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Biomedical subjects

Y I Kim

Publications and source records attributed to Y I Kim.

At least 37 records · Page 2Linked to original sources
PubMed2001

MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators.

BACKGROUND: Although mucin expressions appear to be correlated with prognoses in patients with various cancers, several studies have reported conflicting and inconclusive results on the prognostic significance of mucin expression in gastric carcinomas. METHODS: To clarify the correlations between clinicopathologic profiles and the patients' survival, the expression of MUC1, MUC2, MUC5AC, MUC6 mucins and the p53 protein were evaluated immunohistochemically in 300 consecutive gastric carcinomas using the tissue-array method. In addition, 59 gastric adenomas and 57 adenoma-associated carcinomas were investigated. RESULTS: MUC1 was expressed in 2 (3.4%) cases of gastric adenoma, and MUC2 in 19 (32.2%) cases of gastric adenoma, out of a total of 59 lesions. In consecutive gastric carcinomas, 24.3% of gastric carcinomas expressed MUC1, 27.3% expressed MUC2, 38.0% expressed MUC5AC and 12.7% expressed MUC6. The rate of MUC1 expression in gastric carcinomas was significantly higher than in associated gastric adenomas (P < 0.01). The patients with MUC1-positive carcinomas showed significantly poorer survival than those with MUC1-negative carcinomas. On the other hand, MUC2, MUC5AC and MUC6 expressions were not significantly associated with patient survival. Interestingly, combined evaluation revealed that the group with the MUC1-negative plus p53-negative expression pattern showed a better prognosis than the remaining cases. In contrast, the group with the MUC2-negative plus p53-positive pattern showed a worse prognosis. CONCLUSIONS: Mucin expression is altered in gastric adenoma and carcinoma, and MUC1 mucin expression is significantly associated with poorer outcome in gastric carcinomas. A MUC1-negative plus p53-negative pattern or a MUC2-negative plus p53-positive pattern may predict outcome in patients with gastric carcinomas.

Adenoma↗
PubMed2001

Molecular genetics of ulcerative colitis-associated colon cancer in the interleukin 2- and beta(2)-microglobulin-deficient mouse.

Mice deficient in beta(2)-microglobulin and interleukin 2 (beta(2)m(null) x IL-2(null)) spontaneously develop colon cancer in the setting of chronic ulcerative colitis (UC). We investigated mutations of the Apc and p53 genes and microsatellite instability in colonic adenocarcinomas arising in this model. Mutations of the Apc and p53 genes in the regions corresponding to mutation hot spots in human colorectal cancer were determined by sequencing in 11 colonic adenocarcinomas. Microsatellite instability was determined in matched normal and neoplastic DNA at five loci. All 11 adenocarcinomas harbored Apc mutations. Of these 11 tumors, 5 harbored truncating mutations. A total of 67 Apc mutations were found in these 11 tumors; 59 were missense mutations, whereas 8 were frameshift or nonsense mutations. Six of the 11 adenocarcinomas harbored p53 mutations. A total of seven p53 mutations were found in these 11 tumors; all mutations were transitions, 4 of which were C:G-->T:A transitions occurring in codon 229 at cytosine-guanine dinucleotides. Nine adenocarcinomas exhibited microsatellite instability in at least one of the five loci examined; 1 tumor had microsatellite instability in two loci. Molecular genetics, as well as clinical features, of colon cancer in the beta(2)m(null) x IL-2(null) mice are similar to those of human UC-associated colorectal cancer. As such, this model appears to be an excellent animal model to study UC-associated colorectal carcinogenesis.

Adenocarcinoma↗
PubMed2001

A novel method for convenient assessment of arthritic pain in voluntarily walking rats.

