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Biomedical subjects

X Yang

Publications and source records attributed to X Yang.

At least 73 records · Page 4Linked to original sources

Relationships between factor VIII:Ag and factor VIII in recombinant and plasma-derived factor VIII concentrates.

A variety of plasma-derived (pd) and recombinant (r) factor VIII (FVIII) concentrates are used to prevent and treat bleeding in severe hemophilia A patients. A significant side effect of FVIII replacement is the development of FVIII neutralizing antibodies (inhibitors) in up to 30% of patients receiving FVIII concentrates. The FVIII protein content (FVIII:Ag) per unit of FVIII:C in FVIII concentrates, and how effectively the FVIII:Ag in FVIII concentrates binds to von Willebrand factor (VWF) may provide information relevant for the survival of FVIII:C in vivo and for estimating the risk for inhibitor development. The FVIII:Ag content of nine r-FVIII and nine pd-FVIII concentrates were quantified in this study using two enzyme-linked immunosorbent assay (ELISA) platforms. The two ELISA platforms were based on the use of a monoclonal anti-(FVIII light chain)-IgG and polyclonal anti-FVIII antibodies as capture antibodies and both ELISAs were equally able to detect > or =0.005 IU of FVIII:Ag. Measured in international units, the r-FVIII concentrates contained significantly higher FVIII:Ag per unit of FVIII:C than the pd-FVIII concentrates. The VWF-binding profiles of the r-FVIII and pd-FVIII concentrates were also determined by gel filtration chromatography. Unlike the plasma-derived products, the r-FVIII concentrates invariably contained a fraction of FVIII:Ag molecules (approximately 20%) which was unable to associate with VWF. Given that VWF regulates both factor VIII proteolysis and survival of FVIII:Ag in vivo, the fraction of FVIII:Ag unable to bind to VWF may have a reduced survival and be more susceptible to proteolytic degradation in vivo. The extent to which the fractions of FVIII:Ag in concentrates able and unable to bind to VWF contribute to inhibitor development in severe FVIII-deficient patients is unknown.

Blotting, Western↗

Observation and identification of lactate dehydrogenase anomaly in a postburn patient.

OBJECTIVE: Lactate dehydrogenase (LDH) anomaly is one of the macroenzymes. Macroenzymes are enzymes in serum that have formed high molecular mass complexes, either by self polymerisation or by association with other serum components. The aim of this study was to identify the properties of LDH anomaly and observe the changes from admission to discharge in a postburn patient with LDH anomaly in his serum. METHODS: LDH isoenzymes of the serum were electrophoretically fractionated with terylene cellulose acetate supporting media; LDH anomaly was identified by counter immunoelectrophoresis. RESULTS: An abnormal LDH-4 band and an extra band on the cathode of LDH-5 were observed in the serum of this patient and were found to be part of an LDH-IgG complex. As his symptoms improved, the patient's LDH anomaly gradually disappeared. The appearance and disappearance of the anomaly seemed to be related to the progression of the patient's burns. CONCLUSION: In clinical practice, it is important to keep in mind the possibility of an LDH anomaly in patients when the LDH level is abnormally high or does not seem to be related to the clinical state. Early discovery of an LDH anomaly in a patient's serum may be useful for diagnosis and treatment.

Burns↗

Effects of high intensity focused ultrasound on vascular endothelial growth factor in melanoma bearing mice.

This study was to investigate the effects of high intensity focused ultrasound on vascular endothelial growth factor. A B16 melanoma model was adopted in our study. Melanoma bearing mice were randomly divided into two groups: HIFU group and surgery group. While the control group was only injected with isovolumetric normal saline solution and treated as the surgery group. We detected VEGF both in tissues and sera through immunohistochemical method and ELISA respectively. Tissues were sampled pre- and at the 3rd day post-operation in HIFU group and blood samples were taken pre- and at the 1st, 3rd, and 7th day post-operation in all the groups. As a result, in the tissues, VEGF was expressed in 80% melanomas, but none was detected in the targeted area after HIFU treatment. In the sera, there was a decreasing tendency of serum-VEGF concentrations in group HIFU and surgery after operation, while that in the control group increased after operation. The levels in the HIFU group on day 1, 3, and 7 postoperatively were all lower than that in the surgery group respectively (79.16 pg/ml vs 91.59 pg/ml; 33.64 pg/ml vs 49.39 pg/ml; 30.37 pg/ml vs 46.68 pg/ml), but there wasn't any significant difference (P > 0.05). So HIFU can destroy VEGF in the targeted area and maybe have less of an effect on serum-VEGF than surgery.

