Search PubMed⌕ Search

Biomedical subjects

Feng Lin

Publications and source records attributed to Feng Lin.

At least 55 records · Page 3Linked to original sources

Decay-accelerating factor modulates induction of T cell immunity.

Decay-accelerating factor (Daf) dissociates C3/C5 convertases that assemble on host cells and thereby prevents complement activation on their surfaces. We demonstrate that during primary T cell activation, the absence of Daf on antigen-presenting cells (APCs) and on T cells enhances T cell proliferation and augments the induced frequency of effector cells. The effect is factor D- and, at least in part, C5-dependent, indicating that local alternative pathway activation is essential. We show that cognate T cell-APC interactions are accompanied by rapid production of alternative pathway components and down-regulation of Daf expression. The findings argue that local alternative pathway activation and surface Daf protein function respectively as a costimulator and a negative modulator of T cell immunity and explain previously reported observations linking complement to T cell function. The results could have broad therapeutic implications for disorders in which T cell immunity is important.

Animals↗

Control of hypertension in adults with chronic kidney disease in the United States.

Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.

Antihypertensive Agents↗

Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique.

We have recently developed an organ manufacturing technique that enables us to form cell/biomaterial complex three-dimensional (3D) architectures in designed patterns. This technique employs a highly accurate 3D micropositioning system with a pressue-controlled syringe to deposit cell/biomaterial structures with a lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped with a fine-bore exit needle using which a wide variety of 3D patterns with different arrays of channels (through-holes) were created. The channels can supply living cells with nutrients and allow removing the cell metabolites. The embedded cells remain viable and perform biological functions as long as the 3D structures are retained. The new technology has the potential for eventual high-throughput production of artificial human tissues and organs.

Animals↗

Effect of hormone therapy on mortality rates among women with heart failure and coronary artery disease.

Randomized, controlled trial data from the Heart and Estrogen-progestin Replacement Study were used to evaluate the effect of estrogen plus progestin use on all-cause mortality in women with heart failure and coronary disease. Over the 4.1-year follow-up, estrogen plus progestin use had no effect on all-cause mortality (hazard ratio 1.0, 95% confidence interval 0.7 to 1.4, p = 0.8) in women with heart failure and coronary disease.

Aged↗

Preparation and evaluation of ammonia-treated collagen/chitosan matrices for liver tissue engineering.

To further enhance the properties of existing collagen/chitosan scaffolds for liver tissue engineering, a very simple method was developed to form noncovalently linked mimic of the liver extracellular matrices. Collagen/chitosan mixtures in various proportions (i.e., 1:0, 3:2, 1:1, 2:3, and 0:1 v/v) were lyophilized or evaporated to form sponges or flat films before they were gelled using an aqueous 25% ammonia solution. The porosities of the obtained sponges were above 90% with various pore sizes. The highest mechanical strength (1.9+/-0.7 MPa) and the lowest degradation time (65+/-1.7 days) were achieved by the collagen/chitosan (1:1) matrices. Hepatocytes cultured on the collagen/chitosan (1:1) matrices exhibited relatively high glutamate-oxaloacetate transaminase and glucose secretion functions 25 days post-seeding. Nuclues of the hepatocytes were more elongated and arranged in certain directions on the 1:1 matrices. The cytocompatibility and enhanced biostability of our new ammonia-treated collagen/chitosan matrices suggest that they could be used as scaffolds for liver tissue engineering.

Amines↗

Pattern-constrained multiple polypeptide sequence alignment.

Multiple sequence alignment (MSA) is one of the fundamental research topics in computational biology. The alignments help us to find functional assignment, evolutionary history and conserved region. Previous methods use a substitution matrix and do not incorporate knowledge of the sequences being aligned. Therefore, they do not assure the alignment of similar structures and common patterns in the sequences. We have been investigating into the solution to the problem in multiple and making use of knowledge of the sequences being aligned, including patterns in the Prosite databank, Blocks+, eBlocks databases, as well as motif and structural information. A pattern-constrained algorithm has been developed. Experiments with protein sequences have shown more accurate alignments with incorporation of the domain knowledge available in the sequences.

Amino Acid Sequence↗

Reconstruction of large phylogenetic trees: a parallel approach.