Quantification of arthritic pain can be very useful in elucidating the mechanisms of arthritis and in assessing the effect of anti-arthritic medication or treatment. Here we report a novel method that allows convenient measurements of the severity of arthritic pain in voluntarily walking rats. We constructed a device to measure the weight load on each leg while the animal was walking through a path, the bottom of which was equipped with strain gauge weight sensors. Using this device, we measured the weight load on the right hind leg before and after induction of arthritis by carrageenan injection into the knee joint cavity of this leg. The carrageenan injection resulted in a significant reduction of weight load on the affected leg; the load decreased to the minimum level at 4 h after the injection and gradually returned to the pre-injection level by the fifth day. Intraperitoneal administration of morphine at 5.5 h after carrageenan injection could reverse the weight load change. These results suggest that our new device is an effective tool for convenient measurements of arthritic pain in dynamic conditions like walking.

Analgesics, Opioid↗
PubMed2001

Effects of protein stability and structure on substrate processing by the ClpXP unfolding and degradation machine.

ClpXP is an ATP-dependent protease that denatures native proteins and translocates the denatured polypeptide into an interior peptidase chamber for degradation. To address the mechanism of these processes, Arc repressor variants with dramatically different stabilities and unfolding half-lives varying from months to seconds were targeted to ClpXP by addition of the ssrA degradation tag. Remarkably, ClpXP degraded each variant at a very similar rate and hydrolyzed approximately 150 molecules of ATP for each molecule of substrate degraded. The hyperstable substrates did, however, slow the ClpXP ATPase cycle. These results confirm that ClpXP uses an active mechanism to denature its substrates, probably one that applies mechanical force to the native structure. Furthermore, the data suggest that denaturation is inherently inefficient or that significant levels of ATP hydrolysis are required for other reaction steps. ClpXP degraded disulfide-cross-linked dimers efficiently, even when just one subunit contained an ssrA tag. This result indicates that the pore through which denatured proteins enter the proteolytic chamber must be large enough to accommodate simultaneous passage of two or three polypeptide chains.

Adenosine Triphosphatases↗
PubMed2001

Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus.

Glutamate is considered to be the primary neurotransmitter in the retinohypothalamic tract (RHT), which delivers photic information from the retina to the suprachiasmatic nucleus (SCN), the locus of the mammalian circadian pacemaker. However, substance P (SP) also has been suggested to play a role in retinohypothalamic transmission. In this study, we sought evidence that SP from the RHT contributes to photic resetting of the circadian pacemaker and further explored the possible interaction of SP with glutamate in this process. In rat hypothalamic slices cut parasagittally, electrical stimulation of the optic nerve in early and late subjective night produced a phase delay (2.4 +/- 0.5 hr; mean +/- SEM) and advance (2.6 +/- 0.3 hr) of the circadian rhythm of SCN neuronal firing activity, respectively. The SP antagonist L-703,606 (10 microm) applied to the slices during the nerve stimulation completely blocked the phase shifts. Likewise, a cocktail of NMDA (2-amino-5-phosphonopentanoic acid, 50 microm) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione, 10 microm) antagonists completely blocked the shifts. Exogenous application of SP (1 microm) or glutamate (100 microm) to the slices in early subjective night produced a phase delay ( approximately 3 hr) of the circadian firing activity rhythm of SCN neurons. Coapplication of the NMDA and non-NMDA antagonist cocktail (as well as L-703,606) resulted in a complete blockade of the SP-induced phase delay, whereas L-703,606 (10 microm) had no effect on the glutamate-induced delay. These results suggest that SP, as well as glutamate, has a critical role in photic resetting. Furthermore, the results suggest that the two agonists act in series, SP working upstream of glutamate.

Animals↗
PubMed2001

Fluorescence emission spectral shift measurements of membrane potential in single cells.

Previous measurements of transmembrane potential using the electrochromic probe di-8-ANEPPS have used the excitation spectral shift response by alternating excitation between two wavelengths centered at voltage-sensitive portions of the excitation spectrum and recording at a single wavelength near the peak of the emission spectrum. Recently, the emission spectral shift associated with the change in transmembrane potential has been used for continuous membrane potential monitoring. To characterize this form of the electrochromic response from di-8-ANEPPS, we have obtained fluorescence signals from single cells in response to step changes in transmembrane potentials set with a patch electrode, using single wavelength excitation near the peak of the dye absorption spectrum. Fluorescence changes at two wavelengths near voltage-sensitive portions of the emission spectrum and shifts in the complete emission spectrum were determined for emission from plasma membrane and internal membrane. We found that the fluorescence ratio from either dual-wavelength recordings, or from opposite sides of the emission spectrum, varied linearly with the amplitude of the transmembrane potential step between -80 and +60 mV. Voltage dependence of difference spectra exhibit a crossover point near the peak of the emission spectra with approximately equal gain and loss of fluorescence intensity on each side of the spectrum and equal response amplitude for depolarization and hyperpolarization. These results are consistent with an electrochromic mechanism of action and demonstrate how the emission spectral shift response can be used to measure the transmembrane potential in single cells.

