with classical prognostic marker levels, metastatic recurrence, local relapse, disease-free survival, metastasis-free survival and the overall survival of patients. In the same way, we evaluated the association of the amount of intra-tumor stroma, fibroblasts, collagen deposition, lymphocytic infiltration and myxoid changes in these samples with the clinical-pathological data previously described. This study is the first to demonstrate the high CD105 expression in this stromal cell type as a possible independent marker of unfavorable prognosis in early breast cancer patients. Our study suggests that this new finding can be useful prognostic marker in the clinical-pathological routine.

Association between ligands and receptors related to the progression of early breast cancer in tumor epithelial and stromal cells.

BACKGROUND: Despite advances in the study of breast cancer (BC), it remains the second leading cause of mortality among women. BC is a heterogeneous system, mainly composed of tumor epithelial cells (TEpCs) and stromal cells (SCs); the interaction through the ligands and their receptors (Rs) plays a major role in BC progression. The aim of the present study was to evaluate the association between ligands, such as osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand (RANKL), stromal cell-derived factor (SDF)-1, interleukin (IL)-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2), and their Rs in TEpC and spindle-shaped SCs not closely associated with the vasculature. PATIENTS AND METHODS: We studied the expression of all those factors in 63 primary tumors of untreated patients with BC with infiltrative ductal carcinoma (I/II stage) and 10 non-neoplastic tissues. The percentage of positive cells and the staining intensity were analyzed by immunohistochemistry. Mann-Whitney test and Spearman's rank correlation coefficient were used (P ≤ .05). RESULTS: We found a significant association between the expression of RANKL, IL-6, SDF-1, and CCL-2 in TEpC and the receptor activator of nuclear factor kappa B (RANK), IL-6R, C-X-C chemokine R type 4, and chemokine (C-C motif) R-2 (CCR-2) in spindle-shaped SC. The expression of TRAIL, RANKL, and CCL-2 in spindle-shaped SC also was associated with the expression of TRAIL-receptor 1, TRAIL-receptor 4, RANK, and CCR-2 in TEpC. CONCLUSIONS: Because the described ligands and Rs are implicated in BC progression, our results suggest that these factors could be involved in the crosstalk between TEpC and SC in the early stages of BC.

Prevalence and etiology of congenital hypothyroidism detected through an argentine neonatal screening program (1997-2010).

INTRODUCTION: We retrospectively assessed the incidence of congenital hypothyroidism (CH) detected through our neonatal screening program between 1997 and 2010. We describe the diagnostic characteristics of the detected population and verify the impact of a TSH cutoff (CO) change. PATIENTS AND METHODS: Screening was based on TSH determination on dried blood spot on filter paper samples (IFMA) using a 15 mU/l blood CO until 12/2002 (P1) and 10 mU/l thereafter (P2). Patients were classified as having transient or permanent CH (athyreotic, ectopic, eutopic, with goiter and unknown etiology). Global and diagnostic-related incidences were calculated for the whole studied period with the same CO, and P1 and P2 were compared. RESULTS: Incidences of permanent CH were 1:3,108 (P1) and 1:2,367 (P2). The lower CO detected 22 extra CH, 13 of them definitive (70% with eutopic glands). Only a significant increase (p < 0.05) in eutopic CH was found, partially related to the lower CO applied. A statistically significant association with time was seen for total definitive and ectopic cases (p < 0.05). CONCLUSION: Our findings revealed some changes in the detected population partially related to the CO applied, with only eutopic dysfunctional disorders being more prevalent in the later years. Total permanent CH and ectopic thyroid disorders showed a trend toward higher detection over time, but their prevalence has not changed significantly in our screening program.

Overexpression of the insulin-like growth factor 1 receptor (IGF-1R) is associated with malignancy in familial pheochromocytomas and paragangliomas.

