Development of bioartificial liver system using a fluidized-bed bioreactor.
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Biomedical subjects
Publications and source records attributed to Y I Kim.
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Quantitative ultrasound (QUS) of bone is a new radiation-free, low-cost method that measures both bone mass and bone quality. This study was performed to establish the normative data of QUS for Korean women and to determine the prevalence and risk factors of low quantitative ultrasound values in a Korean elderly population. We studied 238 healthy women aged 20-29 years working at a hospital, and 552 women over 50 years of age living in six villages of Chung-Up district, a rural area of South Korea, using QUS measurement of bone. Broadband ultrasound attenuation and speed of sound were measured at the calcaneus, and an index combining these factors (stiffness index) was calculated. T-score was calculated from the data of young normal subjects. Of the 552 elderly women, 34.2% had T-scores between -1.0 and -2.5, and 11.8% had T-scores below -2.5. The prevalence of low quantitative ultrasound values increased with older age, longer duration following menopause, lower body mass index, younger age at menopause and smoking. In multiple logistic regression analysis, age (odds ratio = 1.40 per 5 years, P < 0.05), duration following menopause (odds ratio = 1.35 per 5 years, P < 0.05) and body mass index (odds ratio = 0.78 per quartile, P < 0.05) were independently associated with low quantitative ultrasound values. These results suggested that quantitative ultrasound measurement of the calcaneus could be a useful tool for epidemiological surveys of bone mass.
Ephrin-A2 and -A5 are thought to be anteroposterior mapping labels for the retinotectal/retinocollicular projection. Here, gene disruptions of both these ephrins are characterized. Focal retinal labeling reveals moderate map abnormalities when either gene is disrupted. Double heterozygotes also have a phenotype, showing an influence of absolute levels. In vitro assays indicate these ephrins are required for repellent activity in the target and also normal responsiveness in the retina. In double homozygotes, anteroposterior order is almost though not completely lost. Temporal or nasal retinal labelings reveal quantitatively similar but opposite shifts, with multiple terminations scattered widely over the target. These results indicate an axon competition mechanism for mapping, with a critical role for ephrins as anteroposterior topographic labels. Dorsoventral topography is also impaired, showing these ephrins are required in mapping both axes.
ClpXP is a protein machine composed of the ClpX ATPase, a member of the Clp/Hsp100 family of remodeling enzymes, and the ClpP peptidase. Here, ClpX and ClpXP are shown to catalyze denaturation of GFP modified with an ssrA degradation tag. ClpX translocates this denatured protein into the proteolytic chamber of ClpP and, when proteolysis is blocked, also catalyzes release of denatured GFP-ssrA from ClpP in a reaction that requires ATP and additional substrate. Kinetic experiments reveal that multiple reaction steps require collaboration between ClpX and ClpP and that denaturation is the rate-determining step in degradation. These insights into the mechanism of ClpXP explain how it executes efficient degradation in a manner that is highly specific for tagged proteins, irrespective of their intrinsic stabilities.
The purpose of the present study was to characterize the Ca2+ channels in smooth muscle cells from human stomach and to examine the effects of osmotic swelling on the channel activity. Ca2+ channel current with either Ca2+ or Ba2+ as charge carrier was recorded from freshly isolated smooth muscle cells using the conventional whole-cell patch clamp technique. The degree of cell swelling as a result of hypotonic challenge was monitored using a video image analysis system. The changes in intracellular Ca2+ concentration ([Ca2+]i) were measured by microfluorimetry. The pharmacological and voltage activation profile suggests a typical dihydropyridine-sensitive L-type Ca2+ current. Cell swelling, induced by hypotonic challenge, enhanced the amplitude of currents through L-type Ca2+ channels without significant effects on steady-state voltage dependency. After treatment with the L-type Ca2+ channel agonist Bay K 8644 (0.1-2 microM), no further significant increase in calcium channel current or corresponding [Ca2+]i transients were provoked by the swelling. The above results demonstrated that the presence of L-type Ca2+ current in smooth muscle cells of the human stomach and the augmentation of the current are closely associated with the volume increase resulting from hypotonic swelling.
