Administering metered dose bronchodilators during general anesthesia.
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Bronchodilator Agents↗
Biomedical subjects
H Vu
Publications and source records attributed to H Vu.
Effects of albumin on lipid synthesis, apo B-100 secretion, and LDL catabolism in HepG2 cells.
This study examines the effects of extracellular albumin on hepatic apo B-100 metabolism. To do so, a transformed human liver cell line, HepG2, was used as a hepatocyte model and the concentration of albumin in the medium was varied between 0 and 5 g%. Apo B-100 and apo A1 concentrations in the medium were determined by specific enzyme-linked immunoassay (ELISA) and intracellular synthesis of cholesterol ester and triglyceride were determined by addition of appropriate radiolabels to the medium. The data demonstrate that the reduction of extracellular albumin concentration resulted in increased apo B-100 concentration in the medium. Apo A1 secretion, however, was unaffected. While the differences in apo B-100 concentration in the medium were statistically significant (33% +/- 7%, P < 0.0025, 0 g% albumin compared to 5 g% albumin in the medium), the absolute magnitude of the effect under these conditions was relatively modest. Nevertheless, the changes were consistent and evident over incubation periods as long as 8 days. Of interest, although triglyceride synthesis was unaffected, cholesterol ester synthesis changed such that as albumin concentration decreased, synthesis of cholesterol ester increased paralleling the changes in apo B-100 (170% +/- 9%, P < 0.005). These findings were extended by studying interventions which altered cholesterol ester synthesis. Addition of the compound 58-035 (5 micrograms/ml, a specific inhibitor of acylcholesterol acyltransferase activity) resulted in substantial inhibition of cholesterol ester synthesis (39% to 66%, P < 0.025 and P < 0.005, respectively) and apo B-100 concentrations in the medium which decreased by 20% to 28%, P < 0.025. Triglyceride synthesis, in contrast, increased significantly by 32% P < 0.025. Therefore, addition of 58-035 confirmed the previous findings of a parallel relation between cholesterol ester synthesis and apo B-100 concentration in the medium. Nonetheless, albumin still had an additional inhibitory effect on cholesterol ester and apo B-100 secretion. Of interest, when chylomicron remnants (25 micrograms/ml cholesterol), which cause apo B-100 secretion to increase by more than threefold, were added to the medium, albumin now had a more pronounced absolute effect on apo B-100 secretion with a 48% inhibition observed as albumin was increased from 0 to 5 g% in the medium (P < 0.0125). The effect of extracellular albumin on the low density lipoprotein (LDL) pathway was also examined. No differences in non-specific cell association component were detected.(ABSTRACT TRUNCATED AT 400 WORDS)
Amides↗
The role of amino acids in ApoB100 synthesis and catabolism in human HepG2 cells.
The object of this study was to examine the effects of extracellular amino acids on hepatic apoB100 metabolism using a transformed human liver cell line (HepG2) as a hepatocyte model. The data demonstrate that reduced extracellular amino acids resulted in marked increases in apoB100 concentrations in the medium (87 +/- 10% increase; p < 0.002). These data contrast with the effects of amino acids on secretion of total hepatic protein into the medium, which increased by 541 +/- 83% at 5.5 mg/ml amino acids compared to the low (0.5 mg/ml) amino acid medium (p < 0.01), pointing to a positive relationship between the concentration of amino acids in the medium and overall secretion of protein by the HepG2 cells. No significant effect of medium amino acid concentration on intracellular synthesis of cholesterol ester, cholesterol, triglyceride, or apoA1 secretion was evident. Amino acids also affected the activity of the low density lipoprotein pathway: at lower medium amino acid concentration, specific cell-associated radioactivity and cellular degradation were increased (117 +/- 24 and 233 +/- 13% at 0.5 versus 5.5 mg/ml amino acids, respectively). Pulse-chase analysis demonstrated that there was no difference in secretion efficiency of apoB (36 +/- 6 versus 46 +/- 8% in low versus high amino acid medium, respectively), but that the initial amount of [3H]apoB synthesized was greater in the low amino acid medium (10.5 +/- 3.8 versus 5.7 +/- 1.7 x 10(3) dpm [3H]apoB/mg of cell protein; p < 0.05). In contrast, the initial amount of [3H]albumin synthesized was much greater in the high amino acid medium (26.6 +/- 5.0 versus 54.6 +/- 19.0 x 10(3) dpm [3H]albumin/mg of cell protein in low versus high amino acid medium, respectively; p < 0.05). Slot blot analysis of apoB mRNA was 87 +/- 22% higher in lower amino acid medium as compared to the high amino acid medium (p < 0.01). These results demonstrate that amino acids have a profound negative regulatory effect on apoB synthesis and secretion and may shed light on the pathogenesis of some clinical dyslipidemias such as the increased plasma apoB levels in patients treated with continuous ambulatory peritoneal dialysis.
