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Biomedical subjects

Y G Park

Publications and source records attributed to Y G Park.

At least 19 recordsLinked to original sources

Inhibitory effects of streptozotocin, tumor necrosis factor-alpha, and interleukin-1beta on glucokinase activity in pancreatic islets and gene expression of GLUT2 and glucokinase.

Treatment of streptozotocin (ST), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) resulted in destroying insulin-secreting beta-cells of pancreatic islets and impairment of islet glucose oxidation and glucose-induced insulin secretion. IL-1beta and TNF-alpha inhibited insulin release and glucose utilization and oxidation. It was shown that the inhibitory effects of ST, IL-1beta, and TNF-alpha were due to impaired glucokinase activity. Glucokinase activity was severely impaired by ST, IL-1beta, and TNF-alpha treatments, as confirmed by assaying enzymes and nucleotides associated with glycolysis and glucose oxidation. On the other hand, nitric oxide was a factor of the deleterious effects of IL-1beta, TNF-alpha, and ST on pancreatic islets. Incubation of mouse pancreatic islets with ST at various concentrations of impairing insulin secretion resulted in generation of nitrite, stimulation of islet guanylyl cyclase and accumulation of cGMP, and inhibition of pancreatic islet mitochondrial aconitase activity to degree similar to those raised by IL-1beta and TNF-alpha. When the effects of IL-1beta and TNF-alpha on the gene expression of pancreatic GLUT2 and glucokinase were examined, the level of GLUT2 and glucokinase mRNA in pancreatic islets was significantly decreased. This suggested that IL-1beta and TNF-alpha downregulate gene expression of GLUT2 and glucokinase in pancreatic beta-cells.

Aconitate Hydratase

Frequent loss of heterozygosity on chromosomes 4, 12 and 19 in radiation-induced lymphomas in mice.

We found frequent loss of heterozygosity (LOH) on chromosomes 4, 12 and 19 in radiation-induced lymphomas from (BALB/cHeA x STS/A) F1 hybrid mice by allelotype analysis at polymorphic microsatellite loci. The incidences of LOH were 27% (20 of 74 lymphomas), 57% (42 of 74 lymphomas) and 50% (37 of 74 lymphomas) on chromosomes 4 (at D4Mit31), 12 (at D12Mit17) and 19 (at D19Mit11), respectively. These frequent LOH regions are homologous to human chromosomes 9p and 1p, chromosome 12q32.1 and chromosome 10q, respectively. Strain-specific preferential allele loss was observed only on chromosome 4. However, no bias in the frequency of loss between alleles of maternal and paternal origin was observed, indicating that genomic imprinting may not be predominantly involved in these lymphomas. The results suggest that these three regions might harbor tumor suppressor genes responsible for this lymphomagenesis.

Animals

Dual blockade of cyclic AMP response element- (CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide. gene-specific inhibition of tumor growth.

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential. Synthetic double-stranded phosphorothioate oligonucleotides with high affinity for a target transcription factor can be introduced into cells as decoy cis-elements to bind the factors and alter gene expression. The CRE (cyclic AMP response element)-transcription factor complex is a pleiotropic activator that participates in the induction of a wide variety of cellular and viral genes. Because the CRE cis-element, TGACGTCA, is palindromic, a synthetic single-stranded oligonucleotide composed of the CRE sequence self-hybridizes to form a duplex/hairpin. Herein we report that the CRE-palindromic oligonucleotide can penetrate into cells, compete with CRE enhancers for binding transcription factors, and specifically interfere with CRE- and AP-1-directed transcription in vivo. These oligonucleotides restrained tumor cell proliferation, without affecting the growth of noncancerous cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases.

Blotting, Western

The Asian upper eyelid: an anatomical study with comparison to the Caucasian eyelid.

