• Korean Journal of Veterinary Research
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• v.50 no.3
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• pp.179-185
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• 2010

The present study was undertaken to establish reference values for the composition blood lymphocyte populations and compare forty three Hanwoo neonatal calves (KC) with twenty one Holstein calves (HC) by blood cell count and immunophynotying. The percentages of CD2+, CD4+, CD8+, CD26+, ACT2+, MHC class, MHC class II and WC1+ T cells, B cells were determined by flow cytometry. The number of lymphocyte and monocyte in HC were higher than those of KC. However, the number of neutrophils was higher in HC than KC. The proportions of CD2+, CD4+, CD8+, MHC class, and WC1+ lymphocytes remained relatively stable during the study period, while there was a moderate increase in the relative percentage of CD26+, ACT2+, MHC class II and B cell from birth to approximately 3 weeks of age. Marked differences in the relative proportions of the lymphocyte subpopulations were noted between the individual calves. The present study shows that the T-cell subpopulations are present in peripheral blood of KC at levels comparable with HC, while the MHC class II and B cell population of KC increases significantly with age. The absolute number of WBC in KC was due to the decrease of absolute number of neutrophil rather than the increase of lymphocyte. The results indicated that KC have significantly higher number of neutrophils, and proportion of MHC class II and B cell than HC.

• Neonatal Medicine
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• v.16 no.1
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• pp.47-54
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• 2009

Purpose: Present evidences suggest that Ureaplasma urealyticum is a cause of pneumonia, septicemia, and bronchopulmonary dysplasia (BPD) in newborn infants, particularly those born prematurely. The purpose of this work was to examine the relationship between Ureaplasma urealyticum in the tracheal aspirates and adverse outcomes, such as BPD and early onset neonatal sepsis in premature infants. Methods: A polymerase chain reaction (PCR) was performed on tracheal aspirates collected within 24 hour after birth in 176 premature infants less than 35 weeks of gestation and admitted to the neonatal intensive care unit of Bundang CHA Hospital. Results: U. urealyticum was detected in 37 of 176 preterm infants (21.0%). Gestational age ($29^{+5}{\pm}2^{+5}$ wk vs. $30^{+6}{\pm}2^+{-5}$ wk, P=0.0l3) and birth weight (1.39${\pm}$0.44 kg vs. 1.59${\pm}$0.55 kg, P=0.037) were lower in the U urealyticum-positive group compared to the control group. The incidence of early onset neonatal sepsis (16.2% vs. 6.5%, P=0.045) and BPD (45.9% vs. 29.5%, P=0.047) was higher in the U urealyticum-positive group compared to the control group, but the severity of BPD was not different between two groups. However, multiple logistic regression analysis revealed that the presence of U. urealyticum was not independently related to the development of early onset neonatal sepsis and BPD. Conclusion: The results suggest that colonization of the lower respiratory tract by U. urealyticum might not be related to the development of neonatal sepsis and BPD directly in preterm infants.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.55-64
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• 2006

The fetal central nervous system (CNS) is sensitive to diverse environmental factors, such as alcohol, heavy metals, irradiation, mycotoxins, neurotransmitters, and DNA damage, because a large number of processes occur during an extended period of development. Fetal neural damage is an important issue affecting the completion of normal CNS development. As many concepts about the brain development have been recently revealed, it is necessary to compare the mechanism of developmental abnormalities induced by extrinsic factors with the normal brain development. To clarify the mechanism of fetal CNS damage, we used one experimental model in which 5-azacytidine (5AZC), a DNA damaging and demethylating agent, was injected to the dams of rodents to damage the fetal brain. 5AzC induced cell death (apoptosis)and cell cycle arrest in the fetal brain, and it lead to microencephaly in the neonatal brain. We investigated the mechanism of apoptosis and cell cycle arrest in the neural progenitor cells in detail, and demonstrated that various cell cycle regulators were changed in response to DNA damage. p53, the guardian of genome, played a main role in these processes. Further, using DNA microarray analysis, tile signal cascades of cell cycle regulation were clearly shown. Our results indicate that neural progenitor cells have the potential to repair the DNA damages via cell cyclearrest and to exclude highly affected cells through the apoptotic process. If the stimulus and subsequent DNA damage are high, brain development proceeds abnormally and results in malformation in the neonatal brain. Although the mechanisms of fetal brain injury and features of brain malformation afterbirth have been well studied, the process between those stages is largely unknown. We hypothesized that the fetal CNS has the ability to repair itself post-injuring, and investigated the repair process after 5AZC-induced damage. Wefound that the damages were repaired by 60 h after the treatment and developmental processes continued. During the repair process, amoeboid microglial cells infiltrated in the brain tissue, some of which ingested apoptotic cells. The expressions of genes categorized to glial cells, inflammation, extracellular matrix, glycolysis, and neurogenesis were upregulated in the DNA microarray analysis. We show here that the developing brain has a capacity to repair the damage induced by the extrinsic stresses, including changing the expression of numerous genes and the induction of microglia to aid the repair process.

