Biomedical subjects

B H Choi

Publications and source records attributed to B H Choi.

At least 55 records · Page 3Linked to original sources

PubMed1998

Physiologic and histologic changes in near-term fetal lambs exposed to asphyxia by partial umbilical cord occlusion.

OBJECTIVES: Our purpose was to characterize the histologic changes in the asphyxiated fetal lamb brain and to correlate the severity of these changes with fetal physiologic parameters during and after asphyxia. STUDY DESIGN: Seventeen near-term fetuses were used for analysis: control group without manipulation (n = 4, 132 +/- 1.1 days of gestation at autopsy, mean +/- SEM), sham-asphyxia control group (n = 3, 132 +/- 1.3 days), and asphyxiated group, which successfully survived 72 hours after asphyxia (n = 10, 130 +/- 1.0 days). Asphyxia was produced by umbilical cord occlusion lasting for approximately 60 minutes until fetal arterial pH diminished to < 6.9 and base excess to < -20 mEq/L. Fetal heart rate, blood pressure, and electrocorticographic activity were continuously monitored. The fetuses were killed 72 hours after asphyxia, and the brains were fixed in formalin and processed for histologic and immunocytochemical studies. RESULTS: Neuropathologic changes varied from case to case, ranging from almost total infarction of cortical and subcortical structures to extremely subtle and patchy white matter alterations characterized by slight vacuolization of the white matter or slight to moderate increases in cellularity confined to the junction of cerebral cortex and white matter. Even fetuses that showed full recovery of all physiologic parameters, including electrocorticographic activity, demonstrated subtle but distinct white matter lesions. The gray matter, including the hippocampal neurons, was generally spared in these cases. Electrocorticographic parameters, duration of hypotension during asphyxia, and delayed recovery of blood lactate concentrations correlated well with the histologic grading of brain damage. CONCLUSIONS: Asphyxia by partial umbilical cord occlusion in near-term fetal lambs produces variable neuropathologic changes. The mildest change is a white matter lesion characterized by vacuolization and loss of myelin or by increased cellularity in the damaged regions.

Animals↗

PubMed1998

Insulin activates the hepatitis B virus X gene through the activating protein-1 binding site in HepG2 cells.

Insulin stimulates cellular oncogenic activators such as c-jun, c-fos, and c-myc; and hepatitis B virus (HBV) X, a viral transactivator, is known to induce liver cancer in transgenic mice. In this respect, the effect of insulin on the expression of HBx protein was investigated in HepG2 cells. Insulin-stimulated transcription from the HBV X promoter in a dose-dependent manner was assessed by chloramphenicol acetyltransferase (CAT) assay. A mutation preventing AP-1 binding to the E element abolished the activation of the HBV X promoter by insulin. In addition, insulin stimulated the minimal thymidine kinase (tk) gene promoter activity through both the HBV E element and the consensus AP-1 binding site in HepG2 cells. An electrophoretic mobility shift assay (EMSA) using insulin-treated HepG2 nuclear extracts showed that insulin actually enhanced the binding of nuclear proteins to the HBV E element as well as to the consensus AP-1 binding site. Both HBV E and AP-1 oligonucleotides were effective competitors for this binding. These results showed that insulin elevated the expression of HBx protein through the AP-1 binding site of HBV EnI. We suggest that insulin can augment the role of HBx in the development of hepatocellular carcinoma (HCC) in HBV-infected liver, probably through interaction with other cellular oncogenes.

Binding Sites↗

PubMed1997

Activating transcription factor 2 (ATF2) down-regulates hepatitis B virus X promoter activity by the competition for the activating protein 1 binding site and the formation of the ATF2-Jun heterodimer.

The hepatitis B viral X promoter is known to be positively autoregulated by its own HBx protein, which also interacts with many cellular regulatory proteins. We investigated the effect of activating transcription factor 2 (ATF2) on the activity of the X promoter. Cotransfection of the ATF2 expression vector with a X promoter-chloramphenicol acetyltransferase plasmid repressed the X promoter activity in HepG2 cells. HBx activated activating protein 1 (AP-1)-mediated transcription through the hepatitis B virus E element by 35-fold, while its activation activity was inhibited in the presence of ATF2, suggesting that ATF2 inhibited the autoactivation of X promoter by HBx and basal transcription mediated by AP-1. Since the binding sites of AP-1 and ATF2 in the hepatitis B virus E element overlap, the repression of X promoter activity by ATF2 is exerted by the competition for the AP-1 binding site and the formation of the ATF2-Jun heterodimer as in the case of the consensus AP-1 element. However, the small X promoter had a ATF2 binding site and was activated by ATF2. These results suggest that the syntheses of X proteins are differentially regulated by ATF2.

