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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

Complications after gamma knife radiosurgery for benign meningiomas.

OBJECTIVES: To analyse the results of gamma knife radiosurgery (GKS) for the treatment of intracranial meningiomas and to assess possible factors related to the outcome and complications of such treatment. METHODS: The authors retrospectively reviewed the clinical and radiological data of 179 patients (194 lesions) treated with GKS for meningiomas between May 1992 and October 2000. The mean follow up duration was 37.3 months (range 6.4 to 86.3 months). The study determined the correlation between radiosurgical outcome including imaging changes after GKS and multiple factors such as tumour location and size, patient characteristics, venous sinus status, pre-GKS degree of oedema, other treatment modalities, and radiosurgical parameters. RESULTS: The radiological control rate was 97.1%. Magnetic resonance imaging (MRI) showed complications after GKS in 35 lesions (25.0%) among the 140 lesions followed up with MRI. Complications were divided into peritumorous imaging changes (33 lesions; 23.6%) and transient cranial nerve dysfunction (two lesions; 1.4%). Radiation induced imaging changes were seen mostly in convexity, parasagittal, and falx meningiomas that were deeply embedded in the cortex. About 60% of these were asymptomatic and the overall rate of symptomatic imaging changes was 9.3%. Neurological deficit related to imaging changes developed in only three patients, and all the symptoms were transient. CONCLUSION: GKS for intracranial meningiomas seems to be a safe and effective treatment. However, meningiomas of the convexity, parasagittal region, or falx cerebri have a higher incidence of peritumorous imaging changes after GKS than those of the skull base. Therefore, the use of GKS needs to be considered very cautiously in cerebral hemispheric meningiomas, taking into consideration patient age and general condition, tumour size and location, pattern of cortical embedding, relation between the tumour and venous sinuses, presenting symptoms, and patient preference.

Adolescent↗

Perifusion model for detoxification of drugs in a bioartificial liver.

Detoxification of a drug in a bioartificial liver (BAL) during an in vitro experiment was theoretically carried out based on a perifusion model. The detoxification capacity assay, the rates of disappearance of the chemicals such as flow-limited and enzyme-limited drugs in the BAL system could be defined from models of hepatic perfusion-elimination relationships. When the flow-limited drug administrated under a quasi-equilibrium condition, a two-compartment model for the concentration behavior of the drug was introduced and compared with a one-compartment model. For both models, equations involving hepatic drug clearance and various pharmacokinetic parameters were derived under initial bolus loading and constant-rate infusion plus bolus loading conditions. The concentration of enzyme-limited drug in the BAL decreased linearly with time in contrast with the concentration profile of the flow-limited drug followed by exponential functions. The perifusion model offers a quantitative understanding of the elimination kinetics of chemicals such as flow-limited and enzyme-limited drugs in a bioartificial liver and a comparison between the BAL and human liver.

Anti-Arrhythmia Agents↗

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers.

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Antibodies, Monoclonal↗

Nuclear localization of beta-catenin is an important prognostic factor in hepatoblastoma.

In this study, mutational and immunohistochemical analyses of beta-catenin were performed in 30 hepatoblastomas, to assess the prevalence of alterations of the Wnt pathway with respect to clinicopathological parameters and survival. Four missense mutations of beta-catenin (13.3%) were detected and there was strong immunoreactivity for beta-catenin in the cytoplasm and/or the nucleus in 97% of hepatoblastomas. Nuclear and cytoplasmic staining was demonstrated in 19 of 30 tumours (63%), while ten revealed only cytoplasmic staining. Statistically, this nuclear beta-catenin staining was significantly higher in the embryonal (Fisher exact test; p=0.00393) or undifferentiated type (p=0.00156) of hepatoblastoma than in the fetal type, but there was no difference between clinical stages I and II and clinical stages III and IV (p=0.175). Cumulative survival curves showed that nuclear beta-catenin staining (generalized Wilcoxon test; p=0.0088), undifferentiated histological type (p=0.0305), and clinical stages III and IV (p=0.0107) were significantly correlated with shorter survival time in these patients. Moreover, Cox multivariate analysis provides evidence that nuclear beta-catenin staining is the most important prognostic factor for survival (p=0.0090). It is therefore concluded that immunohistochemical analysis of beta-catenin might be a useful clinical tool for estimating the prognosis for patients with hepatoblastoma.

