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Biomedical subjects

F Lin

Publications and source records attributed to F Lin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.

OBJECTIVE: The aim of this study was to determine whether 2 photosensitizers, benzoporphyrin-derivative monoacid ring and 5-aminolevulinic acid, are selectively absorbed by dysplastic cervical cells after topical administration. STUDY DESIGN: This phase I clinical trial involved 18 women with biopsy-proven cervical intraepithelial neoplasia at the Beckman Laser Institute, Irvine, Calif. Colposcopically directed cervical biopsy specimens obtained after 1.5, 3, or 6 hours of exposure to a randomly assigned photosensitizer were evaluated for selective drug absorption with hematoxylin and eosin staining and fluorescence microscopy. RESULTS: After exposure to 5-aminolevulinic acid, cervical tissue showed maximal fluorescence in dysplastic cells relative to normal cells, with negligible stromal fluorescence. According to our detection methods benzoporphyrin-derivative monoacid ring demonstrated nonselective, diffusion-driven uptake, with fluorescence appearing in the superficial cells, followed by nonselective drug absorption in the remaining cells and stroma of the epithelium. CONCLUSION: Our data demonstrated selective absorption of 5-aminolevulinic acid by dysplastic cervical cells. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical intraepithelial neoplasia with photodynamic therapy.

Absorption↗
PubMed2001

[Research on the near-infrared (NIR) photon migration in multi-layered structures of biological tissues].

The phenomena of photon migration in multi-layered structures of biological tissue is very important in the field of non-invasive near-infrared optical diagnosis. In this paper, a two-layered structure consisting of the fat and the muscle of poke was used as the sample. Near-infrared light source and detector were located on the surface of the fat and a part of the photons reflected by the two-layered structure of the tissue were detected. The relationship between the optical current and the distance from source to detector and the relationship between the optical current and the thickness of the fat layer were given. In order to analyze the experiment results, Monte-Carlo simulation was used to calculate the photons migration traces in the uniform tissues and the Fresnel's law is used to determine the refraction and reflection components of a photon package at the boundary between the fat and the muscle. The results showed that the simulation data coincident well with the experimental results. The conclusion is that the experiment and the simulation method provided in this study may be useful to analyze the photon migration in a mult-layered tissue and to optimize the design of the transducer.

Adipose Tissue↗
PubMed2000

Peripheral arterial disease in randomized trial of estrogen with progestin in women with coronary heart disease: the Heart and Estrogen/Progestin Replacement Study.

BACKGROUND: Postmenopausal estrogen use has been associated with reduced carotid atherosclerosis in observational studies, but this relationship has not been confirmed in a clinical trial. The impact of estrogen on atherosclerotic disease in other peripheral arteries is unknown. METHODS AND RESULTS: Postmenopausal women with coronary heart disease (CHD) and an intact uterus (n=2763) were randomly assigned to conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) daily or to placebo in a secondary CHD prevention trial. This analysis focuses on incident peripheral arterial procedures and deaths in the 2 treatment groups; peripheral vascular disease was a predefined secondary outcome. During a mean of 4.1 years of follow-up, 311 peripheral arterial events were reported in 213 women, an annual incidence of 2.9%. The number of women who had peripheral arterial events was 99 among those assigned to active estrogen/progestin and 114 among those assigned to placebo, a nonsignificant difference (relative hazard 0. 87, 95% CI 0.66 to 1.14). In the placebo group, hypertension and diabetes mellitus were independently associated with higher rates of peripheral arterial events, and plasma HDL cholesterol and body mass index were associated with lower rates of peripheral arterial events. In the estrogen/progestin group, current smoking and diabetes were independent predictors of peripheral arterial events. Incident peripheral arterial disease was not a significant predictor of coronary, cardiovascular, or total mortality. CONCLUSIONS: Treatment with oral conjugated estrogen plus medroxyprogesterone acetate was not associated with a significant reduction in incident peripheral arterial events in postmenopausal women with preexisting CHD.

Aged↗
PubMed2000

Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3.

TR3, an immediate-early response gene and an orphan member of the steroid-thyroid hormone-retinoid receptor superfamily of transcription factors, regulates apoptosis through an unknown mechanism. In response to apoptotic stimuli, TR3 translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis. Mitochondrial targeting of TR3, but not its DNA binding and transactivation, is essential for its proapoptotic effect. Our results reveal a mechanism by which a nuclear transcription factor translocates to mitochondria to initiate apoptosis.

