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D Kim

Publications and source records attributed to D Kim.

At least 19 recordsLinked to original sources
PubMed1996

Down-regulation of gadd153 by c-myc in rat fibroblasts and its effect on cell growth and radiation-induced apoptosis.

Using differential display reverse transcription PCR (DDRT - PCR), we found that a 360 bp cDNA fragment was absent in several c-myc transfected rat fibroblasts: REC:myc, REC:myc + ras and rat1-myc. These cells also showed enhanced sensitivity to gamma ray-induced apoptosis. This cDNA fragment was present in the parental REC (Rat Embryo Cells) and rat1 cells, and in c-Ha-ras transfected REC (REC:ras), all of which were relatively resistant to gamma ray-induced apoptosis. The cDNA fragment was subsequently cloned and used as a probe to screen a rat1 cDNA library, and identified as one of the growth arrest and DNA damaging-inducible genes, gadd153. In addition to the down-regulation of rat gadd153 in all the c-myc transfectants, methyl methanesulfonate (MMS)-induced transcription of the gadd153 was attenuated. The rat1-myc cells, when successfully transfected with and stably expressing the rat gadd153, showed a significantly longer doubling time compared to the parental cells. However, overexpression of gadd153 in rat1-myc cells did not affect gamma ray-induced apoptosis. Thus, the suppression of gadd153 appears to be inversely correlated with that of myc, but not involved in the myc-dependent apoptotic pathway.

Animals↗
PubMed1996

Accuracy and reproducibility of brain and tissue volumes using a magnetic resonance segmentation method.

Magnetic resonance (MR) imaging now allows the qualitative and quantitative assessment of the human brain in vivo. As MR imaging resolution has improved, precise measurement of small brain structures has become possible. Methods of measuring brain regions from MR images include both manual and semiautomated methods. Despite the development of numerous volumetric methods, there have been only limited attempts so far to evaluate the accuracy and reproducibility of these methods. In this study we used phantoms to assess the accuracy of the segmentation process. Our results with simple and complex phantoms indicate an error of 3-5% using either manual or semiautomated techniques. We subsequently used manual and semiautomated volumetric methodologies to study human brain structures in vivo in five normal subjects. Supervised segmentation is a semiautomated method that accomplishes the division of MR images into several tissue types based on differences in signal intensity. This technique requires the operator to manually identify points on the MR images that characterize each tissue type, a process known as seeding. However, the use of supervised segmentation to assess the volumes of gray and white matter is subject to pitfalls. Inhomogeneities of the radiofrequency or magnetic fields can result in misclassification of tissue points during the tissue seeding process, limiting the accuracy and reliability of the segmentation process. We used a structured seeding protocol that allowed for field inhomogeneity that produced reduced variation in measured tissue volumes. We used repeated segmentations to assess intra- and inter-rater reliability, and were able to measure small and large regions of interest with a small degree of variation. In addition, we demonstrated that measurements are reproducible with repeat MR acquisitions, with minimal interscan variability. Segmentation methods can accurately and reliably measure subtle morphometric changes, and will prove a boon to the study of neuropsychiatric disorders.

Adult↗
PubMed1996

IL-12 p40 messenger RNA expression in target organs during acute graft-versus-host disease. Possible involvement of IFN-gamma.