Animals↗

Clinical and radiological features of odontogenic ghost cell carcinoma: review of the literature and report of four new cases.

OBJECTIVES: To analyse systematically the clinical and radiological features of odontogenic ghost cell carcinoma (OGCC). METHODS: Clinical and radiological features of 22 OGCCs (4 new and 18 from the literature) were analysed. RESULTS: There were 17 (77%) males and 5 (23%) females (male-to-female ratio of 3.4:1). Ages ranged from 13 years to 72 years (mean 36.7) with a peak in the fourth (40.9%) and fifth (27.3%) decades. The maxilla was involved in 68% and the mandible in 32%. Our study confirmed that OGCC is more prevalent in Asians (12/18) than in other racial groups. The mixed radiolucent and radiopaque lesion pattern was the most frequent (14/19) compared with radiolucent lesions (5/19). 89% (17/19) showed poorly defined borders and 11% (2/19) showed well defined borders. Root resorption was reported in 31% (6/19) of patients and tooth displacements in 21%. CONCLUSIONS: OGCC demonstrates clinical and radiographic features of a malignant tumour with high recurrence.

Adult↗

Lysed enterococcus faecalis FK-23 oral administration reveals inverse association between tuberculin responses and clinical manifestations in perennial allergic rhinitis: a pilot study.

BACKGROUND: The interest in anti-allergy immunoregulation by lactic acid bacteria (LAB) has been growing over the last few decades. There is evidence to suggest that lysed Enterococcus faecalis FK-23 (LFK), a kind of LAB preparation, could relieve the clinical symptoms of Japanese cedar pollinosis. However, little is known about how LFK plays a role in combating allergy. OBJECTIVE: The aim of this study was to clarify whether improvement of clinical manifestations is associated with enhancement of tuberculin responses in patients with allergic rhinitis treated by LFK. METHODS: One gram of LFK per day was administered orally to fifty perennial allergic rhinitis patients in an open trial that lasted 28 days. Nasal symptoms and sign scores were rated before and after administration of LFK. Tuberculin responses and peripheral blood cells were also measured before and after LFK treatment. RESULTS: Purified protein derivative (PPD) skin test diameter was 2.14 +/- 2.14 mm before LFK administration versus 7.26 +/- 4.81 mm at day 31 (p < 0.01). A significant inverse correlation was recognized between PPD skin test diameters and total nasal scores in the nasal provocation test before and after treatment (r= - 0.600, p < 0.001). Peripheral blood eosinophils were 248 +/- 149 cells/ml before LFK administration and then they significantly decreased to 76 +/- 98 cells/microl (p < 0.01). CONCLUSIONS: These finding may be interpreted as a result of improved clinical symptoms in allergic rhinitis after LFK oral treatment owing to the enhanced host's Th1-type immune responses and supression of the over-expression of Th2-dominated allergic responses.

Administration, Oral↗

RNA recognition and base flipping by the toxin sarcin.

Sarcin is a member of a fungal toxin family that enters cells and specifically cleaves one of the thousands of RNA phosphodiester bonds in the ribosome. As a result, elongation factor binding is disrupted, translation is inhibited and apoptosis is triggered. The toxin targets a universal RNA structure in the ribosome called the sarcin/ricin loop (SRL). A 1.11 A resolution structure of a minimal SRL RNA substrate (approximately 30-mer) shows that the loop portion of the substrate folds into two common building blocks of RNA structure: a bulged-G motif (recognition site) and a GAGA tetraloop (cleavage site). To elucidate the structural basis of toxin action, we determined two co-crystal structures of the sarcin homologue restrictocin bound to different analogs of a minimal SRL RNA substrate. Our studies argue that site selection by the toxin depends on direct base and shape recognition of the SRL RNA, and that cleavage by the toxin depends on a base flipping mechanism that positions the nucleophile for in-line attack on the scissile bond.

