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Biomedical subjects

F Lin

Publications and source records attributed to F Lin.

At least 19 recordsLinked to original sources
PubMed2003

Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle.

A crude ginseng extract (GS) and the purified ginsenoside R(b1) (R(b1)) were evaluated for their adjuvant effects in dairy cattle at immunisation with ovalbumin (OVA) and/or a Staphylococcus aureus bacterin used for prevention of bovine mastitis. To evaluate a suitable dose of GS as an adjuvant, 36 lactating cows were randomly divided into six groups. The cows were inoculated twice intramuscularly with a 2-week interval, with saline solution, OVA in saline, or OVA in combination with 4, 16 or 64 mg GS, or Al(OH)(3). The level of specific antibodies to OVA in serum and milk whey was measured before immunisations and 1-5 weeks after the second immunisation. The antibody response in serum was significantly higher in animals immunised with OVA and GS than in animals immunised with OVA alone. A significant increase in milk antibody titres compared with OVA only was only found 2 weeks after the second immunisation in the group immunised with OVA and 4 mg GS. In the second part of the study, 18 heifers were randomly divided into three groups and were immunised twice intramuscularly with a two week interval, with the S. aureus bacterin (control), or with the bacterin in combination with 4 mg GS or 1mg R(b1). The specific antibody response to S. aureus and the lymphocyte proliferation after stimulation with PWM, concanavalin A (Con A) or a specific S. aureus antigen was evaluated in blood samples taken before and after immunisations as specified above. Addition of R(b1) resulted both in significantly higher antibody production and lymphocyte proliferation in response to PWM, Con A and S. aureus antigens than in the control group. Addition of GS induced a significantly higher lymphocyte proliferation in response to PWM and Con A than the control, but had no additional effect on the antibody production. In conclusion, both GS and R(b1) were safe adjuvants, and R(b1) had the strongest adjuvant effects, when used for immunisation against S. aureus in dairy cattle. Field trials are warranted to test the ability of GS and R(b1) to enhance the efficacy of mastitis vaccines in protection against intramammary infections.

Adjuvants, Immunologic↗
PubMed2002

Effect of ultrasound on the removal of copper from the model solutions for copper electrolysis process.

A novel combination of an ultrasonic field with electrolysis for the removal of copper is studied. In the ultrasonic field, cavitation acts as jets and agitates the solution and breaks the barrier layer between the cathode surface and the bulk of the solution, thus increases the metal deposition on the cathode surface. The results show that an ultrasonic field is successful for the removal of low copper concentrations in solution.

Copper↗
PubMed2002

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.

Biomarkers, Tumor↗
PubMed2001

Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Animal and observational epidemiologic studies have reported that estrogens may increase the risk for gallstones. No major clinical trials have examined the effect of estrogen plus progestin therapy in postmenopausal women on the risk for biliary tract surgery. OBJECTIVE: To determine the effect of estrogen plus progestin on the risk for biliary tract surgery in postmenopausal women with known coronary artery disease. DESIGN: Randomized, double-blind placebo-controlled trial of postmenopausal hormone therapy for coronary heart disease. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2253 postmenopausal women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and Estrogen/progestin Replacement Study (HERS). INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, daily in one tablet or identical placebo. MEASUREMENTS: Documented biliary tract surgery. RESULTS: A total of 147 women (7%) were hospitalized for biliary tract surgery in HERS. Treatment with estrogen plus progestin resulted in a marginally significant 38% increase in the relative risk for biliary tract surgery (P = 0.05). A small absolute difference in risk suggested that for every 185 women treated with estrogen plus progestin, one additional woman had biliary tract surgery per year. After adjustment for baseline and in-study statin use, the association was attenuated further (P = 0.09). After adjustment for treatment assignment and other variables, increased body mass index, fibric acid use, and a history of nonsurgical gallbladder disease were associated with an increased risk for biliary tract surgery, whereas statin use was associated with a decreased risk (for each comparison, P < 0.05). CONCLUSION: Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a marginally significant increase in the risk for biliary tract surgery.

