Search PubMed⌕ Search

Biomedical subjects

M S Kim

Publications and source records attributed to M S Kim.

At least 109 records · Page 6Linked to original sources
PubMed2001

Effect of somatostatin on cholecystokinin-induced amylase release in rat pancreatic acini.

The effect of somatostatin on cholecystokinin-induced amylase release was investigated in isolated rat pancreatic acini. Acini were isolated by enzymatic digestion and incubated in a HEPES buffered Ringer's solution with testing reagents for 30 minutes at 37 degrees C. The activity of released amylase, cAMP, and inositol phosphate formation were measured. Intracellular calcium concentration ([Ca2+]i) was also checked. Somatostatin 14 and octreotide, a somatostatin analog, inhibited CCK-stimulated amylase release in a concentration-dependent manner. The inhibitory effect of octreotide on CCK-induced amylase release was not shown when the acini were treated with 8-Br-cAMP, irrespective of the presence of IBMX. Forskolin potentiated CCK-induced amylase release and this effect was blocked by octreotide treatment; although CCK-8 (3 x 10(-11) M) failed to stimulate cAMP formation, octreotide significantly inhibited basal cAMP formation in the acini. The increase of [Ca2+]i in response to CCK was inhibited by octreotide. However, CCK-induced inositol phosphate formation was not changed by 10(-9) M octreotide. Octreotide had no effect on CCK-stimulated tyrosine phosphorylation, and tyrosine phosphatase inhibitors (NaF and Na2WO4) did not influence the effect of octreotide on CCK-induced amylase release. From these results, we conclude that octreotide inhibits CCK-induced amylase release by inhibiting basal cAMP formation and decreasing the [Ca2+]i stimulated by CCK.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Effects of amniotic membrane on epithelial wound healing and stromal remodelling after excimer laser keratectomy in rabbit cornea.

AIMS: To investigate if the amniotic membrane (AM) promotes epithelial migration while inhibiting stromal remodelling associated with corneal haze after excimer laser keratectomy. METHODS: A wound 150 microm in depth and 6.0 mm in diameter was produced in 40 rabbits using an excimer laser. One eye was randomly chosen to be covered by the AM while the other eye served as a control. Epithelial wound healing was evaluated, together with any morphological changes of the anterior stroma connected with corneal haze. These morphological changes were histopathologically analysed using dichlortriazinyl aminofluorescein (DTAF), Masson trichrome staining, and an image analyser. RESULTS: The AM group had a short latent phase followed by fast epithelial healing (p<0.001) during the early wound healing period and a significant decrease in the inflammatory response, together with a smaller change in the number of keratocytes than the control group. The mean thickness of the regenerated stroma was significantly thinner in the AM group than in the control group at 8 weeks (p<0.0001). The AM group had a more regular architecture of regenerated stromal lamella at 8 weeks and significantly less haze after 4 weeks than the control group (p<0.05). CONCLUSION: Use of the AM as a dressing on a corneal wound created by excimer laser surgery, in which severe haze is expected, may induce rapid epithelial healing with less inflammatory response. The AM may inhibit the irregular synthesis of stromal collagen that is associated with corneal haze.

Animals↗
PubMed2001

Site-specific localization of protein kinase C isoforms in rat pancreas.

BACKGROUND: Protein kinase C (PKC), a major signal-transducing enzyme, is recognized to play an important role in the regulation of pancreatic exocrine and endocrine secretion, and yet the distribution of PKC isoforms in rat pancreas has remained unclarified. AIM OF THE STUDY: We examined the precise localization of PKC isoforms to elucidate the role of PKC in the normal rat pancreas. METHODS: Male Sprague-Dawley rats were used throughout the experiment. For Western blot analysis, the islet of Langerhans and the acinar tissue were separated by the collagenase digestion method. Also, the whole pancreas was taken out and immunohistochemistry performed. RESULTS: According to Western blot analysis, PKC-alpha, -gamma, -delta, -epsilon, -zeta, and -lambda were detected in both acinar and islet cells while PKC-beta II were observed exclusively in the islet. PKC-beta I was not observed. On immunohistochemistry, the immunoreactivities of PKC isoforms were observed as follows: PKC-alpha, weakly in some endocrine cells and ductal epithelium; PKC-beta II, mainly in the islet center; PKC-gamma, in the islet, intrapancreatic ganglia and ductal epithelium; PKC-delta, in the islet periphery, weakly in some acinar cells and ductal epithelium; PKC-epsilon, strongly in the islet, acinar cell and ductal epithelium; PKC-zeta, in the islet, acinar cell and ductal epithelium; PKC-lambda in some endocrine cells and ductal epithelium. CONCLUSION: These results suggest that the intrapancreatic site-specific existence of PKC isoforms may regulate pancreatic exocrine and endocrine functions via a PKC-mediated signal transduction.