Biomarkers, Tumor↗

Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide.

We have previously demonstrated that the activation of p53 signaling may contribute to tumor growth inhibition by the CRE-decoy oligonucleotide containing CRE sequence (5'-TGACGTCA-3') (Lee et al., Biochemistry 39, 4863-4868, 2000). However, growth inhibition by CRE-decoy treatment was also observed in tumor cells containing a mutant p53 (Park et al., J. Biol. Chem. 274, 1573-1580, 1999). To understand additional mechanisms of the decoy oligonucleotide, we investigated the effect on cyclin D1 expression and a cyclin D1/Cdk4/retinoblastoma protein (pRB) signaling pathway. Here we show that in MCF7 breast cancer cells the CRE-decoy competed with cyclin D1-CRE (5'-TAACGTCA-3') for binding transcription factors and reduced cyclin D1 gene expression (in reporter gene assay, Northern blotting and Western blotting) to modulate cyclin D1/Cdk4/pRB signaling and G1-S progression in a steady state and/or under estrogen stimulation. Decrease of cyclin D1 protein level by CRE-decoy treatment was also observed in p53-mutated cancer cells. Cyclin D1 expression was also diminished in MCF7 cells stably expressing dominant negative mutant CREB indicating that the nonspecific effect of oligonucleotide or its degradation products could be excluded. These data suggest that inhibition of cyclin D1 expression contributes to the growth inhibition induced by the decoy oligonucleotide in MCF7 cells through a cyclin D1/Cdk4/pRB signaling pathway. Downregulation of cyclin D1 expression also provides a mechanism of CRE-decoy-induced growth inhibition in tumor cells having p53 mutation.

Breast Neoplasms↗

Microvascular decompression of the facial nerve for hemifacial spasm in youth.

OBJECTS: The goal of this study was to investigate the differences between clinical findings in youth and in adulthood on microvascular decompression (MVD) of the facial nerve for the treatment of hemifacial spasm (HFS). METHODS: We retrospectively evaluated 855 patients who underwent MVD from January 1985 to July 1999. In our series of 33 young HFS patients, all patients had definite offending vessels. Interestingly, pathologic tortuous vertebral artery as a possible etiology was more rarely observed in young HFS patients (1/33 patients, 3.0%) than in adult patients (61/822 patients, 7.4%) (P < 0.05). We did not observe any atomical variations of the vessels or any arachnoidal thickening around the root entry zone and cerebellopontine cistern in youths. Furthermore, young HFS patients did not necessarily have poorer surgical outcomes than adult HFS patients. CONCLUSIONS: Our results suggest that the cause and progress of HFS are the same in youth as in adulthood, even though the pathogenesis of early onset remains unclear.

Adolescent↗

Radiologically confirmed de novo glioblastoma multiforme and hippocampal sclerosis associated with the first onset of nonconvulsive simple partial status epilepticus.

The authors report a case of an unusual progression of glioblastoma multiforme in the temporal lobe associated with the first onset of nonconvulsive simple partial status epilepticus (SPSE), a rare form of status epilepticus. The patient underwent a left temporal craniotomy and the tumor was removed. Concurrently, the hippocampus was removed as well. The pathological diagnosis of the tumor and the hippocampus were glioblastoma multiforme and hippocampal sclerosis. The patient's postoperative course was uneventful.

Brain Neoplasms↗

Triangular transchamber suture.

A 64-year-old woman with a fibrous membrane at the lens plane after traumatic loss of all the iris and massive intraocular hemorrhage had posterior chamber intraocular lens (PCIOL) implantation anterior to the fibrous membrane with a triangular transchamber suture to prevent possible PCIOL-corneal touch and enhance the stability of the PCIOL. After 3 years, the PCIOL remained in a good position and visual rehabilitation was satisfactory and without complications.

