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Biomedical subjects

D G Kim

Publications and source records attributed to D G Kim.

At least 37 records · Page 2Linked to original sources

Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Base Sequence↗

Establishment and characterization of chromosomal aberrations in human cholangiocarcinoma cell lines by cross-species color banding.

Cholangiocarcinoma (CC), a malignant neoplasm of the biliary epithelium, is usually fatal because of difficulty in early diagnosis and lack of availability of effective therapy. Furthermore, little is known about the genetics and biology of CC. Only a few reports concerning cytogenetic studies of CC have been published, and few cell lines have been established. We recently established four CC cell lines, designated as SCK, JCK, Cho-CK, and Choi-CK, and report the first application of cross-species color banding (RxFISH) and multiple chromosome painting for the characterization of the chromosomal rearrangements of these CC cell lines. Each cell line had unique modal karyotypic characteristics and showed a variable number of numerical and structural clonal cytogenetic aberrations. Chromosomes 3, 6, 7, 8, 12, 14, 17, and 18 were commonly involved in structural abnormalities. Homogeneously staining regions were determined in SCK and JCK, and double minute chromosomes were found in Cho-CK. The chromosomal aberrations of the four CC cell lines were effectively analyzed by RxFISH and FISH with multiple chromosome painting probes. The nonrandom rearrangements suggest candidate regions for isolation of genes related to CC.

Aged↗

Activation of caspase-8 during N-(4-hydroxyphenyl)retinamide-induced apoptosis in Fas-defective hepatoma cells.

We observed that N-(4-hydroxyphenyl)retinamide (4HPR), a chemopreventive and chemotherapeutic agent, effectively induced apoptosis in hepatoma cells. Interestingly, Fas-negative (Hep 3B and PLC/PRF/5) hepatoma cells were shown to be more susceptible to apoptosis induced by 4HPR than were Fas-positive (Hep G2 and SK-HEP-1) hepatoma cells. Thus, we explored the mechanisms underlying 4HPR-induced apoptosis in Fas-defective hepatoma cells. Hep 3B cells stably expressing the dominant-negative Fas-associated death domain (dnFADD) showed no alteration in 4HPR drug susceptibility, but when stably expressing E1B19K, Crm A, or dominant-negative FLICE (dnFLICE), Hep 3B cells were resistant, suggesting that 4HPR-induced apoptosis was mediated by caspase-8 activation. Furthermore, apoptosis could be completely blocked by Z-VAD-FMK (a general caspase inhibitor) or by IETD-CHO (a caspase-8 inhibitor), but was only partially blocked by Ac-DEVD-CMK (a caspase-3 inhibitor), by N-acetyl-L-cysteine (NAC) (an antioxidant), by N-acetyl-leucyl-leucyl-norleucinal (ALLN) (a calpain inhibitor I), or by Z-LEHD-FMK (a caspase-9 inhibitor). Time-sequence analysis of the induction of apoptosis by 4HPR revealed that an initial caspase-8 activation was followed by late mitochondrial cytochrome c release and minor caspase-9 activation, which suggested that caspase-8 activation is the primary upstream regulatory point. Activation of Bid or induction of proapoptotic Bax was not observed during apoptosis. In contrast, Bcl-xL expression was decreased during 4HPR-induced apoptosis. Taken together, these results indicate that 4HPR may be a potential chemotherapeutic drug, which is able to induce apoptosis in Fas-defective hepatoma cells through caspase-8 activation.

Adaptor Proteins, Signal Transducing↗

A cranio-orbital-zygomatic approach to dumbbell-shaped trigeminal neurinomas using the petrous window.

We applied a cranio-orbital-zygomatic approach that extends the temporal craniotomy more posteriorly and minimizes the frontal orbitotomy of an ordinary orbitozygomatic approach in order to provide wide access to the already eroded petrous apices along the long axis of trigeminal neurinomas. We treated seven dumbbell-shaped trigeminal neurinomas between 1991 and 1998 (mean follow-up, 38 months; range, 9 to 109 months). The configuration of the tumor mass was assessed on magnetic resonance imaging by measuring its long diameter in the middle and posterior fossae and the width of petrous erosion. Tumors were then classified into five types based on their distribution over the petrous ridge. Total removal was achieved in six patients, who showed no evidence of tumor recurrence during the follow-up period. The only major complication was one case of anesthesia dolorosa. The one patient with a subtotal removal developed a recurrence 12 months after surgery, in the posterior fossa. The cranioorbital-zygomatic approach could be an effective method for removing dumbbell-shaped trigeminal neurinomas, particularly in cases of wide petrous erosion from the tumor. If, however, the tumor has a larger posterior fossa component, this approach may not provide adequate exposure to achieve a total resection.