Animals↗
PubMed2001

Age dependence of laryngeal chemoreflex in puppies.

Previously collected data have indicated that the laryngeal chemoreflex (LCR) response is exaggerated during a critical period of postnatal development in several experimental animals. These animals had fewer anatomic and physiological similarities to humans than do puppies. This investigation of the LCR in 14 anesthetized puppies was undertaken to determine age-related differences in the response to stimulation of the supraglottic laryngeal mucosa by saline solution, distilled water, cow's milk, and acid at pH 1.0. The dogs were divided into 3 age groups: group 1 consisted of 4 dogs that were 2 weeks old, and in groups 2 and 3 there were 5 puppies each, of 4 and 6 weeks of age, respectively. The LCR response (laryngospasm, apnea, respiratory depression, and bradycardia) was found in the puppies only after stimulation of the laryngeal mucosa with acid at pH 1.0, and it was more easily achieved in the 4- and 6-week age groups than in the 2-week group. These findings suggest that the LCR is an age-dependent response that appears in dogs only after 2 weeks of age. The important implication of this finding is that postnatal neural maturation may influence the laryngeal reflex in humans to some extent.

Age Factors↗
PubMed2001

A new HIF-1 alpha variant induced by zinc ion suppresses HIF-1-mediated hypoxic responses.

The expressions of hypoxia-inducible genes are upregulated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimer of HIF-1alpha and HIF-1beta/ARNT (aryl hydrocarbon receptor nuclear transporter). Under hypoxic conditions, HIF-1alpha becomes stabilized and both HIF-1alpha and ARNT are translocated into the nucleus and codimerized, binding to the HIF-1 consensus sequence and transactivating hypoxia-inducible genes. Other than hypoxia, cobalt and nickel, which can substitute for iron in the ferroprotein, induce the stabilization of HIF-1alpha and the activation of HIF-1. We found previously that, although zinc, another example of a metal substitute for iron, stabilized HIF-1alpha, it suppressed the formation of HIF-1 by blocking the nuclear translocation of ARNT. Here, we identify a new spliced variant of human HIF-1alpha that is induced by zinc. The isoform lacks the 12th exon, which produced a frame-shift and gave a shorter form of HIF-1alpha (557 amino acids), designated HIF-1alphaZ (HIF-1alpha induced by Zn). This moiety was found to inhibit HIF-1 activity and reduce mRNA expressions of the hypoxia-inducible genes. It blocked the nuclear translocation of ARNT but not that of endogenous HIF-1alpha, and was associated with ARNT in the cytosol. These results suggest that HIF-1alphaZ functions as a dominant-negative isoform of HIF-1 by sequestering ARNT in the cytosol. In addition, the generation of HIF-1alphaZ seems to be responsible for the inhibitory effects of the zinc ion on HIF-1-mediated hypoxic responses, because the expressed HIF-1alphaZ behaved in the same manner as zinc in terms of inhibited HIF-1 activity and ARNT translocation.

Active Transport, Cell Nucleus↗
PubMed2001

Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.

In order to develop convenient and reproducible methods for the identification of ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses were applied within Panax species. To authenticate Panax ginseng among ginseng populations, RAPD analysis was carried out using a 20 mer-random primer. The similarity coefficients among the DNA of ginseng plants analyzed were low, ranging from 0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different fingerprints were obtained within Korean ginseng plants. These results suggest that these methods are able to authenticate the concerned Panax species. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.

DNA, Plant↗
PubMed2001

Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas.

