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Biomedical subjects

G Yu

Publications and source records attributed to G Yu.

At least 73 records · Page 4Linked to original sources

APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity.

We report that the tumor neurosis factor homolog APRIL (a proliferation-inducing ligand) stimulates in vitro proliferation of primary B and T cells and increases spleen weight due to accumulation of B cells in vivo. APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-I (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL and block APRIL-stimulated proliferation of primary B cells. BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin and Pneumovax in mice, indicating that APRIL and/or TALL-I signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function.

Animals↗

Effect of MEN 10755, a new disaccharide analogue of doxorubicin, on sarcoplasmic reticulum Ca(2+) handling and contractile function in rat heart.

1. The use of anthraquinone antineoplastic agents is limited by their cardiac toxicity, which is largely due to activation of the sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor). MEN 10755 is a new disaccharide analogue of doxorubicin. We have evaluated its effects on SR function and its toxicity in isolated working rat hearts. 2. In rat SR vesicles, doxorubicin stimulated [(3)H]-ryanodine binding by increasing its Ca(2+)-sensitivity. At 1 microM Ca(2+), ryanodine binding increased by 15.3+/-2.5 fold, with EC(50)=20.6 microM. Epirubicin produced a similar effect, i.e. 9.7+/-0.6 fold stimulation with EC(50)=11.1 microM. MEN 10755 increased ryanodine binding by 1.9+/-0.3 fold (P:<0.01 vs doxorubicin and epirubicin), with EC(50)=38.9 microM. 3. Ca(2+)-induced Ca(2+) release experiments were performed by quick filtration technique, after SR loading with (45)Ca(2+). At 2 microM Ca(2+), doxorubicin (50 microM) increased the rate constant of Ca(2+) release to 82+/-5 s(-1) vs a control value of 22+/-2 s(-1) (P:<0.01), whereas 50 microM MEN 10755 did not produce any significant effect (24+/-3 s(-1)). 4. Ca(2+)-ATPase activity and (45)Ca(2+)-uptake were not significantly affected by doxorubicin, its 13-dihydro-derivative, epirubicin, MEN 10755 and the 13-dihydro-derivative of MEN 10755, at concentrations < or =100 microM. 5. In isolated heart experiments, administration of 30 microM doxorubicin or epirubicin caused serious contractile impairment, whereas 30 microM MEN 10755 produced only minor effects. 6. In conclusion, in acute experiments MEN 10755 was much less cardiotoxic than equimolar doxorubicin or epirubicin. This result might be accounted for by reduced activation of SR Ca(2+) release.

Animals↗

Diagnostic value of lymph node fine needle aspiration cytology: an institutional experience of 387 cases observed over a 5-year period.

Lymph node fine needle aspiration (LNFNA) cytology is valuable in solving the diagnostic problems of clinical adenopathy. The usefulness of the procedure in the staging and diagnosis of various malignant and lymphoproliferative tumours, as well as its role in distinguishing reactive hyperplastic lymph nodes from lymphoma, has been documented in the literature generally on an individual basis. We report our cumulative 5 year experience of LNFNA representing 387 cases. Approximately half (n = 182) were diagnosed as either metastatic carcinoma or melanoma; in 54 cases (30%) excisional biopsy or tissue study was performed to confirm the diagnosis; there was only one false-positive diagnosis of a metastatic squamous carcinoma rendered on a submandibular lymph node. Sixty-one lymphoma cases were successfully diagnosed via LNFNA with no false positives; concurrent flow cytometry was utilized in 51% (n = 31) of the 61 cases and supported the cytologic diagnosis of lymphoma in 27 of the 31 cases (87%). A benign or reactive lymph node process was also diagnosed via LNFNA alone or in combination with flow cytometry in 48 cases with only five false negatives, which included four cases of mantle cell lymphoma and one case of melanoma. Unsatisfactory cases accounted for 12%, and represented specimens obtained by 'Wang needle' or other emerging techniques. Our study demonstrates that LNFNA can be an accurate, economical and rapid diagnostic procedure.

Adult↗

Inhibition of interleukin-1beta (IL-1beta) production in human cells by ribozymes against IL-1beta and IL-1beta converting enzyme (ICE).