Journal Article↗

The Department of Neurosurgery at Seoul National University: past, present, and future.

The Department of Neurosurgery at Seoul National University College of Medicine is one of the oldest neurosurgical departments in Korea, and it is a center of academic leadership in neurosurgery. In September 1957, the department was established by Bo Sung Sim, and it has produced many leaders of neurosurgery in Korea. Chairmen Bo Sung Sim, Kil Soo Choi, Dae Hee Han, and Byung-Kyu Cho each brought special skills and talents to the development of the department. The current and fifth chair, Hyun Jib Kim, assumed the chairmanship in July 2000. The department comprises 11 full-time faculty members, 5 fellows, and 14 residents. More than 1,700 neurosurgical procedures are performed annually in four operating theaters. A gamma knife was installed in 1997, and approximately 200 gamma knife procedures are performed each year. In addition to clinical activities, research and education for graduate and postgraduate students are also particular strengths of the department. This article traces the clinical, academic, and scientific development of the department, its present activities, and its future direction.

Forecasting↗

Chordoid meningioma with polyclonal gammopathy. Case report.

The authors present a case of chordoid meningioma in a 55-year-old woman who manifested headache and personality change. Magnetic resonance imaging of the brain and cerebral angiography demonstrated a mass in the right frontal lobe that resembled a typical convexity meningioma. However, the pathological diagnosis was chordoid meningioma, a rare subtype of this tumor that usually occurs in adolescence and is known to be associated with Castleman syndrome. A meningothelial meningiomatous pattern suggestive of a meningothelial origin was focally present, and cytokeratin-positive squamoid cells were noted in the tumor. The lesion lacked dense infiltration of lymphocytes and plasma cells. Polyclonal gammopathy was the only sign of Castleman syndrome and hypochromic microcytic anemia was absent in this case. Polyclonal gammopathy resolved completely 6 months after total removal of the mass.

Castleman Disease↗

Postoperative spinal seeding of craniopharyngioma. Case report.

The authors present a case of postoperative spinal seeding of papillary craniopharyngioma. This 27-year-old man who had previously undergone subtotal removal of a suprasellar craniopharyngioma was admitted because of low-back and right leg pain. Results of neurological examination showed a limitation in straight-leg raising in the right side with no sensorimotor changes. Magnetic resonance imaging of the lumbar spine demonstrated multiple enhanced intradural extramedullary masses causing spinal cord compression. Pathological examination of the tumor tissue obtained via laminectomy revealed papillary craniopharyngioma, which had the same histological features as those of the previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have been reported; however, the authors believe that this is the first published report of the spinal seeding of craniopharyngioma.

Adult↗

Subdiaphragmatic vagotomy induces NADPH diaphorase in the rat dorsal motor nucleus of the vagus.

Axotomy of the vagal motor neurons by cervical vagotomy induces NADPH diaphorase staining due to increased nitric oxide synthase expression in both the rat dorsal motor nucleus and nucleus ambiguous; furthermore, cerical vagotomy leads to cell death of the dorsal motor nucleus cells. Subdiaphragmatic vagotomy axotomizes the vagal motor cells further from the brainstem than cervical vagotomy, and cuts the fibers running only to the abdominal viscera. Here we report that subdiaphragmatic vagotomy is sufficient to induce NADPH diaphorase staining in the dorsal motor nucleus but does not induce staining in the nucleus ambiguus. Because the neurons of the dorsal motor nucleus do not undergo cell death after subdiaphragmatic vagotomy and are able to re-enervate the gut, the increased nitric oxide synthase expression after distal axotomy may be related more to regeneration than degeneration.

Animals↗

Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398.

Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In hepatocellular carcinoma (HCC), the expression pattern of COX-2 protein has been well correlated with the differentiation grade, suggesting that abnormal COX-2 expression plays an important role in hepatocarcinogenesis. We investigated the expression pattern and clinical significance of COX-2 in HCC tissues. In addition, we evaluated the efficacy of a selective COX-2 inhibitor, NS-398, in three hepatoma cell lines. Thirty-six HCC tissues, 15 hepatoma cell lines, 1 colorectal cell line (HT-29), and 1 fibroblast cell line (SV80) were included in the study. We evaluated serological tests and histological and radiological evaluations of HCC tissues. Immunohistochemical staining for COX-2 was performed on 36 HCC tissues and 17 cancer cell lines. A cell viability assay for growth inhibition of NS-398 in five cell lines was performed. Immunohistochemically, all six well-differentiated HCCs were positive, whereas 83% (10 of 12) of the poorly differentiated HCCs were negative. There was no significant relationship between the intensity of COX-2 expression and the level of alpha-fetoprotein, tumor size, presence of portal vein thrombosis, tumor capsule and metastasis, Tumor-Node-Metastasis staging, and growth types (P > 0.05). According to the cell viability assay, NS-398 suppressed the growth of all cell lines, independent of the degree of COX-2 expression. The inhibitory effect on each cell line was identified in 10 microM NS-398 and was significantly strong in 100 microM NS-398. All cell lines exhibited apoptosis, which was identified by 4'-6-diamidino-2-phenylindole staining. In conclusion, COX-2 may be a determinant of the differentiation grade of HCC, and the inhibition of COX-2 can induce growth suppression of hepatoma cell lines via induction of apoptosis.

Adult↗

The human liver-specific homolog of very long-chain acyl-CoA synthetase is cholate:CoA ligase.

Unconjugated bile acids must be activated to their CoA thioesters before conjugation to taurine or glycine can occur. A human homolog of very long-chain acyl-CoA synthetase, hVLCS-H2, has two requisite properties of a bile acid:CoA ligase, liver specificity and an endoplasmic reticulum subcellular localization. We investigated the ability of this enzyme to activate the primary bile acid, cholic acid, to its CoA derivative. When expressed in COS-1 cells, hVLCS-H2 exhibited cholate:CoA ligase (choloyl-CoA synthetase) activity with both non-isotopic and radioactive assays. Other long- and very long-chain acyl-CoA synthetases were incapable of activating cholate. Endogenous choloyl-CoA synthetase activity was also detected in liver-derived HepG2 cells but not in kidney-derived COS-1 cells. Our results are consistent with a role for hVLCS-H2 in the re-activation and re-conjugation of bile acids entering liver from the enterohepatic circulation rather than in de novo bile acid synthesis.

Amino Acid Sequence↗

L-Pipecolic acid oxidase, a human enzyme essential for the degradation of L-pipecolic acid, is most similar to the monomeric sarcosine oxidases.

L-Pipecolic acid oxidase activity is deficient in patients with peroxisome biogenesis disorders (PBDs). Because its role, if any, in these disorders is unknown, we cloned the associated human gene and expressed its protein product. The cDNA was cloned with the use of a reverse genetics approach based on the amino acid sequence obtained from purified L-pipecolic acid oxidase from monkey. The complete cDNA, obtained by conventional library screening and 5' rapid amplification of cDNA ends, encompassed an open reading frame of 1170 bases, translating to a 390-residue protein. The translated protein terminated with the sequence AHL, a peroxisomal targeting signal 1. Indirect immunofluorescence studies showed that the protein product was expressed in human fibroblasts in a punctate pattern that co-localized with the peroxisomal enzyme catalase. A BLAST search with the amino acid sequence showed 31% identity and 53% similarity with Bacillus sp. NS-129 monomeric sarcosine oxidase, as well as similarity to all sarcosine oxidases and dehydrogenases. No similarity was found to the peroxisomal D-amino acid oxidases. The recombinant enzyme oxidized both L-pipecolic acid and sarcosine. However, PBD patients who lack the enzyme activity accumulate only L-pipecolic acid, suggesting that in humans in vivo, this enzyme is involved mainly in the degradation of L-pipecolic acid.

Amino Acid Sequence↗

Clinical feature and outcome of pediatric cerebrovascular disease: a neurosurgical series.

To investigate the clinical features and surgical outcome of pediatric cerebrovascular disease (CVD), we retrospectively reviewed 280 children (up to 15 years of age) who underwent neurosurgical procedures for CVD between 1979 and 1998. Open surgery (n=448), endovascular procedures (n=22), and stereotactic radiosurgery (n=14) were the main neurosurgical procedures adopted. Clinical features and surgical outcomes were described according to the etiology of the CVD and the number of years of management. The mean duration of follow-up was 34 months. The mean age was 7.1 years, and the male-to-female ratio was 1.2:1. The most frequent CVD was moyamoya disease (62%). The surgical mortality related to CVD was 0.7%. Eighty-seven percent had Karnofsky Performance Scale scores of more than 70. We demonstrate increasing detection rates and improving outcomes in recent years. The clinical course in this study shows that recovery from CVD in children is good after neurosurgical procedures.