• International Journal of Oral Biology
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• v.32 no.1
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• pp.13-22
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• 2007

The stem cell research is emerging as a cutting edge topic for a new treatment for many chronic diseases. Recently, dental stem cell would be possible for regeneration of tooth itself as well as periodontal tissue. However, the study of the cell characterization is scarce. Therefore, we performed the genetic profiling and the characterization of mouse fetus/neonate derived dental tissue and cell to find the identification during dental development. We separated dental arch from mandibles of 14.5 d fetal mice and neonate 0 d under the stereoscope, and isolated dental cells primarily from the tissues. Then, we examined morphology and the gene expression profiles of the primary cells and dental tissues from fetus/neonate and adult with RT-PCR. Primary dental cells showed heterogeneous but the majority was shown as fibroblast-like morphology. The change of population doubling time levels (PDLs) showed that the primary dental cells have growth potential and could be expanded under our culture conditions without reduction of growth rate. Immunocytochemical and flow cytometric analyses were performed to characterize the primary dental cell populations from both of fetus (E14.5) and neonate. Alpha smooth muscle actin (${\alpha}-SMA$), vimentin, and von Willebrand factor showed strong expression, but desmin positive cells were not detected in the primary dental cells. Most of the markers were not uniformly expressed, but found in subsets of cells, indicating that the primary dental cell population is heterogeneous, and characteristics of the populations were changed during culture period. And mesenchymal stem cell markers were highly expressed. Gene expression profile showed Wnt family and its related signaling molecules, growth factors, transcription factors and tooth specific molecules were expressed both fetal and neonatal tissue. The tooth specific genes (enamelin, amelogenin, and DSPP) only expressed in neonate and adult stage. These expression patterns appeared same as primary fetal and neonatal cells. In this study we isolated primary cells from whole mandible of fetal and neonatal mice. And we investigated the characteristics of the primary cells and the profile of gene expressions, which are involved in epithelial-mesenchymal interactions during tooth development. Taken together, the primary dental cells in early passages or fetal and neonatal mandibles could be useful stem cell resources.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.966-971
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• 2006

Purpose : 'Programming' describes the process that stimulus at a critical period of development has lifelong effects. The fact that low birth weight links to the risk of elevated blood pressures in adult life is well known. This study aims to examine whether this link is evident in the newborn by investigating the relationship of the intrauterine growth indices and neonatal blood pressure(BP). Methods : We studied 127 neonates who were born at Ewha Womans' Hospital and their mothers enrolled our cohort study during pregnancy. Data on the mothers and details of the birth records were tracked and collected from medical charts. Neonatal BP was measured within 24 hours after birth. Results : Neonatal SBP was positively correlated to intrauterine growth indices; birth weight(BW)(r=0.4), head circumference(HC)(r=0.4), and birth height(r=0.3). However, an inverse relationship existed, between HC/BW ratio and neonatal SBP(r=-0.4). After adjusting for the baby's sex, maternal BP, and gestational age, neonatal SBP still associated with intrauterine growth indices. SBP was 7 mmHg higher in the highest BW group(${\geq}90percentiles$) compared to the lowest group(<10 percentiles). On the other hand, SBP was 17 mmHg lower in the highest HC/BW group(${\geq}90percentiles$) compared in the lowest group(<10 percentiles). Conclusion : This study could not find the evidence that intrauterine growth retardation affect on elevated neonatal BP. It suggests that the initiating events of BP programming may occur during postnatal growth period. To identify the critical starting period that intrauterine growth retardation leads to elevated BP, a study tracking BP changes from birth to childhood is required.

• Neonatal Medicine
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• v.18 no.2
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• pp.177-181
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• 2011

Bronchopulmonary dysplasia (BPD) is characterized by arrest of vascular and alveolar development in premature infants. Recent advances in neonatology have increased the survival of immature babies. Consequently, the prevalence of BPD is increasing. Animal studies and autopsy findings of BPD have demonstrated interruption in vascular development and reversal of lung injury through promotion of vasculogenesis. Normal lung development is driven by temporal and spatial specific growth factors and cellto-cell signaling in vascular development. Lung injury through various pathways causes disruption in this complex interactive process and results in aberrant vascular development and subsequent BPD. By understanding the regulation of vascular growth of the lung, it would be possible to find new targets in the treatment and prevention of BPD in premature infants.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.255-262
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• 2005

