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Biomedical subjects

K S Song

Publications and source records attributed to K S Song.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effect of erythromycin on gastric emptying in healthy individuals assessed by radio-opaque markers and plasma acetaminophen levels.

We simultaneously recorded gastric emptying of radio-opaque markers (ROMs) and monitored serial changes in plasma acetaminophen (AAP) levels to demonstrate the relationship between the ROM and the AAP methods, and we investigated the effect of a single intravenous dose of erythromycin (EM) on gastric emptying in healthy human subjects. After an overnight fast, subjects were randomized to receive either placebo or EM lactobionate (Abbott, North Chicago, IL, USA) 250 mg intravenously in a single dose, given immediately before a standard meal. Subjects ingested 1.5 g of AAP and ROMs with the test meal. A supine plain abdominal radiograph was taken 1, 2, 3, and 6 h after ingestion of the test meal. Peripheral blood samples were obtained 0, 0.5, 1, 1.5, 2, 3, and 6 h after ingestion of the test meal. EM significantly accelerated gastric emptying of ROMs. By 6 h, no markers remained in the stomach in any of the subjects in the placebo or EM groups. By 120 min, half of the ROMs had passed into the duodenum in 12.5% of subjects after placebo, whereas EM injection resulted in gastric emptying of half of the ROMs in all subjects. There was no difference in plasma AAP concentration between the placebo and EM groups. There were significant correlations between maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r = 0.546; P = 0.019), and between time of maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r = -0.568; P = 0.014). The time taken to reach the peak concentrations ranged from 30 to 90 min after ingestion, whereas most ROMs were emptied 120 min after ingestion. We conclude that the gastric emptying assessed by ROMs and by serial changes in plasma AAP level are good, non-invasive, clinically applicable tests, with a significant correlation between the two tests. A single intravenous dose of EM had a prokinetic effect on gastric emptying, assessed by ROMs, in healthy human subjects.

Acetaminophen↗
PubMed1997

Association of Br polymorphism of platelet GP Ia gene and immune thrombocytopenic purpura.

Studies on the molecular structure underlying Br(a)/Br(b) (HPA-5) platelet alloantigen show that a single base polymorphism at position 1648 on platelet mRNA coding for GP Ia results in a amino acid substitution at position 505 on the mature GP Ia which is associated with the two serologically defined Br types. While this polymorphism has no known effects on platelet function, the possible influence of this polymorphism in immune thrombocytopenia ITP is again unexplored. Therefore, the genotype frequency of Br polymorphism in ITP was compared with that of healthy general Korean population. Interestingly, there was a statistical difference (P=0.03) in genotype frequency of Br polymorphism. The association of Br(a)/Br(b) (HPA-5)genotype and occurrence of ITP may suggest the possible influence of genetic polymorphism on the pathogenesis of ITP.

Journal Article↗
PubMed1997

Localized muscular mucormycosis in a child with acute leukemia.

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.

Acute Disease↗
PubMed1997

Preoperative and postoperative evaluation of intra-articular fractures of the calcaneus based on computed tomography scanning.

OBJECTIVE: To define the relationship between postoperative congruency of the posterior facet of the subtalar joint based on computed tomography (CT) and clinical results. DESIGN: Preoperative and postoperative CT scans were taken prospectively and analyzed. SETTING: University medical center. PATIENTS: Twenty-nine displaced fractures in twenty-five patients. INTERVENTION: All patients were treated with open reduction and internal fixation without bone graft. MAIN OUTCOME MEASURES: Postoperative CT findings were classified into three groups, according to the degree of displacement: anatomic, no displacement; nearly anatomic, displaced less than two millimeters; and approximate, displaced more than two millimeters. RESULTS: The reduction state after operative treatment for the cases with more comminution showed worse results when analyzed in both preoperative and postoperative CT scans. Fifteen of seventeen fractures (88 percent) with anatomic reduction and seven of eight fractures (87 percent) with nearly anatomic reduction had excellent or good clinical results. In contrast, no fracture with an approximate reduction had an excellent result. CONCLUSION: An excellent or good clinical result can be expected when the postoperative displacement of the posterior facet of the subtalar joint is less than two millimeters.

Adolescent↗
PubMed1997

Adaptive mammographic image enhancement using first derivative and local statistics.

