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Biomedical subjects

C Park

Publications and source records attributed to C Park.

At least 145 records · Page 8Linked to original sources

Surgical resection of mucoepidermoid carcinoma at the carina in a 9-year-old boy.

Mucoepidermoid carcinoma of trachea and bronchi is a rare tumor, especially in children. The authors report a case of 9-year-old boy with mucoepidermoid carcinoma at the carina. His presenting symptoms were hemoptysis of recent onset and intermittent cough of 2 years' duration. Preoperative assessment of the tumor was an intraluminal polypoid mass arising from the carina extending into the trachea and right main stem bronchus. A complete resection with reconstruction of carina was successful. The tumor was 12 mm in size, polypoid with a broad base. It had characteristic features of a low-grade mucoepidermoid tumor, namely, admixture of islands of intermediate cells and glandular components with invasion of submucosa. The patient is now 15 months postsurgery free of disease.

Bronchial Neoplasms↗

Mechanical properties of resin composites with filler particles aligned by an electric field.

OBJECTIVES: To explore possible enhancement of the mechanical properties of resin composites by aligning the filler particles. METHODS: The resin for the composites consisted of urethane dimethacrylate (UDMA) and 1,6-hexanediol dimethacrylate (HDDMA) mixed in the ratio of 90 to 10; the filler was silica-zirconia in two particle sizes, 1.7 microns (P50), which was mixed with the resin in the volume fractions of 29 and 48 vol%, and 0.7 micron (Z100), which was mixed with the resin in the volume fractions of 37 and 57 vol%. Particle alignment was obtained by applying a 60 Hz AC electric field across the composite before the resin was photopolymerized. The stress-strain behavior and the elastic modulus of the hardened composite were measured along the alignment axis in compression. RESULTS: The elastic moduli of the aligned composites increased by as much as 20%, and the maximum stress sustainable in compression before significant deformation occurred was elevated. An electric field strength of the order of 1 kV mm-1 was required to obtain sufficient alignment. SIGNIFICANCE: Besides conferring a structure to resin composites that is more like that of the natural tooth, particle alignment increased some of the mechanical properties and may have improved durability.

Composite Resins↗

Clinical significance of clonality in thyroid nodules.

BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.

Adenoma↗

Can bedside assessment reliably exclude aspiration following acute stroke?

OBJECTIVE: To investigate the ability of a bedside swallowing assessment to reliably exclude aspiration following acute stroke. SUBJECTS: Consecutive patients admitted within 24 h of stroke onset to two hospitals. METHODS: A prospective study. Where possible, all patients had their ability to swallow assessed on the day of admission by both a doctor and a speech and language therapist using a standardized proforma. A videofluoroscopy examination was conducted within 3 days of admission. RESULTS: 94 patients underwent videofluoroscopy; 20 (21%) were seen to be aspirating, although this was not detected at the bedside in 10. In 18 (22%) of the patients the speech and language therapist considered the swallow to be unsafe. In the medical assessment, 39 patients (41%) had an unsafe swallow. Bedside assessment by a speech and language therapist gave a sensitivity of 47%, a specificity of 86%, positive predictive value (PPV) of 50% and a negative predictive value (NPV) of 85% for the presence of aspiration. Multiple logistic regression was used to identify the optimum elements of the bedside assessments for predicting the presence of aspiration. A weak voluntary cough and any alteration in conscious level gave a sensitivity of 75%, specificity of 72%, PPV of 41% and NPV of 91% for aspiration. CONCLUSION: Bedside assessment of swallowing lacks the necessary sensitivity to be used as a screening instrument in acute stroke, but there are concerns about the use of videofluoroscopy as a gold standard. The relative importance of aspiration and bedside assessment in predicting complications and outcome needs to be studied.

Acute Disease↗

Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues.