The onset of acute graft-vs-host disease (aGVHD) is accompanied by macrophage (M phi) priming and the presence of bacteria-derived LPS in the sera of transplanted animals. Priming of M phi occurs during aGVHD despite the suppression of T cell function. We have investigated whether IL-12 mediates the continued production of IFN-gamma during the state of T cell immunosuppression that accompanies aGVHD. Acute GVHD was induced in nonirradiated AxC57BL/6F1 mice by the injection of C57BL/6 lymphoid cells. Despite T cell immunosuppression, M phi became primed, as shown by their expression of inducible nitric oxide synthase mRNA and their production of nitric oxide in response to LPS. Continual exposure to IFN-gamma was required to maintain a primed state in M phi during aGVHD. IL-12 p40 peptide mRNA was increased in M phi purified from animals undergoing aGVHD 14 days after transplantation. Target organs of aGVHD, including thymus, salivary gland, and lung, showed increased IFN-gamma mRNA between days 7 and 14 after transplantation. The increase was accompanied by an induction of mRNA for the p40 peptide of IL-12 and inducible nitric oxide synthase within the target organs. These results provide evidence for localized production of IFN-gamma within aGVHD target organs and suggest that it is mediated by LPS-induced production of IL-12 by M phi. Our data elucidate the mechanism of activation of M phi during aGVHD that results in TNF-alpha and nitric oxide production and delineates the effector role of M phi in the pathology of aGVHD.

Acute Disease↗
PubMed1996

Folding pathway of human alpha 1-antitrypsin: characterization of an intermediate that is active but prone to aggregation.

The folding-unfolding kinetics of human alpha 1-antitrypsin (alpha 1-AT) were examined by monitoring intrinsic Trp fluorescence and extrinsic ANS fluorescence. While the unfolding of alpha 1-AT followed a single exponential phase, refolding exhibited three exponential phases. The fast phase (tau 1r < 40 sec). which was independent of urea concentration, appears to be hydrophobic collapse that may be limited by cis-trans isomerization of prolyl residue. The medium phase (tau 2s = 200 sec) yielded an intermediate (IN), which is capable of elastase binding. The slowest (tau 3r = 1000 sec) phase completes refolding to the native protein, which intersects with the unfolding kinetics at the same urea concentration (1.9 M) as the equilibrium midpoint. Concentration-dependence of the amplitude of major refolding phases indicated that IN is prone to kinetic competition between the on-pathway to native protein and aggregation.

Anilino Naphthalenesulfonates↗
PubMed1996

Effects of subtype-selective and balanced angiotensin II receptor antagonists in a porcine coronary artery model of vascular restenosis.

BACKGROUND: Numerous studies have demonstrated the ability of angiotensin II (Ang II) receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors to inhibit intimal hyperplasia after balloon dilation of noncoronary arteries in small-animal models, suggesting an important role for Ang II in the response to injury. Although ACE inhibitors have not been similarly effective in nonhuman coronary models or in human restenosis trials, questions remain regarding the efficacy ACE inhibitors against tissue ACE and the contributions of ACE-independent pathways of Ang II generation. Unlike ACE inhibitors, Ang II receptor antagonists have the potential to inhibit responses to Ang II independent of its biosynthetic origin. METHODS AND RESULTS: In separate studies, three Ang II receptor antagonists, including AT1 selective (L-158,809), balanced AT1/AT2 (L-163,082), and AT2 selective (L-164,282) agents, were evaluated for their ability to inhibit vascular intimal thickening in a porcine coronary artery model of vascular injury. Preliminary studies in a rat carotid artery model revealed that constant infusion of L-158,809 (0.3 or 1.0 mg X kg-1 X d-1) reduced the neointimal cross-sectional area by up to 37% measured 14 days after balloon dilatation. In the porcine studies, animals were treated with vehicle or test compound beginning 2 days before and extending 28 days after experimental angioplasty. Left anterior descending, left circumflex, and/or right coronary arteries were injured by inflation of commercially available angioplasty balloons with placement of coiled metallic stents. Infusion of L-158,809 (1 mg X kg-1 X d-1), L-163,082 (1 mg X kg-1 X d-1), or L-164,282 (1.5 mg X kg-1 X d-1) in the study animals yielded plasma drug levels sufficient either to chronically block or, for L-164,282, to spare pressor responses to exogenous Ang II. Neither L-158,809, L-163,082, nor L-164,282 had statistically significant effects (P=.12, P=.75, and P=.48, respectively, compared with vehicle-treated controls) on neointimal thickness (normalized for degree of injury) measured by morphometric analysis at day 28 after angioplasty. CONCLUSIONS: These findings indicate that chronic blockade of Ang II receptors by either site-selective or balanced AT1/AT2 antagonists is insufficient to inhibit intimal hyperplasia after experimental coronary vascular injury in the pig. The results further suggest that, unlike in the rat carotid artery, Ang II is not a major mediator of intimal thickening in the pig coronary artery.

