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Biomedical subjects

F Fan

Publications and source records attributed to F Fan.

At least 55 records · Page 3Linked to original sources

The pharmacokinetics of lamivudine in healthy Chinese subjects.

AIMS: The purpose of this study was to investigate the pharmacokinetics of daily oral doses of lamivudine administered to healthy Chinese subjects for 1 week. METHODS: Twenty-four subjects were enrolled, 12 males and 12 females, all between the ages of 18 and 40 years. After an overnight fast, all subjects received a single oral dose of 100 mg lamivudine. Blood was obtained before lamivudine administration and at regular intervals to 24 h post dose. Subsequent doses were given once daily for a total of 7 days. On the last day another full pharmacokinetic profile was obtained to 24 h postdose. Timed urine collections were performed for all subjects on day 1 only. Pharmacokinetic parameters were calculated by using standard non compartmental techniques. RESULTS: Lamivudine was well absorbed in all subjects (tmax 1 h). On day 1 and day 7 the overall geometric mean Cmax was 1304 and 1385 ng ml-1, and AUC(0,24h) was 4357 and 4353 ng ml-1 h, respectively. On average 78% of the lamivudine dose was recovered in urine as parent compound. Pharmacokinetic parameters were very similar between male and female subjects, between day 1 and day 7 and in comparison with data obtained in many other pharmacokinetic studies. CONCLUSIONS: This study demonstrated that the pharmacokinetics of lamivudine are essentially identical between Chinese and Caucasian subjects, and between males and females. It confirms 100 mg lamivudine is an appropriate dose for use in Chinese patients, providing adequate exposure for optimal antiviral effect.

Adult↗

[The supporting effects of the pedicle of the subdermal vascular network flap in the rat].

OBJECTIVE: To investigate the role of the pedicle in the survival of the subdermal vascular network skin flap. METHODS: The subdermal vascular network skin flap was created on the back of the rat in the experimental group. The subdermal vascular network skin graft was made at the same position of the rat in the control group. The ratio of length to width of the flap was 4:1. The observation was carried out with naked eyes and instrument. Hair growing on the flap was one of the most important indexes of the observation. RESULTS: It was observed in 116 animals that the proximal 25 percent of the flap possessed regular colour and well-growing hair. CONCLUSION: The pedicle of the subdermal vascular network skin flap in the rat can supply 25 percent of the whole flap.

Animals↗

[Comprehensive evaluation of medical process by constructed polynory function].

This paper describes the concept of "medical process evaluation" and presents a model which is based on constructed polynory function by using the Fuzzy Set theory. This model frame has been used for the prognostic evaluation of patients recovering from acute myocardial infarction and for the comprehensive evaluation of efficacy in treatments of pneumoconiosis. The results are satisfactory. This model frame can be generalized to other medical process evaluation.

Fuzzy Logic↗

[The use of inexact reasoning method for differential diagnosis of pulmonary function].

This article expounds the main idea of the evidence theory and hence presents a mathematical model. Based on the above work, we have developped a computer-aided medical differential diagnosis system with Visual Basic. The system can identify restrictive ventilatory impairment, obstructive ventilatory impairment, mixed ventilatory impairment and normal. according to the valuse of patients' related indexed. In a retrospective test of 290 cases we collected, the rate of agreement between the diagnosis made by this system and the physicians was 93.1%.

Algorithms↗

[The development and application of telemedicine].

Telemedicine, which began in the late 1950s, is the combination of modern technologies such as medicine, digital communications, computer and multimedia. The study of telemedicine in some developed countries has made great progress in 1990s. However it began somewhat late in our country. This article reviews the development of telemedicine and its application. The authors also point out some problems in telemedicine that need to be solved.

Internet↗

cDNA cloning and characterization of Npap60: a novel rat nuclear pore-associated protein with an unusual subcellular localization during male germ cell differentiation.

