Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 235 records · Page 13Linked to original sources

PubMed2001

Actions of the soy phytoestrogen genistein in models of human chronic disease: potential involvement of transforming growth factor beta.

The structural similarity, but non-identity, between 17beta-oestradiol and the soy phytoestrogen genistein suggests that the two compounds will have actions that may be identical in some target biological systems, but different in others. Epidermal growth factor (EGF)-stimulated proliferation of human mammary epithelial cells (that do not express the oestrogen receptor) was significantly suppressed at genistein concentrations (5-10 microM) that are attainable physiologically. Others have shown previously that transforming growth factor beta (TGFbeta) has similar growth-inhibitory effects on human cells. Analysis of the conditioned medium of human mammary epithelial cells exposed to genistein plus EGF showed increased levels of TGFbeta relative to those in the medium of cells exposed to EGF or genistein alone. Related experiments in a primate model of menopause demonstrated that ingestion of soy containing isoflavones was correlated with the suppression of neurodegeneration-relevant phosphorylation of the microtubule-associated protein tau, while intake of Premarin (a hormone replacement therapy that is commonly prescribed for women) was not correlated. The results discussed here indicate that genistein, and probably other related phytoestrogens, have pleiotropic actions, some of which may involve TGFbeta activity.

Animals↗

PubMed2001

The bactericidal effect and chemical reactions of acidified nitrite under conditions simulating the stomach.

AIMS: To examine the hypothesis of non-immune defence mechanisms based on nitrite. METHODS AND RESULTS: The acidified media (nutrient broth or citrate-phosphate buffer) under aerobic conditions with additions of physiological levels of nitrite, L-ascorbic acid, iodide and thiocyanate were used to simulate gastric juice. The bactericidal effects of acidified nitrite on Escherichia coli and lactobacilli were investigated using bacterial plate counts. Conversion of acidified nitrite to nitric oxide, nitrogen dioxide and nitrate was also studied. Nitrite significantly increased the bactericidal effects on E. coli and lactobacilli. The bactericidal effects were enhanced by thiocyanate but not by L-ascorbic acid and iodide. L-Ascorbic acid and thiocyanate, but not iodide, enhanced the decomposition of acidified nitrite in nutrient broth. Acidified nitrite was converted to both nitric oxide and nitrate, but a portion of the acidified nitrite in nutrient broth may have been converted to other unidentified nitrogen compounds. Nitrogen dioxide was not detected in any of the samples. CONCLUSION: The bactericidal effects of nitrite appeared to be primarily related to nitrous acid, and possibly to other unidentified nitrogenous metabolites, but not to nitric oxide and nitrogen dioxide. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential role of nitrite as an antimicrobial substance in the stomach may be of some importance in the ecology of the gastrointestinal tract and in host physiology.

Anti-Bacterial Agents↗

PubMed2001

Occurrence and molecular genotyping of Cryptosporidium spp. in surface waters in Northern Ireland.

AIMS: To investigate the incidence and genotype of Cryptosporidium parvum oocysts in drinking water sources in Northern Ireland for the period 1996-1999, and to compare conventional and molecular methods of detection. METHODS AND RESULTS: Four hundred and seventy-four waters were investigated by conventional methods, namely immuno-fluorescent antibody detection (IFA; 380) and immuno-magnetic separation-IFA (IMS-IFA; 94), of which 14/474 (3%) were positive. Two hundred and fourteen samples (214/474) were also investigated by PCR techniques, targeting both the 18S rRNA and TRAP-C2 genes, of which 11/214 (5.1%) were positive. These 11 samples were classified as genotype II following sequence analysis of the TRAP-C2 amplicon. CONCLUSIONS: This study demonstrated the low incidence of oocysts of C. parvum in water sources in Northern Ireland. SIGNIFICANCE AND IMPACT OF THE STUDY: Such molecular-based techniques offer a number of advantages over conventional detection methodologies, namely greater sensitivity and specificity as well as the ability to provide accurate genotyping data rapidly, which may be valuable in directing operational management in potential outbreak situations.

Animals↗

PubMed2001

Dissection of RNA-mediated ryegrass mosaic virus resistance in fertile transgenic perennial ryegrass (Lolium perenne L.).

Ryegrass mosaic virus (RgMV) frequently reduces yield and persistence of perennial ryegrass. We introduced an untranslatable RgMV coat protein (RgMV-CP) gene into perennial ryegrass using particle bombardment to explore the potential of RNA-mediated virus resistance. Nine months after inoculation with the RgMV-Bulgaria strain, the most resistant transgenic line showed no immuno-detectable RgMV-CP in all replications of the primary transformant and a sexual progeny. A significant influence of the transgenic line, virus strain and the period after inoculation on the RgMV level was observed. Typical examples of recovery resistance from initially susceptible plants were not identified. Molecular analysis revealed RgMV resistance operates by targeted RNA degradation resulting in post-transcriptional transgene silencing (PTGS) along with inhibition of virus RNA replication and was not associated with a threshold of transgene expression. Suppression of PTGS by RgMV differed significantly in two progenies with identical RgMV-CP transgene integration and a similar RgMV-CP transgene methylation pattern, suggesting the presence of quantitative components controlling the stability of PTGS in perennial ryegrass. This study extends RNA-mediated virus resistance, post transcriptional gene silencing and crop improvement by genetic engineering to an agronomically important perennial monocot.