OBJECTIVE: To evaluate the differences between Asian and Caucasian upper eyelid anatomy through cadaver dissection, histopathological study, and magnetic resonance imaging. MATERIALS AND METHODS: Upper eyelids of 9 Korean and 5 Caucasian cadavers were dissected, and then were studied microscopically with hematoxylin-eosin, Masson trichrome, and elastin stains. Four healthy young Korean men were studied by dynamic high-resolution magnetic resonance imaging with regard to demonstration of upper eyelid structure. RESULTS: More subcutaneous and suborbicularis fat, with a pretarsal fat component, is present in Asian eyelids. The Asian double eyelids showed an amount of fat intermediate between Asian single eyelids and Caucasian eyelids. Asian single eyelids showed fusion of the orbital septum to the levator aponeurosis below the superior tarsal border, while fusion is above the superior tarsal border in Caucasians. The preaponeurotic fat pad descends anteriorly to the tarsal plate in the Asian single eyelid, but not in the Caucasian eyelid. A pretarsal fat pad is identified in the Asian single eyelids. CONCLUSIONS: The causes of absent or lower crease in the Asian upper eyelid are as follows: (1) the orbital septum fuses to the levator aponeurosis at variable distances below the superior tarsal border; (2) preaponeurotic fat pad protrusion and a thick subcutaneous fat layer prevent levator fibers from extending toward the skin near the superior tarsal border; and (3) the primary insertion of the levator aponeurosis into the orbicularis muscle and into the upper eyelid skin occurs closer to the eyelid margin in Asians. Structural differences relating to increased fat in the Asian upper eyelid include the presence of a pretarsal fat pad and a moderate fat increase in the double Asian eyelid.

Adipose Tissue

The RIIbeta regulatory subunit of protein kinase A binds to cAMP response element: an alternative cAMP signaling pathway.

cAMP, through the activation of cAMP-dependent protein kinase (PKA), is involved in transcriptional regulation. In eukaryotic cells, cAMP is not considered to alter the binding affinity of CREB/ATF to cAMP-responsive element (CRE) but to induce serine phosphorylation and consequent increase in transcriptional activity. In contrast, in prokaryotic cells, cAMP enhances the DNA binding of the catabolite repressor protein to regulate the transcription of several operons. The structural similarity of the cAMP binding sites in catabolite repressor protein and regulatory subunit of PKA type II (RII) suggested the possibility of a similar role for RII in eukaryotic gene regulation. Herein we report that RIIbeta subunit of PKA is a transcription factor capable of interacting physically and functionally with a CRE. In contrast to CREB/ATF, the binding of RIIbeta to a CRE was enhanced by cAMP, and in addition, RIIbeta exhibited transcriptional activity as a Gal4-RIIbeta fusion protein. These experiments identify RIIbeta as a component of an alternative pathway for regulation of CRE-directed transcription in eukaryotic cells.

3T3 Cells

Antisense depletion of RIalpha subunit of protein kinase A induces apoptosis and growth arrest in human breast cancer cells.

In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RIalpha subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RIalpha subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RIalpha antisense oligodeoxynucleotide correlated with a decrease in the RIalpha mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morphology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RIalpha antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RIalpha and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment.

Apoptosis

Surgical management of intractable epilepsy.

Cortical resective surgery (including amygdalohippocampectomy) and corpus callosotomy are the most widely accepted modes of surgical treatment for intractable epilepsy. Between July 1989 and May 1996, 146 surgeries for epilepsy were done at Severance Hospital, Yonsei University. Resective surgery was performed in 126 patients and corpus callosotomy in 20 patients. Of the 126 patients who underwent resective surgery, surgery for the removal of the epileptic lesion (lesionectomy) was performed in 21 patients (16.7%) while 105 patients (83.3%) underwent surgery without a structural lesion. Current surgical therapy for intractable epilepsy requires the precise localization of a resectable zone of epileptogenesis. Unfortunately, finding a localized focus in an extratemporal region is far more difficult than in the temporal lobe. Surgeries for extratemporal lobe epilepsy without lesions have been less successful than surgeries for temporal lobe epilepsy. Although surgery for intractable epilepsy has been increasingly successful, we still need to refine our techniques to further improve the success rate and to reduce complications of surgery such as language and memory impairment.

