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Biomedical subjects

L Kim

Publications and source records attributed to L Kim.

At least 37 records · Page 2Linked to original sources

Molecular characterization and pathogenesis of transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCV) field isolates co-circulating in a swine herd.

TGEV replicates in intestinal enterocytes and causes diarrhea in young pigs. PRCV, a spike (S) gene deletion mutant of TGEV with an altered respiratory tissue tropism, causes mild or subclinical respiratory infections. Comparisons of TGEV and PRCV strains suggest that tropism and pathogenicity are influenced by the S gene and ORF3, respectively. Recently, outbreaks of TGE of reduced virulence were reported in the field. We investigated a similar suspect TGEV outbreak of reduced virulence in nursery pigs from a swine herd in the Midwest. A TGEV strain (BW021898B) was isolated in swine testicular cells from gut contents of a diarrheic pig and three PRCV strains (BW126, BW154, BW155) were isolated from nasal swabs from normal TGEV-seronegative sentinel pigs in contact with the diarrheic pigs. Sequence analysis of the TGEV isolate in the partial S gene and ORF3/3a and ORF3-1/3b revealed high homology with enteropathogenic TGEV strains. Gnotobiotic pig inoculation and histopathological results revealed that this TGEV isolate retained virulence even though in the field outbreak the diarrheal disease was of reduced severity. Sequence analysis of the S gene deletion region of the three PRCV isolates revealed identical deletions between nt 105-752, which differ from deletions previously reported among PRCV strains. The three PRCV isolates had variable sequence changes in ORF 3/3a and ORF 3-1/3b, affecting the ORF size and amino acid sequence. Thus, sequence analysis and pathogenicity studies indicate that this TGEV isolate resembles other enteropathogenic TGEV strains. Therefore, the reduced severity of TGE observed in this herd may be due to the ongoing PRCV infections, which induce antibodies cross-reactive with TGEV and result in decreased disease severity. The results outlined in this study highlight the need to monitor the molecular epidemiology of TGEV/PRCV strains with sensitive differential diagnostic assays, followed by sequence analysis of the critical regions to identify changes and pathogenicity studies to confirm the disease potential of the TGEV isolates.

Amino Acid Sequence↗

GSK3, a master switch regulating cell-fate specification and tumorigenesis.

Until recently, protein kinase GSK3 (glycogen synthase kinase 3), an essential component for cell-fate specification, had been considered a constitutively activated enzyme subject to developmentally regulated inhibition through hierarchical, linear signaling paths. Data from various systems now indicate more complex scenarios involving activating as well as inhibiting circuits, and the differential formation of multi-protein complexes that antagonistically affect GSK3 function.

Animals↗

Light-induced nuclear import of phytochrome-A:GFP fusion proteins is differentially regulated in transgenic tobacco and Arabidopsis.

Phytochromes (phy) are a family of photoreceptors that control various aspects of light-dependent plant development. Phytochrome A (phyA) is responsible for the very low fluence response (VLFR) under inductive light conditions and for the high irradiance response (HIR) under continuous far-red light. We have recently shown that nuclear import of rice phyA:GFP is regulated by VLFR in transgenic tobacco. The import is preceded by very fast, light-induced formation of sequestered areas of phyA:GFP in the cytosol. Here we report that expression of the Arabidopsis phyA:GFP fusion protein in phyA-deficient Arabidopsis plants complements the mutant phenotype. In these transgenic Arabidopsis lines, both light-dependent cytosolic formation of sequestered areas of the phyA:GFP as well as VLFR or HIR-mediated nuclear import of the fusion protein was observed. By contrast, light-dependent nuclear import of the same fusion protein was induced only by continuous far-red light (HIR) but not by pulses of far-red light (VLFR) in transgenic tobacco. These results demonstrate that photoregulation of intracellular partitioning of the Arabidopsis phyA:GFP differs significantly in different genetic backgrounds.

Arabidopsis↗

Tailgut cyst in a neonate.

Tailgut cyst is a rare lesion of developmental origin located in the retrorectal space, which usually presents as a multilocular cystic mass. It is usually found in adults, and neonatal cases are extremely rare. The authors report a tailgut cyst in a neonate that was found by prenatal ultrasonogram, which was like a teratoma in gross appearance.

Cysts↗

Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression.

Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus. We have investigated the signaling mechanism of CSF-1-induced D2 expression. Analyses of CSF-1 receptor autophosphorylation mutants show that, although certain individual mutation has a partial inhibitory effect, only multiple combined mutations completely block induction of D2 in response to CSF-1. We report that at least three parallel pathways, the Src pathway, the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and the c-myc pathway, are involved. Induction of D2 is partially inhibited in Src(-/-) bone marrow-derived macrophages and by Src inhibitor PP1 and is enhanced in v-Src-overexpressing cells. Activation of myc's transactivating activity selectively induces D2 but not D1. Blockade of c-myc expression partially blocks CSF-1-induced D2 expression. Complete inhibition of the MEK/ERK pathway causes 50% decrease of D2 expression. Finally, simultaneous inhibition of Src, MEK activation, and c-myc expression additively blocks CSF-1-induced D2 expression. This study indicates that multiple signaling pathways are involved in full induction of a single gene, and this finding may also apply broadly to other growth factor-inducible genes.

