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Biomedical subjects

H K Song

Publications and source records attributed to H K Song.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of phosphorus content in normal and osteomalacic rabbit bone by solid-state 3D radial imaging.

In osteomalacia decreased mineralization reduces the stiffness and static strength of bone. We hypothesized that hypomineralization in osteomalacic bone could be quantified by solid-state (31)P magnetic resonance imaging (SS-MRI). Hypomineralization was measured with a 3D radial imaging technique at 162 MHz (9.4T) in rabbit cortical bone of hypophosphatemic (HY) and normophosphatemic (NO) animals. The results were compared with those obtained by quantitative micro-CT (micro-CT) and (31)P solution NMR. 3D images of 277 microm isotropic voxel size were obtained in 1.7 hr with SNR approximately 9. Mineral content was lower in the HY relative to the NO group (SS-MRI: 9.48 +/- 0.4 vs. 11.15 +/- 0.31 phosphorus wet wt %, P < 0.0001; micro-CT: 1114.6 +/- 28.3 vs. 1175.7 +/- 23.5 mg mineral/cm(3); P = 0.003). T(1) was shorter in the HY group (47.2 +/- 3.5 vs. 54.1 +/- 2.7 s, P = 0.004), which suggests that relaxation occurs via a dipole-dipole (DD) mechanism involving exchangeable water protons, which are more prevalent in bone from osteomalacic animals.

Anatomy, Cross-Sectional↗
PubMed2006

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy.

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.

Aged↗
PubMed2005

Off pump coronary artery bypass surgery for significant left ventricular dysfunction: safety, feasibility, and trends in methodology over time--an early experience.

OBJECTIVE: To examine the safety and applicability of off pump coronary artery bypass surgery (OPCAB) in patients with significant left ventricular dysfunction and to discuss the clinical implications for the surgical methods. DESIGN: Retrospective study. SETTING: Tertiary care university affiliated referral centre. PARTICIPANTS: 353 consecutive patients with preoperative left ventricular ejection fraction < or = 35% who underwent coronary artery bypass over a three year period. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality. METHODS: 144 patients operated by OPCAB were compared with 209 patients operated by conventional coronary artery bypass. Multivariate and univariate analyses were performed on the pre- and postoperative variables to predict risk factors associated with hospital morbidity and mortality. RESULTS: Patients in the OPCAB group were more likely to be women and to have congestive heart failure, chronic obstructive pulmonary disease, hypertension, and diabetes; patients in the on pump group were more likely to have had a recent myocardial infarction and to have more severe angina pectoris and an urgent/emergent status. The groups did not differ significantly in length of stay, major postoperative complication rates, or mortality. Comparison of the impact of the procedures on surgical methods over time showed an increase in the use of OPCAB (13% to 67%), without any impact on morbidity or mortality. CONCLUSIONS: OPCAB is feasible and applicable for patients with depressed left ventricular function. This high risk group can potentially benefit from the off pump approach.

Aged↗
PubMed2004

Reproducibility and error sources of micro-MRI-based trabecular bone structural parameters of the distal radius and tibia.

The mechanical competence of trabecular bone is significantly determined, next to material density, by its three-dimensional (3D) structure. Recent advances in micromagnetic resonance imaging (micro-MRI) acquisition and processing techniques allow the 3D trabecular structure to be analyzed in vivo at peripheral sites such as the distal radius and tibia. The practicality of micro-MRI-based noninvasive virtual bone biopsy (VBB) for longitudinal studies of patients hinges on the reproducibility of the derived structural parameters, which largely determine the size of the effect that can be detected at a given power and significance level. In this paper, the reproducibility of micro-MRI-derived trabecular bone structure measures was examined by performing repeat studies in six healthy subjects in whom the distal aspects of the radius and tibia were scanned with a 3D spin-echo sequence at 137 x 137 x 410 microm3 voxel size. Bone volume fraction (BV/TV) and digital topological analysis (DTA) structural parameters including the topological bone surface-to-curve ratio (SCR) and topological erosion index (TEI) were evaluated after subjecting the raw images to a cascade of processing steps. The average coefficient of variation was 4-7% and was comparable for the two anatomic sites and for all parameters measured. The reliability expressed in terms of the intraclass correlation coefficient ranged from 0.95 to 0.97 in the radius and 0.68 to 0.92 in the tibia. Error analysis based on simulations suggests involuntary patient motion, primarily rotation, to be the chief source of imprecision, followed by failure to accurately match the analysis volumes in repeat studies.

