The missing squatting bar. Childbirth education in the 90s.
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Choice Behavior↗
Biomedical subjects
N Lee
Publications and source records attributed to N Lee.
Diagnosis and management of 34 Hürthle cell tumors.
BACKGROUND: Controversies still exist around the diagnosis and management of Hürthle cell tumors. The aim of this study is to reexamine our experience to improve our methods in the future. METHODS: We treated 34 patients with verified Hürthle cell carcinoma and adenoma at Chang Gung Memorial Hospital, Linkou from 1990 through 1996. Clinical characteristics, thyroid ultrasonogram, 131I, 201Tl, 99mTc-methoxy-isobutyl-isonitrile (MIBI) and 99mTc-thyroid scan, fine needle aspiration cytology (FNAC) and histology results were analyzed. RESULTS: Female predominance (82.4%) was noticed among our Hürthle cell tumors. Nine (26.5%) patients had carcinoma. The median size of carcinoma was 4.0 cm, which was significantly larger than the median 3.0 cm for adenoma. No significant differences were found between gender, age, multiplicity or echogenicity between two groups. All 12 adenoma and 3 carcinoma patients who received pre-operative 99mTc and/or 131I thyroid scan showed cold nodules. The sensitivity and specificity of detection Hürthle cell carcinoma as indeterminate and malignant using FNAC was 78% and 18% respectively. These improved to 100% and 86% using frozen sections. One carcinoma patient developed neck lymph node metastasis, with normal serum thyroglobulin, negative 131I but positive 201Tl and 99mTc-MIBI whole body scans. Another one showed mediastinum metastasis with elevated serum thyroglobulin, detected using 131I scan, revealed successful regression after 131I therapeutic scan. CONCLUSION: Tumor size of carcinoma is significantly larger than adenoma. All patients with FNAC suggestive of Hürthle cell tumors should receive surgery for histological diagnosis to differentiate carcinoma from adenoma. Therapeutic radioiodine ablation is indicated whenever there is 131I uptake by tumor cells.
Adenocarcinoma↗
Breastfeeding discrimination and censorship.
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Attitude to Health↗
Design and synthesis of a novel class of nucleotide analogs with anti-HCMV activity.
A novel class of cyclic nucleotide analogs has shown anti-HCMV activity. The synthesis as well as structure-activity relationship studies are presented.
Antiviral Agents↗
Synthesis and evaluation of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir.
A series of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (4-10) and 2-amino-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (1) were synthesized as potential prodrugs of penciclovir and evaluated for their oral penciclovir bioavailability in mice and rats. Treatment of 2-(2-benzyloxyethyl)propane-1,3-diol (11) with 1,1'-carbonyldiimidazole in THF followed by hydrogenolytic removal of the benzyl group of the resulting cyclic carbonate 12 gave 5-(2-hydroxyethyl)-1,3-dioxan-2-one (13). Mesylation of the alcohol 13 and then a coupling reaction of the resulting mesylate 14 with 2-amino-6-chloropurine using anhydrous Cs2CO3 in DMF afforded 2-amino-6-chloro-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (16) after purification by flash column chromatography on silica gel using EtOAc/MeCN/Et3N as eluent. Hydrogenation of the 6-chloro cyclic carbonate 16 followed by a ring-opening reaction of the 6-deoxy cyclic carbonate 1 in a mixture of an appropriate alcohol and CHCl3 using activated SiO2 as a Lewis acid afforded the corresponding alkyl monocarbonate derivatives 3-10 in fair to good yields. Of the prodrugs tested in mice, the isopropyl monocarbonate 6 achieved the highest mean urinary recovery of penciclovir (53%), followed in order by the propyl monocarbonate 5 (51%), the isopentyl monocarbonate 10 (51%), the ethyl monocarbonate 4 (50%), and famciclovir (48%). In rats, the methyl monocarbonate 3, 4, 6, the n-butyl monocarbonate 7, and 10 (39-41%) showed levels of mean urinary recovery of penciclovir similar to that from famciclovir (40%). The alkyl monocarbonates 4-10 were found to be quite stable in the aqueous buffer solutions, and among them, 6 was the most stable with the half-lives (t1/2) of 88, >200, 61, and 26 days at pH 1.2, 6.0, 7.4, and 8.0, respectively. In addition, 6 was highly soluble in H2O (138.8 mg/mL, 20 degrees C).
Acyclovir↗
HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences.