Angiotensin II↗
PubMed1996

Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons.

Capsaicin (CAP), a neurotoxin, has been reported to activate a nonselective cation current in dorsal root ganglion (DRG) neurons. In this paper, we identify and describe the properties of CAP-activated single channels in cultured neonatal rat DRG neurons. We first identified CAP-sensitive whole-cell currents that reversed near 0 mV in physiological solution. In solution containing 140 mM Na+, extracellular application of CAP to outside-out patches caused activation of an ion channel in a concentration-dependent manner (EC50 = 1.1 microM). The channel was blocked by the CAP antagonist capsazepine (10 microM). The channel was also activated by 2-10 nM resiniferatoxin, a potent analog of CAP. In symmetrical 140 mM Na+, the single-channel slope conductances were 45.3 +/- 1.0 and 80.0 +/- 4.2 pS at -60 and +60 mV, respectively, showing outward rectification (n = 9). The reversal potential did not shift significantly when Na+ was replaced by K+, Cs+, Rb+, or Li+, showing that the channel discriminated poorly among cations. The channel was also permeable to Ca2+. Although acid (pH < 6.2) was suggested to be an endogenous activator of the CAP receptor, an acid solution (pH 5.9-6.0) failed to activate the channels in outside-out patches. This is the first clear demonstration of the presence of the CAP-activated ion channel in DRG neuron. Opening of these ligand-gated, cation-selective channels gives rise to the whole-cell CAP-activated current in DRG neurons and may underlie the neurotoxic effects of CAP.

Acids↗
PubMed1996

Pulmonary perfusion: qualitative assessment with dynamic contrast-enhanced MRI using ultra-short TE and inversion recovery turbo FLASH.

The accurate assessment of pulmonary perfusion is especially important in the evaluation of patients with suspected pulmonary embolism, a common and potentially lethal disorder that can be treated by aggressive anticoagulation. In this study, we demonstrate for the first time the use of MR to image pulmonary perfusion in humans by using dynamic imaging after contrast administration. The technique, which uses an inversion recovery turbo FLASH sequence with ultrashort TE (1.4 ms) and 1-s temporal resolution, was tested in a series of eight healthy subjects and in a porcine model of pulmonary embolism. After the administration of gadopentetate dimeglumine in humans and animal models, there was serial enhancement of the systemic veins, right atrium, right ventricle, and pulmonary arteries. The pulmonary arterial tree was visualized beyond the segmental branches, followed by a gradual diffuse increase in signal intensity of the lung parenchyma over a period of 4.0-7.0 s. Pulmonary circulation times ranged from 3.0-3.4 s. Whereas a high dose (20 or 40 ml) of contrast agent tended to produce the most intense parenchymal enhancement, a low dose (5 ml) was best for showing recirculation. In the animal model, a perfusion defect due to a pulmonary embolus was clearly shown and confirmed by cine angiography. It is concluded that MRI of lung perfusion is feasible. With further development, perfusion MRI could eventually have a significant clinical role in the diagnostic evaluation of pulmonary embolism.

Animals↗
PubMed1996

Acquired immunity to TNF: effects on intestinal wound healing.

