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G W Kim

Publications and source records attributed to G W Kim.

At least 19 recordsLinked to original sources
PubMed2001

Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum.

Oxidative stress is involved in the neuropathology of several neurodegenerative diseases and stroke, all of which are related to excitotoxicity. Age-dependent vulnerability is characteristic of these conditions. It is not clear whether apoptosis-related neuronal death is involved in age-dependent vulnerability to excitotoxicity. We evaluated whether apoptosis-related neuronal death after treatment with 3-nitropropionic acid (3-NP) is age-dependent in the mouse striatum. We have demonstrated that oxidative stress occurs early after 3-NP treatment and even more so in aged mice. DNA fragmentation with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and gel electrophoresis occurred in an age-dependent fashion. Expression of the DNA repair enzyme, apurinic/apyrimidinic endonuclease, was more attenuated in old mice. Therefore, these results suggest that oxidative stress induces age-dependent neuronal apoptosis in the mouse striatum after 3-NP treatment, which in turn produces an age-dependent vulnerability to 3-NP.

Aging↗
PubMed2001

Randomly amplified polymorphic DNA-polymerase chain reaction analysis of two different populations of cultured Korean catfish Silurus asotus.

Genetic similarity and diversity of cultured catfish Silurus asotus populations collected from two areas in western Korea were examined using randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Out of 20 random primers tested, 5 produced 1344 RAPD bands ranging from 8.2 to 13.6 polymorphic bands per primer. The polymorphic bands in these populations ranged from 56.4% to 59.6%. Polymorphic bands per lane within populations ranged from 4.9% to 5.3%. The similarity within the Kunsan population varied from 0.39 to 0.82 with a mean (+/- SD) of 0.56 +/- 0.08. The level of bandsharing values was 0.59 +/- 0.07 within the catfish population from Yesan. The genetic similarity in cultured catfish populations may have been caused because individuals from two populations were reared in the same environmental conditions or by inbreeding during several generations. However, in view of bandsharing values, polymorphic bands and also the specific major bands that were inter-population-specific, significant genetic differentiation between these populations were present even if bandsharing (BS) values were somewhat numerically different. Therefore, the number of RAPD polymorphisms identified in this study may be sufficient to permit estimating genetic similarity and diversity. However, in future, additional populations, sampling sites and individuals will be necessary to make up for these weak points.

Animals↗
PubMed2001

The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice.

Oxidative stress has been associated with the development of blood-brain barrier disruption and cellular injury after ischemia. The cytosolic antioxidant, copper/zinc superoxide dismutase, has been shown to protect against blood-brain barrier disruption and infarction after cerebral ischemia-reperfusion. However, it is not clear whether copper/zinc superoxide dismutase can protect against evolving ischemic lesions after thromboembolic cortical ischemia. In this study, the photothrombotic ischemia model, which is physiologically similar to thromboembolic stroke, was used to develop cortical ischemia. Blood-brain barrier disruption and oxidative cellular damage were investigated in transgenic mice that overexpress copper/zinc superoxide dismutase and in littermate wild-type mice after photothrombotic ischemia, which was induced by both injection of erythrosin B (30 mg/kg) and irradiation using a helium neon laser for 3 min. Free radical production, particularly superoxide, was increased in the lesioned cortex as early as 4 h after ischemia using hydroethidine in situ detection. The transgenic mice showed a prominent decrease in oxidative stress compared with the wild-type mice. Blood-brain barrier disruption, evidenced by quantitation of Evans Blue leakage, occurred 1 h after ischemia and gradually increased up to 24 h. Compared with the wild-type mice, the transgenic mice showed less blood-brain barrier disruption, a decrease in oxidative DNA damage using 8-hydroxyguanosine immunohistochemistry, a subsequent decrease in DNA fragmentation using the in situ nick-end labeling technique, and decreased infarct volume after ischemia. From these results we suggest that superoxide anion radical is an important factor in blood-brain barrier disruption and oxidative cellular injury, and that copper/zinc superoxide dismutase could protect against the evolving infarction after thromboembolic cortical ischemia.

