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Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 19 recordsLinked to original sources

A candidate precursor to serous carcinoma that originates in the distal fallopian tube.

The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial BRCA1 or 2 mutations (BRCA+). Somatic p53 tumour suppressor gene mutations in these tumours suggest a pathogenesis involving DNA damage, p53 mutation, and progressive loss of cell cycle control. We recently identified foci of strong p53 immunostaining-termed 'p53 signatures'-in benign tubal mucosa from BRCA+ women. To examine the relationship between p53 signatures and TIC, we compared location (fimbria vs ampulla), cell type (ciliated vs secretory), evidence of DNA damage, and p53 mutation status between the two entities. p53 signatures were equally common in non-neoplastic tubes from BRCA+ women and controls, but more frequently present (53%) and multifocal (67%) in fallopian tubes also containing TIC. Like prior studies of TIC, p53 signatures predominated in the fimbriae (80-100%) and targeted secretory cells (HMFG2 + /p73-), with evidence of DNA damage by co-localization of gamma-H2AX. Laser-capture microdissected and polymerase chain reaction-amplified DNA revealed reproducible p53 mutations in eight of 14 fully-analysed p53 signatures and all of the 12 TICs; TICs and their associated ovarian carcinomas shared identical mutations. In one case, a contiguous p53 signature and TIC shared the same mutation. Morphological intermediates between the two, with p53 mutations and moderate proliferative activity, were also seen. This is the first report of an early and distinct alteration in non-neoplastic upper genital tract mucosa that fulfils many requirements for a precursor to pelvic serous cancer. The p53 signature and its malignant counterpart (TIC) underline the significance of the fimbria, both as a candidate site for serous carcinogenesis and as a target for future research on the early detection and prevention of this disease.

Biomarkers, Tumor↗

Midazolam vs ondansetron for preventing postoperative nausea and vomiting: a randomised controlled trial.

We compared the prophylactic anti-emetic efficacy of midazolam and ondansetron in 90 patients scheduled for minor gynaecological (hysteroscopy) or urological (ureteroscopy) procedures planned to last 1-2 h under sevoflurane anaesthesia with spontaneous ventilation of the lungs via a laryngeal mask airway. Midazolam 2 mg or ondansetron 4 mg were administered intravenously 30 min before the end of surgery. The proportions of patients who experienced postoperative nausea and vomiting in the first 24 h (30% and 27% for the midazolam and ondansetron groups, respectively) were similar in the two groups. The incidence of postoperative nausea and vomiting was significantly smaller in both groups than predicted according to the patients' underlying risks (midazolam group: p = 0.018; ondansetron group: p = 0.017). There were no significant differences in average sedation scores or pain scores. Treatment using ondansetron for anti-emetic prophylaxis did not provide a superior benefit compared to midazolam in the present study.

Adjuvants, Anesthesia↗

Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells.

OBJECTIVES: To characterize mesenchymal stem cell-like cells isolated from human amniotic fluid for a new source of therapeutic cells. MATERIALS: Fibroblastoid-type cells obtained from amniotic fluid at the time of birth. METHODS: The ability of ex vivo expansion was investigated until senescence, and stem cell-like characteristics were analyzed by examining differentiation potential, messenger RNA expression and immunophenotypes. RESULTS AND CONCLUSIONS: A morphologically homogenous population of fibroblastoid-type (HAFFTs) cells, similar to mesenchymal stem cells from bone marrow (BM-MSCs), was obtained at the third passage. The cells became senescent after 27 passages over a period of 8 months while undergoing 66 population doublings. Under appropriate culture conditions, by the 8th passage they differentiated into adipocytes, osteocytes, chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue and anti-NeuN antibody staining, respectively. Immunophenotype analyses at the 17th passage demonstrated the presence of TRA-1-60; SSEA-3 and-4; collagen types I, II, III, IV and XII; fibronectin; alpha-SMA; vimentin; desmin; CK18; CD44; CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase-polymerase chain reaction analysis of the HAFFTs from passages 6-20 showed consistent expression of Rex-1, SCF, GATA-4, vimentin, CK18, FGF-5 and HLA ABC genes. Oct-4 gene expression was observed up to the 19th passage but not at the 20th passage. HAFFTs showed telomerase activity at the 5th passage with a decreased level by the 21st passage. Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed differential gene expression during ex vivo expansion. Taken together, these observations suggest that HAFFTs are pluripotent stem cells that are less differentiated than BM-MSCs, and that their gene expression profiles vary with passage number during ex vivo expansion.

