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Biomedical subjects

X Fu

Publications and source records attributed to X Fu.

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

A pathway for conformational diversity in proteins mediated by intramolecular chaperones.

Conformational diversity within unique amino acid sequences is observed in diseases like scrapie and Alzheimer's disease. The molecular basis of such diversity is unknown. Similar phenomena occur in subtilisin, a serine protease homologous with eukaryotic pro-hormone convertases. The subtilisin propeptide functions as an intramolecular chaperone (IMC) that imparts steric information during folding but is not required for enzymatic activity. Point mutations within IMCs alter folding, resulting in structural conformers that specifically interact with their cognate IMCs in a process termed "protein memory." Here, we show a mechanism that mediates conformational diversity in subtilisin. During maturation, while the IMC is autocleaved and subsequently degraded by the active site of subtilisin, enzymatic properties of this site differ significantly before and after cleavage. Although subtilisin folded by Ile-48 --> Thr IMC (IMCI-48T) acquires an "altered" enzymatically active conformation (SubI-48T) significantly different from wild-type subtilisin (SubWT), both precursors undergo autocleavage at similar rates. IMC cleavage initiates conformational changes during which the IMC continues its chaperoning function subsequent to its cleavage from subtilisin. Structural imprinting resulting in conformational diversity originates during this reorganization stage and is a late folding event catalyzed by autocleavage of the IMC.

Amino Acid Sequence↗
PubMed1999

Abuse of guaifenesin-containing medications generates an excess of a carboxylate salt of beta-(2-methoxyphenoxy)-lactic acid, a guaifenesin metabolite, and results in urolithiasis.

OBJECTIVES: Several urinary calculi were submitted to our institution for compositional analysis. The typical techniques of analysis, polarized light microscopy, electron microprobe analysis, and infrared spectroscopy proved inadequate for a definitive identification. As a result, a more detailed organic analysis was conducted to determine the exact chemical structure of the material. METHODS: Infrared spectroscopy and mass spectrometric analysis were carried out on the solid material, providing information concerning the functional groups and the molecular mass of the organic constituent and its components. The stone was solubilized in deuterated solvents and analyzed by nuclear magnetic resonance spectroscopy, which resulted in a definitive chemical structure. RESULTS: The spectroscopic analysis indicated that the stones were composed of a calcium salt of beta-(2-methoxyphenoxy)-lactic acid, a metabolite of the pharmaceutical guaifenesin, which is used as an expectorant. CONCLUSIONS: Guaifenesin, an expectorant common in over-the-counter cold and allergy remedies, can cause urolithiasis if taken in excess. Discussions with physicians and their patients confirmed that most patients admitted to taking large doses of guaifenesin-containing medications.

Adolescent↗
PubMed1999

Malayenolides A-D, novel diterpenes from the indonesian sea pen veretillum malayense

Malayenolides A-D (1-4), four new briarane diterpenes, were isolated from the sea pen Veretillum malayense collected in Indonesia. The new diterpenes possess benzoate and senecioate substitutents, both of which are rare among marine natural products. The structures of the new compounds were determined from spectral data. Compounds 1-4 are toxic to brine shrimp.

Journal Article↗
PubMed1999

Longithorols A and B, novel prenylated paracyclophane- and metacyclophane-type hydroquinones from the tunicate Aplidium longithorax.

The tunicate Aplidium longithorax collected from Palau contained two novel prenylated paracyclophane- and metacyclophane-type hydroquinones, longithorols A (1) and B (2), in addition to longithorones A-I. Longithorols A and B were very unstable and were therefore isolated as their more stable pentaacetate forms, 3 and 4, respectively. The structures of 3 and 4 were determined by spectral data, especially 2D NMR data.

Animals↗
PubMed1999

mAngiogenin-3, a target gene of oncoprotein E2a-Pbx1, encodes a new angiogenic member of the angiogenin family.