Previous studies showed that HLA-E was expressed in lymphoblastoid cell line (LCL) 721.221 cells, but surface expression was lacking. To determine the signals controlling surface expression, we constructed a series of hybrid genes using complementary portions derived from the HLA-E and HLA-A2 genes. In this manner, a hybrid of HLA-E was identified, designated AEH, which differed from HLA-E by having the HLA-A2 signal sequence substituting for the HLA-E leader peptide. Transfection of LCL 721.221 cells with AEH induced HLA-E surface expression. Analysis of peptides bound to HLA-E revealed that a nonamer peptide derived from the A2 signal sequence was the predominant peptide bound. LCL 721.221 cells transfected with certain class I genes, including HLA-G, were also sufficient to promote peptide binding and HLA-E surface expression without increasing the level of HLA-E heavy chain synthesis. Peptides bound to HLA-E consisted of nine amino acids, with methionine at position 2 and leucine in the carboxyl-terminal position, and were nearly identical to the leader sequence-derived peptide previously shown to be a predominant peptide bound to the murine Qa-1 Ag. Signal peptides derived from certain HLA-B proteins with threonine in position 2 only marginally up-regulated HLA-E surface expression in .221 cells. An examination of HLA-E peptide binding in the TAP negative cell line .134 indicated that peptide binding to HLA-E was dependent on a functional TAP heterodimer regardless of whether peptide was available in cis, as in the AEH construct, or in trans, as in the class I transfectants of .221 cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.
We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.
Antigens, CD↗
Saguenay Lac Saint Jean cytochrome oxidase deficiency: sequence analysis of nuclear encoded COX subunits, chromosomal localization and a sequence anomaly in subunit VIc.
A biochemically distinct form of cytochrome oxidase (COX) deficiency found in the Saguenay region of Quebec is an autosomal recessive trait. The cDNA sequences of all 10 nuclear-encoded subunits from a patient's fibroblasts showed normal coding sequence. Sequences for subunit VIc in two atypical patients showed a heterozygous base substitution. Subunit VIc was localized to chromosome 18.
Animals↗
Development of Immunoassays for Type II Synthetic Pyrethroids. 1. Hapten Design and Application to Heterologous and Homologous Assays.
Immunoassays differing in selectivities for pyrethroid insecticides have been developed for the detection of type II pyrethroids, including deltamethrin, cypermethrin, and lambda-cyhalothrin. Two approaches were employed in hapten synthesis to raise antibodies with different cross-reactions: (1) use of three spacer attachment points to offset different parts of molecules from the points of attachment and (2) use of linkers with and without bulky groups in the enzyme conjugate to reduce antibody affinities for the spacer arm in the immunoassay. The first approach resulted in the preparation of three series of haptens with a spacer attached (1) at the aromatic moiety of pyrethroid, (2) through the middle of the molecule, and (3) at the cyclopropane moiety. Haptens based on the derivatives of the pyrethroid metabolites were also prepared. The second approach involved the use of a linker with a bulky (cyclohexane ring) functionality for preparation of an enzyme conjugate. While most combinations of antibody and conjugate could be used in immunoassays for detection of deltamethrin in the 10-100 µg/L range, in most cases the limits of detection of the assays (for total isomers of a particular target pyrethroid) were lowered 10-50 fold by treatment of the pyrethroid standards with dilute alkali to produce a different isomer mix. Fifteen antisera prepared using 8 haptens were each screened with 14 peroxidase conjugates, and 26 antibody/conjugate combinations were selected for further study on the basis of the assay sensitivity, dynamic behavior, and specificity for deltamethrin, cypermethrin, and cyhalothrin. These immunoassays provided 50% inhibition of antibody binding (IC(50)) values between 1.5 and 4.2 µg/L of isomerized total deltamethrin and limits of detection of 0.2-0.7 µg/L. The most sensitive immunoassay for total deltamethrin was obtained using cypermethric acid-KLH as the immunogen and a conjugate based on a derivative of cypermethrin coupled through the middle of the molecule to peroxidase. These provided an IC(50) of 2 µg/L and a limit of detection of 0.2 µg/L of isomerized total deltamethrin. However, no particular hapten design produced antisera of clearly superior sensitivity or specificity for deltamethrin. Differing cross-reactions with the closely related pyrethroids, deltamethrin, cypermethrin, and cyhalothrin, were obtained, and for several antibodies the cross-reaction as well as the limits of detection could be altered by varying the conjugate combinations. Each of the 12 antibody/enzyme conjugate combinations that sensitively detected deltamethrin were very stereospecific, detecting the alphaS, 1R cis, (DM1), and alphaR, 1R cis (DM2) isomers only; the assay sensitivity was greater for the latter isomer.
