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Biomedical subjects

K Y Lee

Publications and source records attributed to K Y Lee.

At least 19 recordsLinked to original sources
PubMed2006

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer.

We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

Adenocarcinoma, Clear Cell↗
PubMed2006

Application of high-resolution radiochromic film dosimetry in verifying a small-field stereotactic radiosurgery plan.

A high-resolution radiochromic film dosimetry (Hr-RCFD) method has been applied to verify a small-field stereotactic radiosurgery (SRS) plan. This was done by exposing a RCF in a Perspex head phantom undergoing the same treatment plan as the patient. The dose distribution obtained by the Hr-RCFD was verified against that calculated by the stereotactic treatment planning system and the result was satisfactory. The Hr-RCFD method has been found to be an accurate and practical tool in verifying small-field SRS plans.

Dose-Response Relationship, Radiation↗
PubMed2006

Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

Antigens, CD↗
PubMed2006

Data linkage enables evaluation of long-term survival after intensive care.

Outcomes of intensive care are important to the patient and for assessment of benefit. Short-term outcomes after critical illness are well described, but less is known about long-term outcomes. This study describes the use of data linkage, combining intensive care unit (ICU) clinical data with administrative morbidity and mortality data, to assess long-term outcomes after treatment in ICU. The hospital-based cohort study was conducted in a 22-bed general ICU in a metropolitan teaching hospital. All patient admissions admitted to ICU from 1 January 1987 to 31 December 2002 were included. The prospective ICU clinical database with patient demographics, ICU diagnoses, severity of illness, daily assessment of organ failures and common daily treatments used was linked using probabilistic methods to the state-wide hospital morbidity and mortality databases to describe long-term survival. There were 26,019 ICU admissions (22,980 patients) with 25,972 records (99.8%) linked to a hospitalization event that included the index ICU admission. Unadjusted survival was 84.7% at 1 year decreasing progressively to 50.7% at 15 years. Age, type of admission, severity of illness (measured by Acute Physiologic and Chronic Health Evaluation (APACHE) II and the presence of organ failure), ICU length of stay, comorbidity (Chronic Health Evaluation and Charlson comorbidity index) and ICU admission diagnosis, were all associated with survival at 1, 3, 5, 10, and 15 year follow-up (P<0.001 at all time points). Linkage of clinical and administrative data provides a feasible method for ascertaining long-term survival after critical illness. Age, admission severity of illness, diagnosis and comorbidity influenced long-term unadjusted survival.

APACHE↗
PubMed2006

Steroid hormone regulation of Clca3 expression in the murine uterus.

Progesterone (P4) and its cognate receptor, the progesterone receptor (PGR), have important roles in the establishment and maintenance of pregnancy in the murine uterus. In previous studies, using high-density DNA microarray analysis, we identified a subset of genes whose expression is repressed by chronic P4-PGR activation in the uterus. The Clca3 gene is one of the genes whose expression is the most significantly downregulated by P4 and PGR. In the present study, we performed real-time RT-PCR and in situ hybridization to investigate the regulation of Clca3 by P4 and determine the pattern of expression of Clca3 in the uterus during early pregnancy. This analysis shows that Clca3 mRNA transcripts were detected in the luminal and glandular epithelium of the pseudopregnant uterus at day 0.5 and that the expression of Clca3 was not detected after day 3.5. P4 represses Clca3 mRNA synthesis in the luminal epithelial and glandular epithelial cells of the uterus in ovariectomized wild-type mice, but not in Pgr knockout (PRKO) mice. Conversely, estrogen (E2) induces Clca3 expression in the luminal epithelium and glandular epithelium, and this induction was repressed by P4 in the murine uterus. Analysis of the promoter region of Clca3 by in silico and transient transfection analysis in HEC-1A cells identified the regulation of Clca3 by estrogen receptor-alpha (ESR1) within the first 528 bp of 5'-flanking region of the Clca3 gene. Our studies identified Clca3 as a novel downregulated gene of PGR that is a direct target of E2 regulation.

Animals↗
PubMed2005

Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.

One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.

