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Biomedical subjects

C Park

Publications and source records attributed to C Park.

At least 127 records · Page 7Linked to original sources
PubMed1999

Expression of biliary antigen and its clinical significance in hepatocellular carcinoma.

In order to classify the hepatocellular carcinomas (HCCs) which had diverse clinicopathologic characteristics, we divided HCCs into two groups according to the expression of biliary antigen on the basis of the hypothesis that the hepatocyte and biliary epithelial cell originate from the same precursor cell, and then we investigated the clinical and pathologic characteristics in the two groups. Forty HCC cases with no preoperative treatment and at least two-year follow-up data were selected among 202 cases of HCC files from 1991 to 1995. Expression of biliary antigen (AE1, cytokeratin 19), p53, AFP, and Ki-67 in the tumor tissue were assessed by immunohistochemistry. Positive cytokeratin 19 was noted in one case (2.5%); AE1 was detected in 40% of patients; p53 was overexpressed in 20% of patients; and AFP was detected in 45% of patients. No statistical difference between the biliary antigen positive group (16 cases) and the negative group (24 cases) were noted in terms of mean age, sex, presurgical serum AFP level, Child class, and tumor size. HBsAg positive rate was 66.7% for the biliary antigen (-) group and 93.8% for the biliary antigen (+) group with a statistically significant difference (p = 0.048). The number of cases for Edmonson-Steiner grade I/II and III/IV were 15 and 9 in the biliary antigen (-) group, and 4 and 12 in the biliary antigen (+) group, respectively, with a statistically significant difference (p = 0.024). The 1, 3 and 5-year disease-free survival rates were 69.7, 40.9 and 40.9% for the biliary antigen (-) group and 73.7, 39.1, 39.1% for the biliary antigen (+) group with no statistically significant difference. The 1, 3 and 5-year overall survival rates were 91.7, 73.8, 66.4% for the biliary antigen (-) group and 68.8, 34.4, 34.4% for the biliary antigen (+) group, with a significantly greater overall survival rate for the biliary antigen negative group (p = 0.045). Poor histopathological differentiation, a high HBsAg positive rate and poor overall survival rate were noted in the biliary antigen positive group and the differences were statistically significant. In conclusion, HCCs with positive biliary antigen, which originates from more primitive cells, is suggested to be more aggressive than HCCs with negative biliary antigen.

Adult↗
PubMed1999

Lower auricular malformations: their representation, correction, and embryologic correlation.

Seventy-seven lower auricular malformations in 74 patients treated during the last 6 years were analyzed. Sixty cases (77.9 percent) were of malformations involving the earlobe; 54 cases involved the earlobe alone, and 6 cases were of complex deformities involving the earlobe and adjacent helix and/or tragus. Cleft earlobe was the most common lower auricular malformation (49 cases, 63.6 percent); four subtypes and their corrective methods are described. Cases of complex earlobe malformations, corrected by fabricated costal cartilage and expanded skin flap, are presented. A question mark ear (5 cases, 6.5 percent), a malformation with an ectopic anthelical fold (5 cases, 6.5 percent), and a malformation with a lower conchal stria (5 cases, 6.5 percent) are considered to be major lower auricular malformations. An attempt has been made to correlate the presented malformations with the embryologic-fetal development of the auricle. It is suggested that "clefting" ear malformations such as the cleft earlobe, the question mark ear, and the ectopic anthelical fold deformity may provide clues to understanding the embryologic-fetal development of the human auricle. It appears that hillocks 1 and 6 produce the earlobe and that hillock 4 or 5 produces the anthelix or helix.

Adolescent↗
PubMed1998

His...Asp catalytic dyad of ribonuclease A: conformational stability of the wild-type, D121N, D121A, and H119A enzymes.