Animals↗

Three-year follow-up of women with the sole diagnosis of depressive personality disorder: subsequent development of dysthymia and major depression.

OBJECTIVE: The authors sought to determine whether subjects with the sole diagnosis of depressive personality disorder are at higher risk for developing dysthymia and major depression than are healthy comparison subjects. METHOD: Eighty-five women with depressive personality disorder who had no comorbid axis I or axis II disorders and 85 age-matched healthy comparison women were initially recruited and reinterviewed 3 years later to evaluate the cumulative incidence rate of dysthymia and major depression. RESULTS: At the 3-year follow-up assessment, the women with depressive personality disorder had a significantly greater odds ratio for developing dysthymia than did the healthy comparison women. The difference in odds ratios for the development of major depression between women with and without depressive personality disorder did not reach statistical significance. CONCLUSIONS: The present study, the first to determine the subsequent development of dysthymia and major depression in subjects with the sole diagnosis of depressive personality disorder, found that subjects with depressive personality disorder had a greater risk of developing dysthymia than did healthy comparison subjects at 3-year follow-up. Findings of the current study also suggest that depressive personality disorder may mediate the effects of a family history of axis I unipolar mood disorders.

Adult↗

Development of a reverse transcription-nested polymerase chain reaction assay for differential diagnosis of transmissible gastroenteritis virus and porcine respiratory coronavirus from feces and nasal swabs of infected pigs.

Transmissible gastroenteritis virus (TGEV), a coronavirus, replicates in intestinal enterocytes and causes diarrhea in young pigs. Porcine respiratory coronavirus (PRCV), a spike (S) gene natural deletion mutant of TGEV, has a respiratory tissue tropism and causes mild or subclinical respiratory infections. Conventional antigen-based diagnostic tests fail to differentiate TGEV and PRCV, and a blocking ELISA test to serologically differentiate TGEV/PRCV-infected pigs is conducted on convalescent serum retrospectively after disease outbreaks. A reverse transcription (RT)-nested polymerase chain reaction (PCR) with primers targeted to the S gene deletion region to differentiate TGEV/PRCV was developed. The specificity of the RT-nested PCR was confirmed with reference and recent field strains of TGEV/PRCV, and its sensitivity was analyzed by testing nasal and fecal samples collected from pigs at various days postinoculation (DPI) with TGEV or PRCV. Specific PCR products for TGEV/PRCV were detected only with the homologous reference or field coronaviruses and for 10-14 DPI of pigs with TGEV (feces) or PRCV (nasal samples). The RT-nested PCR assay was more sensitive than antigen-based assays on the basis of duration of virus detection in experimentally infected pigs and was directly applicable to nasal as well as fecal specimens from the field.

Animals↗

Evaluation of dental erosion in patients with gastroesophageal reflux disease.

STATEMENT OF PROBLEM: The cause of dental erosion may be difficult to establish because of its many presentations. Determination of the cause is an important aspect of diagnosis before extensive prosthodontic rehabilitation. PURPOSE: This cross-sectional study evaluated the association between loss of tooth structure as a result of dental erosion and gastroesophageal reflux disease. MATERIAL AND METHODS: Twenty consecutive adult dentate subjects referred to the Division of Gastroenterology for investigation of gastroesophageal tract disease were also evaluated for signs of dental erosion. All subjects underwent a dental evaluation that included a patient history to determine potential etiologic factors responsible for dental erosion. Subjects were examined clinically to quantify loss of tooth structure using a Tooth Wear Index (TWI). Endoscopic examination and 24-hour pH manometry were carried out to determine which subjects met the criteria for gastroesophageal reflux disease (GERD). Scores for maxillary versus mandibular dentition and anterior versus posterior dentition were also compared. Data were analyzed with the Kruskal-Wallis test (P =.004). RESULTS: Ten subjects were diagnosed with GERD and 10 subjects had manometry scores below the level indicating GERD. Overall, subjects diagnosed with GERD had significantly higher TWI scores compared with control subjects (mean difference = 0.6554; P =.004). GERD subjects had higher TWI scores in all quadrants, except in the mandibular anterior region where there was no difference. CONCLUSION: The results indicated that a relationship exists between loss of tooth structure, as measured by the TWI index, and the occurrence of GERD in this group of subjects.

Adolescent↗

Integrating specialized application systems into hospital information systems--obstacles and factors for success.

