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Biomedical subjects

J H Choi

Publications and source records attributed to J H Choi.

At least 163 records · Page 9Linked to original sources

Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments.

This study was to investigate a hypothesis that dietary restriction (DR) suppresses learning and memory impairments in dementia animal model SAMP8 mice. Four-week-old female SAMP8 mice were fed either ad libitum (AL) or fed restricted (40% of the food consumed by AL). Results showed that acetylcholine (ACh) levels in hippocampus at aged 12 months of age were 12% higher in DR than that of AL group. Dopamine (DA) and norepinephrine (NE) levels in cerebellum at 8 and 12 months of age were significantly higher (26~94% and 34~43%, respectively) in DR group than those in AL group. Serotonin (5-HT) levels in cerebellum at aged 12 months of age were markedly increased (~53%) in DR group. Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in cerebellum at 8 and 12 months of age were significantly increased (28~41% and 24~64%, respectively) in DR group compared with AL group. In addition, neurotransmitter-related enzymes, choline acetyltransferase (ChAT) and acetylchoinesterase (AChE) activities at 8 and 12 months of age were elevated (6~8% and 5~7%, respectively) in DR group. Monoamine oxidase-B (MAO-B) that catalyzes oxidative deamination in brain were suppressed by 7~10% in DR group. At aged 12 months of age, the generation of basal and induced reactive oxygen species (ROS) in brain significantly decreased by 20% in DR group compared with AL group. These results suggest that inhibitory effect of oxidative stress by DR may play a pivotal role in attenuating the age-related changes observed in dementia animal model SAMP8.

Age Factors↗

Detection of epidermal growth factor receptor in the serum of patients with cervical carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignancies, including breast, lung, gastric, and cervical carcinoma. Its overexpression has been associated with disease progression or poor prognosis in patients with cervical carcinoma. In the present study, the levels of EGFR were determined in serum from 38 patients with cervical carcinoma [invasive or recurrent carcinoma (n = 26) and carcinoma in situ (CIS; n = 12)] and 38 healthy female controls using ELISA. The mean serum level for EGFR in patients with invasive or recurrent carcinoma (165 +/- 60 fmol/ml) was significantly elevated (P < 0.0001) compared with that of healthy controls (66 +/- 17 fmol/ml) and also higher (P = 0.015) than that of patients with CIS (126 +/- 25 fmol/ml). In addition, there was a significant difference in the mean serum levels of EGFR between patients with CIS and healthy controls (P < 0.0001). Thirty-five patients (92%) with cervical carcinoma [invasive or recurrent (n = 24) and CIS (n = 11)] had elevated serum, EGFR levels above the cutoff value of 100 fmol/ml (defined as 2 SD above the mean of the controls). In conclusion, the serum EGFR level was elevated in a significant proportion of patients with cervical carcinoma, and it demonstrated an increasing tendency according to disease progression from normal tissue through CIS to invasive cervical carcinoma. Therefore, it may have a potential usefulness as a biological marker of cervical carcinoma.

Adult↗

Necrotizing enterocolitis: experience of 27 cases from a single Korean institution.

Necrotizing enterocolitis (NEC) can involve any site in the gastrointestinal tract and is a fatal complication of immunosuppression. To characterize NEC, clinical and radiological characteristics were analyzed. A total of 27 cases of NEC were identified from January 1993 to August 1998, and medical records were reviewed. NEC was diagnosed by clinical and radiological criteria, and other mimicking conditions were excluded. Of the NEC cases, 22 (81.5%) occurred in patients with underlying hematologic malignancy. All patients complained of abdominal pain and fever at the time of inclusion. Escherichia coli was the most common pathogen identified. The most common finding by computed tomography was single-layered diffuse bowel wall thickening with variable density. Other findings were ascites, fascial thickening, pneumatosis, and mesenteric lymphadenopathy. Of the patients, 25 were treated with antimicrobials with or without recombinant hematopoietic growth factors, and 2 were treated with surgery because of perforation and profound bleeding. Among the 12 patients who died, NEC was the direct cause of death in 7 patients. In conclusion, computed tomography is an effective tool for early diagnosis of NEC. Bowel rest, broad-spectrum antimicrobials, and recombinant hematopoietic growth factors are important aspects of treatment. Surgery should be reserved for complicated cases.