Amniotic Fluid↗

An intelligent data mining model approach for adverse effects of hormone replacement therapy.

OBJECTIVES: A number of controversial studies have been reported on the potential risk of breast cancer caused by hormone replacement therapy (HRT). Some studies showed a positive relationship between HRT and breast cancer onset, but other studies have not confirmed these results. To clarify the contradictory outcomes in the relationships between HRT and the onset of breast cancer, we have designed an intelligent data mining model (IDM), which is able to find proper prognostic factors for cancer onset and provides alternate measures in interpretation of outcome of clinical data through hierarchies of attributes. METHODS: Based on the selection criteria, we selected 22 sets of random and case-control studies of the last 15 years, which identified any involvements of HRT with breast cancer. We analyzed the relationship between HRT and breast cancer using an IDM model consisting of data mining algorithms and public domain data mining tools. Prognostic factors which underline the major etiological dispositions of breast cancer were identified. RESULTS: The variables which are closely associated with cancer onset to some degree are age 60-69, age at menopause 40-49, parity 0, age 40-49, and types of menopause oophorectomy. An implementation of IDM model on overall pooled data indicated that there is no significant relationship between breast cancer onset and HRT. It is suggested that HRT patients with specific physiological and pathological conditions related with the higher ranks of prognostic factors may have a greater chance to get breast cancer. CONCLUSION: The results of this study may guide biomedical research directed at establishing the causal relationships between various medications and their complications, allowing an accurate assessment of efficacy and side effects of new therapeutic treatment in clinical trials without reliance on a large control population.

Adult↗

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target.

Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n = 55 and n = 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the "metasignature" for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers.

Animals↗

Multicentre, parallel group, randomised, single-blind study of the safety and efficacy of atosiban versus ritodrine in the treatment of acute preterm labour in Korean women.

OBJECTIVE: To compare the efficacy and safety of atosiban with those of ritodrine in preterm labour. DESIGN: Multicentre, single-blind, randomised, controlled trial. SETTING: Obstetric units in six referral centres in Korea. POPULATION: Women with singleton pregnancies with preterm labour, between 24 and 33 + 6 weeks of gestation. METHODS: One hundred and twenty-eight women were randomised to receive intravenous atosiban (n= 63) or ritodrine (n= 65) and were stratified by gestational age (<28 weeks and >or=28 weeks). Atosiban or ritodrine was administered for up to 48 hours. Progression of labour was assessed by the frequency of contractions and cervical dilatation and effacement. Alternative tocolysis could be given as rescue therapy. MAIN OUTCOME MEASURE: Efficacy was assessed as the proportion of women in each group who did not deliver and did not need alternative tocolytic therapy at 48 hours and 7 days after therapy initiation. Safety was assessed as the numbers of maternal adverse events and neonatal morbidity. RESULTS: Tocolytic efficacy after 7 days was significantly better in the atosiban group than in the ritodrine group (60.3 versus 34.9%), but not at 48 hours (68.3 versus 58.7%). Maternal adverse events related to therapy were reported less frequently in the atosiban group (7.9 vs 70.8%; P= 0.0001), resulting in fewer early drug terminations due to adverse events (0 versus 20.0%; P= 0.0001). This, however, was not accompanied by a concurrent improvement in perinatal outcomes. CONCLUSION: The efficacy and safety of atosiban in the treatment of preterm labour were superior to those of ritodrine.

Acute Disease↗

Supportive management of pregnancy-associated aplastic anemia.

OBJECTIVE: To examine maternal and fetal outcomes of pregnancy-associated aplastic anemia treated with supportive care. METHODS: From January 1995 to December 2004, 14 women newly diagnosed as having pregnancy-associated aplastic anemia were recruited for the study. RESULTS: Diagnosis was made during the second or third trimester for 11 (78%) of the 14 patients, and 3 of the 8 severe cases of aplastic anemia were diagnosed at initial presentation. All patients had conservative management with transfusions but no specific immunologic or hormonal therapy during pregnancy. Of the 12 women eligible for follow-up, 1 achieved complete remission and 8 achieved partial remission after delivery. The pregnancies progressed uneventfully in most cases. CONCLUSIONS: This study demonstrated favorable maternal and neonatal outcomes with transfusion support alone for pregnancy-associated aplastic anemia.