Residue His119 acts as an acid/base during the cleavage/hydrolysis reactions catalyzed by bovine pancreatic ribonuclease A (RNase A). In the native enzyme, His119 forms a hydrogen bond with Asp121. This His...Asp dyad is conserved in all homologous pancreatic ribonucleases of known sequence. Yet, replacing Asp121 with an asparagine or alanine residue does not have a substantial effect on either structure or function [Schultz, L. W., Quirk, D. J., and Raines, R. T. (1998) Biochemistry 37, 8886-8898]. Here, the pH dependencies of the conformational stabilities of wild-type RNase A and the D121N, D121A, and H119A variants were determined by monitoring thermal stability over the pH range 1.2-6.0. Replacing Asp121 with an asparagine or alanine residue results in a loss of conformational stability at pH 6.0 of deltadeltaG(o) = 2.0 kcal/mol, from a total of 9.0 kcal/mol. The magnitude of this loss is similar to that to transition-state binding during catalysis. As the pH decreases, the aspartate residue becomes protonated and deltadeltaG(o) decreases. D121N RNase A and D121A RNase A are approximately equivalent in conformational stability. This equivalence arises from compensating changes to enthalpy and entropy. A general analytical method was developed to determine the value of the pKa of a residue in the native and denatured states of a protein by comparing the pH-stability profile of the wild-type protein with that of a variant in which the ionizable residue is replaced with a nonionizable one. Accordingly, Asp121 was found to have pKa values of approximately 2.4 and 3.4 in the native and denatured states, respectively, of wild-type RNase A. This change in pKa can account fully for the differential effects of pH on the conformational stabilities of the wild-type and variant proteins. We conclude that the His...Asp catalytic dyad in pancreatic ribonucleases has two significant roles: (1) to position the proper tautomer of His119 for catalysis and (2) to enhance the conformational stability of the native enzyme. Most enzymic residues contribute to catalysis or stability (or neither). Asp121 of RNase A is a rare example of a residue that contributes equally to both.

Alanine↗
PubMed1998

Expression of fas antigen in the normal mouse brain.

The Fas antigen (Fas/Apo-1/CD95) is a cell surface receptor protein that mediates apoptosis-inducing signals and plays an important role in the immune system. In the central nervous system, during the period of naturally occurring cell death many neurons appear to die by apoptosis. We investigated the involvement of Fas in these events. The expression of Fas transcripts and protein was examined in the juvenile mouse brain. By RT-PCR analysis, Fas mRNA was detected in the cerebrum, cerebellum, and hippocampus of the brain. By immunohistochemistry, we found Fas in neurons localized in the CA2 and CA3 sectors of the hippocampus and in the cortical III layer of the cerebrum, but not neurons in the cerebellum. Furthermore, Fas was expressed on the primary cultured hippocampal and cerebral cells using immunofluorescence and flow cytometry. These results suggest that Fas is specifically expressed on neurons in the mouse brain during postnatal development.

Animals↗
PubMed1998

Son of sevenless binds to the SH3 domain of src-type tyrosine kinase.

To identify molecules which bind to the SH3 domains of p56lck, we screened a mouse T-cell lymphoma cDNA library using the yeast two-hybrid system. As a result, we obtained several positive clones including the Son of Sevenless gene which encodes a mammalian homolog of Drosophila Ras GDP/GTP exchange factor. In a subsequent analysis with the yeast two-hybrid system, Sos associated only with the constitutively active form of p56lck (F505) but not with wild type p56lck (Y505), indicating the requirement for an active conformation of p56lck for binding to Sos. Subsequently, we have demonstrated in vitro that the SH3 domain of p56lck as well as the proline-rich sequences of Sos are responsible for this association. In addition, the proline-rich domain of Sos also bound to the SH3 domains of other src-type tyrosine kinases, src and fyn, but not to that of PLC-gamma. More importantly, the p56lck SH3-Sos interaction was enhanced by serum stimulation, suggesting the possibility that the direct interaction between p56lck SH3 and Sos may contribute to the regulation of the Ras pathway.

Animals↗
PubMed1998

erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.

BACKGROUND: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. METHODS: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. RESULTS: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P=.02), lack of estrogen receptors (P=.008), and the number of positive lymph nodes (P=.0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors--DFS: relative risk of failure (RR)=0.60 (95% confidence interval [CI]=0.44-0.83), P=.001; survival: RR=0.66 (95% CI=0.47-0.92), P =.01; RFS: RR=0.58 (95% CI=0.42-0.82), P=.002; DDFS: RR=0.61 (95% CI=0.44-0.85), P=.003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR=0.96 (95% CI=0.75-1.23), P=.74; survival: RR =0.90 (95% CI=0.69-1.19), P=.47; RFS: RR=0.88 (95% CI=0.67-1.16), P=.37; DDFS: RR=1.03 (95% CI=0.79-1.35), P=.84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P=.02) and DDFS (P=.02) but not for survival (P= .15) or RFS (P=.06). CONCLUSIONS: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

