• Journal of Yeungnam Medical Science
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• v.35 no.2
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• pp.156-164
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• 2018

Environmental contaminants are one of the important causal factors for development of various human diseases. In particular, the perinatal period is highly vulnerable to environmental toxicants and resultant dysregulation of fetal development can cause detrimental health outcomes potentially affecting life-long health. Perfluoroalkyl compounds (PFCs), emerging environmental pollutants, are man-made organic molecules, which are widely used in diverse industries and consumer products. PFCs are non-degradable and bioaccumulate in the environment. Importantly, PFCs can be found in cord blood and breast milk as well as in the general population. Due to their physicochemical properties and potential toxicity, many studies have evaluated the health effects of PFCs. This review summarizes the epidemiological and experimental studies addressing the association of PFCs with neurotoxicity and immunotoxicity. While the relationships between PFC levels and changes in neural and immune health are not yet conclusive, accumulative studies provide evidence for positive associations between PFC levels and the incidence of attention deficit hyperactivity disorder and reduced immune response to vaccination both in children and adults. In conclusion, PFCs have the potential to affect human health linked with neurological disorders and immunosuppressive responses. However, our understanding of the molecular mechanism of the effects of PFCs on human health is still in its infancy. Therefore, along with efforts to develop methods to reduce exposure to PFCs, studies on the mode of action of these chemicals are required in the near future.

• Proceedings of the KOSOMBE Conference
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• v.1992 no.05
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• pp.27-47
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• 1992

Engineers have developed new instruments that aid in diagnosis and therapy Ultrasonic imaging has provided a nondamaging method of imaging internal organs. A complex transducer emits ultrasonic waves at many angles and reconstructs a map of internal anatomy and also velocities of blood in vessels. Fast computed tomography permits reconstruction of the 3-dimensional anatomy and perfusion of the heart at 20-Hz rates. Positron emission tomography uses certain isotopes that produce positrons that react with electrons to simultaneously emit two gamma rays in opposite directions. It locates the region of origin by using a ring of discrete scintillation detectors, each in electronic coincidence with an opposing detector. In magnetic resonance imaging, the patient is placed in a very strong magnetic field. The precessing of the hydrogen atoms is perturbed by an interrogating field to yield two-dimensional images of soft tissue having exceptional clarity. As an alternative to radiology image processing, film archiving, and retrieval, picture archiving and communication systems (PACS) are being implemented. Images from computed radiography, magnetic resonance imaging (MRI), nuclear medicine, and ultrasound are digitized, transmitted, and stored in computers for retrieval at distributed work stations. In electrical impedance tomography, electrodes are placed around the thorax. 50-kHz current is injected between two electrodes and voltages are measured on all other electrodes. A computer processes the data to yield an image of the resistivity of a 2-dimensional slice of the thorax. During fetal monitoring, a corkscrew electrode is screwed into the fetal scalp to measure the fetal electrocardiogram. Correlations with uterine contractions yield information on the status of the fetus during delivery To measure cardiac output by thermodilution, cold saline is injected into the right atrium. A thermistor in the right pulmonary artery yields temperature measurements, from which we can calculate cardiac output. In impedance cardiography, we measure the changes in electrical impedance as the heart ejects blood into the arteries. Motion artifacts are large, so signal averaging is useful during monitoring. An intraarterial blood gas monitoring system permits monitoring in real time. Light is sent down optical fibers inserted into the radial artery, where it is absorbed by dyes, which reemit the light at a different wavelength. The emitted light travels up optical fibers where an external instrument determines O2, CO2, and pH. Therapeutic devices include the electrosurgical unit. A high-frequency electric arc is drawn between the knife and the tissue. The arc cuts and the heat coagulates, thus preventing blood loss. Hyperthermia has demonstrated antitumor effects in patients in whom all conventional modes of therapy have failed. Methods of raising tumor temperature include focused ultrasound, radio-frequency power through needles, or microwaves. When the heart stops pumping, we use the defibrillator to restore normal pumping. A brief, high-current pulse through the heart synchronizes all cardiac fibers to restore normal rhythm. When the cardiac rhythm is too slow, we implant the cardiac pacemaker. An electrode within the heart stimulates the cardiac muscle to contract at the normal rate. When the cardiac valves are narrowed or leak, we implant an artificial valve. Silicone rubber and Teflon are used for biocompatibility. Artificial hearts powered by pneumatic hoses have been implanted in humans. However, the quality of life gradually degrades, and death ensues. When kidney stones develop, lithotripsy is used. A spark creates a pressure wave, which is focused on the stone and fragments it. The pieces pass out normally. When kidneys fail, the blood is cleansed during hemodialysis. Urea passes through a porous membrane to a dialysate bath to lower its concentration in the blood. The blind are able to read by scanning the Optacon with their fingertips. A camera scans letters and converts them to an array of vibrating pins. The deaf are able to hear using a cochlear implant. A microphone detects sound and divides it into frequency bands. 22 electrodes within the cochlea stimulate the acoustic the acoustic nerve to provide sound patterns. For those who have lost muscle function in the limbs, researchers are implanting electrodes to stimulate the muscle. Sensors in the legs and arms feed back signals to a computer that coordinates the stimulators to provide limb motion. For those with high spinal cord injury, a puff and sip switch can control a computer and permit the disabled person operate the computer and communicate with the outside world.

