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A Tong

Publications and source records attributed to A Tong.

At least 19 recordsLinked to original sources
PubMed2006

Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients.

BACKGROUND: Calcimimetic agents have recently been evaluated in the treatment of secondary hyperparathyroidism (SHPT) as add-on therapy to calcitriol and vitamin D analogues and dietary phosphate binders. OBJECTIVES: To evaluate the benefits and harms of calcimimetics for the prevention of secondary hyperparathyroid bone disease (including osteitis fibrosa cystica and adynamic bone disease) in dialysis patients with chronic kidney disease (CKD). SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in pre-dialysis or dialysis patients with CKD. SELECTION CRITERIA: We included all RCTs of any calcimimetic agent, cinacalcet HCl (AMG-073, Sensipar), NPS R-467 or NPS R-568 administered to patients with CKD for the treatment of SHPT. DATA COLLECTION AND ANALYSIS: Data were extracted on all relevant patient-centred and surrogate outcomes. Analysis was by a random effects model and results expressed as relative risk (RR) or weighted mean difference (MD) with 95% confidence intervals. MAIN RESULTS: Eight studies (1429 patients) were identified, which compared a calcimimetic agent plus standard therapy to placebo plus standard therapy. The end of treatment values of parathyroid hormone (pg/mL) (MD -290.79, 95% CI -360.23 to -221.34), serum calcium (mg/dL) (MD -0.85, 95% CI -1.14 to -0.56), serum phosphorus (mg/dL) (MD -0.29, 95% CI -0.50 to -0.08) and the calcium by phosphorus product (mg(2)/dL(2))(MD -7.90, 95% CI -10.25 to -5.54) were significantly lower with calcimimetics compared to placebo. No significant effects on patient-based endpoints were demonstrated except for the risk of hypotension which was significantly reduced with calcimimetics compared to placebo (RR 0.53, 95%CI 0.36 to 0.79). AUTHORS' CONCLUSIONS: Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality, cardiovascular risk and osteitis fibrosa, but patient-based benefits have not yet been demonstrated in trials. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until further RCTs become available.

Calcium↗
PubMed2006

Hyperinsulinism in mice with heterozygous loss of K(ATP) channels.

AIMS/HYPOTHESIS: ATP-sensitive K(+) (K(ATP)) channels couple glucose metabolism to insulin secretion in pancreatic beta cells. In humans, loss-of-function mutations of beta cell K(ATP) subunits (SUR1, encoded by the gene ABCC8, or Kir6.2, encoded by the gene KCNJ11) cause congenital hyperinsulinaemia. Mice with dominant-negative reduction of beta cell K(ATP) (Kir6.2[AAA]) exhibit hyperinsulinism, whereas mice with zero K(ATP) (Kir6.2(-/-)) show transient hyperinsulinaemia as neonates, but are glucose-intolerant as adults. Thus, we propose that partial loss of beta cell K(ATP) in vivo causes insulin hypersecretion, but complete absence may cause insulin secretory failure. MATERIALS AND METHODS: Heterozygous Kir6.2(+/-) and SUR1(+/-) animals were generated by backcrossing from knockout animals. Glucose tolerance in intact animals was determined following i.p. loading. Glucose-stimulated insulin secretion (GSIS), islet K(ATP) conductance and glucose dependence of intracellular Ca(2+) were assessed in isolated islets. RESULTS: In both of the mechanistically distinct models of reduced K(ATP) (Kir6.2(+/-) and SUR1(+/-)), K(ATP) density is reduced by approximately 60%. While both Kir6.2(-/-) and SUR1(-/-) mice are glucose-intolerant and have reduced glucose-stimulated insulin secretion, heterozygous Kir6.2(+/-) and SUR1(+/-) mice show enhanced glucose tolerance and increased GSIS, paralleled by a left-shift in glucose dependence of intracellular Ca(2+) oscillations. CONCLUSIONS/INTERPRETATION: The results confirm that incomplete loss of beta cell K(ATP) in vivo underlies a hyperinsulinaemic phenotype, whereas complete loss of K(ATP) underlies eventual secretory failure.

