Biomedical subjects

H C Kim

Publications and source records attributed to H C Kim.

At least 127 records · Page 7Linked to original sources

PubMed1999

Lead induced thiamine deficiency in the brain decreased the threshold of electroshock seizure in rat.

Many neurological disorders that occur frequently in lead intoxicated animals, have also been observed in thiamine deficient animals. To test whether lead intoxication could decrease the thiamine status and thresholds of electroshock seizure in rats, 3-week-old Wistar rats were treated with lead or lead plus thiamine. For comparison, a thiamine deficient group was included. Thiamine contents and transketolase activity, one of the thiamine dependent enzymes in the brain regions were significantly lowered by lead intoxication and thiamine deficiency. In both cases, thresholds of the electroshock seizure were significantly decreased. Thiamine supplementation reversed these signs and decreased the brain lead concentration in the lead treated group. The results from the present study suggest that the increased seizure susceptibility induced by lead intoxication in rats may be mediated at least in part through the changes of thiamine status.

Animals↗

PubMed1999

Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainic acid.

We have recently reported that dextromethorphan attenuates the neurotoxicity induced by kainic acid in a dose-related fashion. Pretreatments with dextromethorphan (50 mg/kg, p.o. x2) significantly reduced the activator protein-1 DNA-binding activity and the Fos-related antigen-immunoreactive protein induced by kainic acid (10 mg/kg, i.p.) in the CA1, but not the CA3 or the dentate gyrus sector of the rat hippocampus. Paradoxically, dextromethorphan itself caused an elevated activator protein-1 DNA-binding activity and Fos-related antigen-immunoreactive protein in the CA1 region which lasted for at least 4 days. The results suggest that the CA1 area is the critical site for mediating the putative neuroprotective effect induced by dextromethorphan.

Animals↗

PubMed1999

Transforming growth factor beta stimulation of colorectal cancer cell lines: type II receptor bypass and changes in adhesion molecule expression.

The type II transforming growth factor (TGF)-beta receptor gene (TGFBR2) is often mutated in nucleotide repeat sequences in colorectal cancers that are replication error positive (RER+). These mutations are thought to be selected for escape from growth inhibition by TGF-beta rather than representing bystander events because of an increased mutation rate. We investigated the role of TGFBR2 mutations in 12 colorectal cancer cell lines. Six of these were RER+, and these were shown to have homozygous TGFBR2 mutations. All cell lines then were tested for changes in proliferation in response to TGF-beta stimulation. Despite homozygous mutation of the type II TGF-beta receptor, two RER+ cell lines, Lovo and SW48, showed statistically significant growth inhibition when stimulated by TGF-beta1 in serum-free conditions. This shows that the type II TGF-beta receptor can be bypassed in certain cases to maintain growth inhibition. We next investigated whether there was any alternative mode through which TGFBR2 mutation may give a selective advantage, such as a change in adhesion molecule expression. All cell lines were stimulated with TGF-beta1 and adhesion molecules detected by ELISA. No consistent changes were identified between the RER+ and the RER- cell lines, although changes in E-cadherin, beta-catenin, and gamma-catenin were identified in individual cell lines. We conclude that (i) type II TGF-beta receptor activity can be bypassed and thus TGFBR2 mutations in RER+ cancers may, at least sometimes, be just "bystander" events and (ii) TGF-beta can affect adhesion molecule expression so that TGFBR2 mutation may give rise to a selective advantage through an effect other escape from growth inhibition.

Cell Adhesion↗

PubMed1999

Pretreatment of male BALB/c mice with beta-ionone potentiates thioacetamide-induced hepatotoxicity.

A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, beta-ionone, subcutaneously at 600 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with beta-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice.

Alanine Transaminase↗

PubMed1999

Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells.