We have cloned and characterized a cDNA, Npap60, encoding a rat nuclear pore-associated protein. The 3-kb cDNA was obtained by antibody screening of a rat testis expression library. The predicted NPAP60 contains 381 amino acids with a composition of 25.6% charged residues and is highly hydrophilic. The Npap60 gene appears to be conserved in mouse, rat, and human. Immunofluorescence studies with anti-NPAP60 fusion protein antibody show that the NPAP60 protein colocalizes with nuclear pore complexes in RAT1A cells. The expression of Npap60 is about 10-20 times higher in rat testis than in somatic tissues. The subcellular localization of NPAP60 protein changes dramatically during male germ cell differentiation, from nuclear pore complex-like staining in spermatocytes to whole nucleus staining in spermatids and finally to a nuclear surface staining in mature spermatozoa. These changes are temporally and spatially related to nuclear reorganization during male germ cell differentiation.

Amino Acid Sequence↗

Cytokines (IL-1beta and TNFalpha) in relation to biochemical and immunological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats.

Previous studies in different strains of rats and mice have shown that the inhibition of gluconeogenesis as a result of reduced liver phosphoenolpyruvate carboxykinase (PEPCK) activity together with appetite suppression play critical roles in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent immunological studies in rats demonstrated that exposure to low doses of TCDD resulted in an early and enhanced IgG response to immunization with sheep red blood cells (SRBC) and an enhanced delayed-type hypersensitivity (DTH) reaction as well as a positive popliteal lymph node (PLN) response. However, high doses of TCDD suppressed the DTH reaction. This study aimed at examining the involvement of cytokines (IL-1 and TNF) in mediating the above effects. Liver samples from a previous dose-response study on DTH reaction were investigated, in which rats were treated with TCDD (1, 3, 10, 30 and 90 microg/kg) and immunized with an antigen. mRNA levels of IL-1beta were elevated begining at the 1 microg/kg (non-lethal) dosage group with a maximum increase of about 5-fold above controls in the 90 microg/kg (lethal) dosage group. mRNA levels of TNFalpha were also significantly elevated begining at the 30 microg/kg dosage group. These results suggest that at low doses of TCDD, increased IL-1beta could be responsible for immune function stimulation, whereas at high doses of TCDD, greatly elevated TNFalpha and IL-1beta levles may exacerbate or mediate acute toxicity including immune suppression and related biochemical effects. A time course study (60 microg TCDD/kg without immunization) revealed that liver mRNA levels of TNFalpha were significantly elevated starting 24 h, and reaching a maximum 48 h after dosing with TCDD. This change was accompanied by a transient increase of mRNA levels of IL-1beta at day 4 after TCDD dosage. Thus, these data demonstrated that TCDD alone (without immunization) can cause transient increases of mRNA levels of TNFalpha and IL-1beta in liver. Results from these experiments suggest that TCDD-induced cytokine changes may play important roles in various effects of TCDD.

Animals↗

Differential requirements of two insect cell lines for growth in serum-free medium.

The development of a serum-free medium that supports the growth of cells from a Spodoptera frugiperda and a Lymantria dispar cell line is reported. A yeast hydrolysate provided the B-vitamin complex, and a combination of a meat hydrolysate and tryptose provided most of the free amino acids required for cell growth. Supplemental cystine and methionine were required to achieve maximum cell growth. The serum or serum replacements used in earlier formulations were replaced with commercial lipid preparations and increased levels of iron salts. Although the cell growth cycle had a somewhat extended lag phase and the population doubling time of the S. frugiperda cells was longer than on serum-containing medium, the saturation densities were much higher. Spodoptera cells grown in this medium replicated the Autographa californica nuclear polyhedrosis virus well, producing 8.71 x 10(6) TCID50 extracellular virus and 4.4 x 10(6) polyhedra/ml culture. The specific activity of the polyhedra was somewhat less than that of polyhedra produced in insects.

Animals↗

The FliP and FliR proteins of Salmonella typhimurium, putative components of the type III flagellar export apparatus, are located in the flagellar basal body.