Angiogenins are proteins in the pancreatic ribonuclease superfamily that utilize their ribonuclease activity to induce formation of new blood vessels. Recently we identified a new member of the angiogenin gene family, mouse angiogenin-3, by virtue of its transcriptional activation in NIH3T3 fibroblasts coincident with transformation by the chimeric leukemia oncogene, E2a-Pbx1. Here we have isolated the cDNA encoding mouse angiogenin-3 and used it to produce the protein in E. coli. We demonstrate that mouse angiogenin-3 is a ribonuclease whose activity and specificity towards tRNA and dinucleotide substrates differ from those of mouse angiogenin or of mouse angiogenin-related protein, a non-angiogenic factor. Mouse angiogenin-3 induced angiogenesis in both the chicken embryo chorioallantoic membrane assay and the rat cremaster muscle. Electron microscopy revealed that endothelial cells within vessels induced by both mouse angiogenin-3 and mouse angiogenin contain fenestrations similar to those observed in endothelial cells from neovasculature induced by vascular endothelial growth factor and basic fibroblast growth factor. Mouse angiogenin-3 also induced other molecular events typical of rapidly proliferating endothelial cells, such as increases in rough endoplasmic reticulum, polysomes, and mitochondria.

3T3 Cells↗
PubMed1999

A double blind observation for therapeutic effects of the tong luo kai bi tablets on rheumatoid arthritis.

The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P < 0.05).

Adult↗
PubMed1998

The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle.

The effects of the Rho-kinase inhibitor, Y-27632 [1] on Ca2+-sensitization of force induced by arachidonic acid (AA), phorbol 12,13-dibutyrate (PDBu), GTPgammaS, and by the stable thromboxane analog, 9,11-dideoxy-9alpha,11alpha-methanoepoxy-PGF2alpha (U-46619), were determined in alpha-toxin-permeabilized smooth muscles. Y-27632 relaxed (up to 99%) Ca2+-sensitization by GTPgammaS (10 microM) and U46619 (1 microM), but not by PDBu (20 microM), and reduced GTPgammaS-induced myosin light chain (MLC20) phosphorylation from 28% to 17% (P=0.002). GTPgammaS-induced force sensitization was inhibited by Y-27632 more potently when the inhibitor was added during the plateau of force than prior to stimulation. In alpha-toxin-permeabilized smooth muscle, Y-27632 inhibited AA (50 microM)-induced Ca2+-sensitization of force (by 66 +/- 1.3%) and reduced MLC20 phosphorylation. In contrast, Y-27632 did not relax force Ca2+-sensitized by AA in smooth muscle permeabilized with Triton X-100. We conclude that (i) AA induces Ca2+-sensitization through dual mechanisms, one mediated by Rho-kinase (or a related kinase), and (ii) Rho-kinase is not required for phorbol ester-induced Ca2+-sensitization.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns.

BACKGROUND: Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. METHODS: We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. FINDINGS: All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. INTERPRETATION: rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.

Administration, Cutaneous↗
PubMed1998

[DNA sequencing of human ciliary neurotropic factor gene by silver staining method].

OBJECTIVE: To introduce a non-radioactive protocol for DNA sequence analysis which employs a silver staining procedure METHODS: DNA template is amplified by Taq DNA polymerase to generate sequence ladder, No labeled nucleotide or primer is involved in the thermal-cycling sequencing reaction. A sensitive silver staining procedure is employed to visualize bands in sequencing gel. RESULTS: This silver staining method is used for DNA sequence analysis of human cilliary neurotrophic factor (hCNTF) gene. The resulted band resolution is comparable to radioactive sequencing method, and data can be obtain within less than 2 hours after sequencing reaction. CONCLUSION: Silver staining is a rapid, inexpensive and reliable method for DNA sequence analysis.

Ciliary Neurotrophic Factor↗
PubMed1998

Ischemia and reperfusion impair the gene expression of endogenous basic fibroblast growth factor (bFGF) in rat skeletal muscles.