ATP-Binding Cassette Transporters↗
PubMed2005

FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: implications for endochondral ossification.

Fibroblast growth factor receptor 3 (FGFR3) signaling pathways are essential for normal longitudinal bone growth. Mutations in this receptor lead to various human growth disorders, including Achondroplasia, disproportionately short-limbed dwarfism, characterized by narrowing of the hypertrophic region of the epiphyseal growth plates. Here we find that FGF9, a preferred ligand for FGFR3 rapidly induces the upregulation and secretion of the matrix resident phosphoprotein, osteopontin (OPN) in cultured chicken chondrocytes. This effect was observed as early as two hours post stimulation and at FGF9 concentrations as low as 1.25 ng/ml at both mRNA and protein levels. OPN expression is known to be associated with chondrocyte and osteoblast differentiation and osteoclast activation. Unexpectedly, FGF9 induced OPN was accompanied by inhibition of differentiation and increased proliferation of the treated chondrocytes. Moreover, FGF9 stimulated OPN expression irrespective of the differentiation stage of the cells or culture conditions. In situ hybridization analysis of epiphyseal growth plates from chicken or mice homozygous for the Achondroplasia, G369C/mFGFR3 mutation demonstrated co-localization of OPN expression and osteoclast activity, as evidenced by tartarate resistant acid phosphatase positive cells in the osteochondral junction. We propose that FGF signaling directly activates OPN expression independent of chondrocytes differentiation. This may enhance the recruitment and activation of osteoclasts, and increase in cartilage resorption and remodeling in the chondro-osseus border.

Achondroplasia↗
PubMed2005

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization.

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 +/- 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

Adaptation, Physiological↗
PubMed2004

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) is used as substitutive treatment of renal function in a large proportion (15-50%) of the end-stage kidney disease (ESRD) population. The major limitation is peritonitis which leads to technique failure, hospitalisation and increased mortality. Oral, nasal, topical antibiotic prophylaxis, exit-site disinfectants and other antimicrobial interventions are used to prevent peritonitis. OBJECTIVES: The objective of this systematic review of randomised controlled trials (RCTs) was to evaluate what evidence supports the use of different antimicrobial approaches to prevent peritonitis in PD. SEARCH STRATEGY: The Cochrane CENTRAL Registry (issue 1, 2004), MEDLINE (1966-May 2003), EMBASE (1988-May 2003) and reference lists were searched for RCTs of antimicrobial agents in PD. SELECTION CRITERIA: Trials of the following agents were included: antibiotics by any route (oral, nasal, topical), exit-site disinfectants (chlorhexidine, povidone iodine, soap and water), vaccines, and ultraviolet germicidal devices. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data on the number of patients with one or more episodes and rates of peritonitis and exit-site/tunnel infection, catheter removal, catheter replacement, technique failure, toxicity of antibiotic treatments, all-cause mortality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Nineteen trials, enrolling 1949 patients met our inclusion criteria. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (one trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (one trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). Perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (four trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (three trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). No intervention reduced the risk of catheter removal or replacement. REVIEWERS' CONCLUSIONS: This review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. No other antimicrobial interventions have proven efficacy. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered RCTs to inform decision making about strategies to prevent peritonitis is striking.