Apoptosis↗
PubMed2000

Dominant-negative activity of an alpha(1B)-adrenergic receptor signal-inactivating point mutation.

alpha(1)-adrenergic receptors (alpha(1)-ARs) are members of the G-protein-coupled receptor (GPCR) superfamily and activate inositol phosphate (IP) turnover. We show that glycine and asparagine mutations of Phe303 in transmembrane segment VI (TMVI) of the alpha(1B)-AR, a highly conserved residue in GPCRs, although increasing agonist affinity, abolish agonist-activated IP signalling. Co-expression of the Phe303 mutants also inhibited (-)epinephrine-stimulated IP signalling by wild-type alpha(1B)-AR and other G(q)-coupled receptors, as well as IP signalling mediated by AlF(4)(-) stimulation of both wild-type G(q alpha) and a constitutively active mutant. The inability of the Phe303 mutants to signal is due to induction of a receptor conformation that dissociates G-protein binding from activation. As a result, the Phe303 mutants sequester G(q alpha) and stoichiometrically inhibit Gq signalling in a dominant-negative manner. We further show that both the enhanced basal and agonist-stimulated IP-signalling activity of the constitutively active alpha(1B)-AR mutants, C128F and A293E, are inhibited in the double mutants, C128F/F303G and A293E/F303G. Phe303, therefore, appears to be critically involved in coupling TMVI alpha-helical movement, a key step in receptor activation, to activation of the cognate G-protein.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2000

Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization.

Agonist-induced desensitization and resensitization of G-protein-linked receptors involve the interaction of receptors with protein kinases, phosphatases, beta-arrestin, and clathrin organized by at least one scaffold protein. The dynamic composition of the signaling complexes and the role of the scaffold protein AKAP250 (gravin) in agonist-induced attenuation and recovery of beta-adrenergic receptors were explored by co-immunoprecipitation of target elements, antisense suppression, and confocal microscopy. Gravin associated with unstimulated receptor, and the association was increased significantly after agonist stimulation for up to 60 min. Agonist stimulation also induced a robust association of the receptor-gravin complex with protein kinases A and C, G-protein-linked receptor kinase-2, beta-arrestin, and clathrin. Confocal microscopy of the green fluorescence protein-tagged beta(2)-adrenergic receptor showed that the receptor underwent sequestration after agonist stimulation. Suppression of gravin expression via antisense oligodeoxynucleotides disrupted agonist-induced association of the receptor with G-protein-linked receptor kinase-2, beta-arrestin, and clathrin as well as receptor recovery from desensitization. Gravin deficiency also inhibited agonist-induced sequestration. These data reveal that gravin-mediated formation of signaling complexes with protein kinases/phosphatases, beta-arrestin, and clathrin is essential in agonist-induced internalization and resensitization of G-protein-linked receptors.

A Kinase Anchor Proteins↗
PubMed2000

Induction of gynogenesis in muskellunge with irradiated sperm of yellow perch proves diploid muskellunge male homogamety.

Diploid gynogenesis was induced in muskellunge Esox masquinongy using UV-irradiated muskellunge sperm as the first step in producing monosex females. In this approach, we have to rely on negative controls as an indirect reference for sperm genetic material destruction. In the first experiment, equal proportions of gynogenetic females and males were produced. Negative controls, UV-irradiated sperm without heat shock, yielded some normal hatching larvae, described as spontaneous diploids. In the second experiment, muskellunge eggs were activated using sperm from yellow perch. Because hybrids between these species are not viable, we produced unambiguous gynogens. When UV-irradiated yellow perch sperm was used to inseminate muskellunge eggs, haploids resulted (22.5% +/- 2.8% survival to the eyed stage). To produce diploid gynogens, a heat shock of 31 degrees C was applied to inseminated eggs 20 min after activation for a duration of 6 min. This process yielded several hundreds of gynogens for rearing. Several treatments of masculinizing hormone, 17alpha-methyltestosterone (MT), were carried out. Fish were dissected and gonads examined histologically for sex determination. Gynogens produced using yellow-perch sperm confirmed the presence of males in the control group, whereas the MT bath treatment (400 microg/liter) resulted in the production of fish with ovotestis. These results provide evidence for male homogamety in muskellunge and imply that a change of strategy is needed to produce monosex populations.

Animals↗
PubMed2000

Unique anti-activator protein-1 activity of retinoic acid receptor beta.

