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Biomedical subjects

S M Kim

Publications and source records attributed to S M Kim.

At least 127 records · Page 7Linked to original sources

Acute lymphoblastic leukemia with maturation--a new entity with clinical significance.

The diagnosis of 'ALL with maturation' (ALLm) is proposed. One hundred and one patients with untreated ALL were entered into this study. The diagnosis of ALLm was made when more than 20% of all nucleated elements in the bone marrow showed maturation beyond prolymphocytes by light microscopic examination. The mature-appearing leukemic cells showed the same immunophenotype to remaining lymphoblasts. The number of ALLm cases was 19 (18.8%). The mean age at presentation of ALLm was 29 +/- 18, older than that of 18 +/- 16 of the remaining typical ALL (ALLt) (P = 0.015). Remission was induced with daunorubicin, vincristine, prednisone and L-asparaginase. Only two of 19 ALLm patients achieved CR after 4 weeks induction chemotherapy. In contrast, 57 of 82 (69.5%) ALLt patients achieved CR after the same induction chemotherapy. There was no significant difference in immunophenotype of ALLm compared with ALLt. Labeling index of DNA topoisomerase IIalpha (TopoLI) was studied by immunohistochemistry. Initial TopoLI of ALLm (221 +/- 147) was much lower than that of ALLt (609 +/- 262, P = 0.005). Furthermore, the remaining leukemic cells after chemotherapy were not labeled with anti-DNA topoisomerase IIalpha. The P53 protein was expressed in nine of 18 ALLm cases (50.0%) and P-glycoprotein was not expressed in ALLm cases. Twelve of 19 ALLm cases were studied for carrying bcr/abl fusion by karyotyping and/or fluorescent in situ hybridization. Only two cases revealed bcr/abl fusion. In conclusion, ALLm is a separate entity of ALL which has a very poor clinical course and is independent of other prognostic factors. The morphologically mature leukemic cells are in resting GO phase.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The genetics of vitiligo in Korean patients.

BACKGROUND: Vitiligo is a common disorder whose exact cause is unknown, but genetic factors are thought to be involved. We analyzed 120 Korean proband families to clarify which genetic factors are involved in the pathogenesis of vitiligo in Korean patients. METHODS: The genetics of vitiligo were analyzed in 120 Korean proband families out of 1030 vitiligo patients. Each family was analyzed through a proband afflicted with vitiligo. RESULTS: In 51 (42.5%) of 120 proband families, at least one first-degree relative of the proband had vitiligo. The incidence of those affected among 1755 relatives (first-, second-, and third-degree) was found to be 8.0+/-0.6%. There was a statistically significant departure for segregation analysis which was inconsistent with inheritance as an autosomal or X-linked locus model. On the basis of our results, the inheritance pattern of vitiligo is more likely to tend toward the model of multifactorial inheritance. The threshold trait among first-degree relatives (7.2%) appeared to tend more toward the square root of the frequency in the general population (10%) than towards those of dominant (50%) or recessive (25%) models. CONCLUSIONS: These results indicate that there are certain genetic factors involved in the etiology of vitiligo, and that vitiligo seems to have a polygenic nature.

Female↗

The free radical-generating function of a familial amyotrophic lateral sclerosis-associated D90A Cu,Zn-superoxide dismutase mutant.

The free radical-generating functions of the D90A Cu,Zn-superoxide dismutase (SOD) associated with Swedish familial amyotrophic lateral sclerosis (FALS) patients are investigated. The results show that both the wild-type and mutant enzymes have identical dismutase activity, while the free radical-generating activity of the D90A mutant is enhanced relative to that of the wild-type enzyme. The studies suggest that the active channel of the D90A mutant is larger than that of the wild-type enzyme. A higher free radical-generating activity of the mutant enzyme led to the release of copper ions from the damaged protein. The generation of strand breaks in plasmid DNA was enhanced more effectively by the D90A mutant Cu,Zn-SOD than by the wild-type enzyme. The results suggest that the pathology of FALS may be attributed to oxidative damage caused by the gain-of-function of FALS Cu,Zn-SOD mutant.

