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Biomedical subjects

D H Nam

Publications and source records attributed to D H Nam.

30 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Biochemical properties of penicillin amidohydrolase from Micrococcus luteus.

Some biochemical properties of whole-cell penicillin amidohydrolase from Micrococcus luteus have been studied. This whole-cell enzyme showed its maximal activity at 36 degrees C at pH 7.5. It was found that the activation energy of this enzyme was 8.03 kcal (ca. 33.6 kJ) per mol, and this amidohydrolase showed first-order decay at 36 degrees C. The penicillin amidohydrolase was deactivated rapidly at temperatures above 50 degrees C during storage or preincubation for 24 h. The Michaelis constant, Km, for penicillin G was determined as 2.26 mM, and the substrate inhibition constant, Kis, was 155 mM. The whole-cell penicillin amidohydrolase from M. luteus was capable of hydrolyzing penicillin G, penicillin V, ampicillin, and cephalexin, but not cephalosporin C and cloxacillin. This whole-cell enzyme also had synthetic activity for semisynthetic penicillins or cephalosporins from D-(--)-alpha-phenylglycine methyl ester and 6-alpha-aminopenicillanic acid or 7-amino-3-deacetoxycephalosporanic acid.

Amidohydrolases↗

Pineal tumors: experience with 48 cases over 10 years.

The authors retrospectively reviewed 48 patients treated at Seoul National University Hospital (SNUH) between 1986 and 1995. There were 35 children and 13 adults, accounting for 10.1% of 345 pediatric and 0.68% of 1914 adult brain tumors in SNUH during the same period. The 48 cases consisted of 33 cases of germ cell tumor (69%, GCT); 6 of pineoblastoma (PB, 12.5%); 3 of pineocytoma (PC, 6.3%); 3 of anaplastic astrocytoma (6.3%); 1 of astrocytoma; 1 of glioblastoma; and 1 of ependymoma. The median age was 13 years (range 1-59) and the male-to-female ratio was 3.36:1. The most frequent presenting symptom was due to increased intracranial pressure (90%), followed by Parinaud syndrome or diplopia (50%). Patients with a benign tumor, such as teratoma (TE), astrocytoma, or ependymoma, underwent surgery by the occipital transtentorial approach (OTT) for attempted radical resection without adjuvant therapy, while patients with immature teratoma (imTE), PC, and anaplastic astrocytoma underwent regional radiotherapy (RT) after debulking via OTT. Seven patients with nongerminomatous malignant GCT (NG-MGCT) and 3 with germinoma (GE) underwent craniospinal radiation only, 6 with GE, a NG-MGCT, and 2 with GE+TE received craniospinal radiotherapy (CSRT) after debulking via OTT. Three patients with GE, 4 with NG-MGCT, and 3 with PB underwent radiochemotherapy after debulking via OTT. Forty-four patients were followed up after treatment. The median follow-up period was 36 months. All patients with GE were alive after RT at 36 months (median) of follow-up (range 7-70 months). All with GE+TE and TE were alive. Three patients with PC or astrocytoma were also alive with stable or no evidence of disease. In 1 of the 3 cases of imTE there was a recurrence. However, 4 patients with NG-MGCT died, all of whom had undergone CSRT only; 2 PB patients were alive (12, 19 months), 1 in a moribund status (36 months), and 2 were dead (6, 60 months). The overall mean survival time with pineal tumors was 66 months and the 3-year survival rate was 84% with minimal posttreatment complications. It is concluded that pineal region tumors have male and childhood predominances, and the most common tumor is GCT. The majority of pineal region tumors are malignant. Pineal region tumors can be approached safely and effectively and the surgical complications are mostly transient. Their prognosis is dependent on the pathologies and treatment modalities.

Adolescent↗

Recent progress in biomolecular engineering.

During the next decade or so, there will be significant and impressive advances in biomolecular engineering, especially in our understanding of the biological roles of various biomolecules inside the cell. The advances in high throughput screening technology for discovery of target molecules and the accumulation of functional genomics and proteomics data at accelerating rates will enable us to design and discover novel biomolecules and proteins on a rational basis in diverse areas of pharmaceutical, agricultural, industrial, and environmental applications. As an applied molecular evolution technology, DNA shuffling will play a key role in biomolecular engineering. In contrast to the point mutation techniques, DNA shuffling exchanges large functional domains of sequences to search for the best candidate molecule, thus mimicking and accelerating the process of sexual recombination in the evolution of life. The phage-display system of combinatorial peptide libraries will be extensively exploited to design and create many novel proteins, as a result of the relative ease of screening and identifying desirable proteins. Even though this system has so far been employed mainly in screening the combinatorial antibody libraries, its application will be extended further into the science of protein-receptor or protein-ligand interactions. The bioinformatics for genome and proteome analyses will contribute substantially toward ever more accelerated advances in the pharmaceutical industry. Biomolecular engineering will no doubt become one of the most important scientific disciplines, because it will enable systematic and comprehensive analyses of gene expression patterns in both normal and diseased cells, as well as the discovery of many new high-value molecules. When the functional genomics database, EST and SAGE techniques, microarray technique, and proteome analysis by 2-dimensional gel electrophoresis or capillary electrophoresis in combination with mass spectrometer are all put to good use, biomolecular engineering research will yield new drug discoveries, improved therapies, and significantly improved or new bioprocess technology. With the advances in biomolecular engineering, the rate of finding new high-value peptides or proteins, including antibodies, vaccines, enzymes, and therapeutic peptides, will continue to accelerate. The targets for the rational design of biomolecules will be broad, diverse, and complex, but many application goals can be achieved through the expansion of knowledge based on biomolecules and their roles and functions in cells and tissues. Some engineered biomolecules, including humanized Mab's, have already entered the clinical trials for therapeutic uses. Early results of the trials and their efficacy are positive and encouraging. Among them, Herceptin, a humanized Mab for breast cancer treatment, became the first drug designed by a biomolecular engineering approach and was approved by the FDA. Soon, new therapeutic drugs and high-value biomolecules will be designed and produced by biomolecular engineering for the treatment or prevention of not-so-easily cured diseases such as cancers, genetic diseases, age-related diseases, and other metabolic diseases. Many more industrial enzymes, which will be engineered to confer desirable properties for the process improvement and manufacturing of high-value biomolecular products at a lower production cost, are also anticipated. New metabolites, including novel antibiotics that are active against resistant strains, will also be produced soon by recombinant organisms having de novo engineered biosynthetic pathway enzyme systems. The biomolecular engineering era is here, and many of benefits will be derived from this field of scientific research for years to come if we are willing to put it to good use.

Animals↗