Hospital information systems are often huge and heterogeneous systems. To support physicians with their daily clinical work, application systems are developed which are dedicated to particular medical fields or tasks and which have to be integrated into the hospital information system. The integration process is quite complicated, because it makes the information system's infrastructure even more heterogeneous. We developed an application system for documentation and therapy planning in pediatric oncology (DOSPO) and we started to introduce it into the Department of Pediatric Oncology of Heidelberg University Hospital. The fact that DOSPO is developed as a universal system for nationwide use made the integration process more difficult. In any case, the introduction of specialized application systems has to be planned systematically in advance, regarding the prevailing information system's infrastructure, available resources and established processes. To simplify the integration process comprehensive electronic patient records for the future should be designed in a way that they can be enhanced easily by new clinical functions.

Child↗

The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification.

Inhibition of GSK3 by 7-TM Wnt/wg receptor signaling is critical for specifying embryonic cell fate patterns. In Dictyostelium, the 7-TM cAMP receptors regulate GSK3 by parallel, antagonistic pathways to establish a developmental body plan. We describe here a novel tyrosine kinase, ZAK1, downstream of 7-TM cAMP receptor signaling that is required for GSK3 activation during development. zak1-nulls have reduced GSK3 activity and are defective in GSK3-regulated developmental pathways. Moreover, recombinant ZAK1 phosphorylates and activates GSK3 in vitro. We propose that ZAK1 is a positive regulator of GSK3 activity required for cell pattern formation in Dictyostelium and speculate that similar mechanisms exist to antagonize Wnt/wg signaling for metazoan cell fate specification.

Amino Acid Sequence↗

Active immunity and T-cell populations in pigs intraperitoneally inoculated with baculovirus-expressed transmissible gastroenteritis virus structural proteins.

The intraperitoneal inoculation of pigs with baculovirus-expressed transmissible gastroenteritis virus (TGEV) structural proteins (S, N, M) in conjunction with thermolabile Escherichia coli mutant toxin (LT-R192G) in incomplete Freund's adjuvant (IFA) was tested in an attempt to elicit active immunity to TGEV in gut-associated lymphoid tissues (GALT). Four groups of 63 (1-5-week-old) suckling, TGEV-seronegative pigs were used to assess the efficacy of the recombinant protein vaccine (group 3) in comparison with sham (group 1), commercial vaccine (group 2), and virulent TGEV Miller-strain-inoculated pigs (group 4). The TGEV-specific mucosal and systemic immune responses were measured after in vivo and in vitro stimulation with TGEV-antigens. The major T-cell subset distribution was analyzed in vivo and in vitro after stimulation of mononuclear cells with TGEV (from mesenteric lymph nodes of group 3 inoculated with TGEV-recombinant proteins). Induction of active immunity was assessed by challenge of pigs with virulent TGEV at 27 days of age. Baculovirus-expressed TGEV proteins coadministered with LT-R192G in IFA induced mesenteric lymph node immune responses associated with IgA-antibodies to TGEV and partial protection against TGEV-challenge. The high titers of serum IgG- and virus-neutralizing-antibodies to TGEV in group 3 pigs most likely reflected the dose of TGEV S-protein administered. At the day of TGEV-challenge, the in vitro stimulation of mononuclear cells from the mesenteric lymph nodes of group 3 pigs with inactivated TGEV resulted in an increase in double positive (CD4+CD8+), natural killer (CD2+CD4-CD8+dim) and cytotoxic (CD2+CD4-CD8+bright) T-cell phenotypes, accompanied by increased expression of interleukin-2 receptor and a decrease of the null (CD2-CD4-CD8-/SW6+) cell phenotype.

Animals↗

Gamma interferon induces expression of Mad1 gene in macrophage, which inhibits colony-stimulating factor-1-dependent mitogenesis.

Gamma interferon (IFN-gamma) has long been known as an antiproliferative cytokine. The mechanism of its action, however, remains elusive. Monocytes and macrophages are primary targets of IFN-gamma. To understand the antiproliferative signaling of IFNgamma, we studied the effect of IFNgamma on expression of c-Myc, Mad1, Max, cyclin D1, and cyclin D2 genes in both a macrophage cell line and in primary bone marrow-derived macrophages (BMM) in response to colony-stimulating factor-1 (CSF-1). We found that whereas IFNgamma inhibits CSF-1-stimulated c-Myc gene expression, it induces Mad1 expression. Induction of Mad1 mRNA could be detected as early as 90 min following IFNgamma treatment and was maintained for at least 15 h. These results suggest that IFNgamma treatment could shift the Myc-Max complex to the Mad1-Max complex in cells. The levels of Max, cyclin D1, and cyclin D2, however, remained unchanged. Enforced ectopic expression of Mad1 in the cells results in inhibition of [3H]thymidine incorporation and proliferation in response to CSF-1. This study suggests a mechanism by which IFNgamma inhibits CSF-1-stimulated proliferation of macrophages, i.e., by elevating the Mad1 level in the cells.