A cDNA clone coding for adenylate kinase 2B was isolated from fetal liver, and the expression of AK2 was investigated in human tissues. The ORF in the cDNA clone for human AK2B predicted a protein comprising 232 amino acids (25.6 kDa). The features of AK2A and AK2B sequences in human were the same as those in the bovine system. Each of the recombinant proteins, AK2A and AK2B, was expressed in Escherichia coli cells, and the purified recombinant proteins were enzymatically active. The distribution of AK2 transcripts in various human tissues was examined by Northern analysis. Unlike in the bovine system, it was found that the AK2A transcript was the major form of AK2 mRNA species in all human tissues. The transcripts of AK2 isozymes were relatively abundant in heart, liver, and also in skeletal muscle, where the expression level of AK2 was known to be low. Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues. These tissue-specific expressions of the AK isozymes in human might suggest the presence of organ-specific regulation of the AK2 gene including a post-transcriptional control in skeletal muscle.

Adenylate Kinase↗

Analysis of performance measures. A veterans home case study.

The development or adaptation of a comprehensive performance measurement system is vital for the proper assessment of organizational performance. The authors describe their experience in developing and implementing a modified performance measurement questionnaire for the assessment of an existing performance measurement system in a state veterans home. Adapted for a long-term care environment, the questionnaire determines whether the organization's strategies, performance measurement system, and employees' actions match up and support each other.

Data Interpretation, Statistical↗

A single-stage two-flap method for reconstruction of partial auricular defect.

Two flaps, consisting of a postauricular skin flap and a mastoid fascial flap, were used for coverage of both sides of a grafted framework in one stage for repair of one-fourth to half auricular composite defect after trauma or inflammation. The method was safe, and the postauricular donor scar was minimal. Additionally, it was beneficial in restoring similar ear shape and size with a natural cartilage convolution.

Adult↗

ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease.

The valine at position 82 (Val 82) in the active site of the human immunodeficiency virus (HIV) protease mutates in response to therapy with the protease inhibitor ritonavir. By using the X-ray crystal structure of the complex of HIV protease and ritonavir, the potent protease inhibitor ABT-378, which has a diminished interaction with Val 82, was designed. ABT-378 potently inhibited wild-type and mutant HIV protease (Ki = 1.3 to 3.6 pM), blocked the replication of laboratory and clinical strains of HIV type 1 (50% effective concentration [EC50], 0.006 to 0.017 microM), and maintained high potency against mutant HIV selected by ritonavir in vivo (EC50, </=0. 06 microM). The metabolism of ABT-378 was strongly inhibited by ritonavir in vitro. Consequently, following concomitant oral administration of ABT-378 and ritonavir, the concentrations of ABT-378 in rat, dog, and monkey plasma exceeded the in vitro antiviral EC50 in the presence of human serum by >50-fold after 8 h. In healthy human volunteers, coadministration of a single 400-mg dose of ABT-378 with 50 mg of ritonavir enhanced the area under the concentration curve of ABT-378 in plasma by 77-fold over that observed after dosing with ABT-378 alone, and mean concentrations of ABT-378 exceeded the EC50 for >24 h. These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS.

Animals↗

A case of autoimmune cholangitis associated with Sjögren's syndrome and arthropathy.

Autoimmune cholangitis (AC) is a recently proposed entity that describes a specific group of patients presenting overlapping features of primary biliary cirrhosis (PBC) and autoimmune hepatitis. The disease is characterized by dinical cholestasis, high titer antinuclear antibody, negative antimitochondrial antibody, and histologically, findings of PBC coexisting with varying degrees of parenchymal inflammation. In this report, we describe a patient with Sjögren's syndrome who fulfilled the diagnostic criteria of AC associated with unique arthropathy compatible with arthritis of PBC. This case illustrates the unusual coexistence of two diseases that may share similar pathogenic processes.

Autoimmune Diseases↗

A case with sarcomatoid hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) with sarcomatous features is a rare neoplasm which has been found in only 1.8% of surgically resected HCC and has a higher incidence of metastasis than usual HCC. We recently experienced a case of sarcomatoid HCC removed from a 49-year-old man. A surgically resected liver revealed a well-defined grayish-white solid firm mass showing extensive central necrosis and infiltrative growth margin. Microscopically, the entire tumor was composed of pleomorphic spindle cells with prominent nucleoli and frequent mitosis. It showed a sinusoidal infiltrative growth pattern at the tumor-nontumor boundary. The tumor cells reacted positively with AE3 (high molecular cytokeratin) and Vimentin and reacted negatively with AE1 (low molecular cytokeratin), cytokeratin19, carcinoembryonic antigen, alpha-fetoprotein, Factor VIII, CD31 and CD68. The spindle-shaped tumor cells were considered to originate from hepatocyte rather than from bile duct epithelium or mesenchymal elements.