Alanine↗

Evaluation of the viscoelastic properties of pharyngeal tissue.

The viscoelastic properties of the human pharyngeal tissue in tension were evaluated, based on both an experimental protocol-consisting of cyclic load, tensile stress relaxation, and incremental step load tests-and a quasilinear viscoelastic theory. The physical properties of the pharyngeal tissue were evaluated to facilitate the biomechanical modeling of human pharynx. The methodology described has potentially significant clinical importance when one considers engineering a similar type of tissue having the same material properties in the future. Qualitatively, the characteristic features of viscoelastic properties of human pharyngeal tissue were experimentally obtained. Then, the reduced stress relaxation function and the elastic response of the pharyngeal tissue were derived from the experimental results specifically obtained from this tissue, by applying the quasilinear viscoelastic theory. The mathematical expression for analyzing nonlinear viscoelastic properties of human pharyngeal tissue is presented, as is the experimental protocol to evaluate the tissue properties. The characteristic features of the tissue need to be considered when attempting to engineer this tissue equivalent, and the data generated can be utilized to evaluate the function of tissue when it is engineered.

Aged↗

Prooxidant effects of ferrous iron, hemoglobin, and ferritin in oil emulsion and cooked-meat homogenates are different from those in raw-meat homogenates.

Oil emulsion and raw and cooked tissue homogenates were used to determine the mechanisms of various iron forms on the catalysis of lipid peroxidation. Flax oil (0.25 g) was blended with 160 mL maleate buffer (0.1 M, pH 6.5) to prepare an oil emulsion. Raw or cooked turkey leg meat was used to prepare meat homogenates. Samples were prepared by adding iron from each of the various sources, reactive oxygen species, or enzyme (xanthine oxidase and superoxide dismutase) systems into the oil emulsion or meat homogenates. In oil emulsion and cooked-meat homogenates, ferrous iron and hemoglobin had strong prooxidant effects, but ferritin became prooxidant only when ascorbate was present. Hemoglobin and ferritin had no prooxidant effect in raw-meat homogenates. The status of heme iron and the released iron from hemoglobin had little effect on the prooxidant effect of hemoglobin in oil emulsion and cooked meat homogenate systems. The prooxidant effect of ferrous iron in oil emulsion and cooked-meat homogenates disappeared in the presence of superoxide (.O2-), H2O2, or xanthine oxidase systems. In raw-meat homogenates, however, ferrous had strong prooxidant effects even in the presence of .O2-, or H2O2. The status of free iron was the most important factor in the oxidation of oil emulsion and cooked-meat homogenates but the impact in raw-meat homogenates was small.

Animals↗

Effect of superoxide and superoxide-generating systems on the prooxidant effect of iron in oil emulsion and raw turkey homogenates.

Mechanisms of superoxide.O2--generating systems on the pro-oxidant effect of iron from various sources were studied. Reaction mixtures were prepared with distilled water, oil emulsion, or meat homogenates. Free ionic iron (ferrous and ferric), ferritin and hemoglobin (Hb) were used as iron sources, and KO2 and xanthine oxidase (XOD) systems were used to produce .O2-. Thiobarbituric acid reactive substances (TBARS) values and iron contents of the reaction mixtures were determined. Ferric iron and ferritin, in the presence or absence of superoxide-generating systems, had no catalytic effect on the oxidation of oil emulsion but became pro-oxidants when reducing agent (ascorbate) was present. Ferrous iron and Hb had strong catalytic effects on the oxidation of oil emulsion as shown by TBARS values. Superoxide and H2O2, generated from superoxide-generating systems, oxidized ferrous iron and ascorbate, and lowered the pro-oxidant effect of ferrous iron in oil emulsion. Addition of ferric or ferrous iron increased but Hb did not have any effect on the TBARS values of raw meat homogenates. The reaction mechanisms of superoxide and the superoxide-generating systems on the prooxidant effect of various iron sources indicated that .O2- was a strong oxidizer rather than a reducing agent, and the antioxidant effect of XOD system in oil was caused by the oxidation of ferrous iron to the ferric form by .O2- and/or H2O2.