This paper proposes an adaptive image enhancement method for mammographic images, which is based on the first derivative and the local statistics. The adaptive enhancement method consists of three processing steps. The first step is to remove the film artifacts which may be misread as microcalcifications. The second step is to compute the gradient images by using the first derivative operators. The third step is to enhance the important features of the mammographic image by adding the adaptively weighted gradient images. Local statistics of the image are utilized for adaptive realization of the enhancement, so that image details can be enhanced and image noises can be suppressed. The objective performances of the proposed method were compared with those by the conventional image enhancement methods for a simulated image and the seven mammographic images containing real microcalcifications. The performance of the proposed method was also evaluated by means of the receiver operating-characteristics (ROC) analysis for 78 real mammographic images with and without microcalcifications.

Algorithms↗
PubMed1997

Rapid polymerase chain reaction analysis of St14 (DXS52) VNTR: carrier detection of hemophilia A.

OBJECTIVE: To determine the frequency of St14 VNTR allele in Koreans as a marker of the hemophilia A and to evaluate the efficacy of this marker for carrier detection of hemophilia A METHODS: PCR amplified RFLP analysis of St14 VNTR was done in 312 X-chromosomes of 122 unrelated Korean males and 95 females and the same method was applied to carrier detection in the 2 hemophilia A families. RESULTS: There were 13 alleles of different sizes of St14 VNTR locus appeared in 312 X-chromosomes of unrelated Koreans. For carrier detection of hemophilia A, in the family A, the mother showed 1390/ 1330 bp alleles and the father showed 700 bp allele. The affected son has inherited 1390 bp allele from his mother. The daughter at risk showed 1330/700 bp alleles. In family B, the mother showed 1280/700 bp alleles and the stepfather showed 1390 bp allele. The affected son has inherited 1280 bp allele. The daughter at risk showed 1390/700 bp alleles. And so the daughters of the 2 families were not carriers for hemophilia A. CONCLUSION: PCR analysis of St14 VNTR was a useful tool for carrier detection of hemophilia A.

Alleles↗
PubMed1997

Targeting of a G alpha subunit (Gi1 alpha) and c-Src tyrosine kinase to caveolae membranes: clarifying the role of N-myristoylation.

Many signaling molecules contain the consensus protein sequence Met-Gly at their N-termini that specifies N-myristoylation. Additionally, some of these proteins contain a cysteine at position-3 (Met-Gly-Cys) that can undergo palmitoylation. As many acylated proteins [G-protein subunits (alpha and beta gamma); c-Src and Src-family tyrosine kinases; H-Ras and Ras-related GTPases; endothelial nitric oxide synthase] are known to be targeted to caveolae membranes, it has been suggested that acylation is required or greatly facilitates this targeting event. However, it remains unclear whether myristoylation of Src-family kinases is necessary or sufficient for caveolar targeting. Our current study aims at clarifying the role of myristoylation in caveolar targeting using well-characterized acylation mutants of two model proteins, namely Gi1 alpha and c-Src. Here, we have used: i) detergent-free subcellular fractionation and ii) acylation mutants of Gi1 alpha and c-Src to systematically evaluate the relative contribution of myristoylation and palmitoylation to their caveolar targeting. Myristoylation (G2A) and palmitoytation (C3S) mutants of Gi1 alpha were poorly targeted to caveolae-enriched membrane fractions, while approximately 35% of total wild-type Gi1 alpha co-fractionated with caveolin, a caveolar marker protein. Similarly, a myristoylation minus mutant of c-Src was quantitatively excluded from caveolae. In contrast to a previous study, we conclude that myristoylation of Gi1 alpha and c-Src proteins is required for their correct caveolar targeting. However, the caveolar targeting of Gi1 alpha is dramatically augmented approximately 4-fold by palmitoylation. Our current studies are directly supported by the earlier in vivo observation that N-terminal myristoylation of v-Src is required for v-Src to phosphorylate caveolin on tyrosine residues in intact cells.

Acylation↗
PubMed1996

Baculovirus-based expression of mammalian caveolin in Sf21 insect cells. A model system for the biochemical and morphological study of caveolae biogenesis.

