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Biomedical subjects

D H Nam

Publications and source records attributed to D H Nam.

At least 19 recordsLinked to original sources
PubMed2001

The detection of p53 gene mutation using a microdissection technique in primary intracranial germ cell tumors.

Using a microdissection technique, the contribution of the p53 mutation to tumorigenesis and prognosis in each histological subtype of the intracranial germ cell tumors (GCTs) was evaluated. Nineteen patients had primary intracranial GCTs, including 4 germinomas (GEs), 4 teratomas (TEs), 1 mixed tumor of GE and TE, and 10 mixed GCTs containing non-germinomatous malignant germ cell tumors (NG-MGCTs). After microdissection of specific subtypes, genomic DNA was screened for mutations in exons 5-8 of the p53 gene, using the dideoxyfingerprinting (ddF) followed by direct DNA sequencing. The direct sequencing revealed a total of six mutations in PCR products derived from the five cases (26%) which showed mobility shifts in ddF. Among the six mutations detected, four were missense mutations and two were silent. Missense mutations of the p53 gene tended to occur more frequently in the NG-MGCT component than in the GE or TE components (3/15 vs. 1/12 vs. 0/13). The incidence of missense mutations was not different between the survivors (3/13) and the deceased (1/6). This study suggests the possible role of the p53 gene in the tumori-genesis of NG-MGCT. However, p53 gene mutation did not correlate with the prognosis of NG-MGCT.

Adult↗
PubMed2000

Induction of apoptosis by capsaicin in A172 human glioblastoma cells.

Capsaicin induced apoptosis of A172 human glioblastoma cells in a time- and dose-dependent manner. Neither capsazepine, a vanilloid receptor antagonist, nor bis-(o-aminophenoxy)-ethane-N,N,N', N'-tetraacetic acid/acetoxymethyl ester (BAPTA/AM), an intracellular Ca(2+) chelator, significantly inhibited the capsaicin-induced apoptosis, although capsaicin increased intracellular Ca(2+) level. Capsaicin markedly reduced the basal generation of reactive oxygen species (ROS) and lipid peroxidation. Exogenous application of H(2)O(2) significantly prevented the cells from the apoptosis by capsaicin. Treatment with N-acetyl cysteine alone induced both reduction of the basal production of ROS and apoptosis. Taken together, these results suggest that capsaicin induced apoptosis in A172 cells and that vanilloid receptors and intracellular Ca(2+) may not be involved in the apoptotic mechanism of capsaicin. Reduction of the basal generation of ROS may play a role in the induction of apoptosis by capsaicin.

Apoptosis↗
PubMed2000

Vascular endothelial growth factor expression under ischemic stress in human meningiomas.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific antigen and angiogenic factor that plays a role in angiogenesis. We analyzed the expression of four VEGF mRNA isoforms in meningiomas. Among 35 meningiomas, 11 came from patients who underwent complete (n=4) or partial (n=7206=189 in all samples. However, the VEGF121 and 165 isoforms were significantly upregulated in samples from patients who underwent partial preoperative embolization. The diffusible VEGF121 isoform may be important for vascularity and edema formation in meningiomas.

Adolescent↗
PubMed2000

Effects of flupyrazofos on liver microsomal cytochrome P450 in the male Fischer 344 rat.

1. The effects of flupyrazofos on liver microsomal cytochrome P450 were investigated in the male Fischer 344 rat. When rats were treated intraperitoneally with flupyrazofos for 3 consecutive days, the activities of ethoxyresorufin O-deethylase and testosterone 2 beta-hydroxylase were significantly reduced, whereas the activities of pentoxyresorufin beta-depentylase and testosterone 6beta- and 7 alpha-hydroxylases were induced in liver microsomes. 2. Within 24 h after treatment with 50 m kg(-1) flupyrazofos, most enzyme activities were decreased, indicating the interaction of flupyrazofos with cytochrome P450. 3. In Western immunoblotting, cytochrome P4502B1/2 proteins were clearly induced by treatment with flupyrazofos, whereas P4501A1/2 and 2C6 proteins were reduced in liver microsomes. 4. The present results indicate that flupyrazofos modulates the expression of cytochrome P450 in rat.

