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Biomedical subjects

D S Choi

Publications and source records attributed to D S Choi.

At least 73 records · Page 4Linked to original sources

The mouse 5-HT2B receptor: homologous subtype or species variant?

The recently characterized 5-HT2B subfamily of serotonin receptors has now been reported from three different species: human, rat and mouse. Their genomic structures include 2 introns present at identical positions. Despite this similarity, their respective protein sequences show some diversities. In addition, the pharmacology of these receptors is distantly related, and their sites of expression vary amongst species. Thus, it appears difficult at present to unambiguously classify these receptors into the same subfamily, raising the possibility of the existence of other 5-HT2B-like receptors, yet to be discovered.

Animals↗

Change in glutathione S-transferase and glyceraldehyde-3-phosphate dehydrogenase activities in the organs of mice treated with 2-chloroethyl ethyl sulfide or its oxidation products.

Various organs or skin from male ICR mice treated intraperitoneally with 2-chloroethyl ethyl sulfide (CEES) or its oxidation derivatives 2-chloroethyl ethyl sulfoxide (CESSO) and 2-chloroethyl ethyl sulfone were analysed for changes in two thiol-containing enzymes, namely glutathione S-transferase (GST) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). CEES was more potent than its oxidation derivatives with respect to the decrease in organ weight and the loss in GAPDH activity, although the reverse was found in GST induction. Whereas the induction of GST was highest in the lung after multiple intraperitoneal intoxication with CEESO (8 and 32 mg/kg), the decrease in GAPDH activity after exposure to CEES (8 mg/kg body weight) was most remarkable in the spleen, the most susceptible organ to toxicity of CEES. GST and GAPDH activities in the skin of male hairless mice exposed subcutaneously to CEES (2 mg/kg body weight) were not altered significantly at 2-hr exposure, but decreased up to 60% of that of controls at 8 hr, when oedema formation was greatest. Taken together, it appears that GAPDH activity is a more sensitive biochemical parameter than GST activity in organs of mice treated with CEES or its oxidation products.

Animals↗

Characterization of focal hepatic tumors. Value of two-phase scanning with spiral computed tomography.

BACKGROUND: Spiral computed tomography (CT) allows imaging of the liver during the peak contrast material levels due to the capability of fast data acquisition. The objective of this study was to evaluate the usefulness of two-phase spiral CT in the differential diagnosis of focal hepatic tumors. METHODS: One hundred two patients who had hepatic tumors (211 nodules; 149 hepatocellular carcinomas [HCCs], 36 metastases, and 26 hemangiomas) underwent two-phase spiral CT with 10-mm collimation at 10 mm/second table speed and 120 mL of contrast material injected at the rate of 3 mL/second. Computed tomography images of the hepatic arterial phase and late (equilibrium) phase were obtained at 35-second and 180-second delays, respectively. The enhancement patterns of tumors were divided into six types and were compared with the attenuation of surrounding liver parenchyma: totally high, peripherally high, centrally high, mixed, iso, and low. RESULTS: The common enhancement patterns of HCC in two-phase spiral CT were totally high in the arterial phase and low (n = 63, 42%) or iso (n = 28, 19%) in the late phase. Metastasis showed peripherally nonnodular high attenuation (n = 9, 25%) or low attenuation (n = 9, 25%) in the arterial phase and low attenuation in the late phase, followed by totally high attenuation in the arterial phase and iso in the late phase (n = 6, 17%). Hemangiomas showed totally or peripherally nodular enhancement in the arterial and late phases (n = 23, 89%). In distinguishing hemangiomas from malignant tumors, totally high or peripherally nodular high attenuation in the late phase was the most useful contrast enhancement pattern (96% of hemangioma vs. 0% of malignant tumors). In distinguishing HCCs from metastases, a combination of contrast enhancement pattern of totally high attenuation in the arterial phase and low in the late phase was the most useful contrast enhancement pattern (42% of HCCs vs. 0% of metastases). The predictability of differentiation between hemangiomas and malignant tumors and between HCCs and metastases was 99% and 90% with spiral CT, respectively. CONCLUSIONS: Two-phase spiral CT is useful in the differential diagnosis of focal hepatic tumors with evaluation of contrast enhancement patterns.

