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Biomedical subjects

Y W Kim

Publications and source records attributed to Y W Kim.

At least 91 records · Page 5Linked to original sources

Septic arthritis versus transient synovitis at MR imaging: preliminary assessment with signal intensity alterations in bone marrow.

PURPOSE: To find any differential magnetic resonance (MR) imaging findings between septic arthritis and transient synovitis in pediatric patients. MATERIALS AND METHODS: The MR imaging findings in nine pediatric patients with septic arthritis and 14 with transient synovitis were retrospectively studied. The diagnoses were made by means of joint aspiration with bacteriologic study, arthrotomy, and clinical evaluation. MR imaging findings were analyzed with emphasis on the grade of joint effusion and alterations in signal intensity in the soft tissue and bone marrow of the affected hip joint. RESULTS: Signal intensity alterations in bone marrow (i.e., low signal intensity on fat-suppressed gadolinium-enhanced T1-weighted spin-echo images and high signal intensity on fat-suppressed T2-weighted fast spin-echo images) were seen in eight of nine patients with septic arthritis. These signal intensity alterations consisted of mild juxtaarticular changes in six patients without osteomyelitis and extensive changes in the femoral head and neck in two patients with coexistent osteomyelitis. Signal intensity alterations in bone marrow were not seen in the 14 patients with transient synovitis. CONCLUSION: Signal intensity alterations in the bone marrow of the affected hip joint are useful in the differentiation of septic arthritis from transient synovitis.

Adolescent↗

Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients.

Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease of unknown etiology. Observations of significantly increased frequency of human leukocyte antigen (HLA)-B54 in Japanese patients and occurrence of familial cases suggest possible genetic predisposition to the disease susceptibility. To evaluate the possible association of HLA with the disease in Koreans, we have analyzed 30 patients for HLA class I (A, B, C) and class II (DR) antigens by the serologic and DNA typing methods, respectively. The most significant change in the patients compared to the control subjects was increased frequency of HLA-A11 (53.3% versus 17.5%, corrected p [pc] = 1.2 x 10(-)4, odds ratio [OR] = 5.4). In addition, B55 showed significant positive association (16.7% versus 3.5%, pc = 0.05, OR = 5.5), and B62 and Cw4 showed rather weak association with the disease. Certain A11-associated haplotypes showed much stronger positive association with the disease, compared to A11 antigen itself. Observations of a strong association of HLA-A11 in Koreans and B54 in Japanese with DPB suggest that the candidate gene(s) responsible for the disease susceptibility is located within the HLA class I region, most probably between HLA-A and HLA-B loci.

Adult↗

Atypical pulmonary artery sling with diffuse-type pulmonary arteriovenous fistula.

The case of a cyanotic infant with a rare combination of atypical pulmonary artery sling, imperforate anus, absence of the left kidney, interruption of the inferior vena cava, left side hemihypertrophy and diffuse-type pulmonary arteriovenous fistula is described. The clinical features were confusing, because of compounding abnormalities involving the respiratory tract and pulmonary circulation. The diagnostic approach to the etiology of cyanosis is discussed and the embryonic origin of pulmonary artery sling is reviewed.

Arteriovenous Fistula↗

The clinical characteristics of pulmonary alveolar proteinosis: experience at Seoul National University Hospital, and review of the literature.

Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.

Adult↗

Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration.

Adipose Tissue↗

Effects of BCG, lymphotoxin and bee venom on insulitis and development of IDDM in non-obese diabetic mice.

To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.

Adjuvants, Immunologic↗

Adenosquamous carcinoma of the prostate.

An unusual adenosquamous carcinoma originating in the prostate of a 73-year-old man is described. The histological finding showed a well differentiated squamous cell carcinoma admixed in an adenocarcinomatous area. A transitional area of 2 carcinomatous elements was also noted. Seven months prior to the development of this lesion, a diagnosis of adenocarcinoma had been established by transurethral resection of the prostate and the patient had been treated with bilateral orchiectomy. This is the first case of adenosquamous carcinoma of the prostate reported in Korea. The pathogenesis and previous reports of this lesion will be discussed.