Absorption↗
PubMed2001

Early decrease in dna repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: Ku70 and Ku86, multifunctional DNA repair proteins, bind to broken DNA ends, including double-strand breaks, and trigger a DNA repair pathway. To investigate the involvement of these proteins in DNA fragmentation after ischemia/reperfusion, Ku protein expression was examined before and after transient focal cerebral ischemia (FCI) in mice. METHODS: Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal suture blockade of the middle cerebral artery. Ku protein expression was studied by immunohistochemistry and Western blot analysis. DNA fragmentation was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The spatial relationship between Ku expression and DNA fragmentation was examined by double labeling with Ku and TUNEL after reperfusion. RESULTS: Immunohistochemistry showed constitutive expression of Ku proteins in control brains. The number of Ku-expressing cells was decreased in the entire middle cerebral artery territory as early as 4 hours after reperfusion and remained reduced until 24 hours. Western blot analyses confirmed the significant reduction of these proteins (59.4% and 57.7% reduction in optical density at 4 hours of reperfusion from the normal level of Ku70 and Ku86 bands, respectively; P<0.001). DNA gel electrophoresis demonstrated DNA laddering 24 hours after reperfusion, but not at 4 hours. Double staining with Ku and TUNEL showed a concomitant loss of Ku immunoreactivity and TUNEL-positive staining. CONCLUSIONS: These results suggest that the early reduction of Ku proteins and the loss of defense against DNA damage may underlie the mechanism of DNA fragmentation after FCI.

Animals↗
PubMed2001

Neuronal expression of the DNA repair protein Ku 70 after ischemic preconditioning corresponds to tolerance to global cerebral ischemia.

BACKGROUND AND PURPOSE: Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Ku 70/86, multifunctional DNA repair proteins, bind to broken DNA ends and trigger a DNA repair pathway. We investigated the involvement of these proteins in the development of neuronal tolerance to global cerebral ischemia after ischemic preconditioning. METHODS: Adult male Sprague-Dawley rats were subjected to either 5 minutes of lethal global ischemia with or without 3 minutes of sublethal ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was histologically assessed, and DNA damage was visualized by in situ labeling of DNA fragmentation and DNA gel electrophoresis. Ku expression was also examined by immunohistochemistry and Western blot analysis. RESULTS: Hippocampal CA1 neurons underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However, these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days after ischemic preconditioning. Immunohistochemistry showed virtually no constitutive expression of Ku proteins in CA1 neurons; however, ischemic preconditioning induced neuronal Ku 70 expression 1 to 3 days later. Western blot confirmed an increase in Ku 70 in this region at the same time. CONCLUSIONS: The temporal and spatial expression of Ku 70 corresponded to tolerance of the hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of Ku proteins in the development of neuronal tolerance after ischemic preconditioning.

Animals↗
PubMed2001

Characterization of Cre-loxP interaction in the major groove: hint for structural distortion of mutant Cre and possible strategy for HIV-1 therapy.

Although the crystal structure of Cre recombinase complexed with DNA, named loxA, was elucidated a couple of years ago, it has not yet been determined which amino acids of the protein are involved in the specific Cre-loxP interaction. Arg259 and Gln90 interact with DNA substrate in the major groove from which the specificity of protein-DNA interaction comes. In this study, we substituted these residues for other amino acids. Also, two mutated DNA substrates were constructed. In each mutant, one of the bases that interact with Arg259 or Gln90 was changed into another base. In vitro binding assays and recombination assays of variant lox sites with wild-type and mutant-type Cre revealed that Arg259 plays a key role in Cre-loxP binding but Gln90 does not. However, the recombination activity still remained intact, although the binding between Cre and DNA substrate was not ensured.

Base Sequence↗
PubMed2000

Excitotoxicity is required for induction of oxidative stress and apoptosis in mouse striatum by the mitochondrial toxin, 3-nitropropionic acid.

