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Biomedical subjects

J Kwon

Publications and source records attributed to J Kwon.

At least 37 records · Page 2Linked to original sources

Elevated serum vascular endothelial growth factor in children and young adults with Crohn's disease.

Vascular endothelial growth factor (VEGF) is a cytokine released by fibroblasts, epithelial cells, and leukocytes that potentiates vascular permeability and growth of new capillaries. Because of these multiple effects, VEGF has been postulated to play a role in the pathogenesis of autoimmune disease, as well as in wound healing. We hypothesized that VEGF was potentially important in mediating the vascular permeability and angiogenesis seen in Crohn's disease, and therefore that VEGF would be increased in the serum of children with Crohn's disease. Serum was obtained from 73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls. VEGF levels were measured by enzyme-linked immunosorbent assay. Mean VEGF levels were significantly higher in patients with Crohn's disease (436.4 +/- 37.2 pg/ml) than in ulcerative colitis (306 +/- 41.1 pg/ml) or control (167.8 +/- 29.6 pg/ml) patients. Serum VEGF also correlated significantly with disease activity, being elevated in patients with moderate/severe Crohn's disease and ulcerative colitis. We conclude that serum VEGF is released by inflamed tissues in children with Crohn's disease. This multifunctional cytokine could promote inflammation by increasing vascular permeability or promote wound healing by mediating capillary growth.

Adolescent↗

IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation.

Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 -/- mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 -/- mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 -/- mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 -/- mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.

Animals↗

B lymphocyte antigen D8/17 and repetitive behaviors in autism.

OBJECTIVE: Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in rheumatic fever, Sydenham's chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome with repetitive behaviors. The authors examined the rate of D8/17 expression in children with autism and its correlation with severity of repetitive behaviors. METHOD: Blood samples from 18 patients with autism and 14 comparable medically ill children were evaluated for percentage of D8/17-positive B cells by immunofluorescence and for streptococcal antibodies. Severity of repetitive behaviors was also determined. RESULTS: The frequency of individuals with > or =11% D8/17-positive cells was significantly higher in the autistic patients (78%) than the comparison subjects (21%), severity of repetitive behaviors significantly correlated with D8/17 expression, and D8/17-positive patients had significantly higher compulsion scores than D8/17-negative patients. CONCLUSIONS: D8/17 expression is high in patients with autism and may serve as a marker for compulsion severity within autism.

Adolescent↗

Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects.

Eighteen patients with social phobia, 21 normal control subjects, and 42 obsessive-compulsive disorder (OCD) control subjects were challenged with single doses of the partial serotonin agonist oral m-chlorophenylpiperazine (m-CPP) and placebo. Social phobics did not significantly differ from normal or OCD control subjects in prolactin response to m-CPP. There was a significant difference across groups in cortisol response to m-CPP, such that female social phobics had more robust cortisol responses to the m-CPP challenge. Pairwise comparisons only reached trend significance, perhaps due to the relatively small sample sizes. This study offers preliminary evidence for serotonin dysfunction in social phobia, particularly in female social phobics, but needs to be replicated in a larger sample size.

Adult↗

Cloning, characterization, and expression of the CIP2 gene induced under cadmium stress in Candida sp.

We isolated, sequenced, and expressed a cadmium-induced gene, CIP2, that specifically hybridizes to a mRNA of approximately 950 nucleotides. The CIP2 mRNA was barely present in normal Candida cells, but accumulated at higher levels in cadmium-treated cells. Other heavy metals such as copper, mercury, lead, and manganese had no effect on the expression of the CIP2 gene. CIP2 contains an open reading frame encoding a protein of 203 amino acids. This gene was also activated by an oxidant, diamide. Our results suggest that CIP2 may play a crucial role in the specific cellular response to oxidative stress evolved by the cadmium treatment.

Amino Acid Sequence↗

Utility of three-dimensional ultrasound Doppler flow reconstruction of the proximal jet to quantify effective orifice area: in vitro steady and pulsatile flow studies.

We examined the utility of three-dimensional (3D) reconstruction of two-dimensional color Doppler images of the proximal jet to quantify the effective area of an orifice in an in vitro model. Steady and pulsatile flows were directed through various orifices; orifice vena contracta areas were quantified with laser flow visualization, thus providing gold standard effective orifice areas. Three-dimensional areas followed vena contracta areas well, although variations in color Doppler gain and 3D gray levels for thresholding produced significant changes in reconstructed images. These variations were minimized by using minimum color gain and 50% gray level threshold. At these settings, 3D areas still overestimated vena contracta areas by approximately 25% because of the poor lateral resolution of the color Doppler system, which caused bleeding of the flow signal past the edges of the proximal jet. Nevertheless, 3D flow images provided a superior format for qualitative and quantitative appreciation of proximal jet shape and dimensions.

Heart Valve Diseases↗

Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1.

