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S M Kim

Publications and source records attributed to S M Kim.

At least 145 records · Page 8Linked to original sources
PubMed1996

Cytokine transcriptional events during helper T cell subset differentiation.

The molecular basis for changes in cytokine expression during T helper (Th) cell subset differentiation is not well understood. We have characterized transcriptional events related to cytokine gene expression in populations of naive T cell receptor-transgenic T cells as they are driven in vitro toward Th1 or Th2 phenotypes by interleukin (IL)-12 or IL-4 treatment, respectively. Quantitative reverse transcriptase-polymerase chain reaction analysis of cytokine transcripts indicates that interferon (IFN) gamma, IL-4, and IL-2 mRNA are expressed with distinct kinetics after naive T cells are stimulated with antigen and either IL-4 or IL-12. IFN-gamma mRNA appears as early as 6 h in IL-12-treated cultures, IL-4 appears only after 48 h in IL-4-treated cultures, and IL-2 is equivalently expressed in both types of cultures. Analyses were performed to determine if there were any differences in activation of IL-2 or IL-4 transcription factors that accompanied Th1 versus Th2 differentiation. These studies demonstrated that signal transducer and activator of transcription 6 (STAT6) binds to a sequence in the IL-4 promoter and that this STAT6-binding site can support IL-4-dependent transcription of a linked heterologous promoter. Prolonged activation of STAT6 is characteristic of populations undergoing Th2 differentiation. Furthermore, STAT6 is activated in an autocrine manner when differentiated Th2 populations are stimulated by antigen receptor ligation. Th1 populations derived from IL-12 plus antigen treatment of naive T cells remain responsive to IL-4 as indicated by induction of STAT6 and IL-4 mRNA. These data indicate that Th1 and Th2 differentiation represents the combination of different, apparently independently regulated transcriptional events. Furthermore, among transcription factors that bind to the IL-4 or IL-2 promoters, STAT6 is the one whose activation distinguishes Th2 versus Th1 development.

Animals↗
PubMed1996

Large, complex modular structure of a fission yeast DNA replication origin.

BACKGROUND: In the budding yeast, Saccharomyces cerevisiae, each DNA replication origin is associated with an autonomously replicating sequence (ARS) element. Each element contains several modules, including an essential close match to the 11 base-pair (bp) ARS consensus sequence (ACS) and two or three short (< 20 bp) stimulatory motifs, within a stretch of approximately 150 bp or less. To determine whether a similar origin structure exists in the evolutionarily distant fission yeast, Schizosaccharomyces pombe, we used deletion and linker substitution scanning to identify the sequences important for the function of ars3002, a chromosomal replication origin. RESULTS: We detected two large (30-55 bp) essential regions and several additional stimulatory sequences within a 600 bp stretch of a restriction fragment containing ars3002. The two essential regions are similar to each other, and sequences similar to them are found in all known S. pombe ARS elements, suggesting that one or both of them may represent the S. pombe equivalent of the S. cerevisiae ACS. CONCLUSIONS: Like S. cerevisiae origins, the S. pombe origin, ars3002, possesses a modular structure, but the number and size of modules is greater for ars3002, and ars3002 is larger than S. cerevisiae origins. These observations suggest that origin function in S. pombe requires more protein-DNA interactions than in S. cerevisiae.

Base Sequence↗
PubMed1996

Determination of the three-dimensional structure of hordothionin-alpha by nuclear magnetic resonance.

The high-resolution three-dimensional solution structure of the plant toxin hordothionin-alpha obtained from korean barley was determined by using two-dimensional NMR techniques combined with distance geometry and restrained molecular dynamics. Experimentally derived restraints including 292 interproton distances from nuclear Overhauser effect measurements, 16 hydrogen bond restraints together with four disulphide bridge restraints were used as input to calculations of distance geometry and restrained molecular dynamics. Also included in the calculations were 36 phi and 17 chi 1 torsion angles obtained from 33JHN alpha and 3J alpha beta coupling constants in double quantum filtered COSY and primitive exclusive COSY experiments, respectively. The overall protein fold is similar to crambin and purothionin-alpha 1. Two alpha-helices running in opposite directions are found on the basis of 3JHN alpha and 3J alpha beta and deuterium exchange rates for backbone NH protons, and encompass residues 7-18 and 22-28. These two helices are connected by a turn and form a 'helix-turn-helix' motif. A short stretch of an anti-parallel beta-sheet exists between residues 1-4 and 31-34. the two protein termini of hordothionin-alpha are 'well-anchored'; the N-terminus of the protein is immobilized by this short beta-sheet whereas the C-terminus is 'pasted' to the carbonyl group of Cys-4 by a very stable hydrogen bond. The average root-mean-square differences for the backbone and heavy atoms after the restrained molecular dynamics calculations are 0.62 and 1.16 A respectively. These numbers represent a significant improvement over the corresponding values for the previous NMR structures of other thionins. The distance violation from the experimental interproton distances for the final structures is 0.14 for all atoms.

