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Biomedical subjects

S C Hong

Publications and source records attributed to S C Hong.

At least 55 records · Page 3Linked to original sources

Mild hypothermia: therapeutic window after experimental cerebral ischemia.

The treatment of cerebral ischemia remains a formidable challenge in neuroscience today. Mild hypothermia has been shown to be an effective neuroprotective agent. Despite the great volume of published research, the therapeutic window of mild hypothermia has not been precisely elucidated. Using a model of reversible focal cerebral ischemia in the rat, this study was undertaken to define the optimal duration of hypothermic application and the maximal postischemic delay in hypothermic application before which optimal therapeutic effect is noted. Focal ischemia was induced by temporary occlusion of the middle cerebral artery and both carotid arteries in Sprague-Dawley rats for a period of 3 hours. In the first study, mild hypothermia (32-33 degrees C) was induced at the onset of ischemia in four groups of rats for varying lengths of time ranging from 1 to 4 hours. The animals were killed after 3 days, and their brains were sliced and stained. Infarcted volume was measured using a computerized image analyzer. The infarct volumes were 211 +/- 4.5, 214.2 +/- 8.0, 199.5 +/- 5.3, 171.3 +/- 9.1, and 169.8 +/- 6.5 mm3 (mean +/- standard error of the mean, n = 6 per group) for the control, 1-hour, 2-hour, 3-hour, and 4-hour groups, respectively. On the basis of the results from the above study, a 3-hour duration of hypothermia was then applied to animals at 0, 15, 30, or 45 minutes after the ischemic onset. The volumes of infarction for these four respective groups were: 171.3 +/- 9.1, 173 +/- 5.7, 179.3 +/- 5.2, and 206.2 +/- 8.4 mm3 (mean +/- standard error of the mean, n = 6 per group). These results demonstrated that optimal duration of mild hypothermia was at least 3 hours (P < 0.001) when applied within the first 30 minutes after the onset of ischemia (P < 0.001).

Animals↗

CIITA activates the expression of MHC class II genes in mouse T cells.

It has long been a puzzle that MHC class II molecules are expressed in human T cells after activation but not in mouse T cells; this expression is believed to play a role in the cell mediated immune response. Recently the MHC class II transactivator (CIITA) has been reported to be a major regulatory factor for both the constitutive and IFN inducible expression of MHC class II genes. Here we show that human T cells expressing MHC class II have CIITA transcripts while MHC class II-negative human T cells and mouse T cells do not. The expression of MHC class II genes in mouse T cells can be reconstituted upon transfection with the human CIITA cDNA. These data indicate that the expression of CIITA explains the expression or lack of expression of MHC class II in human and mouse T cells respectively.

Animals↗

Calcium-activated proteolysis in rat neocortex induced by transient focal ischemia.

Ischemia-induced elevation of intracellular calcium triggers a cascade of events which is considered to play a major role in neuronal death. One candidate to participate in this process is the calcium-sensitive protease, calpain. This protease is activated by calcium, and is capable of degrading critical cytoskeletal and regulatory proteins. In order to further elucidate the role of calpain in focal ischemic damage, the present study investigated the proteolysis of spectrin, a preferred substrate for calpain, in response to transient focal ischemia. Ischemia was induced by occluding reversibly both carotid arteries and the left middle cerebral artery for three hours in Sprague-Dawley rats. Western blotting techniques were used to identify and quantify the amounts of spectrin breakdown products (BDPs) in neocortical samples from the area destined for infarction, the peri-infarct area, and the contralateral hemisphere. Substantial increases in spectrin proteolysis were observed within the first few hours of ischemia in the areas that will undergo infarction. The increase in spectrin BDPs in these areas reached a plateau around the end of the 3 h ischemic period. In the peri-infarct zone, the levels of spectrin BDPs increased in a biphasic manner. A small to moderate increase was observed by the second hour of ischemia, followed by a larger increase between the 6th and 24th hours post-ischemia. The contralateral neocortex showed a significant increase in BDPs at 2 h after the initiation of ischemia. A smaller increase in BDPs was observed thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Isoforms of the transmembrane tyrosine phosphatase CD45 differentially affect T cell recognition.