Albumins↗
Synthesis of cholesteryl supports and phosphoramidites containing a novel peptidyl linker for automated synthesis of triple-helix forming oligonucleotides (TFOs).
Preparation of G-rich TFOs containing cholesterol at the end presents challenging problems due to low yield in synthesis and loss in purification due to aggregation. These compounds also have low solubility which can result in variability in their uptake properties and cellular efficacy. To overcome these problems we have designed and synthesized cholesteryl -CPG (6) and -TentaGel (7) supports and phosphoramidite (8) containing a triglycyl linker.
Cholesterol↗
Effect of zidovudine on human placental trophoblast and Hofbauer cell functions.
We have optimized a procedure to isolate placental trophoblasts and Hofbauer cells simultaneously in a quantity sufficient for short-term cultures and then used these placental cells to investigate the effects of zidovudine (ZDV) on trophoblast and Hofbauer cell functions. Of more than 10 term placentas tested, ZDV inhibits DNA synthesis of trophoblasts in a concentration-dependent manner with half the maximal inhibitory concentration (IC50) of 9.88 +/- 1.35 microM. Of the hormones evaluated, production of progesterone by trophoblasts is most sensitive to ZDV (IC50 = 3.65 +/- 0.29 microM). The inhibitory effect of ZDV on the secretion of placental lactogen and choriogonadotropin by the trophoblasts was detected only at a much higher concentration (> or = 60 microM). ZDV does not affect trophoblast or Hofbauer cell protein synthesis. Collectively, our results indicate that at clinically relevant concentrations (< or = 10 microM), ZDV significantly inhibits both the DNA synthesis of placental trophoblasts and their production of progesterone, while having a minimal effect on protein synthesis of both types of placental cells.
Cells, Cultured↗
Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apo B levels.
The risk of premature coronary artery disease is related to an important degree to the number of particles of low density lipoproteins (LDL) in plasma, an estimate given by measurement of LDL apo B. In clinical practise, though it is total, not LDL apo B, which is measured. The purpose of the present study therefore was to compare plasma total and LDL apo B in the presence and absence of moderate hypertriglyceridemia. The results demonstrate that within the range of plasma triglyceride levels examined, i.e., values of triglyceride up to 500 mg/dl, there is close correspondence between total and LDL apo B, with the latter more than 90% of the former. VLDL composition was also examined and two patterns found in hypertriglyceridemic patients: those with normal apo B had markedly lipid enriched VLDL while those with elevated apo B had VLDL which was normal in composition except for a moderate increase in triglyceride content. Thus total apo B within the circumstances studied reflects principally LDL apo B. Moreover measurement of apo B allows distinction between two different forms of hypertriglyceridemia, only one of which - that with an increased LDL particle number - has previous work shown to be associated with increased coronary risk. Total apo B, therefore, provides additional information not available from conventional plasma and lipoprotein lipids which allows more precise physiologic classification and may lead to more rational choice of pharmacologic therapy in normolipidemic and hypertriglyceridemic patients.
Apolipoproteins B↗
Electromagnetic field exposure and amyotrophic lateral sclerosis.
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Amyotrophic Lateral Sclerosis↗
Large scale automated synthesis of oligonucleotides.
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Amides↗
Large scale automated synthesis of oligonucleotides.
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Automation↗
New reagents and solid support for automated oligonucleotide synthesis.
The optimal system for the rapid, efficient, convenient, and economical synthesis and purification of synthetic oligonucleotides has been advancing. By recognizing the very rapid reaction kinetics and taking advantage of an efficient, low volume delivery system, cycle times have decreased to about 5.5 minutes, without compromising synthesis performance. A new set of base protecting groups for cyanoethylphosphoramidite nucleoside monomers have been developed, which decreases the post-synthesis time requirements. A particular form of polystyrene has also been developed as a solid support for automated oligonucleotide synthesis. Typical sequencing or PCR primers (20mers) now require less than 2 hours for synthesis and 2 hours for cleavage and deprotection.