Adult↗
PubMed2002

A noncontact, nondestructive method for quantifying intratissue deformations and strains.

The function of soft connective tissues is frequently characterized by quantifying tissue strain (e.g., during joint motion). Conventional techniques for quantifying tendon and ligament strain typically provide surface measures, using markers, stain lines or instrumentation that may influence the tissue. An alternative approach is to quantify intratendinous strain by applying texture correlation analysis to magnetic resonance (MR) images. This paper reports the accuracy and reproducibility of this approach by (1) assessing the reproducibility of MR images, (2) assessing texture correlation accuracy using simulated displacements, and (3) comparing texture correlation measures of displacement and strain from MR images to conventional techniques.

Cadaver↗
PubMed2001

Enhanced IL-18 expression in common skin tumors.

Interleukin-18 (IL-18) has been found to have multiple effects upon various cells involved in inflammatory response. Recently we reported that B16 murine melanoma cells are able to produce IL-18, which is involved in the regulation of intracellular reactive oxygen intermediates (ROI) and Fas-ligand expression, indicating that IL-18 plays key role in the tumor activity of melanoma. In this study, we investigated the pattern of IL-18 expression in the human system. IL-18 production was tested by enzyme linked immunosorbent assay (ELISA) assay in various tumor cell lines, including Raji (Burkitt's lymphoma), IM-9 (B lymphoblast), Jurkat (acute T cell leukemia), SK-MES-1 (squamous cell carcinoma (SCC) cell line), SK-MEL-2, G-361, DM-4, and DX-3 (melanoma cell lines). ELISA tests showed that IL-18 was highly expressed in malignant skin tumors such as SK-MES-1, SK-MEL-2, G-361, DM-4, and DX-3 cell lines, thus suggesting that IL-18 production may be associated with the malignancy of skin tumors. Here, we report that enhanced IL-18 expression is positively correlated with malignant skin tumors such as SCC and melanoma, suggesting the importance role of IL-18 in malignancy of skin tumors. Taken together, expression of IL-18 by tumor cells in human skin tissue may provide an important clue to understand the pathogenesis of malignant skin tumors.

Basal Cell Carcinoma↗
PubMed2001

Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice.

Despite the impressive protection of B cell-deficient (muMT(-/-)) nonobese diabetic (NOD) mice from spontaneous diabetes, existence of mild pancreatic islet inflammation in these mice indicates that initial autoimmune targeting of beta cells has occurred. Furthermore, muMT(-/-) NOD mice are shown to harbor a latent repertoire of diabetogenic T cells, as evidenced by their susceptibility to cyclophosphamide-induced diabetes. The quiescence of this pool of islet-reactive T cells may be a consequence of impaired activation of T lymphocytes in B cell-deficient NOD mice. In this regard, in vitro anti-CD3-mediated stimulation demonstrates impaired activation of lymph node CD4 T cells in muMT(-/-) NOD mice as compared with that of wild-type counterparts, a deficiency that is correlated with an exaggerated CD4 T cell:APC ratio in lymph nodes of muMT(-/-) NOD mice. This feature points to an insufficient availability of APC costimulation on a per T cell basis, resulting in impaired CD4 T cell activation in lymph nodes of muMT(-/-) NOD mice. In accordance with these findings, an islet-reactive CD4 T cell clonotype undergoes suboptimal activation in pancreatic lymph nodes of muMT(-/-) NOD recipients. Overall, the present study indicates that B cells in the pancreatic lymph node microenvironment are critical in overcoming a checkpoint involving the provision of optimal costimulation to islet-reactive NOD CD4 T cells.

Animals↗
PubMed2001

Crystal structure of Klebsiella aerogenes UreE, a nickel-binding metallochaperone for urease activation.

UreE is proposed to be a metallochaperone that delivers nickel ions to urease during activation of this bacterial virulence factor. Wild-type Klebsiella aerogenes UreE binds approximately six nickel ions per homodimer, whereas H144*UreE (a functional C-terminal truncated variant) was previously reported to bind two. We determined the structure of H144*UreE by multi-wavelength anomalous diffraction and refined it to 1.5 A resolution. The present structure reveals an Hsp40-like peptide-binding domain, an Atx1-like metal-binding domain, and a flexible C terminus. Three metal-binding sites per dimer, defined by structural analysis of Cu-H144*UreE, are on the opposite face of the Atx1-like domain than observed in the copper metallochaperone. One metal bridges the two subunits via the pair of His-96 residues, whereas the other two sites involve metal coordination by His-110 and His-112 within each subunit. In contrast to the copper metallochaperone mechanism involving thiol ligand exchanges between structurally similar chaperones and target proteins, we propose that the Hsp40-like module interacts with urease apoprotein and/or other urease accessory proteins, while the Atx1-like domain delivers histidyl-bound nickel to the urease active site.