Epithelial (E)-cadherin and its associated cytoplasmic proteins (alpha-, beta-, and gamma-catenins) are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor/invasion suppressor role for E-cadherin, and loss of expression, as well as mutations, has been described in a number of epithelial cancers. To investigate whether E-cadherin gene (CDH1) mutations occur in colorectal cancer, we screened 49 human colon carcinoma cell lines from 43 patients by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. In addition to silent changes, polymorphisms, and intronic variants in a number of the cell lines, we detected frameshift single-base deletions in repeat regions of exon 3 (codons 120 and 126) causing premature truncations at codon 216 in four replication-error-positive (RER+) cell lines (LS174T, HCT116, GP2d, and GP5d) derived from 3 patients. In LS174T such a mutation inevitably contributes to its lack of E-cadherin protein expression and function. Transfection of full-length E-cadherin cDNA into LS174T cells enhanced intercellular adhesion, induced differentiation, retarded proliferation, inhibited tumorigenicity, and restored responsiveness to the migratory effects induced by the motogenic trefoil factor 2 (human spasmolytic polypeptide). These results indicate that, although inactivating E-cadherin mutations occur relatively infrequently in colorectal cancer cell lines overall (3/43 = 7%), they are more common in cells with an RER+ phenotype (3/10 = 30%) and may contribute to the dysfunction of the E-cadherin-catenin-mediated adhesion/signaling system commonly seen in these tumors. These results also indicate that normal E-cadherin-mediated cell adhesion can restore the ability of colonic tumor cells to respond to trefoil factor 2.

Animals↗

PubMed1999

Somatic mutations of the first 14 exons of APC in hamartomatous polyps of the colon.

Although hamartomatous or hyperplastic polyps are rarely accompanied by adenomatous or carcinomatous foci, the role of APC (MIM# 175100) mutations in these polyps is not clear. The neoplastic potential of these polyps was assessed with regard to somatic mutation of the first 14 exons of APC. DNA from 14 hamartomatous polyps (12 patients with juvenile polyp, JP; two patients with Peutz-Jeghers syndrome, PJS) and 27 hyperplastic polyps was used. Exons 1-14 of APC were amplified using verified oligonucleotide primers, and PCR-SSCP analysis was performed. Translation-terminating mutation in exon 15 was also screened using the protein truncation test. All mutations found were transitions or transversions with heterozygous alleles of both wild-type and mutant APC in exons 2, 9, 10, and 11. Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation. APC mutation was not correlated with previous history of colorectal carcinoma or number of polyps. Since all mutations were missense or silent mutations occurred in exons not previously known to have functionally relevant area, their phenotypic implication appeared to be limited.

Colonic Polyps↗

PubMed1999

Surgically induced degeneration and regeneration of the choriocapillaris in rabbit.

BACKGROUND: Retinal pigment epithelium (RPE) and choriocapillaris play an important role in maintaining the outer retina. Clinical and experimental studies have shown that there is a close relationship between them. To examine the relationship between RPE and choriocapillaris we developed an animal model in which degeneration and regeneration of the choriocapillaris can be created easily and reproducibly. METHODS: Using pigmented rabbits a retinal detachment (about 7 disk diameters) was created in the eye and the detached retina was surgically removed. A half area of the exposed RPE was mechanically debrided using a silicone brush. The other half area remained untouched. The eyes were morphologically examined at 3, 7, and 14 days and 4 and 8 weeks after the surgery using scanning or transmission electron microscopy. Changes in the choriocapillaris after the RPE debridement were also evaluated by corrosion vascular casts. RESULTS: The debrided area was resurfaced with elongated RPE in 7 days after surgery. The replaced RPE was dedifferentiated but it gradually recovered cell polarity by 4 weeks after surgery. The choriocapillaris beneath the debrided area underwent degeneration; however, it regenerated by 4 weeks after surgery, corresponding to the timing of the morphologic recovery of the replaced RPE. CONCLUSION: This animal model of surgically induced degeneration and regeneration of the choriocapillaris may be useful to clarify the relationship between RPE and choriocapillaris and to study potential treatments for choroidal vascular diseases.

Animals↗

PubMed1999

Nitric oxide-enhanced excitotoxicity-independent apoptosis of glucose-deprived neurons.

