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Biomedical subjects

J Song

Publications and source records attributed to J Song.

At least 145 records · Page 8Linked to original sources

Association between triglyceride-rich lipoprotein remnant receptor polymorphisms and lipid traits.

OBJECTIVES: The metabolism of triglyceride-rich lipoproteins (TRL) is, in part, mediated by lipoprotein receptors (such as low density lipoprotein receptor-related protein [LRP] and very low density lipoprotein [VLDL] receptors), which recognize TRL remnants after specific binding with apolipoprotein E. The purpose of this study was to explore the association of the genetic polymorphisms of remnant receptors with lipid, lipoprotein, and apolipoprotein levels including remnant-like particle-cholesterol (RLP-C). DESIGN AND METHODS: Using polymerase chain reaction-amplified DNA, VLDL receptor tetranucleotide repeat polymorphism, LRP trinucleotide repeat polymorphism, and LRP exon 3 polymorphism were analyzed in normal adults (control group: n = 161) and in patients with coronary artery disease (CAD group: n = 102). RESULTS: The allelic distributions of VLDL receptor triple repeat polymorphism, LRP tetranucleotide repeat polymorphism, and LRP exon 3 polymorphism in Koreans were similar to those of Japanese but were significantly different from those of other ethnic groups. There were no significant differences in the allele frequencies of the polymorphisms between the control and CAD groups. VLDL receptor polymorphism in the control group (p = 0.0403) and LRP exon 3 polymorphism in the CAD group (p = 0.0459) showed significant associations with lipoprotein (a) [Lp(a)] levels. CONCLUSIONS: The results of the present study demonstrated significant interracial distribution of remnant receptor polymorphisms. There was no association between the remnant receptor polymorphisms and the RLP-C levels. However, the polymorphisms showed a significant association with Lp(a), which may suggest that the Lp(a) metabolism is in part mediated by the uptake through the remnant receptors.

Aged↗

Effect of hypercholesterolemia on the sequential changes of apoptosis and proliferation after balloon injury to rabbit iliac artery.

To evaluate the effect of hypercholesterolemia on apoptosis and proliferation after vascular injury, iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined after balloon injury using TUNEL, immunohistochemical staining of PCNA, macrophages, smooth muscle actin and p53. In media, apoptosis occurred massively early after injury and then decreased. HC did not affect this early post-injury apoptosis but significantly increased apoptosis 14 days later (D14). Immediate apoptosis in media was followed by active proliferation. HC sustained a high activity of proliferation until D14. The changes of immunoreactivity to p53 over the same 14 day period parallel that of apoptosis. In intima, where cells were scarce initially, proliferative activity reached a peak at D7 and then decreased. HC significantly enhanced proliferation at D14. In intima proliferation was accompanied by a later low-level apoptosis. HC significantly enhanced this low-level apoptosis at D14. These effects of HC resulted in significantly increased areas of intima and media. The fundamental difference between HC and NC was the infiltration of macrophages in HC. In conclusion, balloon injury induces early massive p53-associated apoptosis followed by proliferation in media, whereas in intima, it induces active proliferation followed by a low-level apoptosis. Hypercholesterolemia does not affect the early post-injury apoptosis but enhances proliferation and low-level apoptosis at a later stage, which in turn results in intimal and medial hyperplasia.

Actins↗

Ligament-sparing lumbar microdiscectomy: technical note.

BACKGROUND: The prevention or inhibition of postoperative adhesions is a significant goal for successful lumbar discectomy, not only to reduce the probable risk of recurrent radiculopathy, but also to improve the likelihood of success of re-operation. METHODS: We describe a new technique for sparing the ligamentum flavum in lumbar microdiscectomy. The superficial layer of the ligament is removed by horizontal splitting. Additional horizontal splitting of the ligament yields a paper-thin deep layer. Lateral vertical splitting and retraction is then carried out to provide a sufficient operative window. The split ligament returns to its original position after releasing the retraction, thereby closing the operative window. RESULTS: This method could preserve a layer of the ligamentum flavum to act as a physical barrier, which in turn greatly restricts the peridural fibrosis. CONCLUSIONS: This ligament-sparing technique enables surgeons to preserve the original anatomic plane and to reduce the extent of postoperative adhesion.