Adult↗
PubMed2001

Bulk production and functional analyses of mouse CD55's native and deglycosylated active domains.

We report the use of methylotrophic yeast Pichia pastoris as a host to efficiently express complement control protein repeats (CCPs) 1-4 of mouse decay accelerating factor (DAF, CD55) as a soluble protein. With this system, the mouse DAF CCP1-4-active-domain-containing module linked to a 6x His tag at its C terminus was secreted into the culture supernatant at 15 mg/L after 24 h of induction with methanol. A mouse DAF CCP1-4 mutant protein in which its two potential N-glycosylation sites were deleted by changing Asn(187) and Asn(262) to Gln was also produced. Using Ni(2+)-immobilized agarose affinity chromatography, the recombinant mouse DAF modules with their 6x His tags could be one-step isolated to SDS-PAGE purity. Polyclonal antibody against native mouse DAF CCP1-4 was raised by immunizing NZW rabbits with the purified product. Measurements of the bioactivities of the wild-type and mutant mouse DAF proteins in C3b uptake assays showed no differences in regulatory activities in either the classical or the alternative pathways. With the use of the mutant DAF protein, small rod-shaped crystals were produced and preliminary data obtained. The production of large quantities of functional recombinant mouse DAF CCP1-4 modules and their antibody offers the opportunity to study DAF structure and DAF function in vivo.

Animals↗
PubMed2001

Targeted alpha(1A)-adrenergic receptor overexpression induces enhanced cardiac contractility but not hypertrophy.

Activation of the alpha(1A)-adrenergic receptor (alpha(1A)-AR)/Gq pathway has been implicated as a critical trigger for the development of cardiac hypertrophy. However, direct evidence from in vivo studies is still lacking. To address this issue, transgenic mice with cardiac-targeted overexpression of the alpha(1A)-AR (4- to 170-fold) were generated, using the rodent alpha-myosin heavy chain promoter. Heterozygous animals displayed marked enhancement of cardiac contractility, evident from increases in dP/dt(max) (80%, P<0.0001), dP/dt(max)/LVP(inst) (76%, P<0.001), dP/dt(max):dP/dt(min) (104%, P<0.0001), and fractional shortening (33%, P<0.05). Moreover, changes in the dP/dt(max)-end-diastolic volume relationship provided load-independent evidence of a primary increase in contractility. Blood pressure and heart rate were largely unchanged, and there was a small increase in (-)norepinephrine-stimulated, but not basal, phospholipase C activity. Increased contractility was directly related to the level of receptor overexpression and could be completely reversed by acute alpha(1A)- but not beta-AR blockade. Despite the robust changes in contractility, transgenic animals displayed no morphological, histological, or echocardiographic evidence of left ventricular hypertrophy. In addition, apart from an increase in atrial natriuretic factor mRNA, expression of other hypertrophy-associated genes was unchanged. To our knowledge, these data provide the first in vivo evidence for an inotropic action of the alpha(1A)-AR.

Adenylyl Cyclases↗
PubMed2001

The incidence of unrecognized myocardial infarction in women with coronary heart disease.

BACKGROUND: Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized. OBJECTIVE: To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS). DESIGN: Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up. SETTINGS: Outpatient and community settings at 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus. MEASUREMENTS: Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared. RESULTS: Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction. CONCLUSION: The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.

Aged↗
PubMed2001

Azepanone-based inhibitors of human and rat cathepsin K.