Anti-Bacterial Agents↗
PubMed2004

Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: As many as 15-50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions have been purported to reduce the risk of peritonitis in PD. OBJECTIVES: To evaluate the use of catheter-related interventions for the prevention of peritonitis in PD. SEARCH STRATEGY: The Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966-April 2004), EMBASE (1988-April 2004) and reference lists were searched without language restriction SELECTION CRITERIA: Trials comparing different catheter insertion techniques, catheter types, use of immobilisation techniques or different break in periods were included. Trials of different PD sets were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seventeen eligible trials (1089 patients) were identified, eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, one of single cuff versus double cuff catheters and one of an immobiliser device. The methodological quality was suboptimal. There were no significant differences with laparoscopy compared with laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or catheter removal/replacement. Standard insertion with resting but no subcutaneous burying of the catheter versus implantation and subcutaneous burying was not associated with a significant reduction in peritonitis rate, exit-site/tunnel infection rate or all-cause mortality. Midline compared to lateral insertion showed no significant difference in the risk of peritonitis or exit-site/tunnel infection. There was no significant difference in the risk of peritonitis, peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or catheter removal/replacement between straight versus coiled intraperitoneal portion catheters. One trial compared single versus double cuffed catheters and showed no significant difference in the risk of peritonitis, exit-site/tunnel infection or catheter removal/replacement. One trial compared immobilisation versus no immobilisation of the PD catheter and showed no significant difference in the risk of peritonitis and exit-site/tunnel infection. No trials of different break-in periods were identified. REVIEWERS' CONCLUSIONS: No major advantages from any of the catheter-related interventions which have been purported to reduce the risk of PD peritonitis could be demonstrated in this review. The frequency and quality of available trials are suboptimal.

Catheterization↗
PubMed2003

Expression of chicken 75-kDa gelatinase B-like enzyme in perivascular chondrocytes suggests its role in vascularization of the growth plate.

UNLABELLED: A newly cloned avian 75-kDa gelatinase B-like enzyme is expressed by the cells surrounding the blood vessels of the growth plate and upregulated by angiogenic substances in cultured chondrocytes. Despite its low homology to mammalian gelatinase-B, the avian 75-kDa seems to function similarly in the context of endochondral bone formation. INTRODUCTION: Gelatinase B/metalloproteinase (MMP)-9, a zinc-dependent protease of the MMP family, is a key regulator in the final step of endochondral ossification. Recently an avian 75-kDa gelatinase B-like enzyme that shows low sequence similarity to the mammalian enzyme (59% on the protein level) was cloned and characterized. However, its expression pattern in the chicken growth plate and its role in bone formation have not, so far, been examined. RESULTS: Based on the published sequence, we cloned a 700-bp fragment from cDNA of the chicken growth plate and studied its expression pattern in primary chondrocytes. Because the basal expression level of gelatinase B was almost undetectable, we induced its expression by different culturing conditions, the most dramatic induction achieved by treatment with retinoic acid, which is known as an inducer of vascular invasion in the epiphyseal plates. The gelatinolitic activity, checked by zymography, detected bands corresponding to the gelatinase A and B as well as a new high-molecular weight band of approximately 200 kDa. We further studied the expression pattern of gelatinase B by in situ hybridization. The gelatinase B was expressed by the cells surrounding the blood vessels penetrating the growth plate and by chondrocytes located in the front of these vascular invasions in the borders between the bone and the cartilage, resembling the expression of mouse gelatinase B in the growth plate. The induction of rickets by a vitamin D-deficient diet reduced the expression levels of gelatinase B in the growth plate of 12-day-old chickens but did not affect the expression of gelatinase A mRNA. CONCLUSION: The chicken growth plate has a distinctly different structure from the mammalian one: it is much wider, it contains more cells in each zone, and the blood vessels penetrate deeper into the hypertrophic zone. Nevertheless, the upregulation of the avian 75-kDa gelatinase B-like enzyme by vitamins A and D, coupled with its perivascular expression pattern in the growth plate, implies a similar role for the mammalian and avian genes in bone formation.

Animals↗
PubMed2001

A protein interaction map for cell polarity development.