The anticancer effects of retinoids are mainly mediated by two classes of nuclear receptors, the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are encoded by three distinct genes (alpha, beta, and gamma). Recent studies have demonstrated that RARbeta plays a critical role in mediating anticancer effects of retinoids. However, how RARbeta exerts its potent anticancer effects remains largely unknown. In this study, we investigated anti-Activator Protein-1 (AP-1) activity of RARbeta. In a transient transfection assay, all three RAR subtypes, RARalpha, RARbeta, and RARgamma, could effectively inhibit phorbol ester 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 activity and the activity of oncogenes c-Jun and c-Fos on AP-1 containing reporter genes in the presence of retinoic acid (RA). However, RARbeta showed a strong RA-independent inhibition of AP-1 activity, whereas inhibition of AP-1 activity by RARalpha and RARgamma was RA dependent. By using several hybrid receptors that contain either the COOH-terminal portion or the NH2-terminal portion of RARbeta, we demonstrated that the NH2-terminal portion of RARbeta, the A/B domain, was mainly responsible for the RA-independent inhibition of AP-1 activity. This activity was not attributable to constitutive AF-1 activity of RARbeta, because it did not activate several RA response element-containing reporter genes. In addition, inhibition of histone deacetylase activity by trichostatin A did not overcome the inhibitory effect of RARbeta. In cancer cells, stable transfection of RARbeta exhibited strong inhibition of AP-1 activity, even in the absence of RA. Moreover, expression of endogenous AP-1-responsive gene collagenase I was strongly repressed in cancer cells stably transfected with RARbeta. In studying the antitransforming activity of RARbeta, we observed that the growth of breast cancer MDA-MB231 cells in soft agar was significantly repressed in a RA-independent manner when cells were stably transfected with RARbeta but not RARalpha. Together, our results demonstrate that RARbeta may exert its potent anticancer effect in part through its unique anti-AP-1 activity.

Breast Neoplasms↗
PubMed2000

Epidemiology of primary varicella and herpes zoster hospitalizations: the pre-varicella vaccine era.

To determine the epidemiology and costs of hospitalization with primary varicella and herpes zoster in the prevaccine era and the usefulness of hospital discharge data to determine the population impact of vaccination on these conditions, statewide hospital discharge data in Connecticut from 1986 to 1995 were analyzed. Annual hospitalizations for herpes zoster were 4-fold higher than for primary varicella (16.1 vs. 4.1/100,000). Overall, 69% and 83%, respectively, had no underlying immunosuppressive conditions. Regarding primary varicella, 53% of patients were aged <15 years, there was a marked winter-spring seasonality, and Hispanics and blacks were 4.1 and 2.6 times more likely than whites to be hospitalized. Regarding herpes zoster, 66.9% of patients were aged >64 years, and there was no seasonality. The mean patient charges in 1995 were $12,819 for primary varicella and $15,583 for herpes zoster. Analysis of population-based hospital discharge data is a feasible means of monitoring the impact of varicella immunization on severe morbidity due to primary varicella and herpes zoster.

Adolescent↗
PubMed2000

Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause.

CONTEXT: Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for coronary heart disease (CHD) events. However, few data exist on the clinical importance of Lp(a) lowering for CHD prevention. Hormone therapy with estrogen has been found to lower Lp(a) levels in women. OBJECTIVE: To determine the relationships among treatment with estrogen and progestin, serum Lp(a) levels, and subsequent CHD events in postmenopausal women. DESIGN AND SETTING: The Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled secondary prevention trial conducted from January 1993 through July 1998 with a mean follow-up of 4.1 years at 20 centers. PARTICIPANTS: A total of 2763 postmenopausal women younger than 80 years with coronary artery disease and an intact uterus. Mean age was 66.7 years. INTERVENTION: Participants were randomly assigned to receive either conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in 1 tablet daily (n = 1380), or identical placebo (n = 1383). MAIN OUTCOME MEASURES: Lipoprotein(a) levels and CHD events (nonfatal myocardial infarction and CHD death). RESULTS: Increased baseline Lp(a) levels were associated with subsequent CHD events among women in the placebo arm. After multivariate adjustment, women in the second, third, and fourth quartiles of baseline Lp(a) level had relative hazards (RHs) (compared with the first quartile) of 1.01 (95% confidence interval [CI], 0.64-1.59), 1.31 (95% CI, 0.85-2.04), and 1.54 (95% CI, 0.99-2.39), respectively, compared with women in the lowest quartile (P for trend = .03). Treatment with estrogen and progestin reduced mean (SD) Lp(a) levels significantly (-5.8 [15] mg/dL) (-0.20 [0.53] micromol/L) compared with placebo (0.3 [17] mg/dL) (0.01 [0.60] micromol/L) (P<.001). In a randomized subgroup comparison, women with low baseline Lp(a) levels had less benefit from estrogen and progestin than women with high Lp(a) levels; the RH for women assigned to estrogen and progestin compared with placebo were 1.49 (95% CI, 0.97-2.26) in the lowest quartile and 1.05 (95% CI, 0.67-1.65), 0.78 (0.52-1.18), and 0.85 (0.58-1.25) in the second, third, and fourth quartiles, respectively (P for interaction trend = .03). CONCLUSIONS: Our data suggest that Lp(a) is an independent risk factor for recurrent CHD in postmenopausal women and that treatment with estrogen and progestin lowers Lp(a) levels. Estrogen and progestin therapy appears to have a more favorable effect (relative to placebo) in women with high initial Lp(a) levels than in women with low levels. This apparent interaction needs confirmation in other trials.