Aged↗

A case with intrahepatic double cancer: hepatocellular carcinoma and cholangiocarcinoma associated with multiple von Meyenburg complexes.

Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) is sometimes found in resected livers, however, cases with double cancer of HCC and CC are very rare. As well, the rarity of CC arising in von Meyenburg complexes (VMCs) is appreciated. We report the case of a 74-year-old man found to have intrahepatic double cancer composed of well-differentiated HCC and CC which exhibited a histologic progression from VMCs to adenomatous lesions and CC. To our knowledge, this is the first case report published in the literature of a double HCC and CC associated with multiple VMCs. The pathogenesis and previous associated reports of these lesions are discussed.

Aged↗

The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted cancer cells.

OBJECTIVES: p16 is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. METHODS: We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. RESULTS: The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. CONCLUSION: These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

Carcinoma, Non-Small-Cell Lung↗

Subunit composition and oligomer stability of oat beta-glucosidase isozymes.

Oat beta-glucosidase (EC 3.2.1.21) has two isomeric forms, type I and type II, which are composed of 60 kDa peptides. To study the subunit composition and the stability of multimeric structure, the type I and II were purified from the primary leaves and coleoptiles of the etiolated oat seedlings where the isozymes are expressed organ-specifically. The monomers of the isozymes were isolated by urea-denatured gel electrophoresis followed by electroblotting. N-Terminal amino acid sequencing of the monomers indicated that the type I consisted of a peptide of ALESAKQVKPWQVPKRDWFP (As-Glu 1), and the type II having a peptide of ALESGKLKPWQIPKRDWFP (As-Glu 2) and As-Glu 1 in 1:1 ratio. The C-terminal amino acid of the As-Glu 1 was alanine and that of the As-Glu 2 was lysine. The As-Glu 2 was more negatively charged than the As-Glu 1. The type I isozyme is thus homomultimer of As-Glu 1 monomer and the type II heteromultimer of As-Glu 1 and As-Glu 2 monomers in 1:1 ratio. Partial denaturation of the multimers with urea and CaCl2 broke down the higher multimers to the lower multimers, which were in turn dissociated into homodimers and heterodimer. Denaturation study with urea and CaCl2 indicate that the higher multimers of the homooligomeric type I were more stable than those of the heterooligomeric type II and that hydrophobic interactions were important in the multimer formation. The homodimers were found to be more stable than the heterodimer. These results indicate that different combinations of the As-Glu 1 and As-Glu 2 monomers form the two isozymes of oat beta-glucosidase with different enzymatic properties and structural stability.

Amino Acid Sequence↗

Synthesis and evaluation of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir.

A series of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (4-10) and 2-amino-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (1) were synthesized as potential prodrugs of penciclovir and evaluated for their oral penciclovir bioavailability in mice and rats. Treatment of 2-(2-benzyloxyethyl)propane-1,3-diol (11) with 1,1'-carbonyldiimidazole in THF followed by hydrogenolytic removal of the benzyl group of the resulting cyclic carbonate 12 gave 5-(2-hydroxyethyl)-1,3-dioxan-2-one (13). Mesylation of the alcohol 13 and then a coupling reaction of the resulting mesylate 14 with 2-amino-6-chloropurine using anhydrous Cs2CO3 in DMF afforded 2-amino-6-chloro-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (16) after purification by flash column chromatography on silica gel using EtOAc/MeCN/Et3N as eluent. Hydrogenation of the 6-chloro cyclic carbonate 16 followed by a ring-opening reaction of the 6-deoxy cyclic carbonate 1 in a mixture of an appropriate alcohol and CHCl3 using activated SiO2 as a Lewis acid afforded the corresponding alkyl monocarbonate derivatives 3-10 in fair to good yields. Of the prodrugs tested in mice, the isopropyl monocarbonate 6 achieved the highest mean urinary recovery of penciclovir (53%), followed in order by the propyl monocarbonate 5 (51%), the isopentyl monocarbonate 10 (51%), the ethyl monocarbonate 4 (50%), and famciclovir (48%). In rats, the methyl monocarbonate 3, 4, 6, the n-butyl monocarbonate 7, and 10 (39-41%) showed levels of mean urinary recovery of penciclovir similar to that from famciclovir (40%). The alkyl monocarbonates 4-10 were found to be quite stable in the aqueous buffer solutions, and among them, 6 was the most stable with the half-lives (t1/2) of 88, >200, 61, and 26 days at pH 1.2, 6.0, 7.4, and 8.0, respectively. In addition, 6 was highly soluble in H2O (138.8 mg/mL, 20 degrees C).

