Familial Alzheimer's disease associated with S182 codon 286 mutation.
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Adult↗
Biomedical subjects
N Wang
Publications and source records attributed to N Wang.
Microsphere formation in a series of derivatized alpha-amino acids: properties, molecular modeling, and oral delivery of salmon calcitonin.
A series of benzoylated and phenylsulfonylated amino acids are novel, low molecular weight, self-assembling molecules. At low pH, these compounds form microspheres that dissolve readily under neutral conditions. In a given synthetic series, those molecules with low aqueous solubility formed microspheres more readily than did the molecules possessing high water solubility, suggesting that the hydrophobicity of these compounds contributes to the ability to form microspheres. In addition, molecular modeling studies on selected compounds have shown that microsphere formation may depend also on various aromatic ring and dipole-dipole interactions, which could effect the extent and types of favorable stacking conformations between molecules. The microspheres prepared from these compounds have been used to effect the oral delivery of salmon calcitonin, a model protein drug, in both rodents and primates.
Administration, Oral↗
Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,4-anhydro-D-xylitol.
Described herein is a general method for the synthesis of all positional isomers of methylated and acetylated or benzoylated 1,4-anhydro-D-xylitol. The benzoates are generated simultaneously from 1,4-anhydro-D-xylitol by sequential partial methylation and benzoylation or sequential partial benzoylation and methylation. The individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation and acetylation provided the corresponding acetates. The 1H NMR spectra of the benzoates and the electron ionization mass spectra of the acetates and the tri-O-methyl derivative are reported herein as are the linear temperature programmed gas-liquid chromatography retention indices of the acetates and the tri-O-methyl derivative on three different capillary columns.
Acetates↗
Synthesis and characterization of authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,4-anhydro-L-fucitol.
Described herein is the synthesis of all positional isomers of methylated and acetylated or benzoylated 1,4-anhydro-L-fucitol. The benzoates are generated simultaneously from 1,4-anhydro-L-fucitol by sequential partial methylation and benzoylation or sequential partial benzoylation and methylation. The individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation and acetylation provided the corresponding acetates. The 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tri-O-methyl derivative are reported herein as are the linear temperature programmed gas-liquid chromatography retention indices of the acetates and the tri-O-methyl derivative on three different capillary columns.
Acetates↗
Synthesis and characterization of authentic standards for the analysis of ribofuranose-containing carbohydrates by the reductive-cleavage method.
Described herein is the synthesis of all positional isomers of partially methylated and acetylated or benzoylated 1,4-anhydro-D-ribitol. The benzoates are generated simultaneously from 1,4-anhydro-D-ribitol by sequential partial methylation and benzoylation or sequential partial benzoylation and methylation. The individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation and acetylation provided the corresponding acetates. Reported herein are the 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tri-O-methyl derivative and also for the acetates and the tri-O-methyl derivative, their linear temperature programmed gas-liquid chromatography retention indices on three different capillary columns.
Acetates↗
Cell shape, cytoskeletal mechanics, and cell cycle control in angiogenesis.
Capillary endothelial cells can be switched between growth and differentiation by altering cell-extracellular matrix interactions and thereby, modulating cell shape. Studies were carried out to determine when cell shape exerts its growth-regulatory influence during cell cycle progression and to explore the role of cytoskeletal structure and mechanics in this control mechanism. When G0-synchronized cells were cultured in basic fibroblast growth factor (FGF)-containing defined medium on dishes coated with increasing densities of fibronectin or a synthetic integrin ligand (RGD-containing peptide), cell spreading, nuclear extension, and DNA synthesis all increased in parallel. To determine the minimum time cells must be adherent and spread on extracellular matrix (ECM) to gain entry into S phase, cells were removed with trypsin or induced to retract using cytochalasin D at different times after plating. Both approaches revealed that cells must remain extended for approximately 12-15 h and hence, most of G1, in order to enter S phase. After this restriction point was passed, normally 'anchorage-dependent' endothelial cells turned on DNA synthesis even when round and in suspension. The importance of actin-containing microfilaments in shape-dependent growth control was confirmed by culturing cells in the presence of cytochalasin D (25-1000 ng ml-1): dose-dependent inhibition of cell spreading, nuclear extension, and DNA synthesis resulted. In contrast, induction of microtubule disassembly using nocodazole had little effect on cell or nuclear spreading and only partially inhibited DNA synthesis. Interestingly, combination of nocodazole with a suboptimal dose of cytochalasin D (100 ng ml-1) resulted in potent inhibition of both spreading and growth, suggesting that microtubules are redundant structural elements which can provide critical load-bearing functions when microfilaments are partially compromised. Similar synergism between nocodazole and cytochalasin D was observed when cytoskeletal stiffness was measured directly in living cells using magnetic twisting cytometry. These results emphasize the importance of matrix-dependent changes in cell and nuclear shape as well as higher order structural interactions between different cytoskeletal filament systems for control of capillary cell growth during angiogenesis.