Adult↗

The release of lysosomal arylsulfatase from liver lysosomes exposed to 2-chloroethylethyl sulfide.

Treatment of a lysosome-rich fraction from liver with 2-chloroethylethyl sulfide resulted in a dose-dependent release of arylsulfatase. The inclusion of Ca2+ enhanced the enzyme release by approximately 2.3-fold. The enhancing effect of Ca2+, showing an EC50 value of 30 mM, was mimicked by neither Mg2+ nor Mn2+. Studies on a structural requirement and a time-dependent release suggest that the Ca(2+)-dependent release proceeds via a specific process involving the alkylation of lysosomal membranes by 2-chloroethylethyl sulfide. Furthermore, the Ca(2+)-dependent process was prevented partially by either leupeptin or gentamycin, but neither pepstatin nor PMSF, implying that the enzyme release may be partially mediated by lysosomal cysteine-protease or phospholipase. Meanwhile, the Ca(2+)-independent release seems to be expressed non-specifically by various compounds.

Animals↗

Inactivation of microsomal Ca(2+)-ATPase by 2-chloroethylethyl sulfide.

Exposure of liver microsomes to 2-chloroethylethyl sulfide (CEES) led to a dose-dependent decrease of Ca(2+)-ATPase activity. Studies on a structural requirement and a time dependence suggest that the enzyme inhibition may proceed via an instantaneous process involving an alkylation by an unstable intermediate, presumably a sulfonium form. It is noteworthy that the microsomal Ca(2+)-ATPase was more sensitive to CEES than the Na+/K(+)-ATPase from erythrocyte membranes. The Ca(2+)-ATPase was inhibited non-competitively by CEES, and its inhibitory action was independent of Ca2+ concentrations. The involvement of membrane phospholipid in the enzyme inhibition is excluded, since the temperature dependence of microsomal Ca(2+)-ATPase was not affected by CEES. Moreover, Triton X-100-solubilized Ca(2+)-ATPase was inactivated by the compound to the same extent as the membrane-bound enzyme was. Thus, it is suggested that CEES inactivates Ca(2+)-ATPase by alkylating the enzyme molecule at a region other than the active site.

Adenosine Triphosphate↗

Glyceraldehyde-3-phosphate dehydrogenase as a biochemical marker of cytotoxicity by vinyl sulfones in cultured murine spleen lymphocytes.

Recently, vinyl sulfones have been observed to selectively inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is an important ATP-generating enzyme in glycolysis. The possibility of using GAPDH as a biochemical parameter of cytotoxicity by vinyl sulfones was investigated using mouse lymphocytes. Incubation of lymphocyte GAPDH with ethylvinyl sulfone resulted in a pseudo-first-order loss of enzyme activity. The exposure of lymphocytes to ethylvinyl sulfone resulted in the decrease of GAPDH activity followed by ATP depletion and cell death, which were both dependent on the concentration of ethylvinyl sulfone. A further study on the time-dependent change indicated that cell death was preceded by ATP loss. Compared to ethylvinyl sulfone, divinyl sulfone was more than 8 times more potent in causing either ATP depletion or cell death.

Animals↗

Protection by lysosomal hydrolase inhibitors against cytotoxicity of 2-chloroethylethyl sulfide.

A possible participation of lysosomal hydrolases in the cytotoxicity of 2-chloroethylethyl sulfide in spleen lymphocytes was investigated using inhibitors of lysosomal phospholipases and proteases. Pepstatin (6 microM) and leupeptin (60 microM), inhibitors of lysosomal proteases, raised the viability of lymphocytes exposed to 2-chloroethylethyl sulfide from 63 to 87 and 88% of control, respectively. Serine protease inhibitors showed no significant effect on viability. Aminoglycoside inhibitors of lysosomal phospholipases were also found to prevent the decrease in viability of spleen lymphocytes exposed to 2-chloroethylethyl sulfide, and the effectiveness of these aminoglycosides (30 microM) was as follows: gentamicin > kanamycin > streptomycin, with viability increased to 89, 79 and 67%, respectively. In contrast to a co-operative action between leupeptin and gentamicin, the protection by pepstatin was reduced in the presence of gentamicin. Moreover, the order of the aminoglycosides in terms of the extent to which they antagonized the protective action of pepstatin was the same as their order of efficacy in preventing the cytotoxicity of CEES. It is suggested that inhibitors of lysosomal hydrolases reduce the cytotoxicity of 2-chloroethylethyl sulfide, presumably through lysosomal stabilization in spleen lymphocytes.

