Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 55 records · Page 3Linked to original sources

PubMed2006

Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial.

BACKGROUND AND STUDY AIMS: Intraoperative interstitial brachytherapy has been found to be effective when used during laparotomy to improve local control in patients with locally advanced pancreatic cancer. In this study, we report the results of using endoscopic ultrasound- (EUS-)guided interstitial brachytherapy in patients with advanced pancreatic cancer, with respect to tumor response, clinical response, safety, and complications. PATIENTS AND METHODS: Fifteen patients (eight men, seven women; median age 61 years) with unresectable pancreatic adenocarcinoma were enrolled into the study, eight patients with stage III disease and seven patients with stage IV disease. A mean number of 22 radioactive seeds per patient were implanted into the tumors by EUS-guided needle puncture. The mean total implanted activity was 20 mCi, the minimum peripheral dose was 14,000 cGy, and the mean volume of implants was 52 cm3. Patients were followed-up by examination and by imaging tests every 2-3 months: clinical end points included the Karnofsky performance status and pain responses, tumor response (assessed by computed tomography and/or EUS), and survival. RESULTS: During a median follow-up period of 10.6 months, the objective tumor response was classified as "partial" in 27% of patients (with a median duration of partial response of 4.5 months), "minimal" in 20% patients, and indicative of "stable disease" in 33% of patients. Clinical benefit was shown in 30% of patients, mostly due to reduction in pain, but this lasted for a limited time. Local complications (pancreatitis and pseudocyst formation) occurred in three patients; grade III hematologic toxicity occurred in three patients without serious clinical sequelae. CONCLUSIONS: EUS-guided intraoperative interstitial brachytherapy had a moderate local tumor effect and showed some clinical benefit in 30% of the patients in this study. Combination of this form of treatment with external radiation and/or chemotherapy should be tested in future trials.

Adenocarcinoma↗

PubMed2006

AML-loaded DC generate Th1-type cellular immune responses in vitro.

BACKGROUND: The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols. METHODS: In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts. RESULTS: Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system. DISCUSSION: These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.

Acute Disease↗

PubMed2006

Evidence for biogeographic patterning of mitochondrial DNA sequences in Eastern horse populations.

Equine mitochondrial DNA (mtDNA) phylogeny reconstruction reveals a complex pattern of variation unlike that seen in other large domesticates. It is likely that this pattern reflects a process of multiple and repeated, although not necessarily independent, domestication events. Until now, no clear geographic affiliation of clades has been apparent. In this study, amova analyses have revealed a significant non-random distribution of the diversity among equine populations when seven newly sequenced Eurasian populations were examined in the context of previously published sequences. The association of Eastern mtDNA types in haplogroup F was highly significant using Fisher's exact test of independence (P = 0.00000). For the first time, clear biogeographic partitioning has been detected in equine mtDNA sequence.

Animals↗

PubMed2006

Improvement in quality of life with infliximab induction and maintenance therapy in patients with moderate-to-severe psoriasis: a randomized controlled trial.

BACKGROUND: Psoriasis has a well-documented, markedly negative effect on patient quality of life. OBJECTIVES: To evaluate the impact of long-term infliximab maintenance therapy on health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The Dermatology Life Quality Index (DLQI) and 36-item Short Form Health Survey (SF-36) were administered as part of the pivotal double-blind, placebo-controlled efficacy and safety EXPRESS study of infliximab in chronic plaque psoriasis. In total, 378 patients with moderate-to-severe psoriasis were enrolled at 32 centres in Europe and Canada. Patients were randomized to receive either placebo or infliximab 5 mg kg(-1) induction at weeks 0, 2 and 6 followed by maintenance every 8 weeks; placebo patients crossed over at week 24 to receive the infliximab induction and maintenance regimen. RESULTS: At week 10, infliximab-treated patients had significantly greater improvement in DLQI scores (P < 0.001) and SF-36 physical and mental component summary scores (P < 0.001) than placebo-treated patients. Significant improvement (P < 0.001) was also seen in all eight SF-36 subscales, and was greatest for the "Bodily Pain" and "Social Functioning" scales. Significant improvement in HRQoL persisted with maintenance infliximab treatment at week 24 (P < 0.001), with patients achieving a Psoriasis Area and Severity Index score of 0 reporting the greatest benefit. Treatment-related HRQoL improvement remained substantial at week 50. CONCLUSIONS: Infliximab induction and maintenance regimens resulted in rapid, substantial, sustained and clinically meaningful improvement in both dermatology-specific and general quality of life indices in patients with psoriasis, with total clearance resulting in maximum improvement.