Reconstruction of phylogenetic trees for very large datasets is a known example of a computationally hard problem. In this paper, we present a parallel computing model for the widely used Multiple Instruction Multiple Data (MIMD) architecture. Following the idea of divide-and-conquer, our model adapts the recursive-DCM3 decomposition method [Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T, 2004a. Performance of suptertree methods on various dataset decompositions. In: Binida-Emonds, O.R.P. (Eds.), Phylogenetic Supertrees: Combining Information to Reveal the Tree of Life, vol. 3 of Computational Biology, Kluwer Academics, pp. 301-328; Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T., 2004b. Rec-I-DCM3: A Fast Algorithmic Technique for reconstructing large phylogenetic trees, Proceedings of the IEEE Computational Systems Bioinformatics Conference (ICSB)] to divide datasets into smaller subproblems. It distributes computation load over multiple processors so that each processor constructs subtrees on each subproblem within a batch in parallel. It finally collects the resulting trees and merges them into a supertree. The proposed model is flexible as far as methods for dividing and merging datasets are concerned. We show that our method greatly reduces the computational time of the sequential version of the program. As a case study, our parallel approach only takes 22.1h on four processors to outperform the best score to date (Found at 123.7h by the Rec-I-DCM3 program [Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T, 2004a. Performance of suptertree methods on various dataset decompositions. In: Binida-Emonds, O.R.P. (Eds.), Phylogenetic Supertrees: Combining Information to Reveal the Tree of Life, vol. 3 of Computational Biology, Kluwer Academics, pp. 301-328; Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T., 2004b. Rec-I-DCM3: A Fast Algorithmic Technique for reconstructing large phylogenetic trees, Proceedings of the IEEE Computational Systems Bioinformatics Conference (ICSB)] on one dataset. Developed with the standard message-passing library, MPI, the program can be recompiled and run on any MIMD systems.

Journal Article↗

Dynamic expression of COUP-TFI and COUP-TFII during development and functional maturation of the mouse inner ear.

COUP-TFs (chicken ovalbumin upstream promoter-transcription factors) are orphan members of the nuclear receptor superfamily of ligand-activated receptors for which their ligands have not been identified. The two mammalian proteins, COUP-TFI and COUP-TFII, share 80% sequence identity and regulate many aspects of mammalian development and differentiation. In this report, we systemically examined the temporal and spatial expression of COUP-TFI and COUP-TFII transcripts and, for the first time, their protein during development and functional maturation of the cochlea. Both COUP-TFI and COUP-TFII were expressed early in the developing otic vesicle. COUP-TFI expression correlated with the differentiation of hair cells and support cells in the organ of Corti, whereas COUP-TFII expression was down-regulated with differentiation of the organ of Corti. Furthermore, we report for the first time, that the generally nuclear COUP-TFI receptor protein was localized in the cytoplasm of maturing hair cells and pillar cells. Collectively, although COUP-TFI and COUP-TFII are homologues, the expression of each orphan receptor has a restricted and dynamic expression during cochlea development particularly during patterning and differentiation of the cochlear structures.

Animals↗

Sexual functioning after total compared with supracervical hysterectomy: a randomized trial.

OBJECTIVE: To compare sexual functioning and health-related quality-of-life outcomes of total abdominal hysterectomy (TAH) and supracervical hysterectomy (SCH) among women with symptomatic uterine leiomyomata or abnormal uterine bleeding refractory to hormonal management. METHODS: We randomly assigned 135 women scheduled to undergo abdominal hysterectomy in 4 U.S. clinical centers to either a total or supracervical procedure. The primary outcome was sexual functioning at 2 years, as assessed by the Medical Outcomes Study Sexual Problems Scale. Secondary outcomes included specific aspects of sexual functioning and health-related quality-of-life at 6 months and 2 years. RESULTS: Sexual problems improved dramatically in both randomized groups during the first 6 months and plateaued by 1 year. Health-related quality-of-life scores also improved in both groups. At 2 years, both groups reported few problems with sexual functioning (mean score on the Sexual Problems Scale for SCH group 82, TAH group 80, on a 0-to-100 scale with 100 indicating an absence of problems; difference = +2.95% confidence interval -8 to +11), and there were no significant differences between groups. CONCLUSION: Supracervical and total abdominal hysterectomy result in similar sexual functioning and health-related quality of life during 2 years of follow-up. This information can help guide physicians as they discuss surgical options with their patients.

Adult↗

Sexual activity and function in postmenopausal women with heart disease.

OBJECTIVE: To examine the prevalence and correlates of sexual activity and function in postmenopausal women with heart disease. METHODS: We included baseline self-reported measures of sexual activity and the sexual problem scale from the Medical Outcomes Study in the Heart and Estrogen/Progestin Replacement Study (HERS), a study of 2,763 postmenopausal women, average age 67 years, with coronary disease and intact uteri. We used multivariable linear and logistic regression to identify independent correlates of sexual activity and dysfunction. RESULTS: Approximately 39% of the women in HERS were sexually active, and 65% of these reported at least 1 of 5 sexual problems (lack of interest, inability to relax, difficulty in arousal or in orgasm, and discomfort with sex). In multivariable analysis, factors independently associated with being sexually active included younger age, fewer years since menopause, being married, better self-reported health, higher parity, moderate alcohol use, not smoking, lack of chest discomfort, and not being depressed. Among the 1,091 women who were sexually active, lower sexual problem scores were associated with being unmarried, being better educated, having better self-reported health, and having higher body mass index. CONCLUSION: Many women with heart disease continue to engage in sexual activity into their 70s, and two thirds of these report discomfort and other sexual function problems. Physicians should be aware that postmenopausal patients are sexually active and address the problems these women experience. LEVEL OF EVIDENCE: II-2.