Cell Line↗
PubMed2001

Microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes in the Korean population.

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.

Adult↗
PubMed2001

Development and characterization of a hybrid bioartificial liver using primary hepatocytes entrapped in a basement membrane matrix.

For the development of a bioartificial liver (BAL) support device, it is most important to establish highly differentiated liver cells cultured at high density. When rat hepatocytes were cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, their rates of albumin secretion were very high, as measured by ELISA, and these high rates were maintained for more than three weeks of culturing. This level of activity greatly exceeded that of hepatocytes cultured on a plastic substratum, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), on a single layer of collagen, or in a collagen sandwich culture. In an in vitro perfusion experiment, rat hepatocytes rapidly and completely removed ammonia from Eagle's MEM supplemented with 0.2 mM NH4Cl, although ammonia levels of the medium serially increased in modules containing HepG2 cells. A hybrid liver support system was developed and consisted of plasma perfusion through porous hollow fiber modules inoculated with 10 billion porcine hepatocytes entrapped in EHS gel. This system was applied to pigs with ischemic liver failure 8 hr after creation of a portocaval shunt and hepatic devascularization. In animals treated with the BAL support system, blood bicarbonate levels were increased immediately after treatment, and hemodynamic stability was improved. In control pigs, on the other hand, blood bicarbonate levels and blood pressure remained low. Plasma levels of ammonia and lactate decreased in pigs treated with the BAL device, but not in control animals. These results indicate that primary hepatocytes outperform HepG2 cells as a source of biotransformation functions in a BAL system and that the use of a BAL support device in combination with a hollow fiber module and hepatocytes entrapped in EHS gel has potential advantages for clinical use in patients with fulminant hepatic failure.

Ammonia↗
PubMed2001

Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase.

The Clp/Hsp100 ATPases are hexameric protein machines that catalyze the unfolding, disassembly and disaggregation of specific protein substrates in bacteria, plants and animals. Many family members also interact with peptidases to form ATP-dependent proteases. In Escherichia coli, for instance, the ClpXP protease is assembled from the ClpX ATPase and the ClpP peptidase. Here, we have used multiple sequence alignments to identify a tripeptide 'IGF' in E. coli ClpX that is essential for ClpP recognition. Mutations in this IGF sequence, which appears to be part of a surface loop, disrupt ClpXP complex formation and prevent protease function but have no effect on other ClpX activities. Homologous tripeptides are found only in a subset of Clp/Hsp100 ATPases and are a good predictor of family members that have a ClpP partner. Mapping of the IGF loop onto a homolog of known structure suggests a model for ClpX-ClpP docking.

ATP-Dependent Proteases↗
PubMed2001

Microsatellite instability in double primary cancers of the colorectum and stomach.

Little is known about genetic alterations of patients who present multiple primary cancers. We hypothesized that microsatellite instability (MSI) is one of the underlying genetic factors in the development of double primary cancers in colorectal cancer patients. We examined for MSI in 41 colorectal cancer patients who presented with extra-colonic primary cancers consisted of 17 gastric and 24 non-gastric cancers. Coincident MSI+ in tumors of two organs were observed in 3 (17.7%) of 17 patients with colon and stomach cancers and 0 of 24 patients with colon and non-gastric cancers (P =.03). In 17 patients with colon and stomach cancers, 6 (31.6%) of 19 colon cancers and 3 (17.7%) of 17 gastric cancers exhibited MSI+. Among four patients with metachronous colon cancers who were identified within the 41 double primary cancer patients, two patients were associated with the MSI+ phenotype. In summary, the prevalent coincidence of MSI suggests that genetic defect of mismatch repair deficiency may be responsible for a small subset of double primary cancers of the colorectum and stomach.