Actin Cytoskeleton↗
The clonal nature of mediastinal germ cell tumors and acute myelogenous leukemia. A case report and review of the literature.
The clonal identity of a mediastinal germ cell malignant tumor and acute myelogenous leukemia is described in an 11-year-old boy in whom both tumors presented simultaneously. The relationship between these two histologically distinct malignancies is discussed in relation to this patient and 34 previously reported patients.
Child↗
The characterization of chromosomal rearrangements by a combined micro-FISH approach in a patient with myelodysplastic syndrome.
We report the application of a combined strategy: chromosome microdissection, degenerate oligonucleotide primed-PCR, and reverse chromosome painting (micro-FISH), as well as forward chromosome painting, for the characterization of chromosomal rearrangements in a MDS patient with the karyotype 46,XX, -11, +r analyzed by G-banding. The karyotype was refined as 46,XX,der(2)t(2;11) (q35;?p13),der(11)dic r(11)(:p13-->q13::p13-->q13:). Our study demonstrated that the chromosome composition of a neoplasia can be identified more systematically and accurately using these combined molecular cytogenetic approaches. The DOP-PCR methodology modified is suitable for the practical application of micro-FISH on specimens prepared for routine banding analysis.
Aged↗
Assay of HIV-1 protease activity by use of crude preparations of enzyme and biotinylated substrate.
An enzyme immunoassay was developed for monitoring protease reactions of human immunodeficiency virus (HIV). The protease and its substrate, the gag precursor, were generated separately in Escherichia coli. The HIV-1 protease was generated with a glutathione-S-transferase expression system and the gag substrate, named Pin17/24, was prepared with a PinPoint expression system. Pin17/24 consists of an N-terminal peptide, which is biotinylated in E. coli, fused with a C-terminal peptide that contains a protease cleavage site flanked by p17 and p24 segments. Through its biotin in the N-terminal region, Pin17/24 bound to ELISA plates coated with avidin, whereas through its C-terminal region, the same molecule of Pin17/24 could be recognized by an anti-p24 monoclonal antibody. When the protease was added to Pin17/24, the p24 fragment was released from the biotinylated fusion protein and could no longer be retained on the avidin plates, and as a result, binding of the anti-p24 monoclonal antibody decreased. The binding was specific and the reaction was inhibited by a known HIV protease inhibitor. Due to the specific interactions between avidin and biotin, monoclonal antibody and antigen, and the HIV protease and the gag substrate, crude preparations of these reagents can be used readily in the assay. The simplicity and feasibility of this method should be useful for simultaneous monitoring of many enzyme reactions, particularly for screening possible HIV protease inhibitors.
Animals↗
C/EBP alpha: a critical regulator of genes governing integrative metabolic processes.
The role of C/EBPalpha in the developmental expression of a subset of genes governing essential metabolic processes has recently been elucidated using a mutant mouse model that lacks this transcription factor. The mutation results in a failure of the liver and white and brown adipose tissue to develop normal metabolic functions in the immediate perinatal period, including hepatic glycogen synthesis and gluconeogenesis and the synthesis and deposition of triglyceride in adipose tissue. The metabolic alterations are very similar to those of human infants born prior to the third trimester and suggest that many of the medical complications of prematurity are a result of the lack of activation of C/EBPalpha in development.
Adipose Tissue, Brown↗
Leukemic glaucoma: the effects on outflow facility of chronic lymphocytic leukemia lymphocytes.
The purpose of this study was to investigate the mechanisms of the leukemic glaucoma. We established a cell culture from leukemic cells collected from the aqueous humor of a living patient with chronic lymphocytic leukemia (CLL) and glaucoma secondary to the leukemia. We then perfused 16 pairs of fresh cadaver normal human eyes at a constant pressure of 10 mmHg at 37 degrees C. We delivered as a bolus either cultured CLL cells or cultured normal lymphocytes, using 3 x 10(2), 3 x 10(3), 3 x 10(4) or 3 x 10(5) cells in Bárány's solution, into one eye of each pair. The other eye of the pair served as a control, receiving a sham bolus of Bárány's solution alone. In addition, CLL and normal lymphocytes were perfused through 0.2, 0.6, 2, and 3 microns millipore filters. Following perfusion, the tissue and the filters were examined histopathologically by light, transmission and scanning electron microscopy. Cultured leukemic lymphocytes perfused into normal cadaver eyes caused a significantly more profound reduction in outflow facility than normal lymphocytes (P < 0.05); however, there was no significant difference in the effect on outflow facility between leukemic and normal lymphocytes when they were perfused through the millipore filters. Histopathology confirmed the presence of lymphocytes in the trabecular meshwork and Schlemm's canal, deforming on passage through the inner wall. Our results suggest that leukemic lymphocytes in CLL may reduce outflow facility by means of a biological interaction with the tissues of the outflow pathways, rather than by mechanical obstruction due to a lack of distensibility. Questions remain as to the nature of this biological interaction.