Eye Injuries↗

Expression of bisecting N-acetylglucosaminyltransferase-III in human hepatocarcinoma tissues, fetal liver tissues, and hepatoma cell lines of Hep3B and HepG2.

In this paper, uridine diphosphate (UDP)-N-acetylglucosamine/beta-D-mannoside beta-1,4 N-acetylglucosaminyltransferase III (GlcNAc-transferase-III C 2.4.1.144) activity was determined in human hepatoma cell lines of Hep3B and HepG2, and also compared with those of normal liver tissues and primary hepatocytes. GlcNAc-transferase-III enzymes of Hep3B and HepG2 were mainly detected in the membrane fraction. When GlcN,GlcN-biant-PA and UDP-GlcNAc were used as substrates, the Km values (4.7 mM for UDP-GlcNAc and 1.1 mM for GlcN, GlcN-biant-PA) of Hep3B GlcNAc-transferase-III were distinguishable from those of HepG2 GlcNAc-transferase-III (6.8 mM for UDP-GlcNAc and 3.4 mM for GlcN,GlcN-biant-PA). Furthermore, Hep3B enzyme in membrane fraction showed about 1.5-fold higher specific activity (1423 pmol/hr/mg) than that of HepG2 (1066 pmol/hr/mg). Normal liver cells and primary adult hepatocytes are characterized by a very low level of GlcNAc-transferase-III activity, whereas human hepatoma cells exhibited high activities. These data were supported by reverse transcription-polymerase chain reaction results, showing that expression of the GlcNAc-transferase-III mRNA increased in proportion to the enzymatic activities. Although the mechanism underlying the induction of this enzyme is unknown, lectin blot analysis showed that oligosaccharides in many glycoproteins were observed in hepatoma cells. By treating hepatocarcinoma cultures that express GlcNAc-transferase-III with inhibitors (tunicamycin, deoxymannojirimycin, and swainsonine) of different steps of the glycosylation, we provide evidence that expression of GlcNAc-transferase-III mRNA is dependent on glycosylation of cellular proteins.

Adult↗

Derivation of pharmacokinetics equations for quantitative evaluation of bioartificial liver functions.

A bioartificial liver (BAL) is an extracorporeal medical device incorporating living hepatocytes in a cartridge. A variety of BALs have been developed and new devices are being introduced. Some of them have been clinically applied and from the results obtained they are claimed to be useful devices for assisting the liver functions of patients. However, there is still uncertainty as to their efficacy and their limitations are not clear. It is important to establish methods to quantitatively evaluate the metabolic and synthetic functions of BAL. In this paper, we derive simple equations for the quantitative evaluation of BAL functions on the basis of pharmacokinetics. Pharmacokinetics was originally developed to understand the processes of absorption, distribution, and elimination of administered drugs. Metabolic functions of the natural liver have been analyzed using pharmacokinetics and values of the useful parameters, clearance (CL) and intrinsic clearance (CLint), have been reported. The metabolic functions of the BAL expressed using values of CL and CLint are easily compared with those of the normal human liver. We believe that our method provides a useful basis for estimating the clinical effectiveness of BAL.

Bioartificial Organs↗

Detection of rifampin-resistant Mycobacterium tuberculosis in sputa by nested PCR-linked single-strand conformation polymorphism and DNA sequencing.

Either PCR-mediated single strand conformation polymorphism (SSCP) analysis or DNA sequencing of rpoB DNA (157 bp) can be used as a rapid screening method for the detection of mutations related to the rifampin resistance of Mycobacterium tuberculosis. However, due to the nonspecific amplification of rpoB DNA from nontuberculous mycobacteria these methods cannot be directly applied to clinical specimens such as sputa. We developed a nested PCR method that can specifically amplify the rpoB DNA of M. tuberculosis on the basis of rpoB DNA sequences of 44 mycobacteria. Nested PCR-linked SSCP analysis and the DNA sequencing method were applied directly in order to detect M. tuberculosis and determine its rifampin susceptibility in 56 sputa. The results obtained by nested PCR-SSCP and DNA sequencing were concordant with those of conventional drug susceptibility testing and DNA sequencing performed with culture isolates.