Animals↗
PubMed2005

Endocrine gland-derived vascular endothelial growth factor is expressed in human peri-implantation endometrium, but not in endometrial carcinoma.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is a newly identified angiogenic and permeability-enhancing factor, predominantly expressed in steroidogenic tissues. Recently, we found that EG-VEGF is also expressed in the normal peri-implantation endometrial samples from patients of reproductive ages (80%). Immunohistochemistry analysis showed that EG-VEGF is predominantly expressed in the glandular epithelial cells and its expression is dynamic during the menstrual cycle with a peak expression at the mid-luteal phase. We also found that EG-VEGF transcripts are up-regulated in all the peri-implantation endometrial samples from the patients after the ovulating dose of human chorionic gonadotropin in gonadotropin-stimulated cycles and patients receiving hormone replacement therapy. In in vitro endometrial cell culture, EG-VEGF mRNA was detected in endometrial cells only in the presence of steroids, suggesting that EG-VEGF expression is highly dependent on the steroid hormones. Subsequent expression analyses on the EG-VEGF receptors showed that hPK-R1 and hPK-R2 are differentially expressed in human endometrium, but show no significant correlation with the hormonal treatments. On the other hand, EG-VEGF transcript was rarely detected in the endometrial samples from the postmenopausal patients and patients with endometrial carcinoma. It may imply that EG-VEGF may only play a role in vascular function of peri-implantation endometrium, but is unlikely to be associated with the etiology of endometrial cancer development.

Cells, Cultured↗
PubMed2005

Post-natal changes of cyclin-dependent kinase 5 activator expression in the developing rat cerebellum.

cDNA of cyclin-dependent kinase 5 (Cdk5) was cloned based on its primary sequence homology to Cdc2 and Cdk2. Cdk5 requires the neuronal Cdk5 activators such as p35 or p39(nck5ai) (p39) for its activity. In this study, we examined post-natal changes in the p39 expression pattern during the development of the rat cerebellum. p39 began to express in somata and dendrites of Purkinje cells at post-natal day 3 (PD3). In particular, at PD12, parasagittal bands (stripes) with p39 immunoreactivity were weakly observed. At PD21, p39-immunoreactive stripes were developed when compared with the PD12 group. At this age stage, p39 immunoreactivity became weak in somata of Purkinje cells, not forming stripes. At PD28, a series of parasagittal bands were more distinct than those of the PD21 group, and p39 immunoreactivity disappeared in Purkinje cells, not forming p39 immunoreactive stripes. In the adults, p39 immunoreactivity in Purkinje cells was similar to that found in the PD28 group which showed that parasagittal bands were very narrow, and became progressively more slender. Therefore, we suggest that the post-natal changes of p39 expression in Purkinje cells in the cerebellum is an autonomous characteristic of Purkinje cells with a role of Cdk5 activators.

Animals↗
PubMed2005

Dual-peak dose measurement for radiochromic films by a newly developed spectral microdensitometer.

Radiochromic film (RCF) dosimetry is usually based on densitometric methods which use an analyzing light source of a fixed or a broad spectrum of wavelengths. These methods have not exploited the sensitivity of the dose response of the RCF otherwise attainable by using a light source with wavelengths peaked at the two absorption peaks in the absorption spectrum of the RCF. A new algorithm of dual-peak dose measurement for the RCF has been proposed in this paper to make use of these dual absorption peaks to achieve the maximum attainable sensitivity. This technique relies on the measurement of the transmittance of the RCF at the wavelength of the major and minor absorption peaks, respectively. The dual-peak dose measurement is accomplished with the aid of a novel spectral microdensitometer developed in our Institute. The microdensitometer utilizes a monochromator to provide a light source of which the wavelength can be matched precisely to the wavelength of the absorption peaks of the RCF. The doses obtained at these wavelengths are fed into a weighted objective function and an optimum dose is searched by minimizing the objective function to give the best estimate of the dose deposited on the film. An initial test shows that there is a good agreement between the estimated and actual dose deposited; and the maximum discrepancy was found to be less than 1%.

Algorithms↗
PubMed2004

Development and initial evaluation of a spectral microdensitometer for analysing radiochromic films.