Carcinoma↗

Deletion of the M6P/IGF2r gene in primary hepatocellular carcinoma.

To evaluate the different alteration patterns of the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) gene in hepatocellular carcinoma (HCC), 41 HCCs were screened for homozygous deletion and loss of heterozygosity (LOH) at the M6P/IGF2r gene with a dinucleotide repeat polymorphic marker. Of these, three (8.8%) were heterozygous and LOH was observed in two (66.7%) of these informative cases. Five (14.7%) out of 34 informative cases showed homozygous deletions for the dinucleotide repeat polymorphic marker. The frequent allelic loss and homozygous deletion of the M6P/ IGF2r gene suggest that the M6P/IGF2r gene functions as a tumor suppressor gene in the development of HCC.

Carcinoma, Hepatocellular↗

Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis.

Notch, a transmembrane receptor member of the homeotic epidermal growth factor-like family of proteins, participates in cell-to-cell signaling to control cell fate during development. Activated Notch-1 constructs lacking the extracellular region prevent differentiation of several mammalian cells in vitro. This effect, however, bypasses the normal mechanisms of cell-to-cell interactions in which Notch-1 participates. We investigated the role of Notch-1 in the hormone-induced adipocyte differentiation of 3T3-L1 fibroblasts, a paradigmatic model of adipogenesis that requires cell-to-cell contact. Unlike other differentiation models, Notch-1 expression and function were necessary conditions for adipogenesis. Impaired Notch-1 expression by antisense Notch-1 constructs prevented adipocyte differentiation. Strategies aimed at blocking putative Notch/ligand interactions also blocked adipogenesis, implicating Notch as a critical molecule in cell-to-cell signaling necessary for differentiation. Inhibition of Notch-1 expression or function decreased the expression of peroxisomal proliferator-activated receptors delta and gamma, transcription factors that control adipocyte differentiation and that are up-regulated at cell confluence. These results implicate Notch in the commitment of 3T3-L1 cells to undergo adipogenesis by controlling the expression of the principal regulators of this process.

3T3 Cells↗

Characterization of citrate synthase purified from Drosophila melanogaster.

Citrate synthase which condenses acetyl-CoA and oxaloacetate to citrate was purified from Drosophila melanogaster. Some physicochemical as well as enzymatical properties were investigated. The optimum pH and temperature were pH 8.0-9.0 and 45 degrees C, respectively. The molecular weight of the enzyme was determined as 81,000 Da by gel filtration and the purified active enzyme consisted of two identical subunits which had a molecular mass of 48,700 on SDS-PAGE. Homogeneity of the purified enzyme was confirmed by SDS-PAGE and also by N-terminal amino acid sequence analysis. The Michaelis constants (K(m)) of the enzyme for acetyl-CoA and oxaloacetate were 6.7 microM and 3.1 microM, respectively. Kinetic studies showed that citrate synthase follows the concerted mechanism which forms a ternary complex. Propionyl-CoA, ATP, and intermediates of the TCA cycle, succinyl-CoA and alpha-ketoglutarate, behaved as inhibitors in vitro. Using pig and chicken heart enzymes for comparison, we found similarities at the N-terminal region. However, in the Ouchterlony immunodiffusion test, the polyclonal antibody raised against Drosophila citrate synthase did not show any crossreaction with pig, chicken or pigeon enzymes.

Animals↗

Fission yeast dihydrolipoamide dehydrogenase gene is involved in G1/S cell cycle progression.