Sixty-three cases of stomach resections harboring both adenoma and carcinoma were analyzed for microsatellite instability (MSI). The cases included 28 carcinomas arising from adenoma (Type I) and 35 carcinomas with separate adenoma (Type II). The results of MSI assessed by 49 markers were the same for BAT-26 instability. The incidence of MSI was 21% in gastric adenoma and 30% in gastric carcinoma, which is significantly higher than gastric carcinoma without associated adenoma (p < 0.01). Five of eight (63%) cases of multiple carcinomas associated with adenoma showed MSI+ in adenoma and in one or more carcinoma lesion(s). Eight of thirteen (62%) MSI+ adenomas were associated with carcinoma, whereas 20 of 50 (40%) MSI adenomas were associated with carcinoma. MSI+ adenomas of Type I showed a higher mutation rate of the TGF-beta RII gene than Type II (88% versus 40%). Gastric adenoma with TGF-beta RII gene mutation was more prone to transform into carcinoma (p = 0.03). This study revealed that gastric carcinoma arising from adenoma is frequently associated with a mismatch repair deficiency mechanism. In the gastric adenoma-carcinoma sequence, TGF-beta RII gene mutation occurred early in the adenoma stage and it persisted after malignant transformation.
To identify the chromosomal loci of allelic loss in intrahepatic cholangiocarcinoma (ICC), we performed an allelotype study of 36 ICCs using 55 genome-wide microsatellite markers. Loss of heterozygosity was found most frequently on 8p (65.6%), 17p (64.7%), and 9p (64.5%), followed by 18q (54.2%), 1p (48.5%), 3p (44.8%), 9q (42.1%), 14q (41.7%), 6q (41.7%), and 1q (40.6%). The fractional allelic loss (FAL) values ranged from 0 to 0.731 (mean, 0.322). Analysis of the relationship between FAL values and clinicopathologic parameters disclosed significantly higher FAL values in moderately to poorly differentiated ICCs than in well-differentiated ones (P < .05). In summary, this study defined for the first time the overall number of chromosomes having allelic loss and the chromosomal arms and/or regions potentially involved in the development of ICC.
AIMS: To clarify the relationship between the Epstein-Barr virus (EBV) and gastric carcinoma with lymphoid stroma (GCLS) in Koreans, and to characterize the EBV-positive GCLS. METHODS AND RESULTS: EBV infection was examined using EBER in-situ hybridization and polymerase chain reaction in 45 cases of GCLS among Koreans, and in 292 consecutive cases of gastric carcinomas without lymphoid stroma (non-GCLS) as controls. EBV infection was found in 30 tumours (67%) of GCLS and 10 tumours (3.4%) of non-GCLS (P < 0.05). EBV-positive GCLS was more prevalent in males, poorly differentiated histological type and diffuse type in Lauren's classification, and tended to be located more in the middle third of the stomach than EBV-negative GCLS (P < 0.05). p53 overexpression was observed in 22% of GCLS (17% of EBV-positive GCLS and 33% of EBV-negative GCLS), and 34% of non-GCLS (EBV-positive GCLS vs. non-GCLS: P = 0.056). The survival of the patient with GCLS was not correlated with EBV infection or p53 immunoexpression (follow-up period: 11-97 months). CONCLUSIONS: GCLS in Koreans is strongly associated with EBV infection. The prognosis in GCLS is not dependent upon either the status of EBV infection or the status of p53 immunoexpression.
