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Biomedical subjects

J Hong

Publications and source records attributed to J Hong.

At least 73 records · Page 4Linked to original sources
PubMed2000

t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF).

A t(9;11)(p22;p15) chromosomal translocation was identified in an adult patient with de novo acute myelogenous leukemia. Fluorescence in situ hybridization and Southern blot analysis mapped the 11p15 break-point to the NUP98 gene. Using 3' rapid amplification of cDNA ends, we have identified a chimeric mRNA that fused the NUP98 FXFG repeats in frame to the COOH-terminal portion of the gene encoding the transcriptional coactivators p52 and p75, also known as lens epithelium-derived growth factor (LEDGF). As expected, both NUP98-p52 and NUP98-p75 (LEDGF) chimeric mRNAs were detected by reverse transcription-PCR; however, the reciprocal p52/p75 (LEDGF)-NUP98 fusion mRNA was not detected. Our results demonstrate that this is the most 5' NUP98 fusion reported and reveal a previously unrecognized genetic target, the gene encoding p52/p75 (LEDGF).

Adaptor Proteins, Signal Transducing↗
PubMed2000

Immunoregulation and blocking antibodies induced by interferon beta treatment in MS.

OBJECTIVE: To examine the in vivo immunoregulatory properties of interferon beta-1a (IFN beta-1a) on the T cell responses to myelin basic protein (MBP) and to evaluate the occurrence of the blocking antibodies characterized by the ability to reverse the effects of IFN beta on T cells in MS patients treated with IFN beta. METHODS: The precursor frequency of T cells recognizing MBP and control antigens was estimated in a microwell culture system. The cytokine profile of T cell lines was measured in ELISA. The binding antibodies were determined in ELISA and Western blot. Cytopathic test and the T cell functional assays were used to determine the blocking effects of the binding antibodies. RESULTS: Treatment with IFN beta resulted in a substantial reduction in the precursor frequency of MBP-reactive T cells in MS patients. The cytokine profile of MBP-reactive T cells that sustained the treatment was altered toward an increased production of interleukin (IL)-10 and decreased production of tumor necrosis factor (TNF)alpha and IFN-gamma. The immunoregulatory properties of IFN beta on T cells could be blocked by the binding antibodies derived from a proportion of patients treated with IFN beta (4 of 64, 6.25%). The blocking antibodies also neutralized anti-viral activity of IFN beta in cytopathic assays, corresponding to previously described neutralizing antibodies. CONCLUSIONS: Treatment with IFN beta alters the cytokine profile by enhancing the production of IL-10 and downregulating Th1 cytokines, which may contribute to clinical benefit in MS. The treatment also induces blocking antibodies that impair the immunoregulatory properties of IFN beta in some individuals.

Adjuvants, Immunologic↗
PubMed2000

Characterization of CYP1A1 and CYP1A3 gene expression in rainbow trout (Oncorhynchus mykiss).

The rainbow trout CYP1A1 and CYP1A3 genes share 96% amino acid identity and have similar enzymatic activity. The expression of CYP1A1 and 1A3 genes was investigated in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rainbow trout tissues, sac fry and cell lines. Both CYP1A1 and CYP1A3 were induced by TCDD in all the tissues examined. While CYP1A3 gene was expressed constitutively at higher levels than CYP1A1 in trout intestine, preferential expression of CYP1A1 occurred in trout liver, heart, kidney and trout sac fry. In rainbow trout gonad (RTG)-2 and rainbow trout hepatoma (RTH)-149 cell lines, CYP1A1 was constitutively expressed and induced by exposure to TCDD, but CYP1A3 message was not detected, even after TCDD treatment. Quantitative analysis of CYP1A genes expression in rainbow trout liver revealed that TCDD induced CYP1A1 expression more than 50-fold and CYP1A3 RNA levels increased at least 100-fold over untreated fish. The cell- and tissue-specific expression indicates that these closely related CYP1A genes are independently regulated and that negative regulation may play a role in CYP1A3 gene expression.

Journal Article↗
PubMed2000

Preferential recognition of TCR hypervariable regions by human anti-idiotypic T cells induced by T cell vaccination.