Our previous studies showed that the amount of endogenous basic fibroblast growth factor (bFGF) was reduced after ischemia and reperfusion insult. One of the mechanisms involved in the decrease of endogenous bFGF is the increased destruction of this growth factor associated with oxygen free radical activation and inflammation. We hypothesized that the wounding also impairs the secretion of bFGF and examined the bFGF gene expression in skeletal muscles after ischemia and reperfusion insult. In this study, a rat leg ischemia (4 h) and reperfusion (24 h) injury model was prepared and the in situ hybridization method and reverse transcriptase polymerase chain reaction technique (RT-PCR) were used to evaluate the bFGF gene expression and its localization in control (normal) and injured rat skeletal muscles. The results showed that the bFGF mRNA expression was localized in the cytoplasm in control skeletal muscle, especially at the periphery inside the cells. According to the intensity of the stain, four main classes of fibers could be identified: strongly, moderately, weakly, and negatively stained fibers. Based on the positive stain, about 82% of the total fibers examined were positive for bFGF mRNA stain. In ischemic or ischemic and reperfused rat skeletal muscles, the localization of bFGF mRNA expression was similar to that in normal skeletal muscles, but only 52% in ischemic muscles and 22% in ischemic and reperfused muscles had positive bFGF mRNA staining. RT-PCR confirmed a significant decrease in bFGF mRNA expression in ischemic and reperfused rat skeletal muscles. These results suggest that the acute ischemia and reperfusion not only induce the destruction of endogenous bFGF molecule, which is stored at the extracellular matrix of the fibers, but also downregulate the bFGF gene expression. The simultaneous dysregulation of endogenous bFGF gene expression and decreased synthesis of bFGF protein suggest a possible role of this growth factor in delayed wound healing.

Animals↗
PubMed1998

New imidazole alkaloids and zinc complexes from the micronesian sponge Leucetta cf. chagosensis.

Four new imidazole alkaloids, 2-5, along with the known isonaamidine B (1) were isolated from a Pacific sponge, Leucetta cf. chagosensis, collected from Yap, Federated States of Micronesia. Among these, 4 and 5 are zinc complexes derived from isonaamidine B and isonaamidine D. The structures of the new compounds were elucidated from spectral data. Isonaamidine D (3) showed weakly antifungal activity against Aspergillus niger with MIC = 100 micrograms/mL.

Alkaloids↗
PubMed1998

Agelasines H and I, 9-methyladenine-containing diterpenoids from an Agelas sponge.

Two new diterpenes possessing a 9-methyladeninium substituent, agelasines H (5) and I (6), along with five related known ones, 1-4 and 7, were isolated from a sponge, Agelas sp. The structures of the new compounds were determined from spectral data. Compounds 2-4, 6, and 7 exhibited varying degrees of antimicrobial activity.

Adenine↗
PubMed1998

New diketopiperazines from the sponge Dysidea chlorea.

Twelve new polychlorinated diketopiperazines (7-18), along with six known ones (1-6) and a known sterol (19), were isolated from the sponge Dysidea chlorea, collected from Yap, Federated States of Micronesia. The structures of dysamides I-T (7-18) were elucidated by spectroscopic methods, and one (8) was confirmed by chemical conversion. The stereochemistry of the dysamides is discussed.

Animals↗
PubMed1998

New cyclic peptides from the ascidian Lissoclinum patella.

Four new cyclic peptides, patellamide G (2) and ulithiacyclamides E-G (3-5), along with the known patellamides A-C (6-8) and ulithiacyclamide B (9), were isolated from the ascidian Lissoclinum patella collected in Pohnpei, Federated States of Micronesia. The planar structures of these peptides were determined from 1D and 2D 1H and 13C NMR spectra. The absolute stereochemistries of the amino acid units, except for cysteine, were assigned by chiral GC analysis of N(O)-trifluoroacetyl isopropyl ester derivatives of amino acids obtained by acid hydrolysis of the intact and ozonized peptides. The structures of ulithiacyclamides E-G (3-5) were confirmed by chemical conversion. Patellamides B (7) and C (8) exhibited in vitro modulation of multidrug resistance in CEM/VBL100 cells.

Animals↗