Activation of T cells has been shown to require CD45. CD45 is expressed on T cells as distinct isoforms and these isoforms are expressed differentially on subsets of CD4 T cells. We have generated T cell lines expressing a T cell receptor (TCR) of known specificity, with or without CD4, and examined the effect of different CD45 isoforms on stimulation through the antigen receptor. We find that isoforms differ in their ability to participate in antigen recognition, with the null isoform that is predominantly found on memory CD4 T cells being the most effective. The ability of the CD4 T cells being the most effective. The ability of the CD45 ectodomain to differentially affect sensitivity to specific ligands represents a novel way of regulating the efficacy of signaling through a receptor without altering its specificity. It may play a crucial role both in immunological memory and during intrathymic maturation of T cells.

Animals↗

Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia.

BACKGROUND AND PURPOSE: Excessive elevation of intracellular calcium and uncontrolled activation of calcium-sensitive events are believed to play a central role in ischemic neuronal damage. Calcium-activated proteolysis by calpain is a candidate to participate in this form of pathology because it is activated under ischemic conditions and its activation results in the degradation of crucial cytoskeletal and regulatory proteins. The present studies examined the effects of a cell-penetrating inhibitor of calpain on the pathological outcome after transient focal ischemia in the brain. METHODS: Twenty-five male Sprague-Dawley rats were divided into four groups: a saline-treated group, a vehicle-treated group, and two calpain inhibitor-treated groups (Cbz-Val-Phe-H; 30-mg/kg and 60-mg/kg cumulative doses). Ischemia was induced by occluding the left middle cerebral artery and both common carotid arteries for 3 hours followed by reperfusion. Animals were killed 72 hours after surgery, and quantitative measurements of infarction volumes were performed using histological techniques. Eight additional rats were killed 30 minutes after ischemia and examined for the extent of proteolysis using immunoblot techniques. A final group of 12 animals was decapitated after injection of vehicle or calpain inhibitor, and the proteolytic response was measured after 60 minutes of total ischemia. RESULTS: Rats treated with Cbz-Val-Phe-H exhibited significantly smaller volumes of cerebral infarction than saline-treated or vehicle-treated control animals. Intravenous injections of cumulative doses of 30 mg/kg or 60 mg/kg of Cbz-Val-Phe-H were effective in reducing infarction, edema, and calcium-activated proteolysis. The proteolytic response to postdecapitation ischemia was also reduced by the calpain inhibitor. CONCLUSIONS: These results demonstrate the neuroprotective effect of a cell-penetrating calpain inhibitor when administered systemically. The findings suggest that targeting intracellular, calcium-activated mechanisms, such as proteolysis, represents a viable therapeutic strategy for limiting neurological damage after ischemia.

Analysis of Variance↗

Effects of two dual-function compounds, U92798 and U92032, on transient focal ischemia in rats.

Two newly-developed compounds (U92798 and U92032), which inhibit lipid peroxidation and block calcium entry, were studied for their effects on neocortical damage after transient focal ischemia. Ischemia was induced in Sprague-Dawley rats by simultaneous occlusion of the left middle cerebral artery and both common carotid arteries for a period of 3 hours. Compounds (1 mg/kg) were administered intravenously 30 minutes before occlusion and again 2.5 hours after the cessation of blood flow. After a 72-hour period of reperfusion, the animals were killed and examined for cerebral infarction and edema. Treatment with U92798 or U92032 significantly reduced the volume of cortical infarction. Edema was also reduced in these groups; however, this effect did not achieve statistical significance. These results suggest that dual function compounds, which both inhibit lipid peroxidation and block calcium entry, are promising therapeutic agents for the amelioration of ischemic cerebral damage.

Animals↗

Histopathologic changes in the olfactory epithelium in mice after exposure to sulfur dioxide.