Battler and Bartter-like syndromes, which include classic Bartter syndrome(type III), neonatat Bartter syndrome(type I, II or IV) and Gitelman syndrome, are autosomal - recessively inherited renal tubular disorders characterized b)r hypokalemic metabolic alkalosis, salt wasting and normal to low blood pressure. Neonatal Bartter syndrome is characterized by intrauterine polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration, subsequent failure to thrive, and severe hypercalciuria with nephrocalcinosis and osteopenia. It is caused by mutations in NKCC2(type I), ROMK(type II) or BSND(type IV) genes. If diagnosed and treated early, the progression to renal failure can be prevented and catch-up growth and normal development are achieved. We report here a 6 month-old infant with neonatal Bartter syndrome who presented with hypokalemic metabolic alkalosis, polyhydramnios and premature delivery, persistent high fever and dehydration, failure to thrive, hypercalciuria, and nephrocalcinosis. He received indomethacin and potassium chloride per os and show ed catch-up growth and normal developmental profile at 19 months of age. (J Korean Soc Pediatr Nephrol 2005;9:255-262)

• Toxicological Research
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• v.19 no.4
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• pp.267-275
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• 2003

The purpose of our study was to evaluate the toxicity of the thimerosal in embryos and neonates. Thimerosal (also known as mercurothiolate) is a mercury-containing compound used in trace amounts to prevent bacteria and other organisms from contaminating vaccines, especially in opened multi-dose vials. The toxicity of mercury is well known and those most at risk occurrs in unborn babies and newborn babies. Test methods included in vitro whole embryo culture (WEC) system and in vivo test of neonatal toxicity in Wistar rats. Ethylmercury and methylmercury were used as positive controls for the evaluating of toxic effects of mercury. In WEC assay, treated concentrations of thimerosal, ethylmercury and methylmercury were up to 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2.5 and 5 $\mu\textrm{g}$/$\textrm{m}{\ell}$, respectively. All compounds didn't show any morphological abnormalities, but showed retardation of growth and development in dose dependent manner (> 0.5 $\mu\textrm{g}$/$\textrm{m}{\ell}$). These data indicated that thimerosal showed developmental toxicity in vitro. In vivo neonatal toxicity, Wistar rats were administered subcutaneously with thimerosal, ethyl mercury, or methylmercury (5, 25, 50, 250, and 500 $\mu\textrm{g}$/kg) during from postnatal day (PND) 4 to 25. Significant effects of these compounds on relative organ weights and organ morphology were not observed in this experiment. However, accumulation of mercury was detected in the kidney and testis when treated with thimerosal, ethylmercury, or methylmercury. These results suggest that thimerosal may be a harmful compound to embryo and neonate, but used concentration of thimerosal in these experiments is much higher than that of clinical application. Further investigation is needed on the safety of vaccine components, i.e. a thimerosal using in vitro and in vivo tests in the future.

• Clinical and Experimental Pediatrics
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• v.64 no.7
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• pp.313-321
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• 2021

Here we describe the neurodevelopmental outcomes of very low birth weight (VLBW) infants (birth weight ≤1,500 g) at 3 years of age in the Neonatal Research Network of Japan (NRNJ) database in the past decade and review the methodological issues identified in follow-up studies. The follow-up protocol for children at 3 years of chronological age in the NRNJ consists of physical and comprehensive neurodevelopmental assessments in each participating center. Neurodevelopmental impairment (NDI)-moderate to severe neurological disability-is defined as cerebral palsy (CP) with a Gross Motor Function Classification System score ≥2, visual impairment such as uni- or bilateral blindness, hearing impairment requiring hearing amplification, or cognitive impairment with a developmental quotient (DQ) of Kyoto Scale of Psychological Development score <70 or judgment as delayed by pediatricians. We used death or NDI as an unfavorable outcome in all study subjects and NDI in survivors using number of assessed infants as the denominator. Follow-up data were collected from 49% of survivors in the database. Infants with follow-up data had lower birth weights and were of younger gestational age than those without follow-up data. Mortality rates of 40,728 VLBW infants born between 2003 and 2012 were 8.2% before discharge and 0.7% after discharge. The impairment rates in the assessed infants were 7.1% for CP, 1.8% for blindness, 0.9% for hearing impairment, 15.9% for a DQ <70, and 19.1% for NDI. The mortality or NDI rate in all study subjects, including infants without follow-up data, was 17.4%, while that in the subjects with outcome data was 32.5%. The NRNJ follow-up study results suggested that children born with a VLBW remained at high risk of NDI in early childhood. It is important to establish a network follow-up protocol and complete assessments with fewer dropouts to enable clarification of the outcomes of registered infants.