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Biomedical subjects

K Yee

Publications and source records attributed to K Yee.

At least 19 recordsLinked to original sources
PubMed2005

Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells.

Up-regulation of pro-inflammatory cytokines, cyclooxygenase (COX-2) and prostaglandins is a critical factor driving human term labour and inflammation-associated preterm labour. Nuclear factor kappa B (NF-kappaB) is activated in response to a number of inflammatory mediators, including cytokines and lipopolysaccharide (LPS). The aim of this study was (i) to investigate if TNF-alpha and LPS activate the NF-kappaB pathway; and (ii) to use short interfering RNA (siRNA) against inhibitor kappaB kinase (IKK)-beta to confirm the role of the NF-kappaB pathway in the regulation of pro-inflammatory mediators in human placental JEG-3 cells. JEG-3 cells (3 independent experiments) were (i) incubated in the presence or absence of 10 microg/ml LPS or 20 ng/ml TNF-alpha, or (ii) transfected with 100 nM IKK-beta siRNA. Incubation of JEG-3 cells with LPS and TNF-alpha increased the expression of cytoplasmic IKK-beta and phosphorylated IkappaB-alpha, and nuclear NF-kappaB proteins p50 and p65. This was associated with a concurrent increase in COX-2 protein, and IL-6 and PGF2alpha release from JEG-3 cells. Treatment of cells with BAY 11-7082 at 50 microM significantly inhibited basal, LPS- and TNF-alpha-induced NF-kappaB and COX-2 expression, and IL-6 and PGF2alpha release. Transfection of JEG-3 cells with IKK-beta siRNA significantly decreased IL-6 and PGF2alpha release. The data presented in this study demonstrate that pro-inflammatory mediators regulate the NF-kappaB transcription pathway in human JEG-3 cells, and the IKK-beta/NF-kappaB pathway is a regulator of inflammatory mediators in placental JEG-3 cells.

Cell Line, Tumor↗
PubMed2004

Subdural hematomas during CML therapy with imatinib mesylate.

Seven of one hundred twenty-one patients with chronic myeloid leukemia (CML) treated with imatinib mesylate developed subdural hematomas. All had advanced disease and were treated initially at a dose of 600 mg per day. Three patients had thrombocytopenia (platelet < 10 x 10(9)/l), one had leukocytosis (white blood cell count > 150 x 10(9)/l) and three had neither around the time of diagnosis of the subdural hematomas. Four patients required surgical evacuation. One patient, in blast crisis, died as a consequence of the subdural hematoma. Three patients survived but died of progressive CML. The remaining three patients having recommenced imatinib, are alive and well, and one has achieved a major cytogenetic response. Subdural hematomas must be considered even in mildly symptomatic patients receiving imatinib regardless of their peripheral blood counts. Patients who survive can be cautiously restarted on imatinib. Further studies are required to study the potential relationship between imatinib mesylate and subdural hematomas.

Aged↗
PubMed2003

Quantitative PCR identifies a minimal deleted region of 120 kb extending from the Philadelphia chromosome ABL translocation breakpoint in chronic myeloid leukemia with poor outcome.

Fluorescence in situ hybridization (FISH) analysis has shown previously that 10-15% of chronic myeloid leukemias (CML) have hemizygous deletions of variable sizes affecting regions that flank the ABL and BCR translocation breakpoints on the derivative chromosome 9, and these patients have a poor outcome. FISH studies using large commercial genomic probes have previously suggested that haploinsufficiency of sequences flanking either ABL or BCR modify the disease process of CML and lead to an unfavorable prognosis. In this present study, real-time quantitative PCR (Q-PCR) analysis was used to identify and map much smaller hemizygous microdeletions in a subset of CML patients that were not deleted using large genomic FISH probes. Microdeletions were identified by Q-PCR in 25 of 71 patients selected based on less favorable outcome (chronic phase duration of less than 96 months and a survival time of less than 84 months). In contrast, no microdeletion was detected in any of 18 CML samples selected from a group with a more favorable outcome. Detailed mapping of the 25 Q-PCR microdeletions showed that the minimal deleted region extended approximately 120 kb from the 5' end of the ABL gene in the centromeric direction on the derivative chromosome 9, and the region 3' to BCR on chromosome 22 was excluded. Of the four ESTs and/or genes that map to the 120 kb region, the putative tumor suppressor PRDM12 is the strongest candidate gene. The potential role for each sequence in modifying the clinical behavior of CML is presented.