To investigate the effects of sulfur dioxide (SO2) on olfactory epithelium, an experiment was performed with 56 mice from the same colony. Experimental animals were divided into three groups consisting of a 30-min exposure group (group 1), a 60-min exposure group (group 2), and a 120-min exposure group (group 3). The olfactory mucosa in these mice were studied by light microscopy immediately, and after 24 h, 48 h, or 72 h exposure to 20 ppm of SO2. Edema, loss of cilia, epithelial thinning, and epithelial desquamation in the olfactory epithelium were observed in groups 2 and 3. The basal lamina and the connective tissue were well preserved throughout the entire mucosa. Injuries to olfactory epithelium became severer with exposure time. These changes were further pronounced 24 h after exposure. Regenerated epithelia were not observed in any group. Scanning electron microscopic findings were consistent with light microscopic findings. Olfactory epithelial surface were consistent with light microscopic findings. Olfactory epithelial surface was sloughed off and revealed, underlining intact basal lamina. The results of this study suggest that early lesions of olfactory epithelium after exposure to SO2 may be primarily degenerative.

Administration, Inhalation↗

Illness associated with contamination of drinking water supplies with phenol.

An accidental spill of phenol (100%) into the Nakdong river with subsequent contamination of the tap water for about two million consumers in Teagu city of Korea occurred in March 1991. A historical cohort study of 6,913 individuals was undertaken to determine association with illness. Population subjects were divided into two groups of exposed and unexposed. Exposed subjects were reported to have significantly more phenol associated symptoms than those in a nearby unexposed area (39.6% vs. 9.4%, p < 0.01). Especially, in the related symptoms, highly significant differences were noted in the number of subjects reporting gastrointestinal illness such as nausea, vomiting, diarrhea, or abdominal pain. During the accident, study subjects who experienced peculiar taste or odor in the tap water were significantly more in the exposed areas (92% vs. 34.3%).

Accidents↗

Interphase cytogenetics of lung tumors using in situ hybridization: numerical aberrations.

OBJECTIVES: Since conventional cytogenetic analysis for bronchogenic carcinogenesis is limited by the difficulty to get enough number of high quality metaphase spreads, the development of new method to overcome above problems is strongly needed. Therefore, the introduction of non-radioactive in situ hybridization (ISH) with pericentromeric chromosome probes gave us the way to investigate the genetic events during carcinogenic process. We applied this method on lung cancer tissue to validate the possibility of this method for general usage and to analyze numerical chromosome aberration status and their clinical correlations. METHODS: A set of satellite DNA probes specific for chromosome 3, 7, 9, 11, and 17 was hybridized directly to paraffin-embedded tissue section of 30 non-small cell lung cancers. Mean chromosome index of each chromosome and frequency of polysomy for each chromosome were calculated. RESULTS: Mean chromosome indices for chromosome 3, 7, 9, 11, and 17 were 1.10, 1.13, 1.17, 1.12, and 1.17, respectively. Polysomy for a set of chromosomes was detected in all 30 cases except 4 cases which showed hypoploidy only for chromosome 3 or 7 in 2 cases and diploidy only for chromosome 3 or 11 in 2 cases. Among the set of chromosomes, mean chromosome index and polysomy frequency for chromosome 9 & 17 were significantly higher than that for others. Mean chromosome index or polysomy pattern for each chromosome was not much different among cell types or clinical stages. CONCLUSIONS: Our results show that chromosome ISH can be used to screen for numerical chromosome aberrations on paraffin tissue sections and further studies for ISH analysis with different probes on same tumor area or double-target ISH in large scale are needed to confirm above results and to elucidate the specific meanings.

Carcinoma, Non-Small-Cell Lung↗

Selective loss of NADPH-diaphorase-containing neurons in the dentate gyrus following transient ischemia.

The effect of transient forebrain ischemia on NADPH-diaphorase-containing neurons was examined in the dentate gyrus of the gerbil. NADPH-diaphorase histochemistry was performed in animals subjected to temporary occlusion of the common carotid arteries and sham-operated animals. Seven days following transient ischemia, the number of NADPH-diaphorase-positive neurons in the infragranular zone of the dentate gyrus was reduced by approximately 50% compared with control animals. Since neighboring granule cells are known to be resistant to this level of ischemic challenge, the present observations indicate that NADPH-diaphorase-containing neurons in the dentate gyrus are selectively vulnerable to brief ischemia.