Amino Acid Sequence↗
PubMed1996

Cystic fibrosis mutation detection by hybridization to light-generated DNA probe arrays.

We have combined photochemistry and photolithography with solid-phase DNA synthesis chemistry to form a new technology that makes high density oligonucleotide probe array synthesis possible. Hybridization to these two-dimensional arrays containing hundreds or thousands of oligonucleotide probes provides a powerful DNA sequence analysis tool. Two types of light-generated DNA probe arrays have been used to test for a variety of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. One array, made up of 428 probes, was designed to scan through the length of CFTR exon 11 and identify differences from the wild type reference sequence. The second type of array contained 1480 probes chosen to detect known deletions, insertions, or base substitution mutations. The validity of the probe arrays was established by hybridizing them with fluorescently labeled control oligonucleotide targets. Characterized mutant CFTR genomic DNA samples were then used to further test probe array hybridization specificity. Finally, ten unknown patient samples were genotyped using the CFTR probe array assay. The genotype assignments were identical to those obtained by PCR product restriction fragment analysis. Our results show that light-generated DNA probe arrays are highly effective in analyzing complex mutation and polymorphism patterns in a relatively large gene such as CFTR.

Base Sequence↗
PubMed1996

Chromosomal numerical aberrations in gastric carcinoma: analysis of eighteen cases using in situ hybridization.

Paraffin-embedded tumor cells of 18 cases of gastric carcinoma were hybridized with digoxigenin-labeled repetitive DNA probes specific for the centromeric regions of chromosomes X, Y, 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, and 20. All cases demonstrated numerical chromosomal aberrations. The most exciting aberration, polysomy (five or more copies) of several chromosomes, was found in all cases except a case of mucinous adenocarcinoma, which showed trisomy 9 as the sole chromosomal numerical aberration. In nine cases of tubular adenocarcinoma, poorly-differentiated polysomies of several chromosomes were the consistent numerical aberration and monosomy 7, 18(2 cases each), 10, and 17(1 case each) were also found. In moderately-differentiated tubular adenocarcinoma all three cases also showed polysomies of several chromosomes. The total number of extra chromosomes (polysomy was counted as 5 copies) was higher in the intestinal type (mean 20.9) than in the diffuse type (mean 14.1). Regional lymph node metastasis, vein invasion, or perineural invasion was not related to any specific chromosomal numerical aberration in gastric cancer. Chromosomes X, 1, 2, 3, 4, 15, 17, and 20 had extra copies especially polysomy in most cases. However, chromosomes 7 and 18 revealed monosomy in many cases (31.3% and 33.3% respectively, and chromosome 9 and 11 revealed trisomy in 35.7% and 75% each. Numerically, the most conserved chromosome in gastric cancer was chromosome 12 (62.5%). By flow cytometry, two diploidy and 8 aneuploidy cases with the DNA indices from 1.30 to 1.85 were found.

Adult↗
PubMed1996

Tc-99m MIBI brain SPECT of cerebellopontine angle tumors.