Glucose deprivation has been shown to elicit neuronal death via extracellular glutamate accumulation. Here we report that immunostimulated glial expression of inducible nitric oxide synthase enhances the apoptotic death of glucose-deprived cerebellar granule cells (CGC) via the excitotoxicity-independent pathway. CGC cultures were immunostimulated by interferon-gamma (100 U/ml) and lipopolysaccharides (1 microg/ml) and 2 days later were challenged by glucose deprivation. Neither a 2-h Glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly enhanced the apoptotic death of CGC glucose-deprived for 1 h. The increased apoptotic death of glucose-deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (200 microM, 30 min) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The enhanced apoptotic death was not blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphovalerate (APV) and dizocilpine (MK-801) or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, the NO-induced enhanced apoptotic death occurred without a significant increase of the concentration of glutamate in the bathing medium. Our data indicate that immunostimulated glial cells potentiate the apoptotic death of glucose-deprived CGC in part through the expression of inducible NOS but not through NMDA receptor activation. Potentiation of glucose-deprived CGC death by immunostimulated glial cells may be clinically implicated in the tendency of recurrent ischemic insults to be more severe and fatal than an initial ischemic insult.

Animals↗

PubMed1999

Evaluation of left ventricular diastolic function when mitral E and A waves are completely fused: role of assessing mitral annulus velocity.

Mitral inflow parameters have been used most widely in the evaluation of left ventricular (LV) diastolic function. However, when the mitral E and A waves are completely fused, mitral inflow parameters cannot provide information about the LV diastolic function. LV filling pressure, mitral inflow, mitral annulus velocity, and tau (tau) were measured in 59 patients with sinus rhythm when mitral E and A waves were completely fused with right atrial pacing. When mitral E and A waves were completely fused, tau correlated with the peak fused mitral annulus velocity (r = -0.60, P <.001), and peak fused mitral annulus velocity of less than 12.5 cm/s best discriminated prolonged (>/=50 ms) from normal tau, with a sensitivity of 78% and specificity of 69%. The peak fused mitral inflow velocity to peak fused mitral annulus velocity ratio correlated with LV filling pressure (r = 0.62, P <.001). A ratio of at least 8, could predict elevated LV filling pressure (>/=15 mm Hg) with a sensitivity of 65% and specificity of 74%. In conclusion, even when mitral E and A waves are completely fused, mitral annulus velocity can be used in the evaluation of LV diastolic function.

Cardiac Catheterization↗

PubMed1999

Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation.

This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function in patients with atrial fibrillation. Atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice. The clinical usefulness of conventional Doppler indexes is limited in atrial fibrillation because of the altered left atrial pressure and loss of synchronized atrial contraction. Mitral inflow and mitral annulus velocities were measured simultaneously with tau in 27 patients with nonrheumatic atrial fibrillation at the cardiac catheterization laboratory. Among deceleration time of mitral inflow, peak mitral inflow velocity (E), and peak diastolic mitral annulus velocity (E), only E correlated with tau (r = 0.51, P =.007). Prolonged tau (>/=50 ms) could be predicted by E <8 cm/s with a sensitivity of 73% (16 of 22) and a specificity of 100% (5 of 5). The E/E ratio correlated with left ventricular filling pressure (r = 0.79, P <.001). The E/E ratio of >/=11 could predict elevated left ventricular filling pressure (>/=15 mm Hg) with a sensitivity of 75% (9 of 12) and a specificity of 93% (14 of 15). Mitral annulus velocity is useful in the detection of impaired left ventricular relaxation and estimation of filling pressure even in patients with atrial fibrillation.

Adult↗

PubMed1999

A novel glutamic acid to aspartic acid mutation near the end of the 2B rod domain in the keratin 1 chain in epidermolytic hyperkeratosis.

We report a mutation in a mild case of epidermolytic hyperkeratosis that results in a glutamic acid to aspartic acid substitution in a novel location, codon 477 or position 106 of the 2B rod domain of the keratin 1 chain. This residue has been conserved in all intermediate filament chains and lies near the beginning of the highly conserved helix termination sequence and just prior to the predicted molecular overlap region. Keratin filaments assembled in vitro from chains bearing this substitution are abnormal, indicating that the glutamic acid residue is critically involved in ionic interactions in intermediate levels of filament structure.

Amino Acid Substitution↗

PubMed1999

Alterations in protein tyrosine kinase pathways following retinal vein occlusion in the rat.