Adult↗

Responding to DNA double strand breaks in the nervous system.

Within the nervous system appropriate responses to DNA damage are required to maintain homeostasis and prevent disease. In this tissue, DNA double-strand breaks (DSBs) initiate a molecular response to repair DNA, or in many cases, activate apoptosis. The repair of DNA DSBs occurs via nonhomologous end-joining (NHEJ) or homologous recombination (HR). These mechanistically distinct pathways are critical for maintenance of genomic integrity. During nervous system development there are discrete requirements for each DNA DSB repair pathway at different stages of development. For example, in the nervous system HR is particularly important for proliferating cells, while NHEJ is critical for differentiating cells. Inactivation of either of these pathways can lead to embryonic lethality, neurodegeneration or brain tumors. Human syndromes that result from defective responses to DNA damage often feature overt neuropathology. A prime example is the neurodegenerative syndrome ataxia telangiectasia (A-T), which results from inactivation of the ATM kinase, a crucial nexus for the cellular response to DNA DSBs. This type of DNA damage activates ATM via the Mre11-Rad50-NBS1 (MRN) complex, which leads to selective phosphorylation of ATM substrates resulting in apoptosis or cell cycle arrest and DNA repair. Furthermore, DNA DSBs resulting from chronic genotoxic stress can also result in tumorigenesis, as inactivation of either HR or NHEJ can lead to certain types of brain tumors. Thus, there are distinct requirements for each DNA DSB repair pathway during neural development, which have important implications for understanding diseases of the nervous system.

Animals↗

The use of the GlideScope for tracheal intubation in patients with ankylosing spondylitis.

BACKGROUND: The GlideScopeVideo Laryngoscope is a new intubating device. The aim of the study was to investigate the use of the GlideScopefor tracheal intubation in patients with ankylosing spondylitis (AS) undergoing general anaesthesia. METHODS: Twenty AS patients were chosen to undergo tracheal intubation by the GlideScope. Preoperative airway assessments were carried out to predict the difficulty of tracheal intubation. Before intubation all patients were given a modified Cormack and Lehane (MCLS) grade and percentage of glottic opening (POGO) score by a separate anaesthetist using a Macintosh size 3 blade. The patients were then intubated, using the GlideScope, by a different anaesthetist during which the larynx was inspected and given another MCLS grade and POGO score. RESULTS: Twelve of the AS patients were judged to have had difficult intubation by preoperative airway assessment. Eleven of the twelve patients had MCLS grades III or IV by direct laryngoscopy and were considered to have had a difficult laryngoscopy. Naso-tracheal intubations by the GlideScope were successful on 17/20 occasions, including 8 of the 11 difficult laryngoscopy. The GlideScope improved the MCLS grade and POGO score in the majority of AS patients compared with direct laryngoscopy (P<0.01). CONCLUSIONS: The GlideScope provides a better laryngoscopic view than that of direct laryngoscopy. Most of the AS patients presenting with MCLS grade III or IV by direct laryngoscopy can be intubated successfully by the GlideScope. In elective patients with AS, awake fibreoptic intubation offers a higher level of security because it can be applied while maintaining spontaneous breathing. The use of GlideScope for tracheal intubation may be an alternative option in these patients who prefer their airway management under anaesthesia.

Adult↗

Anomalous decrease in groundwater radon before the Taiwan M6.8 Chengkung earthquake.

On December 10, 2003, an earthquake of magnitude (M) 6.8, the strongest since 1951, occurred near the Chengkung area in eastern Taiwan. Approximately 65 d prior to the 2003 Chengkung earthquake, precursory changes in the groundwater radon concentration were observed at the Antung radon-monitoring station located 20 km from the epicenter. The radon anomaly was a decrease from a background level of 28.9 BqL(-1) to a minimum of 12.2 BqL(-1). Observations at the Antung hot spring suggest that the groundwater radon, when observed under suitable geological conditions, can be a sensitive tracer for strain changes in the crust preceding an earthquake.

Disasters↗

Multicomponent variance estimation for binary traits in family-based studies.