Antibiotics, Antitubercular↗

Microvascular decompression for hemifacial spasm: a long-term follow-up of 1,169 consecutive cases.

We analyzed the records of 1,169 patients with hemifacial spasm (HFS) who underwent microvascular decompression (MVD) and were followed up for more than 6 months from January 1987. The mean follow-up duration was 23.8 months (6-145 months). Excellent surgical outcome was obtained in 90.5% and good in 4.5%, giving an overall success rate of 95.0%. There was statistically significant relationship between vertebral artery (VA) shift and side of symptom. Permanent facial weakness and hearing impairment were 1.4% and 2.3%, respectively. There were no anatomical differences at the root entry zone (REZ) and significant differences of surgical outcome in young HFS (34 patients). Factors such as type of offender, severity of compression on the facial nerve root, and the degree of decompression of the REZ on postoperative MRI did not correlate with surgical outcome.

Adult↗

Gamma knife radiosurgery for metastatic brain tumors.

We reviewed our series of metastatic brain tumors treated by Gamma Knife Radiosurgery. From May 1992 to January 2001, 115 consecutive patients with 425 lesions were treated over 128 treatment sessions. Forty three patients were known to have died at the end of the recording period. The mean follow-up duration was 11.6 months and mean number of lesions was 3.5. The most common primary sites were lung and breast. Mean tumor volume was 4.2 cm(3) and mean margin dose was 16.2 Gy. 6-month, 1-year, and 18-month survival rates were 73.6, 58, and 46%, respectively. Multivariate analysis revealed that higher KPS scores, no evidence of extracranial metastasis, and controlled primary disease were significantly related to longer survival. Adjuvant whole brain irradiation did not significantly influence on the prolongation of survival time and local control of radiosurgically treated lesions.

Brain Neoplasms↗

Histological characteristics of the pelage skin of rough fur mice (C3H/HeJ- ruf/ruf).

Pelage skin of C3H/HeJ mice homozygous at an autosomal recessive mutant locus, rough fur (ruf) which is located on chromosome 9, was histologically analyzed. Sebaceous glands synthesizing lipids were larger in the mutant mice than in controls in an examination by Sudan IV staining. Electron microscopic analysis of the sebaceous gland showed that lipid droplets were denser in mutant mice than in control mice, and that they were irregular in shape in ruf mice while those of controls were round. Our results suggested that rough fur (ruf) mice might be an animal model for hyperlipogenesis of the pelage skin.

Animals↗

Antiallodynic effects produced by stimulation of the periaqueductal gray matter in a rat model of neuropathic pain.

It has been well documented that there is opioid resistance in neuropathic pain. This indicates that the endogenous opioid system may not be involved effectively in modulating neuropathic pain. The present study sought to determine if activation of the descending pain inhibition system might produce analgesia in the animal neuropathic model we developed. Under ketamine anesthesia, male Sprague-Dawley rats were chronically implanted with stimulating electrodes in the ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of the sciatic nerve branches were severed. Pain sensitivity was measured with a von Frey filament and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain syndrome after transection of the tibial and sural nerves were tested as to the analgesic effects of ventral PAG stimulation for an additional two weeks. Electrical stimulation of the ventral PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed the antiallodynic effects of ventral PAG stimulation. These results suggest that activation of the descending pain inhibition system including the ventral PAG reduces neuropathic pain syndrome and that opiates are involved in this system.

Analgesia↗

Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar lai.