To prospectively evaluate the imaging feasibility of Tc-99m sestamibi brain SPECT of cerebellopontine angle (CPA) tumors, seven patients with CPA lesions seen on CT or MRI and five normal control subjects underwent brain SPECT using a triple-headed camera. Five of these patients had acoustic neuromas, one had a meningloma, and the other had a vascular loop. Subsequently, four patients underwent surgery. In normal control subjects and patients with CPA lesions, there was Tc-99m sestamibi activity in the pituitary gland, choroid plexi, and extraocular muscles. The uptake in these structures, especially the choroid plexi could not be blocked by the oral administration of potassium perchlorate in two normal subjects. Four of seven patients with CPA lesions larger than 1.0 cm in diameter showed tumor uptake (3 acoustic schwannomas, 1 meningloma). Two small ( > 1.0 cm in diameter) intracanalicular type acoustic neuromas failed to show uptake, despite additional attenuation correction for the petrous bone. There was no abnormal uptake in the patient with a vascular loop in the CPA. Preliminary data suggest that, with the exception of small intracanalicular neuromas, CPA tumors can be imaged using Tc-99m sestamibi brain SPECT.

Adult↗
PubMed1996

Interphase cytogenetics of non-Hodgkin's lymphoma using non-fluorescent in situ hybridization in paraffin embedded tissue.

Paraffin-embedded tissue samples from 30 cases of non-Hodgkin's lymphoma(NHL) and 10 of reactive hyperplasia, were processed for interphase cytogenetic chromosomal study. We performed non-fluorescent in situ hybridization(NFISH) using the enzymatic method with digoxigenin-labeled DNA centromeric probes for chromosome 7,12,18 and X, and a painting probe for chromosome 18. Chromosomal aberrations were observed in 27(90%) out of 30 cases of NHL. The most commonly observed numerical aberration was extracopy of X chromosome. There were some characteristic aberrations corresponding to each grade and group of NHL by International Working Formulation: In low grade NHL(9 cases), a third were associated with extracopy of chromosome 12, and disomy X was frequently found in small lymphocytic lymphoma(75%). With intermediate grade(16 cases), tetraploidy(25%), translocation of chromosome 18(25%), and extracopy of chromosome 18(19%) were characteristically associated. These results suggest that interphase NFISH is an easily performable method in retrograde cytogenetic study of archival materials. Some specifically correlated chromosomal aberrations corresponding to the histopathologic grades and groups could provide us more valuable information for determining pathologic diagnosis and assessing the clinical outcome of NHL.

Chromosome Aberrations↗
PubMed1996

HTLV-I associated adult T cell leukemia/lymphoma: report of two cases from an Amerindian population in coastal northwest British Columbia.

Epidemiological studies of HTLV-I infection have demonstrated the presence of this virus in certain Amerindian populations in Central and South America. We have recently reported the first evidence of endemic HTLV-I infection in North American Amerindians from the coastal regions of British Columbia, Canada. While the predominant HTLV-I-associated disease observed in British Columbia Amerindians is the HTLV-I associated neurological disease (HTLV-I-associated myelopathy/tropical spastic paraparesis), we report here the first two cases of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). Clinical and PCR evidence to support the diagnosis of HTLV-I-associated ATL in these two Amerindians is presented. Both cases of ATL were found in the same tribe although neither patient was directly related to each other. While reports of HTLV-I-associated ATL have been reported in Circumartic native peoples, reports of ATL in North American single ancestry Amerindians have not been previously made to our knowledge.

Adult↗
PubMed1996

Single-photon-emission computed tomography (SPECT) in neurotologic assessment: a preliminary report.

The single-photon-emission computed tomography (SPECT) scan enables clinicians to probe dynamic and metabolic changes in brain tissue through measurement of regional cerebral blood flow (rCBF). Diagnostic benefits of the SPECT scan in clinical neurology have been demonstrated. SPECT scanning has been shown to be more sensitive than morphologic imaging techniques [magnetic resonance imaging (MRI) and computed tomography (CT)] in many conditions. However, the use of the scan in assessing neurotologic complaints remains inadequately investigated. Few studies have explored the value of SPECT in establishing the causes of dizziness, hearing loss, and tinnitus. We studied SPECT along with MRI, CT scan, electroencephalogram (EEG), and other evaluations in patients with these neurotologic complaints, SPECT abnormalities were more frequent and prominent than those visualized by other imaging modalities. Overall, 78% of SPECT scans revealed abnormalities. Abnormalities were found in 46% of MRIs, 40% of CTs, and 29% of EEGs. The disparity between SPECT scanning and other procedures was also seen once patients were divided by their chief complaints. This study illustrates the sensitivity of SPECT scanning in evaluating neurotologic complaints and highlights the need for additional research into the importance of SPECT scanning in comprehensive neurotologic evaluation.