Acyclovir↗

The human hepatitis B virus transactivator X gene product regulates Sp1 mediated transcription of an insulin-like growth factor II promoter 4.

Human hepatitis B virus (HBV) is one of the causative agents of hepatocellular carcinoma (HCC). The virus encodes a 17 kDa protein, X, which is known to be a causative agent in the formation of HCC. An insulin-like growth factor-II (IGF-II) is expressed during the formation of HCC. Among the four promoters of the IGF-II gene, promoters 2, 3 and 4 become activated during the formation of HCC. The high frequency of detection of hepatitis B virus X (HBV-X) antigen in liver cells from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that the expressions of HBV-X and IGF-II are associated. Studies were carried out to test the relationship between the HBV-X gene product and the activation of IGF-II promoter 4. We demonstrated that the HBV-X protein increases the endogenous IGF-II expression from promoter 3 and 4 of IGF-II gene. Analysis of the fourth promoter of IGF-II gene showed that the HBV-X gene product positively regulates transcription. Two copies of a motif are responsible for conferring HBV-X regulation on the fourth promoter of IGF-II. These motifs have been identified as Sp1 binding sites. Sp1 binding to IGF-II P4 promoter was identified by gel mobility shift assay using purified Sp1. By using a GAL4-Sp1 fusion protein it was demonstrated that HBV-X positively regulates the Spl mediated transcriptional activity of IGF-II in vivo. A protein-affinity chromatography experiment showed that HBV-X protein does not bind directly to Sp1, but HBV-X does augment the DNA binding activity of the phosphorylated form of Sp1 in HepG2 cells. Sp1 was phosphorylated by HBV-X and its DNA-binding activity was up-regulated upon HBV-X transfections. Various HBV-X mutant expression vectors were used for the demonstration of specific interactions between Sp1 and HBV-X. These results indicate that HBV-X functions as a positive regulator of transcription, and that Sp1 is a direct target for the transcriptional regulation of IGF-II. Increasing the DNA binding ability of the phosphorylated form of Sp1 by HBV-X might be an important mechanism for regulating the IGF-II gene expression and possibly promoting cell division during hepatic carcinogenesis. Our experimental results suggest that expression of HBV-X might induce the expression of IGF-II and the IGF-II might play a role in hepatitis B virus pathogenesis during the formation of HCC.

Binding Sites↗

Molecular and enzymatic characterization of a maltogenic amylase that hydrolyzes and transglycosylates acarbose.

A gene encoding a maltogenic amylase of Bacillus stearothermophilus ET1 was cloned and expressed in Escherichia coli. DNA sequence analysis indicated that the gene could encode a 69,627-Da protein containing 590 amino acids. The predicted amino acid sequence of the enzyme shared 47-70% identity with the sequences of maltogenic amylase from Bacillus licheniformis, neopullulanase from B. stearothermophilus, and cyclodextrin hydrolase (CDase) 1-5 from an alkalophilic Bacillus 1-5 strain. In addition to starch, pullulan and cyclodextrin, B. stearothermophilus could hydrolyze isopanose, but not panose, to glucose and maltose. Maltogenic amylase hydrolyzed acarbose, a competitive inhibitor of amylases, to glucose and a trisaccharide. When acarbose was incubated with 10% glucose, isoacarbose, containing an alpha-1,6-glucosidic linkage was produced as an acceptor reaction product. B. stearothermophilus maltogenic amylase shared four highly similar regions of amino acids with several amylolytic enzymes. The beta-cyclodextrin-hydrolyzing activity of maltogenic amylase was enhanced to a level equivalent to the activity of CDase when its amino acid sequence between the third and the fourth conserved regions was made more hydrophobic by site-directed mutagenesis. Enhanced transglycosylation activity was observed in most of the mutants. This result suggested that the members of a subfamily of amylolytic enzymes, including maltogenic amylase and CDase, could share similar substrate specificities, enzymatic mechanisms and structure/function relationships.