Journal Article↗
Development of Immunoassays for Type II Synthetic Pyrethroids. 2. Assay Specificity and Application to Water, Soil, and Grain.
Cross-reactions of a panel of immunoassays developed for type II (alpha-cyano-) synthetic pyrethroids were evaluated with type I and II compounds. Cross-reactions of both groups were affected by alkali treatment. The treatment typically increased sensitivities of type II compounds, and decreased cross-reactions of type I compounds. After isomerization, each of the 12 combinations studied provided more sensitive detection of deltamethrin than the other compounds, even in the case of antisera and enzyme conjugates based on cypermethrin, cyhalothrin, or their fragments. Several immunoassays were selective for deltamethrin. Assays with the broadest specificities detected type I and II compounds with IC(50) values of 20-400 µg/L. None of the assays detected compounds lacking a cyclopropane ring (fenvalerate, fluvalinate). Spike and recovery studies for deltamethrin in water, soil, and wheat grain indicated that the selected immunoassays quantified it with high precision and good recoveries. Good correlations between immunoassay and gas chromatography/mass spectrometry data were also obtained for incurred residues of deltamethrin and bifenthrin extracts of water and soil samples.
Journal Article↗
HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer.
The HLA-E class Ib molecule constitutes a major ligand for the lectin-like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class I leader sequence-derived nonapeptides bind to endogenous HLA-E molecules in the HLA-defective cell line 721.221, inducing HLA-E surface expression, and promote CD94/NKG2A-mediated recognition. We compared the ability of NK clones which expressed either inhibitory or activating CD94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.221 cells loaded with a panel of synthetic nonamers derived from the leader sequences of most HLA class I molecules. Our results support the notion that the primary structure of the HLA-E-bound peptides influences CD94/ NKG2-mediated recognition, beyond their ability to stabilize surface HLA-E. Further, CD94/ NKG2A+ NK clones appeared more sensitive to the interaction with most HLA-E-peptide complexes than did effector cells expressing the activating CD94/NKG2C receptor. However, a significant exception to this pattern was HLA-E loaded with the HLA-G-derived nonamer. This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity. These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions.
Antigens, CD↗
Signaling via cAMP in fungi: interconnections with mitogen-activated protein kinase pathways.
The cAMP signal transduction pathway controls a wide variety of processes in fungi. For example, considerable progress has been made in describing the involvement of cAMP pathway components in the control of morphogenesis in Saccharomyces cerevisiae, Ustilago maydis, and Magnaporthe grisea. These morphological processes include the establishment of filamentous growth in S. cerevisiae and U. maydis, and the differentiation of an appressorial infection structure in M. grisea. The discovery that appressorium formation requires cAMP signaling provides an immediate connection to fungal virulence. This connection may have broader implications among fungal pathogens because recent work indicates that cAMP signaling controls the expression of virulence traits in the human pathogen Cryptococcus neoformans. In this fungus, cAMP also influences mating, as has been found for Schizosaccharomyces pombe and as may occur in U. maydis. Finally, cAMP and mitogen-activated protein kinase pathways appear to function coordinately to control the response of certain fungi, e.g., Saccharomyces cerevisiae and Schizosaccharomyces pombe, to environmental stress. There are clues that interconnections between these pathways may be common in the control of many fungal processes.
Calcium-Calmodulin-Dependent Protein Kinases↗
Effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women.