Aged↗
PubMed2000

MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin.

The "MAN antigens" are polypeptides recognized by autoantibodies from a patient with a collagen vascular disease and localized to the nuclear envelope. We now show that one of the human MAN antigens termed MAN1 is a 82.3-kDa protein with an amino-terminal domain followed by two hydrophobic segments and a carboxyl-terminal tail. The MAN1 gene contains seven protein-coding exons and is assigned to human chromosome 12q14. Its mRNA is approximately 5.5 kilobases and is detected in several different cell types that were examined. Cell extraction experiments show that MAN1 is an integral membrane protein. When expressed in transfected cells, MAN1 is exclusively targeted to the nuclear envelope, consistent with an inner nuclear membrane localization. Protein sequence analysis reveals that MAN1 shares a conserved globular domain of approximately 40 amino acids, which we term the LEM module, with inner nuclear membrane proteins lamina-associated polypeptide 2 and emerin. The LEM module is also present in two proteins of Caenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization.

Amino Acid Sequence↗
PubMed2000

Crocidolite induces cell transformation and p53 gene mutation in BALB/c-3T3 cells.

Cell transformation is one of the most common assays used to study morphological changes in the multistep process of carcinogenesis. The present study was initiated to investigate the ability of crocidolite to induce cell transformation in BALB/c-3T3 cells and to analyze the relationship between p53 mutations and crocidolite-induced cell transformation, if any. Cell transformation was carried out according to standard procedures. Exponentially growing cells were exposed to different concentrations (0.2-20 microg/cm(2)) of crocidolite fibers for 72 h. Foci obtained from cell transformation were analyzed for their ability to grow in soft agar (anchorage-independence) and p53 alterations. The results of this study demonstrate that there was an increase in transformation frequency (TF) with an increase in concentration of crocidolite. Also, focal cells were able to grow on soft agar, indicating anchorage-independence. cDNA was prepared from RNA isolated from Type 3 foci and subjected to mutational analysis. Eleven exons of the p53 gene from eight transformed cell lines were analyzed for alterations using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Alterations were found in seven of eight cell lines, two of them were in exons 4-6, and five in exons 9-11. The alterations were randomly scattered among the crocidolite dose groups. These results suggest that crocidolite induces mutations predominantly in exons 9-11 of the p53 gene in a nondose-dependent manner.

3T3 Cells↗
PubMed2000

The full-length, cytoplasmic C-terminus of the beta 2-adrenergic receptor expressed in E. coli acts as a substrate for phosphorylation by protein kinase A, insulin receptor tyrosine kinase, GRK2, but not protein kinase C and suppresses desensitization when expressed in vivo.

The ability of the cytoplasmic, full-length C-terminus of the beta 2-adrenergic receptor (BAC1) expressed in Escherichia coli to act as a functional domain and substrate for protein phosphorylation was tested. BAC1 was expressed at high-levels, purified, and examined in solution as a substrate for protein phosphorylation. The mobility of BAC1 on SDS-PAGE mimics that of the native receptor itself, displaying decreased mobility upon chemical reduction of disulfide bonds. Importantly, the C-terminal, cytoplasmic domain of the receptor expressed in E. coli was determined to be a substrate for phosphorylation by several candidate protein kinases known to regulate G-protein-linked receptors. Mapping was performed by proteolytic degradation and matrix-assisted laser desorption ionization, time-of-flight mass spectrometry. Purified BAC1 is phosphorylated readily by protein kinase A, the phosphorylation occurring within the predicted motif RRSSSK. The kinetic properties of the phosphorylation by protein kinase A displayed cooperative character. The activated insulin receptor tyrosine kinase, which phosphorylates the beta-adrenergic receptor in vivo, phosphorylates BAC1. The Y364 residue of BAC1 was predominantly phosphorylated by the insulin receptor kinase. GRK2 catalyzed modest phosphorylation of BAC1. Phosphorylation of the human analog of BAC1 in which Cys341 and Cys378 were mutated to minimize disulfide bonding constraints, displayed robust phosphorylation following thermal activation, suggesting under standard conditions that the population of BAC1 molecules capable of assuming the "activated" conformer required by GRKs is low. BAC1 was not a substrate for protein kinase C, suggesting that the canonical site in the second cytoplasmic loop of the intact receptor is preferred. The functional nature of BAC1 was tested additionally by expression of BAC1 protein in human epidermoid carcinoma A431 cells. BAC1 was found to act as a dominant-negative, blocking agonist-induced desensitization of the beta-adrenergic receptor when expressed in mammalian cells. Thus, the C-terminal, cytoplasmic tail of this G-protein-linked receptor expressed in E. coli acts as a functional domain, displaying fidelity with regard to protein kinase action in vivo and acting as a dominant-negative with respect to agonist-induced desensitization.