Aged↗
PubMed2001

Survival of conditionally immortalized hepatocytes in the spleen of syngeneic rats.

BACKGROUND: Hepatocyte transplantation has been shown to be effective in the treatment of liver failure; however, the shortage of donor organs limits its clinical application. Several reports have suggested that conditionally immortalized hepatocytes (CIH) could be an alternative to primary hepatocytes. However, CIH are known to undergo apoptosis in vitro at a non-permissive temperature, which is similar to body temperature. METHODS: To investigate the duration of survival and in vivo apoptosis of CIH in the syngeneic host, the L2A2 cells (a kind of CIH) that were established from hepatocytes of a Lewis rat with a gene for a temperature-sensitive Simian Virus 40 (SV40) large T antigen were transplanted into the spleen. Cells were isolated from the spleen that was removed periodically up to 6 months, and used to detect the presence of the L2A2 cells among them with the selective culture for CIH and T-antigen PCR. In situ apoptosis of L2A2 cells was also examined. In order to improve the survival of transplanted L2A2 cells in the host, a group of rats were partially hepatectomized 1 day before transplantation was performed. RESULTS: The L2A2 cells secreted albumin at a rate of 1.17 +/- 0.18 microg/24 h per 10(6) cells in vitro. After transplantation, L2A2 cell colonies and PCR amplification bands appeared up to 14 and 7 days, respectively, but this duration was not prolonged by a partial hepatectomy. The spleen showed a large number of hepatocytes that were in the process of dying on the 5th day, and only a number of ghost hepatocytes were present on the 7th day of transplantation. No tumors were found during the 6-month observation period. CONCLUSIONS: Conditionally immortalized hepatocytes can survive in the spleen for a limited period, in spite of the growth stimulation, most likely because they undergo apoptosis in vivo as well as in vitro at a non-permissive temperature. These data suggest that the use of these cells in hepatocyte transplantation be limited to temporary hepatic support.

Albumins↗
PubMed2001

Clinicopathologic characteristics of Epstein-Barr virus-incorporated gastric cancers in Korea.

We evaluated the rate of Epstein-Barr virus (EBV) infection in gastric carcinomas of Korean patients and investigated the associations between EBV infection and clinicopathological characteristics, the survival rates of patients, and p53 overexpression. EBV-encoded small RNA (EBER)-in situ hybridization and immunohistochemistry for p53 protein were done in 306 consecutive gastric carcinoma cases, of which 17 (5.6%) showed EBV infection. Of these 17 EBV-positive cases, one case strongly expressed p53 protein, while 98 (34%) of 285 EBV-negative cases overexpressed p53 (p < 0.05). The EBV-positive gastric carcinomas tended to have lymphoid stroma. They were mostly of the poorly differentiated type, negative for p53 immunoexpression, more prevalent in male patients, and diffuse according to Lauren's classification (p < 0.05). There was no significant difference in the survival rate for the EBV status. In conclusion, the EBV infection rate among gastric carcinomas in Korea is similar to that ascertained in other countries. An inverse correlation between EBV and p53 overexpression was disclosed. Further study is needed to find out whether or not two genetic changes could be functionally overlapping during gastric carcinogenesis.

Adenocarcinoma↗
PubMed2001

The analysis of resectability and survival in pancreatic cancer patients with vascular invasion.