Most of the structural components of the flagellum of Salmonella typhimurium are exported through a flagellum-specific pathway, which is a member of the family of type III secretory pathways. The export apparatus for this process is poorly understood. A previous study has shown that two proteins, about 23 and 26 kDa in size and of unknown genetic origin, are incorporated into the flagellar basal body at a very early stage of flagellar assembly. In the present study, we demonstrate that these basal body proteins are FliP (in its mature form after signal peptide cleavage) and FliR respectively. Both of these proteins have homologues in other type III secretion systems. By placing a FLAG epitope tag on FliR and the MS-ring protein FliF and immunoblotting isolated hook basal body complexes with anti-FLAG monoclonal antibody, we estimate (using the FLAG-tagged FliF as an internal reference) that the stoichiometry of FliR is fewer than three copies per basal body. An independent estimate of stoichiometry was made using data from an earlier quantitative radiolabelling analysis, yielding values of around four or five subunits per basal body for FliP and around one subunit per basal body for FliR. Immunoelectron microscopy using anti-FLAG antibody and gold-protein A suggests that FliR is located near the MS ring. We propose that the flagellar export apparatus contains FliP and FliR and that this apparatus is embedded in a patch of membrane in the central pore of the MS ring.

Autoradiography↗

The FliO, FliP, FliQ, and FliR proteins of Salmonella typhimurium: putative components for flagellar assembly.

The flagellar genes fliO, fliP, fliQ, and fliR of Salmonella typhimurium are contiguous within the fliLMNOPQR operon. They are needed for flagellation but do not encode any known structural or regulatory components. They may be involved in flagellar protein export, which proceeds by a type III export pathway. The genes have been cloned and sequenced. The sequences predict proteins with molecular masses of 13,068, 26,755, 9,592, and 28,933 Da, respectively. All four gene products were identified experimentally; consistent with their high hydrophobic residue content, they segregated with the membrane fraction. From N-terminal amino acid sequence analysis, we conclude that fliO starts immediately after fliN rather than at a previously proposed site downstream. FliP existed in two forms, a 25-kDa form and a 23-kDa form. N-terminal amino acid analysis of the 23-kDa form demonstrated that it had undergone cleavage of a signal peptide--a rare process for prokaryotic cytoplasmic membrane proteins. Site-directed mutation at the cleavage site resulted in impaired processing, which reduced, but did not eliminate, complementation of a fliP mutant in swarm plate assays. A cloned fragment encoding the mature form of the protein could also complement the fliP mutant but did so even more poorly. Finally, when the first transmembrane span of MotA (a cytoplasmic membrane protein that does not undergo signal peptide cleavage) was fused to the mature form of FliP, the fusion protein complemented very weakly. Higher levels of synthesis of the mutant proteins greatly improved function. We conclude that, for insertion of FliP into the membrane, cleavage is important kinetically but not absolutely required.

Amino Acid Sequence↗

[A comprehensive evaluation of efficacy in treatments of pneumoconiosis with model method].

Pneumoconiosis is an occupational disease which can cause serious damage to the health of exposed workers. The study on the treatment of pneumoconiosis has been designated as a tackle-key-proble,. The exploration of comprehensive evaluation techniques is a component of this project. The model based on FUZZY SET is a mutivariate function [formula: see text], which can be used in the determination and evaluation of the efficacy in the treatments of pneumoconiosis. Its good performance has been proved in practice.

Evaluation Studies as Topic↗

Enzymatic characterization of FliI. An ATPase involved in flagellar assembly in Salmonella typhimurium.