Caveolae were originally defined morphologically as 50-100 nm noncoated vesicular organelles located at or near the plasma membrane. Caveolin, a vesicular integral membrane protein of 21 kDa, is a principal protein component of caveolae membranes in vivo. Caveolin interacts with itself to form high molecular mass oligomers, suggesting that it might play a structural role in the formation of caveolae membranes. However, it remains controversial whether recombinant expression of caveolin is necessary or sufficient to generate caveolae membranes in vivo. To directly address this issue, we have taken a different experimental approach by exploiting a heterologous expression system. Here, we have recombinantly expressed mammalian caveolin in Sf21 insect cells using baculovirus-based vectors. Two isoforms of caveolin have been identified that differ at their extreme N terminus; alpha-caveolin contains residues 1-178, and beta-caveolin contains residues 32-178. After recombinant expression in Sf21 insect cells, both alpha- and beta-caveolin formed SDS-resistant high molecular mass oligomers of the same size as native caveolin. Morphologically, expression of either caveolin isoform resulted in the intracellular accumulation of a homogeneous population of caveolae-sized vesicles with a diameter between 50 and 120 nm (80.3 +/- 14.8 nm). This indicates that each caveolin isoform can independently generate these structures and that caveolin residues 1-31 are not required for this process. Using caveolin as a marker protein and a detergent-free procedure to purify caveolae from mammalian cells, we purified these recombinant caveolin-induced vesicles from insect cells. These purified recombinant vesicles: (i) have the same buoyant density as mammalian caveolae; (ii) appear as approximately 50-100 nm membranous structures by whole-mount electron microscopy; and (iii) contain approximately 95% of the recombinantly expressed caveolin protein by Western blotting. Immuno-labeling of these structures with anti-caveolin IgG confirmed that they contain caveolin. Thus, ectopic overexpression of caveolin in this heterologous system is sufficient to drive the formation of caveolae-like vesicles. Further functional analysis demonstrated that caveolin was capable of interacting with a known caveolin-interacting protein, Ha-Ras, when coexpressed in insect cells by co-infection with two recombinant baculoviruses. Taken together, our results demonstrate that baculovirus-based expression of caveolin in insect cells provides an attractive experimental system for studying the biogenesis of caveolae.

Animals↗
PubMed1996

Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins.

Caveolae are microdomains of the plasma membrane that have been implicated in signal transduction. Caveolin, a 21-24-kDa integral membrane protein, is a principal component of the caveolae membrane. Recently, we and others have identified a family of caveolin-related proteins; caveolin has been retermed caveolin-1. Caveolin-3 is most closely related to caveolin-1, but caveolin-3 mRNA is expressed only in muscle tissue types. Here, we examine (i) the expression of caveolin-3 protein in muscle tissue types and (ii) its localization within skeletal muscle fibers by immunofluorescence microscopy and subcellular fractionation. For this purpose, we generated a novel monoclonal antibody (mAb) probe that recognizes the unique N-terminal region of caveolin-3, but not other members of the caveolin gene family. A survey of tissues and muscle cell types by Western blot analysis reveals that the caveolin-3 protein is selectively expressed only in heart and skeletal muscle tissues, cardiac myocytes, and smooth muscle cells. Immunolocalization of caveolin-3 in skeletal muscle fibers demonstrates that caveolin-3 is localized to the sarcolemma (muscle cell plasma membrane) and coincides with the distribution of another muscle-specific plasma membrane marker protein, dystrophin. In addition, caveolin-3 protein expression is dramatically induced during the differentiation of C2C12 skeletal myoblasts in culture. Using differentiated C2C12 skeletal myoblasts as a model system, we observe that caveolin-3 co-fractionates with cytoplasmic signaling molecules (G-proteins and Src-like kinases) and members of the dystrophin complex (dystrophin, alpha-sarcoglycan, and beta-dystroglycan), but is clearly separated from the bulk of cellular proteins. Caveolin-3 co-immunoprecipitates with antibodies directed against dystrophin, suggesting that they are physically associated as a discrete complex. These results are consistent with previous immunoelectron microscopic studies demonstrating that dystrophin is localized to plasma membrane caveolae in smooth muscle cells.

Amino Acid Sequence↗
PubMed1996

Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains.