Excitotoxicity is implicated in the pathogenesis of several neurologic diseases, such as chronic neurodegenerative diseases and stroke. Recently, it was reported that excitotoxicity has a relationship to apoptotic neuronal death, and that the mitochondrial toxin, 3-nitropropionic acid (3-NP), could induce apoptosis in the striatum. Although striatal lesions produced by 3-NP could develop through an excitotoxic mechanism, the exact relationship between apoptosis induction and excitotoxicity after 3-NP treatment is still not clear. The authors investigated the role of excitotoxicity and oxidative stress on apoptosis induction within the striatum after intraperitoneal injection of 3-NP. The authors demonstrated that removal of the corticostriatal glutamate pathway reduced superoxide production and apoptosis induction in the denervated striatum of decorticated mice after 3-NP treatment. Also, the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, prevented apoptosis in the striatum after 3-NP treatment for 5 days, whereas the non-NMDA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, was ineffective. The authors also evaluated the initial type of neuronal death by 3-NP treatment for different durations from 1 to 5 days. In early striatal damage, apoptotic neuronal death initially occurred after 3-NP treatment. Our data show that excitotoxicity related to oxidative stress initially induces apoptotic neuronal death in mouse striatum after treatment with 3-NP.

Animals↗
PubMed2000

Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice.

Apoptosis-related cell death is linked to oxidative stress and caspases in experimental cerebral ischemia. However, the role of oxidative stress in caspase activation and subsequent apoptotic cell death after cerebral ischemia is unknown. The authors evaluated the role of oxidative stress in ischemic cerebral infarction after photothrombosis and the relation between oxidative stress and caspase-related cell death 6 and 24 hours after ischemia with and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minutes before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were detected in early ischemic lesions. Western blot analysis showed the cleaved form and the increased level of the proform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the antioxidant-treated group after ischemia. Decreased DNA fragmentation and laddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrome c release occur in the ischemic lesion after photothrombotic ischemia. The free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentation, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarction after photothrombotic ischemia.

Animals↗
PubMed2000

Arterial pulsatility as an index of cerebral microangiopathy in diabetes.

BACKGROUND AND PURPOSE: This study was designed to evaluate cerebral hemodynamic changes related to diabetes mellitus (DM) with transcranial Doppler ultrasonography (TCD). METHODS: We measured the flow velocities and the Gosling pulsatility index (PI) of the middle cerebral artery (MCA), extracranial internal carotid artery (ICA), and basilar artery (BA) in 56 stroke-free, normotensive patients with type 2 DM and 70 age- and gender-matched healthy volunteers. Patients were divided into 2 groups according to the presence of microvascular complications such as retinopathy, nephropathy, and neuropathy. RESULTS: Patients showed slightly lower hematocrit and higher serum fibrinogen levels than control subjects, but other clinical profiles, including stroke risk factors except for diabetes, were comparable between patients and controls. The flow velocity of the ICA but not the MCA and BA in patients regardless of the complication was significantly higher than that in controls. The PIs of the MCA and ICA were significantly higher in patients with complication than those without complication, as well as in controls. The PI of the BA was also significantly higher, even in patients without complication, than in controls. The PIs of the MCA and ICA but not the BA were closely correlated with the duration of DM (r(2)=0.46 and 0.34, respectively). CONCLUSIONS: This study defines TCD findings of diabetes-related cerebral hemodynamic changes and suggests that the PI reflects microangiopathic changes of cerebral vessels.

Aged↗
PubMed2000

An engineered lox sequence containing part of a long terminal repeat of HIV-1 permits Cre recombinase-mediated DNA excision.

In our previous report, one 34-bp sequence from a long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) clone, loxLTR-1, was proposed as a target site for site-specific excision by modified Cre recombinase. To support this suggestion, an engineered lox sequence, designated loxIL1, was made. This variant lox has the corresponding sequence of loxLTR-1 at the spacer region and the last two bases of inverted repeat sequence. Through in vitro recombination assay, loxIL1 also allowed the wild-type Cre to specifically recombine the sequence. An in vitro DNA binding experiment with mutants CreK244R and CreK244L revealed that lysine 244 of Cre plays an important role in interaction with the engineered lox. This result suggests that loxLTR-1 would be a candidate for antiviral strategy using site-specific recombinase.

DNA, Intergenic↗
PubMed1999

Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme.

We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia.

Animals↗
PubMed1999

Inhibition of interleukin-1beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice.

The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with z-VAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the z-VAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 +/- 1.80 mm3, z-VAD.FMK-treated animals; 7.46 +/- 3.53 mm3, vehicle-treated animals; mean +/- SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1beta converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after cold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family proteases appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Rheumatoid arthritis associated with myelodysplastic syndrome: a case report.

