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Biomedical subjects

B Pimentel

Publications and source records attributed to B Pimentel.

10 recordsLinked to original sources
PubMed2000

c-Raf regulates cell survival and retinal ganglion cell morphogenesis during neurogenesis.

The signaling cascade Ras/Raf/mitogen-activated protein kinases modulates cell proliferation, differentiation, and survival, all key cellular processes during neural development. To better define the in vivo role of Raf during chick retinal neurogenesis, we interfered with Raf-dependent signaling during days 4.5 to 7.5 of embryonic development by expressing a dominant negative mutant of c-Raf (DeltaRaf), which blocks Ras-dependent Raf activation, and by overexpressing wild-type c-Raf. DeltaRaf expression induced an increase in cell death by apoptosis, whereas it did not affect overall cell proliferation and differentiation. In parallel, the number of Islet-1/2-positive and TUJ1-positive retinal ganglion cells were diminished in their definitive layer, whereas there was an increase in the number of mislocated Islet-1/2-positive cells. This disturbed morphogenesis correlated with a disruption of the optic fiber layer. Conversely, c-Raf overexpression caused moderate opposite effects on apoptosis. These results frame in vivo early neurogenesis processes in which c-Raf is essential.

Animals↗
PubMed1999

Apoptotic cell death of proliferating neuroepithelial cells in the embryonic retina is prevented by insulin.

The role of programmed cell death is well established for connecting neurons. Conversely, much less is known about apoptosis affecting proliferating neuroepithelial cells. Chick retina from day 4 to day 6 of embryonic development (E), essentially proliferative, presented a defined distribution of apoptotic cells during normal in vivo development, as visualized by TdT-mediated dUTP nick end labelling (TUNEL). Insulin, expressed in the early chick embryonic retina as proinsulin, attenuated apoptosis in growth factor-deprived organotypic culture of E5 retina. This effect was demonstrated both by TUNEL and by staining of pyknotic nuclei, as well as by release of nucleosomes. Application of a 1 h [methyl-3H]thymidine pulse in ovo at E5, followed by organotypic culture in the presence or absence of insulin, showed that this factor alone decreased the degradation of labelled DNA to nucleosomes by 40%, as well as the proportion of labelled pyknotic nuclei. Both features are a consequence of apoptosis affecting neuroepithelial cells, which were in S-phase or shortly after. In addition, when the E5 embryos were maintained in ovo after the application of [methyl-3H]thymidine, 70% of the apoptotic retinal cells were labelled, indicating the in vivo prevalence of cell death among actively proliferating neuroepithelial cells. Apoptotic cell death is thus temporally and spatially regulated during proliferative stages of retinal neurogenesis, and embryonic proinsulin is presumably an endogenous protective factor.

Animals↗
PubMed1998

(Pro)insulin and insulin-like growth factor I complementary expression and roles in early development.

Evidence that the insulin-like growth factors play a role in embryonic as well as postnatal growth and central nervous system development has accumulated recently from studies using knock-out mice models. However, no effects of IGF-I and II have been demonstrated prior to organogenesis in these studies. We summarize here results supporting the role of insulin (or its precursor proinsulin) in vertebrate development prior to the expression of IGFs. (Pro)insulin mRNA is expressed in the chick embryo during neurulation and early organogenesis and its inhibition by antisense oligodeoxynucleotides increase apoptosis. In another system, proliferative neuroretina, (pro)insulin expression predominates over IGF-I expression. Modulation of apoptosis by (pro)insulin in retina may be largely responsible for the observed stimulation of DNA synthesis and neuronal differentiation. These effects are elicited as well by IGF-I, expressed later in neuroretina. Thus, these polypeptides have complementary expression in early embryos which suggests coordinated actions during development.

Animals↗
PubMed1996

Insulin acts as an embryonic growth factor for Drosophila neural cells.

The isolation of the Drosophila insulin receptor gene and the recent analysis of loss of function mutants have clearly implicated insulin signalling in embryonic nervous system development. Here we study the presence of insulin in the embryo and we characterize the cellular processes affected by insulin in embryonic neural cells. We find that 7.5% of the cells in the 15-18 h Drosophila embryo contain insulin immunoreactivity by flow cytometry. In the embryonic-derived cell line Schneider 1, we show that human insulin is capable of stimulating proliferation and neural differentiation. Thus, the action of insulin on the developing Drosophila nervous system appears to be as pleiotropic as in vertebrates.

Animals↗
PubMed1993

Infant mortality statistics do not adequately reflect the impact of short gestation.

OBJECTIVE: To determine the accuracy of National Center for Health Statistics cause-specific infant mortality data. The National Center for Health Statistics compiles these data by applying World Health Organization (WHO) selection rules to death certificate data. The WHO rules arrange medical entities into a hierarchical order and select a single underlying cause of death (ULCD). DESIGN: A comparison was made between ULCD assigned to a cohort of 335 infant death certificates by (1) a neonatologist panel, and (2) application of WHO selection rules by the Florida State Office of Vital Statistics (OVS). RESULTS: Among the 146 infants with birth weights 1500 to 4649 g, agreement between neonatologists and OVS was 88%, while among the 189 infants with birth weights 0 to 1499 g (very low birth weight), agreement was just 41%. Neonatologists selected short gestation as the underlying cause of death for 82% of very low birth weight infant records, vs 25% by OVS. Due to the application of specific WHO selection rules, OVS frequently selected immediate causes of death, such as "cardiac arrest," as the ULCD, even when the medical certifier had indicated short gestation as the ULCD. In vital statistics reports, many of these immediate causes are reported as "other respiratory conditions of newborn," or "all other perinatal conditions." CONCLUSION: WHO ULCD selection rules should be modified to allow short gestation to have a higher priority over immediate causes of infant death.

Birth Weight↗
PubMed1991

Infant feeding effects on flow cytometric analysis of blood.

Flow cytometric analysis was performed on purified mononuclear cells isolated from whole blood samples of 11 adults, 7 breast-fed (BF) infants and 11 formula-fed (FF) infants, mean ages 34.2 +/- 4.3 years, 6.3 +/- 1.3 months, and 6.2 +/- 1.2 months, respectively. Infants were receiving at least 70% of calories from formula or breast milk. Infant mononuclear cell populations contained a higher percentage of lymphocytes and a lower percentage of monocytes compared with adults. Within the lymphocyte population, infants had a higher CD4+/CD8+ ratio (T helper-inducer/T cytotoxic-suppressor), a higher percentage of CD19+ (pan B) and CD4+ cells, and a lower percentage of CD8+ and CD16+ (natural-killer) cells compared with adults. CD3+ (pan T) and CD4+ lymphocyte percentages were higher and CD19+ lymphocyte percentages were lower in FF compared with BF infants. Although sample size is small, our data indicate that diet may influence lymphocyte subset distribution during infancy when the majority of calories is derived from infant formula or human milk.

Adult↗
PubMed1991

Dietary nucleotide effects upon immune function in infants.

Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast-fed and NT+ groups compared with the NT- group (41.7 +/- 4.7, 32.2 +/- 3.4, 21.7 +/- 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 +/- 0.28 U/mL, 0.27 +/- 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant.

Breast Feeding↗