The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone-based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are described. These compounds show improved configurational stability of the C-4 diastereomeric center relative to the previously published five- and six-membered ring ketone-based inhibitor series. Studies in this series have led to the identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) = 0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic analysis of 20 established the C-4 S stereochemistry as being critical for potent inhibition and that unbound 20 adopted the expected equatorial conformation for the C-4 substituent. Molecular modeling studies predicted the higher energy axial orientation at C-4 of 20 when bound within the active site of cathepsin K, a feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of the cyclic and acyclic analogues through CaCo-2 cells suggests that oral bioavailability of the acyclic derivatives is limited by a P-glycoprotein-mediated efflux mechanism. It is concluded that the introduction of a conformational constraint has served the dual purpose of increasing inhibitor potency by locking in a bioactive conformation as well as locking out available conformations which may serve as substrates for enzyme systems that limit oral bioavailability.

Administration, Oral↗
PubMed2001

BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model.

It is well accepted that the Bcr-Abl oncoprotein encoded by the Philadelphia chromosome is responsible for causing chronic myelogenous leukemia (CML). We have previously demonstrated that expression of Bcr interferes with the oncogenic effects of Bcr-Abl. To examine the effects of increased Bcr expression on Bcr-Abl oncogenic effects in a more physiological system, we tested the leukemogenic potential of a clone of K562 cells (K6 K562) containing an inducible BCR gene in NOD/scid mice. In this clone, the BCR gene was placed under the control of a tetracycline (Tet) repression system with a cytomegalovirus (CMV) promoter. Induction of exogenous Bcr protein by removal of Tet from the culture medium caused a dramatic increase in Bcr serine kinase activity, yielding predominantly phosphoserine Bcr, despite the presence of Bcr-Abl in the kinase reaction mixture. Prior to induction, the endogenous Bcr was predominantly in the phosphotyrosine form because of phosphorylation by Bcr-Abl, which we previously have shown suppresses Bcr serine/threonine kinase activity. Injection of K6 K562 cells into NOD/scid mice under conditions where BCR expression was suppressed resulted in death or terminal illness in 100% of the mice within 35 days after injection. These mice had a severe wasting syndrome characterized by atrophy of bone marrow hematopoiesis, and/or neoplasia of liver, bone marrow and spleen. Neoplastic spleens from these mice usually contained b3a2 Bcr-Abl transcripts. In contrast, induction of BCR expression at the time of injection allowed 80% survival; these healthy mice had no detectable microscopic lesions in blood forming organs. This difference in survival was significant with P<0.0001. Of interest, mice that were fed Tet for 19 days to initiate the disease syndrome and then released from the BCR transcriptional block had a significantly better survival pattern than mice exposed to Tet throughout the entire period. Moreover, 30% of these mice (three mice) survived through day 50. We conclude from these findings that BCR gene expression strongly inhibits the oncogenic effects of Bcr-Abl in NOD/scid mice, yielding healthy mice in most cases.

Animals↗
PubMed2001

Cytologic diagnosis of gastrointestinal stromal tumors of the stomach by endoscopic ultrasound-guided fine-needle aspiration biopsy: cytomorphologic and immunohistochemical study of 12 cases.

Gastrointestinal stromal tumor (GIST) is an uncommon tumor, which was usually diagnosed by endoscopic biopsy or surgical resection. This study evaluated the efficacy and accuracy of endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) biopsy in the diagnosis of GIST and reported its cytomorphologic features. Twelve patients with gastric GIST were diagnosed through EUS-guided FNA. Immediate on-site evaluation and cytologic diagnoses were given in nine cases (75.0%) with an average of three passes. Cell blocks provided diagnostic material in three cases (25.0%). Spindle cells were present in the cytologic material in all cases. Two patients had subsequent surgical resections. Immunohistochemical (IHC) studies performed in cell blocks and two surgical specimens all supported the original diagnoses. In the two cases with surgical resections, IHC results in cell blocks were similar to that in the resected specimens. This study demonstrated that when combining smears and cell blocks, EUS-guided FNA is accurate and efficient in the diagnosis of GIST. IHC reactivity in cell blocks correlated with that of the main tumors.

Adult↗
PubMed2001

Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers.