Adult↗
PubMed1998

Deletion mapping of chromosome 4q in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) frequently shows a loss of heterozygosity (LOH) on chromosome 4q. In order to define the commonly affected region on chromosome 4q for further positional cloning of the putative tumor suppressor gene, we carried out allelic imbalance (AI) studies in 41 HCCs using a panel of 43 microsatellite markers. Thirty-four cases (82.9%) showed AI at one or more loci. Detailed deletion mapping identified 7 independent, frequently deleted regions on this chromosome arm. These were the (1) D4S1615 locus, (2) D4S1598 locus, (3) D4S620 locus, (4) D4S1566 and D4S2979 loci, (5) D4S1617 and D4S1545 loci, (6)D4S1537 locus; and (7) from the D4S2920 to D4S2954 locus. Among these 7 frequently deleted regions, 5 were associated with tumor differentiation. Our results suggest that several putative tumor suppressor genes may be present on chromosome 4q and that the AI of chromosome 4q may play a role in the aggressive progression of HCC.

Autoradiography↗
PubMed1998

Priority of pentose utilization at the level of transcription: arabinose, xylose, and ribose operons.

When E. coli cells were grown in minimal medium supplemented with D-ribose and D-xylose, a diauxic growth preferring D-xylose was observed. Transcription of the ribose (rbs) operon was repressed in the presence of D-xylose, phenotypically similar to catabolite repression by D-glucose, although D-ribose did not affect transcription of the xylose (xyl) operon. Complementation analysis with xylR revealed that the repression of the rbs operon by D-xylose is exerted at the transcriptional level through XylR, suggesting a novel mechanism for catabolite repression. Furthermore, it was shown that L-arabinose reduced transcriptions of both xyl and rbs operons, whereas the arabinose operon was not affected by D-xylose or D-ribose, suggesting a priority mechanism for pentose utilization.

Arabinose↗
PubMed1998

Utilization of D-ribose through D-xylose transporter.

An Escherichia coli mutant defective in high-affinity D-ribose transport is able to utilize the sugar as a sole carbon source, suggesting that other transport systems for D-ribose exist. In order to search for such transporters, transposon mutagenesis was carried out in an rbsB-negative strain containing ribokinase (rbsK) for sugar phosphorylation. Insertions showing an enhanced ribose growth were isolated and mapped in xylA and its promoter region. The mutations increased not only the ribose uptake but also the expression of xylFGH encoding an ABC (ATP-binding cassette)-type transporter for D-xylose. Secondary mutations abolishing the ribose-utilizing phenotype were obtained both in the xylFG genes coding for the xylose high-affinity transporter and in xylR that is required for the xyl gene expression. Ribose uptake was also reduced by the secondary mutations. An overexpression of xylFGH under Ptrc promoter supported enhanced growth on ribose. These results indicate that D-ribose can be transported through the XylFGH transporter.

ATP-Binding Cassette Transporters↗
PubMed1998

Partial structural functions of binary liquids estimated from anomalous X-ray scattering measurements.

A new apparatus has been built for structural studies of high-temperature liquids using the anomalous X-ray scattering (AXS) method with synchrotron radiation. AXS measurements were made in the asymmetrical reflection mode for a free liquid surface by changing the beam direction using an additional mirror system. The usefulness and capabilities of this new equipment were confirmed by obtaining the individual partial structural functions of liquid Bi(30)Ga(70) alloy.

Journal Article↗
PubMed1998

Homozygous deletions of the CDKN2 gene and loss of heterozygosity of 9p in primary hepatocellular carcinoma.

To elucidate the alterations of CDKN2 in hepatocarcinogenesis, we performed a loss of heterozygosity (LOH) study using eight polymorphic markers surrounding the CDKN2 gene and analyzed the homozygous deletions and mutations of the CDKN2 gene in 41 primary hepatocellular carcinomas (HCCs). Frequent LOH (27.8-44%) was found in the eight loci on chromosome 9p, however, no intragenic mutations of CDKN2 were observed by PCR-SSCP analysis. Homozygous deletions were detected in 25 of 41 HCCs (61%) by a comparative multiplex PCR. No expression of the CDKN2 protein was noted in five out of nine available HCCs by Western blot analysis. These results suggest that inactivation of the CDKN2 gene in HCC is a frequent event in which homozygous deletions are the most common mechanism of CDKN2 inactivation.

Carcinoma, Hepatocellular↗
PubMed1998

Allelotype analysis of hepatocellular carcinoma.