CONTEXT: Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumours derived from chromaffin cells. Although mostly benign, up to 26% of pheo/pgl will undergo malignant transformation. Reliable histological signs to differentiate benign pheo/pgl from malignant tumours are currently lacking. Increased IGF-1R expression has been shown during progression to metastatic phenotypes of several types of cancer. OBJECTIVE: To analyse the distribution and expression of the IGF-1R in pheo/pgl of different genetic origin and degree of malignancy. MEASUREMENTS: We studied the expression of the IGF-1R protein by immunohistochemistry, in 40 primary tumours from patients with pheo/pgl from different genetic aetiology (11 of 29 metastatic/nonmetastatic diseases). RESULTS: We found a strong association between increased expression of IGF-1R and malignant behaviour regardless of the age at diagnosis and the genetic aetiology. IGF-1R labelling was mostly weak in primary tumours from patients with nonmetastatic pheo/pgl. Conversely, intense IGF-1R labelling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11·7 times higher if tumour IGF-1R labelling was intense independently of age at diagnosis. The probability of remaining free of metastases was higher in patients with pheo/pgl scored weak for IGF-1R at 60 months and more than twofold higher at 120 months of follow-up than in patients with intense IGF-1R labelling in their primary tumours. CONCLUSIONS: Our results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumour might be a useful tool to detect those patients harbouring pheo/pgl who have an increased risk of metastasis.

Can waist circumference identify children with the metabolic syndrome?

OBJECTIVE: To determine in children the association between waist circumference (WC) and insulin resistance determined by homeostasis modeling (HOMA-IR) and proinsulinemia and components of the metabolic syndrome, including lipid profile and blood pressure (BP). METHODS: Eighty-four students (40 boys) aged 6 to 13 years and matched for sex and age underwent anthropometric measurements; 40 were obese; 28, overweight; and 16, nonobese. Body mass index (BMI), WC, BP, and Tanner stage were determined. An oral glucose tolerance test, lipid profile, and insulin and proinsulin assays were performed. Children were classified as nonobese (BMI < 85th percentile), overweight (BMI, 85th-94th percentile), and obese (BMI > or = 95th percentile). RESULTS: There was univariate association (P < .01) between WC and height (r = 0.73), BMI (r = 0.96), Tanner stage (r = 0.67), age (r = 0.56), systolic BP (r = 0.64), diastolic BP (r = 0.61), high-density lipoprotein cholesterol level (r = 0.45), triglyceride level (r = 0.28), proinsulin level (r = 0.59), and HOMA-IR (r = 0.59). Multiple linear regression analysis using HOMA-IR as the dependent variable showed that WC (beta coefficient = 0.050 [95% confidence interval, 0.028 to 0.073]; P = .001) and systolic BP (beta coefficient = 0.033 [95% confidence interval, 0.004 to 0.062]; P = .004) were significant independent predictors for insulin resistance adjusted for diastolic BP, height, BMI, acanthosis nigricans, and high-density lipoprotein cholesterol level. CONCLUSION: Waist circumference is a predictor of insulin resistance syndrome in children and adolescents and could be included in clinical practice as a simple tool to help identify children at risk.

¿Es la circunferencia de cintura un componente del síndrome metabólico en la infancia? / Is waist circumference a component of the metabolic syndrome in childhood?

Objetivo.Determinar en niños,la asociación entre la circunferencia de la cintura (CC)y diferentes componentes del síndrome metabólico,incluyendo obesidad,índice de masa corporal(IMC),insulinorresistencia(HOMA-IR),proinsulina,perfil lipídico y tensión arterial (TA)Población, material y método. Se evaluaron las medidas antropométricas de 2.182 estudiantes (1.126 masculinos)de 6 a 13 años de edad. Se aleatorizaron 68 niños:28 con sobrepeso y 40 obesos que se aparearon según el sexo y la edad con 16 niños de peso normal en los que se realizaron evaluaciones posteriores.Conclusiones. La CC es un predictor del síndrome de insulinorresistencia en niños y podría incluirse en la práctica clínica como una herramienta simple para identificar niños y podría incluirse en la práctica médica como una herramienta simple para identificar niños con riesgo de presentar en el futuro enfermedad cardiovascular (ECV) y diabetes tipo 2

¿Es la circunferencia de cintura un componente del síndrome metabólico en la infancia? / Is waist circumference a component of the metabolic syndrome in childhood?