Animals↗
PubMed2001

Comparison of activation requirements and activation phenotype of allogeneic and xenogeneic rodent responses in vivo and in vitro.

BACKGROUND: Both discordant and concordant xenogeneic responses are dominated by humoral immunity. Recent advances in molecular engineering approaches may largely prevent rejection by means of this pathway, leaving the cellular arm of the immune response as the principal remaining barrier to successful engraftment. METHODS: To characterize further the cellular response to xenogeneic tissues, we used the intracellular fluorescent marker CFSE (5-(and-6)-carboxyfluorescein diacetate succinimidyl ester) to track the mitotic record of T cells (and T cell subsets) after either xenogeneic or allogeneic activation in vitro or in vivo. Activation marker expression was monitored by simultaneous labeling with antibodies for either CD25 or CD134. RESULTS: The in vitro and in vivo responses of Lewis lymphocytes were generally similar in magnitude and timing comparing activation with allogeneic or xenogeneic stimulators. However, the xenogeneic T cell precursor frequency was found to be markedly higher than that previously reported and were comparable to that seen in allogeneic responses. Xenogeneic responses were unique in the continued expression of activation markers in later division cycles. In addition, CD4 and CD8 T-cell proliferation was highly dependent on stimulator class II expression, highlighting the importance of CD4 T cells and the indirect pathway in the xenogeneic response. CONCLUSIONS: An unexpectedly high precursor frequency was detected for xenogeneic cellular responses in the rat anti-mouse combination and was comparable to that seen in allogeneic responses. Differences in xenogeneic versus allogeneic activation profiles exist that may result from the cellular pathways used for activation.

Animals↗
PubMed2001

Structural basis of non-specific lipid binding in maize lipid-transfer protein complexes revealed by high-resolution X-ray crystallography.

Non-specific lipid-transfer proteins (nsLTPs) are involved in the movement of phospholipids, glycolipids, fatty acids, and steroids between membranes. Several structures of plant nsLTPs have been determined both by X-ray crystallography and nuclear magnetic resonance. However, the detailed structural basis of the non-specific binding of hydrophobic ligands by nsLTPs is still poorly understood. In order to gain a better understanding of the structural basis of the non-specific binding of hydrophobic ligands by nsLTPs and to investigate the plasticity of the fatty acid binding cavity in nsLTPs, seven high-resolution (between 1.3 A and 1.9 A) crystal structures have been determined. These depict the nsLTP from maize seedlings in complex with an array of fatty acids.A detailed comparison of the structures of maize nsLTP in complex with various ligands reveals a new binding mode in an nsLTP-oleate complex which has not been seen before. Furthermore, in the caprate complex, the ligand binds to the protein cavity in two orientations with equal occupancy. The volume of the hydrophobic cavity in the nsLTP from maize shows some variation depending on the size of the bound ligands. The structural plasticity of the ligand binding cavity and the predominant involvement of non-specific van der Waals interactions with the hydrophobic tail of the ligands provide a structural explanation for the non-specificity of maize nsLTP. The hydrophobic cavity accommodates various ligands from C10 to C18. The C18:1 ricinoleate with its hydroxyl group hydrogen bonding to Ala68 possibly mimics cutin monomer binding which is of biological importance. Some of the myristate binding sites in human serum albumin resemble the maize nsLTP, implying the importance of a helical bundle in accommodating the non-specific binding of fatty acids.

Binding Sites↗
PubMed2001

MRI measurement of brain iron in patients with restless legs syndrome.

Brain iron insufficiency in the restless legs syndrome (RLS) has been suggested by a prior CSF study. Using a special MRI measurement (R2'), the authors assessed regional brain iron concentrations in 10 subjects (five with RLS, five controls). R2' was significantly decreased in the substantia nigra, and somewhat less significantly in the putamen, both in proportion to RLS severity. The results show the potential utility of this MRI measurement, and also indicate that brain iron insufficiency may occur in patients with RLS in some brain regions.

Aged↗
PubMed2001

Trabecular bone volume fraction mapping by low-resolution MRI.

