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Biomedical subjects

F Chu

Publications and source records attributed to F Chu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray, matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry.

Liquid chromatography/electrospray ionization mass spectrometry was used to investigate the peptide composition of the venom of Conus pennaceus, a molluscivorous cone shell from the Red Sea. Based on observed M(r)s, this venom contained all known conotoxins previously isolated and identified from this species. Interestingly, the doubly protonated species of only two of these conotoxins, alpha-PnIA and alpha-PnIB, showed additional related ions at +40 m/z (+80 Da), indicating the presence of either sulfation or phosphorylation in both components. High-performance liquid chromatographic (HPLC) fractions containing these two conotoxins were examined by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry in both positive and negative ion modes, as well as by MALDI high-energy collision-induced dissociation. These experiments established the presence of a single sulfated tyrosine residue within both alpha-PnIA and alpha-PnIB. Hence their post-translationally modified sequences are GCCSLPPCAANNPDY(S)C-NH2 (alpha-PnIA) and GCCSLPPCALSNPDY(S)C-NH2 (alpha-PnIB). This assignment was supported by comparison of their mass spectral behavior with that of known sulfated and phosphorylated peptides. This data clarified further the distinguishing features of the ionization and fragmentation of such modified peptides. Selective disulfide folding of synthetic alpha-PnIB demonstrated that both sulfated and non-sulfated toxins co-elute on reversed-phase HPLC and that alpha-PnIB possesses the same disulfide connectivity as other 'classical' alpha-conotoxins reported previously.

Amino Acid Sequence↗
PubMed1999

A rapid, sensitive HPLC method for the determination of ganciclovir in human plasma and serum.

A method for ganciclovir determination in human serum and plasma has been developed and validated. The method has a lower limit of quantification (LLOQ) adequate for sensitive pharmacokinetic studies ( < or = 0.05 microg/ml), has run times of < or = 15 min, and uses aliquot volumes adequate for pediatric studies (0.25 ml). In the method, proteinaceous material in serum or plasma is precipitated by trichloroacetic acid. An aliquot of the supernatant is analyzed by HPLC; automated column switching removes late-eluting materials that might interfere with the analyte peak in subsequent runs. Detection and quantification of ganciclovir is by fluorescence (lambda(ex) = 278 nm; lambda(em) = 380 nm). The method has a validated range of 0.0400-4.00 microg/ml and an LLOQ of 0.0400 microg/ml. All intra- and inter-assay % C.V. values were < 8%; all recoveries (accuracy) were within 7% of nominal values. No interference was observed by mycophenolic acid or its glucuronide metabolite, by AZT, salicylic acid, acetaminophen, ibuprofen, naproxen prednisone, acyclovir, or cyclosporine. Ganciclovir is very stable in the samples and the extract during storage and sample processing. Both serum and plasma methods have been validated for use and have been successfully used to analyze samples from clinical studies.

Antiviral Agents↗
PubMed1999

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.

Alternative Splicing↗
PubMed1999

[Comparison of operation mode and clinical effect of different surgical treatments of gluteus muscle contracture (with 98 cases reports)].

OBJECTIVE: To explore a better surgical mode to treat gluteal muscle contracture. METHODS: In 98 cases, superior cross incision of large tuberosity was performed in 20 cases, posterosuperior curve incision of large tuberosity was performed in 20 cases, and exteroinferior cross incision of iliac spine in the other 58 cases. The patients were observed after operation and followed up. RESULTS: The patients who received exteroinferior cross incision of iliac spine recovered soon without bleeding and infection after operation, which indicated the lowest incidental rate of postoperative complication. CONCLUSION: Exteroinferior cross incision of iliac spine is a safe and effective surgical operation to loosen the gluteal muscle contracture.

Adolescent↗
PubMed1998

[Studies on the structure-activity relationship of retinoids--Hansch analysis and 3D-OSAR studies on specific ligands of retinoid x receptor].

Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retinoids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitative structure-activity relationships of specific ligands of RXR, we carried out mimesis of environment of ligands interacting with their receptor and, to some extent, mapping the topological and physico-chemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.

Alitretinoin↗
PubMed1997

Comparative molecular field analysis of a series of paclitaxel analogues.

A series of 94 paclitaxel analogues exhibiting antitumor activity by promoting the assembly of microtubules and inhibiting the disassembly process of microtubules to tubulin were investigated using the comparative molecular field analysis (CoMFA) method. These compounds belonging to 10 structural classes were randomly divided into a training set of 80 compounds and a test set of 14 compounds. Since the three-dimension structure of ligand--receptor complex is unknown, from X-ray and NMR data we rationally selected the three-dimension structure of paclitaxel in a polar solution as the active conformation and starting structure for molecule modeling, the other molecules were aligned using this molecule model as the template. The most optimal CoMFA yielded a two-components model, with significant cross-validation r2cv of 0.640 and conventional r2 of 0.868. The predictive ability of training set model was tested on the test set of 14 compounds. The tests not only revealed the robustness of the CoMFA model but demonstrated that for our model r2pred based on the mean activity of test set compounds can accurately estimate external predictivity but r2pred based on the mean activity of training set compounds overestimated the model. The CoMFA model explained why the activity of taxoid is sensitive to the stereochemistry of the atoms at C-2' and C-3' positions and the presence of hydroxyl group at C-2' position. The other factors affecting activity were also elucidated according to standard coefficient contour maps of steric and electrostatic fields derived from the CoMFA model.