Adult↗

PubMed2006

Immunosuppression: evolution in practice and trends, 1994-2004.

Over the last 10 years, there have been important changes in immunosuppression management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens. An organ-by-organ review of OPTN/SRTR data showed several important trends in immunosuppression practice. There is an increasing trend toward the use of induction therapy with antibodies, which was used for most kidney, pancreas after kidney (PAK), simultaneous pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72-81%) and for approximately half of all intestine, heart and lung recipients. The highest usage of the tacrolimus/mycophenolate mofetil combination as discharge regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the original discharge regimen through the first 3 years following transplantation varied significantly by organ and drug. The usage of calcineurin inhibitors for maintenance therapy was characterized by a clear transition from cyclosporine to tacrolimus. Corticosteroids were administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal protocols have become increasingly common. The percentage of patients treated for acute rejection during the first year following transplantation has continued to decline, reaching 13% for those who received a kidney in 2003, 48% of which cases were treated with antibodies.

Evolution, Molecular↗

PubMed2006

Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1.

BACKGROUND: High myopia is a common genetic variation in most cases, affecting 1-2% of people, and is the fourth most common disorder causing blindness worldwide. Six autosomal dominant loci and one X-linked recessive locus have been reported, but no genes responsible for high myopia have been identified. OBJECTIVE: To report a Chinese family in which six males presented with high myopia consistent with an X linked recessive trait. RESULTS: Affected individuals shared three common features: high myopia, reduced visual acuity, and fundal changes of high myopia. Protan and deutan were observed in the family, but they did not co-segregate with the high myopia phenotype. X-chromosome-wide linkage analysis mapped the high myopia locus to a 25 cM (14.9 Mb) region on Xq23-q25 between DXS1210 and DXS8057, with maximum two point lod scores at theta = 0 of 2.75 and 2.29 for DXS1001 and DXS8059, respectively. CONCLUSIONS: This new myopia locus is outside the linked region of the first high myopia locus (MYP1). Refinement of the linkage region with additional families and screening candidate genes for mutation may lead to the identification of the defect gene.

Adult↗

PubMed2006

Novel IRF6 mutations in Chinese patients with Van der Woude syndrome.

Van der Woude syndrome (VWS) (OMIM 119300) is a dominantly inherited, developmental disorder that is characterized by pits and/or sinuses of the lower lip and a cleft lip and/or cleft palate. Mutations in the interferon regulatory factor 6 gene (IRF6) have been recently identified in patients with VWS, with more than 60 mutations reported. However, the VWS phenotype, IRF6 mutation genotypes, and their interrelationships in Chinese VWS patients have not been studied. Here, we report 11 Chinese families with variable clinical phenotypes of VWS and identified mutations in all patients. Of the 11 mutations, 8 appeared to be novel: CC5.6GT, T342A, 566delA, C748T, C756A, C989A, C1209G, and 1316delT. Seven mutations caused a change or loss of the IRF6 domain. The marked phenotypic variation may be caused by the action of certain modifier genes on IRF6 function.

Adult↗

PubMed2005

Redox control of K+ channel remodeling in rat ventricle.

Electrical remodeling of the diseased heart contributes to contractile dysfunction and arrhythmias, and is characterized by down-regulation of K(+) channels that control action potential morphology. We have recently shown that remodeling of K(+) channels underlying the transient outward current (I(to)) involves a shift in cell redox balance that is reflected by a depletion of the endogenous redox buffer, glutathione (GSH). This study used a pharmacological model to further examine the role of redox-mediated mechanisms in regulating cardiac K(+) currents. Inhibition of major redox pathways was elicited in normal rats by daily injections of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of thioredoxin and glutathione reductases, and buthionine sulfoximine (BSO), a blocker of GSH synthesis. Fluorescence microscopy studies showed that [GSH] in isolated ventricular myocytes was decreased ~50% from control after 3 days of BCNU/BSO treatment (P<0.05), consistent with a shift in cell redox state. In voltage-clamp experiments, maximum I(to) density was decreased 33% from control in left ventricular myocytes from BCNU/BSO-treated rats (P<0.05), while the inward rectifier and steady state outward currents were not significantly altered. Decreased I(to) density correlated with significant decreases in Kv4.2 mRNA and proteins levels of Kv4.2 and Kv1.4. Down-regulation of I(to) in myocytes from BCNU/BSO rats was reversed in vitro by exogenous GSH or N-acetylcysteine, a GSH precursor and antioxidant. I(to) density and [GSH] were also up-regulated by receptor tyrosine kinase activation with insulin or a tyrosine phosphatase inhibitor. The effect of these activators on I(to) was blocked by inhibitors of PI 3-kinase, MEK and p38 MAP kinases. These data suggest that expression of cardiac I(to) channels is regulated by endogenous oxidoreductase systems and that receptor tyrosine kinase signaling functionally impacts K(+) channel remodeling through its control of cell redox state.