Increased concentrations of tumor necrosis factor (TNF) damage normal tissue and produce a shock-like syndrome--changes that can be prevented with anti-body-specific antisera. These findings suggest that TNF-stimulated immunity should protect normal tissue and promote wound healing. To test this hypothesis, 30 Fischer 344 rats (150-200 g) were serially immunized against TNF (20 micrograms/kg). Convalescent sera assayed (micro-ELISA) for circulating antibodies revealed titers (2.54 +/- 0.08 au) significantly higher (P < 0.00001) in immunized animals than in nonimmunized controls (0.11 +/- 0.06 au). Following this, 10 immunized (Group I), 10 nonimmunized (Group II), and 10 control rats underwent partial cecectomy with primary anastomosis. Animals from Groups I and II received TNF (25 micrograms/kg) while controls received saline intravenously on Postoperative Days 1, 3, and 5. Animals were then sacrificed to determine: (1) hydroxyproline content of the anastomosis, (2) mitochondrial respiratory control ratio, and (3) pyruvate dehydrogenase activity of the muscle. We found that (1) exposure to increased concentrations of TNF (Group II) depresses (P < 0.01) biologic markers of wound healing and (2) acquired immunity to TNF (Group I) eliminates this response. In conclusion, acquired immunity to TNF protects the healing intestinal anastomosis from the effects of exposure to increased levels of TNF.

Animals↗
PubMed1996

A compendium of potential energy maps of zeolites and molecular sieves.

We present potential maps of xenon in 20 different zeolites and molecular sieves. The potential maps reveal both the accessible pore volume and localized adsorption sites and so are important in understanding adsorption and diffusion processes in nanoporous materials. We examine zeolites and molecular sieves with one-dimensional channel-like nanopores (zeolite-Theta 1, AlPO4-5, zeolite-Omega, zeolite-L, ZSM-12, AlPO4-8, and VPI-5), with two-dimensional intersecting channel-like nanopores (ZSM-5 [silicalite], ZSM-11, ferrierite, mordenite, and zeolite-Beta), and with three-dimensionally connected cagelike nanopores (zeolite-A, zeolite-Rho, zeolite-Y, sodalite, chabazite, cloverite, cation-poor zeolite-A, and cation-rich zeolite-A). We report the fraction of pore volume accessible, the maximum energy well depth at the adsorption sites, and the activation energy to move between sites. We note several examples of surprising similarities and differences between various molecular sieves. In several instances, we show that these potential profiles are relevant for other small Lennard-Jones-like molecules. By comparison with published Monte Carlo and molecular dynamics simulations, we show that the density distributions of adsorbates at low density are well predicted by the potential maps.

Cations↗
PubMed1996

Mushroom-shaped choroidal hemangioma.

PURPOSE: We examined the clinicopathologic features of a mushroom-shaped choroidal tumor that originated in the right eye of a 13-year-old girl. METHODS: The clinical, ultrasonographic, and histopathologic features of the enucleated eye were studied. RESULTS: On clinical examination, the choroidal tumor appeared mushroom-shaped with ultrasonic characteristics of high internal reflectivity and choroidal excavation. The enucleation specimen contained a cavernous hemangioma that extended through Bruch's membrane. CONCLUSION: Choroidal hemangioma may extend through Bruch's membrane and be mushroom shaped.

Adolescent↗
PubMed1996

Stereotactic breast biopsy is accurate, minimally invasive, and cost effective.

BACKGROUND: We reviewed our experience with stereotactic core needle breast biopsy (SCNBB) for accuracy, complication rate, and staging profile of malignancies diagnosed. METHODS: Since March 1993, 530 stereotactic biopsies were performed. Of these, 25 cases underwent stereotactic core needle biopsy with subsequent wire-guided biopsy. RESULTS: In 25 patients with stereotactic and open biopsy, there was an accuracy for SCNBB of 96%. The number of biopsies rose from 100 to 250 biopsies annually, with an equivalent pre-test positive predictive value for mammography (17% to 19% historical versus 20% with SCNBB). The total number of de novo cancer diagnoses have increased from a mean of 57 to a mean of 71 annually. The percentage of tumors in situ, stage I or stage II, has increased from 60% to 69%. CONCLUSIONS: Stereotactic core needle biopsy combines a high accuracy with a low complication rate. Its aggressive application for tissue diagnosis in suspicious nonpalpable mammographic lesions has increased the proportion of early (in situ and T1 or T2) tumors discovered, and increased the total number of breast cancers diagnosed.