Objetivo.Determinar en niños,la asociación entre la circunferencia de la cintura (CC)y diferentes componentes del síndrome metabólico,incluyendo obesidad,índice de masa corporal(IMC),insulinorresistencia(HOMA-IR),proinsulina,perfil lipídico y tensión arterial (TA)Población, material y método. Se evaluaron las medidas antropométricas de 2.182 estudiantes (1.126 masculinos)de 6 a 13 años de edad. Se aleatorizaron 68 niños:28 con sobrepeso y 40 obesos que se aparearon según el sexo y la edad con 16 niños de peso normal en los que se realizaron evaluaciones posteriores.Conclusiones. La CC es un predictor del síndrome de insulinorresistencia en niños y podría incluirse en la práctica clínica como una herramienta simple para identificar niños y podría incluirse en la práctica médica como una herramienta simple para identificar niños con riesgo de presentar en el futuro enfermedad cardiovascular (ECV) y diabetes tipo 2

Fosfatasa acida leucocitaria tartrato resistentecomo marcador de la transformacion del monocito en macrofago / Leucocyte tartrate-resistant acid phosphatase as marker for the transition of monocyte to macrophage

Se investigó la presencia de la 5 isoenzima de la fosfatasa ácida leucocitaria tartrato resistente (FATRE) en los monocitos de sangre periférica humana en 32 muestras: 26 normales, 4 plaquetopenias, 1 anemia y 1 tricoleucemia. Se empleó el separador celular Cobe Spectra Versión 4 en 3 muestras y en las demás se obtuvo la concentración celular por centrifugación sin y con partículas de látex, para estudiar monocitos y macrófagos, respectivamente. Empleando el Kit Sigma para las dos reacciones de fosfatasa ácida total y de FATRE, se demostró la presencia de dos poblaciones de monocitos, una minoritaria para FATRE y otra negativa. Con la adición de látex los monocitos se transformaron en macrófagos haciéndose fuertemente positivos para FATRE. En consecuencia se concluye que la FATRE debe desempeñar un papel principal en la función macrofágica y por ende en la inmunidad celular humana.

Fosfatasa acida leucocitaria tartrato resistentecomo marcador de la transformacion del monocito en macrofago / Leucocyte tartrate-resistant acid phosphatase as marker for the transition of monocyte to macrophage

Se investigó la presencia de la 5 isoenzima de la fosfatasa ácida leucocitaria tartrato resistente (FATRE) en los monocitos de sangre periférica humana en 32 muestras: 26 normales, 4 plaquetopenias, 1 anemia y 1 tricoleucemia. Se empleó el separador celular Cobe Spectra Versión 4 en 3 muestras y en las demás se obtuvo la concentración celular por centrifugación sin y con partículas de látex, para estudiar monocitos y macrófagos, respectivamente. Empleando el Kit Sigma para las dos reacciones de fosfatasa ácida total y de FATRE, se demostró la presencia de dos poblaciones de monocitos, una minoritaria para FATRE y otra negativa. Con la adición de látex los monocitos se transformaron en macrófagos haciéndose fuertemente positivos para FATRE. En consecuencia se concluye que la FATRE debe desempeñar un papel principal en la función macrofágica y por ende en la inmunidad celular humana. (AU)

Revisión de 34 casos de esferocitosis hereditaria / Review of 34 cases of hereditary spherocytosis

La esferocitosis hereditaria (EH), una patología basada en un desorden en la membrana del eritrocito y de herencia autosómica dominante, se manifiesta con presencia de microesferocitos en sangre periférica, anemia crónica hemolítica, esplenomegalia, ictericia, e incremento en la fragilidad osmótica de los eritrocitos, con prueba de Coombs negativa. Nuestro objetivo en la presente revisión es exponer el criterio de diagnóstico de la EH en base a técnicas sencillas de efectuar en un laboratorio de hematología y conocer los datos de estos pacientes en nuestro medio poblacional. En el trabajo se presentan datos de 34 pacientes de ambos sexos (niños y adultos) seleccionados por tener las características descriptas, y 55 individuos normales que constituyen el grupo control. Con respecto a las variables estudiadas, se obtuvieron diferencias altamente significativas entre el grupo control y el de pacientes. En este último, las medias fueron: hematocrito: 34,06 por ciento, fragilidad corpuscular media basal: 0,48 g/dl, fragilidad corpuscular media post-incubación: 0,64 g/dl, y las medianas: hematíes: 4,2x10 elevado a la 12/l, hemoglobina: 11,0 g/dl, reticulocitos: 6,6 por ciento, bilirrubina indirecta: 33,7 umoles/l, láctico deshidrogenasa: 221 UI/l, hemoglobina libre en plasma: 2,4 mg/dl, autohemólisis espontánea: 14,7 por ciento con el agregado de glucosa: 2,0 por ciento, hemólisis incipiente basal: 0,60 g/dl. El 70 por ciento de las haptoglobinas fueron ausentes. El analizar estas determinaciones y más aún, conocer los distintos detalles del test de resistencia globular, nos permitieron llegar al diagnóstico presuntivo de la EH. Asimismo pudimos conocer los valores de estos pacientes en nuestro medio poblacional, de lo cual no había referencia en bibliografía.