Age Distribution↗

Postmenopausal hormone therapy: does it cause incontinence?

OBJECTIVE: To estimate the effect of hormone therapy on risk of stress and urge urinary incontinence. METHODS: The Heart Estrogen/progestin Replacement Study was a randomized, placebo-controlled, double-blinded trial to evaluate daily oral conjugated estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) therapy for the prevention of heart disease events in women with established heart disease. The 1,208 participants in Heart Estrogen/progestin Replacement Study who reported no loss of urine in the previous 7 days at baseline are included in this analysis. RESULTS: During 4.2 years of treatment, 64% of women randomly assigned to hormone therapy compared with 49% of those assigned to placebo reported weekly incontinence (P < .001). The higher risk of incontinence in the hormone group was evident at 4 months, persisted throughout the treatment period, and was independent of the age of the women. The odds ratios for weekly incontinence among women on hormone therapy compared with placebo were 1.5 for urge incontinence (95% confidence interval [CI] 1.2-1.8; P < .001) and 1.7 for stress incontinence (95% CI 1.5-2.1; P < .001). Four years of treatment with hormone therapy caused an excess risk of 12% for weekly urge incontinence and 16% for weekly stress incontinence; the corresponding numbers needed to harm were 8.6 (95% CI 5.8-16.6) and 6.2 (95% CI 4.6-9.4). CONCLUSION: Estrogen plus progestin therapy increases risk of urge and stress incontinence within 4 months of beginning treatment. LEVEL OF EVIDENCE: I.

Administration, Oral↗

On the verification of intransitive noninterference in mulitlevel security.

We propose an algorithmic approach to the problem of verification of the property of intransitive noninterference (INI), using tools and concepts of discrete event systems (DES). INI can be used to characterize and solve several important security problems in multilevel security systems. In a previous work, we have established the notion of iP-observability, which precisely captures the property of INI. We have also developed an algorithm for checking iP-observability by indirectly checking P-observability for systems with at most three security levels. In this paper, we generalize the results for systems with any finite number of security levels by developing a direct method for checking iP-observability, based on an insightful observation that the iP function is a left congruence in terms of relations on formal languages. To demonstrate the applicability of our approach, we propose a formal method to detect denial of service vulnerabilities in security protocols based on INI. This method is illustrated using the TCP/IP protocol. The work extends the theory of supervisory control of DES to a new application domain.

Algorithms↗

Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver.

A new type of collagen/chitosan/heparin matrix, fabricated by gelation of collagen/ chitosan with heparin sodium containing ammonia, was produced to construct livers by tissue engineering and regenerative engineering. The obtained collagen/chitosan/heparin matrix was found to be highly porous, swelled rapidly in PBS solution and was stable in vitro for at least 60 days in collagenase/lysozyme containing buffered aqueous solution (PBS, pH 7.4) at 37 degrees C. The collagen/chitosan/heparin matrix resulted in a superior blood compatibility compared to the ammonia-treated collagen and collagen/chitosan matrices. The morphology and behavior of the cells on the collagen/chitosan/heparin membrane were found to be similar to those on the collagen membrane but different from those on the collagen/chitosan membrane. Hepatocytes cultured on the collagen/chitosan/heparin matrices exhibited highest urea and triglyceride secretion functions 25 days post seeding. These results suggest that this collagen/chitosan/heparin matrix is a potential candidate for liver tissue engineering.

Animals↗

The chemistry and biology of human relaxin-3.

A novel member of the human relaxin subclass of the insulin superfamily was recently discovered during a genomics database search and named relaxin-3. Like human relaxin-1 and relaxin-2, relaxin-3 is predicted to consist of a two-chain structure and three disulfide bonds in a disposition identical to that of insulin. To undertake detailed biophysical and biological characterization of the peptide, its chemical synthesis was undertaken. In contrast to human relaxin-1 and relaxin-2, however, relaxin-3 could not be successfully prepared by simple combination of the individual chains, thus necessitating recourse to the use of a regioselective disulfide bond formation strategy. Solid phase synthesis of the separate, selectively S-protected A and B chains followed by their purification and the subsequent stepwise formation of each of the three disulfides led to the successful acquisition of human relaxin-3. Comprehensive chemical characterization confirmed both the correct chain orientation and the integrity of the synthetic product. Relaxin-3 was found to bind to and activate native relaxin receptors in vitro and stimulate water drinking through central relaxin receptors in vivo. Recent studies have demonstrated that relaxin-3 will bind to and activate human LGR7, but not LGR8, in vitro. Secondary structural analysis showed it to adopt a less ordered confirmation than either relaxin-1 or relaxin-2, reflecting the presence in the former of a greater percentage of nonhelical forming amino acids. NMR spectroscopy and simulated annealing calculations were used to determine the three-dimensional structure of relaxin-3 and to identify key structural differences between the human relaxins.

