• Development and Reproduction
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• v.13 no.2
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• pp.105-114
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• 2009

Ethane 1,2-dimethane sulfonate (EDS) is a well-known alkylating agent used as selective Leydig cell (LC) toxicant to create a testicular dysfunction model. Previous studies including our own clearly demonstrated the dramatic weight loss of the androgen dependent accessory sex organs such as epididymis, seminal vesicle and prostate gland in this 'LC knock-out' rats. The present study was performed to evaluate the effect of EDS administration on histological changes of the epididymis, seminal vesicle and prostate in adult rats. Adult male Sprague-Dawley rats (350$\sim$400 g B.W.) were injected with a single dose of EDS (75 mg/kg, i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights (testis, epididymis, seminal vesicle and prostate gland) were measured. The histological changes of tissue were observed by a light microscopy using hematoxylin & eosin staining. Weights of the reproductive and accessory organs progressively declined after the EDS treatments (weeks 1, 2 and 3). After this, the decrease was stopped, then gradually returned to the normal levels. There was a partial (about 60%) recovery of the epididymis weight during weeks $6{\sim}7$. The cross section of epididymis revealed an increase in thickness of the epithelium during weeks $1{\sim}3$. In contrast, considerable reduction of epithelial thickness in seminal vesicle was observed during same period. Similarly, a reduction in thickness of prostate epithelial layer was found during weeks $1{\sim}3$, then it was back to normal thickness after week 4. Taken together, the present study demonstrated that the temporally induced androgen-deficiency by EDS treatment could result the prominent alterations in histology of the accessory sex organs. Further studies on the physiological and molecular regulation of these androgen-sensitive organs using EDS model will be helpful to understand the normal and pathological development and differentiation mechanism of these organs.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.12 no.2
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• pp.87-94
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• 1979

In order to study the water pollution in Suyeong Bay, Busan, some chemical constituents were determined at 25 stations in the neap tides on 9 Aug. 1977 and spring tides on 30 Aug. 1977. Range and mean values of the constituents in the spring tides are as follows: $pH\;6.54\~8.06,\;7.54;$ electrical conductivity $0.413\~0.481\times10^5\;\mu\mho/cm,\;0.467\times10^5\;\mu\mho/cm;\;transparency\;0.2\~5.5m,\;2.2m;$ turbidity $1\~60ppm$, 14ppm, chlorosity $15.20\~18.11g/\ell,\;17.67g/\ell;$ fluoride ion $0.94\~1.03ppm$, 0.99ppm; dissolved oxygen $0.17\~7.60ppm$, 4.77ppm; sulfide $0\~0.46ppm$, 0.07ppm; chemical oxygen demand $1.20\~40.74ppm$, 6.11ppm; ammonia-nitrogen $0.060\~0.520ppm$, 0.180ppm; nitrite-nitrogen $0.001\~0.026ppm$, 0.009ppm; nitrate-nitrogen $0\~0.037ppm$, 0.014ppm; phosphate-phosphorus $0.002\~0.261ppm$, 0.050ppm; n-Hexane soluble $0.5\~5.4ppm$, 2.1ppm ; iron $1.0\~104.11\;ppb$, 24.15ppb ; copper $0\~27.45ppb$, 4.19ppb; lead $0\~2.50ppb$, 0.92ppb; zinc $0\~5.15ppb$, 1.47ppb ; cadmium $0\~0.26ppb$, 0.04ppb; and mercury $0.05\~0.37ppb$, 0.11ppb respectively. The variations of the contents of the chemical constituents in the spring tides were larger than in the neap tides. The contents of COD, sulfide, nutrient salts and heavy metals were the highest in the estuary of Suyeong River, and decreased in order of off Kwangan-Ri region, outer Bay and off Haeun-Dae region. The water quality in Suyeong Bay was particularly shown that the concentrations of COO, iron, copper and mercury were higher than those of other coastal aseas and deficiency in dissolved oxygen was observed in some parte of Suyeong Bay. In consideration of the relationship between the chlorosity and the concentrations of nutrient salts, COD and total heavy metals, water pollution of this area is considered due to the inflow of Suyeong River which was extremely polluted by sewage and industrial wastewaters.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.292-297
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• 2006