Adolescent

A new technique for repositioning a posteriorly dislocated intraocular lens.

Pars plana vitrectomy was performed to treat a complete posterior dislocation of an intraocular lens in seven patients. The method that the authors have developed appears to be safer and simpler than those previously described. The haptics are externalized for a secure tie at the proper site, and are then reinternalized back through the pars plana sclerotomies. Only two small needle perforations are made for the scleral fixation of the intraocular lens in the ciliary sulcus. Perfluorocarbon liquid is used to prevent intraoperative retinal damage.

Fluorocarbons

Putative tumor suppressor gene region within 0.85 cM on chromosome 12 in radiation-induced murine lymphomas.

Analyses of genetic alterations in tumors from F1 hybrid mice produced by inter-subspecific crosses between genetically well-characterized inbred strains provide precise and comprehensive evidence for genetic abnormalities such as allelic loss. We performed loss of heterozygosity (LOH) analyses of 125 radiation-induced lymphomas of (BALB/cHeA x MSM/Ms)F1 hybrid mice by polymerase chain reaction (PCR) analysis of microsatellite DNA polymorphic markers. Very frequent LOH was found at a distal region on chromosome 12. To precisely define the most common region of LOH, we first determined the order of and distances between the available microsatellite loci around the region by using 586 (CXSD x MSM/Ms)F2 hybrid mice (1172 meiosis). The locus order and distances were [centromere]-D12Mit132-(0.34 cM)-D12Mit5O-(2.05 cM)-[D12Mit122, D12Mit53]-(0.85 cM)-D12Mit233-(0.43 cM)-D12Mit279-(O.17 cM)-D12Mit181-[telomere]. We then investigated the features of LOH at these loci. The highest frequency of LOH (83 of 125, 66%) was found at D12Mit233. The LOH patterns of individual lymphomas indicated that the most common region of LOH was within the 0.85 cM between D12Mit53 and D12Mit233, a region homologous to human chromosome 14q32.1. These results suggest that a putative novel tumor suppressor gene exists within this region.

Animals

An analysis of the natural history of cavernous malformations.

BACKGROUND: The treatment of cavernous malformations has been controversial. Some reports suggest that surgical resection of the lesion for the prevention of recurrent hemorrhage should not be considered because of low hemorrhagic risk. However, the role of surgery in management of cavernous malformations is undergoing reevaluation. The decision for surgical resection should be based on a careful analysis of the natural history of this lesion, which is not well understood. METHODS: We investigated, retrospectively, the natural history of 108 cavernous malformations in 62 patients. Individual cavernous malformations were divided into four categories on the basis of magnetic resonance (MR) findings. The pattern of clinical and radiologic presentation and outcomes of management were analyzed. RESULTS: The age of the patients ranged from 4-63 years (mean: 32.2 years). Multiple lesions were found in 13 of 62 patients (21%) and two of these patients were siblings. Twenty-five out of 62 patients had suffered recurrent symptoms. The bleeding rate was 2.3%/person/year (1.4%/lesion/year) during 2509.6 patient years. There were no significant differences between the bleeding rates of each type of lesion. During the follow-up period of 12-48 months (mean: 22.4 months), two of 28 patients conservatively treated had recurrent hemorrhages (rebleeding rate: 3.8%/person/year). During the follow-up period of 12-66 months (mean: 21.7 months), recurrent hemorrhages were observed in two of 17 patients with radiosurgery (rebleeding rate: 7.8%/person/year). CONCLUSION: Our study has provided a profile of the natural history of these lesions. Based on our results, we recommend surgical excision of cavernous malformations in those patients with recurrent symptoms or acute progressive symptoms.