Revisión de 34 casos de esferocitosis hereditaria / Review of 34 cases of hereditary spherocytosis

La esferocitosis hereditaria (EH), una patología basada en un desorden en la membrana del eritrocito y de herencia autosómica dominante, se manifiesta con presencia de microesferocitos en sangre periférica, anemia crónica hemolítica, esplenomegalia, ictericia, e incremento en la fragilidad osmótica de los eritrocitos, con prueba de Coombs negativa. Nuestro objetivo en la presente revisión es exponer el criterio de diagnóstico de la EH en base a técnicas sencillas de efectuar en un laboratorio de hematología y conocer los datos de estos pacientes en nuestro medio poblacional. En el trabajo se presentan datos de 34 pacientes de ambos sexos (niños y adultos) seleccionados por tener las características descriptas, y 55 individuos normales que constituyen el grupo control. Con respecto a las variables estudiadas, se obtuvieron diferencias altamente significativas entre el grupo control y el de pacientes. En este último, las medias fueron: hematocrito: 34,06 por ciento, fragilidad corpuscular media basal: 0,48 g/dl, fragilidad corpuscular media post-incubación: 0,64 g/dl, y las medianas: hematíes: 4,2x10 elevado a la 12/l, hemoglobina: 11,0 g/dl, reticulocitos: 6,6 por ciento, bilirrubina indirecta: 33,7 umoles/l, láctico deshidrogenasa: 221 UI/l, hemoglobina libre en plasma: 2,4 mg/dl, autohemólisis espontánea: 14,7 por ciento con el agregado de glucosa: 2,0 por ciento, hemólisis incipiente basal: 0,60 g/dl. El 70 por ciento de las haptoglobinas fueron ausentes. El analizar estas determinaciones y más aún, conocer los distintos detalles del test de resistencia globular, nos permitieron llegar al diagnóstico presuntivo de la EH. Asimismo pudimos conocer los valores de estos pacientes en nuestro medio poblacional, de lo cual no había referencia en bibliografía.(AU)

Disminución del puntaje de la reacción de mieloperoxidasa y presencia de polimorfonucleares neutrófilos negativos en sangre de cordones umbilicales y de neonatos humanos / Diminution of the score of myeloperoxidase reaction and presence of negative polymorphonuclear neutrophils in blood of human umbilical cords and newborns

Se estudia comparativamente la reacción de mieloperoxidasa en polimorfonucleares neutrófilos de sangre periférica de 10 testigos adultos normales, 15 cordones umbilicales y 10 neonatos humanos, comprobando la disminución del puntaje en los neutrófilos de los cordones umbilicales y la sangre periférica de los neonatos y la presencia de neutrófilos negativos en ambos. Ninguno de estos hechos se produjo en los testigos adultos normales. El análisis estadístico demuestra que la diferencia es significativa. Se considera que la misma no implica disminución de la inmunidad celular.

Disminución del puntaje de la reacción de mieloperoxidasa y presencia de polimorfonucleares neutrófilos negativos en sangre de cordones umbilicales y de neonatos humanos / Diminution of the score of myeloperoxidase reaction and presence of negative polymorphonuclear neutrophils in blood of human umbilical cords and newborns

Se estudia comparativamente la reacción de mieloperoxidasa en polimorfonucleares neutrófilos de sangre periférica de 10 testigos adultos normales, 15 cordones umbilicales y 10 neonatos humanos, comprobando la disminución del puntaje en los neutrófilos de los cordones umbilicales y la sangre periférica de los neonatos y la presencia de neutrófilos negativos en ambos. Ninguno de estos hechos se produjo en los testigos adultos normales. El análisis estadístico demuestra que la diferencia es significativa. Se considera que la misma no implica disminución de la inmunidad celular. (AU)