Amino Acid Oxidoreductases↗

TCR-CD4 and TCR-TCR interactions as distinctive mechanisms for the induction of increased intracellular calcium in T-cell signalling.

Specific activation of CD4 T cells involves recognition of a peptide: MHC class II complex by the heterodimeric alpha beta TCR and its CD4 co-receptor. The activation of T cells initiates a signal transduction cascade that includes a substantial and rapid increase in cytosolic calcium. In this work we study the role of the interactions between the TCR and the CD4 molecule in inducing this [Ca2+]i increase in the cloned CD4 T-cell line D10. Ligating CD3 or the TCR with mAb leads to proliferation of this cloned line and an increase in intracellular free calcium. An exceptional antibody, 16A, was able to stimulate proliferation but did not induce an increase in intracellular free calcium, even when extensively cross-linked with anti-Ig. However, when 16A was cross-linked to CD4 a rise in [Ca2+]i was observed. This demonstrated the ability of TCR-CD4 interactions to trigger a [Ca2+]i response in a situation where no signal was obtained from TCR-TCR interactions. Because CD4 molecules can associate with the TCR, we also studied whether CD4 is involved in the observed increases in intracellular free calcium obtained with other anti-TCR antibodies. This was examined in CD4-negative T cells transfected with cDNA encoding the D10 TCR. These cells could be induced to flux calcium by the same anti-TCR antibodies that gave this response in D10 cells, and again 16A failed to induce such a response. In the transfectants, anti-CD3 antibodies, in contrast to TCR antibodies, could induce a calcium signal in the absence of cross-linking by anti-Ig indicating that CD3 antibodies may signal distinctly from alpha beta TCR ligation. These studies document that antibodies binding different TCR/CD3 epitopes signal distinctively, and that CD4 can participate in, but is not absolutely required for, the induction of increased intracellular calcium.

Animals↗

Cerebral aspergillosis in immunologically competent patients.

Aspergillosis of the central nervous system is a rare disease, especially if the patient's immune system is not compromised. The authors report three cases of cerebral aspergillosis in the immunocompetent state: a rhinocerebral form in a diabetic patient, a direct extension from chronic Aspergillus otitis media, and a postoperative Aspergillus brain abscess after brain tumor surgery. In spite of the poor prognosis of cerebral aspergillosis, two of the patients survived. The pathogenesis, predisposing factors, radiologic findings including magnetic resonance image, and the outcome are presented. The pertinent literature of cerebral aspergillosis is also reviewed.

Adult↗

An MHC interaction site maps to the amino-terminal half of the T cell receptor alpha chain variable domain.

We have used cloned T cell receptor (TCR) genes from closely related CD4 T cell lines to probe the interaction of the TCR with several specific major histocompatibility complex (MHC) class II ligands. Complementarity determining region 3 (CDR3) equivalents of both alpha and beta TCR chains are required for antigen-MHC recognition. Our data provide novel information about the rotational orientation of TCR-MHC contacts in that exchange of the amino terminal portion of the TCR alpha chain containing the putative CDR1 and CDR2 regions results in both gain and loss of MHC class II specificity by the resulting receptor. These two TCRs differ primarily in recognition of polymorphisms in the second hypervariable region of the MHC class II alpha chain. These results document the involvement of CDR1 and/or CDR2 of the TCR alpha chain in MHC recognition and suggest a rotational orientation of this TCR to its MHC ligand.

Amino Acid Sequence↗

Sequence analysis of peptides bound to MHC class II molecules.

CD4 T cells recognize peptide fragments of foreign proteins bound to self class II molecules of the major histocompatibility complex (MHC). Naturally processed peptide fragments bound to MHC class II molecules are peptides of 13-17 amino acids which appear to be precessively truncated from the carboxy terminus, perhaps after binding to the MHC class II molecule. The finding of predominant self peptides has interesting implications for antigen processing and self-non-self discrimination.