Animals↗

PubMed2005

Silica encapsulation and magnetic properties of FePt nanoparticles.

Core-shell nanoparticles have emerged as an important class of functional nanostructures with potential applications in many diverse fields, especially in health sciences. We have used a modified aqueous sol-gel route for the synthesis of size-selective FePt@SiO2 core-shell nanoparticles. In this approach, oleic acid and olyel amine stabilized FePt nanoparticles are first encapsulated through an aminopropoxysilane (APS) monolayer and then subsequent condensation of triethoxysilane (TEOS) on FePt particle surface. These well-defined FePt@SiO2 core-shell nanoparticles with narrow size distribution become colloidal in aqueous media, and can thus be used as carrier fluid for biomolecular complexes. In comparison, the scarce hydrophilic nature of oleic acid monolayers on FePt particle surface yields an edgy partial coating of silica when only TEOS is applied for the surface modification. The synthesized core-shell nanoparticles were characterized by direct techniques of high resolution transmission electron microscopy (HRTEM), EDS and indirectly via UV-vis absorption and FTIR studies. The FePt@SiO2 nanoparticles exhibit essential characteristics of superparamagnetic behavior, as investigated by SQUID magnetometry. The blocking temperatures (T(B)) of FePt and FePt@SiO2 (135 and 80 K) were studied using zero field cooled (ZFC)/field cooled (FC) curves.

Adsorption↗

PubMed2005

A comparison between long-term survivors of Hodgkin's disease and their siblings on fatigue level and factors predicting for increased fatigue.

PURPOSE: To compare the level of fatigue in survivors of Hodgkin's disease and their siblings, and to explore factors associated with increased fatigue. METHODS: Survivors of Hodgkin's disease 5 years or more from diagnosis and their siblings completed a questionnaire study. Fatigue level was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) instrument, with lower scores reflecting increased fatigue. Multiple regression models were used to identify factors associated with fatigue level in the two populations. RESULTS: Five hundred and eleven survivors (median age 44 years; range 16-82) and 224 siblings (median age 44 years; range 16-79) returned the completed questionnaire. The response rates were 61% and 58%, respectively. Compared with siblings, survivors were significantly more likely to report the presence of cardiac disease (26% versus 16%; P = 0.001) and hypothyroidism (65% versus 3%; P <0.001), and had a significantly lower mean FACIT-F score (40.7 and 42.2; P = 0.05). On multivariable analysis, factors significantly associated with increased fatigue in survivors were reports of cardiac disease (P <0.001), psychiatric condition (P <0.001), history of tobacco use (P = 0.004) and low exercise frequency (P = 0.03). For siblings, the only independent factor associated with increased fatigue was low exercise frequency (P = 0.03). CONCLUSIONS: Survivors of Hodgkin's disease were more fatigued than their siblings. The difference was modest but statistically significant. The significant association between fatigue and cardiac disease suggests the importance of screening for underlying cardiac dysfunction in survivors with symptoms of fatigue. The association between fatigue and smoking history may be due to exacerbation of late medical complications of Hodgkin's disease by tobacco use.

Adolescent↗

PubMed2005

In vivo action of a new octadecaneuropeptide antagonist on neuropeptide Y and corticotropin-releasing hormone mRNA levels in rat.