Binding Sites↗

Epigenetic characteristics of bovine donor cells for nuclear transfer: levels of histone acetylation.

Donor cell type, cell-cycle stage, and passage number of cultured cells all affect the developmental potential of cloned embryos. Because acetylation of the histones on nuclear chromatin is an important aspect of gene activation, the present study investigated the differences in histone acetylation of bovine fibroblast and cumulus cells at various passages and cell-cycle stages. The acetylation was qualitatively analyzed by epifluorescent confocal microscopy and quantitatively by immunofluorescent flow cytometry. Specifically, we studied levels of histone H4 acetylated at lysine 8 and histone H3 acetylated at lysine 18; acetylation at these lysine residues is among the most common for these histone molecules. We also studied levels of linker histone H1 in donor cells. Our results show that stage of cell cycle, cell type, and number of cell passages all had an effect on histone content. Histone H1 and acetyl histone H3 increased with cell passage (passages 5-15) in G0/G1- and G2/M-stage cumulus and fibroblast cells. We also found that acetyl histone H4 was lower in early versus late cell passages (passage 5 vs. 15) for G0/G1-stage cumulus cells. In both cell types examined, acetyl histones increased with cell-cycle progression from G0/G1 into the S and G2/M phases. These results indicate that histone acetylation status is remodeled by in vitro cell culture, and this may have implications for nuclear transfer.

Acetylation↗

ATP modulates load-inducible IL-1beta, COX 2, and MMP-3 gene expression in human tendon cells.

Tendon cells receive mechanical signals from the load bearing matrices. The response to mechanical stimulation is crucial for tendon function. However, overloading tendon cells may deteriorate extracellular matrix integrity by activating intrinsic factors such as matrix metalloproteinases (MMPs) that trigger matrix destruction. We hypothesized that mechanical loading might induce interleukin-1beta (IL-1beta) in tendon cells, which can induce MMPs, and that extracellular ATP might inhibit the load-inducible gene expression. Human tendon cells isolated from flexor digitorum profundus tendons (FDPs) of four patients were made quiescent and treated with ATP (10 or 100 microM) for 5 min, then stretched equibiaxially (1 Hz, 3.5% elongation) for 2 h followed by an 18-h-rest period. Stretching induced IL-1beta, cyclooxygenase 2 (COX 2), and MMP-3 genes but not MMP-1. ATP reduced the load-inducible gene expression but had no effect alone. A medium change caused tendon cells to secrete ATP into the medium, as did exogenous UTP. The data demonstrate that mechanical loading induces ATP release in tendon cells and stimulates expression of IL-1beta, COX 2, and MMP-3. Load-induced endogenous IL-1beta may trigger matrix remodeling or a more destructive pathway(s) involving IL-1beta, COX 2, and MMP-3. Concomitant autocrine and paracrine release of ATP may serve as a negative feedback mechanism to limit activation of such an injurious pathway. Attenuation or failure of this negative feedback mechanism may result in the progression to tendinosis.

Adenosine Triphosphate↗

Twin brothers with MIDAS syndrome and XX karyotype.

Twin brothers with microphthalmia, facial dermal hypoplasia, sclerocornea, and supraventricular tachycardia, are reported. Their clinical features are compatible with MIDAS syndrome, a known X-linked and hemizygous male lethal condition. Their karyotypes showed an XX sex chromosome modality with a subtle Xp/Yp translocation proven by the presence of SRY gene. The pregnancy was complicated with fetal supraventricular tachycardia, which was treated with digoxin prenatally. Postnatally, both twins required treatment with adenosine, digoxin, and propanolol to remain in normal sinus rhythm. The possible involvement of the heart, only in the form of cardiomyopathy with arrhythmia is emphasized. Both twins had a selective X-inactivation of the derivative chromosome X with Xp/Yp translocation.