The reported frequencies of Gs alpha mutations (gsp mutations) in growth hormone (GH)-secreting pituitary adenomas are variable (ranging from 4.4 to 43%), and the presence of these mutations in the other pituitary adenomas is still a matter of controversy. Previous clinical and biochemical analyses of patients with GH-secreting pituitary adenomas and gsp mutations produced conflicting results and did not demonstrate obvious characteristics. Therefore, we investigated the prevalence of gsp mutations in Korean patients with pituitary adenomas and elucidated the characteristics of these patients. Forty-four GH-secreting adenomas, 7 prolactin (PRL)-secreting adenomas and 32 clinically non-functioning adenomas were examined for the presence of point mutations in codon 201 and 227 of the Gs alpha gene using a nested PCR and direct sequencing of DNA extracted from fresh tissue or paraffin-embedded pituitary adenoma samples. Seven of the 44 GH-secreting pituitary adenomas had point mutations at codon 201 or 227; of these, five mutations were in codon 201 and two were in codon 227. In patients with gsp mutations, mean tumor size was significantly smaller than in patients without gsp mutations (15.9+/-8.7 mm vs. 24.9+/-14.9 mm, P<0.05). Age, sex, basal GH levels, GH response to oral glucose loading, GH response to octreotide and surgical outcome were not different in the two groups. One of the 32 clinically non-functioning pituitary adenomas had a point mutation at codon 201; none of the seven prolactinomas had these mutations. These results show that gsp mutations are not rare in Korean acromegalic patients and mean tumor size is significantly smaller in acromegalic patients with gsp mutations. Our results also confirm the low frequency of gsp mutations in clinically non-functioning pituitary adenomas and the absence of gsp mutations in prolactinoma.

Acromegaly↗
PubMed2001

Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.

Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.

The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.

Adipose Tissue↗
PubMed2001

Satisfaction and perception of performance norms of sport teams.

To examine the association of rated satisfaction by 447 team members with their perception of performance norms in team sports analysis suggested that the members who hold higher performance norms than those of the majority of their team rate their satisfaction higher than those who hold lower performance norms.

Cooperative Behavior↗
PubMed2001

The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas.

Adult↗
PubMed2001

Clinical usefulness of magnetic resonance cisternography in patients having hemifacial spasm.

To evaluate the usefulness of MR cisternography fourteen patients that had hemifacial spasm and 20 control patients underwent MR cisternography. All the patients with hemifacial spasm had a confirmed vascular compression after surgery. MR cisternography was performed using a 1.5-tesla superconducting MR magnet in which a 3D (dimensional) heavily T2-weighted turbo spin-echo sequence was used. In 34 randomly selected individuals, we retrospectively determined whether MR cisternography images could be used to evaluate symptoms, and what the benefits of obtaining this image was. The results were correlated with the surgical findings. The sensitivity was 100% and the specificity was 94% in all patients having a hemifacial spasm. The offending vessels were the anterior inferior cerebellar artery (AICA) in six patients cases, the posterior inferior cerebellar artery (PICA) in six, both the vertebral artery and PICA in one, and the vertebral artery in one. All the images showed good resolution and contrast, and also showed the exact correlation between the facial nerve and intracranial vessels in the multiplaner image. The findings of neurovascular compression were well correlated with the surgical findings. We believe that high-resolution 3D MR cisternography is a very useful method for evaluating the neurovascular compression in patients that have hemifacial spasm.

Adult↗
PubMed2001

Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a central role in angiogenesis. In this study, we investigated the mechanism of VEGF expression in HepG2 human hepatoblastoma cells under hypoglycemia. The shortage of glucose significantly enhanced VEGF mRNA expression in a time-dependent manner as well as increased DNA-binding activity of AP-1 that plays an important role in VEGF transcription. In addition, treatment of a potent PKC inhibitor, H-7 in glucose-deprived HepG2 cells suppressed hypoglycemia-elevated VEGF expression as well as the increased AP-1 DNA-binding activity. Moreover, we observed that Ca2+ levels remarkably increased under low glucose condition. Consistently, an intracellular Ca2+ chelator, BAPTA/AM significantly decreased hypoglycemia-induced VEGF expression and AP-1 DNA-binding activity. Therefore, these results indicate that increase of intracellular Ca2+ level induces the activation of PKC, which induce the activation of AP-1 leading to the increase of VEGF in glucose-deprived environment. Furthermore, it provides one link in regulation of VEGF with hypoglycemia as well as information to understand how hypoglycemia induces VEGF expression and subsequently leads to tumor angiogenesis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Detection of large pKa perturbations of an inhibitor and a catalytic group at an enzyme active site, a mechanistic basis for catalytic power of many enzymes.