Activating Transcription Factor 2↗

PubMed1997

Cytotoxic effects of repin, a principal sesquiterpene lactone of Russian knapweed.

Repin is the principal sesquiterpene lactone isolated from Russian knapweed (Centaurea repens), a perennial weed found in many parts of the United States. Ingestion of Centaurea repens by horses has been reported to cause a movement disorder simulating Parkinson's disease (PD) and nigrostriatal degeneration, called equine nigrostriatal encephalomalacia (ENE). To understand the mechanisms whereby ingestion of Centaurea repens induces ENE and a PD-like disorder, repin cytotoxicity was examined to explore its pathogenetic relationship to ENE and to PD. Repin was highly cytotoxic to both PC12 cells and mouse astrocytes in a dose- and time-dependent manner. The cytotoxic effects were accompanied by depletion of glutathione (GSH), a rise in the level of reactive oxygen species (ROS) and damage to cellular membranes. Although repin is a highly reactive electrophile that can readily conjugate GSH, GSH depletion may not be the sole mechanism underlying repin cytotoxicity as shown by our study using buthionine sulfoximine, in which severe GSH depletion did not result in a parallel increase in cell death. However, pre-treatment with GSH-glycoside or with lipoic acid provided significant protection from repin-induced cell death. These data suggest that oxidative stress plays a major role in repin cytotoxicity. Since oxidative stress is considered to play a major role in neuronal degeneration accompanied by depletion of mitochondrial GSH and an increase in lipid peroxides in the substantia nigra of PD, further elucidation of mechanisms of repin neurotoxicity may generate clues regarding not only the mechanisms of neuronal degeneration but also the possible role of environmental factors in the pathogenesis of PD.

Animals↗

PubMed1997

Magnetic resonance imaging of the temporomandibular joint after functional treatment of bilateral condylar fractures in adults.

The position and functioning of discs in ten adult patients, whose bilateral condylar fractures were treated following a nonsurgical protocol, were investigated by means of magnetic resonance imaging. In seven temporomandibular joints (TMJs), where the condylar fragments were situated in the confines of the glenoid fossa, the discs were not displaced and were functioning normally. In 13 TMJs, where the condylar fragments were medially dislocated out of the fossa, the discs were displaced together with the condylar head but moved forward together with the condyle during mouth opening. This relationship between disc and condyle appears to play an important role in the reestablishment of function using nonsurgical treatment in patients with condylar fractures.

Adult↗

PubMed1996

The effects of glutathione glycoside in methyl mercury poisoning.

The use of glutathione glycoside (GSH-glyc), a compound newly synthesized in our laboratory, was highly effective in raising cellular GSH levels both in vitro and in vivo. Based on mass spectrometry and 1H NMR data, the structure of GSH-glyc was determined to be that of an S-glycoside. Rapid GSH uptake was observed by confocal microscopy in both A549 cells and mouse astrocytes following incubation with GSH-glyc. Intraperitoneal (i.p.) and per oral administration of GSH-glyc in C57BL/6J mice raised GSH concentrations in brain and liver to significantly higher levels than normal. Methyl mercury (MeHg) poisoning of mice with multiple doses of methylmercuric chloride (MMC) induced severe toxic effects associated with marked depletion of brain and liver GSH progressing to death in all animals, whereas the animals primed with GSH-glyc and given MMC and GSH-glyc concurrently were devoid of toxic signs. We suggest, on the basis of D-[3H]glucose and [2- 3H]deoxyglucose uptake studies, that the transport of GSH-glyc across the blood-brain barrier may occur through one of the glucose transport pathways. Although the precise mechanism by which GSH-glyc protects against MeHg poisoning is not clear, it is probable that any one of a number of factors, including conjugation of MeHg, scavenging of free radicals, restoration of reactive thiol groups, and enhancement of MeHg efflux, may have been instrumental. GSH-glyc is a nontoxic compound that can be used to transport GSH into cells, including those of brain and liver, and may prove to be useful for prophylaxis and therapy of tissue injury induced by various neurotoxic compounds, particularly when the capacity to synthesize or regenerate GSH has been compromised.