Animals↗
PubMed2000

Surgical treatment of intractable epilepsy accompanying cortical dysplasia.

OBJECT: Surgical treatment of cortical dysplasia (CD) together with intractable seizures is challenging because both visualization and localization of the lesion are difficult, correlation with seizure foci requires comprehensive study, and the surgical outcomes reported thus far are unsatisfactory. The authors report their experience in the surgical treatment of CD classified according to a surgical point of view. METHODS: The definition of CD used in this study was a dysplastic lesion visible on magnetic resonance (MR) images or a lesion that, although not visible on MR images, was diagnosed as moderate-to-severe dysplasia by using pathological analysis. During the last 4.5 years, the authors treated 36 patients with intractable epilepsy accompanied by CD. They divided the 36 cases of CD into four characteristic groups: Group A, diffuse bilateral hemispheric dysplasia; Group B, diffuse lobar dysplasia; Group C, focal dysplasia; and Group D, a moderate to severe degree of CD with a normal appearance on MR images. All but one patient in Group C were monitored in the epilepsy monitoring unit by using subdural electrodes for seizure localization and functional mapping. The incidence of CD among a cohort of 291 patients who had undergone epilepsy surgery at the authors' center during the study period was 12.4%. The mean age of the 36 patients was 21.3 years and the mean age at seizure onset was 8.5 years. The mean follow-up period was 26 months. Twenty-six patients (72.2%) belonged to Engel Class I or II (20 and six, respectively). There were five cases in Group A, nine in Group B, nine in Group C, and 13 in Group D. Patients in Groups A and B were significantly younger at seizure onset and had significantly poorer surgical outcomes compared with patients in Groups C and D (p < 0.05). If outcome is compared on the basis of the extent of removal of CD, patients in whom CD was completely removed had significantly better outcomes than those in whom CD was only partially removed (p < 0.001). CONCLUSIONS: The authors conclude that intractable epilepsy accompanied by CD can be treated surgically using comprehensive preoperative approaches. Deliberate resective procedures aimed at complete removal of dysplastic tissue ensure excellent seizure control without permanent neurological deficit.

Adolescent↗
PubMed2000

The effect of isochromosome 17q presence, proliferative and apoptotic indices, expression of c-erbB-2, bcl-2 and p53 proteins on the prognosis of medulloblastoma.

Medulloblastoma accounts for 20 to 25% of all intracranial neoplasms in children. The significance of the presence of isochromosome 17q (i(17q)), proliferative potential, apoptotic activity, and expression of c-erbB-2, bd-2, and p53 proteins in predicting long-term survival of patients with medulloblastomas was investigated. Twenty children were divided into two groups (favorable and poor outcome groups). Ten children with favorable outcome (FO) were disease-free during the follow-up period (median: 61.5 months). The other ten children with poor outcome (PO) died of disease progression, having a median survival of 18 months. Fluorescent in situ hybridization (FISH) for i(17q), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry for Ki-67, c-erbB-2, bcl-2, and p53 proteins was performed in these patients. Nine out of 17 children showed i(17q). There was no difference in the rate of positive i(17q) between the FO and PO groups. The presence of i(17q) was not significantly related to biological factors that we investigated. Unlike the prominent presence of the proliferative potential and p53 expression in children with PO, apoptotic activity and expression of c-erbB-2 and bcl-2 had no correlation with the outcome.

Adolescent↗
PubMed1999

A simple method of predicting hormonal outcome in children with intracranial germinoma.