Aqueous Humor↗
Percutaneous transluminal coronary angioplasty failures in patients with multivessel disease. Is there an increased risk?
In recent years, there has been a nationwide trend toward performing percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease. The clinical course of 57 consecutive patients who required emergency first-time coronary artery bypass grafting operations were reviewed to assess for difference in outcome between the 28 patients (49%) with single-vessel disease and the 29 patients (51%) with multivessel disease. The two groups were similar in preoperative characteristics except for a higher proportion of chronic obstructive pulmonary disease in the patients with multivessel disease (p = 0.03). Twice as many patients with multivessel disease were in shock (single-vessel disease = 4 [14%], multivessel disease = 8 [28%], p = not significant) en route to the operating room and significantly more patients with multivessel disease required on-going cardiopulmonary resuscitation (single-vessel disease = 0 [0%], multivessel disease = 5 [17%], p = 0.03). Significantly more coronary artery bypass grafts were placed in the patients with multivessel disease (single-vessel disease = 1.5 +/- 0.6, multivessel disease = 2.9 +/- 0.7, p < 0.01), which required longer aortic clamping time (p = 0.02) and cardiopulmonary bypass time (p < 0.01). There were seven postoperative deaths; all but one occurred in patients with multivessel disease (single-vessel disease = 1 [4%], multivessel disease = 6 [21%], p = 0.05). According to multivariate analysis, incremental risk factors of mortality were preoperative shock (p < 0.01), urgent or emergency percutaneous transluminal coronary angioplasty (p = 0.06), and multivessel disease (p = 0.12). Despite a similar incidence of myocardial infarction (single-vessel disease = 8 [29%], multivessel disease = 12 [41%], p = not significant), patients with multivessel disease had a higher incidence of cardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 11 [38%], p = 0.04) and noncardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 12 [41%], p = 0.02). By multivariate analysis, incremental risk factors of morbidity were preoperative shock (p < 0.01), multivessel disease (p = 0.02), and ejection fraction < 50% (p = 0.07). In the subset of patients with multivessel disease, preoperative shock, ejection fraction < 50, and an age of 60 years or greater were associated with higher morbidity and mortality. In conclusion, the risk of percutaneous transluminal coronary angioplasty failure is considerably higher in patients with multivessel disease. In certain subsets of patients with multivessel disease, coronary artery bypass grafting would be a safer procedure when compared with percutaneous transluminal coronary angioplasty for initial myocardial revascularization.
Age Factors↗
Tumor necrosis factor-alpha regulates nicotinic responses in mixed cultures of sympathetic neurons and nonneuronal cells.
It is recognized that tumor necrosis factor-alpha (TNF-alpha), a pleiotropic cytokine, influences hormone secretion and transmitter release from central neurons. To examine the role of TNF-alpha as a modulator of autonomic function of the PNS, we measured [3H]norepinephrine ([3H]NE) secretion evoked by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, in cultures from neonatal rat superior cervical ganglia (SCG). We found that (1) DMPP-evoked [3H]NE secretion was enhanced in SCG mixed cultures treated for 48 h with recombinant human TNF-alpha (rhTNF-alpha) plus rat interferon-gamma (IFN-gamma) but not in cultures treated with either cytokine alone; (2) an increase in [3H]NE secretion was also observed in mixed cultures treated with recombinant murine TNF-alpha (rmTNF-alpha) alone; and (3) the presence of nonneuronal cells or soluble factors released by them was required for the effect of these cytokines on secretion. Electrophysiologic experiments revealed an increase in nicotinic receptor current density in neurons from mixed cultures treated with rhTNF-alpha plus IFN-gamma or with rmTNF-alpha when compared with control cultures. We conclude that prolonged exposure to rhTNF-alpha plus IFN-gamma or rmTNF-alpha regulates nicotinic responses in SCG cultures via a soluble factor or factors secreted by nonneuronal cells.
Animals↗
Utilization of sialic acid-binding synthetic peptide sequences derived from pertussis toxin as novel anti-inflammatory agents.