We and others have shown previously that hairpin ribozyme genes, when stably expressed in cells, can reduce the steady-state levels of target mRNA and their cognate proteins. Despite this capability, ribozymes have not been as widely used in knockdown experiments as one might expect, probably because specific rules governing the selection of ribozymes that will have high activity have not been described. In this report, we show that parallel screening of less than 10 ribozyme expression constructs, with no advanced knowledge of cleavage activity or preselection, can efficiently identify knockdown ribozymes. This empirical selection study, which used interleukin-1beta (IL-1beta) and IL-1beta converting enzyme (ICE) as example targets, resulted in (1) the rapid identification of ribozymes that can reduce the production of IL-1beta in THP-1 cultures by 10-fold and (2) the consequent direct generation of stable knockdown cell lines. We conclude, based on these and similar studies, that parallel screening of ribozyme constructs could be used in high throughput gene functional analysis programs as a means of rapidly generating specific knockdown cell lines.

Caspase 1↗

Preparation and structural determination of dermatan sulfate-derived oligosaccharides.

Eight oligosaccharides were prepared from dermatan sulfate (DS) and their structures were elucidated. Porcine intestinal mucosal DS was subjected to controlled depolymerization using chondroitin ABC lyase (chondroitinase ABC). The oligosaccharide mixture formed was fractionated by low-pressure gel permeation chromatography (GPC). Size uniform mixtures of disaccharides, tetrasaccharides, hexasaccharides, octasaccharides, decasaccharides, and dodecasaccharides were obtained. Each size-fractionated mixture was then purified on the basis of charge by repetitive semi-preparative strong-anion-exchange (SAX) high-performance liquid chromatography (HPLC). This approach has led to the isolation of six homogeneous oligosaccharides. The size of the oligosaccharides were determined using GPC-HPLC. Treatment of tetrasaccharide and hexasaccharide fragments with Hg(OAc)2 afforded trisaccharide and pentasaccharide products, respectively. The purity of the oligosaccharides obtained was confirmed by analytical SAX-HPLC, and capillary electrophoresis (CE). The molecular mass and degree of sulfation of the eight purified oligosaccharides were elucidated using electrospray ionization (ESI) mass spectrometry and their structures were established with high field nuclear magnetic resonance (NMR) spectroscopy. These DS-oligosaccharides are currently being used to study for interaction of the DS with biologically important proteins.

Animals↗

Secondary stroke prevention in atrial fibrillation: lessons from clinical practice.

BACKGROUND AND PURPOSE: Secondary prevention trials do not distinguish outcomes according to stroke cause. The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology. METHODS: A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation (mean age 76 years; 55% women) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0. Comparisons were made of (1) patient characteristics, anticoagulation control, and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and (2) cause of recurrent stroke by initial stroke subtype. RESULTS: Subjects were 5 years older (95% CI 3 to 7 years), and more patients had small-vessel stroke (26% versus 14%; 95% CI 3% to 17%) compared with corresponding trial data. The duration spent in the target anticoagulation range (55% versus 59%), recurrent stroke rate (5.1% versus 3.6% per year), and major (2.3% versus 2.2% per year) or minor (9.5% versus 11.8% per year) hemorrhage rates were comparable with those in patients receiving warfarin in the randomized study. Ten of 14 (71%) of embolic recurrences occurred in patients with a previous cardioembolic episode, and 8 of 11 (73%) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation (P:=0.025). Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation. CONCLUSIONS: Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of randomized trials. Nearly 26% of qualifying strokes and 40% of recurrences were nonembolic; stroke subtype should be considered when making treatment decisions.

Aged↗

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers.

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.

Alleles↗

Evidence that the beta-catenin nuclear translocation assay allows for measuring presenilin 1 dysfunction.

