Genetic regulation of linear growth

Linear growth occurs at the growth plate. Therefore, genetic defects that interfere with the normal function of the growth plate can cause linear growth disorders. Many genetic causes of growth disorders have already been identified in humans. However, recent genome-wide approaches have broadened our knowledge of the mechanisms of linear growth, not only providing novel monogenic causes of growth disorders but also revealing single nucleotide polymorphisms in genes that affect height in the general population. The genes identified as causative of linear growth disorders are heterogeneous, playing a role in various growth-regulating mechanisms including those involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. Understanding the underlying genetic defects in linear growth is important for clinicians and researchers in order to provide proper diagnoses, management, and genetic counseling, as well as to develop better treatment approaches for children with growth disorders.

Hydroxyl Radical Production after Intrastriatal Injection of Dopamine and the Effect of Growth Hormone on the Apoptosis of Striatal Neurons Injured by Hypoxia-ischemia in Newborn Rat Brain / 대한소아내분비학회지

PURPOSE:We investigated the production of oxygen hydroxyl radicals in the striatum of neonatal rat brain after intrastriatal injection of dopamine (DA) and the effect of growth hormone (GH) on the apoptosis of striatal neurons injured by hypoxia-ischemia. METHODS:The extracellular striatal levels of 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA as indicators of hydroxyl radical(OH-) production were measured by in vivo microdialysis in the striatums of 7 day-old newborn rats (n=10) after direct intrastriatal infusion of dopamine hydrochloride (1.0 micromol/microL). The samples of perfused artificial cerebrospinal fluid (CSF) were collected every 10 minutes interval. The levels of DA, 2,3-DHBA and 2,5-DHBA of CSF were analysed by HPLC (high performance liquid chromatography). Also, the brains were removed at 24 hour after hypoxic-ischemic injury by Rice-Vannucci method. The coronal sections (12 micrometer) of paraffin-fixed brains were stained by TUNEL (terminal transferase-mediated dUTP nick-end-labelling) technique, and the neuronal cells undergoing apoptosis in the striatum were observed by fluorescent microscopy and compared between GH-treated (50 mg/kg, Dong-Ah Pharmacy Co.) and saline-treated rats. RESULTS:The extracellualr striatal levels of 2,3-DHBA and 2,5-DHBA increased abruptly in the first 10 minutes samples after intrastriatal injection of DA. After then, the levels declined slowely. The levels of striatal extracelluar 2.3-DHBA increased up to 621.8+/-508.7% of basal levels (P<0.05), and the levels of 2.5-DHBA increased up to 262.8+/-198.1% of basal levels (P<0.05). GH reduced markedly the number of apoptotic neuronal cells in the striatum after hypoxic-ischemic brain injury. CONCLUSION: The level of hydroxyl radicals increased abruptly after intrastriatal injection of DA and GH reduced markedly the number of apoptotic neuronal cells in the striatum after hypoxic-ischemic brain injury.

Possible Neuroprotective Role of Exogenous Growth Hormone on Hypoxic-Ischemic Brain Injury in Neonatal Rats / 소아과

PURPOSE: This study was performed to evaluate the possible neuroprotective effect of exogenous growth hormone on hypoxic-ischemic brain injury in neonatal rats. METHODS: After ligation of the right common carotid artery, seven-day old Sprague-Dawley rats(n= 75) were exposed to 8% oxygen for two hours. In a growth hormone(GH)-treated group(n=25), each animal was subcutanously injected by GH(50 mg/kg, Grotrpin, Dong-Ah Pharmacy Co. KOREA) just before exposing to 8% oxygen, and then injected for the next two consecutive days by the same method. In a saline-treated group(n=25), the same amounts of saline were injected instead of GH. Other twenty five animals were sham-operated without hypoxia as a sham control group. The gross morphologic changes of extracted brains at three and seven days after injury were observed, and the ratios of wet and dry weight of each cerebral hemisphere ipsilateral and contralateral to hy poxic-ischemic injury were compared among three groups for evaluating the severity of brain edema. Also, the microscopic changes of cerebral cortex on coronal sections of paraffin-embedded brains were observed at three days after injury by light microscopy. RESULTS: The GH injection reduced the severities of gross changes at seven days after HI injury. The brain edemas of ipsilateral cerebral hemispheres to the site of ligation of the right common carotid artery were significantly decreased in GH-treated animals at three days after HI injury, compared to those in saline-treated animals(P<0.05). On light microscopic examination, neurons with pyknosis of nucleus were remarkably reduced on cerebral cortex at three days after hypoxic-ischemic injury by GH treatment. CONCLUSION: Exogenous GH might have a some neuroprotective role in hypoxic-ischemic brain injury of newborn rats.