Animals↗

Comparative assessment of four different Tl-201 tumor uptake indices in the evaluation of brain tumors.

The objective of this study was to determine which semi-quantitative thallium-201 brain tumor index correlated best with clinical outcome. Fifty-two patients had Tl-201 brain single-photon emission computer tomography (SPECT) performed for the evaluation of recurrent brain tumor. A semi-quantitative tumor index was calculated utilizing four currently available techniques: 1) the ratio of average counts of the region of interest (ROI) in the lesion area and its mirror image in normal brain tissue, 2) the ratio of maximum counts of the region of interest in the lesion area and its average counts in the mirror image, 3) the ratio of maximum counts of the region of interest in the lesion area and its mirror image and 4) the ratio of the average counts of the region of interest in the lesion area and the region of interest of the scalp. A two-tailed Student's t test was performed. The mean value plus one standard deviation was used to assess the sensitivity and specificity correlated with clinical follow-up evaluation, defined as inactive or active at the time of brain SPECT by the referring neurosurgeons. Results of correlation coefficient, P value, mean, standard deviation, sensitivity, and specificity of each index using cutoff values were obtained. For those patients with recurrence or residual malignant tumor after therapy, the maximum count ratio index correlated best with clinical outcome. It provided a sensitivity of 92% and specificity of 88% in differentiating active from inactive brain tumors.

Brain Neoplasms↗

Computer-assisted myocardial thickening analysis of gated MIBI SPECT images.

RATIONALE AND OBJECTIVES: The purpose of this study is to use the relationship between the partial volume effect, count density, matrix size, and reconstruction filter in gated single photon emission computer tomography (SPECT) to recover myocardial thickness, and to validate measurements generated using a computer-assisted automatic contour method with a phantom model and with thickness changes measured by echocardiography. METHODS: Regional myocardial contour was defined automatically using shape constraints, gray level thresholding, and a gradient method applied to gated technetium-99m (99mTc)-methoxy-isobutyl-isonitile (MIBI) SPECT images. A heart phantom with wall thickness ranging from 0.8 cm to 1.3 cm was constructed. SPECT images were acquired and reconstructed using different matrix sizes, count densities, and filters. Wall thickness determinations derived from the reconstructions made with each combination of matrix size, type of filter, and cutoff frequency were correlated with the measured thicknesses. The best combination was applied to the gated MIBI SPECT images of 55 patients who also had echocardiography and coronary arteriography. Count density measurements were made across each regional myocardial segment to evaluate wall thickness at end-diastole and end-systole. Systolic wall thickening measurements made with this automated computer-assisted contour technique were compared with echocardiographic measurements made from segments with normal perfusion and from regions containing infarcted tissue. RESULTS: Different reconstruction filters and cutoff frequencies affected the accuracy of measurements of myocardial wall thickness determined from gated myocardial SPECT images. A matrix size of 64 x 64, with a minimum of 10 counts/pixel/frame, and use of a Hanning filter with 0.5 cyc/cm cutoff frequency gave the best combination for myocardial thickness determination and spatial resolution. Application of these factors to the phantom yielded results that correlated very well with the thickness measurements (r = 0.986, P < 0.001). Application of the technique to the clinical SPECT studies yielded measurements of myocardial wall thickening that were not significantly different from that determined by echocardiography. CONCLUSION: Computer-assisted contour analysis of gated SPECT images enables accurate determination of regional wall thickening using the count density changes within each myocardial segment.

Analysis of Variance↗

Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR.