Indicators and Reagents↗
Jejunal angiodysplasia presenting as acute lower gastrointestinal bleeding.
Vascular malformations of the bowel are uncommon sources of gastrointestinal (GI) tract bleeding with the majority of cases occurring in the right colon in elderly patients. Angiodysplasia can be difficult to diagnose, thereby complicating management as well. In the past, the diagnosis of angiodysplasia was rarely made early and rested upon a high index of suspicion in patients with lower GI bleeding and multiple negative diagnostic evaluations. Consequently, surgery was often performed late with increased morbidity and high recurrence rates. With the advent of pre- and intraoperative selective angiography, these vascular malformations are readily demonstrated in most cases and will often respond to conservative interventional radiologic procedures. Failing this, angiographic localization has made segmental resection both safe and quite accurate, thus obviating extensive, blind excision.
Acute Disease↗
The effect of ASP on the adipocyte of the morbidly obese.
The control of triglyceride synthesis within the adipocyte is not fully understood. Insulin is considered to be the most potent stimulant of triglyceride synthesis. In this paper, we report on the effect of a small (14000 Da), basic (pI 9.0) protein isolated from human serum. This protein has been called acylation stimulating protein (ASP). It is a potent stimulant of triglyceride synthesis in adipocytes from both normal weight and morbidly obese subjects. Its stimulatory effect on adipocytes is both rapid, occurring between 15-30 min after the start of incubation, and prolonged, lasting for up to 3 hr. Compared to insulin, it is sixfold more potent in its effect on triglyceride synthesis. As well as acting on isolated cells, ASP also has a fourfold stimulatory effect on triglyceride synthesis in human adipose microsomes at a concentration of 25 micrograms/ml. This study indicates that ASP is a potent stimulant of triglyceride synthesis and therefore may play a role in the pathogenesis of morbid obesity.
Adipose Tissue↗
Metabolic response of Acylation Stimulating Protein to an oral fat load.
Acylation Stimulating Protein (ASP) is a small (mol wt 14,000), basic (pI 9.0) protein present in human plasma. When examined in vitro with normal human cultured skin fibroblasts and adipocytes, ASP appears to be the most potent stimulant of triglyceride synthesis yet described. In this study, a competitive ELISA assay for ASP has been developed using immunospecific polyclonal antibodies, and ASP levels have been measured in seven normal subjects. Following an oral fat load, a sustained significant increase in ASP occurs, whereas after an oral glucose load, ASP levels do not change significantly. These responses are entirely opposite to those of insulin, which rises sharply but transiently after an oral glucose load but is unchanged after an oral fat load. Both the fasting and peak ASP levels were significantly related to the postprandial lipemia. These data provide the first in vivo evidence that Acylation Stimulating Protein may play an important physiological role in the normal response to an oral fat load.
Adult↗
The effect of a plasma protein fraction on lipid synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia.
Lipid synthesis was measured in cultured skin fibroblasts obtained from normals and patients with Hyperapobetalipoproteinemia (HyperapoB). Using lipoprotein-deficient serum medium, triglyceride synthesis and cholesterol esterification were greater in normals than in HyperapoB due to differences in de novo synthesis, not to differences in re-esterification or to different rates of hydrolysis. When normal and HyperapoB cells were incubated in serum-free medium, however, lipid synthesis was the same. Serum was then fractionated chromatographically and a partially purified protein fraction shown to be responsible for the stimulatory effect in normals.
Adult↗
Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams.