Acarbose↗

Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human cervical cancers.

OBJECTIVE: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolytic protein. A higher level of GAPDH mRNA was found in lung, pancreas, and prostate cancers, but in cervical carcinoma there have not been any reports about the level of GAPDH gene expression. So, we tried to investigate the GAPDH gene expression patterns in cervical carcinomas compared to normal cervical tissues, and the relationships between the expression levels of this gene and conventional clinicopathological parameters were evaluated. MATERIALS AND METHODS: In this study, 25 normal exocervical tissues, 35 primary untreated cervical cancer tissues, 2 cervical cancer cell lines, and 2 post-nude-mouse-derived cervical cancer cell lines were subjected to Northern blot analyses for GAPDH gene expression. RESULTS: Northern blot analyses revealed that the levels of GAPDH gene expression were elevated in 34 of 35 (97%) cervical carcinoma tissues and all of the 4 cervical cancer cell lines compared to normal cervical tissues. The levels of GAPDH gene expression were more prominent in rapidly proliferating cervical carcinoma cells. The levels of the GAPDH gene expressions in cervical cancer tissues were not associated with conventional clinicopathological parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION: These results suggest that increased GAPDH gene expression is characteristic of human cervical carcinomas and that rapidly proliferating carcinoma cells express more enhanced GAPDH gene. Future gene therapy using antisense oligodeoxynucleotide directed against GAPDH mRNA might be another therapeutic tool for human uterine cervical carcinoma.

Female↗

Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease.

BACKGROUND & AIMS: To understand the molecular etiology of Cowden disease-associated gastrointestinal polyps, we analyzed the mutational status of PTEN/MMAC1, a recently identified Cowden disease gene located at 10q23, in gastric hamartomas, colonic adenoma, and juvenile polyps of 3 patients with Cowden disease. METHODS: Messenger RNA expression, gene deletion, and sequence alteration of PTEN/MMAC1 were evaluated by quantitative polymerease chain reaction (PCR), PCR-single-strand conformation polymorphism, and sequencing analysis. RESULTS: Germline missense mutation at codon 289 (AAA to GAA, Lys to Glu) and deletion of the wild-type allele were detected in the polyps of 2 patients with Cowden disease in the same family. Germline allelic deletion and transcriptional silencing of the remaining allele, probably caused by abnormal methylation, were also observed in a gastric hamartoma of 1 patient. CONCLUSIONS: The germline mutation and alteration of the remaining allele observed in this study strongly support that PTEN/MMAC1 functions as a tumor suppressor in Cowden disease. This study is the first to show that the mutational abrogation of PTEN/MMAC1 plays a causal role in the genesis of gastrointestinal polyps in Cowden disease, providing molecular genetic evidence that colonic adenoma, juvenile polyp, and gastric hamartoma could be included in the manifestations of Cowden disease.

Adolescent↗

Telomerase activity in lung cancer cell lines and tissues.

Using TRAP assay, we studied the activity of the telomerase in the lung cancer cell lines, and lung cancer and normal tissues in which expression appears to be related to the immortality of cancer cells. All the human lung cancer cell lines and the majority of human lung cancer tissues (78%) expressed telomerase activity, but this was undetectable in normal human lung tissues. Positivity for telomerase activity in lung cancer cell lines was higher than in lung cancer tissues; this result implies the expression of telomerase activity may play a crucial role in the development or progression of lung cancer, and also suggests that improved method of detection may lead to the higher positivity for telomerase activity in primary lung cancer tissues. To determine whether there is a definite causal relationship between telomerase and cancer, and to develop new anti-cancer agents which inhibit telomerase, further study is needed.

Humans↗