Animals↗

PubMed1996

Comparison of computed tomography imaging before and after functional treatment of bilateral condylar fractures in adults.

Bilateral condylar fractures in 10 adult patients were successfully treated nonsurgically. The patients were studied with computed tomography (CT). In all patients, the pretreatment images of both condyles showed medially displaced or dislocated condyles which were accompanied clinically by an anterior open bite. In all patients, the anterior open bite was eliminated and the occlusion was normal 2-3 months after treatment, while jaw function was normal and the patients were free of pain. Follow-up CT images showed that the fractured condyles had healed by bony consolidation but were still displaced or dislocated. The relationships with the glenoid fossa had not improved. The reestablishment of occlusion and function appears to occur not as a result of anatomic restitution of condylar height, but as a result of adaptation of the masticatory muscles.

Adaptation, Physiological↗

PubMed1996

Radiographic comparison of osseous healing after maxillary sinusotomy performed with and without a periosteal pedicle.

OBJECTIVE: To assess the postoperative fate of bone trapdoors in patients with a trapdoor in the facial wall of the maxillary sinus that was replaced after removal of sinus disease. STUDY DESIGN: Twenty patients were studied. In 10 patients (group A) the trapdoor was made as a free bone graft; in the other 10 patients (group B), an osteoperiosteal trapdoor was made. The postoperative fate of bone trapdoors was studied by means of computed tomography. RESULTS: In group A there was poor bony consolidation at the trapdoors' junction with the surrounding bone and a significantly reduced density of the osteotomized bone. In two of the group A patients there was a partial loss of the trapdoor. In group B, however, bony consolidation took place in that all the trapdoors were completely connected again to the surrounding bone and there was no reduction of the bone density. CONCLUSION: The results indicate that a trapdoor with a periosteal pedicle appears to be more reliable than one without a periosteal pedicle.

Adult↗

PubMed1996

Oxidative stress in neurotoxic effects of methylmercury poisoning.

The effects of methylmercuric chloride (MMC) on the rate of oxygen uptake were determined in purified cultures of oligodendrocytes, astrocytes, and cerebral cortical and cerebellar granular neurons obtained from embryonic and neonatal rat brains. Rapid and profound inhibition of oxygen uptake took place in all cell types following MMC exposure. However, the sensitivity of cellular respiration to the toxic effects of MMC appeared to parallel the normal oxygen demands of the cell type. To assess the effects of MMC on mitochondrial electron transport chain (ETC) activity, complex-specific electron donating substrates were used to stimulate the mitochondria obtained from both control and MMC-injected rat brains. Significant increases in reactive oxygen species (ROS) and thiobarbituric acid-reactive substances (TBARS), and a reduction in glutathione levels were observed in the MMC group following stimulation of complex III, but not with stimulation of either complex I or II, suggesting that MMC induces alterations in electron transport in the ubiquinol: cytochrome c oxidoreductase region. The rapidity of oxygen uptake inhibition by MMC in cultured CNS cells and the demonstration of MMC effects on specific enzyme complexes in the mitochondrial ETC strongly support the contention that mitochondria may be the earliest target of MeHg neurotoxicity, and that the mitochondrial ETC is the most likely site where excess ROS are generated in the brain to induce oxidative stress in MeHg poisoning.

Animals↗

PubMed1995

Stability testing of a two miniplate fixation technique for mandibular angle fractures. An in vitro study.

In the case of mandibular angle fractures, a two miniplate fixation technique in which one plate is applied ventral to the oblique line and a second plate at the inferior border of the buccal cortex was used to stabilize the fracture. In this paper, the stability of the two miniplate fixation technique was tested in a three-dimensional in vitro model. The results of this study showed that in cases of angle fractures this fixation technique provides stable fixation under functional loading.

Bone Plates↗

PubMed1995

Clinical and in vitro evaluation of mandibular angle fracture fixation with the two-miniplate system.