Chromosomes, Human, X↗

Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-2'-deoxycytidine.

Development to blastocyst following nuclear transfer is dependent on the donor cell's ability to reprogram its genome to that of a zygote. This reprogramming step is inefficient and may be dependent on a number of factors, including chromatin organization. Trichostatin A (TSA; 0-5 microM), a histone deacetylase inhibitor, was used to increase histone acetylation and 5-aza-2'-deoxycytidine (5-aza-dC; 0-5 microM), a DNA methyl-transferase inhibitor, was used to decrease methylation of chromatin in donor cells in an attempt to improve their reprogrammability. Adult fibroblast cells treated with 1.25 or 5 microM TSA had elevated histone H3 acetylation compared to untreated controls. Cells treated with 0.3 microM 5-aza-dC had decreased methylation compared to untreated controls. Both drugs at 0.08 microM caused morphological changes of the donor cells. Development to blastocysts by embryos cloned from donor cells after 0.08 or 0.3 microM 5-aza-dC treatments was lower than in embryos cloned from untreated control cells (9.7% and 4.2%, respectively, vs. 25.1%), whereas 0.08 microM TSA treatment of donor cells increased blastocyst development compared to controls (35.1% vs. 25.1%). These results indicate that partial erasure of preexisting epigenetic marks of donor cells improves subsequent in vitro development of cloned embryos.

Acetylation↗

Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) co-activator 1 (PGC-1) regulates glucose metabolism and energy expenditure and, thus, potentially insulin sensitivity. We examined the expression of PGC-1, PPAR gamma, insulin receptor substrate-1 (IRS-1), glucose transporter isoform-4 (GLUT-4), and mitochondrial uncoupling protein-1 (UCP-1) in adipose tissue and skeletal muscle from non-obese, non-diabetic insulin-resistant, and insulin-sensitive individuals. PGC-1, both mRNA and protein, was expressed in human adipose tissue and the expression was significantly reduced in insulin-resistant subjects. The expression of PGC-1 correlated with the mRNA levels of IRS-1, GLUT-4, and UCP-1 in adipose tissue. Furthermore, the adipose tissue expression of PGC-1 and IRS-1 correlated with insulin action in vivo. In contrast, no differential expression of PGC-1, GLUT-4, or IRS-1 was found in the skeletal muscle of insulin-resistant vs insulin-sensitive subjects. The findings suggest that PGC-1 may be involved in the differential gene expression and regulation between adipose tissue and skeletal muscle. The combined reduction of PGC-1 and insulin signaling molecules in adipose tissue implicates adipose tissue dysfunction which, in turn, can impair the systemic insulin response in the insulin-resistant subjects.

Adipose Tissue↗

IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.

Overuse injuries and trauma in tendon often involve acute or chronic pain and eventual matrix destruction. Anti-inflammatory drugs have been used as a treatment, however, the cellular and molecular mechanisms of the destructive processes in tendon are not clearly understood. It is thought that an inflammatory event may be involved as an initiating factor. Mediators of the inflammatory response include cytokines released from macrophages and monocytes. Interleukin-1 beta (IL-1 beta) is a candidate proinflammatory cytokine that is active in connective tissues such as bone and cartilage. We hypothesized that tendon cells would express receptors and respond to IL-1 beta in an initial "molecular inflammation" cascade, that is, connective tissue cell expression of cytokines that induce matrix destructive enzymes. This cascade results in expression of matrix metalloproteinases (MMPs) and aggrecanases that may lead to matrix destruction. Normal human tendon cells from six patients were isolated, grown to quiescence and treated with human recombinant IL-1 beta in serum-free medium for 16 h. Total RNA was isolated and mRNA expression assessed by semiquantitative RT-PCR. IL-1 beta (1 nM) induced mRNAs for cyclooxygenase 2 (COX2), MMP-1, -3, -13 and aggrecanase-1 as well as IL-1 beta and IL-6, whereas mRNAs for COX1 and MMP-2 were expressed constitutively. The IL-1 beta-treated tendon cells released prostaglandin E(2) (PGE(2)) in the medium, suggesting that the inducible COX2 catalyzed this synthesis. Induction of PGE(2) was detectable at 10 pM IL-1 beta. IL-1 beta also stimulated MMP-1 and -3 protein secretion. Induction of MMP-1 and -3 was detectable at 10 pM IL-1 beta. Post-injury or after some other inciting events, exogenous IL-1 beta released upon bleeding or as leakage of local capillaries may drive a proinflammatory response at the connective tissue cell level. The resulting induction of COX2, MMP-1 and -3 may underscore a potential for nonlymphocyte-mediated cytokine production of MMPs that causes matrix destruction and a loss of tendon biomechanical properties. Endogenous IL-1 beta might contribute to the process through a positive feedback loop by stimulating expression and accumulation of MMPs in the tendon matrix.