Radiation dose deposited on a radiochromic film is considered as a dose image. A precise image extraction system with commensurate capabilities is required to measure the transmittance of the image and translate it to radiation dose. This paper describes the development of a spectral microdensitometer which has been designed to achieve this goal under the conditions of (a) the linearity and sensitivity of the dose response curve of the radiochromic film being highly dependent on the wavelength of the analysing light, and (b) the inherent high spatial resolution of the film. The microdensitometer consists of a monochromator which provides an analysing light of variable wavelength, a film tray on a high-precision scanning stage, a transmission microscope coupled to a thermoelectrically cooled CCD camera, a microcomputer and corresponding interfaces. The measurement of the transmittance of the radiochromic film is made at the two absorption peaks with maximum sensitivities. The high spatial resolution of the instrument, of the order of micrometres, is achieved through the use of the microscope combined with a measure-and-step technique to cover the whole film. The performance of the instrument in regard to the positional accuracy, system reproducibility and dual-peak film calibration was evaluated. The results show that the instrument fulfils the design objective of providing a precise image extraction system for radiochromic films with micrometre spatial resolution and sensitive dose response.

Calibration↗
PubMed2003

Interleukin-8 production in tuberculous pleurisy: role of mesothelial cells stimulated by cytokine network involving tumour necrosis factor-alpha and interleukin-1 beta.

Interleukin-8 (IL-8) plays an important role in the host immune response to Mycobacterium tuberculosis by recruiting inflammatory cells to the site of infection. Here, we investigated the role of pleural macrophages and mesothelial cells in the production of IL-8 in tuberculous pleurisy. Large concentrations of IL-8 were detected in tuberculous pleural effusions, but not in pleural effusions associated with congestive heart failure (CHF). Tuberculous pleural macrophages and M. tuberculosis-infected CHF pleural macrophages produced large concentrations of IL-8. When immunohistochemistry was performed on pleural tissues, antigenic IL-8 was detected in the mesothelial cells lining the tuberculous pleura. Direct stimulation of cultured CHF pleural mesothelial cells with M. tuberculosis induced IL-8 secretion. However, conditioned media from M. tuberculosis-infected pleural macrophages (CoMTB) induced greater mesothelial cell IL-8 secretion. Tumour necrosis factor-alpha (TNF-alpha) and IL-1beta induced mesothelial cell IL-8 mRNA expression, and neutralizing anti-TNF-alpha antibody and IL-1 receptor antagonist nearly completely obliterated CoMTB-induced mesothelial cell IL-8 mRNA expression and protein secretion. These findings demonstrate that both pleural macrophages and mesothelial cells produce IL-8 in tuberculous pleurisy, and cytokines produced by M. tuberculosis-infected macrophages mediate mesothelial cell IL-8 production.

Adult↗
PubMed2003

Estimation of bacterial risk in extending the shelf life of PLT concentrates from 5 to 7 days.

BACKGROUND: The use of bacterial culture to prevent bacterial contamination of blood components has renewed interest for extending the shelf life of PLT concentrates to 7 days after collection. STUDY DESIGN AND METHODS: This study was therefore conducted to determine the residual risk of bacterial contamination in PLT concentrates at the end of 5 and 7 days after collection in a center where all PLT concentrates are routinely screened by taking samples on Day 2 for culture. PLT units with no growth after 48 hours were sampled a second time on Day 5 or Day 7 after collection, followed by inoculation into aerobic culture bottles. The inoculated bottles were then monitored for up to 7 days at 35 degrees C in an automatic monitoring and detection system. RESULTS: During a 16-month study period, a total of 6020 PLT concentrates were tested 5 days (Group A, n=3010) and 7 days (Group B, n=3010) after collection. Four units in each group (0.133%) were found to be contaminated. In 6 units, bacteria were seen on direct Gram stain. In addition, 5 of the associated RBC units grew the same organisms on culture. The organisms include three coagulase-negative staphylococci and five Propionibacterium acnes. The positive rate of routine short-term bacterial culture was 0.035 percent during the same study period. CONCLUSION: Despite routine short-term bacterial culture, a significant risk of bacterial contamination remains at 5 and 7 days after collection. For now, the shelf life of PLT concentrates should remain 5 days.

Bacteria↗
PubMed2002

Acute encephalitis associated with measles: MRI features.