Alkylation↗

Contrast-enhanced MR angiography for the diagnosis of intracranial vascular disease: optimal dose of gadopentetate dimeglumine.

OBJECTIVE: Although contrast-enhanced MR angiography has been shown useful in evaluating intracranial vascular lesions, particularly those with slow flow, the optimal dose of contrast material has not been found. Accordingly, we performed a study to determine the optimal dose of gadopentetate dimeglumine for contrast-enhanced MR angiography of intracranial vascular diseases. SUBJECTS AND METHODS: In this prospective study, 152 consecutive adult patients suspected of having intracranial vascular diseases had cerebral MR angiograms. Images were obtained with a three-dimensional time-of-flight sequence with magnetization transfer saturation on a 1.5-T unit. Imaging parameters (43/8 [TR/TE], 20 degrees flip angle, 64 1-mm-thick sections) were identical in each MR angiogram. One hundred twenty-two of 152 patients were randomly assigned to receive one of four doses (0, 5, 10, or 20 ml) of gadopentetate dimeglumine for MR angiography (36, 37, 38, and 11 patients, respectively). In patients who had normal major cerebral arteries on MR angiograms, degree and extent of visualization of the cerebral veins and small intracranial arteries were rated blindly on a three-point scale, and the results were compared among the four groups given different doses of contrast material. In another 30 patients who had unenhanced and enhanced MR angiograms, the presence or absence of artifactual narrowing of the internal carotid artery or major cerebral arteries (caused by signal loss due to slow or turbulent flow seen only on unenhanced images) and the visibility of arteriovenous malformation were determined. RESULTS: In nearly all patients, regardless of the dose of contrast material, the cerebral veins were well visualized on MR images. Degree and extent of visualization of the cerebral veins appeared to depend on the dose of contrast material. In the 20-ml injection group, venous overlap limited interpretation of the small and large arteries, whereas in the 5- and 10-ml groups, the signal intensity of the veins was much less intense, causing no difficulty in interpretation. However, no significant differences in visibility of the small arteries were apparent between the unenhanced and enhanced MR angiograms, even though the small vessels were better visualized in some patients who received either 5 or 10 ml of contrast material. In six of the 30 patients who had both unenhanced and enhanced MR angiograms, the unenhanced images showed artifactual narrowing of the internal carotid or middle cerebral arteries, which proved to be normal on contrast-enhanced MR angiograms. Venous sinuses or draining veins were better delineated on contrast-enhanced MR angiograms in all six patients with arteriovenous malformation. CONCLUSION: Five to 10 milliliters of gadopentetate dimeglumine appears to be an optimal dose range for contrast-enhanced cerebral MR angiography. Use of this dose can help in differentiating true stenosis of large arteries from artifactual narrowing and in depicting small arteriovenous malformation with slow flow.

Adolescent↗

Cushing's syndrome due to primary pigmented nodular adrenocortical disease--a case report reviews of the literature.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome in infants, children and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. Biochemically, PPNAD is characterized by elevated levels of plasma and urinary cortisol that are not suppressed by high doses of dexamethasone (8mg/d for 2 days). Pathologically, the adrenal glands contain multiple dark brown or black nodules and the intervening cortical tissue is atrophic. Recognition of this diagnosis, although rare, is important, as bilateral adrenalectomy is the treatment of choice. We experienced a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease and report it with reviews of the literature.

Adrenal Cortex↗

The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors.