B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding protein, stimulates V(D)J cleavage of nucleosomal templates. This HMG1 stimulation is differentially affected by the rotational or translational positioning of the recombination signal sequence on the histone octamer, with cleavage of the 12 bp spacer RSS showing sensitivity to rotational position and the 23 bp spacer RSS affected by its displacement from the dyad. These results suggest that V(D)J recombination can be modulated by controlling substrate accessibility and cleavage at the level of an individual nucleosome.

Base Pairing↗

Fos-immunoreactive responses in inferior colliculi of rats with experimental audiogenic seizure susceptibility.

Audiogenic seizure (AGS) susceptibility is a reflex epilepsy of rodents in which acoustic stimulation evokes wild running attacks and subsequent convulsions. Susceptibility can be induced in non-susceptible strains by treatments causing transient or permanent hearing losses as long as these occur during the neonatal period. The defect which is the basis of susceptibility has been proposed to be a failure of developmental organization of inferior colliculus (IC) into frequency selective zones. That is, high frequency stimuli evoke responses in broader arrays of neurons in ICs of susceptible rats than in those of neonatally untreated (non-susceptible) controls. Nonetheless, this observation has been made only in rats in which susceptibility was induced by exposure to intense noise on postnatal day (PND) 14. By contrast, the present study examines whether unusually broad topographic responses are also characteristic in ICs of rats made susceptible by the neonatal administration of low doses of the ototoxic antibiotic, kanamycin (KM). Patterns of Fos-like immunoreactivity (Foslir) induced by seizures or pure tone stimuli were compared in ICs of adult Wistar rats which neonatally had been (a) sham-treated; (b) noise-exposed on PND 14; or (c) injected on PNDs 9-12 with 100 mg/kg KM. It was found that sound-triggered seizures in the two experimental groups resulted in induction of Foslir primarily within cortical areas of IC. By contrast, pure tones evoked unusually broad responses in the central nucleus of ICs of both susceptible groups but not in those of controls. Additionally, in the KM-treated rats, the range of frequencies evoking abnormal responses extended one octave lower than was characteristic of noise-exposed rats. The earlier schedule of treatments in the KM model may account for this inasmuch as low frequency response domains undergo development at younger ages. The similarity of results in the two models suggests failure of development of frequency selective fields in IC is indeed the common basis of experimentally induced susceptibility to sound-triggered seizures.

Acoustic Stimulation↗

Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in intraepidermal neutrophilic IgA dermatosis.

Intraepidermal neutrophilic IgA dermatosis, a rare skin disease entity manifested with blisters and pustules clinically and lower epidermal blister, acantholysis, and neutrophilic infiltration pathologically, was first reported in 1985. Although the disease is characterized by IgA autoantibodies targeting the epithelial cell surface component, the target antigen has not been determined. We investigated a patient with this disease by histopathology, direct and indirect immunofluorescence, immunoblotting, and immunoadsorption studies. The pustular lesion was characterized by blister at the lower epidermis, acantholysis, and neutrophilic infiltration. Nonsecretory IgA1 subclass autoantibodies targeting the lower epithelial cell surfaces were detected in the patient's skin and serum. The patient's IgA autoantibodies labeled a recombinant desmosomal protein desmoglein 3 on immunoblotting and the immunolabeling of epithelial cell surfaces was eliminated by preadsorption with desmoglein 3. Thus, desmoglein 3 is identified as a target antigen in intraepidermal neutrophilic IgA dermatosis. The ability of IgA1 autoantibodies to bind neutrophils may be responsible for the prominent neutrophilic infiltration observed histopathologically and for the pustular lesions observed clinically.

Aged↗

A 3' cis-acting element is involved in tumor necrosis factor-alpha gene expression in astrocytes.

Tumor necrosis factor-alpha (TNF-alpha) contributes to demyelinating diseases in the central nervous system. Astrocytes, the major glial cells in the CNS, do not constitutively express TNF-alpha, but the TNF-alpha gene is transcriptionally activated in response to a variety of stimuli, including TNF-alpha itself. Because of the importance of TNF-alpha in the CNS, we examined the mechanisms underlying transcriptional regulation of the TNF-alpha gene in astrocytes. In transient transfection assays, a plasmid construct containing 1.3 kilobase pairs (kb) of 5' flanking sequence of the rat TNF-alpha gene showed high basal activity that could not be further enhanced by TNF-alpha stimulation. A "marked" 10-kb TNF-alpha gene construct, which contains the whole TNF-beta gene with 1.2 kb of 5' flanking sequence, 1.1 kb of intergenic sequence, and the whole TNF-alpha gene with 3 kb of 3' flanking sequence, was able to respond to TNF-alpha stimulation. Analysis of a series of 5' and 3' deletion constructs of the marked TNF-alpha genes demonstrated that upstream sequence elements such as NF-kappaB are not required for TNF-alpha induction and that TNF-alpha responsive elements are located in the 3' flanking region of the TNF-alpha gene. We also found that a TNF-alpha-inducible DNase I-hypersensitive (DH) site is present in this 3' region whose deletion abolishes TNF-alpha inducibility of the marked TNF-alpha gene. Electrophoresis mobility shift assays showed that TNF-alpha-inducible nuclear proteins, consisting of p50 and p65 NF-kappaB proteins, specifically bind to two consecutive NF-kappaB binding sites within the 3' DH site. These results indicate that TNF-alpha-induced TNF-alpha gene expression in astrocytes involves p50 and p65 NF-kappaB proteins binding to downstream NF-kappaB sites and concomitant modulation of the chromatin structure.