• Clinical and Experimental Pediatrics
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• v.46 no.9
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• pp.865-870
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• 2003

Purpose : We measured the umbilical cord arterial concentrations of isoprostane($8-iso-PGF_{2{\alpha}}$) and intended to decide whether the umbilical cord arterial concentrations of isoprostane could be used as a useful parameter for lipid peroxidation in newborn infants. Methods : The isoprostane and malondialdehyde(MDA) concentrations of the umbilical cord were measured by enzyme immunoassay and TBARS(thiobarbituric acid reactive substance) assay in 33 preterm and 28 term infants, respectively. The concentrations of isoprostane and MDA were compared between preterm infants and term infants, and were analysed for association with perinatal risk factors and neonatal complications. Results : Umbilical cord arterial concentrations of isoprostane were $704.7{\pm}635.6pg/mL$ and $421.9{\pm}306.5pg/mL$ in preterm and term infants, respectively. Umbilical cord arterial concentrations of MDA were $44.0{\pm}22.9{\mu}M/L$ and $26.2{\pm}10.7{\mu}M/L$ in preterm and term infants, respectively. Umbilical cord arterial concentrations of isoprostane and MDA in preterm infants were significantly higher than those in term infants(P<0.05). The umbilical cord arterial concentrations of isoprostane were significantly associated with perinatal risk factors such as fetal distress, oligohydramnios, and breech delivery in preterm infants and pregnancy-induced hypertension in term infants(P<0.05). Conclusion : Umbilical cord arterial concentrations of isoprostane in preterm infants were higher than those in term infants, and those are significantly associated with some perinatal risk factors.

• Neonatal Medicine
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• v.28 no.3
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• pp.133-138
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• 2021

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.

• Development and Reproduction
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• v.16 no.4
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• pp.339-351
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• 2012

Fetal bovine serum (FBS) is the most frequently used serum for the cultivation of mammalian cells. However, since animal-derived materials might not be appropriate due to safety issues, allogeneic human serum (HS) has been used to replace FBS, particularly for the culture of human cells. While there has been a debate about the advantages of HS, its precise effect on human adult stem cells have not been clarified. The present study aimed to investigate the effect of HS on the human eyelid adipose stem cells (HEACs) in vitro. When HEACs were cultivated in a medium containing 10% HS, many cells moved into several spots and aggregated there. The phenomenon was observed as early as 9 days following 10% HS treatment, and 12 days following 5% HS plus 5% FBS treatment. However, the aggregation was never observed when the same cells were cultivated with 10% FBS or bovine serum albumin. To examine whether cell density might affect the aggregation, cells were seeded with different densities on 12-well dish. Until the beginning of aggregation, cells seeded at low densities exhibited the longest culture period of 16 days whereas cells seeded at high densities showed the shortest period of 9 days to form aggregation. The number of cells was $15.1{\pm}0.2{\times}10^4$ as the least for the low density group, and $29.3{\pm}2.8{\times}10^4$ as the greatest for the high density group. When human cord blood serum or normal bovine serum was examined for the same effect on HEACs, interestingly, cord blood serum induced the aggregation of cells whereas bovine serum treatment has never induced. When cells were cultivated with 10% HS for 9 days, they were obtained and analyzed by RT-PCR. Compared to FBS-cultivated HEACs, HS-cultivated HEACs did not express VIM, and less expressed GATA4, PALLD. On the other hand, HS-cultivated HEACs expressed MAP2 more than FBS-cultivated HEACs. In conclusion, human adult stem cells could move and form aggregates by the treatment with human body fluids.