Using functional complementation with a Schizosaccharomyces pombe genomic library, we have isolated a clone complementing a G1/S phase progression defective mutant. The newly isolated temperature-sensitive mutant, cyj150, showed elongated morphology at a restrictive temperature of 36 degrees C and DNA content analysis of the mutant indicated a defect in cell cycle progression at the G1/S phase. Sequence analysis of the genomic and cDNA clones complementing this elongated phenotype at 36 degrees C show that it encodes a protein that has 50% amino acid identity with dihydrolipoamide dehydrogenase from Saccharomyces cerevisiae and garden pea. Alignment of the deduced amino acid sequence of S. pombe dihydrolipoamide dehydrogenase (dld1+) with glutathione reductase and mercuric reductase revealed extensive homologies throughout the primary sequence and protein structure, and contained amino acid sequences of the active site region conserved from prokaryote to higher eukaryote. Gene disruption and tetrad analysis showed that dld1+ is an essential gene for cell viability. Northern analysis indicates that transcriptional expression of this gene is not fluctuated according to the cell cycle. However, it is certain that malfunction of this Dld1 protein blocks the progression of cell cycle from G1 to S phase. The sequence of the dld1+ gene is available in EMBL/GenBank under Accession Number L40360.

Amino Acid Sequence↗

Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human tumors in Asia and Africa. The molecular genetic changes involving both protooncogenes and tumor suppressor genes are known to be involved in hepatocarcinogenesis, but the roles of the known tumor suppressor genes in hepatocarcinogenesis are not fully elucidated. In this study, the authors analyzed the loss of heterozygosity (LOH) of known tumor suppressor genes in HCC and evaluated the relationship between LOH of tumor suppressor genes and clinicopathologic features. METHODS: The authors assessed the LOH of the 10 known tumor suppressor genes (VHL, APC, EXT1, WT1, Rb1, p53, BRCA1, nm23, DPC4, and DCC) with microsatellite markers in 29 consecutively resected HCC specimens. RESULTS: The authors found frequent LOH of tumor suppressor genes in HCC. Twenty five of 29 cases (86%) had LOH of tumor suppressor genes and 17 cases (59%) had LOHs involving 2-4 tumor suppressor genes. Among the tumor suppressor genes, frequent LOH was noted in the p53 (66%), Rb1 (33%), EXT1 (33%), and APC (20%) genes. LOH of the p53 gene and multiple LOH of the tumor suppressor genes were more frequent in poorly differentiated HCCs (P = 0.02). CONCLUSIONS: The LOH of tumor suppressor genes is frequent in HCCs and LOH of the p53 gene and accumulated LOHs are related to poorly differentiated HCC. Abnormalities of the p53 gene or the accumulated abnormalities of the tumor suppressor genes may play a role in the aggressive progression of HCC.

Adult↗

A novel protein, Psp1, essential for cell cycle progression of Schizosaccharomyces pombe is phosphorylated by Cdc2-Cdc13 upon entry into G0-like stationary phase of cell growth.

A novel gene, psp1(+), which functionally complements a temperature-sensitive mutant defective in cell cycle progression both in G1/S and G2/M has been isolated from the genomic and cDNA libraries of Schizosaccharomyces pombe. Disruption of this gene is lethal for cell growth at 30 degrees C indicating that it is an essential gene for vegetative cell growth. Western analysis of the protein by polyclonal antibody made from glutathione S-transferase-Psp1 fusion protein indicated that the Psp1 protein exists in two different molecular weight forms depending on the growth state of the cell. In vitro experiments with a phosphatase showed that this difference is due to phosphorylation. The dephosphorylated form of the protein is dominant in actively growing cells whereas the phosphorylated form becomes the major species when cells enter the stationary phase. The Cdc2-Cdc13 complex is shown to phosphorylate the GST-Psp1 fusion protein in vitro, and site-directed mutagenesis and phosphoamino acid analysis indicated that the serine residue at position 333 in the carboxyl-terminal region is required for phosphorylation. In situ fluorescein isothiocyanate-conjugated antibody staining showed that this protein tends to be localized to both ends of the cell upon entry into the stationary phase of cell growth. However, overexpression of the novel protein Psp1 in actively growing cells inhibits cell growth causing accumulation of DNA (4n or 8n). Thus we speculate that Psp1 can function at both G1/S and G2/M phases complementing the defect of the new mutant we have isolated. It is likely that Psp1 is required both for proper DNA replication and for the process of mitosis.

Amino Acid Sequence↗