BACKGROUND: Mutations in the presenilin (PSEN) genes are responsible for the majority of early-onset Alzheimer disease (AD) cases. PSEN1 is a component of a high molecular weight, endoplasmic reticulum, membrane-bound protein complex, including beta-catenin. Pathogenic PSEN1 mutations were demonstrated to have an effect on beta-catenin and glycogen synthase kinase-3beta(GSK-3beta), two members of the wingless Wnt pathway. The nuclear translocation and the stability of beta-catenin, and the interaction between GSK3beta and PSEN1 were influenced. MATERIALS AND METHODS: Stably transfected human embryonic kidney (HEK) 293 cells overexpressing wild-type (wt) and mutant (mt) PSEN1, treated with and without LiCl, were used to isolate cytoplasmic and nuclear fractions. By Western blot analysis, endogenous beta-catenin levels were examined. By analyzing cytosolic fractions of PSEN1, transfected and nontransfected HEK 293 cells, and total brain extracts of AD patients and controls, we evaluated the effect of PSEN1 overexpression on beta-catenin stability. Finally, we analyzed the effect of pathogenic PSEN1 mutations on the interaction between PSEN1 and GSK3beta by co-immunoprecipitation experiments. RESULTS: We report reduced nuclear translocation of beta-catenin in cells stably expressing I143T, G384A, and T113-114ins PSEN1. The G384A PSEN1 mutation showed a similar pronounced effect on nuclear translocation of beta-catenin, as reported for processing of amyloid precursor protein (APP) into amyloid beta(Abeta). Overexpression of PSEN1 and the presence of pathogenic mutations in PSEN1 had no significant effect on the stability of beta-catenin. Nonspecific binding of overexpressed PSEN1 to endogenous GSK3beta was observed when GSK3beta was immunoprecipitated. Immunoprecipitation of PSEN1 in cells overexpressing PSEN1 and in native cells, however, did not result in co-immunoprecipitation of endogenous GSK3beta. CONCLUSION: Our results further establish the nuclear translocation assay of beta-catenin as an adequate alternative for traditional Abeta measurement to evaluate the effect of PSEN1 mutations on biochemical processes. We detected no significant effect of overexpressed wt or mt PSEN1 on the stability of beta-catenin. Finally, co-immunoprecipitation between PSEN1 and GSK3beta was not observed in our experimental setup.

Active Transport, Cell Nucleus↗

The expression kinetics of myogenin in facial muscle denervation.

OBJECTIVE: To study the expression kinetics of myogenin in long-term denervated facial muscle and to explore the possibility of gene therapy for facial muscle paralysis with myogenin gene. MATERIALS AND METHODS: In 48 New Zealand rabbits, buccal muscle paralysis of one side was produced by excision of 1 cm segment buccal branch of the facial nerve. The opposite side served as controls. The animals were sacrificed and the buccal muscles of both sides were removed for examination at 1 day, 3 days, 1 week, 2 weeks, 1 month, 2 months, 4 months, and 6 months after the initial operation. The myogenin expression in denervated and innervated buccal muscles was analyzed by Western blot. Satellite cell proliferation was detected with proliferating cell nuclear antigen (PCNA) analysis. Muscle nucleic acid concentration was determined through acridine orange (AO) staining method. RESULTS: Myogenin expression increased to the highest level at 3 days after denervation, thereafter it gradually decreased. The Western blotting signal for myogenin intensified again after 1 month and at 4 months. In contrast, the highest expression of the controls (innervated muscles) were observed at 1 month. These changes in myogenin expression in denervated buccal muscles were consistent with the change in satellite cell proliferation and in muscle nucleic acid concentration. CONCLUSION: Myogenin protein expression in longterm facial muscle denervation is closely associated with satellite cell regeneration. Myogenin may promote satellite cell differentiation, and therefore may improve the treatment of facial paralysis.

Acridine Orange↗

[The expression of cathepsin-D in salivary adenoid cystic carcinoma].

OBJECTIVE: To investigate the relationship between Cathepsin-D(Cath-D) and the prognosis of patients with salivary adenoid cystic carcinoma (SACC). METHODS: The immunoactivity of Cath-D of 52 cases with SACC was determined by immunohistochemistry method (Streptavidin-Biotin method). The relationship between Cath-D and the histological type, clinical stage, local recurrence, distant metastasis of the tumor and survival rate of the patients with SACC were analysed. RESULTS: Statistical analysis showed that the expression levels of Cath-D were correlated positively with distant metastasis potential and clinical stage (P < 0.05), and had no significant relation with histological type, local recurrence and survival rate (P > 0.05). CONCLUSIONS: Cath-D can facilitate invasiveness and distant metastasis of SACC; evaluation of Cath-D can act as a predictor of distant metastasis of SACC and direct the clinical treatment.

Adult↗

[A clinicopathologic study on membranous basal cell adenoma].

OBJECTIVE: To investigate the clinicopathologic features and behaviour of membranous basal cell adenoma. METHODS: Twelve cases with membranous basal cell adenoma of salivary gland were analysed clinicopathologically. RESULTS: The tumors were composed of epithelial islands of various sizes and shapes. Its histologic finding was characterized by palisading of peripheral cells and excessive hyaline basal membrane. Four cases had co-existing dermal cylindromas of the scalp. In 8 cases, the tumors demonstrated multiple origin. One case showed malignant transformation and cervical lymph node metastasis. CONCLUSIONS: The differential diagnosis involved the solid variant of basal cell adenoma, basal cell adenocarcinoma, solid subtype of adenoid cystic carcinoma and basal squamous cell carcinoma. Total parotidectomy rather than superficial parotidectomy is suggested to avoid the recurrence of the tumor. A close follow up after treatment is necessary.