FliI is a protein needed for flagellar assembly in Salmonella typhimurium. It shows sequence similarity to the catalytic beta subunit of the F0F1-ATPase and is even more closely related to putative ATPases in Type III bacterial secretory pathways. A His-tagged version of FliI, which was fully functional in complementation tests, was purified to homogeneity. It had an ATPase activity of 0.16 s-1 at 25 degrees C and pH 7, and a Km for ATP of 0.3 mM; Mg2+ was required. The activity was not affected by inhibitors of the F-, V- or P-type ATPases, or inhibitors of the Type I or Type II bacterial secretory pathways. Mutations K188I and Y363S decreased the ATPase activity about 100-fold, increased the Km about 10-fold, blocked flagellar assembly, and were dominant. Other FliI mutations that disrupted flagellar protein export were found near the N terminus; they permitted essentially wild-type ATPase activity, were not dominant, and showed a dosage-dependent phenotype. We propose that FliI has a C-terminal ATPase domain and an N-terminal domain that interacts with other components in the flagellum-specific export apparatus.

Adenosine Diphosphate↗

NOE-derived conformation of GRGDSP cell adhesion recognition site in the presence of SDS micelles and integrin receptor GPIIB/IIIA.

The tripeptide RGD is well known for its role in integrin receptor-mediated cell-cell surface adhesion. Here, NMR and transferred NOE studies have been done with the fibrinogen/fibronectin-derived hexapeptide GRGDSP in the presence of sodium dodecyl sulfate (SDS) and purified platelet glycoprotein integrin receptor GPIIb/IIIa. In the presence of SDS and absence of receptor, GRGDSP gives NOE-based distance geometry-generated structures characteristic of two "nested' beta-turns centered at RG and GD. In the presence of integrin GPIIb/IIIa, GRGDSP resonances are chemically shifted and broadened consistent with a dynamic equilibrium between free and receptor "bound' peptide. NOEs characteristic of the nested beta-turns are either absent or weaker indicating a significant conformational change in GRGDSP in the receptor bound state. GRGDSP appears to bind the receptor in a more extended backbone conformation which positions aspartic acid and arginine residues spatially close for potential electrostatic interactions.

Amino Acid Sequence↗

Integrin receptor GPIIb/IIIa bound state conformation of the fibrinogen gamma-chain C-terminal peptide 400-411: NMR and transfer NOE studies.

The C-terminal dodecapeptide from human fibrinogen gamma-chain, residues 400-411, HHLG-GAKQAGDV (gamma12), is known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet glycoprotein integrin receptor GPIIb/IIIa. NMR studies of gamma12 in the presence of purified GPIIb/IIIa (230 kDa) demonstrate that two gamma12 binding states (gamma12-I and gamma12-II) are present on the integrin receptor. The N-terminal sequence HHLG is crucial to formation of gamma12 state I since in a shorter gamma-chain octapeptide, GAKQAGDV, gamma12-I is not observed. Addition of the hexapeptide GRGDSP to the gamma12-receptor preparation effectively removes the gamma12-I population, suggesting either that gamma12 and GRGDSP share one binding site or that their binding sites are allosterically linked. Distance geometry calculations using transfer NOEs from gamma12-I (gamma12-II shows practically no NOEs) indicate the presence of helix conformation when bound to the receptor. Line broadening and chemical shift changes relative to free gamma12 suggest that gamma12 interacts with GPIIb/IIIa primarily through N-terminal residues H400 to Q407.

Amino Acid Sequence↗

Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice.

The objective of this study was to determine whether the development of tolerance to CP 55,940, a potent cannabinoid agonist, was due to changes in the receptor or second messenger system. ICR mice treated with CP 55,940 (2 mg/kg) twice a day for 6 and one-half days developed a high degree of tolerance to the pharmacological effects of CP 55,940. The ability of CP 55,940 to produce motor hypoactivity, hypothermia and immobility was reduced 163-, 97- and 19-fold, respectively. Evaluation of 3H-CP 55,940 binding to rat brain membranes indicated no difference in receptor affinity between the vehicle- and CP 55,940-treated animals. However, these binding studies revealed a 50% decrease in receptor number in the cerebellum of the CP 55,940-tolerant mice. Although cAMP is generally considered to be the second messenger for cannabinoid receptors, little difference was observed in the inhibitory effects of CP 55,940 on adenylyl cyclase activity in cerebellum between vehicle and drug-treated mice. However, there was an increase in receptor mRNA which suggests a compensation for receptor loss. There are several possible explanation for these results. There may be sufficient spare receptors such that CP 55,940-tolerant mice are capable of producing a maximal effect on the second messenger system. On the other hand, one could conclude that cannabinoid receptor down-regulation does not account for the development of tolerance to all of the effects of CP 55,940 in mice.