Adult↗

Cognitive and linguistic correlates of children's discourse after closed head injury: a three-year follow-up.

The discourse of 91 children who had sustained severe (n = 68) or mild (n = 23) closed head injury (CHI) was examined at least three years postinjury. The groups' retellings of a narrative story were analyzed according to two domains, information and language. In comparison to the mild CHI group, the severe group produced stories characterized by reduced content and information, impaired organization, fewer words, and less complex sentences. The relationships between discourse production and the groups' performance on measures of language, executive function, memory, and processing speed were examined. Correlations were found between discourse production and general verbal ability including verbal fluency. Correlations were also found for discourse performance and executive function measures associated with problem solving and working memory. Site and extent of lesion were not useful in predicting discourse production. These findings indicate that children who sustain a severe closed head injury during early to middle childhood are at risk for persisting deficits in discourse processing and other cognitive abilities.

Adolescent↗

The 18-month impact of an emergency room intervention for adolescent female suicide attempters.

Following a suicide attempt by female adolescents, the impact of a specialized emergency room (ER) care intervention was evaluated over the subsequent 18 months. Using a quasi-experimental design, this study assigned 140 female adolescent suicide attempters (SA), ages 12-18 years, and their mothers (88% Hispanic) to receive during their ER visit either: (a) specialized ER care aimed at enhancing adherence to outpatient therapy by providing a soap opera video regarding suicidality, a family therapy session, and staff training; or (b) standard ER care. The adjustment of the SA and their mothers was evaluated over 18 months (follow-up, 92%) using linear mixed model regression analyses. SA's adjustment improved over time on most mental health indices. Rates of suicide reattempts (12.4%) and suicidal reideation (29.8%) were lower than anticipated and similar across ER conditions. The specialized ER care condition was associated with significantly lower depression scores by the SA and lower maternal ratings on family cohesion. Significant interactions of intervention condition with the SA's initial level of psychiatric symptomatology indicated that the intervention's impact was greatest on maternal emotional distress and family cohesion among SA who were highly symptomatic. SA's attendance at therapy sessions following the ER visit was significantly associated with only one outcome--family adaptability. Specialized ER interventions may have substantial and sustained impact over time, particularly for the parents of youth with high psychiatric symptomatology.

Adolescent↗

Efficient and sustained transgene expression in human corneal cells mediated by a lentiviral vector.

The development of vectors and techniques able to transfer potentially therapeutic genetic information to corneal tissues efficiently may have broad clinical applications. Although a variety of vectors have been tested for their ability to transduce corneal tissue, these systems have been ineffective at transducing all cell types or have been associated with a relatively short duration of transgene expression. Towards the implementation of efficient, long-term transgene expression in all corneal cell types, we have studied the ability of a recombinant lentiviral vector, containing the enhanced green fluorescent protein (eGFP), to mediate gene transfer into human corneal tissue in vitro and in situ. Human primary keratocytes, cultured in vitro, were efficiently transduced by a lentiviral vector as determined by fluorescent-activated cell sorting (FACS) and by fluorescent microscopy. Transduction efficiency was found to be dependent upon multiplicity of infection (MOI); 92% of keratocytes were transduced at an MOI of 1000. The proportion of eGFP-positive cells remained unchanged throughout continuous culture for 60 days, indicating stable expression and a lack of selective pressure for or against transduced cells. Human corneal tissue, obtained at the time of penetrating keratoplasty, demonstrated efficient in situ transduction with this vector. Endothelial cells, epithelial cells and stromal keratocytes at the exposed cut edge of the corneal tissue in situ demonstrated eGFP expression. Underlying stromal cells not in direct contact with vector-containing media, were not transduced, implying that virus-cell contact is required for transduction. Transduced corneal tissues expressed eGFP in situ for the life of the corneal button in extended organ culture (60 days). These results imply that lentiviral vectors may prove to be useful tools, able to transduce corneal tissue efficiently, and that transgene expression is temporally stable. Gene Therapy (2000) 7, 196-200.