Amino Acid Sequence↗
PubMed2000

Swine vesicular disease: an overview.

Swine vesicular disease (SVD) is a notifiable viral disease of pigs included on the Office International des Epizooties List A. The first outbreak of the disease was recognized in Italy in 1966. Subsequently, the disease has been reported in many European and Asian countries. The causative agent of the disease is SVD virus which is currently classified as a porcine variant of human coxsackievirus B5 and a member of the genus enterovirus in the family picornaviridae. From a clinical point of view, SVD is relatively unimportant, rarely causing deaths and usually only a minor setback to finishing schedules. However, the clinical signs which it produces are indistinguishable from those caused by foot-and-mouth disease, and its presence prevents international trade in pigs and pig products. This article reviews recent findings on all aspects of the virus and the disease which it causes.

Animals↗
PubMed2000

Quantitative imaging using a time-domain eigenfunction method

An inverse scattering method that uses eigenfunctions of a scattering operator at a single frequency is extended to include the full range of frequencies present in the incident pulse waveform. The resulting so-called time-domain eigenfunction method is shown to yield a modulated version of the scattering potential. The potential is recovered by a demodulation process using cross correlation with a reference. Including an adaptive delay in the reference is shown to compensate partially for the linearization of the Born approximation and to extend its valid range. The k-space window of the time-domain solution is expressed in terms of the incident waveform and shown to be smoother than that of a single-frequency solution. The time-domain method is examined using both calculated and measured data. In the calculations, an exact solution for scattering from one or multiple nonconcentric cylinders is used to obtain the scattered field. In the measurements, a novel ring-transducer system was employed to obtain the incident and total fields. The results of simulations and experiments show that the method is robust and accurate for the size of objects considered and that the point resolution approaches one-half the wavelength at the pulse center frequency.

Journal Article↗
PubMed2000

Deletions of structural glycoprotein E2 of classical swine fever virus strain alfort/187 resolve a linear epitope of monoclonal antibody WH303 and the minimal N-terminal domain essential for binding immunoglobulin G antibodies of a pig hyperimmune serum.

The major structural glycoprotein E2 of classical swine fever virus (CSFV) is responsible for eliciting neutralizing antibodies and conferring protective immunity. The current structural model of this protein predicts its surface-exposed region at the N terminus with a short stretch of the C-terminal residues spanning the membrane envelope. In this study, the N-terminal region of 221 amino acids (aa) covering aa 690 to 910 of the CSFV strain Alfort/187 E2, expressed as a fusion product in Escherichia coli, was shown to contain the epitope recognized by a monoclonal antibody (WH303) with affinity for various CSFV strains but not for the other members of the Pestivirus genus, bovine viral diarrhea virus (BVDV) and border disease virus (BDV). This region also contains the sites recognized by polyclonal immunoglobulin G (IgG) antibodies of a pig hyperimmune serum. Serial deletions of this region precisely defined the epitope recognized by WH303 to be TAVSPTTLR (aa 829 to 837) of E2. Comparison of the sequences around the WH303-binding site among the E2 proteins of pestiviruses indicated that the sequence TAVSPTTLR is strongly conserved in CSFV strains but highly divergent among BVDV and BDV strains. These results provided a structural basis for the reactivity patterns of WH303 and also useful information for the design of a peptide containing this epitope for potential use in the detection and identification of CSFV. By deletion analysis, an antigenic domain capable of reacting with pig polyclonal IgG was found 17 aa from the WH303 epitope within the N-terminal 123 residues (aa 690 to 812). Small N- or C-terminal deletions introduced into the domain disrupt its reactivity with pig polyclonal IgG, suggesting that this is the minimal antigenic domain required for binding to pig antibodies. This domain could have eliminated or reduced the cross-reactivity with other pestiviruses and may thus have an application for the serological detection of CSFV infection; evaluation of this is now possible, since the domain has been expressed in E. coli in large amounts and purified to homogeneity by chromatographic methods.

Adenovirus E2 Proteins↗