Toxigenic strains of Clostridium difficile have been reported to produce both toxins A and B nearly always, and nontoxigenic strains have been reported to produce neither of these toxins. Recent studies indicate that it is not always true. We established a PCR assay to differentiate toxin A-negative, toxin B-positive (toxin A-, toxin B+) strains from both toxin-positive (toxin A+, toxin B+) strains and both toxin-negative (toxin A-, toxin B-) strains as an alternative to cell culture assay and enzyme-linked immunosorbent assay (ELISA). By using the PCR primer set NK11 and NK9 derived from the repeating sequences of the toxin A gene, a shorter segment (ca. 700 bp) was amplified from toxin A-, toxin B+ strains compared to the size of the segment amplified from toxin A+, toxin B+ strains (ca. 1,200 bp), and no product was amplified from toxin A-, toxin B-strains. We examined a total of 421 C. difficile isolates by PCR. Of these, 48 strains showed a shorter segment by the PCR, were negative by ELISAs for the detection of toxin A, and were positive by cell culture assay. Although the cytotoxin produced by the toxin A-, toxin B+ strains was neutralized by anti-toxin B serum, the appearance of the cytotoxic effects on Vero cell monolayers was distinguishable from that of toxin A+, toxin B+ strains. By immunoblotting, the 44 toxin A-, toxin B+ strains were typed to serogroup F and the remaining four strains were serogroup X. Pulsed-field gel electrophoresis separated the 48 strains into 19 types. The PCR assay for the detection of the repeating sequences combined with PCR amplification of the nonrepeating sequences of either the toxin A or the toxin B gene is indicated to be useful for differentiating toxin A-, toxin B+ strains from toxin A+, toxin B+ and toxin A-, toxin B- strains and will contribute to elucidation of the precise role of toxin A-, toxin B+ strains in intestinal diseases.

Adolescent↗

Multiple orientation-dependent, synergistically interacting, similar domains in the ribosomal DNA replication origin of the fission yeast, Schizosaccharomyces pombe.

Previous investigations have shown that the fission yeast, Schizosaccharomyces pombe, has DNA replication origins (500 to 1500 bp) that are larger than those in the budding yeast, Saccharomyces cerevisiae (100 to 150 bp). Deletion and linker substitution analyses of two fission yeast origins revealed that they contain multiple important regions with AT-rich asymmetric (abundant A residues in one strand and T residues in the complementary strand) sequence motifs. In this work we present the characterization of a third fission yeast replication origin, ars3001, which is relatively small ( approximately 570 bp) and responsible for replication of ribosomal DNA. Like previously studied fission yeast origins, ars3001 contains multiple important regions. The three most important of these regions resemble each other in several ways: each region is essential for origin function and is at least partially orientation dependent, each region contains similar clusters of A+T-rich asymmetric sequences, and the regions can partially substitute for each other. These observations suggest that ars3001 function requires synergistic interactions between domains binding similar proteins. It is likely that this requirement extends to other fission yeast origins, explaining why such origins are larger than those of budding yeast.

Base Sequence↗

Vascular leiomyoma of an extremity: MR imaging-pathology correlation.

OBJECTIVE: The objective of our study was to analyze MR images of vascular leiomyoma of the extremity and to compare these images with histopathologic findings to determine if a correlation exists. CONCLUSION: T2-weighted MR images of vascular leiomyoma of an extremity showed a mass with mixed areas that were both hyper- and isointense to skeletal muscle and also revealed a hypointense rim; these images correlate with histopathologic findings of smooth muscle, vessels, fibrous tissue, an intravascular thrombus, and a fibrous capsule.

Adult↗

Isolated bilateral abducens nerve palsy due to carotid cavernous dural arteriovenous fistula.

Carotid cavernous dural arteriovenous fistula (DAVF) usually presents with conjunctival injection, proptosis, loss of visual acuity and ophthalmoplegia. There have been some carotid cavernous DAVF case reports presenting with isolated oculomotor, abducens and trochlear nerve palsy. We experienced a patient presenting with bilateral abducens nerve palsy and no other ocular signs who was diagnosed as carotid cavernous DAVF after conventional angiography. According to this case, carotid cavernous DAVF should be considered in the differential diagnosis of isolated bilateral abducens nerve palsy, in which case conventional angiography may be helpful in diagnosis.

Abducens Nerve↗

DNA cleavage by hydroxyl radicals generated in the Cu,Zn-superoxide dismutase and hydrogen peroxide system.