Adolescent↗

Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis.

Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). The mRNA level of cyclin D1 was increased 1.2-fold in adenocarcinomas but not significantly in adenomas, when compared with normal rat colonic mucosa (p<0.05). The cyclin E mRNA level was increased 2.7-fold in adenomas and 3.3-fold in adenocarcinomas (p<0.05). The PCNA mRNA level was also increased 1.9-fold in adenomas and 1.8-fold in adenocarcinomas (p<0.05). Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression.

1,2-Dimethylhydrazine↗

A successful delivery of a baby from a D--/D-- mother with strong anti- Hr0.

We describe the first reported case in Korea of a woman with a D--/ D-- phenotype, a high-titer anti-Hr0, and the successful delivery of her newborn. The mother had a history of spontaneous abortion and artificial termination. In her third pregnancy, a live infant was delivered, but died of severe hemolytic disease of the newborn due to anti- Hr0 in spite of intensive medical intervention. In her fourth pregnancy, at 22 weeks gestation, the titer of anti- Hr0 was 1024, fetal cells were direct antiglobulin test positive and the blood type was group O, D+ (CDe). We performed plasma exchanges in the mother; however, the titer of antibody rebounded to its initial level after the third plasma exchange. At 26 weeks gestation, cord blood Hb decreased to 7.1 g/dL and three intrauterine transfusions were performed using the mother's washed red blood cells (RBCs). At 34 weeks gestation, a live baby was delivered by cesarean section. The infant was hydropic with hyperbilirubinemia and severe anemia. However, after two exchange transfusions using the washed RBCs of the mother's sister, who was also D--/D--, laboratory and clinical findings returned to normal.

Journal Article↗

Expression of cytokine genes and increased nuclear factor-kappa B activity in the brains of scrapie-infected mice.

A number of aspects of the pathogenesis of scrapie remain to be elucidated. The cellular and molecular aspects of the neuropathology in scrapie suggest the possibility that the proinflammatory cytokines could act as pathogenic mediators in this neurodegenerative disease. To understand this possibility, we examined the expression of proinflammatory cytokine genes in brains of IM mice-infected with 87V scrapie agent. Additionally, we also analyzed the activity of nuclear factor-kappa B (NF-kappaB), which is the major transcriptional activator for inflammatory cytokines, and formation of reactive oxygen species (ROS) as a common upstream messenger for its activation. The induction of mRNAs of the inflammatory cytokines, IL-1alpha, IL-1beta and TNF-alpha, was detected only in the brains of scrapie-infected mice. The activity of NF-kappaB was significantly increased in the nuclear extracts from brains of the scrapie-infected group and the immunoreactivity of NF-kappaB was increased in the hippocampus and thalamus in the brains of scrapie-infected mice. The NF-kappaB immunoreactivity was observed mainly in GFAP-positive astrocytes and also detected in the PrP-amyloid plaques in the brains of 87V scrapie-infected mice. Gene expression of IL-6 and iNOS, the representative target genes for NF-kappaB activation, were activated only in the infected group. The production of ROS was significantly increased in the brain mitochondrial fractions of scrapie-infected mice. These results suggest that prion accumulation in astrocytes might activate NF-kappaB through the increase of ROS generation, and thus alterations in NF-kappaB-directed gene expression may contribute to both the neurodegeneration and proinflammatory responses which occur in scrapie.

Animals↗

Synthesis and in vitro activity of new oxazolidinone antibacterial agents having substituted isoxazoles.

Two series of oxazolidinone derivatives having substituted isoxazoles were synthesized and tested for antibacterial activities against several Gram-positive strains including the resistant strains of Staphylococcus and Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed in vitro activities (MIC) comparable or superior to the reference compound vancomycin.

Anti-Bacterial Agents↗

Calcium and phospholipid activation of a recombinant calcium-dependent protein kinase (DcCPK1) from carrot (Daucus carota L.).