The human serotonin 5-HT2B receptor, isolated from a human liver cDNA library, was transfected in COS-1 cells. Its pharmacological profile shows divergence with serotonin 5-HT2B receptors of other species. In particular, although strong correlation is observed between the human and the rat 5-HT2B receptor pharmacology, the correlation is almost as significant for the mouse 5-HT2B and the human 5-HT1D receptor agonists. The major sites of expression of its mRNA are in the human liver and kidney, with detectable expression in lung and heart. Therefore, this human 5-HT2B receptor could account for functions attributed to the peripheral 5-HT1D/5-HT2-like receptors, especially in the cardiovascular system. Thus, its detailed original pharmacology is of prime importance for therapeutic drug development.

Amino Acid Sequence↗

A case of primary hyperparathyroidism with hypercalcemic nephropathy in children.

Primary hyperparathyroidism is a rare disease in children and is characterized by conspicuous skeletal and renal changes. A 12 year old male patient presented with symptoms of polydipsia, polyuria, general weakness, nausea, and vomiting which had begun 3 months earlier, and showed typical laboratory findings of primary hyperparathyroidism. Confirmatory diagnosis was made by elevated parathyroid hormone concentration in serum, technetium-thallium subtraction scan imaging method and histopathologic finding of chief cell hyperplasia. The laboratory findings revealed elevated levels of BUN, creatinine and decreased GFR. Kidney biopsy showed typical calcium deposits in tubules with marked tubulointerstitial infiltration. After subtotal parathyroidectomy, clinical findings improved remarkably.

Child↗

The mouse 5-HT2B receptor: possible involvement in trophic functions of serotonin.

The novel serotonin receptor 5-HT2B shows the highest homology to the 5-HT2 family of receptors. The pharmacological profile of membranes from 5-HT2B cDNA stably transfected LMTK- cell line, corresponds to a new 5-HT2-like receptor named 5-HT2B, although some difference exists between the mouse and rat pharmacology. A similar pharmacological profile is detected on the immortalized teratocarcinoma-derived cell line 1C11 upon 2 days of serotoninergic differenciation by cAMP. In both cell lines, the analysis 125I-DOI binding reveals the presence of a single class of sites, the affinity of which is one order of magnitude lower than the one reported for the 5-HT2A receptor. This demonstrates that the 5-HT2B receptor is functionally expressed before the complete serotoninergic differentiation of 1C11 cells. These observations are in good agreement with the presence of 5-HT2B mRNA in early mouse embryonic development. Furthermore, the major sites of 5-HT2B mRNA embryonic expression are in the heart, and in the neural fold before the closure of the neural tube. Therefore, this receptor could account at least in part for the trophic functions attributed to the 5-HT2-like receptors.

Animals↗

Selective inactivation of glyceraldehyde-3-phosphate dehydrogenase by vinyl sulfones.

Incubation of glyceraldehyde-3-phosphate dehydrogenase with vinyl sulfones resulted in a pseudo first-order loss of enzyme activity. The selective inactivation of the enzyme by vinyl sulfones is suggested from the structural requirement analysis and the enzyme susceptibility test. The enzyme inactivation was strongly reduced in the presence of NAD or glyceraldehyde-3-phosphate, and the prior treatment of the enzyme with 5,5'-dithio-bis-(2-nitrobenzoic acid) prevented the enzyme from the inactivation by vinyl sulfones (> or = 90%). Moreover, the early rapid phase of inactivation was much more responsive to L-cysteine reactivation, compared with the slower phase. Based on these results, it is proposed that vinyl sulfones inactivate the enzyme by inducing the oxidation of cysteine residue and/or covalent binding to cysteine residue in active site.

Animals↗

Induction of an organ-specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy.