Caveolae are plasma membrane specializations that have been implicated in signal transduction. Caveolin, a 21-24-kDa integral membrane protein, is a principal structural component of caveolae membranes in vivo. G protein alpha subunits are concentrated in purified preparations of caveolae membranes, and caveolin interacts directly with multiple G protein alpha subunits, including G(s), G(o), and G(i2). Mutational or pharmacologic activation of G alpha subunits prevents the interaction of caveolin with G proteins, indicating that inactive G alpha subunits preferentially interact with caveolin. Here, we show that caveolin interacts with another well characterized signal transducer, Ras. Using a detergent-free procedure for purification of caveolin-rich membrane domains and a polyhistidine tagged form of caveolin, we find that Ras and other classes of lipid-modified signaling molecules co-fractionate and co-elute with caveolin. The association of Ras with caveolin was further evaluated using two distinct in vitro binding assays. Wild-type H-Ras interacted with glutathione S-transferase (GST)-caveolin fusion proteins but not with GST alone. Using a battery of GST fusion proteins encoding distinct regions of caveolin, Ras binding activity was localized to a 41-amino acid membrane proximal region of the cytosolic N-terminal domain of caveolin. In addition, reconstituted caveolin-rich membranes (prepared with purified recombinant caveolin and purified lipids) interacted with a soluble form of wild-type H-Ras but failed to interact with mutationally activated soluble H-Ras (G12V). Thus, a single amino acid change (G12V) that constitutively activates Ras prevents or destabilizes this interaction. These results clearly indicate that (i) caveolin is sufficient to recruit soluble Ras onto lipid membranes and (ii) membrane-bound caveolin preferentially interacts with inactive Ras proteins. In direct support of these in vitro studies, we also show that recombinant overexpression of caveolin in intact cells is sufficient to functionally recruit a nonfarnesylated mutant of Ras (C186S) onto membranes, overcoming the normal requirement for lipid modification of Ras. Taken together, these observations suggest that caveolin may function as a scaffolding protein to localize or sequester certain caveolin-interacting proteins, such as wild-type Ras, within caveolin-rich microdomains of the plasma membrane.

Animals↗
PubMed1996

Expression and characterization of recombinant caveolin. Purification by polyhistidine tagging and cholesterol-dependent incorporation into defined lipid membranes.

Caveolin, a 22-24-kDa integral membrane protein, is a principal component of caveolar membranes in vivo. Caveolin has been proposed to function as a scaffolding protein to organize and concentrate signaling molecules within caveolae. Because of its unusual membrane topology, both the N- and C-terminal domains of caveolin remain entirely cytoplasmic and are not subject to luminal modifications that are accessible to other integral membrane proteins. Under certain conditions, caveolin also exists in a soluble form as a cytosolic protein in vivo. These properties make caveolin an attractive candidate for recombinant expression in Escherichia coli. Here, we successfully expressed recombinant full-length caveolin in E.coli. A polyhistidine tag was placed at its extreme C terminus for purification by Ni(2+)-nitrilotriacetic acid affinity chromatography. Specific antibody probes demonstrated that recombinant caveolin contained a complete N and C terminus. Recombinant caveolin remained soluble in solutions containing the detergent octyl glucoside and formed high molecular mass oligomers like endogenous caveolin. By electron microscopy, recombinant caveolin homo-oligomers appeared as individual spherical particles that were indistinguishable from endogenous caveolin homo-oligomers visualized by the same technique. As recombinant caveolin behaved as expected for endogenous caveolin, this provides an indication that recombinant caveolin can be used to dissect the structural and functional interaction of caveolin with other protein and lipid molecules in vitro. Recombinant caveolin was efficiently incorporated into lipid membranes as assessed by floatation in sucrose density gradients. This allowed us to use defined lipid components to assess the possible requirements for insertion of caveolin into membranes. Using a purified synthetic form of phosphatidylcholine (1,2-dioleoylphosphorylcholine), we observed that incorporation of caveolin into membranes was cholesterol-dependent; the addition of cholesterol dramatically increased the incorporation of caveolin into these phosphatidylcholine-based membranes by approximately 25-30-fold. This fits well with in vivo studies demonstrating that cholesterol plays an essential role in maintaining the structure and function of caveolae. Further functional analysis of these reconstituted caveolin-containing membranes showed that they were capable of recruiting a soluble recombinant form of G(i)2 alpha. This is in accordance with previous studies demonstrating that caveolin specifically interacts directly with multiple G protein alpha-subunits. Thus, recombinant caveolin incorporated into defined lipid membranes provides an experimental system in which the structure, function, and biogenesis of caveolin-rich membrane domains can be dissected in vitro.

Caveolin 1↗
PubMed1996

Cytotoxic benzyl dihydroflavonols from Cudrania tricuspidata.