Amino Acid Sequence↗

Percutaneous absorption-enhancing activity of urea derivatives.

The effect of urea and urea derivatives on the percutaneous absorption of salicylic acid and sodium salicylate through the skin of rabbit from petrolatum ointment was investigated. It was found that addition of urea or urea derivatives to the ointment base significantly increased the percutaneous absorption of the drugs in proportion to the concentration of the additive. The percutaneous absorption-enhancing activities of these compounds were that urea derivatives with the more and longer alkyl substituents showed the stronger activities. These activities of urea and urea derivatives were ascribed to the binding of these compounds with the lipids and proteins of the stratum corneum of the skin and the swelling of the tissues, which leads to the reduction of the barrier property of the layer. The preliminary skin irritation test showed that urea and urea derivatives were quite non-irritating to the skin. These results suggest that urea derivatives have a strong possibility to be developed as a percutaneous absorption enhancer.

Animals↗

Etiologic considerations of nonspecific pleuritis.

Twenty-three patients with nonspecific pleuritis were studied to determine clinical outcome. After a mean follow-up period of 6 months (1 to 36 months), a diagnosis was reached in 17 patients, while 6 patients remained unknown. The causes of the nonspecific pleuritis diagnosed on initial pleural biopsy were tuberculosis (11 patients, 48%), neoplasm (2 patients, 8.7%), parapneumonic effusion (1 patient), subphrenic abscess (1 patient), congestive heart failure (1 patients), and nephrotic syndrome (1 patient). The diagnosis was made by therapeutic trials (tuberculosis: 11 patients, parapneumonic effusion: 1 patient, congestive heart failure: 1 patient), by repeat pleural biopsy in 1 hepatoma, by open thoractomy in 1 lung cancer, by exploratory laparotomy in 1 subphrenic abscess, and by kidney biopsy in 1 nephrotic syndrome. The WBC counts (more than 2,000/mm3) and lymphocyte percentage (more than 60%) in the pleural fluid were significantly elevated in the patients with tuberculosis compared to those with malignant pleurisy, and other laboratory data were meaningless. As a result of this investigation, we suggest that tuberculous pleurisy is the most common cause of nonspecific pleuritis in Korea and that therapeutic trial with antituberculous medication for patients with high WBC count and lymphocyte percent in pleural fluid can help to locate the nonspecific pleuritis.

Adult↗

[Analysis of antigenic specificities of Paragonimus westermani developmental stages using immunoblot technique].

Serodiagnosis of parasitic infections is widely used, since parasites or their eggs are not always detected by ordinary methods. The sensitive tests such as ELISA are highly dependent on the purity of antigens used. To solve this problem, many workers have tried to find species-specific components of antigens. The present study was performed to determine the antigenic profile of crude saline extracts of 3, 5, 8 and 12-week old P. westermani worms, which were collected from experimentally infected cats, based on SDS-PAGE and immunoblot technique. The results were as follows: 1. The SDS-PAGE showed at least 30 protein bands ranging from 229 kDa to 10 kDa molecular weight. The protein components of P. westermani changed chronologically during its developmental period. The 229 kDa band was recognized only in 12-week old worms (SEP12). 2. Analysis by ELISA showed a significant increase in antibody levels at 3 weeks in infected cats using crude saline extract antigens (SEP3, SEP5, SEP8, SEP12). 3. By EITB using SEP3 and SEP5, infected cats recognized major protein bands with molecular weight of 60, 35, 28, 25 or 21 kDa at 3-12 weeks of infection, and 3 additional antigens, 19, 13 and 10 kDa, were detected at 8-12 weeks of infections. 4. Using SEP8, 5 antigens, 91, 85, 31, 25 and 21 kDa, were consistently detected by all infected sera tested. In addition, 3 antigens of 19, 13 and 10 kDa were detected at 8-12 weeks of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