In biometrical genetic analyses of binary traits, the use of family data overcomes some limitations of twin studies, particularly in terms of sample size and types of genetic or environmental factors that can be estimated. However, because of computational problems, recent methods in the application of generalized linear mixed models for family data structure have limited the ability to handle large data sets with general covariates. In this paper, we investigate the use of the hierarchical likelihood approach to the analysis of binary traits from family data. In a simulation study, the method is shown to be highly accurate for the estimation of both the variance components and fixed regression parameters, even for small family sizes. For illustration, we analyze a real data set of familial aggregation of preeclampsia, a pregnancy-induced hypertension. When possible, the analysis is compared with the exact maximum likelihood approach.

Analysis of Variance↗

Effects of a structured treatment algorithm on blood pressure goal rates in both stage 1 and stage 2 hypertension.

This study analysed the efficacy of an angiotensin receptor blocker-based treatment algorithm for achieving goal blood pressure (BP) in patients with stage 1 (systolic BP (SBP) 140-159 mmHg or diastolic BP (DBP) 90-99 mmHg) or stage 2 (SBP > or = 160 mmHg or DBP > or = 100 mmHg) hypertension. In this 24-week, open-label, multicentre study, patients followed a six-step algorithm until goal BP (< or = 130/85 mmHg) was attained. Initially, olmesartan medoxomil 20 mg/day was administered for 4 weeks. The regimen was modified every 4 weeks until goal BP was attained: increase olmesartan medoxomil to 40 mg/day; add hydrochlorothiazide (HCTZ) 12.5 mg/day; increase HCTZ to 25 mg/day; add amlodipine besylate 5 mg/day; increase amlodipine besylate to 10 mg/day. In patients with stage 1 hypertension, 80% (63/79) and 56% (44/79) achieved BP goals of < or = 140/90 mmHg and < or = 130/85 mmHg, respectively, with olmesartan medoxomil monotherapy (94% (74/79) and 89% (70/79) with olmesartan medoxomil/HCTZ double therapy, and 96% (76/79) and 98% (77/79) with addition of amlodipine besylate (triple therapy)). Mean SBP/DBP reductions were 16.7/11.6, 24.8/15.8, and 26.4/16.5 mmHg for mono-, double-, and triple-therapy, respectively. In patients with stage 2 hypertension, 42% (42/100) and 19% (19/100) achieved BP goals of < or = 140/90 mmHg and < or = 130/85 mmHg, respectively, with monotherapy (75% (75/100) and 54% (54/100) with double therapy, and 90% (90/100) and 81% (81/100) with triple-therapy). Mean SBP/DBP reductions in stage 2 patients were 18.4/10.0, 32.7/16.3, and 39.1/19.4 mmHg for mono-, double, and triple therapy, respectively. Overall, most patients with stage 1 or stage 2 hypertension achieved goal BP.

Adult↗

The transmission of anaerobic periodontopathic organisms.

The oral microbial flora is unique, and available evidence indicates that it is passed vertically from parents to children. In this investigation, we used a chairside assay for the N-benzoyl-DL-arginine-2-naphthylamide (BANA)-sensitive enzyme found in Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythensis, to determine the prevalence of these BANA-positive species in young children and their caregivers. We predicted that if the BANA enzyme was found in plaque samples of children, it would also be present in the plaque samples of the caregivers. Forty-four percent of 150 children had at least one plaque sample positive for the BANA enzyme. If the caregiver was BANA-positive, the odds of the child also being BANA-positive was 35 times more than for a child with a BANA-negative caregiver, after adjustment for the child's age and papillary bleeding score (PBS). Other significant predictors were the PBS of children (p < 0.001), a history of periodontal disease, and the ages of the caregivers (p < 0.001).

Bacteria, Anaerobic↗

Size removal on polyester fabrics by plasma source ion implantation device.