Amino Acid Sequence↗

Insulin-relaxin family peptide signaling and receptors in mouse brain membranes and neuronal cells.

Several orphan G-protein-coupled receptors (GPCRs), LGR7 and LGR8, GPCR135 and GPCR142, were recently identified as putative, native receptors for different relaxin-family peptides, and their cell signaling mechanisms were elucidated in stably transfected cell lines. Anatomic studies have demonstrated that discrete populations of neurons in rat brain express relaxin and relaxin-3 mRNA/peptide, relaxin and relaxin-3 binding sites, and LGR7 and GPCR135 mRNAs. Thus, we began to assess the ability of relaxin-family peptides to alter cAMP production in brain and the involvement of the different native receptors. In mouse cortical membranes, a fixed concentration of relaxin peptides (100 nM) inhibited forskolin-induced cAMP production, but further studies in normal and receptor knockout mouse strains are required to assess the specificity of these effects. In addition, whole-cell signaling mechanisms are being investigated in a mouse hypothalamic cell line, GT1-7. Such studies will help to establish the actions of relaxin-family peptides via their different GPCRs in different brain pathways.

Animals↗

[Changes in nutritional status and immune function in patients with colorectal cancer after operation].

OBJECTIVE: To evaluate the changes in the nutritional status and immune function in patients with colorectal cancer after operation. METHODS: The indexes of the nutritional status and immune function were measured in 40 patients with colorectal cancer before and after operation and compared with the control group. RESULTS: The levels of IgM, IgG, prealbumin and transferrin were lowered after operation in these colorectal cancer patients (P<0.05), but no significant difference was noted after operation in the control group. CONCLUSION: The nutritional status and immune function in colorectal cancer patients obviously deteriorate after operation.

Adenocarcinoma↗

Parallelisation of the blast algorithm.

Retrieving homologous DNA and protein sequences from existing databases is a fundamental routine in bioinformatics research. Programs of the NCBI BLAST family are widely used for this purpose. We evaluated paraBLAST, a parallelised version of the NCBI BLAST algorithm, using a Message Passing Interface (MPI) on a multi-node compute cluster. Here, we propose static and dynamic database-partitioning schemes based on the availability of the cluster. We evaluated the application of the algorithm in querying nucleotide sequences against a large-scale sequence database with different numbers of database partitions, and hence, different numbers of CPUs. Since the program's tasks are performed independently of each other, each available CPU can run its own copy of BLAST queries, resulting in reduced interference between processes and leading to a highly scalable solution.

Algorithms↗

[Expression and amplification of steroid receptor coactivator-3 gene in colorectal carcinoma and its clinicopathological significance].

OBJECTIVE: To investigate the expression and amplification of steroid receptor coactivator- 3(SRC- 3) gene in colorectal carcinoma (CRC) and its clinicopathological significance. METHODS: Immunohistochemistry and fluorescence in situ hybridization (FISH) were used to detect the expression and amplification of SRC- 3 gene in CRC, and its association with patient's clinical pathological features was analyzed. RESULTS: A total of 60 patients with CRC were studied. SAR- 3 proteins were overexpressed in 23 cases (38% ). There was a significant association between SAR- 3 overexpression and neoplasm staging (P< 0.01). SRC- 3 protein was overexpressed in 62% of patients with Dukes C or D stage, whereas SRC- 3 protein was normally expressed in 74% of patients with Dukes A or B stage. As for FISH study, 47 cases were informative. High- level amplification of SRC- 3 gene was detected in 6 cases(13% ) and all showed overexpression of SRC- 3 protein. Low- level amplification of SRC- 3 was observed in 9 cases (19% ). Overexpression of SRC- 3 was detected in 6 cases. The remaining 9 of 32 patients(28% ) without amplification of SRC- 3 gene were observed with overexpression of SRC- 3 protein. In addition, 91% patients with CRC were found overexpression of SRC- 3 as well as overexpression of P53. CONCLUSION: The abnormal expression of SRC- 3 gene might impact on the function of P53 and development of CRC. There might exist some unknown mechanisms other than gene amplification of SRC- 3 to regulate its encoded protein expression in CRC.

Biomarkers, Tumor↗