It has been reported that several of the effects induced by an octadecaneuropeptide (ODN), derived from an 86-amino-acid polypeptide termed diazepam-binding inhibitor, could be mediated by activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in the regulation of corticotropin-releasing factor (CRH) and neuropeptide Y (NPY) expression in the paraventricular nucleus and arcuate nucleus, respectively, we studied the effects of the acute intracerebroventricular administration of ODN (2 microg/rat) and the ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu5]OP (20 microg/rat), on the gene expression of the two neuropeptides in castrated male rat. ODN administration resulted in a 45% increase in CRH mRNA expression, an effect which was reversed by cyclo(1-8)[Dleu5]OP. When cyclo(1-8)[Dleu5]OP was administered alone, it induced a 19% decrease in CRH mRNA levels. ODN administration induced a 17% decrease in NPY mRNA expression while cyclo(1-8)[Dleu5]OP increased by 21% the hybridization signal. The administration of both ODN and ODN antagonist completely abolished the depressing effect of ODN on NPY mRNA. These data suggest that the effects of ODN on CRH and NPY mRNA might be mediated by interaction with metabotropic receptors. Moreover, since cyclo(1-8)[Dleu5]OP can by itself influence the expression of two peptide mRNAs, it might be suggested that ODN is exerting a tonic influence on NPY and CRH neurons.

Animals↗

PubMed2005

Integrated RF probe for in vivo multinuclear spectroscopy and functional imaging of rat brain using an 11.7 Tesla 89 mm bore vertical microimager.

To acquire high quality in vivo NMR data from rat brain using a vertical 89-mm bore magnet, specially designed NMR probes with integrated RF coils and animal handling capability are required. An RF probe design that is also capable of rat head fixation, body support and suitable for physiology monitoring and maintenance was constructed for an 89 mm bore, 11.7 T, vertical microimager which is equipped with a 57-mm i.d. gradient insert. Design concept and practical aspects of probe construction are described in detail. The device allows accurate and highly reproducible positioning of rat head inside the magnet while providing excellent RF performance. Typical results from fMRI, localized in vivo proton and multinuclear spectroscopy using this probe system are presented.

Animals↗

PubMed2005

A high-pressure structure in curium linked to magnetism.

Curium lies at the center of the actinide series and has a half-filled shell with seven 5f electrons spatially residing inside its radon core. As a function of pressure, curium exhibits five different crystallographic phases up to 100 gigapascals, of which all but one are also found in the preceding element, americium. We describe here a structure in curium, Cm III, with monoclinic symmetry, space group C2/c, found at intermediate pressures (between 37 and 56 gigapascals). Ab initio electronic structure calculations agree with the observed sequence of structures and establish that it is the spin polarization of curium's 5f electrons that stabilizes Cm III. The results reveal that curium is one of a few elements that has a lattice structure stabilized by magnetism.

Journal Article↗

PubMed2005

Role of FOXO1A in the regulation of insulin-like growth factor-binding protein-1 in human endometrial cells: interaction with progesterone receptor.

Insulin-like growth factor-binding protein-1 (IGFBP1) is a major secretory product of the decidualized endometrium. In the present study, we investigated the role of two transcription factors, progesterone receptor (PGR) and a member of the forkhead box class O family of transcription factors (FOXO1A), in the regulation of the IGFBP1 gene in endometrial cells. Human endometrial fibroblasts (HuF) expressed FOXO1A, progesterone receptor A (PGRA), and progesterone receptor B (PGRB) proteins, whereas the endometrial adenocarcinoma cell line, HEC-1B cells, expressed only FOXO1A and no detectable PGR proteins. When FOXO1A expression was silenced using small interference RNA, IGFBP1 expression decreased in both HuF and HEC-1B cells. Using the chromatin immunoprecipitation technique, we demonstrated that liganded PGR was recruited to the IGFBP1 promoter region (-358 to -49). In addition, immunoprecipitation of HuF nuclear proteins with a PGR antibody followed by immunoblotting with anti-FOXO1A revealed that these two proteins interact in these cells. Reporter studies demonstrated that whereas liganded PGRA or PGRB increased a progesterone response element-linked reporter construct, pPRE/ GRE.E1b.Luc, coexpression of FOXO1A inhibited the PGRB response in HuF and synergistically increased PGRA and PGRB response in HEC-1B cells. Furthermore, in HEC-1B cells, FOXO1A increased IGFBP1 promoter activity, and coexpression of PGRA or PGRB further increased the promoter activity in a cooperative manner. In HuF, the response to FOXO1A and PGR was not additive; in fact, it was lower than the sum of the individual responses. Thus, FOXO1A and PGR associate with one another, and each influences the transactivating potential of the other. The cell type-dependent responses strongly implicate the involvement of other cofactors.