OBJECTIVE: To investigate changes in plasma lipoprotein profile, hemostatic factors, platelet aggregation, endothelin-1, and cardiac function during postmenopausal sequential 6-month hormone replacement therapy (HRT). DESIGN: Open longitudinal prospective study. SETTING: Gynecologic department of a medical center. PATIENT(S): Twenty-one healthy hysterectomized postmenopausal women. INTERVENTION(S): Oral E2 valerate (2 mg/d) combined with medroxyprogesterone acetate (MPA) (10 mg/d) during the last 10 days of each 21-day cycle. The treatment period was 6 months. MAIN OUTCOME MEASURE(S): Plasma lipoprotein profile, hemostatic parameters, platelet aggregation, endothelin-1, and left ventricular function. RESULT(S): After 6 months of treatment, total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol were significantly progressively reduced. Atherogenic indices of total cholesterol-to-high-density lipoprotein (HDL) cholesterol and LDL-to-HDL cholesterols also showed a significant progressive decline. The concentrations of antithrombin III were significantly increased. The maximum aggregation and slope of platelet aggregation were significantly reduced, but all parameters were more pronounced at 1 month of HRT than at 3 or 6 months. The concentrations of endothelin-1 were significantly reduced (by 16.1%). In the evaluation of left ventricular function, only peak atrial diastolic velocity was significantly reduced. CONCLUSION(S): Combined HRT had favorable effects on lipids and lipoproteins, hemostatic factors, platelet aggregation, endothelin-1, and left ventricular function. However, further study is needed to evaluate the long-term effects of combined HRT, especially on platelet aggregation and cardiac function.
Blood Coagulation Factors↗
Histopathology in pediatric recipients of living related liver transplantation.
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Adolescent↗
Microphone and electroglottographic data from dysphonic patients: type 1, 2 and 3 signals.
Recently, it has been suggested that statistics which are dependent upon the reliable extraction of a single fundamental period, such as jitter and shimmer, are valid only for nearly periodic signals. This study explored the incidence of nearly periodic and nonperiodic microphone and electroglottographic signals obtained from 202 dysphonic patients. It was found that approximately 42% were type 1 (nearly periodic); approximately 35% were type 2 (containing bifurcations, modulations or subharmonic structure); and approximately 22% were type 3 (chaotic). Discriminating between type 2 and 3 signals was very difficult for 40% of the signals which were ultimately rated type 3. This was due to the brevity of the apparently chaotic segment, and/or the persistence of some harmonic structure within the chaos. Irrespective of that difficulty, the results suggest that there may be a substantial incidence of nontype 1 signals in a given clinical population. It was concluded, therefore, that signal typing is a necessary step in the analyses of microphone and electoglottographic data.
Adolescent↗
Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine esters as potential prodrugs of acyclovir.
2-Amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a-d were synthesized as potential prodrugs of acyclovir, and were evaluated for their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2-hydroxyethoxymethyl)purine (3) with trimethylamine in THF/DMF (4:1) followed by a reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2 in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) in DMF in the presence of a catalytic amount of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%) and comparable to that of valacyclovir (50%). The prodrug 4d protected dose-dependently the mortality of HSV-1-infected mice, and the group treated with 4d at a dose of 400 mg/kg showed the longest mean survival day (14.6+/-3.1 days) (mean+/-S.D.).
Acyclovir↗
Parallel solution synthesis of pyridinethiones, pyridinones and thienopyridines.
The parallel solution synthesis of three classes of heterocycles is described. Arrays of pyridinethiones, pyridinones and thienopyridines were prepared using one-step chemistry starting from readily accessible building blocks. The latter class of compounds was accessed by utilising a library-from-library approach.
Combinatorial Chemistry Techniques↗
The use of serum CA-125 as a marker for endometriosis in patients with dysmenorrhea for monitoring therapy and for recurrence of endometriosis.
BACKGROUND: To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea, as well as its significance in monitoring therapy and follow-up. METHODS: One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospectively studied for serum CA-125 concentration. For those with advanced endometriosis receiving danazol treatment after conservative surgery, CA-125 was also determined every month during medication and once every 12 months after treatment. RESULTS: The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1% and 87.5% respectively. Elevated CA-125 (>35 U/ml) was noted in 65/75 cases (86.70%) with advanced endometriosis, but in only 15/56 patients (26.8%) with minimal and mild endometriosis. Although there were significantly higher CA-125 levels in unmarried women, and a negative correlation (r=-0.1970, p=0.0284) between CA-125 and parity, there was no statistical difference in incidence of endometriosis by the status of marriage or parity. Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment, even though they tested with normal CA-125 levels (<35 U/ml) at that time. Fifteen patients had elevated CA-125 levels before and one year after therapy, and were confirmed with recurrence of endometriosis by laparoscopy. Nine women with elevated CA-125 levels before treatment, were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy. CONCLUSION: For endometriosis, CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels. It is not an effective screening tool for patients with dysmenorrhea, or for monitoring therapy. There was no significant correlation between the development of endometriosis and reproductive factors.
Adolescent↗