Trabecular bone volume fraction (TBVF) is highly associated with the mechanical competence of trabecular bone. TBVF is ordinarily measured by histomorphometry from bone biopsies or, noninvasively, by means of high-resolution microcomputed tomography and, more recently, by micro-MRI. The latter methods require spatial resolution sufficient to resolve trabeculae, along with segmentation techniques that allow unambiguous assignment of the signal to bone or bone marrow. In this article it is shown that TBVF can be measured under low-resolution conditions by exploiting the attenuation of the MR signal resulting from fractional occupancy of the imaging voxel by bone and bone marrow, provided that a reference signal is available from a marrow volume devoid of trabeculation. The method requires accurate measurement of apparent proton density, which entails correction for various sources of error. Key among these are the spatial nonuniformity in the RF field amplitude and effects of the slice profile, which are determined by B(1) field mapping and numerical integration of the Bloch equations, respectively. By contrast, errors from variations in bone marrow composition (hematopoietic vs. fatty) between trabecular and reference site are predicted to be small and usually negligible. The method was evaluated in phantoms and in vivo in the distal radius and found to be accurate to 1% in marrow volume fraction. Finally, in a group of 12 patients of varying skeletal status, TBVF in the calcaneus was found to strongly correlate with integral bone mineral density of the lumbar vertebrae (r(2) = 0.83, p < 0.0001). The method may fail in large imaging objects such as the human trunk at high magnetic field where standing wave and RF penetration effects cause intensity variations that cannot be corrected. Magn Reson Med 46:103-113, 2001.

Animals↗
PubMed2001

Simultaneous acquisition of multiple resolution images for dynamic contrast enhanced imaging of the breast.

An imaging technique is described that allows the reconstruction of a series of images at high temporal rates, while simultaneously providing images at high spatial resolution. The method allows one to arbitrarily choose from among several combinations of temporal/spatial resolutions during postprocessing. This flexibility is accomplished by strategically interleaving multiple undersampled projection reconstruction datasets (or subapertures), in which each set can be used to reconstruct a high temporal resolution image. Images with increasingly higher spatial resolutions can subsequently be formed by combining two or more subaperture datasets. The technique is demonstrated in vivo to assess the kinetics of contrast enhancement and to visualize the architectural features of suspicious breast lesions.

Aged↗
PubMed2001

Pulmonary MR angiography with contrast agent at 4 Tesla: a preliminary result.

In this study, pulmonary MR angiography (MRA) using a tailored coil at 4 Tesla in conjunction with an intravenous injection of contrast agent is described. Three-dimensional gradient-echo images were obtained during the intravenous injection of 0.05, 0.1, and 0.2 mmol/kg body weight of gadodiamide to investigate the signal enhancement effect of the contrast agent in pulmonary arteries qualitatively and quantitatively. In the qualitative analysis, the subsegmental branches were visualized on every dose. In the quantitative analysis, the average contrast-to-noise ratios (CNRs) of the main pulmonary arteries increased in a dose-dependent manner. However, the CNRs of segmental arteries did not increase as the dose of contrast agent increased, as observed at 1.5 Tesla MRI. These observations demonstrate the feasibility of delineating the pulmonary vasculature using a contrast agent; however, our results also suggest possible high-field-related disabilities that need to be overcome before high-field (> or =4 Tesla) MRI can be used to full advantage.

Adult↗
PubMed2001

The quaternary arrangement of HslU and HslV in a cocrystal: a response to Wang, Yale.

Protease HslV and ATPase HslU form an ATP-dependent protease in bacteria. We have previously determined the structure of the components of this protease. In the case of HslU, the structure was derived from HslU-HslV cocrystals, combining phase information from MAD and the previously determined HslV model. Whereas the structures of the components were confirmed in detail by later structures, the quaternary arrangement of HslV and HslU was not reproduced in later crystal forms. In a recent communication to this journal, Wang attempted a reinterpretation of our original data to account for this difference. In response, we demonstrate that difference Pattersons, difference Fouriers, molecular replacement calculations, R factors, and omit maps all support our original analysis and prove that the suggested reinterpretation is false by these criteria. In particular, we show that our crystals are essentially untwinned and that only the originally reported quaternary arrangement of HslV and HslU particles is consistent with the experimental data. We finally demonstrate that Wang's newly introduced R(tpart) method to predict translational corrections for a subset of the unit cell contents is systematically flawed.

ATP-Dependent Proteases↗
PubMed2001

Nutritional support for Crohn's disease.

This article reviews nutritional considerations that arise in the care of patients with Crohn's disease. The causes and presentation of malnutrition in these patients are discussed, and a rational method is presented for comprehensive nutritional assessment. The indications for nutritional intervention, either as supportive or primary therapy for Crohn's disease, are reviewed.

Acute Disease↗