T cell responses to myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). Immunization with irradiated MBP-reactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that suppress circulating MBP-reactive T cells. This T cell-T cell interaction is thought to involve the recognition of TCR expressed on target T cells. The study was undertaken to define the idiotypic determinants responsible for triggering CD8+ cytotoxic anti-idiotypic T cell responses by T cell vaccination in patients with MS. A panel of 9-mer synthetic TCR peptides corresponding to complementarity-determining region 2 (CDR2) and CDR3 of the immunizing MBP-reactive T cell clones were used to isolate anti-idiotypic T cell lines from immunized MS patients. The resulting TCR-specific T cell lines expressed exclusively the CD8 phenotype and recognized preferentially the CDR3 peptides. CDR3-specific T cell lines were found to lyze specifically autologous immunizing MBP-reactive T cell clones. The findings suggest that CDR3-specific T cells represented anti-idiotypic T cell population induced by T cell vaccination. In contrast, the CDR2 peptides were less immunogenic and contained cryptic determinants as the CDR2-specific T cell lines did not recognize autologous immunizing T cell clones from which the peptide sequence was derived. The study has important implications in our understanding of in vivo idiotypic regulation of autoimmune T cells and the regulatory mechanism underlying T cell vaccination.

Amino Acid Sequence↗
PubMed2000

Chiral and electrokinetic separation of amino acids using polypyrrole-coated adsorbents.

An optically active and electroconductive polymeric adsorbent has been developed for the use in chromatographic resolution of nonderivatized amino acids. The chiral selectivity of the adsorbent is based upon ligand exchange of coordinated copper(II) complexes of D or L-amino acids and a molecular imprinting technique by modifying the resin surface with polypyrrole coating. Applying a potential difference of +/-1.5 V to the chiral and conductive column, racemic amino acids are separated according to their charge characteristics, and simultaneously resolved with respect to their optical isomerisms. A pH-controlled mixture of D,L-lysine and D,L-aspartic acid is resolved displaying enantioselectivity values of 1.19 and 2.08, respectively, and a baseline separation of the two amino acids is accomplished by alternating the polarity of the electric field. The synthesized adsorbent also exhibits size exclusion factor discriminating amino acids with larger side chains.

Amino Acids↗
PubMed2000

ABFs, a family of ABA-responsive element binding factors.

Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

Abscisic Acid↗
PubMed2000

Th2 immune regulation induced by T cell vaccination in patients with multiple sclerosis.

T cell responses to myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). In this study, we demonstrated that subcutaneous inoculations with irradiated autologous MBP-reactive T cell clones (T cell vaccination) elicited CD8+ anti-idiotypic T cell responses and CD4+ Th2 cell responses in patients with MS. Both regulatory cell types induced by T cell vaccination contributed to the inhibition of MBP-reactive T cells while they differed in the recognition pattern and functional properties. We describe for the first time that the Th2 regulatory cells reacted with activated but not resting T cells in the context of MHC class II molecules and inhibited the proliferation of MBP-reactive T cells through the secretion of IL-4 and IL-10. The T-T cell interaction mediated by Th2 regulatory cells was independent of the antigen specificity of activated T cells. The findings have important implications for our understanding of the regulatory mechanism induced by T cell vaccination.

Autoimmunity↗
PubMed2000

Magnetic resonance imaging measurements of bone density and cross-sectional geometry.

Magnetic resonance imaging (MRI) is commonly used in the assessment of the musculoskeletal system and associated pathology. The ability of MRI to measure the signals from water and lipid protons enables quantitative measurements of bone porosity. The goal of this investigation was to demonstrate that the density and cross-sectional geometry of whole bones can be noninvasively measured using MRI. Ten trabecular specimens cored from whale vertebrae were used to compare apparent bone density measured directly, and using a quantitative MRI algorithm. Bone density and several cross-sectional geometric properties were also measured using MRI in the distal tibia of 14 volunteers. The MRI measurements were compared with measurements made using quantitative-computed tomography (QCT). A proton density sequence was used for all MRI studies. A porosity phantom was included in the MRI examinations and used to convert the MRI signal intensity to bone volume fraction. Bone density and cross-sectional bone geometry were calculated from the bone volume fractions by assuming constant tissue properties. The apparent density of trabecular bone cores measured directly and using quantitative MRI were linearly related (r(2) = 0.959; P < 0. 01). A strong linear relation also existed between MRI and QCT measurements of ash density (r(2) = 0.923; P < 0.01) and cross-sectional geometric properties (r(2) = 0.976-0.992; P < 0.01). MRI data can be used to measure bone density and cross-sectional geometry of whole bones if a proton density sequence is used to homogenize differences in marrow composition and a porosity phantom is used for slice-specific volume fraction calibration.