Pertussis toxin, a virulence factor produced by the organism Bordetella pertussis, has been shown to have functional similarities with selectins and to bind to similar sialic acid-containing oligosaccharides structures. Previously, we demonstrated that the amino-terminal region of the S2 subunit of pertussis toxin contained a short six amino acid sequence (SPYGRC) which displayed reasonable homology to a sequence that constitutes a portion of the sialic acid binding site in wheat germ agglutinin. Synthetic peptides containing this hexapeptide motif had the ability to bind to sialic acid-containing glycoconjugates including the putative oligosaccharide receptors (sialyl Lewis X and sialyl Lewis A) for selectins. Control peptides containing randomized sequences were inactive at inhibiting binding, indicating that the hexapeptide motif is important for interacting with sialic acid. Since pertussis toxin-derived peptides demonstrated the ability to interact with selectin receptors, we speculated that they should antagonize selectin-mediated inflammatory activity. To test this hypothesis, we evaluated the peptides for the ability to reduce neutrophil binding to activated endothelial cells as well as the anti-inflammatory activity in the mouse footpad swelling assay. Both S2 peptides were active at reducing neutrophil binding and footpad swelling, while the randomized control peptides were inactive.
Amino Acid Sequence↗
Impairment of the melanogenic pathway in B16 melanoma cells transfected with class I H-2 genes.
Transfection of class I H-2Kb or H-2Kd into cells of a pigmented subclone of B16-F10 BL6 (termed BL6-8) results in the loss of melanin production. In contrast, transfected BL6-8 cells expressing H-2Dd, H-2Ld, class I H-21Ak and/or the neor genes maintained their pigmented phenotype. Melanogenesis was also inhibited in cells which expressed the endogenous H-2Kb, but not the endogenous H-2Db, gene. In order to identify the specific defects in the melanogenic pathway responsible for the absence of melanin production, factors known to be related to the regulation of pigment formation were evaluated in H-2K-expressing cells. These studies showed that: (1) transfection of BL6-8 cells with the H-2Kb or H-2Kd, but not with the H-2Dd, H-2Ld or H-21Ak, genes was associated with complete inhibition of tyrosinase activity; (2) alpha-melanocyte-stimulating hormone (MSH) and theophylline (an inhibitor of cAMP phosphodiesterase) failed to stimulate tyrosinase activity in H-2K-positive cells, whereas tyrosinase activities in untransfected, or H-2DdH-2Ld, neor or H-21Ak-transfected cells were dramatically increased by those agents; (3) treatment with MSH had no effect on cAMP levels in H-2K-positive cells but stimulated cAMP levels more than 100-fold in H-2K-negative cells; (4) in contrast to MSH, forskolin, a stimulator of adenylate cyclase, was able to stimulate cAMP levels in all cell lines tested, but in H-2Kb-positive cells the levels of forskolin-induced cAMP were significantly less than those elicited in H-2Kb-negative cells; (5) electron microscopy showed that H-2K-positive cells lacked mature melanosomes; (6) Northern blot analyses showed that H-2K-positive cells lacked mRNA for tyrosinase or for the MSH receptor. Taken together, expression of the endogenous or transfected H-2K gene in BL6 melanoma cells results in down-regulation of the entire melanogenic pathway, including the inhibition of tyrosinase and MSH receptor gene expression, cAMP responses and melanosomal biogenesis.
Animals↗
Near dipole-dipole effects in electromagnetically induced transparency.
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Journal Article↗
Optimal control of optical pulse propagation in a medium of three-level systems.
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Journal Article↗
Incomplete expression of the tyrosinase gene family (tyrosinase, TRP-1, and TRP-2) in human malignant melanoma cells in vitro.
Sequence analysis of two clones found repressed in melanoma cell lines in earlier studies showed 9F2 to be identical with the TRP-1 gene and 6F5 with TRP-2 containing a long untranslated 3' end. For further investigation of the expression of the tyrosinase gene family in normal and malignant melanocytic cells, a series of melanoma cell lines and of cultured melanocytes were analyzed by Northern blotting and by reverse transcriptase-polymerase chain reaction (RT-PCR). The Northern blots were probed with cDNA fragments specific for TRP-1, TRP-2, and tyrosinase, for nested tyrosinase-PCR the outer primers specified a 284 bp and the nested primers a 207 bp fragment. Investigations on 14 established melanoma cell lines grown in different media compared with seven normal human melanocyte (NHM) cultures revealed that all three pigment genes were expressed in NHM, whereas pigment gene expression was found repressed in nearly all melanoma cell lines and was completely absent in 4 of 14 specimen. In particular, tyrosinase and TRP-2 genes were found always to be expressed together, and TRP-1 mRNA alone was absent in four melanoma cell lines. Negativity of cultured melanoma cells for tyrosinase mRNA was confirmed by nested RT-PCR, and gene deletion was ruled out by genomic Southern blots. The gene expression seemed independent from the type of medium used for cultivation. These findings indicate repressed or lacking expression of pigment genes in melanoma cell lines, most likely due to regulatory mechanisms, and that differences may exist between tyrosinase and TRP-2 on one hand and TRP-1 on the other. Overall, it seemed that RT-PCR for tyrosinase has limited value for identifying melanoma cells in the peripheral blood of melanoma patients; TRP-1, TRP-2, and other, additional markers may be required.
Base Sequence↗