Many genes required for cell polarity development in budding yeast have been identified and arranged into a functional hierarchy. Core elements of the hierarchy are widely conserved, underlying cell polarity development in diverse eukaryotes. To enumerate more fully the protein-protein interactions that mediate cell polarity development, and to uncover novel mechanisms that coordinate the numerous events involved, we carried out a large-scale two-hybrid experiment. 68 Gal4 DNA binding domain fusions of yeast proteins associated with the actin cytoskeleton, septins, the secretory apparatus, and Rho-type GTPases were used to screen an array of yeast transformants that express approximately 90% of the predicted Saccharomyces cerevisiae open reading frames as Gal4 activation domain fusions. 191 protein-protein interactions were detected, of which 128 had not been described previously. 44 interactions implicated 20 previously uncharacterized proteins in cell polarity development. Further insights into possible roles of 13 of these proteins were revealed by their multiple two-hybrid interactions and by subcellular localization. Included in the interaction network were associations of Cdc42 and Rho1 pathways with proteins involved in exocytosis, septin organization, actin assembly, microtubule organization, autophagy, cytokinesis, and cell wall synthesis. Other interactions suggested direct connections between Rho1- and Cdc42-regulated pathways; the secretory apparatus and regulators of polarity establishment; actin assembly and the morphogenesis checkpoint; and the exocytic and endocytic machinery. In total, a network of interactions that provide an integrated response of signaling proteins, the cytoskeleton, and organelles to the spatial cues that direct polarity development was revealed.

Actins↗
PubMed2001

Study of properties on non-protected room temperature phosphorescence and delayed excimer fluorescence of pyrene solution.

A strong and stable room temperature phosphorescence (RTP) and delayed excimer fluorescence signal located at 596 and 475 nm, respectively, can be induced for pyrene solution in the absence of any protective medium only use KI or TlNO3 as a heavy atom perturber (HAP) and Na2SO3 as a deoxygenator. Both lifetimes of RTP and the delayed fluorescence are in the order of X-ms and the intensities are changed with kind and amount of HAP, but the peak positions are same and there is a iso-luminescent point in the emission spectra corresponding to emission at 475 nm and at 596 nm. The optimum conditions and the effects of kind and amount of HAP and organic solvents on luminescence properties of pyrene solution were studies in detail, and the photophysical process in the presence of KI or TlNO3 for phosphorescence and delayed excimer fluorescence emission of pyrene solution was discussed.

Fluorescent Dyes↗
PubMed2001

Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.

Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 x 10(10) to 2 x 10(13) particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, gamma-IFN, TNF-alpha and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses > or = 2 x 10(12) particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 x 10(13) particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.

Adenocarcinoma↗
PubMed2001

Adhesive retention dressings are more comfortable than alginate dressings on split skin graft donor sites--a randomised controlled trial.

A prospective randomised trial examining the effectiveness, comparative comfort and ease of care of two different split skin graft donor site dressings was performed. One of the dressings was an alginate (Kaltostat), and the other an adhesive retention tape (Mefix). Alginates are the standard plastic surgical dressing, whereas the use of adhesive retention tapes as a donor site dressing presents a novel use of a readily available product. A total of 30 consecutive patients requiring split skin grafts were randomised to receive either alginate or retention donor site dressings. Dressings were assessed by interview and questionnaire at 24 h and 48 h and at 2 weeks, and by wound review at 2 weeks. Retention dressings were found to be more comfortable. They also required less nursing care and attention. The retention dressings allowed the patients easier mobility and a greater range of daily activities, especially washing. There was no significant difference in wound healing nor in complications. Adhesive retention tape applied directly to the split skin graft donor site wound is an effective, cheap and comfortable dressing requiring little postoperative care.

Adhesiveness↗
PubMed2001

[Study on the determination of photophysical parameters of the non-protected fluid room temperature phosphorescence by lifetime method].

The heavy atom pertuber (HAP) can promote the intersystem crossing and the rates of radiative and nonradiative processes of triplet state, thus shortens the phosphorescence lifetime. The determination of kinetic parameters for luminescence process is very importance to understand luminescence process and the mechanisms of the heavy atom effects. In this paper, 1-chloronaphthalene and 1-bromonaphthalene were selected as the modal compounds, the possibility of determination of photophysical parameters for emission of nonprotected fluid room temperature phosphorescence (NP-RTP) by RTP lifetime method was studied based on the definition on the phosphorescence lifetime and relation with the concentration of HAP. The results obtained by two ways prove that the RTP lifetime method can be used to determine photophysical parameters for RTP emission.