A calmodulin-like domain protein kinase (DcCPK1, previously designated CDPK431) cloned from carrot (Daucus carota L.) was expressed at high levels in Escherichia coli and partially purified. Ca(2+)-induced gel mobility shift and (45)Ca(2+) ligand binding assays confirmed that recombinant DcCPK1 binds Ca(2+) through its calmodulin-like domain and undergoes a significant conformational change. Ca(2+) activated the kinase activity of recombinant DcCPK1 (K(0.5)=1.7 microM) up to 20-fold. Ca(2+) combined with certain lipids, including phosphatidic acid, phosphatidylserine and phosphatidylinositol, but not diolein or lysophosphatidylcholine, provided even greater Ca(2+)-dependent protein kinase activity. DcCPK1 phosphorylated casein and histone III-S, and a variety of peptide substrates containing a hydrophobic and a basic residue situated P-5 and P-3 amino acids N-terminal to a Ser or Thr residue. The calmodulin and protein kinase inhibitors, W-7 and staurosporine, inhibited CDPK activity. The similarities between DcCPK1 and mammalian protein kinase C (PKC) in substrate specificity, sensitivity to inhibitors, and activation by Ca(2+) and phospholipid suggest that various CDPK isoforms may be responsible for some PKC-like activities in plant cells.

Amino Acid Sequence↗

Duplicate genes for Fe-containing superoxide dismutase in Streptomyces coelicolor A3(2).

Streptomyces coelicolor Müller contains two types of superoxide dismutase (SOD) containing Ni (encoded by sodN) or Fe (encoded by sodF). Unlike a single species of Fe-containing SOD in Müller strain, multiple forms of FeSODs were detected in S. coelicolor A3(2) strain by activity staining and Western blot analysis. Genomic Southern hybridization suggested the presence of at least two copies of the sodF-like gene in A3(2). Two different genes for FeSOD (sodF1 and sodF2) were isolated from the phage library of A3(2) genome. The nucleotide sequence of the sodF1 coding region was identical with the unique sodF gene from Müller while that of sodF2 shared 88% identity. The gene products of sodF1 and sodF2 were identified by activity staining and immunoblot analysis. Expression from the sodF1 gene was repressed by nickel as sensitively as Müller sodF, suggesting the presence of Ni-responsive regulatory site within the region shared by the two genes. Among 12 other Streptomyces species examined, only S. fradiae contained two FeSOD-like polypeptides. We postulate that the additional copy of the sodF gene (sodF2) was provided by the horizontal transfer from remotely related bacteria.

Amino Acid Sequence↗

Regulation of phosphatidylinositol 4-phosphate 5-kinase from Schizosaccharomyces pombe by casein kinase I.

Phosphatidylinositol ()P 5-kinase (PtdIns(4)P 5-kinase) catalyzes the last step in the synthesis of phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is a precursor of diacylglycerol and inositol 1,4,5-trisphosphate and is also involved in regulation of actin cytoskeleton remodeling and membrane traffic. To satisfy such varied demands in several aspects of cell physiology, synthesis of PtdIns(4,5)P2 must be stringently regulated. In this paper we describe extraction, purification, and characterization of PtdIns(4)P 5-kinase from the plasma membranes of Schizosaccharomyces pombe. We also provide evidence that PtdIns(4)P 5-kinase is phosphorylated and inactivated by Cki1, the S. pombe homolog of casein kinase I. Phosphorylation by Cki1 in vitro decreases the activity of PtdIns(4)P 5-kinase. In addition, and most importantly, overexpression of Cki1 in S. pombe results in a reduced synthesis of PtdIns(4,5)P2 and in a lower activity of PtdIns(4)P 5-kinase associated with the plasma membrane. These results suggest that PtdIns(4)P 5-kinase is a target of Cki1 in S. pombe and that Cki1 is involved in regulation of PtdIns(4, 5)P2 synthesis by phosphorylating and inactivating PtdIns(4)P 5-kinase.

Casein Kinases↗

Glucocorticoids prevent NF-kappaB activation by inhibiting the early release of platelet-activating factor in response to lipopolysaccharide.