Enterobacter cloacae strains producing chromosomally mediated beta-lactamase constitutively show high degrees of resistance to most of the third-generation beta-lactams. It has been proposed that this resistance is due to the nonhydrolytic binding or trapping of beta-lactams by the enzyme. We found that the outer membrane of E. cloacae strain 55M indeed had permeability to cefazolin about 14-fold lower than that of Escherichia coli, and that the number of beta-lactamase molecules produced by this constitutive mutant was exceptionally large (2 X 10(5) per cell). These conditions are expected to produce a low degree of resistance, but could not explain the high resistance level of the mutant. We showed that the beta-lactamase of this strain hydrolyzed third-generation beta-lactams at measurable rates. Although the V max for these compounds was less than 0.01% of that for cefazolin, the enzyme could hydrolyze them at rates comparable to the rate for cefazolin when the substrate concentration was near 0.1 microM, a concentration thought to be physiologically relevant for the inhibition of cell growth, because of the exceptionally high affinity of the enzyme to many third-generation compounds. Calculations based on kinetic parameters of the enzyme, outer membrane permeability, and affinity toward penicillin-binding proteins succeeded in predicting the MICs for several third-generation beta-lactams. The data suggest that hydrolysis may be more important than nonhydrolytic binding for the expression of the resistant phenotype, and that studies on the susceptibility of beta-lactams to beta-lactamases should be carried out at physiologically relevant, very low concentrations of the drug, rather than the customary very high concentrations, such as 100 microM.
Anti-Bacterial Agents↗
Synthesis and properties of cholesteryl-modified triple-helix forming oligonucleotides containing a triglycyl linker.
In order to enhance the nuclear uptake of triple-helix forming oligonucleotides (TFOs), a triglycylcholesterol group was attached to the 3' end. The peptide unit was introduced as a "labile" linker with the aim of releasing the oligonucleotide from the endosomes by the action of peptidases after crossing the cell membrane. Cholesteryl-CPG (8) and -TentaGel (9) supports containing 2-[N-(glycylglycylglycyl)amino]propane-1,3-diol (GAP-3) linker were prepared and used for automated oligonucleotide synthesis. The synthesis, characterization, and stability of these compounds are described.
Base Sequence↗
Use of phthaloyl protecting group for the automated synthesis of 3'-[(hydroxypropyl)amino] and 3'-[(hydroxypropyl)triglycyl] oligonucleotide conjugates.
The chemical stability of oligonucleotides (ODNs) containing 3'-propanolamine was investigated. Invariably, all the ODNs synthesized from Fmoc-protected 3-aminopropane-1,2-diol-CPG support gave a mixture of three compounds at the end of automated synthesis as analyzed by denaturing PAGE and HPLC. On the basis of analytical procedures, these compounds were identified to be 3'-[N-acetyl-N-(hydroxypropyl)amino],3'-[(hydroxypropyl)amino], and 3'-hydroxyl ODNs. The instability of the amino protecting group under the synthesis conditions was responsible for this observed heterogeneity. In order to evaluate the stability, a comparative study on the chemical stability of the ODN containing amino-protecting groups such as [(9-fluorenylmethyl)oxy]carbonyl (Fmoc), trifluoroacetyl (TFA), and phthaloyl was undertaken. The results indicate that the phthaloyl group provided the best stability for the synthesis of 3' amine-modified ODNs, and the protecting group is cleaved and deprotected in concentrated ammonium hydroxide:40% aqueous methylamine, 1:1, for 5-10 min, at 56 degrees C. The 3'-hydroxypropyl)triglycyl] ODN conjugates were also synthesized from Fmoc- and phthaloyl-protected (hydroxypropyl)triglycine-CPG supports.
Base Sequence↗
Diagnosis of malignant granular cell tumor by fine needle aspiration cytology:.
BACKGROUND: Malignant granular cell tumors (GCT) are the rarest of all sarcomas, and the histologic differentiation from their benign counterpart may be extremely difficult or impossible unless metastatic disease is demonstrated. To our knowledge, this is the first report of a malignant GCT diagnosed by fine needle aspiration (FNA) cytology. CASE: A 70-year-old, Caucasian female presented with a progressively enlarging left supraclavicular mass. FNA of the mass revealed a metastatic tumor cytologically consistent with GCT. With this diagnosis, a search for other metastatic sites was initiated. Computed tomography (CT) scan revealed several tumor nodules in the lungs and liver. CT-guided FNA and tru-cut needle biopsy of a liver mass confirmed the diagnosis of metastatic GCT. In searching for a primary site, the patient revealed a clinical history of having had a tumor removed from her back two months before; it was reported to be an atypical GCT. Comparison of the three tumors revealed similar histologic, cytologic and immunohistochemical features. CONCLUSION: Evidence of mild to moderate cytologic atypia; increased mitotic activity; locally aggressive growth; increased proliferative activity as demonstrated by immunohistochemical evaluation of proliferation markers; and DNA ploidy analysis, as reported for this case, may be helpful in predicting malignant behavior of GCTs.
Aged↗