One of the major limitations of curative resection in patients with pancreatic cancer is local tumor extension to the mesenteric vessels. Thus, the purposes of our study were to assess the clinical value of contrast-enhanced spiral computed tomography (CT) in predicting the resectability and survival of patients with pancreatic cancer with suspicious vascular invasion and to assess the influence of curative resection on the survival of these patients. We enrolled 40 patients with pancreatic cancer who were suspected of having an involvement of the adjacent large vessels and who subsequently underwent operation with curative intent in the study. Resectability and survival were correlated with CT findings such as segment length, degree of encasement, and type and number of vessels involved. The survival rate was compared between the curative and palliative resection groups, and survival rate was compared between the resected and unresected groups. Of the 40 patients with adenocarcinoma of the pancreas, 14 had curative resections and 26 had palliative resections. The probability of curative resection was higher in patients with segment lengths less than 2 cm, as compared with segment lengths more than 2 cm. However, there was no difference in survival between the two groups. There were no differences in resectability and survival according to the degree of encasement and type and number of vessels involved. There was no difference in survival between the curative and palliative resection groups. There was no difference in survival between the resected and unresected groups. A survival benefit was not achieved by curative resection in patients with pancreatic cancer with vascular invasion. Therefore, it would be better to avoid aggressive surgery in patients with pancreatic cancer with vascular invasion.

Humans↗
PubMed2001

Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial.

OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations (p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr (p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5-8 at 6 months and 1 yr (p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials.

Adenoma↗
PubMed2001

Vegetables, fruits, and colorectal cancer risk: what should we believe?

Among dietary factors implicated in the development of colorectal cancer (CRC), the inverse relationship between vegetable and fruit consumption and CRC risk has long been believed to represent the strongest epidemiologic evidence. However, recently published large prospective studies have produced conflicting results and the results of one randomized intervention human trial do not support the protective role of vegetable and fruit consumption in colorectal carcinogenesis. Conflicting data with regard to the effect of dietary factors, including vegetables and fruits, on CRC risk likely reflect inherent, probably irresolvable, limitations of currently available tools to detect a real beneficial or harmful effect associated with these factors.

Colorectal Neoplasms↗
PubMed2001

To feed or not to feed: tube feeding in patients with advanced dementia.

Caring for demented patients with eating difficulties poses formidable challenges to health care providers and family members. Tube feeding has been routinely used in this situation to improve survival and functional status, to prevent or decrease consequences of malnutrition and wasting, and to provide comfort and palliation. However, a recent comprehensive review on this issue provides convincing arguments against the routine use of tube feeding in advanced dementia. At present, no data exist to support the theory that tube feeding improves any of the important clinical outcomes. More importantly, tube feeding is associated with significant rates of morbidity and mortality. The use of tube feeding should be highly individualized and appropriately used after careful assessment of the benefits and risks of such therapy, and with specific short- and long-term goals in mind.

Dementia↗
PubMed2001

Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number.

PURPOSE: To correlate the conspicuity of hepatocellular carcinomas and dysplastic nodules on ferumoxides-enhanced magnetic resonance (MR) images with the number of Kupffer cells in the hepatic lesions, as compared with that in background liver in histopathologic findings. MATERIALS AND METHODS: Sixty-nine histopathologically proved moderately or poorly differentiated hepatocellular carcinomas, 10 well-differentiated hepatocellular carcinomas, and 19 dysplastic nodules were retrospectively studied in 68 patients with cirrhosis who underwent ferumoxides-enhanced MR imaging. The contrast-to-noise ratio between the nodules and surrounding parenchyma was calculated at T2-weighted fast spin-echo imaging, and the difference in the number of Kupffer cells between the nodules and surrounding hepatic tissue was calculated histopathologically. The results of MR imaging and histopathologic examination were correlated. RESULTS: All 69 moderately or poorly differentiated hepatocellular carcinomas had high contrast-to-noise ratios at MR imaging and large differences in the number of Kupffer cells. Six of the 10 well-differentiated hepatocellular carcinomas had contrast-to-noise ratios of zero or nearly zero, and five of these had little difference in the number of Kupffer cells. All 19 dysplastic nodules had contrast-to-noise ratios of zero or nearly zero, and there were virtually no differences in the number of Kupffer cells. CONCLUSION: Hepatocellular nodule conspicuity at ferumoxides-enhanced MR imaging depends on differences in the number of Kupffer cells within a nodule and the surrounding cirrhotic liver; moderately or poorly differentiated hepatocellular carcinomas can be distinguished from well-differentiated hepatocellular carcinomas and dysplastic nodules.

Adult↗