Adult↗
PubMed2000

Ventricular volume, chamber stiffness, and function after anteroapical aneurysm plication in the sheep.

OBJECTIVE: The success of left ventricular aneurysm plication depends on how the procedure affects both end-systolic elastance and diastolic compliance and how those changes affect ventricular function (stroke work/end-diastolic volume [PRSW] and stroke volume/end-diastolic pressure [Starling] relationships). METHODS: Five male Dorsett sheep were surgically instrumented with coronary artery snares, an inferior vena caval occluder, and an ascending aortic ultrasonic flow probe. One week later an anteroapical myocardial infarction was produced by tightening the coronary snares. Ten weeks after myocardial infarction, the left ventricular aneurysm was plicated. Absolute left ventricular volume was measured by long-axis transdiaphragmatic echocardiography, and relative changes in left ventricular volume were measured with a conductance catheter. End-systolic elastance, diastolic compliance, PRSW, and Starling relationships were measured immediately before myocardial infarction, 10 weeks after myocardial infarction (immediately before plication), and immediately after and 6 weeks after aneurysm plication. RESULTS: After plication, end-diastolic and end-systolic left ventricular volumes return to preinfarction values. The slopes of end-systolic elastance, diastolic compliance, and PRSW decrease 10 weeks after myocardial infarction, increase with aneurysm plication, and then decrease 6 weeks after aneurysm plication. The Starling relationship undergoes a downward parallel shift with aneurysm plication. CONCLUSION: Aneurysm plication abruptly decreases left ventricular volume and diastolic compliance, increases end-systolic elastance and PRSW, but decreases the Starling relationship. The net effect on left ventricular function is mixed. Furthermore, left ventricular remodeling 6 weeks after aneurysm plication causes left ventricular volume, end-systolic elastance, diastolic compliance, PRSW, and the Starling relationship to return to preplication values.

Animals↗
PubMed2000

Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes.

Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.

Brain Injuries↗
PubMed2000

Is narcolepsy a REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans.

Narcolepsy is a chronic sleep disorder marked by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Since the discovery of sleep onset REM periods (SOREMPs) in narcoleptic patients, narcolepsy has often been regarded as a disorder of REM sleep generation: REM sleep intrudes in active wake or at sleep onset, resulting in cataplexy, sleep paralysis, or hypnagogic hallucinations. However, this hypothesis has not been experimentally verified. In the current study, we characterized the sleep abnormalities of genetically narcoleptic-cataplectic Dobermans, a naturally occurring animal model of narcolepsy, in order to verify this concept. Multiple sleep latency tests during the daytime revealed that narcoleptic Dobermans exhibit a shorter sleep latency and a higher frequency of SOREMPs, compared to control Dobermans. The total amount of time spent in wake and sleep during the daytime is not altered in narcoleptic dogs, but their wake and sleep patterns are fragmented, and state transitions into and from wake and other sleep stages are altered. A clear 30 min REM sleep cyclicity exists in both narcoleptic and control dogs, suggesting that generation of the ultradian rhythm of REM sleep is not altered in narcoleptics. In contrast, cataplexy displays no cyclicity and can be elicited in narcoleptic animals anytime with emotional stimulation and displays no cyclicity. Stimulation of a cholinoceptive site in the basal forebrain induces a long-lasting attack of cataplexy in narcoleptic dogs; however, bursts of rapid eye movements during this state still occur with a 30 min cyclicity. Sites and mechanisms for triggering cataplexy may therefore be different from those for REM sleep. Cataplexy and a dysfunction in the maintenance of vigilance states, but not abnormal REM sleep generation, may therefore be central to narcolepsy.

Animals↗
PubMed2000

Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy.

The effects on cataplexy and daytime sleep of acute and chronic oral administration of CG-3703, a potent TRH analog were assessed in canine narcolepsy. CG-3703 was found to be orally active and to reduce cataplexy (0.25 to 16 mg/kg) and sleep (8 and 16 mg/kg) in a dose-dependent manner. Two-week oral administration of CG-3703 (16 mg/kg) significantly reduced cataplexy and daytime sleep. The anticataplectic effects of CG-3703 were not associated with changes in general behavior, heart rate, blood pressure, rectal temperature, blood chemistry and thyroid function. Although drug tolerance for the effects on cataplexy and sleep were observed during the second week of chronic drug administration, therapeutic efficacy on cataplexy was improved with individual dose adjustment (final dose range: 16 to 28 mg/kg, p.o.). These results suggest that TRH analogs could be a promising new form of treatment for human narcolepsy.