Cells, Cultured↗

Self-trapped excitons at the quartz(0001) surface.

We have studied self-trapped excitons in alpha-quartz using density functional theory (DFT), both in the crystal and at the (0001) surface. The excitons are triplet excited states that distort the crystal locally. They have a long lifetime, of the order of a millisecond, and become thermally equilibrated. We have calculated the drop in the exciton energy as it approaches the surface from the interior of the crystal. In the subsurface layer of the -OH terminated (0001) surface, the energy has dropped by 0.7 eV. Another 0.4 eV drop occurs as the exciton enters the surface layer, where it breaks off an OH radical. The drop in energy can be understood from the greater ease of structural distortion at the surface. These calculations illustrate that excitons formed in the bulk could migrate out to the surface and form chemically active surface species. Molecules adsorbed at the surface could also serve as traps for the excitons and could, in principle, be induced to undergo structural or chemical transitions.

Journal Article↗

Dissociation of frequency and recency processing from list recall after severe closed head injury in children and adolescents.

To investigate judgment of the frequency and recency of events relative to word list recall in children following closed head injury (CHI), 124 children and adolescents, including 79 severe CHI patients (mean age at test = 13.2 years), 27 mild CHI cases (mean age at test = 12.1 years), and 18 uninjured comparison subjects (mean age = 12.8 years) were studied. The mean postinjury interval was 63.6 months for the severe and 46.7 months for the mild CHI groups. The experimental tasks included estimation of the frequency of presentation of words and designs and recency judgment to select the most recently presented of two stimuli on verbal (words) and nonverbal (faces) tasks. To compare frequency and recency judgments to performance on a task which has been shown to be sensitive to CHI severity and age at test, verbal recall was tested using the California Verbal Learning Test-Children's Version. Severity of CHI (group) affected verbal recall across trials and after delays, but had no effect on estimating frequency and isolated effects on judgment of recency. Age was also primarily related to verbal recall. A subgroup of severe CHI patients with frontal lesions was impaired on delayed recall. The results are discussed in relation to previous research on the effects of CHI on processing the frequency and recency of events.

Adolescent↗

Use of misoprostol in obstetrics and gynecology.

UNLABELLED: Misoprostol is prostaglandin E1 analogous and marketed for prevention and treatment of peptic ulcer disease. However, it has been used widely in obstetrics and gynecology practice because of its effectiveness, low cost, stability in light and hot climate conditions, and ease of administration compared with its licensed counterparts--dinoprostone and gemeprost. A large number of studies have shown that misoprostol is effective in first and second trimester abortion, late pregnancy labor induction, and third stage of labor management (misoprostol has not been approved by the U.S. Food and Drug Administration for these indications). Because misoprostol is not registered for such use, it has not undergone the extensive testing for appropriate dosage and safety required for registration. Serious complications such as teratogenesis after failed abortions and uterine rupture during second trimester abortions and third trimester labor induction have been reported as the result of increasingly wide use of misoprostol in obstetric and gynecology practice. There is an urgent need to evaluate all the available data and organize a large randomized trial to determine the safety of its use in obstetric and gynecology practice. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the various uses of misoprostol, to describe the potential complications of misoprostol use and its teratogenic effects, to compare the various routes of administration, and to define the appropriate dose.

Abnormalities, Drug-Induced↗

Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity.