Brain↗
PubMed1995

Prognostic significance of ST-segment depression during adenosine perfusion imaging.

To determine the significance of ST-segment depression during adenosine perfusion imaging for predicting future cardiac events, 188 patients with interpretable electrocardiograms were assessed 1 to 3 years (mean 21.5 +/- 6.6 months) after adenosine testing. At least 1 mm of ST-segment depression was observed in 32 (17%) patients, with > or = 2 mm of ST-segment depression in 10 (5.3%). Thirty-seven cardiac events occurred during the study period: 2 cardiac deaths, 5 nonfatal myocardial infarctions, 6 admissions for unstable angina, and 24 revascularizations. Univariate predictors of events were a history of congestive heart failure, previous non-Q-wave myocardial infarction, previous coronary angioplasty, use of antianginal medication, ST-segment depression during adenosine infusion (particularly > or = 2 mm), any reversible perfusion defect, transient left ventricular cavity dilation, and the severity of perfusion defects. Multivariate analysis identified > or = 2 mm ST-segment depression as the most significant predictor of cardiac events (relative risk [RR] = 6.5; p = 0.0001). Other independent predictors of events were left ventricular dilation (RR = 3.8; p = 0.002), previous coronary angioplasty (RR = 3.3; p = 0.001), a history of non-Q-wave myocardial infarction (RR = 2.3; p = 0.01), and the presence of any reversible defect (RR = 2.0; p = 0.05). We conclude that ST-segment depression occurs uncommonly during adenosine infusion, but the presence of > or = 2 mm of ST-segment depression is an independent predictor of future cardiac events and provides information in addition to that obtained from clinical variables and the results of adenosine perfusion imaging.

Adenosine↗
PubMed1995

Delayed radioiodine organification in Plummer's disease.

Hyperfunctioning thyroid adenomas causing thyrotoxicosis (Plummer's disease) is not an uncommon cause of hyperthyroidism in the elderly. Most commonly, the adenoma appears as a so-called "hot" nodule on thyroid scintigraphy causing suppression (i.e., nonvisualization) of the remainder of the gland. This report describes a case of Plummer's disease in an elderly patient in whom the toxic nodule primarily responsible for causing the hyperthyroidism became scintigraphically apparent at 96 hours after I-131 therapeutic ablation.

Adenoma↗
PubMed1995

Association of exposure to polycyclic aromatic hydrocarbons (estimated from job category) with concentration of 1-hydroxypyrene glucuronide in urine from workers at a steel plant.

OBJECTIVES: Increased risk of lung cancer has been associated with employment in the steel industry. This association is thought to be due in part to increased concentrations of polycyclic aromatic hydrocarbons (PAHs) in air found in this work environment. Measurement of PAH metabolites in human urine provides a means of assessing individual internal dose of PAHs. This study examined the relative contribution of occupation and smoking to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG) among a group of workers at a steel plant. METHODS: Concentrations of 1-OHPG in urine from 44 workers with jobs associated with increased air concentrations of PAHs and 40 workers with jobs with low or no exposure to PAHs were measured. 20 workers in each group were not current smokers. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy after immunoaffinity chromatography specific for PAH metabolites. RESULTS: Mean (SEM) urinary 1-OHPG concentration was 2.16 (0.42) pmol/ml urine among the 44 occupationally exposed workers compared with 0.38 (0.05) among the 40 workers with no or low exposure (P < 0.0001). Mean urinary 1-OHPG concentration was 1.82 (0.41) pmol/ml urine among the 44 current smokers compared with 0.75 (0.20) among the 40 non-smokers (P < 0.005). Mean 1-OHPG concentrations in non-smokers were 0.26 (n = 20), 0.70 (n = 15), and 2.84 pmol/ml urine (n = 5) for strata of exposure to PAHs (no or low, mid, and high) based on job category; the corresponding values in smokers were 0.55 (n = 20), 0.94 (n = 12), and 4.91 pmol/ml (n = 12), respectively. Multiple linear regression showed significant differences between subjects in different PAH exposure with increased concentrations of 1-OHPG in urine. Amounts of foods containing PAHs ingested by this group of workers were relatively low and did not contribute significantly to urinary 1-OHPG concentrations. CONCLUSIONS: These results indicate that 1-OHPG is a common urinary metabolite in people with recent occupational exposure to PAHs and is associated with both job category and estimated stratum of PAH exposure.