Delta(5)-3-Ketosteroid isomerase catalyzes cleavage and formation of a C-H bond at a diffusion-controlled limit. By determining the crystal structures of the enzyme in complex with each of three different inhibitors and by nuclear magnetic resonance (NMR) spectroscopic investigation, we evidenced the ionization of a hydroxyl group (pK(a) approximately 16.5) of an inhibitor, which forms a low barrier hydrogen bond (LBHB) with a catalytic residue Tyr(14) (pK(a) approximately 11.5), and the protonation of the catalytic residue Asp(38) with pK(a) of approximately 4.5 at pH 6.7 in the interaction with a carboxylate group of an inhibitor. The perturbation of the pK(a) values in both cases arises from the formation of favorable interactions between inhibitors and catalytic residues. The results indicate that the pK(a) difference between catalytic residue and substrate can be significantly reduced in the active site environment as a result of the formation of energetically favorable interactions during the course of enzyme reactions. The reduction in the pK(a) difference should facilitate the abstraction of a proton and thereby eliminate a large fraction of activation energy in general acid/base enzyme reactions. The pK(a) perturbation provides a mechanistic ground for the fast reactivity of many enzymes and for the understanding of how some enzymes are able to extract a proton from a C-H group with a pK(a) value as high as approximately 30.

Binding Sites↗
PubMed2000

Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation.

NO, produced from l-arginine in a reaction catalyzed by NO synthase, is an endogenous free radical with multiple functions in mammalian cells. Here, we demonstrate that endogenously produced NO can suppress c-Jun N-terminal kinase (JNK) activation in intact cells. Treatment of BV-2 murine microglial cells with IFN-gamma induced endogenous NO production, concomitantly suppressing JNK1 activation. Similarly, IFN-gamma induced suppression of JNK1 activation in RAW264.7 murine macrophage cells and rat alveolar macrophages. The IFN-gamma-induced suppression of JNK1 activation in BV-2, RAW264.7, or rat alveolar macrophage cells was completely prevented by N(G)-nitro-l-arginine, a NO synthase inhibitor. Interestingly, the IFN-gamma-induced suppression of JNK1 activation was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylyl cyclase. 8-Bromo-cGMP, a membrane-permeant analogue of cGMP, did not change JNK1 activation in intact cells either. In contrast, S-nitro-N-acetyl-dl-penicillamine (SNAP), a NO donor, inhibited JNK1 activity in vitro. Furthermore, a thiol reducing agent, DTT, reversed not only the in vitro inhibition of JNK1 activity by SNAP but also the in vivo suppression of JNK1 activity by IFN-gamma. Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-gamma or SNAP on JNK1 activity in vivo or in vitro, respectively. Moreover, IFN-gamma enhanced endogenous S-nitrosylation of JNK1 in RAW264.7 cells. Collectively, our data suggest that endogenous NO mediates the IFN-gamma-induced suppression of JNK1 activation in macrophage cells by means of a thiol-redox mechanism.

Animals↗
PubMed2000

Activation of c-Jun N-terminal kinase 1 (JNK1) in mistletoe lectin II-induced apoptosis of human myeloleukemic U937 cells.

Extracts of mistletoe (Viscum album var. coloratum) have been used for several decades as an anticancer immunomodulating agent in clinical fields. However, the mechanism by which the plant extracts kill tumor cells has remained elusive. We investigated the direct effects of beta-galactoside- and N-acetyl-d-galactosamine-specific mistletoe lectin II in inducing apoptotic death of U937 cells. Three distinct components of mistletoe, including beta-galactoside- and N-acetyl-D-galactosamine-specific lectin II (60 kDa), polysaccharides, and viscotoxin (5 kDa), induced apoptotic cell death, characterized by DNA ladder pattern fragmentation of U937 cells at 12 hr after treatment. Consistent with apoptosis of the cells, mistletoe extracts markedly increased the phosphotransferase activity of c-Jun N-terminal kinase 1 (JNK1)/stress-activated protein kinase (SAPK) in U937 cells. Among the three components, lectin II was the most potent in inducing apoptosis as well as JNK1 activation of U937 cells in a dose- and time-dependent manner. Catalytic activation of JNK1 induced by mistletoe lectin II was inhibited by the addition of peptide aC-DEVD-CHO, but not by aC-YVAD-CHO. In addition, mistletoe lectin II induced apoptosis in a variety of cell types including Jurkat T cells, RAW 264.7 cells, HL-60 cells, DLD-1 cells, and primary acute myelocytic leukemic cells.

Apoptosis↗