Effect of Hypoxia-Ischemia on Striatal Monoamine Metabolism in Neonatal Rat Brains

PURPOSE: We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. METHODS: The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indoleacetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. RESULTS: The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P0.05). DOPAC showed the most remarkable decrease(23.0+/-4.2%, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation(120.8+/-54.9%, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia(35.3+/-7.6% of basal level, P<0.05) and reoxygenation (105.8+/-32.3%). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased(74.9+/-3.1%) and increased(118.1+/-7.8%) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). CONCLUSION: Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

Risk Factors Related to Progression to Threshold Retinopathy of Prematurity in Extremely Premature Infants

PURPOSE: This study was intended to evaluate the risk factors related to the progression to threshold retinopathy of prematurity(ROP) after the first diagnosis of ROP in extremely premature infants. METHODS: We retrospectively reviewed the medical records of 41 infants with gestational ages of less than 28 weeks and birth weight of less than 1,250 g who took ophtalmologic examination for ROP during admission to NICU from January 1997 to December 2001. The infants who were diagnosed as ROP were classified into two groups the group that progressed to threshold ROP ("threshold ROP group", n=15) and the self-regressed prethreshold ROP group("prethreshold ROP group", n=18). We compared the risk factors and the changes of daily transcutaneous oxygen saturation during the two weeks after the first diagnosis of ROP between these two groups. RESULTS: Thirty three(80.5%) of 41 infants developed ROP. Fifteen(36.6%) progressed to threshold ROP after the diagnosis of ROP. The incidences of threshold ROP increased according to the lower birth weight in extremely premature infants. The progression to threshold ROP after the first diagnosis of ROP was significantly associated with the number of transfusions and birth weight(P<0.05, P<0.05, respectively). Daily mean arterial oxygen saturations of infants with threshold ROP during two weeks after the first diagnosis of ROP were higher than those of infants with prethreshold ROP(P<0.05). CONCLUSION: The occurrences of threshold ROP were related to lower birth weight and more frequent transfusions and higher daily mean transcutaneous oxygen saturation during two weeks after the first diagnosis of ROP.

Intra-arterial Blood Pressure Changes in Very Low Birth Weight Infants During the First Seven Days of Life

PURPOSE: We aimed to assess the influence of perinatal factors on intra-arterial mean blood pressures of very low birth weight infants during the first seven days of life and the association of intra-arterial mean blood pressures on the common morbidities and neonatal death of very low birth weight infants. METHODS: The retrospective study on intra-arterial mean blood pressures over the first seven days of life in 103 very low birth weight infants who admitted to the neonatal intensive care unit at the Dankook University Hospital from Jan. 1996 to Dec. 2000 was done. Trend data for each infants were assessed in 9 time periods until seven days of age. Perinatal factors that might influence intra-arterial mean blood pressures and the association of intra-arterial mean blood pressures on neonatal death and common morbidities were assessed. RESULTS: Intra-arterial mean blood pressures of very low birth weight infants increased with birth weight and gestational age (P<0.05), and significantly increased with postnatal age over the seven day periods from 35.0+/-4.9 mmHg (period 1) to 44.2+/-6.5 mmHg (period 9). Intra-arterial mean blood pressures of infants weighing less than 1,000 g were significantly lower than infants weighing 1,000 to 1,499 g at all each time periods (P< 0.05). Intra-arterial mean blood pressures were found to correlate significantly with antenatal steroid (P<0.005), and correlate inversely with PDA (P<0.001), pulmonary hemorrhage (P<0.005) and ROP (P<0.05). CONCLUSION: Intra-arterial mean blood pressures in very low birth weight infants during the first seven days were found to correlate significantly with postnatal age, gestational age, birth weight and antenatal steroid and probably correlate with some common morbidities of very low birth weight infants. It is therefore important to maintain adequate blood pressure ranges during the first seven days of life that are the most critical periods of illness for the majority of very low birth weight infants.

A Case of Adams-Oliver Syndrome which was Observed in Two Brothers

Adams-Oliver syndrome is characterized by the presence of scalp aplasia cutis congenita with distal limb anomalies. Cutis mammorata and dilated scalp veins are additional frequent manifestations of the condition. In almost all reported patients with Adams- Oliver syndrome, the trait of inheritance was autosomal dominant. Only three reports suggested autosomal recessive inheritance characterized by multiple affected offsprings in unaffected parents. But a number of sporadic cases have been described. We have experienced a boy with this syndrome, who showed large congenital scalp defect with exposed dural membrane and bony defect beneath it, cutis mammorata on whole body, equinovarus, and no metatarsal ossification center of left foot. His brother also had these symptoms, but their parents were not affected. He was complicated by bacterial meningitis, and cured with antibiotics. The skin defect was closed spontaneously with atrophic scar. We report this case with the brief review of literature.