• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.92-95
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• 2017

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an ${\alpha}$-galactosidase A (GLA, MIM 300644) enzyme deficiency due to pathogenic variants in the ${\alpha}$-galactosidase A gene (GLA). The disease leads to accumulation of globotriaosylceramide (Gb3) and related glycophospholipids affecting nearly all major organ systems, with the primary sites damaged by Gb3 including renal glomeruli, myocardium, neurons of the dorsal ganglion and autonomic nervous system, and vascular endothelial and smooth muscle. Progressive deposition in these organ systems present with various clinical manifestations including acroparesthesia, renal failure and heart failure. Here, we report a Chinese male diagnosed with Fabry disease in his late $4^{th}$ decades showing improvement of acroparesthesia during enzyme replacement therapy (ERT). A 48-year-old Chinese man who presented with chronic recurrent severe burning pain in his fingers and toes since the age of 10, with worse involvement of the former visited to our clinic for further evaluation. His medical history included a transient ischemic attack aged 40 and diagnosed with stage 4-5 chronic kidney disease aged 47. In the family history, the patient's brother was found to be have Fabry disease 1 month before his visit. Except for his brother, all other members of the family are healthy. Based on his medical history and family history, he was strongly suspicious for Fabry disease. He was found to have a galactose-alpha-1,3-galactose level 4.96 (Reference range, 42.5-67.9) suggestive of Fabry disease. The followed sequencing of GLA coding region in our patient revealed hemizyosity for the mutation c.988C>T (Q330X) in Exon 7. Since ERT start, he showed significant improvement in his symptoms of burning sensation of fingers and toes. On the contrary, due to deteriorating kidney function even with ERT, he is considered for kidney transplantation. Despite of diagnostic delay until late 4th decades, ERT showed a potential improvement of acroparesthesia in our patient. However, late start of ERT can lead to poor outcome in multiorgan function. Therefore, early diagnosis with high index of suspicion followed by continuous ERT with regular monitoring have an impact on quality of life in Fabry disease.

• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.323-334
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• 2005

Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

• Journal of Life Science
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• v.21 no.10
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• pp.1415-1421
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• 2011

The purpose of this study was to identify the effects of an L-arginine supplementation and regular exercise training on NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1, eNOS and Ang II in the aortas of D-galactose (D-gal) induced aging rats. The male Strague-Dawley rats were treated with a D-galactose aging inducing agent; the D-gal injection (50 mg/kg) was given intraperitoneally for 12 wk. Experimental groups were divided into five groups: (1) Young control group (Y-Con, n=8), (2) Aging control group (A-Con, n=8), (3) Aging exercise group (A-Ex, n=8), (4) Aging exercise group with L-arginine supplementation group (A-Ex+A, n=8), and (5) Aging with L-arginine supplementation group (A-A, n=8). The exercise consisted of running on a treadmill for 60 min/day at 20 m/min for 6 day/wk, at 0% gradient for 12 wk. The L-arginine supplementation was given orally at a dose of 150 mg/kg/day for 12 wk. The findings of this study were as follows: 1. NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins in the aortas of D-gal induced rats were significantly increased, however, L-arginine supplementation and regular exercise resulted in a significant inhibition in the expression of NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins. 2. eNOS protein in the aortas of D-gal induced rats was significantly decreased, however, L-arginine supplementation and regular exercise resulted in a significant increase in the expression of eNOS proteins. In conclusion, the findings of the present study reveal that L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation for 12 wk increases anti-inflammatory effects by decreasing NF-${\kappa}B$, TNF-${\alpha}$, and iNOS protein expressions within the aortic tissue. In addition, L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation may prevent endothelial function by up-regulation of eNOS protein in the aortas of D-gal induced aging rats.

• Applied Microscopy
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• v.30 no.2
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• pp.173-183
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• 2000

This study was designed to observe the ultrastructural localization of synoviocytes, which are concerned with the function of phagocytic synovial cells (type A synoviocytes, macrophage-like synoviocytes), in the knee joint of the human for CD14 and CD105 by cryo-immune-electron microscopic technique. The synovium were dissected and fixed for two hours (in 4% paraformaldehyde and 0.1% glutaraldehyde mixture), and were immerged in 2.3 M sucrose and 20% PVP solution. Finally, they were cut with the cryoultramicrotome and labelled with primary antibodies (monoclonal mouse anti-human CD14, monoclonal mouse anti-human CD105 (endoglin) and secondary (donkey anti-mouse IgG) tagged with 6 nm colloidal gold particles. The tissues were observed under transmission electron microscope. This study was resulted as follows. 1. In the synovium of the human knee joint, CD14+ cells were identified. These cells showed phagocytic synovial cell's features. In the phagocytic synoviocyte, the distributions of CD14 were marked in the cytoplasm, around vacuoles, and in cytoplasmic process, but not detected inside of vacuoles. 2. In the synovium of the human knee joint, CD105+ cells were identified. These cells were recognized endothelial cells and phagocytic synovial cells. In the phagocytic synovial cells, the distributions of CD105 (endoglin) were marked in cytoplasic process, around vacuoles, and in cell membrane, but not detected inside of vacuoles. On the basis of above findings, it is obvious that phagocytic synovial cells were marked at CD 14 and CD 105, and might be play the role of activated macrophages or phagocytes in the synovial membrane.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.105-110
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• 2008

Purpose: Preecalmpsia is a pregnancy-specific disorder that reflects widespread endothelial dysfunction resulting from increases of adhesion molecule expression. Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenetic mechanisms responsible for preeclampsia, and ICAM-1 plasma levels and/or function is genetically influenced. Therefore, we evaluated the distribution of ICAM-1 gene K469E polymorphism in pregnant Korean women with preeclampsia and evaluated the association between this polymorphism and preeclampsia. Methods: The K469E polymorphism was analyzed in peripheral blood samples from 197 preeclamptic pregnancies and 193 normotensive pregnancies by a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypic and allelic frequencies of ICAM-1 gene polymorphism (K469E) did not differ between preeclamptic and normotensive pregnancies. The distributions of the KK, KE, and EE genotypes were 40.6%, 43.7%, and 15.7%, respectively, in preeclamptic pregnancies and 38.9%, 45.1%, and 16.1%, respectively, in normotensive pregnancies. The frequencies of K and E alleles were 0.62 and 0.38, respectively, in preeclamptic pregnancies and 0.61 and 0.39, respectively, in normotensive pregnancies. By multiple logistic regression analysis, there was no increased risk of preeclampsia in subjects with ICAM-1 KE (OR, 1.08; P=0.74) or EE (OR, 1.07; P=0.88) genotypes. Conclusion: This study suggests that the ICAM-1 gene K469E polymorphism does not associate with an increased risk of preeclampsia in pregnant Korean women.

• Clinical and Experimental Pediatrics
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• v.45 no.9
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• pp.1106-1113
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• 2002

Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.31-42
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• 2005

Background : Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce $H_2O_2$ and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess $H_2O_2$, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. Methods : This study examined the effect of exogenous, excess $H_2O_2$ on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. Result : The addition of excess $H_2O_2$ to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the $H_2O_2$ treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated $H_2O_2$ treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. Conclusion : The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.