Purpose : In medulloblastoma, craniospinal radiation therapy combined with chemotherapy improves the prognosis of tumors but results in significant endocrine morbidities. We studied the endocrine morbidity, especially growth pattern changes. Methods : The medical records of 37 patients with medulloblastoma were reviewed retrospectively for evaluation of endocrine function and growth. We performed the growth hormone stimulation test in 16 patients whose growth velocity was lower than 4 cm/yr. Results : The height loss was progressive in most patients. The height standard deviation score (SDS) decreased from $-0.1{\pm}1.3$ initially to $-0.6{\pm}1.0$ after 1 year(P<0.01). Growth hormone deficiency(GHD) developed in 14 patients. During the 2 years of growth hormone(GH) treatment, the improvements of height gain or progressions of height loss were not observed. Twelve patients(32.4 percent) revealed primary hypothyroidism. One of six patients diagnosed with compensated hypothyroidism progressed to primary hypothyroidism. Primary and hypergonadotropic hypogonadism were observed in two and one patients respectively. There was no proven case of central adrenal insufficiency. Conclusion : Growth impairment developed frequently, irrespective of the presence of GHD in childhood survivors of medulloblastoma. GH treatment may prevent further loss of height. The impairment of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroidal axis is less common, while central adrenal insufficiency was not observed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.96-102
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• 2017

Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.18-23
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• 2016

Objective: Newborn screening leads to improved treatment and disease outcomes, but false-positive newborn screening results may impact include parental stress and anxiety, perception of child as unhealthy, parent-child relationship dysfunction, and increased infant hospitalizations. The purpose of this study was to investigate of the false positive rates and the causative factors of false positive results in Tandem Mass Spectrometry (TMS) in single center. Methods: Records were reviewed for all 18,872 subjects who were born in Cheill General Hospital, during January 1st, 2012 to December 31st, 2014. 17,292 neonates (91.62%) were tested for tandem mass screening almost in 2-5th day of life. Newborn babies whose first results were abnormal had been tested repeatedly by same methods in 7-14 day. If the results were abnormal again, further evaluation was performed. TMS analysis included data for the 43 disorders screened for using TMS broken down into three categories: fatty acid oxidation disorders, organic acidurias, and aminoacidopathies. The impact of several factors on increased false positive rates was analyzed using a multivariate analysis: time from birth to sample collection, birth weight, birth height, BMI, gender, gestational age, delivery type. Results: Males of the subjects were 8942 (51.7%), female 8350 (48.3%), the mean gestational age was $38.6{\pm}1.7$ weeks, the average birth weight $3,155.6{\pm}502.4g$, the average birth height $49.1{\pm}2.9cm$, and the average BMI $13.0{\pm}3.8(kg/m^2)$. Vaginal delivery cases were 9713 (56.2%), caesarean section 7,579 (43.8%). The average date of the inspection was $2.8{\pm}1.1$ days. 224 cases were identified as TMS positive. All the subjects were false positive (222/17,292, 1.30%) except 2 cases (1 male; benign phenylketonuria and 1 female; Short chain acyl-CoA dehydrogenase deficiency). The false positive rates were 0.61% in fatty acid oxidation disorders, 0.25% in organic acidurias, and 0.45% in aminoacidopathies. In our study, the date of inspection got late, the false positive rates got higher. Because almost the cases of late test date were in treatment in neonatal intensive care unit so their test date was affected by their medical conditions. False positive rate was higher in extreme immaturity${\leq}27$ weeks than newborns of gestational age >27 weeks [OR=6.957 (CI=1.273-38.008), p<0.025] and extremely low birth weight<1,000 g than newborns of birthweight ${\geq}1,000g$ [OR=5.616 (CI=1.134-27.820), p<0.035]. Conclusion: False positive rate of TMS was 1.30% in Cheil General Hospital. Lower gestational age and birth weight impacted on increased false positive rates. Better understanding of factors that influence the reporting of screening tests, and the ability to modify these important factors, may improve the screening process and reduce the need for retesting. of screening tests, and the ability to modify these important factors, may improve the screening process and reduce the need for retesting.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.135-141
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• 2014