Plasma treatment was evaluated as an alternative clean desizing technology in this work. As indicated by weight loss, O2 plasma treatment efficiently removed sizing agents such as polyvintyl alcohol (PVA), polyacrylic acid esters and their mixture (MIX) on polyethylene terephthalate (PET) fabrics. SEM pictures of the plasma treated samples directly proved the disappearance of the sizing agents. XPS analysis showed apparent changes in chemical composition and functional groups of the PET surface after O2 plasma treatment. Carbon content decreased due to the removal of sizing agents while oxygen content increased. O2 plasma treatment also increased hydrophilic functional groups of sizing agents, which is confirmed by C1s and O1s deconvolution analyses. After O2 plasma treatment, the PET fabric was subjected to conventional desizing process at different temperatures. Except for the PET fabric sized with PVA, plasma-treated fabrics showed more efficient desizing results when compared with untreated fabrics. Furthermore, the desizing effluent from the treated fabric gave lower TOC, COD and BOD values.

Acrylic Resins↗

BmiGI: a database of cDNAs expressed in Boophilus microplus, the tropical/southern cattle tick.

We used an expressed sequence tag approach to initiate a study of the genome of the southern cattle tick, Boophilus microplus. A normalized cDNA library was synthesized from pooled RNA purified from tick larvae which had been subjected to different treatments, including acaricide exposure, heat shock, cold shock, host odor, and infection with Babesia bovis. For the acaricide exposure experiments, we used several strains of ticks, which varied in their levels of susceptibility to pyrethroid, organophosphate and amitraz. We also included RNA purified from samples of eggs, nymphs and adult ticks and dissected tick organs. Plasmid DNA was prepared from 11,520 cDNA clones and both 5' and 3' sequencing performed on each clone. The sequence data was used to search public protein databases and a B. microplus gene index was constructed, consisting of 8270 unique sequences whose associated putative functional assignments, when available, can be viewed at the TIGR website (http://www.tigr.org/tdb/tgi). A number of novel sequences were identified which possessed significant sequence similarity to genes, which might be involved in resistance to acaricides.

Acetylcholinesterase↗

A new drug carrier, Nalpha-deoxycholyl-L: -lysyl-methylester, for enhancing insulin absorption in the intestine.

AIMS/HYPOTHESIS: The development of an orally active insulin formulation will offer great advantages over conventional injectable insulin therapy in the treatment of patients with diabetes mellitus. Since insulin absorption in the intestine is restricted by the natural physiological characteristics of insulin, we developed a small synthetic compound, Nalpha-deoxycholyl-L: -lysyl-methylester (DCK), as an insulin carrier to enhance oral delivery. METHODS: Streptozotocin-induced diabetic rats orally received single doses of insulin (42 U/kg) or insulin/DCK formulation (10, 21, 30 and 42 U/kg) under fasting conditions. Blood glucose levels and plasma insulin concentrations were measured for 6 h following the administration of the agents. An OGTT was also performed immediately after the administration of the oral insulin/DCK formulation. RESULTS: The administration of 21, 30 and 42 U/kg (based on insulin activity) of insulin/DCK formulation reduced plasma glucose levels by up to 33.0% (median; range 30.6-70.2%), 78.5% (39.4-86.8%) and 75.2% (67.0-87.4%), respectively, compared with baseline levels. Furthermore, plasma insulin concentrations were observed to rapidly increase. In the OGTT, the insulin/DCK formulation reduced the AUC0-240 for glucose by 30.8% (22.3-54.9%) (p<0.01), and stabilized glycaemia for up to 4 h. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that the insulin/DCK formulation can be absorbed in the intestine and that it is biologically efficacious. We therefore suggest that this oral formulation could be used as an alternative to injectable insulin with enhanced clinical effects.

Animals↗

The TIGR Gene Indices: clustering and assembling EST and known genes and integration with eukaryotic genomes.

Although the list of completed genome sequencing projects has expanded rapidly, sequencing and analysis of expressed sequence tags (ESTs) remain a primary tool for discovery of novel genes in many eukaryotes and a key element in genome annotation. The TIGR Gene Indices (http://www.tigr.org/tdb/tgi) are a collection of 77 species-specific databases that use a highly refined protocol to analyze gene and EST sequences in an attempt to identify and characterize expressed transcripts and to present them on the Web in a user-friendly, consistent fashion. A Gene Index database is constructed for each selected organism by first clustering, then assembling EST and annotated cDNA and gene sequences from GenBank. This process produces a set of unique, high-fidelity virtual transcripts, or tentative consensus (TC) sequences. The TC sequences can be used to provide putative genes with functional annotation, to link the transcripts to genetic and physical maps, to provide links to orthologous and paralogous genes, and as a resource for comparative and functional genomic analysis.

Animals↗