Prostate cancer is one of the leading causes of cancer-related deaths for men in the United States. Like other malignancies, prostate cancer is underscored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently identified among prostate cancers, few genes have been identified thus far as critical to the development of invasive prostate cancers. In this report, we used the recently developed technology, the "differential subtraction chain," to perform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence was deleted in >50% of prostate cancers we tested. We mapped this sequence to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 cases, or 80%). Statistical analysis indicates that deletion of myopodin is highly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers.

Amino Acid Sequence↗
PubMed2001

Identification of a novel gene with increasing rate of suppression in high grade prostate cancers.

Prostate cancer is the second leading cause of cancer-related deaths in the United States. However, the underlying molecular events for prostate cancer development are not clear. In this study, we applied the recently developed technology known as differential subtraction chain (DSC) to identify a novel gene whose expression is inactivated in high grade prostate cancer. This gene, designated as SAPC, is expressed in normal prostate acinar cells. Its expression is dramatically down-regulated in high grade prostate cancers (4/4) but is unaltered in low grade prostate cancers. It encodes a 7.7-kd protein. Its sequence shares some homology with the cysteine-rich domain of 2-5A-dependent RNase L, which is a critical component of the interferon-induced apoptosis cascade. The selective inactivation in the more aggressive prostate cancers holds promise for SAPC as a potential prognostic marker for high grade prostate cancer.

Amino Acid Sequence↗
PubMed2001

Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease.

OBJECTIVES: This study sought to determine the independent association of renal insufficiency with cardiovascular risk among women with known coronary heart disease (CHD). BACKGROUND: Although patients with end-stage renal disease and proteinuria are at high risk for cardiovascular events, little is known about the cardiovascular risk associated with moderate renal insufficiency. METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a clinical trial among 2,763 women with coronary disease who were randomized to conjugated estrogen plus progestins or identical placebo and followed for a mean of 4.1 years. Women were categorized as having normal renal function (creatinine < 1.2 mg/dl; n = 2,012), mild renal insufficiency (1.2 mg/dl to 1.4 mg/dl; n = 567) and moderate renal insufficiency (>1.4 mg/dl; n = 182). We examined the independent association of renal function with incident cardiovascular events including CHD death, nonfatal myocardial infarction, hospitalization for unstable angina, stroke and transient ischemic attacks. RESULTS: Compared with women with normal renal function, those with mild and moderate renal insufficiency were older, more likely to be black, have a history of hypertension and diabetes and have higher serum levels of triglycerides and lipoprotein(a). After multivariate adjustment, both mild (relative hazards [RH] = 1.24; 95% confidence interval [CI]: 1.0 to 1.5) and moderate renal insufficiency (RH = 1.57; 95% CI: 1.2 to 2.1) were independently associated with increased risk for cardiovascular events compared with women with normal renal function. CONCLUSIONS: Renal insufficiency is an independent risk factor for cardiovascular events in postmenopausal women with known coronary artery disease. Renal function may add helpful information to CHD risk stratification.

Aged↗
PubMed2001

Mining time dependency patterns in clinical pathways.

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length of hospital stay of each patient. The development of clinical pathways is a lengthy process, and may require the collaboration among physicians, nurses, and staffs in a hospital. However, the individual differences cause great variances in the execution of clinical pathways. It calls for a more dynamic and adaptive process to improve the performance of clinical pathways. This paper reports a data mining technique we have developed to discover the time dependency pattern of clinical pathways for managing brain stroke. The mining of time dependency pattern is to discover patterns of process execution sequences and to identify the dependent relation between activities in a majority of cases. By obtaining the time dependency patterns, we can predict the paths for new patients when he/she is admitted into a hospital; in turn, the health care procedure will be more effective and efficient.

Algorithms↗
PubMed2001

Persistent infection is a rare sequel following infection of pigs with swine vesicular disease virus.