ADAM Proteins↗

Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects.

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.

Age of Onset↗

Age-related thymic involution in C57BL/6J x DBA/2J recombinant-inbred mice maps to mouse chromosomes 9 and 10.

A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t)=beta(0) x exp(-beta(1)t), where t represents the age (day). This regression model was applied to C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice to identify the genetic loci influencing age-related thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the age-related thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.

Aging↗

Natural marine sponge fiber skeleton: a biomimetic scaffold for human osteoprogenitor cell attachment, growth, and differentiation.

Identification of suitable scaffolds onto which human stem cells can be seeded to generate functional three-dimensional tissues is a major research goal. A natural marine sponge skeleton was selected as a potential scaffold on the basis of the hydration potential of the fiber, the presence of open interconnected channels created by the fiber network, the collagenous composition of the fiber, and the structural diversity of fiber architecture. The skeleton of an undetermined species of Spongia (Class Demospongiae: Order Dictyoceratida: Family Spongiidae), composed of spongin, supported growth of human osteoprogenitor cells. Cell attachment and invasion into the framework were observed within 16 h, followed by development into membranous sheets between the sponge fibers by concentric infilling. Histochemical staining for alkaline phosphatase and type I collagen indicated formation of bone matrix as confirmed by birefringence. At 9 and 14 days alkaline phosphatase-specific activity in sponge fiber-osteoprogenitor cell cultures was significantly greater than in control cultures on cell culture plastic. Adsorption with recombinant human bone morphogenetic protein 2 confirmed the potential of this sponge skeleton as a delivery scaffold for osteogenic factors. The abundance and structural diversity of natural marine sponge skeletons and their potential as multifunctional, cell conductive and inductive frameworks indicate a promising new source of scaffold for tissue regeneration.

Animals↗

Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to day 62.

STUDY OBJECTIVE: To report the evolution in perceptions and behaviours of the general public in response to the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. DESIGN: Ten similar and sequential telephone surveys were conducted during outbreak of SARS, which are classified as belonging to the first and second phases of the epidemic. SETTING: Hong Kong, China. PARTICIPANTS: 1397 Hong Kong residents between 18 and 60 years of age. MAIN OUTCOME MEASURES: Perceptions and behaviours to SARS and its prevention. RESULTS: Most of the respondents believed that SARS could be transmitted via direct body contact and droplets. About half of respondents believed that SARS was curable, which increased in the initial phase and decreased in the second phase. Perceived chance of infection was low (9%) but fear of infection in public places was high (48%). Perceived efficacy of hygiene measures (wearing a mask: 82%, hand washing: 93%, and home disinfection: 75%) remained high in both phases and the perceived efficacy of avoiding crowded place, and using public transportation, etc, increased initially and decreased in the second phase. In parallel, use of the three hygiene measures increased significantly in the first phase and remained high for wearing a mask and washing hands in the second phase. Percentages of people avoiding crowded place and public transportation significantly increased initially and decreased in the second phase. CONCLUSION: SARS related perceptions and behaviours evolved rapidly during the epidemic and Hong Kong residents quickly adopted appropriate SARS prevention measures. Timely dissemination of information seems effective in public health crises management.

Adolescent↗