We document the MRI features in six patients aged 5-14 years with acute encephalitis following measles. The diagnosis was made on a characteristic morbiliform rash and detection of specific IgM and IgG antibodies. The symptoms of encephalitis occurred 1-11 days after the appearance of the rash. All patients underwent MRI within 1-4 days of the onset of neurological symptoms. Diffusion weighted images (DWI) were obtained in three patients. In all patients, T2-weighted images showed widely distributed, multifocal high signal in both cerebral hemispheres with swelling of the cortex, with bilateral, symmetrical involvement of the putamen and caudate nucleus. The lesions had showed low apparent diffusion coefficients. Three patients showed subacute gyriform haemorrhage, and asymmetrical gyriform contrast enhancement on follow-up MRI.

Acute Disease↗
PubMed2002

Calreticulin enriched as an early-stage encapsulation protein in wax moth Galleria mellonella larvae.

To investigate the molecular mechanism of the early-stage encapsulation reaction in insects, we purified a 47kDa protein from injected beads into Galleria mellonella larvae. When a cDNA clone was isolated, the 47kDa protein showed high homology with Drosophila and human calreticulin. Western blotting analysis showed that the 47kDa protein was present in the hemocytes, but not in the plasma. When the early-stage encapsulated beads were coated with 47kDa protein antibody and reinjected into G. mellonella larvae, any further encapsulation reaction was inhibited. These results suggest that calreticulin is involved in non-self recognition in invertebrate cellular defense reactions.

Amino Acid Sequence↗
PubMed2002

Molecular characterization of the insect immune protein hemolin and its high induction during embryonic diapause in the gypsy moth, Lymantria dispar.

During the embryonic (pharate first instar) diapause of the gypsy moth, Lymantria dispar, a 55 kDa protein is highly up-regulated in the gut. We now identify that protein as hemolin, an immune protein in the immunoglobulin superfamily. We isolated a gypsy moth hemolin cDNA and demonstrated a high degree of similarity with hemolins from three other moth species. Hemolin mRNA levels increased at the time of diapause initiation and remained high throughout the mandatory period of chilling required to terminate diapause in this species, and then dropped in late diapause. This mRNA pattern reflects the pattern of protein synthesis. These results suggest that hemolin is developmentally up-regulated in the gut during diapause. Diapause in this species can be prevented using KK-42, an imidazole derivative known to inhibit ecdysteroid biosynthesis, and gypsy moths treated in this manner failed to elevate hemolin mRNA. Conversely, this diapause appears to be initiated and maintained by the steroid hormone, 20-hydroxyecdysone, and the addition of 20-hydroxyecdysone to the culture medium elevated hemolin mRNA in the gut. Our results thus indicate a role for 20-hydroxyecdysone in the elevation of hemolin mRNA during diapause. Presumably, hemolin functions to protect the gypsy moth from microbial infection during its long, overwintering diapause.

Amino Acid Sequence↗
PubMed2002

Morphological characteristics of C1 and C2 adrenergic neurone groups in marmoset monkey brainstem by using antibody against phenylethanolamine-N-methyltransferase.

This work describes a mapping study of phenylethanolamine-N-methyltransferase (PNMT) immunoreactive neurones and fibres in the medulla oblongata of the marmoset monkey, Callithrix jacchus. Two groups of PNMT-immunoreactive neurones were found in the marmoset monkey medulla oblongata: a ventrolateral (C1 group) and a dorsomedial PNMT-immunoreactive cells group (C2 group). The PNMT-immunoreactive cells in the ventrolateral group C1 were found to be located around the lateral reticular nucleus. The PNMT-immunoreactive somata within the ventrolateral medulla are round to oval, and mostly multipolar with branched processes. In the dorsomedial group C2, PNMT-immunoreactive cell bodies appeared near the obex. The majority of the dorsomedial PNMT-immunoreactive neurones were observed in the nucleus tractus solitarius; although some were present in the dorsal motor nucleus of the vagus. The PNMT-immunoreactive somata in the dorsomedial medulla were small and round or ovoid. These results provide information upon the adrenergic system in the medulla oblongata of a species that presents a useful model of a small primate brain, the marmoset monkey.

Adrenergic Fibers↗