Chromosome Breakage↗
PubMed2001

NKIATRE is a novel conserved cdc2-related kinase.

The mitogen-activated protein kinases (MAPKs) and the cyclin-dependent kinases (CDKs) are key mediators of cell proliferation in response to extracellular signals. Recent additions to each of these families and the identification of kinases with structural features of both have provided insights into fundamental processes, such as cell division and differentiation. To identify novel serine kinases with features of MAPKs or CDKs, a degenerate PCR-based amplification approach was undertaken. The 57- and 52-kDa isoforms of a novel protein kinase, termed NKIATRE, were molecularly cloned from rat brain and jejunum cDNA libraries. Like the MAPKs, NKIATRE has a Thr-Xaa-Tyr motif in kinase subdomain VIII. NKIATRE also shows close homology to the cyclin-dependent kinase class of protein kinases and the cdc2-related kinases NKIAMRE, KKIALRE, and KKIAMRE, containing both conserved inhibitory phosphorylation sites and a putative cyclin-binding domain. Two isoforms of NKIATRE that differ in their carboxy-terminal ends have been identified. A functional nuclear localization signal is specific to the longer 57-kDa alpha isoform. Sequence similarity to the putative human tumor suppressor gene NKIAMRE, which is lost in leukemic patients with chromosome 5q deletions, suggests that NKIATRE may have a role in restricting cell growth or maintaining differentiation.

Amino Acid Sequence↗
PubMed2000

Novel Cystic Fibrosis mutation L1093P: functional analysis and possible Native American origin.

A novel mutation was detected using single-strand conformation polymorphism and heteroduplex analysis in a cystic fibrosis subject of mixed ancestry. Mutation 3410T-->C in exon 17b caused the novel missense mutation L1093P; the other chromosome has mutation N1303K. The 31-year-old subject is pancreatic insufficient, had an FEV(1) score that was 33% of normal prior to a heart/lung transplant, and sweat chloride values of 116 and 95 mM when tested at ages 1 and 11. Functional analysis using forskolin-stimulated efflux of (125)I in HEK cells transfected with an ABCC7 construct harboring the L1093P mutation confirmed that cAMP-mediated anion efflux was abnormal, but some function was preserved. Analysis of parental DNA established that N1303K was of English origin, while L1093P was of Greek, Irish or Native American (Cherokee) origin. Given the intensive screening for CF mutations in European populations, we hypothesize that L1093P is of Native American origin. Hum Mutat 15:208, 2000.

Adult↗
PubMed1999

Two novel mutations in a cystic fibrosis patient of Chinese origin.

Cystic fibrosis is rare in non-Caucasian populations, and in such populations little is known about the spectrum of mutations and polymorphisms in the CFTR gene. We studied a 23-year-old patient of Chinese ethnicity with sweat chloride values of 104 mM/l, pancreatic sufficiency, an FEV1 60% of normal, sputum cultures positive for Staphylococcus aureus and Burkholderia cepacia, and a history of allergic bronchopulmonary aspergillosis. Genetic screening for 31 common CFTR mutations was negative, leading us to search for unknown mutations using single-strand conformation polymorphism and heteroduplex analysis (SSCP/HA). Two novel mutations were detected. In exon 4, a deletion of 8 bp (451458, deltaGCTTCCTA) causes a frameshift and immediately creates a stop codon. In exon 16, mutation 3041G-->A causes the missense change G970D. Functional analysis using an isotopic flux assay indicated that the G970D mutation retains partial function; western blotting indicated that the protein is glycosylated. The patient is heterozygous for the common polymorphisms (2694T/G) in exon 14a and (GATT)6/7 in intron 6a, indicating that these variants arose in ancestors common to Caucasians and Chinese.

Adult↗
PubMed1999

Is outpatient laparoscopic cholecystectomy safe and cost-effective? A model to study transition of care.

BACKGROUND: There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting. METHODS: Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed. RESULTS: Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient. CONCLUSIONS: The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.

Adult↗
PubMed1998

Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia.

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis.

Adolescent↗
PubMed1997

Effects of Nd: and Ho:yttrium-aluminium-garnet lasers on human dentine fluid flow and dental pulp-chamber temperature in vitro.