Adenoma↗

[An experimental study on physiotherapy for traumatic facial nerve injury].

OBJECTIVE: To investigate the effects of electric stimulation, iontophoresis and electric stimulation with iontophoresis therapy in treating traumatic facial nerve injury. METHODS: Fifty rabbits were used. All right buccal branch of facial nerve were injured. The rabbits were randomly divided into five groups and treated by different stimulation pattern: (a) electric stimulation group; (b) iontophoresis group; (c) iontophoresis with electric stimulation group; (d) routine therapy group; (e) control group. The histologic morphology, quantitative indices of nerve fibers and electroneurography(ENoG) indices were analyzed. RESULTS: (a) Iontophoresis with Vitamin B1 and Vitamin B12 improved the regeneration of facial nerve myelin sheath. And had the best effect among these groups. (b) Electric stimulation had great effect on axon regeneration. (c) The group of electric stimulation with iontophoresis therapy had the best comprehensive effect on the nerve injury. CONCLUSIONS: Both electric stimulation and iontophoresis have good effects on nerve regeneration, when they are used in combination, the best comprehensive effect will be expected.

Animals↗

[Histogenesis and development of membranous basal cell adenoma of the salivary gland].

OBJECTIVE: To investigate the histogenesis and development of membranous basal cell adenoma in the salivary glands. METHODS: A histological and immunohistochemical study was carried out on 12 cases of membranous basal cell adenoma in the salivary glands. RESULTS: In 4 cases, multiple focal proliferations of striated ducts in the surrounding salivary gland were conspicuous, which allowed tracing the development of the tumors from their origin. The earliest changes were characterized by hyperplasia of the basal cells of striated ducts. Continuous ductal proliferation lead to the formation of microadenomas. CONCLUSIONS: Proliferation of basal cells of the striated ducts apparently participate in, and play a main role in the histogenesis of some membranous basal cell adenomas of the salivary glands.

Adenoma↗

[Study on beta-adrenoceptors mechanism of cadmium immunotoxicity].

OBJECTIVE: To study if the beta-adrenoceptors mechanism plays important role in the immunotoxicity of cadmium. METHODS: The beta-adrenoceptor density, cellular cyclic adenosine 3',5' monophosphate (cAMP) levels, and DNA damage of rat spleen lymphocytes were studied. Beta-antagonist propranolol was used to block the beta-adrenoceptor. RESULTS: In the single Cd administration group: beta-adrenoceptor density of spleen lymphocytes in the middle and high Cd concentration groups was higher than that in the non-Cd treated control group (P < 0.05), the levels of cAMP increased with the increase of Cd doses, and the result of the high Cd group was higher than that of the control group (P < 0.05). The proliferation function of T lymphocytes was lower in each Cd group than that in the control group (P < 0.05). Single cell gel electrophoresis (SCGE) detected that DNA damage of spleen lymphocytes in each Cd group were more severe than the control (P < 0.05). Pretreated with Pro group: After blocked with propranolol, beta-adrenoceptor density increased in the Pro control group and the density in all Cd treated groups was higher than the control group (P < 0.05), but all Cd treated groups showed no statistical significance than the Pro control group (P > 0.05). The cAMP levels, MTT and the subsets of T lymphocytes showed no statistical significance among all the groups (P > 0.05). The results of SCGE showed that DNA damage was most severe only in the high Cd group than other groups (P < 0.05). CONCLUSION: The results suggest that the nerve-internal secretion system plays an important role in the immunotoxicity of cadmium, and the beta-adrenoceptor mechanism is important in the immunotoxic mechanism of cadmium.

Adrenergic beta-Antagonists↗

[Synthesis and spectroscopic characterization of a new blue light-emitting material complexes and study of its photoluminescence and electroluminescence characterization].

The Zn-complexe emitting blue light was synthesised and characterized spectroscopically by elemental analysis, UV, EX, EM, IR. Photoluminescence and electroluminescence characterization of the light-emitting diodes using Zn-complexe as the emissive layer was studied, it could emit blue light with a peak wavelength at 455 nm and a brightness of about 37.2 cd.m-2.

Chelating Agents↗

Purification and characterization of heparan sulphate proteoglycan from bovine brain.