Biopsy, Needle↗
PubMed1996

Mid-term and long-term results with directional atherectomy of vein graft stenoses.

PURPOSE: The purpose of this study was to evaluate the outcomes of our 6-year experience with directional atherectomy used for treatment of stenoses in infrainguinal vein grafts. METHODS: From March 1988 to April 1994, 52 directional atherectomy procedures were undertaken in 42 patients to treat 67 stenoses in 44 vein grafts. Follow-up consisted of periodic physical examinations and graft surveillance; ankle/brachial indexes, pulse volume recordings, and color-flow duplex ultrasonography. Follow-up angiography (n = 18) was performed for recurrent symptoms, reproducible drop in ankle/brachial index of greater than 0.15, a twofold to threefold focal increase in peak systolic velocity, or incidentally during evaluation of the opposite leg. RESULTS: Forty-nine of 52 (94%) procedures were technically successful. In two the residual diameter stenosis was greater than 30%, and in one atherectomy could not be performed. Complications were minor in six (11%) and major in three (6%): two acute graft occlusions and one delayed pseudoaneurysm at the atherectomy site. There were no deaths at 30 days. With a mean follow-up of 21 +/- 18 months, 36 of 44 grafts (82%) remained patent without restenosis; 6 others were patent but considered "failed"--5 (11%) with restenosis, 1 with a pseudoaneurysm; and 2 grafts (5%) occluded. Clinically 33 of 44 extremities (75%) were asymptomatic during follow-up. Claudication improved in five, recurred in three, and was unchanged in one. There was one below-knee amputation. Life-table analysis including all 52 procedures reveals cumulative primary atherectomy patency rates for the 44 grafts of 82%, 78%, and 78%, respectively, at 1, 2, and 3 years after atherectomy, and 86%, 83%, and 83% for the 67 individual stenoses treated. CONCLUSIONS: Directional atherectomy of vein graft stenoses has high technical and clinical success rates, acceptably low morbidity rates, and offers better sustained patency rates than balloon angioplasty. Its long-term patency rate seems to approach that of surgical vein patch angioplasty.

Aged↗
PubMed1996

Modulation of thermal induction of hsp70 expression by Ku autoantigen or its individual subunits.

Previously, we proposed a dual control mechanism for the regulation of the heat shock response in mammalian cells: a positive control mediated by the heat shock transcription factor HSF1 and a negative control mediated by the constitutive heat shock element-binding factor (CHBF). To study the physiological role of CHBF in the regulation of heat shock response, we purified CHBF to apparent homogeneity and showed it to be identical to the Ku autoantigen, a heterodimer consisting of 70-kDa (Ku-70) and 86-kDa (Ku-80) polypeptides. To study further the functional significance of Ku/CHBF in the cellular response to heat shock, we established rodent cell lines that stably and constitutively overexpressed one or both subunits of the human Ku protein, and examined the thermal induction of hsp70 and other heat shock proteins in these Ku-overexpressing ing cells. We show that expression of the human Ku-70 and Ku-80 subunits jointly or of the Ku-70 subunit alone specifically inhibits heat-induced hsp70 expression. Conversely, expression of human Ku-80 alone does not have this effect. Thermal induction of other heat shock proteins in all of the Ku-overexpressing cell lines appears not to be significantly affected, nor is the state of phosphorylation or the DNA-binding ability of HSF1 affected. These findings support a model in which hsp70 expression is controlled by a second regulatory factor in addition to the positive activation of HSF1. The Ku protein, specifically the Ku-70 subunit, is involved in the regulation of hsp70 gene expression.

Animals↗
PubMed1996

Regulation of atrial muscarinic K+ channel activity by a cytosolic protein via G protein-independent pathway.