Studies on the Hsp70 chaperone machine in eukaryotes have shown that Hsp70 and Hsp40/Hdj1 family proteins are sufficient to prevent protein misfolding and aggregation and to promote refolding of denatured polypeptides. Additional protein cofactors include Hip and Bag1, identified in protein interaction assays, which bind to and modulate Hsp70 chaperone activity in vitro. Bag1, originally identified as an antiapoptotic protein, forms a stoichiometric complex with Hsp70 and inhibits completely Hsp70-dependent in vitro protein refolding of an unfolded polypeptide. Given its proposed involvement in multiple cell signaling events as a regulator of Raf1, Bcl2, or androgen receptor, we wondered whether Bag1 functions in vivo as a negative regulator of Hsp70. In this study, we demonstrate that Bag1, expressed in mammalian tissue culture cells, has pronounced effects on one of the principal activities of Hsp70, as a molecular chaperone essential for stabilization and refolding of a thermally inactivated protein. The levels of Hsp70 and Bag1 were modulated either by transient transfection or conditional expression in stably transfected lines to achieve levels within the range detected in different mammalian tissue culture cell lines. For example, a twofold increase in the concentration of Bag1 reduced Hsp70-dependent refolding of denatured luciferase by a factor of 2. This effect was titratable, and higher levels of wild-type but not a mutant form of Bag1 further inhibited Hsp70 refolding by up to a factor of 5. The negative effects of Bag1 were also observed in a biochemical analysis of Bag1- or Hsp70-overexpressing cells. The ability of Hsp70 to maintain thermally denatured firefly luciferase in a soluble state was reversed by Bag1, thus providing an explanation for the in vivo chaperone-inhibitory effects of Bag1. Similar effects on Hsp70 were observed with other cytoplasmic isoforms of Bag1 which have in common the carboxyl-terminal Hsp70-binding domain and differ by variable-length amino-terminal extensions. These results provide the first formal evidence that Bag1 functions in vivo as a regulator of Hsp70 and suggest an intriguing complexity for Hsp70-regulatory events.

Animals↗

Roles of Fas and Fas ligand during mammary gland remodeling.

Mammary involution is associated with degeneration of the alveolar structure and programmed cell death of mammary epithelial cells. In this study, we evaluated the expression of Fas and Fas ligand (FasL) in the mammary gland tissue and their possible role in the induction of apoptosis of mammary cells. FasL-positive cells were observed in normal mammary epithelium from pregnant and lactating mice, but not in nonpregnant/virgin mouse mammary tissue. Fas expression was observed in epithelial and stromal cells in nonpregnant mice but was absent during pregnancy. At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 were observed and coincided with the appearance of apoptotic cells in ducts and glands. During the same period, no apoptotic cells were found in the Fas-deficient (MRL/lpr) and FasL-deficient (C3H/gld) mice. Increase in Fas and FasL protein was demonstrated in human (MCF10A) and mouse (HC-11) mammary epithelial cells after incubation in hormone-deprived media, before apoptosis was detected. These results suggest that the Fas-FasL interaction plays an important role in the normal remodeling of mammary tissue. Furthermore, this autocrine induction of apoptosis may prevent accumulation of cells with mutations and subsequent neoplastic development. Failure of the Fas/FasL signal could contribute to tumor development.

Animals↗

Comparative localization of cathepsin B protein and activity in colorectal cancer.

Cathepsin B is a lysosomal cysteine proteinase that may participate in cancer progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protein expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expression was moderate in stroma and variable in epithelium, whereas activity was mainly present in distinct areas of stroma directly underneath the surface of the colon and in epithelium at the surface of the colon. Stroma in adenomas and carcinomas contained moderate to high protein levels but little activity except for areas of angiogenesis, inflammation, and necrosis, in which activity was high. In adenomas and the majority of well-differentiated carcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the basement membrane. Protein and activity levels were low and diffusely distributed in cancer cells in the remainder of the well-differentiated and moderately differentiated carcinomas and in all poorly differentiated carcinomas. Invasive fronts in most cancers contained moderate protein levels but high activity. We conclude that (a) activity localization is essential to understand the role of cathepsin B in cancer progression, and (b) cathepsin B activity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necrotic.

Adenomatous Polyps↗

Heterogeneous distribution of isoactins in cultured vascular smooth muscle cells does not reflect segregation of contractile and cytoskeletal domains.