Even a small intracranial germinoma (GE) frequently provokes pituitary hypofunction. We evaluated the relationships between preoperative hormonal status and hormonal outcome and between size of suprasellar mass and hormonal outcome in 22 children with intracranial pure GE to determine whether or not these can reflect the degree of hypothalamo-pituitary axis destruction. Preoperative hormonal status was graded from I to IV according to the serum prolactin level (s-PRL) and thyroid function (TF). The hormonal outcome was estimated by the type and the number of hormonal replacement medications taken on the basis of the triple load test and endocrinological examinations at the time of the last follow-up (median period: 43 months). Fifteen of the 22 patients had suprasellar lesions. All 13 patients who had diabetes insipidus (DI) at presentation needed desmopressin acetate (DDAVP) during the follow-up period. The correlation between increment of preoperative grade and the increment in the number of hormones to be replaced was statistically significant (P<0.05). This preoperative grading was a more reliable predictor than the size of suprasellar tumor. In conclusion, preoperative grading by s-PRL and TF test is useful for the prediction of posttreatment hormonal replacement in children with intracranial pure GE.

Adolescent↗
PubMed1999

Treatment of intracranial nongerminomatous malignant germ cell tumor in children: the role of each treatment modality.

To investigate the role of surgical tumor resection, radiotherapy and chemotherapy, the outcome of treatment in 17 children with nongerminomatous malignant germ cell tumor (NG-MGCT) was reviewed. The median follow-up period was 38 months after diagnosis, and the overall 3-year survival rate was 75%. Eleven patients who underwent craniospinal radiation (CSRT) did not receive chemotherapy. In 4 of them more than 90% of the tumor was removed, and they were free of disease at 16, 30, 93 and 111 months after surgery. Among the other 7, who did not undergo tumor resection (n=5) or had considerable residual tumor (n=2), 2 were disease-free at 73 and 88 months after diagnosis, and 5 died of recurrences. Of 6 patients who received cisplatin and etoposide chemotherapy in addition to CSRT, none showed intracranial recurrence, regardless of the extent of removal. The authors believe that multimodal treatment is the preferred choice and that chemotherapy plays an important role, especially when a significant amount of tumor remains after surgery. CSRT plays a major role at least in some patients. If chemotherapy is not feasible, radical removal plus CSRT seems to be an alternative.

Adolescent↗
PubMed1999

Supratentorial primitive neuroectodermal tumor in children: clinical features, treatment outcome and prognostic factors.

To investigate clinical features, treatment outcome and prognostic factors of pediatric supratentorial primitive neuroectodermal tumors(ST-PNETs), 28 ST-PNET cases were retrospectively analyzed. The prognostic importance of age, sex, size of tumor, M stage, extent of surgical resection, histological features, immunohistochemical labelling indices (Ki-67, p53), and apoptotic index were assessed. The mean age at diagnosis was 6.8 years, and the male-to-female ratio was 18:10. The presenting symptoms in 22 cases were increased intracranial pressure and focal neurological deficits. Gross total resection was achieved in 17 cases, near-total (>90%) resection in 3, and subtotal in 7; biopsy was performed in 1 case. The mean duration of follow-up was 37 months. For 25 patients who completed planned adjuvant therapy, the 3-year survival rate was 73%. Univariate analysis showed that the presence of tumor necrosis (P=0.002) and extent of resection (P=0.04) correlated with survival. Patients with a high Ki-67 labelling index (>10%) tended to have shorter survival (P=0.095). In multivariate analysis, tumor necrosis showed statistical significance(P=0.03).

Adolescent↗
PubMed1998

Intramedullary anaplastic oligodendroglioma in a child.

Primary intramedullary anaplastic oligodendroglioma is a rare tumor, only four cases of which have been reported. The authors present the case of a 38-month-old boy with primary intramedullary anaplastic oligodendroglioma. He underwent partial removal of the tumor and spinal radiation therapy. The residual tumor disappeared 12 months after radiation, and 48 months after treatment there was no evidence of recurrence. This case shows that in primary intramedullary anaplastic oligodendroglioma, postoperative radiation therapy confined to the spinal cord can yield an optimal result.

Child, Preschool↗
PubMed1998

Brain tumor in the first year of life: a single institute study.