Adolescent

Volume changes following gamma knife radiosurgery of intracranial tumors.

BACKGROUND: The primary goal of radiosurgery for brain tumors is the prevention of further growth. The purpose of this article is to evaluate temporal changes of tumor volume after Gamma Knife radiosurgery on intracranial tumors. METHOD: Some 137 patients with 148 intracranial tumors who were treated with Gamma Knife radiosurgery and underwent radiological follow-up were reviewed. The tumors with high radiosensitivities to conventional external radiation were excluded. RESULT: The median radiological follow-up period was 12 months (range 1.5-38 months). Volume decreased after radiosurgery in 15 of 45 meningiomas; 10 of 37 schwannomas; 6 of 21 pituitary adenomas; 4 of 15 benign gliomas, including both of 2 subependymal giant cell astrocytomas; and 2 of 8 malignant gliomas. Some 87% of meningiomas and 60% of schwannomas whose volume had decreased began to shrink within 12 months and after 12 months, respectively. Transitory increase in volume preceded shrinkage in 16.2% of schwannomas, 13.3% of benign gliomas, 4.8% of pituitary adenomas, and 2.2% of meningiomas. Marked shrinkage occurred in 17 of 19 metastatic tumors and in all 3 neurocytomas shortly after radiosurgery. Of eight malignant gliomas, five began to grow 2-14 months (median = 5 months) after radiosurgery. CONCLUSION: Several points should be considered carefully while following up on patients after radiosurgery: the possibility of transient volume increase, tumor-specific volume change patterns, and the tumor-specific goals of radiosurgery.

Adolescent

Microvascular decompression and percutaneous rhizotomy in trigeminal neuralgia.

We analyzed 417 patients with trigeminal neuralgia who underwent microvascular decompression (MVD; n = 146) or percutaneous procedures, i.e. radiofrequency rhizotomy (RFR; n = 235) and glycerol rhizotomy (GR; n = 36) between March 1973 and December 1996. MVD and RFR showed the highest rates of initial pain relief (MVD 96.5%; RFR 92.3%; GR 82.8%). RFR and GR had 5.1 and 3.3% rates of facial dysesthesia, respectively, and MVD had the lowest rate (0.3%). Among 9 cases (8.6%) with recurrences after MVD, 8 cases underwent RFR and all of them obtained good long-term results (7.2 years on average). We concluded that MVD is the treatment of choice for tolerant younger patients and should be recommended for patients who desire no sensory deficit. We also determined that radiofrequency rhizotomy is the procedure of choice for patients in whom MVD failed.

Catheter Ablation

Percutaneous radiofrequency lumbar facet rhizotomy in mechanical low back pain syndrome.

During the period from March 1992 to June 1996, we performed percutaneous radiofrequency (RF) facet rhizotomy in 324 patients with low back pain. Employing the lesion generator, we coagulated branches of the zygapophyseal nerve to treat low back pain. The follow-up period was 6-51 months (average: 22.5 months). There were no complications during the procedure and the follow-up period and no poor results were observed. Two-hundred and thirty-one patients (103 females and 128 males) had mechanical low back pain syndrome and showed marked improvement of pain after the procedure, including 29 cases with previous spinal surgery. We concluded that percutaneous RF facet rhizotomy is a safe and effective procedure for low back pain patients, especially for those with mechanical low back pain syndrome.

Electrocoagulation

Dapsone maculopathy.

After the injection of about 10 gm of dapsone, a 38-year-old male showed a whitish-yellow patch in the macular region of both eyes, with decreased visual acuity of the counting finger in the right and 0.04 in the left eye. Two weeks after the start of systemic steroid therapy the patch disappeared, and on follow-up at 11 months, visual acuity was 0.02 in the right and 0.08 in the left eye, with macular degeneration and foveal nonperfusion. This retinal damage seems to be ischemic in origin and to be caused by a combination of acute severe peripheral hypoxemia and the vascular obstructive effect of red cell fragmentation resulting from massive hemolysis.