PURPOSE: To determine whether an experimental retinal vein occlusion in the rat activates protein tyrosine kinase pathways and increases angiogenic growth factors in the retina. METHODS: Retinal vein occlusion (RVO) was induced in the rat retina with argon laser photocoagulation. Retinas were collected at 2 days, 1, 2, and 4 weeks after RVO and divided into halves: one half represented an area within the distribution of the occluded vein [RVO(IN)] and the other half represented an area outside the distribution of the occluded vein [RVO(OUT)]. RVO(IN) and (OUT) were examined by western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and 3 signal proteins in the tyrosine kinase pathways: phospholipase Cgamma (PLCgamma), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). RESULTS: RVO caused a severe capillary nonperfusion in RVO(IN). Overall tyrosine-phosphorylated proteins were increased after RVO, especially in RVO(IN) at 2 days and 1 week. VEGF and bFGF were markedly increased in RVO(IN) at 2 days and 1 week. Tyrosine-phosphorylated PLCgamma, PI3K, and MAPK were also increased in RVO(IN) at these time points. CONCLUSIONS: RVO caused an increase in overall protein tyrosine phosphorylation in the rat retina. This increase was associated with an increase in angiogenic growth factors (VEGF and bFGF). These results suggest that protein tyrosine kinase pathways are activated during retinal ischemia and may play a role in mitogenesis of vascular endothelial cells and other responses in the retina after RVO.

Animals↗

PubMed1999

Innovative ambulatory drug delivery system using an electrolytic hydrogel infusion pump.

This report describes an ambulatory infusion device developed to provide parenteral drug delivery at a precisely controlled rate. The device is based on the innovative and unique concept of utilizing electrohydrolysis of a negatively charged hydrogel. The system consists of two modules: a pump unit and an electronic control unit. The pump module, which can be a disposable unit, contains medication separated by a flexible membrane from a gas generating chamber; this latter is an electrolytic cell comprising a hydrogel block and two platinum electrodes. The microcontroller-based control module is constructed with a user interface which includes input keys and a liquid crystal display, as well as a control to alter driving current level, depending on the infusion rate required. A microprocessor instantaneously calculates the current level required; this is based on operator-selected infusion rate, ambient pressure, and temperature sensor output. The accuracy and precision of the device were verified for all flow rates and for different environmental conditions; in vitro test results showed acceptable accuracy with less than +/- 5% error over the whole operating range of 0.1-100 [ml/h]. The device is small, lightweight, simple and easy to manufacture, and is also designed to be comfortably and conveniently worn by patients. It can be used for a variety of regimens including, for example, chemotherapy, insulin delivery, and pain management, antibiotic and AIDS therapy.

Ambulatory Care↗

PubMed1999

Voltage-dependent sodium and calcium currents in acutely isolated adult rat trigeminal root ganglion neurons.

Voltage-dependent sodium (INa) and calcium (ICa) currents in small (<30 microM) neurons from adult rat trigeminal root ganglia were characterized with a standard whole cell patch-clamp technique. Two types of INa showing different sensitivity to tetrodotoxin (TTX) were recorded, which showed marked differences in their activating and inactivating time courses. The activation and the steady-state inactivation kinetics of TTX-resistant INa were more depolarized by about +20 and +30 mV, respectively, than those of TTX-sensitive INa. Voltage-dependent ICa was recorded under the condition that suppressed sodium and potassium currents with 10 mM Ca2+ as a charge carrier. Depolarizing step pulses from a holding potential of -80 mV evoked two distinct inward ICa, low-voltage activated (LVA) and high-voltage activated (HVA) ICa. LVA ICa was first observed at -60 to -50 mV and reached a peak at about -30 mV. Amiloride (0.5 mM) suppressed approximately 60% of the LVA ICa, whereas approximately 10% of HVA ICa was inhibited by the same concentration of the amiloride. LVA ICa was far less affected by the presence of external Cd2+ or the replacement of Ca2+ by 10 Ba2+ than HVA ICa. The omega-conotoxin GVIA (omega-CgTx), an N-type ICa blocker, suppressed approximately 65% of the whole cell HVA ICa at the concentration of 1 microM. The omega-CgTx-resistant HVA ICa was sensitive to nifedipine (10 microM), a dihydropyridine (DHP) calcium channel antagonist, which produced an additional blockade by approximately 25% of the drug-free control ( approximately 70% of the omega-CgTx-resistant ICa). The combination of 10 microM nifedipine and 1 microM omega-CgTx left approximately 13% of the drug-free control ICa unblocked. The DHP agonist S(-)-BayK8644 (5 microM) shifted the activation of the HVA ICa to more negative potentials and increased its maximal amplitude. Additionally, S(-)-BayK8644 caused the appearance of a slowed component of the tail current. These results clearly demonstrate that the presence of two types of sodium channels, TTX sensitive and resistant, and three types of calcium channels, T, L, and N type, in the small-sized adult rat trigeminal ganglion neurons.