To study the catalytic activity of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxyl radical (.OH) from H2O2, we investigated the mechanism of DNA cleavage mediated by human Cu,Zn-SOD and H2O2. When plasmid DNA was incubated with 5 microM Cu, Zn-SOD and 1.0 mM H2O2, DNA cleavage occurred within 15 min. A spectrophotometric study using a 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) showed that free .OH formation was proportional to concentrations of Cu,Zn-SOD and H2O2. .OH formation and DNA cleavage were inhibited by hydroxyl radical scavengers such as cyanide, azide, and formate. These results indicated that .OH generated early in the peroxidative reaction of Cu,Zn-SOD with H2O2 was implicated in DNA cleavage. Incubation with H2O2 resulted in a time-dependent release of copper ions from the Cu,Zn-SOD molecule. The released copper ions then likely participated in a Fenton-like reaction to produce .OH that may have caused DNA cleavage. Evidence that DTPA protected the DNA cleavage induced by the Cu,Zn-SOD/H2O2 system supports this mechanism. We suggest that DNA cleavage is mediated in the Cu,Zn-SOD/H2O2 system via the generation of .OH by a combination of the peroxidative reaction of Cu,Zn-SOD and the Fenton-like reaction of free copper ions released from oxidatively damaged SOD.

Benzothiazoles↗

Fragmentation of human Cu,Zn-superoxide dismutase by peroxidative reaction.

We investigated the fragmentation of human Cu,Zn-superoxide dismutase (SOD) by H2O2. When Cu,Zn-SOD was incubated with H2O2, the fragmentation of protein proceeded rapidly within 1 min. The amounts of .OH radical formed in the Cu,Zn-SOD/H2O2 system reached a maximum in about 3 min. This result suggested that .OH was implicated in the fragmentation step. Copper ions released from Cu,Zn-SOD were gradually increased up to 30 min after starting the incubation with H2O2 in a time-dependent manner. However, the fragmentation was not inhibited by 5 mM DTPA. The results suggested that the fragmentation of Cu,Zn-SOD by H2O2 was due to the peroxidative reaction of SOD rather than the Fenton-like reaction by free copper released from oxidatively damaged SOD. A radical scavenger, azide anion, inhibited the fragmentation of Cu,Zn-SOD and the formation of .OH whereas ethanol did not. These results indicated that azide anions had easy access inside the active channel of Cu,Zn-SOD and thus protected the damage of the enzyme by .OH radicals whereas neutral alcohols stayed outside the active channel and could hardly intercept the newly-formed .OH radicals. Thus we conclude that the fragmentation of Cu,Zn-SOD by H2O2, is due to the oxidative damage resulting from free .OH radicals generated by the peroxidative reaction of SOD.

Copper↗

Peroxidative activity of human Cu,Zn-superoxide dismutase.

In addition to the usual superoxide dismutation activity, Cu,Zn-superoxide dismutase (SOD) has a peroxidative function that utilizes its own dismutation product, H2O2 as a substrate. The peroxidative activity of human Cu,Zn-SOD was studied by using a chromogen, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) which reacts with OH radicals to form ABTS+. The optimal pH for the peroxidative activity of human Cu,Zn-SOD was 7.6-9.5. The peroxidative activity retained about 50% of the maximum activity when exposed at 40 degrees C for 5 min. The peroxidative activity showed a typical Michaelis-Menten kinetics for ABTS and H2O2 whose K(m) values were 16 microM and 9.3 mM, respectively. The peroxidative activity of human Cu,Zn-SOD was inhibited about 60% by the copper chelator, diethyldithiocarbamate (DDC) at 10 microM while the dismutation activity was not inhibited under a similar condition. We found that there are differences in the effects of temperature and DDC on the dismutation and peroxidative activities of human Cu,Zn-SOD. These results suggest that the amino acid residues which affect the activities of this enzyme may be different between dismutation and peroxidation.

Benzothiazoles↗

NMR structure determination of a novel conotoxin, [Pro 7,13] alpha A-conotoxin PIVA.