Dentine specimens were prepared from freshly extracted third molars and initial permeability measured. Each specimen was subjected to Nd:yttrium-aluminium-garnet (YAG) (1.06 or 1.32 microns wavelength) or Ho:YAG (2.10 microns wavelength) laser energy while temperatures in the pulp chambers were recorded. Permeability was again measured and the surfaces examined by scanning electron microscopy. Six crown segments were used for each laser variable and eight permeability measurements were taken before and eight after laser exposure, while temperature was recorded during treatment. All wavelengths reduced permeability but temperature rises were high enough to have caused pulpal damage, indicating that shorter treatment times and lower power settings may be necessary if used in vivo.

Aluminum Silicates↗
PubMed1995

Intraembryonic hematopoietic cell migration during vertebrate development.

Vertebrate hematopoietic stem cells are derived from vental mesoderm, which is postulated to migrate to both extra- and intraembryonic positions during gastrula and neurula stages. Extraembryonic migration has previously been documented, but the origin and migration of intraembryonic hematopoietic cells have not been visualized. The zebrafish and most other teleosts do not form yolk sac blood islands during early embryogenesis, but instead hematopoiesis occurs solely in a dorsal location known as the intermediate cell mass (IM) or Oellacher. In this report, we have isolated cDNAs encoding zebrafish homologs of the hematopoietic transcription factors GATA-1 and GATA-2 and have used these markers to determine that the IM is formed from mesodermal cells in a posterior-lateral position on the yolk syncytial layer of the gastrula yolk sac. Surprisingly, cells of the IM then migrate anteriorly through most of the body length prior to the onset of active circulation and exit onto the yolk sac. These findings support a hypothesis in which the hematopoietic program of vertebrates is established by variations in homologous migration pathways of extra- and intraembryonic progenitors.

Amino Acid Sequence↗
PubMed1994

Ventral expression of GATA-1 and GATA-2 in the Xenopus embryo defines induction of hematopoietic mesoderm.

The early embryonic events involved in the commitment of mesoderm to form blood have not been studied in detail for lack of molecular markers. We have studied the expression of the hematopoietic transcription factors GATA-1 and GATA-2 during Xenopus embryogenesis. During development GATA-1 expression is localized to the ventral region of the embryo and precedes the expression of embryonic globins. GATA-2 is highly expressed in the ventral region of the embryo by the end of gastrulation and later is expressed in the blood island region and the central nervous system. Lithium-induced dorsalization of embryos abrogates GATA-2 expression, and uv-induced ventralization of embryos leads to a radially symmetrical expression of GATA-2. Therefore, GATA-2 expression reflects the ventral character of the embryo. The expression of the GATA-binding proteins and globin in ventral marginal zone explants demonstrates that hematopoiesis is programmed as early as the blastula stage. GATA-1 and GATA-2 are also expressed in cultured animal cap explants, suggesting that these cells have hematopoietic potential. The developmental expression of GATA-1 and GATA-2 is consistent with their role in hematopoiesis in higher organisms and defines the ventral regions of the early embryo that give rise to hematopoietic progenitors. Our studies indicate that these genes will be useful in defining the inductive events that lead to the formation of hematopoietic mesoderm.

Animals↗
PubMed1993

Isolation of a novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors.

Activation of distinct receptor tyrosine kinases (RTK), such as the products of the c-fms and c-kit proto-oncogenes, profoundly affects hematopoietic development. We have isolated a novel RTK cDNA, called met-related kinase (MRK), which is expressed on early erythroid progenitors. MRK is also expressed in many hematopoietic cell lines, and is not lineage restricted. Several regions within the catalytic domain of MRK have amino acid similarity to the c-met proto-oncogene and v-sea oncogene. Specific polyclonal anti-MRK antisera detects an 84-Kd polypeptide in COS cells transfected with an expression vector containing the MRK cDNA. Further studies of this novel RTK will provide potential insight into its role during hematopoiesis.

Amino Acid Sequence↗
PubMed1993

Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription.

The expression of the hematopoietic transcription factors GATA-1, GATA-2, and GATA-3 was studied in eosinophils and basophils. Eosinophils express mRNA for GATA-1, GATA-2, and GATA-3. Basophils express GATA-2 and GATA-3. Treatment of HL-60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes, whereas levels of GATA-2 mRNA remained relatively constant. The presence of mRNA for these proteins in eosinophils and basophils suggests that gene transcription in these lineages may be regulated by GATA-binding proteins.

Base Sequence↗