Clinicopathological analysis, microsatellite analysis, detection of Epstein-Barr virus (EBV), and immunohistochemistry on p53 protein were performed in 26 cases of gastric remnant cancer (GRC). They were divided into two groups; Group A (n = 14) who had undergone a primary gastrectomy for benign gastric disease, and Group B (n = 12) who had undergone the same operation for gastric cancer. EBV infection was present in 29% of Group A, 8% of Group B and 6% of the conventional gastric carcinoma (CGC) (Group A vs CGC, P = 0.01). Microsatellite instability (MSI) was found in 7% of Group A, 25% of Group B, and 9% of the CGC (Group B vs CGC; P = 0.08). p53 Overexpression was observed in 46% of the GRC and 33% of the CGC. p53 Overexpression was observed in 90% of the intestinal type of GRC, but in only 20% of the diffuse type of GRC (P = 0.002). The cancer stage was a significant factor in the univariate analysis of survival (P = 0.04). In conclusion, GRC is different from CGC in terms of MSI or EBV association. The pathogenetic differences between the two groups require further investigation. EBV infection may have been involved in the carcinogenesis of Group A. MSI may be an important factor in the carcinogenesis of metachronous multiple gastric cancer (Group B).
Microsatellite instability (MSI) due to defective DNA mismatch repair (MMR) is a form of genomic instability underlying the tumorigenesis of various human neoplasms. To evaluate the roles of MSI in the pathogenesis of gastric carcinomas with squamous differentiation, 17 primary stomach cancer patients (15 adenosquamous and two squamous cell carcinomas) were examined for MSI frequency using five microsatellite markers and the criteria for MSI recommended by the National Cancer Institute Workshop. The molecular causes and consequences of MSI in these neoplasms were further researched through the immunohistochemistry of MMR proteins and the mutational analysis of cancer-associated genes targeted by MSI, respectively. Two of the 17 (12%) cases demonstrated MSI at the most examined loci and were classified as having high level MSI (MSI-H). These tumors also exhibited frame-shift mutations at mononucleotide repeats in the target genes, including TGFbetaRII, IGFIIR, BAX, and hMSH6. It is interesting to note that the mutations of the serine (AGC)13 repeats within the E2F-4 gene were found only in the squamous cell carcinoma portions of them, whereas such alterations were not detected in any of the adenocarcinomatous portions. This suggests that E2F-4 might be implicated in the transformation of adenocarcinoma into squamous cell carcinoma and further studies are needed to understand its role in squamous differentiation.
AIMS: To assess the diagnostic value of magnetic resonance (MR) cholangiography versus conventional cholangiography in patients with choledochal cyst and to determine whether MR cholangiography can be considered an alternative to conventional cholangiography. MATERIALS AND METHODS: Thirteen patients with choledochal cyst were examined by MR cholangiography and conventional cholangiograms. Magnetic resonance cholangiography employed T2-weighted axial and coronal fast spin-echo, single and multislab single-shot fast spin-echo sequences, including source images with maximum intensity projections. The diagnostic value of MR cholangiography and conventional cholangiograms was assessed and compared using the criteria of depiction of morphology, anomalous pancreaticobiliary duct union and demonstration of complications such as stones. A four-point diagnostic scale was applied to the delineation of the ductal anatomy with the Wilcoxon signed-ranks test and McNemar's test used for statistical analysis. RESULTS: The depiction of the choledochal cyst was significantly better with MR cholangiography than with conventional cholangiography (P = 0.03). The detection rate of an anomalous pancreaticobiliary duct union was not significantly different with either method (P = 0.641), nor was the detection rate of bile duct stones (P = 0.375). CONCLUSION: Magnetic resonance cholangiography provides data equivalent to or superior to those from conventional cholangiography in evaluating choledochal cyst. Magnetic resonance cholangiography is recommended as a non-invasive examination of choice for the evaluation of choledochal cyst.