Fluorescent Dyes↗
PubMed2000

Study on using I- as heavy atom perturber in cyclodextrin-induced room temperature phosphorimetry.

A cyclodextrin induced room temperature phosphorimetry (CD-RTP) for determine beta-NOA, which using I- as a heavy atom perturber (HAP) and sodium sulfite as a deoxygenator, was developed. The phosphorescence peak wavelength maxima lambda(ex)/lambda(em) = 287/496,521 nm. The analytical curve of beta-NOA gives a linear dynamic range of 2.0 x 10(-7)-6.0 x 10(-6) mol/l and a detection limit of 4 x 10(-8) mol/l. The relative standard deviation (RSD; n = 7) was 3.2% for the 4.0 x 10(-6) mol/l beta-NOA in spiked apple samples. The influence of I- concentration on RTP lifetime of beta-NOA was studied in detail, the static Stern-Volmer equation for phosphorescence was derived and the luminescence kinetic parameters were calculated. It is found that the relation between I- concentration (x) and RTP lifetime (tau) can be expressed as tau = 1.047 e(-0.354x) and the rate constants of phosphorescence emission k(p) and non-radiation process k(i) from T1 --> S0 were 0.9551 s(-1) and 0.4276 s(-1) l(-1) mol, respectively.

Cyclodextrins↗
PubMed2000

Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516).

We determined the prognostic role of K-ras mutation in tumor tissue of patients with refractory colon cancer who received Marimastat (BB2516). DNA was extracted from paraffin-stored tumor tissue of 27 patients who previously failed 5-fluorouracil and were treated with BB2516. The presence of K-ras mutation was characterized by Polymerase Chain Reaction using ras- and p53-specific primers. ras and p53 oncoprotein expression was analyzed by an automated biotin-avidin immunoproxidase technique. Seventeen patients had a normal K-ras sequence and 10 patients had a K-ras mutation. Median survival of patients with a normal ras sequence was 330 days from the time of BB2516 treatment compared with 160 days for patients with a K-ras mutation (p = 0.0442, Wilcoxon; 0.0130 Log-Rank). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. Abnormalities involving ras expression did not affect survival. By comparison, median survival for patients with p53 mutation or p53 overexpression was both 158 days after BB2516 treatment. Patients having both K-ras and p53 mutations had the poorest median survival of 113 days (p = 0.035). There is a suggestion by univariate analysis that the presence of a K-ras mutation may predict survival in patients with progressive colon cancer. Further assessment with larger patient numbers and multivariate analysis is indicated.

Adult↗
PubMed2000

[Effects of fluoride on the expression of c-fos and c-jun genes and cell proliferation of rat osteoblasts].

OBJECTIVE: To investigate the effects of sodium fluoride (NaF) on the expression of c-Fos and c-Jun genes and osteoblast cell proliferation of rat osteoblasts. METHODS: Osteoblastic cells were isolated from baby rat calvaria, and cultured in the presence of different doses of NaF (10(-5) mol/L, 10(-4) mol/L, and 10(-3) mol/L). Cell proliferation was measured by the MTT method, and c-Fos and c-Jun expression was detected by the immunohistochemistry combined with image analysis compute system. RESULTS RESULTS: from the MTT assay showed that NaF increased the proliferation of rat osteoblast and induced the expression of c-Fos and c-Jun genes. The increases of c-Fos and c-Jun expression by the 3 different doses of NaF were 5.4%, 15.4% and 42.3% for the c-Fos gene and 12.1%, 14.4% and 38.6% for c-Jun gene respectively (P < 0.05 and P < 0.01). CONCLUSION: NaF increased rat osteoblastic cell proliferation and the expression of genes involved in cell proliferation.

Animals↗