We have previously demonstrated that alpha-smooth muscle (alpha-SM) actin is predominantly distributed in the central region and beta-non-muscle (beta-NM) actin in the periphery of cultured rabbit aortic smooth muscle cells (SMCs). To determine whether this reflects a special form of segregation of contractile and cytoskeletal components in SMCs, this study systematically investigated the distribution relationship of structural proteins using high-resolution confocal laser scanning fluorescent microscopy. Not only isoactins but also smooth muscle myosin heavy chain, alpha-actinin, vinculin, and vimentin were heterogeneously distributed in the cultured SMCs. The predominant distribution of beta-NM actin in the cell periphery was associated with densely distributed vinculin plaques and disrupted or striated myosin and alpha-actinin aggregates, which may reflect a process of stress fiber assembly during cell spreading and focal adhesion formation. The high-level labeling of alpha-SM actin in the central portion of stress fibers was related to continuous myosin and punctate alpha-actinin distribution, which may represent the maturation of the fibrillar structures. The findings also suggest that the stress fibers, in which actin and myosin filaments organize into sarcomere-like units with alpha-actinin-rich dense bodies analogous to Z-lines, are the contractile structures of cultured SMCs that link to the network of vimentin-containing intermediate filaments through the dense bodies and dense plaques.

Actinin↗

Remnant-like particle cholesterol levels in Korean patients with coronary artery disease and non-insulin dependent diabetes mellitus.

Several studies have provided evidence that the remnants of lipoproteins may be the atherogenic components of triglyceride-rich lipoproteins. The purpose of this study was to investigate whether the remnant-like particle cholesterol (RLP-C) is an independent risk factor for coronary artery disease (CAD) and non-insulin dependent diabetes mellitus (NIDDM) in the Korean population and to explore the relationship between RLP-C and other biochemical markers as well as the apolipoprotein (apo) E genotypes. Lipid and lipoproteins including RLP-C and apo E genotypes were analyzed in 98 normal adults (control group), 68 patients with CAD (CAD group), 88 patients with NIDDM (DM group), and 19 patients with both CAD and NDDM (CAD + DM group). RLP-C levels were significantly higher in the DM (p < 0.0001), CAD (p = 0.0012) and the CAD + DM groups (p = 0.0184) than in the controls. To determine which variable could discriminate most effectively and independently among the different groups, stepwise linear discriminant analysis was performed for all the variables that showed p < 0.15 by univariate analysis. RLP-C was selected as an independent discriminator between the control and patient groups. RLP-C levels showed a strong positive correlation with trigylceride levels in the control, CAD and DM groups (r = 0.783, r = 0.610 and r = 0.746, respectively). In overall groups, apo epsilon4 and epsilon2 carrier genotypes showed a significant increase in RLP-C levels compared with epsilon3/3 wild-type (p = 0.0085). After adjusting for the effect of apo E genotypes, a significant increase of the RLP-C levels in the disease groups remained. In conclusion, RLP-C was determined to be an independent risk factor in Korean patients with CAD and NIDDM and showed a strong correlation with triglyceride levels. We suggest that the increased cardiovascular risk associated with the epsilon4 and epsilon2 allele may be mediated by more atherogenic RLP-C.

Adult↗

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and coagulation factor VII Arg353-->Gln polymorphism in Korean patients with coronary artery disease.

An increased risk for arterial thrombosis is associated with high plasma levels of coagulation and fibrinolytic factors such as PAI-1 and FVII. In this study, the 4G/5G polymorphism in the promoter of PAI-1 gene and Arg353-->Gln polymorphism in the FVII gene were analysed in 139 normal adults and 158 patients with coronary artery disease (CAD), and their association with plasma lipid traits was investigated. There were no significant differences in the allele frequencies of PAI-1 and FVII polymorphisms between control and patient groups. The allelic distributions of both polymorphisms in Koreans were similar to those in Japanese but significantly different from those in Caucasians. In the CAD group, the 4G homozygotes of PAI-1 polymorphism showed significantly higher levels of total (p=0.0250) and LDL cholesterol (p=0.0335) with individuals having other genotypes. However, FVII polymorphism showed no association with lipid levels. In conclusion, the 4G/5G PAI-1 promoter polymorphism and Arg353-->Gln FVII polymorphism are not major genetic risk factors for CAD in Koreans. However, 4G allele of PAI-1 polymorphism revealed to be associated with the levels of cholesterol, especially LDL cholesterol levels in CAD patients.

Aged↗