More stable fixation and greater resistance against infection are achieved in mandibular angle fractures if the two-miniplate-fixation technique is used. One plate is applied at the superior border and a second plate is applied at the inferior border of the buccal cortex. Strong support for this argument was demonstrated in these in vitro and pilot clinical studies. It is concluded that the two-miniplate-fixation technique is indicated in cases of mandibular angle fracture to achieve stability of the fracture site and early mobility of the jaw.

Adolescent↗

PubMed1995

Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes.

We studied the effects of organic and inorganic mercury (Hg) on the uptake of L-[3H] glutamate (L-GLU) in cultured mouse astrocytes. Following exposure to mercuric chloride (MC) [0.2 approximately 5.0 microM], selective and dose-dependent inhibition of L-GLU uptake to 50% of control levels was observed, whereas 2-deoxyglucose (2-DG) uptake was not significantly affected. Methylmercuric chloride (MMC) also inhibited L-GLU uptake but 50% reduction was reached only at a concentration of 10 microM. Inhibition of L-GLU uptake by MMC appears to be closely linked to voltage-sensitive calcium channels as evidenced by the lack of L-GLU uptake inhibition by MMC in calcium-free medium or in the presence of the channel blocker verapamil. Exposure to a variety of divalent metallic ions, including CuCl2, FeCl2 and ZnCl2, did not affect L-GLU uptake in astrocytes in vitro. Exposure to PbCl2, however, resulted in a decline in L-GLU uptake, though to a much smaller degree than that observed with Hg compounds. Selective impairment of astroglial L-GLU transport may represent a critical early pathogenetic feature of Hg-induced neurotoxicity.

Animals↗

PubMed1994

Role of the basement membrane in neurogenesis and repair of injury in the central nervous system.

Although remarkable progress has been made during the last two decades concerning the biosynthesis, expression and assembly of extracellular matrix (ECM) macromolecules in nonneural cells, we are still far from a complete understanding of the role and function of the ECM and the basement membrane (BM) in the central nervous system (CNS). With the aid of correlative light and electron microscopic, Golgi and immunohistochemical studies of the developing neural tube of both early human fetus and mouse, we have shown that the establishment of the pial-glial barrier (PGB) is one of the earliest histogenetic events in neurogenesis. This is accomplished by coordinated interaction among the processes of radial glia, various ECM components, and mesenchymal cells at the pial surface, with the formation of a BM that tightly abuts the glia limitans. The PGB and the BM appear to be critical to the migration and final positioning of neurons and to the differentiation of the laminar cortical pattern within the developing neopallium. This hypothesis is further supported by our study of the brain of a human newborn infant in whom multiple sites of disruption of the BM and PGB resulted in abnormal neuronal migration and massive ectopia of neurons within the subarachnoid space, with abnormal cortical lamination. Finally, studies of the experimental cryogenic injury to the neonatal rat cerebrum have shown that the final positioning of neurons within the developing cortical plate appears to depend largely on the reconstitution of the BM and PGB, which presumably provide crucial positional signals for migrating neurons. Also, one of the essential reparative features seen following cryogenic injury to the adult rat cerebrum is an orderly and dynamic interaction between various ECM components and neural cells, resulting in the formation of the BM.

Animals↗

PubMed1994

Methylmercury poisoning induces oxidative stress in the mouse brain.

C57BL/6J mice were intoxicated by injection of 2.5 mg/kg body wt of methylmercuric chloride (MMC) daily for 3, 7, and 14 days, and the relative concentrations of superoxide and hydrogen peroxide and the specific activity of superoxide dismutase (SOD) were determined in various cellular fractions of the brain. High brain levels of Hg were associated with significantly increased amounts of superoxide and hydrogen peroxide by Days 3, 7, and 14 and with markedly reduced SOD activity by Days 7 and 14. Such a rise in the levels of reactive oxygen species indicates the induction of oxidative stress within brain tissue. This suggests that suppression of antioxidant activity, including that of SOD and glutathione, together with disturbances in the mitochondrial electron transport chain, may contribute to the induction of oxidative stress in the mouse brain following MMC poisoning.

Animals↗

PubMed1994

Comparison of magnetic resonance imaging before and after nonsurgical treatment of closed lock.