To elucidate the genetic events which may play important roles in hepatocarcinogenesis, we examined every non-acrocentric chromosome arm of 22 hepatocellular carcinomas (HCCs) for loss of heterozygosity (LOH) using 68 highly polymorphic microsatellite markers. Thirty-six (92%) of 39 chromosome arms showed LOH in at least one patient, however 3 chromosome arms, 2p, 2q, and 20q, did not show any LOH. High to moderate frequency of LOH (> 30% of informative cases) was observed at chromosomes 1q (68.1%), 4q (72.7%), 8p (63.6%), 8q (77.3%), 10q (33.3%), 13q (40%), 14q (46.1%), 16q (59.1%), and 17p (46.2%). Among these, LOH on chromosomes 1q and 8q have not been previously identified in HCC. Our results suggest that novel tumor suppressor genes may be involved in the development and progression of HCC.

Alleles↗
PubMed1998

Chromatin configuration during meiosis I prophase of spermatogenesis.

During the pachytene stage of meiotic prophase in male mammals, the X and Y chromosomes become transcriptionally inactive and establish a chromatin domain, the sex body, that is visually distinct from the transcriptionally active autosomes. We used objective criteria to assess these chromatin differences by DNase I sensitivity (DS) of sex chromosome and autosomal sequences at both the cytological and molecular levels. For cytological studies, in situ nick translation techniques were used on air-dried preparations of testicular cells. For molecular studies, nuclei from pachytene spermatocytes were subjected to nuclease sensitivity assays. Both sex-linked and autosomal sequences were assessed, including some gene sequences that are expressed and some that are not expressed in pachytene spermatocytes. There was a wide range of DS in different genomic sequences; however, the sex-linked sequences generally were less nuclease sensitive than were autosomal sequences. Interestingly, a hot spot of recombination (within the Eb gene) showed a high level of nuclease sensitivity, while a cold spot of recombination (centromeric satellite region) exhibited lower sensitivity, more similar to that of sex-linked sequences. We also examined the nuclease sensitivity of a tyrosinase transgene insert, TyBS. In one line of mice, the transgene insert is X-linked, whereas in another, it is autosomal. The transgene was less nuclease sensitive when X-linked than as an autosomal insert. These results support the hypothesis that in pachytene spermatocytes the XY chromosome pair is more condensed and inaccessible to enzymatic digest, whereas the autosomal chromatin is in a more open configuration. In addition, we examined the nuclease sensitivity of some of the same genes in the earlier leptotene/zygotene prophase stage, when the sex chromatin is not maximally condensed. We found that while autosomal gene nuclease sensitivity was equivalent to that at the pachytene stage, X-linked sequences were more nuclease sensitive. Overall, these differences in chromatin nuclease sensitivity correlate with differences in meiotic recombination activity and may be mechanistically related.

Animals↗
PubMed1998

Germ cell loss in the XXY male mouse: altered X-chromosome dosage affects prenatal development.

Male mammals with two X chromosomes are sterile due to the demise of virtually all germ cells; however, the underlying reasons for the germ cell loss remain unclear. The use of a breeding scheme for the production of XXY male mice has allowed us to experimentally address the question of when and why germ cells die in the XXY testis and whether the defect is due to the presence of an additional X chromosome in the soma, the germ cells themselves, or both. Our studies demonstrate that altered X-chromosome dosage acts to impair germ cell development in the testis at a much earlier stage than suggested by previous studies of XX sex-reversed males or XX/XY chimeras. Specifically, we noted significantly reduced germ cell numbers in the XXY testis during the period of germ cell proliferation in the early stages of testis differentiation. Although the somatic development of the XXY testis is morphologically and temporally normal, our studies indicate that germ cell demise reflects a defect in somatic/germ cell communication, since, in an in vitro system, the proliferative potential of fetal germ cells from XXY males is indistinguishable from that of normal males.

Animals↗
PubMed1998

Protein-DNA interactions in interferon-gamma signaling.

The ability to rapidly activate new genes is essential for the biological effects mediated by IFN-gamma. Studies directed at understanding how these genes are induced by this ligand led to the identification of the STAT family of transcription factors. STATs are rapidly activated at the receptor, whereupon they translocate to the nucleus and bind to a unique enhancer found in the promoter of target genes. The ability to identify this IFN-gamma response element and the proteins that bind it was critical for the elucidation of this pathway. These techniques are the focus of this review.

Base Sequence↗
PubMed1998

Surgical resection of lung cancer originating in a tracheal bronchus.

We experienced a case of lung cancer that developed from a tracheal bronchus in an 80-year-old man. The tumor was completely resected by right upper lobectomy and resection of the tracheal bronchus as well as dissection of the mediastinal lymph nodes. Postsurgical pathologic staging was stage IB (T2 N0 M0) adenocarcinoma.

Adenocarcinoma↗