Rapid desensitization of the muscarinic K+ current (KACh current) is observed in cell-attached patches with 10 microM acetylcholine in the pipette. When inside-out patches were formed within approximately 1 s after formation of cell-attached patches and GTP was applied to the cytoplasmic side of the membrane, desensitization was not observed, indicating that a cytosolic factor mediated the desensitization. Applying the atrial cytosolic extract directly to the cytoplasmic side of such inside-out patches elicited a rapid desensitization of the KACh current. ATP (1-4 mM) reversed this effect of the cytosol and reverted the KACh channel to the undesensitized state. These effects of ATP and cytosol on the KACh channel could occur in the absence of GTP or in the presence of 100 microM guanosine 5'-O-(3-thiotriphosphate), indicating that G protein was not involved. Treatment of the cytosol with proteases (trypsin, chymotrypsin, bacterial protease) or heat denaturation abolished the effect of the cytosol on the KACh channel kinetics, indicating that the cytosolic factor was a protein. Functional assay of the fractions collected from gel filtration column indicated that the molecular mass of the native protein was 95-130 kDa. We conclude that a large cytosolic protein mediates the rapid desensitization of the KACh channel current via a G protein-independent pathway.

Adenosine Triphosphate↗
PubMed1996

Cloning and characterization of rat Ku70: involvement of Ku autoantigen in the heat-shock response.

To study the role of the Ku autoantigen in the heat-shock response, we have cloned the 70-kDa subunit (the DNA-binding component of Ku) from a rat cDNA library. The deduced amino acid sequence of rat Ku70 bears extensive homology with the human and murine counterpart (83 and 97% identity, respectively). Overexpression of Ku70 in rat fibroblasts results in the specific repression of hsp-70 upon heat shock. The inhibition of induction of hsp-70 was greatest in cells expressing the highest level of Ku70. Induction of other heat-shock proteins besides hsp-70 by hyperthermia appears normal, as does the activation of the heat-shock transcription factor, HSF-1. It is likely that other factors besides HSF-1 are involved in controlling heat-shock gene transcription. While the formation of the Ku70 and Ku80 complex is important for repair of DNA double-strand breaks our data suggest that the 70-kDa subunit of Ku plays a role in regulating hsp-70 expression.

Amino Acid Sequence↗
PubMed1995

Perioperative imaging strategies for carotid endarterectomy. An analysis of morbidity and cost-effectiveness in symptomatic patients.

OBJECTIVE: To assess the cost-effectiveness of four diagnostic strategies for the preoperative evaluation of symptomatic patients who are potential candidates for carotid endarterectomy (ie, 70% to 99% stenosis): (1) duplex sonography (DS), (2) magnetic resonance angiography (MRA), (3) contrast angiography (CA), and (4) the combination of DS and MRA supplemented by CA for disparate results. METHODS: Cost-effectiveness analysis based largely on published clinical trial data. Sensitivities and specificities of noninvasive tests were estimated from 81 patients undergoing prospective evaluation with DS, MRA, and CA. OUTCOME MEASURE: Incremental cost per quality-adjusted year of life gained. RESULTS: For a hypothetical cohort of symptomatic patients undergoing evaluation for carotid endarterectomy, the combination of tests resulted in the greatest quality-adjusted life expectancy of the four options considered. After incorporating the costs of testing, surgery, and stroke, we found that neither the MRA nor the CA strategy was cost-effective. The combination of tests was more effective but more costly than DS, resulting in an additional cost of $22,400 per quality-adjusted year of life gained. For centers that do not have adequate MRA, CA resulted in an additional cost of $99,200 per quality-adjusted year of life saved compared with DS. CONCLUSIONS: Our results suggest that for the preoperative detection of a 70% to 99% carotid stenosis, the combination of DS and MRA, supplemented by CA for disparate results, is associated with the lowest long-term morbidity and mortality and has a favorable cost-effectiveness ratio. The combination of tests, or DS alone when MRA is not available, could potentially replace the current practice of using CA alone in the preoperative evaluation of patients with symptomatic carotid stenosis.

Aged↗