Animals↗

PubMed1999

Detection of transforming growth factor-alpha in the serum of gastric carcinoma patients.

Transforming growth factor-alpha (TGF-alpha) is a ligand for epidermal growth factor receptor (EGFR) and it is overexpressed in various malignancies including lung, esophageal, colorectal, ovarian and gastric carcinomas. In patients with gastric carcinoma, its overexpression may be associated with advanced stage or poor prognosis. We have recently demonstrated that the mean serum level for EGFR in gastric carcinoma patients was significantly elevated compared with that of healthy controls. Using the enzyme-linked immunosorbent assay, the levels of TGF-alpha were determined in serum from 40 patients with gastric carcinoma (5 patients with stage I, 2 stage II, 4 stage III, and 29 stage IV patients) and 33 healthy controls. The mean serum level for TGF-alpha in the gastric carcinoma patients was significantly elevated as compared with that of healthy controls (104 +/- 235 vs. 22 +/- 16 pg/ml; p = 0.03). Eleven patients with gastric carcinoma (27.5%) showed elevated serum TGF-alpha levels above the cutoff value of 54 pg/ml (defined as 2 standard deviations above the mean of the control group). No significant association was noted between the positivity of TGF-alpha and clinicopathologic characteristics including gender, age and stage. However, poorly differentiated adenocarcinoma showed a higher positivity of serum TGF-alpha (43.8%) compared with other histologic types, which was marginally significant (p = 0.06). These results suggest that serum TGF-alpha could be useful as a tumor marker of gastric carcinoma for predicting prognosis and follow-up after surgery in patients whose initial serum TGF-alpha levels are elevated.

Adult↗

PubMed1999

Extramammary Paget's disease with aggressive behavior: a report of two cases.

Extramammary Paget's disease (EMPD) is an intraepithelial neoplastic disorder which is included as a rare malignant condition. However, it sometimes shows aggressive behavior of local recurrence and coexisting malignancy. We had experienced nine cases of EMPD involving the scrotum for seven years. Two cases of them presented metastasis. The first case presented extensive inguinal lymph node metastasis with underlying adnexal adenocarcinoma one year after wide local excision. The second case initially presented multiple metastasis to the liver and in the lymph node. The latter, showing fulminant progression with liver metastasis, may be only the second case reported in English literature. EMPD is considered as a malignant neoplasm with aggressive behavior from initial presentation. Because wide local excision of the lesion alone may be occasionally insufficient, a careful follow-up must be done to detect recurrence or internal malignancy.

Aged↗

PubMed1999

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Animals↗

PubMed1999

Age-dependent resistance to Cryptosporidium muris (strain MCR) infection in golden hamsters and mice.

An age-dependent aspect of resistance to Cryptosporidium muris (strain MCR) infection was monitored in Syrian golden hamsters, Mesocricetus auratus, at 1-, 5- and 10-week of age and in ICR mice. Mus musculus, at 3-, 12-, and 15-week of age orally inoculated with a single dose of 2 x 10(6) oocysts, respectively. The prepatent periods for both animals were similar, independent of age, but the patency was significantly longer in younger hamsters (P < 0.001) and a long tendency in younger mice. Hamsters infected at 1-week of age excreted about 10 times higher oocysts than those at 5- and 10-week of age. However, the total oocyst output was similar among mice of different ages. There was a good correlation between the length of the patency and the total oocyst output in hamsters (R = 0.9646), but not in mice (R = 0.4561). The immunogenicity of the parasite to homologous challenge infections was very strong in hamsters and relatively strong in mice. These results indicate that acquired resistance to C. muris infection is age-related and the innate resistance is independent of age of hamsters, and that both innate and acquired resistance, on the contrary, are irrespective of age of mice.

Aging↗