• Development and Reproduction
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• v.11 no.3
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• pp.235-243
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• 2007

Human umbilical cord blood(HUCB) contains a rich source of hematopoietic stem cells, mesenchymal stem cells and endothelial cell precursors. Mesenchymal stem cells(MSCs) in HUCB are multipotent stem cells, differ from hematopoietic stem cells and can be differentiated into neural cells. We studied on transdifferentiation-promoting conditions in neural cells and cholinergic neuron induction of HUCB-derived MSCs. Neural differentiation was induced by addingdimethyl sulphoxide(DMSO) and butylated hydroxyanisole(BHA) in Dulbeco's Modified Essential Medium(DMEM) and fetal bovine serum(FBS). Differentiation of MSCs to cholinergic neurons was induced by combined treatment with basic fibroblast growth factor(bFGF), retinoic acid(RA) and sonic hedgehog(Shh). MSCs treated with DMSO and BHA rapidly assumed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including $\beta$-tubulin III, GFAP and MBP, was markedly elevated during this acute differentiation. The differentiation rate was about $32.3{\pm}2.9%$ for $\beta$-tubulin III-positive cells, $11.0{\pm}0.9%$ for GFAP, and $9.4{\pm}1.0%$ for Gal-C. HUCB-MSCs treated combinatorially with bFGF, RA and Shh were differentiated into cholinergic neurons. After cholinergic neuronal differentiation, the $\beta$-tubulin III-positive cell population of total cells was $31.3{\pm}3.2%$ and of differentiated neuronal population, $70.0{\pm}7.8%$ was ChAT-positive showing 3 folds higher in cholinergic population than neural induction. Conclusively, HUCB-derived MSCs can be differentiated into neural and cholinergic neurons and these findings suggest that HUCB are alternative cell source of treatment for neurodegenerative diseases such as Alzheimer's disease.

• Journal of Nutrition and Health
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• v.18 no.3
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• pp.209-216
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• 1985

The plasma levels of 23 free amino acids in both the umbilical circulation (umbilical vein and artery) and the maternal circulation (antecubital vein, uterine vein and iliac artery ) of 34 pregnant women were measured at delivery by the cesarean section. Each amino acid with the exception of glutamate was found to be in higher concentration in the fetal blood and the cord plasma characterized by hyperaminoacidemia with a marked increase of the lysine and ornithine levels. The linear relationships found between the amino acids concentrations of iliac artery and those of umbilical vein suggest three transport groups across the placental membrane One group consists of neutral amino acids whose slopes are equal to one and the other two groups are characterized by their slopes higher and lower than unity respectivly. This division into three groups is tentatively explained by the result of a dynamic equilibrium between active transport towards the fetus and diffusion back towards the maternal circulation.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.221-227
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• 2004

Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.11-15
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• 2020