Adult↗
PubMed1995

Localization of intracellular monoclonal antibody specific for mycobacteria in experimentally induced pulmonary tuberculous lesion.

To determine the intracellular localization of intravenously injected infection-specific monoclonal antibodies (mAbs) in the infected cells, immunohistochemical staining was carried out in an animal model having pulmonary tuberculous lesions induced by inoculation of heat-killed Mycobacterium tuberculosis H37Rv. One milligram of intact mouse mAb against mycobacteria (group I, n = 10) and F(ab')2 (group II, n = 6) was intravenously injected to the rabbits of each group. Immunohistochemical staining using an antimouse Ab was performed at days 1, 3, 5, 7 and 8 in group I and at days 1, 2 and 3 in group II by the streptavidin-biotin method. For the control study, 1 ml of nonspecific polyclonal human IgG (group III, n = 10) and 100 micrograms of normal rabbit IgG F(ab')2 (group IV, n = 6) was injected to rabbits and guinea pigs having tuberculous inflammation, respectively. Both groups (group I and II) showed a positive antigen (Ag)-Ab reaction within the cytoplasm of monocytes. A weak but positive reaction was observed intracellularly in group III; however, no positive reaction was seen in group IV. Our results suggest that an intracellular Ag-Ab reaction plays an important role in the localization of infection by immunoscintigraphy using specific mAb fragments.

Animals↗
PubMed1995

Systemic lupus erythematosus with obstructive uropathy. Case report and review.

We report a case of patient with documented SLE who displayed dysuria, gastrointestinal (GI) symptoms and renal insufficiency associated with the unusual occurrence of bilateral hydroureteronephrosis due to urterovesical junction stricture (obstructive uropathy). Pathologic investigations disclosed chronic interstitial cystitis (IC) with evidence of focal immune complex deposition in the blood vessel walls of the bladder. The GI symptoms and dysuria regressed with initial therapy for SLE with steroids. However, the persistent obstructive uropathy (OU) and renal insufficiency required bilateral nephrostomy followed by steroids plus intravenous pulse injection of cyclophosphamide. The obstructive uropathy was relieved even after removing the nephrostomy tube and renal function remained stable. Including this case, nineteen SLE patients associated with clinical and radiographic findings of OU were found in the world literature and reviewed to find any consistent pattern of clinical features. Most of the patients with OU in SLE were female (mean age, 31.7 yr) and orientals (63%), and had interstitial cystitis (89%) as a common underlying cause with concomitant involvement of the GI tract (89%) and WHO class IV or V advanced glomerulonephritis (67%). Despite the remarkable response (68%) to steroids in majority of OU patients associated with SLE, certain patients still required surgical correction (32%) and some even died (32%). OU, potentially reversible, was not an exception in patients with SLE, which might be overshadowed by other major organ involvement of SLE.

Adolescent↗
PubMed1994

Differential inhibition of T and B cell responses to individual antigenic determinants in orally tolerized mice.

Immunological tolerance of systemic immunity can be induced by the oral administration of an exogenous antigen, which is termed oral tolerance. We examined whether there was a difference in the degree of tolerance between individual antigenic determinants in oral tolerance. Feeding bovine alpha s1-casein, a major protein in cow's milk, as a constituent of the diet induces oral tolerance in mice. However, a weak antibody response can be elicited in the alpha s1-casein-fed animals by subsequent immunization with the antigen. We examined the fine specificity of such anti-alpha s1-casein antibodies produced in alpha s1-casein-fed mice. The results demonstrated that there was a difference in the inhibition of antibody response between different B cell determinants. Differential inhibition could also be observed for T cell responses. T cells specific for dominant determinants were preferentially tolerized, while those for cryptic determinants escaped oral tolerance. Our results imply the importance of antigen presentation for this differential inhibition of antigenic determinants. We suggest that orally administered antigen does not induce tolerance to some of the B and T lymphocyte repertoire which could potentially induce harmful food hypersensitivity.

Administration, Oral↗