Antineoplastic Agents↗
PubMed1997

Effects of weight change on plasma leptin concentrations and energy expenditure.

Circulating concentrations of leptin are closely correlated with body fat mass, and may thus constitute an afferent limb of a system regulating body fatness, with efferent limbs that affect energy expenditure and food intake. We studied 50 subjects (27 males, 23 premenopausal females; 31 never-obese, 19 obese) at usual body weight during active weight loss or weight gain and during the maintenance of body weights 10% above usual (WT + 10%) and 10% and/or 20% below usual body weight (Wt -10% and Wt -20%) to test the hypotheses that the dynamic process of weight change and the maintenance of an altered body weight are associated with significant changes in circulating concentrations of leptin and/or the relationship between fat mass and leptin, and such changes in the plasma concentration of leptin are related to changes in energy expenditure at altered body weight. Subjects were admitted to the Rockefeller University Hospital, and energy metabolism (24-h energy expenditure, resting energy expenditure, thermic effect of feeding, and nonresting energy expenditure) and circulating concentrations of leptin and insulin were examined at various weight plateaus (usual body weight, 10% above usual body weight, 10% below usual body weight, and 20% below usual body weight). Plasma leptin was also measured in some subjects during dynamic periods of weight gain or loss. Though both plasma leptin concentrations and fat mass were significantly correlated with resting energy expenditure, only the correlation of fat mass and energy expenditure remained significant in a multiple stepwise linear regression analysis. Neither absolute nor relative changes in plasma leptin between weight plateaus were significantly correlated with any of the observed changes in energy expenditure. Plasma leptin concentrations were significantly lower during weight loss than during weight maintenance at the same body composition. Plasma leptin concentrations, normalized to fat mass, were significantly lower during the maintenance of a reduced body weight in females and higher during the maintenance of an elevated body weight in males than in the same subjects at usual body weight. At all weight plateaus, plasma leptin concentrations normalized to fat mass were significantly higher in females than in males, but gender was not a significant covariate of the relationship between leptin and energy expenditure. Postabsorptive serum concentrations of insulin was a significant covariate of plasma leptin concentration in males, but not females, at Wt initial and Wt + 10%. Although plasma leptin is significantly reduced during dynamic weight loss compared with static weight maintenance at the same body weight, the lack of correlation between changes in plasma leptin and changes in energy expenditure between weight plateaus suggests that leptin is not the primary signal that mediates the changes of energy expenditure that accompany the maintenance of an altered body weight in humans.

Body Composition↗
PubMed1997

Immunoassay and other ligand assays: present status and future trends.

Immunoassay and other ligand assays have made a major impact on medical research and diagnosis since the first modern (radioisotopically-based) methods emerged. These ubiquitous microanalytic techniques are broadly classifiable as first generation (generally of "competitive" design, e.g., radioimmunoassay), and second generation (generally "noncompetitive," and relying on nonisotopic labels) these (often described as "ultrasensitive") being distinguished by dramatic improvements in sensitivity and performance time. A third generation is now in prospect (based on microarrays of antibody microspots) capable of ultrasensitive determination of hundreds of analytes in a drop of blood. Analogous technology (based on oligonucleotide arrays) is under intensive development for DNA analysis. Array technologies are likely to transform diagnostic medicine in the next decade.

Animals↗
PubMed1996

Manual and automated (robotic) high-performance liquid chromatography methods for the determination of mycophenolic acid and its glucuronide conjugate in human plasma.

A manual and an automated (Zymark PyTechnology robot) HPLC method for simultaneous determination of plasma mycophenolic acid (MPA) and its glucuronide conjugate (MPAG) are described here. Both methods are reproducible and accurate, and both are equivalent in all respects, including quantification limits (MPA, 0.100 microgram/ml; MPAG, 4.00 micrograms/ml), range (using 0.05-0.5 ml of plasma: MPA, 0.0500-20.0 micrograms/aliquot; MPAG, 2.00-200 micrograms/aliquot), precision, and accuracy. MPA and MPAG were stable under the conditions used with both methods. Results from aliquots of paired control samples, analyzed by the manual method over three years at six analytical laboratories, showed excellent agreement in precision and accuracy.

Chromatography, High Pressure Liquid↗
PubMed1996

Fibroblasts are in a position to provide directional information to migrating neutrophils during pneumonia in rabbit lungs.

Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast organization within the interstitium was assessed by transmission electron microscope observations of serial-sectioned rabbit lung tissue. Interstitial fibroblasts were found to physically interconnect the endothelial basal lamina holes to epithelial basal lamina holes. Morphometric assessment of rabbit lung tissue instilled with Streptococcus pneumoniae revealed that approximately 70% of the surface area density of migrating neutrophils is in close contact (15 nm or less) with interstitial fibroblasts and extracellular matrix elements (30 and 40%, respectively). Although migrating neutrophils were close enough to adhere to both fibroblasts and extracellular elements, the interstitial fibroblasts are organized in a manner that would allow them to provide directional information to the neutrophils. A model illustrating this process is proposed.

Animals↗
PubMed1996

Effects of gender, body composition, and menopause on plasma concentrations of leptin.

Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1) Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se: and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 postmenopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] was determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin]) was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not differ significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition (pre-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin].

Adipose Tissue↗
PubMed1995

Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia.

The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation. Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes. The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact. The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts. Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs. We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium. We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts. We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells. From there, neutrophils migrate into the alveolar airspace.

Animals↗