A high-resolution solution conformation of a novel conotoxin, [Pro 7,13] alpha A-conotoxin PIVA, GCCGSYPNAACHPCSCKDROSYCGQ-NH2, has been determined by two-dimensional 1H NMR methods and distance geometry calculations. The total of 324 NOE-derived interproton distance restraints including 33 long-range NOE restraints as well as 11 phi and 7 chi 1 torsion angle restraints was used for computation of structures. Back-calculation from the experimental NOE spectrum has provided 49 new NOE restraints and yielded the final R-factors of Ra = 0.641 and Rb = 0.157. The final RMSD values are 0.90 and 1.16 A for the backbone and the heavy atoms, respectively. The C-terminal half of the molecule involving the residues 12-24 is extremely well-defined with a backbone RMSD value of 0.56 A, whereas the N-terminal 3-11 disulfide loop is relatively flexible, possessing a backbone RMSD value of 1.09 A. The [Pro 7,13] alpha A-conotoxin PIVA does not contain any significant secondary structure although the 21S-24G nearly completes one turn of a 3(10) helix. The overall protein fold is largely maintained by the three disulfide bridges of 2-16, 3-11, and 14-23. The presence of the three disulfide bridges imposes geometric constraints that force the molecule to form six continuous bends involving the following residues: 3C-5S, 7P-10A, 12H-14C, 15S-17K, 17K-19R, and 21S-25Q. The overall shape of the [Pro 7,13] alpha A-conotoxin PIVA can be described as an "iron". Residues 15S-19R form a loop that protrudes out of the "bottom plate" formed by the rest of the protein and constitute the handle of the iron. The N-terminal tip of the molecule is relatively immobile due to attractive electrostatic interactions between the gamma-hydroxyl group of 20 Hyp and the phenolic hydroxyl group of 22Y. The flexible 3-11 disulfide loop consists mostly of hydrophobic residues, while the best-defined 14-23 disulfide loop contains the highly charged hydrophilic 15S-19R "handle" domain exposed to the exterior of the protein. Binding to nicotinic acetylcholine receptor can be mediated through two different types of interactions: one involving the aromatic hydrophobic residues such as 6Y and 12H and the other involving the positively charged hydrophilic side chain of the 19R. The side chain of the 19R in the [Pro 7, 13] alpha A-conotoxin PIVA and that of the 9R of the alpha-conotoxin G1, and also the side chains of the 12H and 6Y in the former and those of 10H and 11Y in the latter can be aligned to point to the same direction when the corresponding backbone atoms are superimposed to an RMSD value of 2.5 A.

Amino Acid Sequence↗

Effect of egg size and strain and age of hens on the solids content of chicken eggs.

A study was conducted to determine the effect of egg size and the age and strain of hens on the content of egg solids. Eggs were obtained from commercial farms from four strains of hens with similar age groups and received diets formulated to contain the same dietary energy and protein levels across the strains within a farm. Eggs were collected on 2 different d when the flocks reached the average ages of 28, 55, 75, and 97 wk. The eggs collected form each farm were pooled and sorted by size. Each individual egg was used as a replicate for yolk:white ratio; however, five yolks, five whites, and five whole eggs from each strain at each age period were pooled, homogenized, and then used as a replicate to determine the solids contents of yolk, white, and whole eggs. The yolk:white ratio of eggs from 28-wk-old hens was the lowest, that from 55- and 78-wk-old hens was the highest, and that from 97-wk-old hens was intermediate; however, the solids content (percentage) of whole eggs increased with the age of the hens. The solids content of egg white was highest in eggs from 28-wk-old hens. The white solids content of extra large eggs was greater than that of medium eggs, and yolk solids increased with egg size; however, the solids of whole egg were not affected by egg size. The strain of hens had a significant effect on the solids of whole egg, white, and yolk; however, the strain effect on yolk:white ratio was not significant. The results showed that young (28-wk-old) and old birds (97-wk-old) produced eggs with low solids content and intermediate aged hens (55- to 78-wk-old) produced eggs with high solids content. Therefore, it may be more beneficial for egg producers and processors to use young (28-wk-old) and old birds (97-wk-old) for table egg production and birds of intermediate age (55- to 78-wk-old) for liquid egg production.

Aging↗