Lipopolysaccharide (LPS) is a known inducer of numerous pro-inflammatory events including the production of platelet-activating factor (PAF). PAF released in response to LPS is a major contributor to the pathological events associated with endotoxemia. The present study demonstrates that dexmethasone (DEX) inhibited the LPS-induced early plasma PAF raise in a dose- and time-dependent manner. In addition, DEX prevented the subsequent PAF-mediated pathological phenomena such as anaphylactic shock-like symptoms, symptoms of disseminated intravascular coagulation and hemorrhage in renal medullae. DEX or the PAF antagonist BN 50739 significantly inhibited LPS-induced NF-kappaB activation. The inhibition of NF-kappaB activation by DEX was overcome by the injection of exogenous PAF. Administration of PAF or LPS resulted in a rapid loss of IkappaBalpha protein. The LPS-induced degradation of IkappaBalpha was prevented by pretreatment with BN 50739, suggesting that PAF is a critical intermediate in the LPS-triggered degradation of IkappaBalpha protein. DEX prevented the LPS-induced IkappaBalpha degradation, which was also reversed by exogenous PAF. Administration of DEX or BN 50739 caused an increase in cytoplasmic IkappaBalpha level. Our results indicate that DEX inhibits IkappaBalpha degradation and subsequent NF-kappaB activation through blocking the initial release of PAF.

Animals↗

Intrahepatic cholangiocarcinoma in Korea.

We reviewed surgically treated patients with intrahepatic cholangiocarcinoma to evaluate the clinical and pathologic features of intrahepatic cholangiocarcinoma that may affect long-term survival in Korean patients with the disease. Between 1990 and 1997, 28 patients with intrahepatic cholangiocarcinoma underwent laparotomy. Resection was performed in 25 patients, and wedge resection alone in 3 patients. The liver resections consisted of right lobectomy in 5 patients, right trisegmentectomy in 1, left lobectomy in 7, extended left lobectomy in 3, hepatopancreatoduodenectomy in 2, and segmentectomy in 7. Curative resection was performed in 15 patients. Histological sections of all resected specimens were immunohistochemically stained with p53 and Ki-67 monoclonal antibodies to assess the biological behavior of the tumor cells. Cumulative survival rate and clinicopathological factors that may influence the prognosis, including biological markers (p53, Ki-67), were analyzed statistically. Patients who underwent curative resection survived significantly longer than patients who underwent noncurative resection. The median survival time of the patients who underwent curative resection was 24 months (mean, 34 +/- 8 months), with 1-, 2-, and 3-year survival rates of 66.6%, 44.4%, and 35.6%, respectively. The median survival time of the patients who underwent noncurative resection was 3 months (mean, 8 +/- 3 months), with 1- and 2-year survival rates of 26.7% and 13. 4%, respectively. Univariate analysis showed that positive regional lymph nodes correlated significantly with poor outcome (P = 0.004) and that curative resection significantly correlated with better prognosis (P = 0.001). Age, sex, tumor size, degree of cell differentiation, gross type of tumor, and p53 and Ki-67 labeling index were not significantly correlated with outcome. Our findings support the concept that aggressive liver resection, along with regional lymph node dissection, be recommended for long-term survival. The validity of molecular biologic tumor markers (p53, Ki-67) as prognostic factors has not yet been clearly demonstrated.

Adult↗

Reduction in hMSH2 mRNA levels by premature translation termination: implications for mutation screening in hereditary nonpolyposis colorectal cancer.

We have used single-strand conformational polymorphism (SSCP) and heteroduplex analysis to examine DNA from 50 colorectal carcinoma patients coming from families meeting the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC) or having developed colorectal carcinoma at age 45 or younger. We identified mutations in 12 of these patients, with seven of these being novel mutations. We examined four of the truncating mutations using in vitro transcription and translation (IVTT) assays and determined that the mutation causing an in-frame deletion of exon 5 could easily be detected by the IVTT assay, but the three mutations resulting in premature translation termination were not detected because the steady-state levels of the mutant allele transcripts are too low. Our findings suggest that some but not all mutant hMSH2 alleles have significantly lower steady-state mRNA levels than the normal allele. Under ideal circumstances, where lymphoblastoid cell lines are available for RNA extraction, IVTT may be useful for detecting truncating mutations. However, our data suggest that caution should be taken in using IVTT in routine screening of clinical samples for truncating HNPCC mutations, as many mutations may go undetected.

Colorectal Neoplasms, Hereditary Nonpolyposis↗