Animals↗
PubMed2000

Rehabilitation of executive functioning: an experimental-clinical validation of goal management training.

Two studies assessed the effects of a training procedure (Goal Management Training, GMT), derived from Duncan's theory of goal neglect, on disorganized behavior following TBI. In Study 1, patients with traumatic brain injury (TBI) were randomly assigned to brief trials of GMT or motor skills training. GMT, but not motor skills training, was associated with significant gains on everyday paper-and-pencil tasks designed to mimic tasks that are problematic for patients with goal neglect. In Study 2, GMT was applied in a postencephalitic patient seeking to improve her meal-preparation abilities. Both naturalistic observation and self-report measures revealed improved meal preparation performance following GMT. These studies provide both experimental and clinical support for the efficacy of GMT toward the treatment of executive functioning deficits that compromise independence in patients with brain damage.

Adult↗
PubMed2000

New acetylenic compounds from the stony coral Montipora sp.

Six new acetylenic compounds (1-6) with cytotoxic activities against human solid tumor cell lines (SK-OV-3, SK-MEL-2, XF498, and HCT15) have been isolated from the stony coral Montipora sp. Structures of the compounds 1-6 were elucidated based on analysis of the NMR and MS data.

Animals↗
PubMed2000

Radio frequency heating of chronic ovine infarct leads to sustained infarct area and ventricular volume reduction.

OBJECTIVE: Myocardial infarct expansion and subsequent left ventricular remodeling are associated with increased incidence of congestive failure and mortality. Collagen is known to denature and contract when heated above 65 degrees C. We therefore tested the hypothesis that radio frequency heating of myocardial infarct tissue with application of a restraining patch causes a sustained reduction in myocardial infarct area and left ventricular volume. METHODS: Thirteen male Dorset sheep underwent surgical coronary artery ligation. At least 14 weeks later, animals were randomized to either radio frequency infarct heating (95 degrees C) with application of a restraining patch or a sham operation. Before treatment, after treatment, and 10 weeks later, left ventricular volume was measured with transdiaphragmatic echocardiography and myocardial infarct area was measured with an array of sonomicrometry crystals. RESULTS: Radio frequency infarct heating causes an acute decrease of 34% (-215 +/- 82 mm(2); P =.0002) in infarct area at end-diastole that is maintained at 10 weeks (-144 +/- 79 mm(2); P =.0002). Radio frequency infarct heating causes a downward trend in end-diastolic left ventricular volume measured by echocardiography of 20% (-15.7 +/- 6.3 mL; P = no significant difference) and end-systolic left ventricular volume of 32% (-17.1 +/- 9.8 mL; P =.09), which are significantly decreased at 10 weeks (-13.6 +/- 22.3 mL; P =.007 and -15.3 +/- 21.9 mL; P =.008, respectively). Radio frequency infarct heating causes an acute improvement in systolic function (P <.001), a sustained increase in left ventricular ejection fraction (+0.11%; P =.06), and preserved stroke volume. CONCLUSION: Radio frequency heating of chronic left ventricular myocardial infarct causes a sustained reduction in infarct area and left ventricular volume. This technique may beneficially reverse infarct expansion and left ventricular remodeling after myocardial infarction.

Animals↗
PubMed2000

Aberrant T cell migration toward RANTES and MIP-1 alpha in patients with multiple sclerosis. Overexpression of chemokine receptor CCR5.

Trafficking of inflammatory T cells into the central nervous system (CNS) plays an important role in the pathogenesis of multiple sclerosis. The directional migratory ability of peripheral T cells is associated with interactions of chemokines with their receptors expressed on T cells. In this study, transmigration of peripheral T cells toward a panel of chemokines was examined in patients with multiple sclerosis and healthy individuals using Boyden chemotactic transwells. A significantly increased migratory rate preferentially toward RANTES and MIP-1alpha, but not other chemokines, was found in T cells obtained from multiple sclerosis patients as opposed to healthy individuals (P: < 0.001). The migratory T-cell populations represented predominantly Th1/Th0 cells while non-migratory T cells were enriched for Th2-like cells. The study demonstrated further that aberrant migration of multiple sclerosis-derived T cells toward RANTES and MIP-1 alpha resulted from overexpression of their receptors (CCR5) and could be blocked by anti-CCR5 antibodies. These findings have important implications for our understanding of the mechanism underlying aberrant T cell trafficking in multiple sclerosis.

Cell Movement↗