Glycosylated, membrane-associated E1 (58-kDa) and E2 (47- to 49-kDa) rubella virus proteins and unglycosylated nucleoprotein C (33 kDa), from separately expressed vaccinia virus recombinants, were injected into golden Syrian hamsters. Rubella virus E1 and E2 glycoproteins consistently induced an organ-specific autoimmune disease, autoimmune lymphocytic hypophysitis, which was evidenced by the induction of autoantibodies against pituitary cells and by lymphocytic infiltration of the pituitary. Neonatal thymectomy prevented the disease. In contrast, rubella virus nucleoprotein C did not induce either autoantibodies against pituitary cells or lymphocytic infiltration of the pituitary. This finding raises the possibility that virus-specific protein itself can induce an organ-specific autoimmune disease in certain circumstances.

Animals↗

RFLP analysis of HLA-DR beta and -DQ beta genes in the Korean patients with insulin-dependent diabetes mellitus.

Human genomic DNA samples from 19 Korean patients and 31 controls of known serological DR antigen specificity were studied for insulin-dependent diabetes mellitus (IDDM)-associated variation in HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs). Genotyping allowed for accurate assignment of HLA-DR types. For HLA-DRw6, a 12kb/DR beta/Taq I fragment was decreased in Korean IDDM (p less than 0.05). However, we could not find an increased frequency of a 12kb/DQ beta/Bam HI fragment or decreased frequency of a 3.7kb/DQ beta/Bam HI fragment in Korean IDDM. These results suggest a possible protective role of the HLA-DRw6 specificity in IDDM, irrespective of ethnic background, the absence of a specific DQ beta RFLP pattern associated with IDDM in Koreans, and the difference of the Korean population in the genetic of IDDM, compared to the Caucasoid population.

Asian People↗

Molecular assembly of the lipoprotein trimer on the peptidoglycan layer of Escherichia coli.

The molecular assembly of the major outer membrane lipoprotein on the peptidoglycan layer was studied using two hybrid genes coding for different OmpF-lipoprotein hybrid proteins. One gene codes for a "lipoprotein" in which the diacylglyceryl cysteine residue is replaced with the Ala-Glu residue of the NH2 terminus of the OmpF protein (hybrid protein I). The other gene codes for the lipid-free "lipoprotein" from which the COOH-terminal lysine residue was further deleted (hybrid protein II). Hybrid protein I existed as a trimer. A significant portion of it was found to be composed of only the free form, which was noncovalently associated with the peptidoglycan layer. The purified hybrid protein I trimer was dissociated into the subunit in the presence of guanidine-HCl and reassociated on dialysis. Both the native and reassociated trimers were bound to the lipoprotein-free peptidoglycan layer. No enhancement of the binding was observed when the reassociation reaction was carried out simultaneously. Hybrid protein II, on the other hand, did not exhibit association with peptidoglycan in both the cellular fractionation and in vitro binding experiments, although it existed as a trimer. It is concluded that 1) the protein domain of the lipoprotein exists as a trimer which is noncovalently as well as covalently associated with the peptidoglycan layer and 2) although the deletion of the COOH terminal lysine residue did not interfere with the trimerization, it interfered with the noncovalent interaction with the peptidoglycan layer.

Cell Membrane↗

Trimeric structure and localization of the major lipoprotein in the cell surface of Escherichia coli.

A hybrid gene consisting of the ompF promoter, the coding regions for the signal peptide, and the Ala-Glu residue of the OmpF NH2 terminus and the coding region for the major outer membrane lipoprotein devoid of the NH2-terminal cysteine residue was constructed. Escherichia coli carrying the cloned gene produced the predicted hybrid protein that is the same as the major lipoprotein except that the diacyl glycerylcysteine residue at the NH2 terminus is replaced by the Ala-Glu residue. The hybrid protein was localized in the periplasmic space as a trimer with a noncovalent interaction in addition to the previously known covalent interaction with the peptidoglycan. These results strongly indicate that the major lipoprotein exists as a trimer in the periplasmic space with covalent and noncovalent interactions with the peptidoglycan layer through the protein domain on one side and with the hydrophobic interaction with the outer membrane through the lipid domain on the other side. The trimeric structure of the lipoprotein was directly demonstrated by the chemical cross-linking of the native lipoprotein with both cleavable and uncleavable reagents. The cross-linking study also revealed interaction between the lipoprotein and the OmpA protein, a major outer membrane protein.

Base Sequence↗