Objectives: Fabry disease (FD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide (Gb3) in tissues due to a deficiency in the enzyme ${\alpha}$-galactosidase A. Hypertrophic cardiomyopathy is one of the chronic complications of FD. We tried to evaluate the prevalence of Fabry disease in the Korean patients with left ventricular hypertrophy (LVH). Methods: A total of 257 patients with LVH were recruited and they were 172 males (mean 56 years, range 30-81 years) and 84 females (mean 66 years, range 45-85 years). Urinary Gb3 was used to screen FD by high performance liquid chromatography-tandem mass spectrometry. Confirmatory tests were done by alpha-galactosidaseA activity using fluorometric assay and by GLA mutation analysis using sequencing. Results: Four patients were screening positive by urinary Gb3 analysis (cutoff, 25 ug/mmol creatinine). But, one female patient was diagnosed with FD confirmed by enzyme analysis in leukocytes as well as by genetic analysis (1/257 patients, 0.4%). She showed 54.3 ug/mmoL creatinine of Gb3 and 15.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alphagalactosidase A activity. And she had a heterozygous GLA mutation of c.796G>A (p.D266N). Her daughter was found to be a carrier for FD confirmed by GLA mutation analysis. Asymptomatic carrier showed 25.5ug/mmol creatinine of Gb3 and 42.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alpha-galactosidase A activity. Conclusions: The prevalence of FD in Koran patients with LVH was detected as 0.4%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.

• The korean journal of orthodontics
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• v.30 no.4 s.81
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• pp.399-411
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• 2000

This study was designed to evaluate the correlations between the morphology and growth of cranial base and the position of nasomaxillary complex and mandible in complete unilateral cleft lip and palate patients. Craniofacial skeletal morphology Pattern was analyzed on the lateral cephalometric radiographs of the 100 subjects of complete unilateral cleft lip and palate group and the 100 normal grower group and each group was divided three sub-groups by age-range like spheno-ethmoidal synchodrosis growing group, spheno-occipital synchondrosis growing group and finished synchondrosis growth group. These data were statistically analyzed to examine significant difference between both groups and between each sub-groups. The results of this study were as follows: 1. In complete unilateral cleft group, the length, thickness of clivus, and the rate of increase in length of clivus showed smaller amount by adolescence. The anterior length of cranial base and the rotation pattern of clivus with age showed no significant difference between two group. 2. In complete unilateral cleft group, nasomaxillary complex were located more posteriorly. This difference between two groups is larger by adolescent group than adult. Vertical position showed no significant difference between two groups. There was significant correlation between the cranial base of cleft group and the horizontal measurements(p<0.01). PtmS showed no significant increment in cleft group. This showed the deficiency of growth in posterior part of maxilla. 3. In mandible, there was no significant difference between normal group and complete unilateral cleft group but articular angle showed significantly smaller in cleft group than in normal one. And the measurements of nasomaxillary complex position, cranial base and the position of mandible had significant correlation(p<0.01).

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.262-266
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• 2008

Purpose: Many patients suffer with anemia after gastrectomy. Iron deficiency due to a decreased oral intake and malabsoption is the most common cause of anemia in gastrectomized patients. This study evaluated the efficacy of administering intravenous iron sucrose for treating patients with anemia. Materials and Methods: From May 2007 to October 2007 at Yonsei University Severance Hospital, we reviewed 47 outpatients whose hemoglobin levels were below 11 g/dl after gastrectomy. Iron sucrose was used for iron supplementation. To determine the difference between before and after the treatment (at 1 week, 2 weeks, 3 weeks, 3 months and 6 months after treatment), we prospectively examined such anemia parameters as the hemoglobin level (Hgb), the hematocrit (Hct), serum iron, TIBC, ferritin and transferin. Results: Out of the 47 patients, only 36 completed their treatment. Eleven were male and 25 were female. The Hgb levels, which indicate anemia, were elevated 0.6, 0.8, 1.3, 2.1 and 2.2 g/dl after 1 week, 2 weeks, 3 weeks, 3 months and 6 months after administration, respectively (P<0.001). The changes from 1 week to 3 months were statistically significant, but those from 3 to 6 months were not. The Hgb levels of 26 patients, which accounted for 72% of all the patients, elevated up to 12 g/dl or more. No side effects or complications were found, but there was one case of temporary nausea. Conclusion: Anemia after gastrectomy is safely treated in a relatively short time with administering iron sucrose. The patients' Hgb levels are expected to increase in a week and keep increasing up to 3 months.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.2
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• pp.55-62
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• 2020