A heparan sulphate proteoglycan was purified from adult bovine brain tissues and its structure was characterized. The major heparan sulphate proteoglycan from whole bovine brain had a molecular mass of >200 kDa on denaturing SDS/PAGE and a core protein size of 66 kDa following the removal of glycosaminoglycan chains. Fractionation on DEAE-Sephacel showed that this proteoglycan consisted of three major forms having high, intermediate and low overall charge. All core proteins were identical in size and reacted with heparan sulphate proteoglycan-stub antibody and an antibody made to a synthetic peptide based on rat glypican. The three forms of proteoglycans had identical peptide maps and their amino acid compositional analysis did not match any of the known glypicans. The internal sequence of a major peptide showed only 37.5% sequence similarity with human glypican 5. The glycosaminoglycan chain sizes of the three forms of this proteoglycan, determined after beta-elimination by PAGE, were identical. The disaccharide compositional analysis on the heparan sulphate chains from the three forms of the proteoglycan, determined by treatment with a mixture of heparin lyases followed by high-resolution capillary electrophoresis, showed that they differed primarily by degree of sulphation. The most highly sulphated proteoglycan isolated had a disaccharide composition similar to heparan sulphate glycosaminoglycans found in brain tissue. Based on their sensitivity to low pH nitrous acid treatment, the N-sulphate groups in these proteoglycans were found to be primarily in the smaller glycosaminoglycan chains. The heparan sulphate proteoglycans were also heavily glycosylated with O-linked glycans and no glycosylphosphatidylinositol anchor could be detected.

Amino Acids↗

DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation.

The homeobox genes in the Dlx family are required for differentiation of basal forebrain neurons and craniofacial morphogenesis. Herein, we studied the expression of Dlx-1, Dlx-2, and Dlx-5 RNA and protein in the mouse forebrain from embryonic day 10.5 (E10.5) to E12.5. We provide evidence that Dlx-2 is expressed before Dlx-1, which is expressed before Dlx-5. We also demonstrate that these genes are expressed in the same cells, which may explain why single mutants of the Dlx genes have mild phenotypes. The DLX proteins are localized primarily to the nucleus, although DLX-5 also can be found in the cytoplasm. During development, the fraction of Dlx-positive cells increases in the ventricular zone. Analysis of the distribution of DLX-1 and DLX-2 in M-phase cells suggests that these proteins are distributed symmetrically to daughter cells during mitosis. We propose that DLX-negative cells in the ventricular zone are specified progressively to become DLX-2-expressing cells during neurogenesis; as these cells differentiate, they go on to express DLX-1, DLX-5, and DLX-6. This process appears to be largely the same in all regions of the forebrain that express the Dlx genes. In the basal telencephalon, these DLX-positive cells differentiate into projection neurons of the striatum and pallidum as well as interneurons, some of which migrate to the cerebral cortex and the olfactory bulb.

3T3 Cells↗

Predictors of optimal virological response to potent antiretroviral therapy.

BACKGROUND: Current potent antiretroviral therapy (using a protease inhibitor and two nucleoside reverse transcriptase inhibitors) produces a durable suppression of HIV replication in less than 75% of treated patients. Identification of predictors of successful therapy might allow the development of improved strategies to increase response rates. METHODS: We analyzed retrospectively the results from a multicenter, randomized, double-blind Phase III study of combination anti-HIV therapy with nelfinavir, zidovudine, and lamivudine to evaluate the relationship between virological response over 48 weeks of treatment to variables which could potentially serve as early predictors of long-term response. The goal was to produce long-term suppression of viral load to sensitive (<400 copies HIV RNA/ml) and ultrasensitive (<50 copies HIV RNA/ml) limits of quantification with the Amplicor PCR assay. FINDINGS: Baseline viral load, the change in viral load over the first 4 weeks of treatment, the 2 h post-dose nelfinavir levels and the time to respond to HIV RNA levels of <400 copies/ml and <50 copies/ml have the best predictive value in determining response and response duration. Patients who achieved very low viral nadirs (<50 copies HIV RNA/ml) had significantly longer responses than those who achieved nadirs of 50-400 copies HIV RNA/ml. INTERPRETATION: Parameters that can be measured easily at baseline or early after therapy is started can identify patients at high risk of failure with standard treatment. Such patients may be candidates for more aggressive therapy or for alternative strategies designed to improve outcome. In addition, these results support the use of ultra-sensitive HIV RNA assays to predict long-term outcome of anti-HIV therapy.

Adult↗