BACKGROUND & AIMS: Diminished folate status has been observed to increase colorectal cancer risk. Folate plays an important role in DNA synthesis and repair. This study investigated the effects of dietary folate on DNA strand breaks in the p53 and Apc genes, and how these changes are related to steady-state levels of the corresponding transcripts. METHODS: Three groups of rats were fed diets containing 0, 2 (basal requirement), or 8 mg folate/kg for 5 weeks. At each weekly time point, plasma and colonic mucosal folate concentrations were determined. Site-specific DNA strand breaks were assessed by semiquantitative PCR. Steady-state levels of messenger RNA were measured by semiquantitative RT-PCR. RESULTS: Dietary folate deficiency produced progressive DNA strand breaks within exons 5-8 of the p53 gene in rat colon (P<0.02). Accumulation of strand breaks was not observed in other exons of the p53 gene, in the Apc and beta-actin genes, or at the genomic level. Folate supplementation at 4 times the basal requirement significantly increased p53 integrity compared with the basal and deficient diets (P<0.05). p53 integrity in exons 5-8 was significantly correlated with folate status (P<0.03). Dietary folate deprivation progressively decreased, whereas supplementation increased, steady-state levels of p53 transcript over 5 weeks (P<0.05). No such changes were observed for the Apc gene. Steady-state levels of p53 transcript were significantly correlated with folate status and p53 integrity in exons 5-8 (P<0.002). CONCLUSIONS: These data provide a plausible mechanism by which folate deficiency promotes, and folate supplementation suppresses, colorectal carcinogenesis.
OBJECTIVE: To compare the predictive power of International Classification of Diseases 10th Edition (ICD-10)-based International Classification of Diseases 9th Edition-based Injury Severity Score (ICISS) with Trauma and Injury Severity Score (TRISS) and ICD-9CM-based ICISS in the injury severity measure. METHODS: ICD-10 version of survival risk ratios was derived from 47,750 trauma patients from 35 emergency centers for 1 year. The predictive power of TRISS, the ICD-9CM-based ICISS and ICD-10-based ICISS were compared in a group of 367 severely injured patients admitted to two university hospitals. The predictive power was compared by using the measures of discrimination (disparity, sensitivity, specificity, misclassification rates, and receiver operating characteristic curve analysis) and calibration (Hosmer-Lemeshow goodness-of-fit statistics), all calculated by logistic regression procedure. RESULTS: ICD-10-based ICISS showed a lower performance than TRISS and ICD-9CM-based ICISS. When age and Revised Trauma Score were incorporated into the survival probability model, however, ICD-10-based ICISS full model showed a similar predictive power compared with TRISS and ICD-9CM-based ICISS full model. ICD-10-based ICISS had some disadvantages in predicting outcomes among patients with intracranial injuries. However, such weakness was largely compensated by incorporating age and Revised Trauma Score in the model. CONCLUSION: The ICISS methodology can be extended to ICD-10 horizon as a standard injury severity measure in the place of TRISS, especially when age and Revised Trauma Score were incorporated in the model. For patients with intracranial injuries, the predictive power of ICD-10-based ICISS was relatively low because of differences in the classifying system between ICD-10 and ICD-9CM.
Tea is a pleasant, popular, socially accepted, economical, and safe drink that is enjoyed every day by hundreds of millions of people across all continents. Tea also provides a dietary source of biologically active compounds that help prevent a wide variety of diseases. It is the richest source of a class of antioxidants called flavonoids and contains many other beneficial compounds such as vitamins and fluoride. A growing body of evidence suggests that moderate consumption of tea may protect against several forms of cancer, cardiovascular diseases, the formation of kidney stones, bacterial infections, and dental cavities. Future research needs to define the actual magnitude of health benefits, establish the safe range of tea consumption associated with these benefits, and elucidate potential mechanisms of action.
Recent epidemiologic studies suggest that common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in the general North American population may modulate cancer risk. In some cancers, folate and other nutrients involved in the MTHFR metabolic pathway appear to interact with MTHFR polymorphisms to further modify cancer risk. In carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient interactions, an emerging and important topic in the field of nutrition and cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide an opportunity to identify an ideal target group of individuals, at high risk of developing cancer, for rational, effective, and safe chemoprevention using these nutrients.
BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.
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