A 22-month-old girl who had taken iron supplements due to iron deficiency anemia, presented bloody mucoid stool for one month. She had a bruise at the right periorbital area due to minor trauma and hepatosplenomegaly. Laboratory studies showed anemia, thrombocytopenia, elevated alkaline phosphatase (ALP), hypophosphatemia, decreased haptoglobin, hypocomplementemia, negative direct/indirect Coomb's test, normal vitamin D3 level and high PTHi. Wrist x-ray showed no signs of rickets. The abdominal ultrasound showed only accessory spleen. Tandem mass spectrometry was normal. During follow up, bloody stool regressed after seven days of withdrawal of iron supplement and cow milk, and the total CO2 level had been within 15-20 mEq/L with normal anion gap. NGS (next generation sequencing) panel test for evaluation of renal tubular acidosis showed negative results. After low dose steroid and vitamin D supplements under the impression of hypocomplementemic vasculitis, thrombocytopenia, C3/C4, decreased haptoglobin, and elevated ALP level became normal. At 57 months of age, laboratory findings showed elevated liver enzyme, ALP and gamma-glutamyl transferase again. And liver cirrhosis with splenomegaly and diffuse renal disease were reported with abdomen CT scan. Liver biopsy reported macro- and micronodular cirrhosis. Urine organic acid profile showed elevated succinylacetone level. Whole exome sequencing revealed novel compound heterozygous mutations (NM_00137.2:c.107T>C, NM_00137, 2:c.614T>C) in FAH gene and confirmed by Sanger sequencing. Consequently, the patient was diagnosed as chronic hereditary tyrosinemia type I. She started low phenylalanine/tyrosine diet and nitisinone treatment. Our case had presented symptoms very slowly, which is the first case of chronic tyrosinemia type I in South Korea.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.399-414
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• 1997

There are several factors concerning to anemia in chronic renal failure patients. But when rHuEPO is used, most of these factors can be overcome, and the levels of hemoglobin are increased. However, about 10% of the renal failure patients represent rHuEPO-resistant anemia eventhough high dosage of rHuEPO. For these cases, desferrioxamine can be applied to correct rHuEPO resistnacy, and many mechanism of DFO are arguing. So we are going to know whether DFO can be applied to correct anemia of the such patients, how long its effect can be continued. The seven pateients as experimental group(DFO+EPO) who represent refractoriness to rHuEPO and the other seven patients as control group(EPO) were included. Experimental group had lower than 9 g/dL of hemoglobin levels despite high rHuEPO dosage (more than 4000U/Wk) and showed normocytic normochromic anemia. There were no definitve causes of anemia such as hemorrhage or iron deficiency. Control group patients had similar characteristics in age, mean dialysis duration but showed adequate response to rHuEPO. DFO was administered to experimental group for 8 weeks along with rHuEPO(the rHuEPO individual mean dosage had been determined by mean dosage of the previous 6 months. Total mean dosage; 123.5 U/Kg/Wk). After 8 weeks of DFO administration, the hemoglobin and rHuEPO dosage levels were checked for 15 consecutive months. It should be noted that the patients determined their own rHuEPO dosage levels according to hemoglobin levels and economic status. In conrol group, rHuEPO was administered by the same method used in experimental group without DFO through the same period. Fifteen months of observation period after DFO trial were divided as Time I(7 months after DFO trial) and Time II(8 months after Time I). The results are as follows: Before DFO trial, mean hemoglobin level of experimental group was 7.8 g/dL, which is similar level(p>0.05) to control group(mean Hb; 8.2 g/dL). But in experimental group, significantly(p<0.05) higher dosages of rHuEPO(mean; 123.5 U/Kg/Wk) than control group (mean; 41.6 U/Kg/Wk) had been used. It means resistancy to rHuEPO of experimental group. But after DFO trial, the hemoglobin levels of the experimental group were increased significantly(p<0.05), and these effect were continued to Time II.(Time I; mean 8.6g/dL, Time II; mean 8.6g/dL) The effects of DFO to hemoglobin were continued for 15 months after DFO trial with similar degree through Time I, Time II. Also, rHuEPO dosages used in the experimental group were decreased to similar levels of the control group after DFO trial and these effect were also continued for 15 months(Time I; mean 48.1 U/Kg/Wk. Time II; mean 51.8 U/Kg/Wk). In the same period, hemoglobin levels and rHuEPO dosages used in the control group were not changed significantly. Notibly, hemoglobin increment and rHuEPO usage decrement in experimental group were showed maxilly in the 1st month after DFO trial. That is, after the use of DFO, erythopoiesis was enhanced with a reduced rHuEPO dosage. So we think rHuEPO reisistancy can be overcome by DFO therapy. In conclusion, the DFO can improve the anemia caused by chronic renal failure at least over 1 year, and hence, can reduce the dosage of rHuEPO for anemia correction. Additional studies in order to determine the mechanism of DFO on erythropoiesis and careful attention to potential side effects of DFO will be needed.