Adolescent↗

Meningioma manifesting intracerebral haemorrhage: a possible mechanism of haemorrhage.

We present a possible mechanism of intracerebral peritumoural haemorrhage in meningioma based on the clinical data of three of our cases. A meningioma manifesting intracerebral haemorrhage is uncommon and some sporadic case reports have been presented, but without any proven mechanisms. We are presenting three cases of convexity meningioma manifesting spontaneous intracerebral haemorrhage with apoplectiform onset. All three patients had no evidence of bleeding tendency or other predisposing factors for haemorrhage. Preoperative radiological studies showed a solid mass attached to the dura with intracerebral peritumoural haematoma. Total removal of the tumour and haematoma could be achieved in every case. Histological investigation revealed extensive tumour infarction in two cases and fibrosis related to pre-existing ischaemia in the other case. The diagnoses were atypical meningioma in two cases and transitional type in one case. We suggest that extensive tumour infarction might be a cause of spontaneous intracerebral peritumoural haemorrhage in our series of patients.

Aged↗

Endobronchial tuberculosis with expectoration of tracheal cartilages.

A case of endotracheal tuberculosis with expectorations of the lateral one-third of the multiple tracheal cartilages is reported. Fibreoptic bronchoscopy revealed caseous materials and loosening of the tracheal cartilages. The patient expectorated cartilaginous material several times before and after fibreoptic bronchoscopy. In spite of the loss of tracheal cartilages, tracheal lumen was maintained with a mild airflow limitation. The remaining two-thirds of the tracheal cartilage rings seemed to be strong enough to support the tracheal lumen opening during the respiratory cycle. Although rare, expectoration of bronchial cartilage can be one of the clinical features of endobronchial tuberculosis.

Adult↗

In vivo proton magnetic resonance spectroscopy of central neurocytomas.

OBJECTIVE: The authors report on the metabolic features of central neurocytomas observed during in vivo single-voxel proton magnetic resonance spectroscopy. METHODS: Volume-selective single-voxel proton magnetic resonance spectroscopy was performed with a 1.5-T unit using a point-resolved spectroscopy sequence (TR/TE = 2000 ms/135 and 270 ms) to obtain spectra of a single 8-cc voxel. The subjects were five patients in the Department of Neurosurgery of Seoul National University Hospital whose central neurocytomas had been diagnosed histologically. The peak intensities of compounds containing choline (Cho), N-acetylaspartate, creatine/phosphocreatine, and lactate were analyzed. RESULTS: The ratios of Cho to creatine/phosphocreatine and Cho to N-acetylaspartate were significantly higher than ratios in normal brains. A lactate signal was present, and an unidentified signal was also observed at 3.55 ppm, which might have been produced by inositol or glycine. CONCLUSION: A combination of the signal at 3.55 ppm and a prominent Cho peak seems to be a characteristic feature of central neurocytomas. Volume-selective single-voxel proton magnetic resonance spectroscopy could provide additional information to aid in diagnosing this condition.

Adolescent↗

Brain abscess related to metal fragments 47 years after head injury. Case report.

The authors report a case of symptomatic brain abscess in a 51-year-old man who presented with personality changes and generalized seizures. He had survived a grenade explosion injury during the Korean War 47 years previously. Computerized tomography scanning revealed multiple conglomerate rim-enhancing lesions and metallic foreign bodies in the right frontal lobe. The mass was totally removed and Pseudomonas aeruginosa was isolated from microbial cultures. Retained foreign bodies in the brain, whether bone or metal, should be removed at the time of injury if at all possible. If this cannot be accomplished, patients with such retained foreign bodies should be carefully monitored for life.

Brain Abscess↗

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

Neonatal footshock stress alters adult behavior and hippocampal corticosteroid receptors.

To determine the effects of stress early in life on adult behavior and hippocampal corticosteroid receptors, rats were exposed to footshocks (0.8 mA, 60 times/day, randomly apart) on postnatal days 14, 17 and 20. When they reached 6 months of age, neurobehavioral alterations were measured. The footshock-experienced rats learned more rapidly in the autoshaped learning test than similarly handled controls. They also stabilized more quickly after exposure to a novel environment than the handled controls, but only at the same rate as animals which had not been handled except for weighing. The density of [3H]dexamethasone binding sites increased and that of [3H]corticosterone binding sites decreased in the hippocampi of these rats. These results indicate that early life stress results in altered behavior and hippocampal corticosteroid receptors at adulthood, and suggest that the mineralocorticoid and the glucocorticoid receptors are differentially regulated by early life stress.

Animals↗