Purpose: The objective of this study was to analyze the results of several noninvasive prenatal tests (NIPTs) from a single center and confirm their efficacy and reliability. In addition, we aimed to confirm the changes in the number of invasive tests performed after introducing NIPT. Materials and Methods: NIPT data from a large single center from March 2014 to November 2018 were analyzed. Karyotyping was confirmed based on chorionic villus sampling, amniocentesis, or postnatal cord/peripheral blood sampling. Data on maternal age, gestational age, fetal fraction, and ultrasonographic results were analyzed. As the secondary outcome, the number of amniocentesis cases before and after the introduction of NIPT was compared. Results: Overall, 1,591 single pregnancy cases that underwent NIPT were enrolled. The mean maternal age was 36.05 (22-45) years. The average gestational age and fetal fraction were 12⁺¹ (9⁺³ to 27⁺¹) weeks and 10.95% (3.6% to 31.3%), respectively. A total of 1,544 cases (97.0%) were reported to have negative NIPT results and 40 (2.5%) had positive NIPT results. The sensitivity and specificity of the overall abnormalities in NIPT were 96.29% and 99.36%, respectively. The positive predictive value (PPV) and negative predictive value were 72.22% and 99.93% respectively. The mean number of amniocentesis cases were 21.7 per month (21.7±3.9), which significantly decreased from 31.5 per month (31.5±4.8) before conducting NIPT as a screening test. Conclusion: NIPT is currently a useful, powerful, and safe screening test. In particular, trisomy 21 is highly specific due to its high PPV. NIPT can reduce the potential risks of procedure-related miscarriages during invasive testing.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.27-37
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• 1990

The extrafetal transfer of $Li^{+}$ in amniotic fluid was studied in 45 pregnant rabbits. LiCl solution was administered either intravenously to mother or directly into the amniotic sac and monitored the appearance and disappearance of $Li^{+}$ in the amniotic fluid, then calculated the transfer rate of $Li^{+}$ of extrafetal origin. To study the transplacental $Li^{+}$ transfer, a solution of 150 mM LiCl was infused continuously via maternal vein (initial dose: 0.7 mmol/kg, maintaining dose: 0.03 mmol/kg/min) and the $Li^{+}$ concentration was measured in maternal blood and amniotic fluid after 60 and 120 minutes of infusion. Change in the volume of aminotic fluid was determined by Congo red dilution method at the same time. Effects of duration of gestation was not considered in this study. Extrafetal transport of $Li^{+}$ into the amniotic fluid was estimated by comparing the $Li^{+}$ concentration and volume of amniotic fluid determined before and after ligating the placental vessels. Extrafetal $Li^{+}$ transport from the amniotic fluid was determined by observing the time dependent disappearance of $Li^{+}$ and Congo red in amniotic fluid after injecting 0.5 ml solution of 15 mM or 90 mM LiCl and 50 mg/ml Congo red. Following are the results obtained: 1) During infusion of LiCl through maternal vein the ratio of the aminotic $Li^{+}$/maternal plasma $Li^{+}$ increased significantly along with the increment of fetal weight. 2) The volume of amniotic fluid of larger fetuses than 20.5 gm increased significantly during administration of LiCl while that of smaller fetuses did not change. 3) After umbilical cord ligation the $Li^{+}$ concentration of amniotic fluid of larger fetuses than 20.5 gm was decreased to $59.9{\pm}10.3%$ and $56.9{\pm}42.9%$ $(mean{\pm}S.D.)$ of those of control group after 60 and 120 minutes of LiCl infusion respectively. In amniotic fluid of smaller fetuses than 20.5 gm, there was no significant difference between control and ligation groups. 4) The disappearance rate of Congo red in the amniotic fluid was $45.2{\pm}8.2%/hr$. 5) The disappearance rate of $Li^{+}$ after intraamniotic injection of LiCl depended on the amount injected. On injecting $7.5\;{\mu}mol$ LiCl, $Li^{+}$ disappeared rapidly from the amniotic fluid and the rates after 60 min and 90 min were $97.0{\pm}2.8,\;98.5{\pm}2.0%$ respectively. On injecting $45\;{\mu}mol$ LiCl, the rates were $56.0{\pm}15.4,\;78.9{\pm}14.5%$ at 60 and 90 min. 6) From the above results it was concluded: a) $Li^{+}$ transfer into the amniotic fluid increased along with the fetal growth and one half of $Li^{+}$ influx is through the extrafetal route even after the maturation of fetal kidney. b) One half of the $Li^{+}$ transfer from the amniotic fluid was through swallowing of fetus, while the remaining half was transfered rapidly through amniotic membrane, which was concentration limited.