Adult

Intravitreal cysticercosis.

Examination of a 36-year-old man with naked visual acuity of 20/20 revealed a floating, conspicuous cyst of Cysticercus cellulosae in the vitreous cavity of the right eye. A vitreous traction band from the vitreous base and the optic disc was connected to the lodging bulb of the cyst. In the superonasal area, an ovoid retinal break surrounded by a white retinal lesion with two elliptical retinal hemorrhages was found, and this seems to be the previous lodging site of the cyst. A pars plana vitrectomy was performed to remove the parasite, and laser photocoagulation was carried out around the retinal break. Four months after the operation, the patient was satisfied with naked visual acuity of 25/20 without any complication in the affected eye.

Adult

Gamma knife surgery in pituitary microadenomas.

The application of transsphenoidal microsurgery in the management of pituitary microadenoma, long regarded as effective surgical treatment, has had a relatively low mortality and morbidity rate. However early failure and late recurrence has been reported in no small numbers. It has been proposed that stereotactic radiosurgery is an alternative treatment modality. Recent advances in neuroimaging permits precise targeting in radiosurgery of microadenomas. Additionally, a prompt hormonal reduction after the treatment is important for the patients with hormonally active microadenomas. The authors performed Gamma Knife radiosurgery in 27 patients with pituitary adenomas and observed the hormonal changes after radiosurgery in 19 patients with functioning microadenomas (5 with Cushing's disease, 7 with acromegaly, and 7 with prolactinoma). The maximum dose administered ranged from 25 to 75 Gy. The margin of the tumor was encompassed within the 50 to 90% isodose volume. The endocrinological status was assessed pre- and post-operatively. We measured the serum growth hormone and prolactin level, as well as the 24-hour urinary free-cortisol level. Normalization of the hormonal level was achieved in 6 cases, the majority of them within 10 months. The other 6 cases showed marked reduction of hormonal levels (less than 50% of preoperative levels) with a strong possibility of hormonal remission at further follow-up. The remaining 6 were failures. The cure for one case is still pending. It took approximately 1 approximately 3 months after the radiosurgery before the reduction of hormonal secretion began to show up with some improvement of symptoms. When the GKS was successful, hormonal secretion seemed to return to normal within 10 months. Although further follow-up is necessary to evaluate the long-term tumor control rate and hormonal effect, these initial results indicate a potential therapeutic role of radiosurgery in controlling hormone hypersecretion in pituitary microadenomas. Gamma knife radiosurgery is very promising in managing pituitary microadenoma with complementary of the transsphenoidal surgery.

Adenoma

Taxol and related compounds in Korean native yews (Taxus cuspidata).

The concentrations of taxol and related compounds in the bark and needles of Taxus cuspidata grown on Mt. Jiri, Mt. Sobaek, and Cheju Island, and T. cuspidata var. latifolia on Ullung Island in Korea were determined by high performance liquid chromatography (HPLC). The taxane content significantly varied with the location and plant part. The taxol content in the bark of native yews from Mt. Jiri and Mt. Sobaek was high when compared to that reported for Pacific yew (T. brevifolia), whereas bark from trees on Cheju and Ullung islands contained a much lower level. Surprisingly, the needles from Cheju and Ullung islands contained a much higher level of taxol (0.022% and 0.0173%, respectively) than those of intermountain locations (0.0058% to 0.0085%), on the basis of dry weight. The bark and needles of T. cuspidata var. latifolia on Ullung Island also contained relatively high concentrations of 10-deacetylbaccatin III, 0.0497% and 0.0545%, respectively, and indicated that environmental factors may affect the quantity. Taxol in the needles was confirmed by electrospray mass spectrometry. These results suggest that foliage from yew trees growing in their natural habitats on Cheju and Ullung islands may provide a renewable source for taxol.

Chromatography, High Pressure Liquid