Myelodysplastic syndromes (MDS) are a group of refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. There is increasing recognition of immunological abnormalities in patients with MDS, including defective B- and T-cell function, hyper- or hypogammaglobulinemia and monoclonal gammopathy. MDS have been associated with Sjögren's syndrome, polymyalgia rheumatica, relapsing polychondritis and systemic lupus erythematosus. Although there may be various rheumatologic features, including acute arthritis in MDS, chronic inflammatory arthritis is uncommonly combined. There have been a few reports that described cases of rheumatoid arthritis (RA) concurrent with MDS, but advanced rheumatoid arthritis with typical joint deformities has rarely been reported. We report a case of rheumatoid arthritis with atlantoaxial subluxation combined with refractory anemia in a 31-year-old woman.

Adult↗
PubMed1998

Dopaminergic influences on the P300 abnormality in Parkinson's disease.

This study was designed to evaluate the contribution of central dopaminergic mechanisms to the P300 event-related potential (P300) abnormality in Parkinson's disease. We measured the P300 in 37 non-demented patients with Parkinson's disease (19 de novo and 18 levodopa-treated) and 15 age-matched healthy volunteers. The P300 measurement was repeated in 14 de novo patients, after 6-12 months levodopa therapy. The severity of parkinsonian symptom was assessed using the UPDRS-motor scale. De novo patients showed prolonged P300 latency compared with levodopa-treated patients, as well as healthy volunteers. The levodopa therapy for 6-12 months significantly shortened the P300 latency and reduced the UPDRS-motor examination score in de novo patients. However, the percent changes in the P300 latency were not correlated with those in the UPDRS-motor examination score. These results indicate that the central dopaminergic mechanisms apart from those responsible for motor symptoms, may contribute to the P300 abnormality in Parkinson's disease.

Acoustic Stimulation↗
PubMed1997

Blood flow velocity changes in the middle cerebral artery as an index of the chronicity of hypertension.

This study was designed to demonstrate cerebral hemodynamic changes related to hypertension using transcranial Doppler ultrasonography. We measured the flow velocities and the Gosling pulsatility index of the middle cerebral artery and the internal carotid artery in 94 stroke-free, hypertensive patients and 81 age- and gender-matched healthy controls. Compared with the control subjects, patients with a longer duration (> or = 5 years) of hypertension showed significantly lower flow velocities of the middle cerebral artery and a higher Gosling pulsatility index of the middle cerebral- and the internal carotid artery. These differences were not observed in patients with a shorter duration of hypertension (<5 years). In the patient group, the mean velocity of the middle cerebral artery was significantly and inversely correlated with the duration of hypertension. Decreased flow velocity with increased pulsatility observed in this study suggest that alterations in the small cerebral vessels and arterioles contribute primarily to cerebral hemodynamic changes occurring in long-standing hypertension and also suggest the possible usefulness of transcranial Doppler in monitoring the progression of cerebral atherogenesis related to hypertension.

Adult↗
PubMed1997

Do hematocrit and serum fibrinogen influence transcranial Doppler measurements?

To investigate the effect of hematocrit and serum fibrinogen on transcranial Doppler ultrasound (TCD) measurements, we performed, TCD tests and measured hematocrit and serum fibrinogen concentrations in 112 healthy adult volunteers. The mean velocities of the middle cerebral (r = -.37, p < .0001), internal carotid at siphon (r = -.14, p < .05) and cervical level (r = -.14, p < .05), vertebral (r = -.21, p < .005) and the basilar artery (r = -.33, p < .001) were significantly and inversely correlated with hematocrit, while serum fibrinogen weakly affected the mean velocities of the internal carotid artery. The subjects with low hematocrit (< or = 40%) showed significantly higher mean velocities of the middle cerebral, vertebral and basilar arteries than those with high hematocrit (> 40%). Considering the influence of the subject's age and gender, hematocrit is the strongest factor influencing the velocities of the middle cerebral and the basilar artery. These results suggest that hematocrit is an important variable for TCD measurements of the cerebral blood velocities and should be taken into account in TCD application.

Adult↗