Ten temporomandibular joints with the closed lock in 10 patients who were successfully treated clinically nonsurgically with the occlusal splint, were studied with magnetic resonance imaging. In all patients, the pretreatment images of temporomandibular joints showed anteriorly dislocated disks that failed to recapture together with various changes in disk morphology. Three to four months after the treatment, all patients could open their mouths more than 47 mm at the incisor position and were asymptomatic. But the follow-up magnetic resonance images showed that the disks were still anteriorly displaced and deformed and their relationships with the condyles were unchanged. The reestablishment of mouth opening appeared to occur not by recapturing of the disks but by improvement in condylar mobility and the adaptation of the posterior attachment.

Adolescent↗

PubMed1993

Multiple spinal meningiomas: a case of 47 distinct lesions in the absence of neurofibromatosis or identified chromosomal abnormality.

The authors present a unique case of multiple spinal meningiomas with the late development of intracranial lesions. The patient had 47 distinctly separate, yet histologically identical, lesions excised, with many others noted at the time of surgery and by radiographic studies. He was evaluated for neurofibromatosis and was found to have neither Type I nor Type II. Genetic analysis, including restriction fragment length polymorphism analysis, was performed and detected no abnormalities.

Adult↗

PubMed1993

Oxygen, antioxidants and brain dysfunction.

Brain is a logical target of free radical damage, considering the large lipid content of myelin sheaths and the high rate of brain oxidative metabolism. Thus, the hypothesis that free radicals may be involved in the pathogenesis of certain CNS diseases has gained increasing popularity in recent years. In CNS ischemia-reperfusion injury, the role of free radicals appears to be well established, however, involvement of other factors, such as excitatory amino acids and prostaglandins, may also contribute to the production of neuronal necrosis following ischemia. Liberation of free iron appears to play a crucial role in the generation of reactive oxygen species in posttraumatic epilepsy. Although there is no direct evidence to indicate free radical involvement in the pathogenesis of Alzheimer's disease, brain trauma with release of iron, amyloid angiopathy and disturbances in blood-brain barrier function all appear to contribute to the development of ischemic episodes with free radical generation and neuronal degeneration. In Parkinson's disease, the substantia nigra appears to be under oxidative stress as evidenced by the findings of increased lipid peroxidation, reduced GSH levels, high concentration of iron and free radical generation via autocatalytic mechanisms within neuromelanin-containing catecholaminergic neurons. Regardless of the initial insult, a cascade of events involving both reactive oxygen radicals and mitochondrial metabolism is likely to contribute to cell injury.

Brain Diseases↗

PubMed1992

Expression of protease nexin-II in human dorsal root ganglia. A correlative immunocytochemical and in situ hybridization study.

Protease nexin-II (PN-II) is a potent chymotrypsin inhibitor that forms SDS-stable inhibitory complexes with epidermal growth factor binding protein, the gamma-subunit of nerve growth factor, and trypsin, and represents the secreted form of the amyloid beta-protein precursor (APP) that contains the Kunitz-type protease inhibitor domain. To determine the expression of PN-II within the peripheral nervous system, human dorsal root ganglia were processed for immunocytochemistry using well-characterized monoclonal antibodies against PN-II and for in situ hybridization studies using 35S-RNA PN-II probes for both APP751 and APP770. Highly specific immunoperoxidase staining of PN-II was demonstrated within the cytoplasm of dorsal root ganglia neurons and their processes in cryostat (fresh frozen) and vibratome (paraformaldehyde-fixed) sections. In situ hybridization using an anti-sense 35S-RNA PN-II probe demonstrated the presence of intense neuronal labeling. Labeling was not observed when the corresponding sense 35S-RNA PN-II probe was used. Although the precise functional role of PN-II/APP is not clear, the accumulation of amyloid beta-protein within the neuropil appears to be one of the earliest events in the pathogenesis of Alzheimer's disease (AD). Thus knowledge of the cell populations expressing the PN-II/APP gene would certainly be helpful for studies of the molecular mechanisms leading to the morphological and functional changes of AD. The results of this study clearly establish the expression of PN-II and its mRNA within the dorsal root ganglia neurons and their processes, and provide another point of departure for studies of the molecular mechanisms underlying the deposition of amyloid beta-protein and its relationships to the formation of neuritic plaques and neurofibrillary tangles.

Amyloid beta-Protein Precursor↗