Nine isolates from pigs persistently infected with a recent Italian isolate of swine vesicular disease (SVD) virus, ITL/9/93, were collected sequentially over 121 days and were characterized antigenically and biochemically. There was an accumulation of amino acid (aa) substitutions in the capsid proteins throughout the carrier state that could be correlated with alterations in antigenicity in virus isolates collected late stage in infection. The aa substitutions detected mainly occurred in VPI and antigenic changes were detected in late isolates both at antigenic site 1, resulting in loss of binding of Mab 4GO7, and at a closely located site which has not yet been named, recognized by Mab C29. In further experiments groups of pigs were exposed to a range of SVD viruses, but no virus was isolated beyond 16 days post infection (dpi) nor viral RNA detected beyond 42 dpi. Attempts to transfer infection to sentinel pigs introduced some time after initial infection of the original pigs were largely unsuccessful. The carrier state was established in only one out of five experimental infections of pigs with SVD virus and can therefore be considered a rare sequel toinfection with SVD virus and is of limited significance in the epidemiology of the disease.

Amino Acid Sequence↗
PubMed2001

Tissue distribution of products of the mouse decay-accelerating factor (DAF) genes. Exploitation of a Daf1 knock-out mouse and site-specific monoclonal antibodies.

Decay-accelerating factor (DAF) is a membrane regulator of C3 activation that protects self cells from autologous complement attack. In humans, DAF is uniformly expressed as a glycosylphosphatidylinositol (GPI)-anchored molecule. In mice, both GPI-anchored and transmembrane-anchored DAF proteins are produced, each of which can be derived from two different genes (Daf1 and Daf2). In this report, we describe a Daf1 gene knock-out mouse arising as the first product of a strategy for targeting one or both Daf genes. As part of the work, we characterize recently described monoclonal antibodies against murine DAF protein using deletion mutants synthesized in yeast, and then employ the monoclonal antibodies in conjunction with wild-type and the Daf1 knock-out mice to determine the tissue distribution of the mouse Daf1 and Daf2 gene products. To enhance the immunohistochemical detection of murine DAF protein, we utilized the sensitive tyramide fluorescence method. In wild-type mice, we found strong DAF labelling of glomeruli, airway and gut epithelium, the spleen, vascular endothelium throughout all tissues, and seminiferous tubules of the testis. In Daf1 knock-out mice, DAF labelling was ablated in most tissues, but strong labelling of the testis and splenic dendritic cells remained. In both sites, reverse transcription-polymerase chain reaction analyses identified both GPI and transmembrane forms of Daf2 gene-derived protein. The results have relevance for studies of in vivo murine DAF function and of murine DAF structure.

Animals↗
PubMed2001

Development of a competitive ELISA using a truncated E2 recombinant protein as antigen for detection of antibodies to classical swine fever virus.

The sequence encoding a truncated E2 glycoprotein of the Alfort/187 strain of classical swine fever virus (CSFV) was expressed in Escherichia coli using the pET expression system and the recombinant product purified by Ni-NTA agarose affinity chromatography. The antigenicity of this recombinant protein was demonstrated by immunoblot using anti- CSFV-specific antibodies. A monoclonal antibody was produced against the truncated E2 protein and used as competitor in an ELISA for the detection of antibodies to CSFV. Specific antibodies were demonstrated by competitive ELISA (C-ELISA) as early as 21 days post-infection (dpi) in experimentally infected pigs. Seroconversion was demonstrated by C-ELISA and neutralising peroxidase-linked assay (NPLA) in all infected animals by 4 weeks. No cross-reaction with antibodies to bovine viral diarrhoea virus (BVDV) was seen in the C-ELISA using sera from experimentally infected pigs. The C-ELISA is not intended as a substitute for the NPLA. However, it is expected it will be useful for monitoring and prevalence studies. It will also assist in testing a large number of samples in the event of an outbreak.

Animals↗