It has been suggested that leptospiral hemolysins are important in the virulence and pathogenesis of leptospirosis. We have isolated an Escherichia coli clone carrying the 7.8kb DNA insert from a genomic library of Leptospira interrogans serovar lai by plaque hybridization using a sequence derived from the sphingomyelinase C gene (sphA) of L. borgpetersenii. The clone showed a clear beta-hemolytic zone on sheep blood agar and high hemolytic activities on both human and sheep erythrocytes in liquid assays. The clone carried at least two genes responsible for the hemolytic activities, encoded by two open reading frames of 1662 and 816 nucleotides, which are named sphH and hap-1 (hemolysis associated protein-1), respectively. The SphH showed 75% homology to the SphA at the amino acid level, and the Hap-1 showed no significant homology in major databases. Interestingly, however, E. coli cells harboring sphH did not show sphingomyelinase or phospholipase activities. Moreover, SphH-mediated hemolysis was osmotically protected by polyethylene glycol 5000, suggesting that the hemolysis is likely to be caused by pore formation on the membrane. The SphH was successfully expressed in E. coli as a histidine (His)-SphH fusion protein. Both sphH and hap-1 were highly conserved among the Leptospira species, except for the absence of sphH in non-pathogenic L. biflexa serovar patoc. We concluded that the SphH is a novel hemolysin of a pathogenic Leptospira species, which may be a putative pore-forming protein.

Amino Acid Sequence↗

Effect of Jindangwon on streptozotocin-induced diabetes.

The inhibitory effects of the traditional herbal medicine Jindangwon (JDW) on streptozotocin (ST)-induced diabetic mellitus were studied using the ST-treated diabetic model. Glucokinase activity of pancreatic islets was severely impaired by ST treatment. However, when ST-treated islets were treated with 1 mg/ml of JDW, the enzyme activities of glucokinase and hexokinase were protected, glucose-6-phosphatase was not. When the effects of JDW on ST-induced ATP/ADP ratio of islets were assayed, JDW was effective in restoring of ATP/ADP ratio. In addition, ST decreased the enzyme activities of PDH, while JDW had a protective effect on the enzyme. ST-induced cGMP accumulation was significantly inhibited by JDW treatment. Furthermore, ST-induced nitrite formation was significantly inhibited by JDW treatment. JDW also showed the suppressed nitrite production in ST-treated pancreatic islet cells. When the islets (200/condition) were treated with ST (5 mM for 30 min), and then JDW was added to the ST-treated cells, 1.0 mg/ml of JDW showed the activated and recovered aconitase activity in pancreatic islet cells. When the effect of ST on the gene expression of pancreatic GLUT2 and glucokinase were examined, the level of GLUT2 and glucokinase mRNA in pancreatic islets was significantly decreased. However, JDW protected and improved the expression of protein and genes, indicating that JDW is effective on ST-induced inhibition of gene expression of GLUT2, glucokinase and proinsulin in islets. These results suggested that JDW is effective in this model to treat ST-induced diabetes.

Adenosine Diphosphate↗

Microinjection of opiates into the periaqueductal gray matter attenuates neuropathic pain symptoms in rats.

We have previously demonstrated that electrical stimulation of the ventral periaqueductal gray matter (PAG) produced analgesia in neuropathic pain in rats. Opioids were also shown to be involved in analgesic effects. This study sought to determine whether opiates microinjected into the ventral PAG produce analgesia. Male Sprague-Dawley rats were chronically implanted with a guide cannula in the PAG under pentobarbital anesthesia and both the tibial and sural nerves were completely cut. Pain sensitivity was postoperatively measured with a von Frey filament and acetone applied to the sensitive area for 1 week. Opioids such as [D-Ala2,N-MePhe4,Gly(ol)5]-enkephalin (DAMGO) and [D-Pen ,D-Pen5]-enkephalin (DPDPE) were injected into the PAG. DAMGO, a mu-opioid agonist, and DPDPE, a delta-opioid agonist, were highly effective in reducing neuropathic pain. These effects were reversed by naloxone. These results suggest that the neurons in the ventral PAG are activated by opioids to produce analgesia and that specific opioid receptors are involved in the descending pain inhibition system from the PAG.

Analgesics, Opioid↗