Adenocarcinoma↗

PubMed2005

Localization of type 5 17beta-hydroxysteroid dehydrogenase mRNA in mouse tissues as studied by in situ hybridization.

The mouse enzyme type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD) catalyzes the conversion of androstenedione to testosterone and, to a lesser degree, the conversion of estrone to estradiol. In order to determine the exact sites of action of type 5 17beta-HSD, we studied the cellular localization of the mRNA of the enzyme in mouse tissues by using in situ hybridization. Specific hybridization signal was found in the liver, ovary, adrenal cortex, and kidney. In the liver of mice of both sexes, a strong signal was observed in all hepatocytes. In the ovary, specific labeling was detected in the granulosa and theca interna cells in growing follicles and in luteal cells. In the female adrenal cortex, intense labeling was restricted to the zona reticularis, whereas no type 5 17beta-HSD mRNA expression could be found in the male adrenal cortex. In the kidney of mice of both sexes, type 5 17beta-HSD mRNA was expressed in epithelial cells in both the proximal and distal convoluted tubules. The data indicate that androgens and estrogens are formed via the action of type 5 17beta-HSD in specific cell types in the liver, ovary, adrenal cortex, and kidney.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.

BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.

Adult↗

PubMed2005

Regulation of membrane trafficking by a novel Cdc42-related protein in Caenorhabditis elegans epithelial cells.

Rho GTPases are mainly known for their implication in cytoskeleton remodeling. They have also been recently shown to regulate various aspects of membrane trafficking. Here, we report the identification and the characterization of a novel Caenorhabditis elegans Cdc42-related protein, CRP-1, that shows atypical enzymatic characteristics in vitro. Expression in mouse fibroblasts revealed that, in contrast with CDC-42, CRP-1 was unable to reorganize the actin cytoskeleton and mainly localized to trans-Golgi network and recycling endosomes. This subcellular localization, as well as its expression profile restricted to a subset of epithelial-like cells in C. elegans, suggested a potential function for this protein in polarized membrane trafficking. Consistent with this hypothesis, alteration of CRP-1 expression affected the apical trafficking of CHE-14 in vulval and rectal epithelial cells and sphingolipids (C(6)-NBD-ceramide) uptake and/or trafficking in intestinal cells. However, it did not affect basolateral trafficking of myotactin in the pharynx and the targeting of IFB-2 and AJM-1, two cytosolic apical markers of intestine epithelial cells. Hence, our data demonstrate a function for CRP-1 in the regulation of membrane trafficking in a subset of cells with epithelial characteristics.

Actins↗

PubMed2005

Localization of type 7 17beta-hydroxysteroid dehydrogenase in mouse tissues. In situ hybridization studies.

The enzyme type 7 17beta-hydroxysteroid dehydrogenase (17beta-HSD) selectively catalyzes the conversion of estrone (E1) into estradiol (E2). In order to obtain detailed information about the exact sites of action of type 7 17beta-HSD, we have studied the cellular localization of type 7 17beta-HSD mRNA in mouse tissues using in situ hybridization (ISH). In parallel studies, we also measured the enzyme mRNA levels by quantitative real time (RT)-PCR. In the ovary, strong hybridization signal was restricted to corpus luteum cells. In the female mammary gland, type 7 17beta-HSD mRNA was found to be expressed in stromal cells surrounding the ducts. In the clitoral and preputial glands, specific labeling was observed in the epithelial cells of both acini and small ducts. In the adrenal gland, hybridization signal was observed in the zona fasciculata and reticularis in the cortex. In the liver, hybridization signal was found in all the hepatocytes. In the colon, type 7 17beta-HSD mRNA expression was restricted to epithelial cells of the mucosa. From the results obtained with quantitative real time RT-PCR, it appears, with a very few exceptions, that in tissues exhibiting low mRNA expression no ISH signal could be detected. The present data suggest that E2 can be formed through the action of type 7 17beta-HSD in specific cell types in the ovary and peripheral tissues, in addition to type 1 17beta-HSD, thus providing tissues with an alternative route of formation of E2.

17-Hydroxysteroid Dehydrogenases↗