Brain tumors in infants present special diagnostic and therapeutic challenges. To figure out the clinical features, pathological classification of the tumors and the treatment outcome of infantile brain tumors, 458 children (age<16) with brain tumors were reviewed retrospectively. Among them 21 cases (4.6%) were diagnosed during the first 12 months of life. Two tumors were definitely of congenital origin. The majority of infants with brain tumors presented with increased intracranial pressure. Fourteen tumors were located at the supratentorial area. Sixteen cases had neuroepithelial tumors; astrocytoma (optic pathway), supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma were found in three cases each. There were two treatment-related mortalities. Compared with the outcomes in older children, the treatment outcome was poorer in medulloblastoma and the optic pathway glioma which showed a higher growth potential. Because of the limited application of postoperative adjuvant therapy, radical surgical removal played a more important role in this age group. The prognosis of patients in whom the tumors could not be totally removed, largely depended on the pathological malignancy of the tumors. Though the treatment outcome was not always dismal, immaturity of the brain, higher growth potential, perioperative risks, limitations in adjuvant therapy, and pessimistic attitude on the part of parents made management more challenging.

Adolescent↗
PubMed1997

Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6- fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304).

New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C5-NH2) > F (C5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C5-NH2) > naphthyridine = F (C5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (microgram/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Actinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

Animals↗
PubMed1997

Moyamoya disease in adults: characteristics of clinical presentation and outcome after encephalo-duro-arterio-synangiosis.

To determine the clinical characteristics and the effectiveness of encephalo-duro-arterio-synangiosis (EDAS) in adulthood-onset Moyamoya disease (MMD), the authors retrospectively reviewed 26 patients suffering from MMD who were admitted to Seoul National University Hospital between 1987 and 1995. When they showed major symptoms, all were more than 16 years-old. The most common presenting symptom was intracranial hemorrhage (ICrH), found in 12 patients or 46% of the total; the second was infarction and transient ischemic attack, each found in seven or 27% of them. Only one patient was found to have seizures, which were associated with a cerebral infarction. The Suzuki angiographic stage 3 and less than stage 3 accounted for 73% of all 52 hemispheres. A total of 15 patients underwent single photon emission computed tomography (SPECT) preoperatively. When the derangement of cerebral perfusion was estimated with four SPECT grades (SG), 70% of their hemispheres revealed normal (SG1) or localized decreased-perfusion (SG2). The other 30% had extensive decreased-perfusion or localized perfusion defects (SG3). There was no case who had extensive perfusion defects (SG4). A total of 17 patients underwent EDAS operations (EDAS group) and nine did not undergo any operation (no-op group). The EDAS group had significantly better clinical outcomes than the no-op group after a 12-month median follow-up period (P < 0.05). The angiographic and SPECT follow-up studies comprised six and seven cases, respectively. There was also satisfactory angiographic revascularization in all follow-up cases and improvement in cerebral perfusion at SPECT follow-up in six of seven cases. It is concluded that the involvement of posterior circulation of MMD is not frequent and cerebral perfusion is preserved in adulthood-onset MMD patients. These findings may explain the reason why hemorrhages are frequent and the late onset of symptoms in adulthood-onset MMD. Surgical treatment with EDAS seems to be effective in adulthood-onset MMD in terms of clinical improvement.

Adolescent↗
PubMed1996

Primary central nervous system lymphoma: variety of clinical manifestations and survival.