Animals↗

Compliance with universal precautions among emergency department personnel caring for trauma patients.

STUDY OBJECTIVE: Emergency department personnel are at high risk of occupational infection with bloodborne pathogens. The objective of this study was to observe and analyze the use of barrier precautions among ED personnel caring for trauma patients. METHODS: This observational study used videotapes of trauma cases seen at an urban Level I trauma center. Study participants were ED and trauma team personnel. Trained observers scored breaks in the use of barrier precautions during the first 15 minutes of 88 videotaped Level I trauma cases. "Major" breaks were scored when ED personnel performed invasive procedures without gloves, mask, gown, and adequate eye protection. "Minor" breaks were scored when ED personnel were adjacent to a trauma patient (within 1 m) without wearing these items. RESULTS: We observed 1 or more major breaks in 33.6% of 304 invasive procedures. The most common major break was failure to wear a mask (32.2% of procedures), followed by inadequate eyewear (22.2%), no gown (5.6%), and no gloves (3.0%). We observed minor breaks during 55.5% of 752 patient encounters. Large and statistically significant variations were seen in use rates of barrier precautions among different groups of personnel; surgery residents were most likely to use precautions, whereas attending surgeons were least likely. CONCLUSION: Compliance with universal precautions is poor in this high-risk clinical setting. These data provide a baseline for measuring the effectiveness of interventions to improve compliance. Videotaped observations are a novel and effective tool in this setting.

Blood-Borne Pathogens↗

Light quality-dependent nuclear import of the plant photoreceptors phytochrome A and B

The phytochrome (phy) family of plant photoreceptors controls various aspects of photomorphogenesis. Overexpression of rice phyA-green fluorescent protein (GFP) and tobacco phyB-GFP fusion proteins in tobacco results in functional photoreceptors. phyA-GFP and phyB-GFP are localized in the cytosol of dark-adapted plants. In our experiments, red light treatment led to nuclear translocation of phyA-GFP and phyB-GFP, albeit with different kinetics. Red light-induced nuclear import of phyB-GFP, but not that of phyA-GFP, was inhibited by far-red light. Far-red light alone only induced nuclear translocation of phyA-GFP. These observations indicate that nuclear import of phyA-GFP is controlled by a very low fluence response, whereas translocation of phyB-GFP is regulated by a low fluence response of phytochrome. Thus, light-regulated nucleocytoplasmic partitioning of phyA and phyB is a major step in phytochrome signaling.

Journal Article↗

Characterization of MAP kinase and PKC isoform and effect of ACE inhibition in hypertrophy in vivo.

Protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation appear important in conferring hypertrophy in vitro. However, the response of PKC and MAP kinase to stimuli known to induce hypertrophy in vivo has not been determined. We recently demonstrated that pressure-overload hypertrophy induced a transiently transfected gene driven by an hypertrophy responsive enhancer (HRE) through a marked increase in binding activity of its interacting nuclear factor (HRF). These data suggested that the HRE/HRF could serve as a target for evaluating the signal transduction events responsible for hypertrophy in vivo. Accordingly, we characterized MAP kinase and PKC isoform activation, injected HRE driven reporter gene expression, and HRF binding activity in rat hearts subjected to ascending aortic clipping or sham operation in the presence of the angiotensin-converting enzyme (ACE) inhibitor fosinopril, hydralazine, or no treatment. Analyses showed that PKC-epsilon and MAP kinase were acutely activated following ascending aortic ligature and that fosinopril significantly inhibited but did not completely abrogate PKC-epsilon and MAP kinase activation. However, fosinopril completely prevented pressure overload-mediated induction of HRE containing constructs and obviated increased HRF binding activity. These results suggest a direct relationship between ACE activity and HRE/HRF-mediated gene activation and imply that PKC-epsilon and MAP kinase may be involved in transducing this signal.

Angiotensin-Converting Enzyme Inhibitors↗

Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea.

RNA, extracted from peripheral blood mononuclear cells (PBMC) obtained from 81 Korean psychiatric patients (39 with schizophrenia, 33 with bipolar affective disorders and nine with major depression), was analyzed for a 391-nucleotide, highly conserved region of the p24 protein-encoding ORF II of Borna disease virus (BDV), using nested reverse transcription-polymerase chain reaction (RT-PCR). BDV genomic RNA was not detected in PBMC from any of the 81 Korean psychiatric patients. These data do not support an etiologic association between BDV infection and neuropsychiatric disorders in humans.

Adult↗

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors.

OBJECT: In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema. METHODS: Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water. CONCLUSIONS: Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

Antineoplastic Agents, Hormonal↗