Three new dihydroflavonols, gericudranins A-C were isolated from the stem bark of Cudrania tricuspidata. They were identified as 6,8-di-p-hydroxybenzyltaxifolin, 8-p-hydroxybenzyltaxifolin and 6-p-hydroxybenzyltaxifolin, respectively, by means of spectral studies. These compounds were cytotoxic to human tumor cell lines, such as CRL 1579 (skin), LOX-IMVI (skin), MOLT-4F (leukemia), KM12 (colon) and UO-31 (renal) in culture, with ED50 values of 2.7-31.3 micrograms ml-1.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Predicting the histology of anterior mediastinal masses: comparison of chest radiography and CT.

The objective of this study was to compare chest radiography with computed tomography (CT) in the prediction of a specific diagnosis in adult patients with anterior mediastinal masses. Chest radiographs and CT scans of 128 patients with anterior mediastinal masses were randomized and analyzed retrospectively by two independent observers. The observers listed the three most likely diagnoses in order of probability and recorded the degree of confidence in their first-choice diagnosis. Findings from chest radiographs and CT scans were recorded by each observer and used for a stepwise discriminant analysis between diagnoses. Results showed that the correct first-choice diagnosis, regardless of the degree of confidence, was made in 36% of chest radiographs and 48% of CT scans (p < 0.05). The correct diagnosis was included among top three diagnoses in 59% and 72% of the studies, respectively (p < 0.001). A high confidence diagnosis (level 1) was reached in 9% and 34% of each study, respectively, (p < 0.001), and was correct in 58% and 80% of the studies, respectively. Interobserver agreement (k statistics) on the correct first-choice diagnosis was 0.45 and 0.53, respectively. Interpretations of the CT scans were most often accurate in the confident diagnosis of benign germ cell tumors (n = 10, 100%), thymolipomas (n = 3, 100%), and omental hernia (n = 2, 100%). Seven of 15 radiographic findings and 11 of 22 CT findings were discriminant. We conclude that although CT is better then chest radiography in determining the pathologic diagnosis of an anterior mediastinal mass, CT is still poor at making that prediction with confidence. However, several anterior mediastinal masses could be diagnosed accurately by CT.

Adolescent↗
PubMed1996

Characterization of carbohydrate-peptide linkage of acidic heteroglycopeptide with immuno-stimulating activity from mycelium of Phellinus linteus.

The carbohydrate-peptide linkage in acidic heteroglycopeptide from Phellinus linteus was characterized. Amino acid analysis showed large amounts of serine and threonine. Beta-Elimination results in the reduction of serine and threonine and a subsequent increase in alanine after reduction. These results indicated the presence of O-type linkage in the polymer.

Adjuvants, Immunologic↗
PubMed1996

A case of combined gastrojejunal and gastrocolic fistula secondary to gastric cancer.

A rare case of gastric cancer associated with gastrojejunal and gastrocolic fistula is presented. A 56-year-old man who had been diagnosed with advanced gastric cancer(Borrmann's type III) 5 months previously was admitted due to watery diarrhea and frequent vomiting for 2 weeks. Fluoroscopic examination was visualized two abnormal passage of contrast medium from the stomach, one to the colon, and the other to the jejunum. Gastrofiberscopy revealed that the tumor on the great curvature of the body appeared to penetrate into the colon, while the other one on the antrum directly invaded into the jejunum. The patient was treated conservatively with total parenteral nutrition and pain control.

Colonic Diseases↗
PubMed1995

Oligomeric structure of caveolin: implications for caveolae membrane organization.

A 22-kDa protein, caveolin, is localized to the cytoplasmic surface of plasma membrane specializations called caveolae. We have proposed that caveolin may function as a scaffolding protein to organize and concentrate signaling molecules within caveolae. Here, we show that caveolin interacts with itself to form homooligomers. Electron microscopic visualization of these purified caveolin homooligomers demonstrates that they appear as individual spherical particles. By using recombinant expression of caveolin as a glutathione S-transferase fusion protein, we have defined a region of caveolin's cytoplasmic N-terminal domain that mediates these caveolin-caveolin interactions. We suggest that caveolin homooligomers may function to concentrate caveolin-interacting molecules within caveolae. In this regard, it may be useful to think of caveolin homooligomers as "fishing lures" with multiple "hooks" or attachment sites for caveolin-interacting molecules.

Animals↗