A retrospective analysis of 23 non-immune compromised patients with primary central nervous system lymphoma (PCNSL) is reported. The patients consist of 14 males and 9 females and the median age is 50 years. Most patients presented with focal neurological deficits or symptoms of increased intracranial pressure (ICP) due to mass effects around the periventricular area. However, there were four cases of diffuse type, one case of intramedullary tumour, and four cases with rapid disease progression. All the patients underwent histological confirmation by craniotomy (16 cases) or stereotactic biopsy (7 cases). The radiation therapy started after histological diagnosis in all and 6 cases received additional chemotherapy. The median survival after diagnosis of overall patients was 23 months. Six patients are in disease free status at a mean of 35 months follow-up. The uni- and multi-variative risk analysis revealed five favourable factors on survival: (1) age less than 60 years (0.05 < p < 0.1); (2)pre-operative Karnofsky performance scale (KPS) > or = 70 (p < 0.05); (3) symptom duration over four weeks (p < 0.05); (4) radiation dosage > or = 5500 cGy (p < 0.05); (5)absence of malignant cells in cerebrospinal fluid (CSF) (p < 0.05). The most frequent site of recurrence was the local area as shown in seven cases out of 11 recurrent cases. But six patients had diffuse recurrence (4 cases), systemic recurrence (2 cases), and drop metastasis (1 case). Although the recurred PCNSL had rapid progression and a grave prognosis, aggressive treatment prolonged the postrecurrence survival time significantly. Our experience suggests that 1) there are various clinical and radiological presentations and progressions of the disease; 2) treatment method should be decided along with the clinical presentation, progression of disease, and prognostic factors; 3) early diagnosis and early detection of recurrence enable the start of definitive treatment when the medical condition is still satisfactory.

Adult↗
PubMed1985

Relationship between butirosin biosynthesis and sporulation in Bacillus circulans.

The relationship between butirosin biosynthesis and certain biochemical characteristics related to sporulation in a strain of Bacillus circulans NRRL B-3313 was examined. The cellular content of dipicolinic acid increased while the amount of poly-beta-hydroxybutyrate decreased with changes in antibiotic productivity. Oligosporogenous mutants failed to synthesize the antibiotic and to degrade poly-beta-hydroxybutyrate. These observations suggest that spore formation may be related to antibiotic production in this strain of B. circulans.

Anti-Bacterial Agents↗
PubMed1984

An improved synthesis of captopril.

An improved synthesis of captopril using methacrylic acid as the starting material is described. Treatment of methacrylic acid (I) with a hydrogen halide gave the 3-halogeno-2-methylpropanoic acids II and III, which were treated with thionyl chloride to yield the corresponding 3-halogeno-2-methylpropanoyl chlorides IV and V. Treatment of IV or V with L-proline yielded the N-(R,S-3-halogeno-2-methylpropanoyl)-L-prolines VI and VII, which were separated into optically pure R- and S-diastereoisomers using dicyclohexylamine. Treatment of halides of VI or VII with methanolic ammonium hydrosulfide gave captopril in 28% yield.

Captopril↗
PubMed1984

Enzymatic synthesis of phenoxymethylpenicillin using Erwinia aroideae enzyme.

Enzymatic synthesis of phenoxymethylpenicillin from 6-aminopenicillanic acid and phenoxyacetic acid methyl ester was attempted by using partially purified alpha-acylamino-beta-lactam acylhydrolase I (ALAHase I) enzyme from Erwinia aroideae NRRL B-138. The reaction rates were carefully followed by determination of 6-aminopenicillanic acid (6-APA), phenoxymethylpenicillin (PNV), phenoxyacetic acid (POA), phenoxyacetic acid methyl ester (POM), and phenoxyacetylglycine (POG) using high performance liquid chromatography. Among the acyl donors tested, POM gave the highest yield (12.2% based on 6-APA). The overall conversion increased almost linearly with an increase in molar ratio of POM to 6-APA up to 4:1. The effects of organic solvents on the overall yield were also evaluated. Some improvement of PNV yield was observed when ethanol, 2-propanol, and acetone were used. ALAHase I was found to carry out three reactions simultaneously: transfer of acyl group to acyl acceptor to form semisynthetic beta-lactam antibiotic; hydrolysis of acyl donor in amide or ester bond, and hydrolysis of semisynthetic beta-lactam antibiotic which was produced by the enzyme. It was also observed that the hydrolysis reactions of POM and PNV were irreversible in this reaction system. The optimal pH for the three reactions was different. They were: pH 9.0 for POM hydrolysis, 6.8 for the transfer of phenoxyacetyl group to 6-APA, and 6.0 for the PNV hydrolysis. The apparent Km values for POM, 6-APA and PNV were estimated as 33, 25 and 31 mM, respectively.

Erwinia↗