Adenylyl Cyclase Inhibitors↗

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on humoral and cell-mediated immunity in Sprague-Dawley rats.

There is much discussion about the occurrence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the human immune system. Extensive studies have been conducted in mice, but those results cannot explain some of the epidemiological data obtained in exposed humans. Therefore, studies in other laboratory animal species are needed. The aim of these experiments was to examine effects of TCDD on cell- and humoral-mediated immunity in male Sprague-Dawley (SD) rats. A delayed-type hypersensitivity (DTH) assay was used to examine cell-mediated immunity. A time-course study demonstrated that TCDD treatment on day -5 relative to immunization (day 0) produced the greatest effect on cell-mediated immunity. In a dose-response experiment, rats were treated with 1, 3, 10, 20, 30, 40 and 90 micrograms TCDD/kg The effect of TCDD on cell-mediated immunity displayed an inverted U-shaped dose-response curve, in that low doses enhanced and high doses suppressed this immune function. This is the first study to demonstrate an U-shaped dose-response curve of TCDD on the immune system. Primary antibody response to sheep red blood cells (SRBC) was used as endpoint to study the effect of TCDD on humoral immunity. Serum anti-SRBC IgM and IgG levels were measured using an enzyme-linked immunosorbent assay (ELISA). In the dose range examined (10, 20 and 40 micrograms TCDD/kg), serum IgM levels were not affected by TCDD compared to controls at 7 and 14 days after immunization. In contrast, serum IgG levels were dose-dependently elevated both 7 and 14 days after immunization, with a maximum increase of 59% over controls.

Animals↗

RGD induces conformational transition in purified platelet integrin GPIIb/IIIa-SDS system yielding multiple binding states for fibrinogen gamma-chain C-terminal peptide.

Fibrinogen gamma-chain C-terminal peptide HHLG-GAKQAGDV (gamma 12) and alpha-chain peptide GRGDSP are known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet integrin receptor GPIIb/IIIa. NMR studies of gamma 12 in the presence of purified GPIIb/IIIa in SDS/water solution have demonstrated the presence of two gamma 12 binding states, one of which is eliminated by GRGDSP (RGD) up to a RGD: gamma 12 ratio of 2:1. RGD: gamma 12 ratios greater than 2:1 produce multiple sets of gamma 12 NMR signals in TOCSY spectra. At a ratio of 4:1, two to four such resonance sets can be resolved for A405, Q407, A408, G409, D410 and V411 spin systems. The number of multiple resonances remains unchanged at ratios of 6:1 and 8:1. Addition of gamma 12 to reverse the ratio to 8:8 (1:1) has no apparent effect on the RGD-induced distribution. Results suggest that RGD irreversibly induces a conformational transition(s) in GPIIb/IIIa to produce multiple gamma 12 binding sites on the receptor.

Amino Acid Sequence↗

[The principle of nasal defects repair based on the frontal and temporal vessels anatomy].

After dissection of 9 corpes' (18 sides) vessels of the forehead, nose and temporal, we have discovered that the superatrochlear arteries run upward bilaterally, the branches of the supertrochelear arteries, the superficial branches of the supraorbital arteries and the front branches of the superficial temporal form a network--the frontal artery anastomotic net. The main trank and the parital branches of the superficial temporal arteries give off 2-3 ear branches. Based on these findings, we have made a series of explor atire researches, designed several new kinds of skin flaps for repairing the nasal defects, and improved a number traditional skin flaps. Guided by the above mentioned principles, we have successfully reconstructed 32 different kinds of nasal defects and achieved good results.

Adolescent↗