Animals↗

Digital particle image velocimetry (DPIV) measurements of the velocity profiles through bileaflet mechanical valves: in vitro steady.

Although velocity profiles downstream of mechanical valves have been measured in-vitro using Laser Doppler Anemometry (LDA), these studies have not measured velocities in the immediate proximity of the leaflets since the LDA technique prevents velocities from being measured in the immediate vicinity of any structure. Laser based Digital Particle Image Velocimetry (DPIV) is a new technique that allows for accurate measurement of an entire two-dimensional velocity field with no beam angulation. DPIV was used to measure two-component velocity vectors immediately proximal and distal to a 25 mm bileaflet mechanical valve (St. Jude) mounted in a transparent steady flow in-vitro model. Measurements of flow similar in Reynolds number (Re) to mitral inflow (Re = 2000-4000) showed clear hemi-elliptical isovelocity convergence zones proximal to each of the three orifices. DPIV measurements of flow distal to the orifice revealed clear vortex rollups generated from the internal ring of the valve with separate velocity profiles immediately distal to the leaflets. These studies prove the feasibility of the DPIV technique to provide accurate velocity measurements of flow profiles through mechanical valves.

Blood Flow Velocity↗

Abdominal fetal EKG noise removal.

UNLABELLED: Accurate detection of the fetal heart signal (FEKG) early during pregnancy enhances the physician's ability to diagnose possible congenital cardiac defects. However, FEKG acquisition is hampered by excessive noise contamination from the maternal ekg (MEKG) and uterine muscular contraction. METHODS: A new computerized system was developed to record FEKG and MEKG signals from multiple leads. Removal of noise sources was performed using a blanking procedure, which selectively removes MEKG signal, and signal averaging procedure. RESULTS: 20 subjects showed 11 positive and 9 negative findings of FEKG. Blanking out the maternal QRS complex also removed part of the fetal signal making it unusable. The signal averaging procedure applied to 10-20 maternal QRS's still produced false positive fetal QRS signals. Two of the negative results were from biological noise with QRS type waveform and frequency of 8.75Hz. The depth of the fetus (5-10 cm) and period of gestation (17-40 weeks) had no bearing on finding FEKG. CONCLUSION: Blanking is not an optimal method for maternal noise removal because of removal of some fetal QRS complex. Averaging is a viable method except in cases where the peak fetal signals are less than 75 micro Volts. Preliminary studies using an adaptive algorithm with the maternal chest EKG as reference promises to be a better solution for maternal EKG removal.

Electrocardiography↗

When combining intrinsic motivations undermines interest: a test of activity engagement theory.

Three studies with elementary school children demonstrated that combining reading with coloring pictures can undermine children's later interest in reading, while also reducing their interest in coloring. Undermining is maximized when an activity is identified as secondary during the initial engagement, but other conditions must also be met as specified by activity engagement theory (Higgins & Trope, 1990): (a) the multiple input activities must be separately identified and considered simultaneously as alternatives, (b) the activity identified as primary during initial engagement must not be perceived as very attractive, and (c) the responses connected to an identified activity during the initial engagement must be activated subsequently. Conditions for enhancing interest in an activity are also considered.

Child↗

Differential modulation of astrocyte cytokine gene expression by TGF-beta.

In this study, we demonstrate that TGF-beta inhibits TNF-alpha expression, and induces/enhances IL-6 expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta alone had no effect on TNF-alpha mRNA or protein expression; however, TGF-beta suppressed induction of TNF-alpha expression by three different stimuli (IFN-gamma/LPS, IFN-gamma/IL-1 beta, TNF-alpha) at both the protein and mRNA level. The extent of TGF-beta-mediated inhibition was greatest when astrocytes were pretreated with TGF-beta for 6 to 24 h, then exposed to the inducing stimuli. Inhibition of TNF-alpha mRNA steady-state levels by TGF-beta was a result of inhibition of TNF-alpha gene transcription, rather than degradation of the TNF-alpha message. In contrast, TGF-beta alone induced expression of IL-6 by astrocytes and synergized with two other cytokines, IL-1 beta and TNF-alpha, for enhanced IL-6 expression. TGF-beta-induced/enhanced IL-6 expression was mediated by transcriptional activation of the IL-6 gene. These results indicate that TGF-beta is an important regulator of cytokine production by astrocytes under inflammatory conditions in the brain.

Animals↗