Capsid↗

PubMed2001

Effects and mechanisms of somatostatin analogs on apoptosis of pancreatic acinar cells in acute pancreatitis in mice.

AIM: To investigate the effects of somatostatin analogs (SSa) on apoptosis of pancreatic acinar cells and apoptosis-regulated gene bax, and p53 in treating acute pancreatitis in mice. METHODS: In cerulein-induced pancreatitis, with or without treatment of somatostatin, analogs (Octreotide) in CD-1 (BALB/c x DBetaAlpha/1) mice, apoptosis of pancreatic acinar cells was detected by using the TdT-mediated dUTP nick-end labeling (TUNEL) method, and the expression of apoptosis-regulated gene bax and p53 was determined by using the streptavidin-peroxidase immunohistochemical technique and the RT-PCR method, respectively. RESULTS: On HE staining, acinar cells in the pancreas showed pyknotic nuclei and the formation of apoptotic bodies, which are the typical morphological features of apoptosis. Regarding TUNEL use, the apoptotic index of pancreatic acinar cells in the non-treated group at 5 and 14 h after induction of acute pancreatitis was significantly lower than those of the SSa-treated group, respectively (P < 0.01). On immunohistochemistry and RT-PCR, there was an expression of neither bax nor p53 in normal pancreatic tissues. The expression of bax in the SSa-treated group at 5 and 14 h after treatment of SSa was markedly higher than those of the non-treated group, respectively (P < 0.01), but there was no significant difference in the expression of p53 between the SSa-treated group and the non-treated group. CONCLUSIONS: The induction of apoptosis in pancreatic acinar cells injury to reduce inflammatory reaction might be one of the mechanisms of SSa in treating acute pancreatitis in mice, and the mechanisms of apoptosis probably correlated with the expression of apoptosis-regulated gene bax, but have no relationship with the expression of p53.

Acute Disease↗

PubMed2001

Differential expression of adenylyl cyclases in the rat nephron.

BACKGROUND: Adenylyl cyclases (ACs) are a family of enzymes that catalyze the formation of the second-messenger cyclic adenosine 3',5'-monophosphate (cAMP). At least nine isoforms of AC have been cloned. These isoforms differ in their tissue distribution and basal activity. AC isoforms also differ in their capacity to be stimulated or inhibited by G protein alpha(i), alpha(s) and beta/gamma subunits, protein kinase C, and intracellular calcium. The distribution of ACs in the kidney is only partially known, although it is known that ACs play important roles in kidney signal transduction. Several receptors are known to couple to AC, but their linkage to individual AC isoforms in the kidney is not known. METHODS: This study investigated the tissue distribution of AC isoforms along the nephron of Wistar-Kyoto rats using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblotting. RESULTS: While AC VI and IX mRNA were found in all nephron segments, there was no expression of AC VIII mRNA. ACs II through V and VII mRNA were variably found in specific nephron segments. mRNA for AC isoforms II, III, VI, VII, and IX were expressed in renal proximal tubules. All of the AC isoforms studied, except VIII, were found in glomeruli. Immunoblotting and immunohistochemistry confirmed the mRNA results. AC isoforms II, III, IV, and IX were expressed in luminal rather than in basolateral membranes. However, immunohistochemical studies were not feasible for the other isoforms that could be expressed in basolateral membranes. CONCLUSION: Knowledge of the distribution of ACs may help establish the linkage between receptors and specific AC isoforms and define their functions.

Adenylyl Cyclases↗

PubMed2001

Comparative study of different surgical procedures using sensory nerves or neurons for delaying atrophy of denervated skeletal muscle.

To observe the effect of sensory components on muscle atrophy, 4 surgical procedures applying sensory nerves or neurons to the denervated muscle were conducted in a rat model: sensory nerve implantation (group B), sensory motor nerve crossover (group C), dorsal root ganglia implantation (group D), and implantation of preganglionically avulsed sensory nerve (group E). Rats with complete denervation served as controls (group A). The degree of muscle atrophy was evaluated after surgery by fibrillation potential amplitude, muscle wet weight, muscle fiber cross-sectional area, collagen content, and protein content. Compared with group A, the results in groups B, D, and E were superior 1 month after surgery and the results in groups B, C, and E were superior 3 months after surgery. Implantation of normal or preganglionically avulsed sensory nerve delayed atrophy. Dorsal root ganglia implantation only had a short-term trophic influence. In the animal model setting, sensory motor nerve crossover is effective only after it is maintained for at least 3 months.

Animals↗

PubMed2001

Population pharmacokinetics of dapsone in children with human immunodeficiency virus infection.

BACKGROUND: Previous studies of dapsone pharmacokinetics in children have been too small to allow assessment of the relationships between dapsone pharmacokinetic parameters and patient characteristics or markers of efficacy and toxicity. METHODS: We used population analysis to estimate dapsone pharmacokinetic parameters in children participating in a phase I/II study of daily and weekly dapsone in children with human immunodeficiency virus (HIV) infection. With use of the program NONMEM and a 1-compartment open model, the influence of demographic and clinical characteristics on oral clearance (CL/F) and oral volume of distribution (V/F) were examined. Measures of drug exposure (area under the concentration-time curve [AUC] and predicted concentrations just before and 2 hours after administration) were estimated for each patient and correlated with markers of efficacy and toxicity. RESULTS: Sixty children (median age, 3 years; age range, 2 months to 12 years) contributed 412 dapsone concentrations collected after 175 study doses. Final parameter estimates were 1.40 L/kg for V/F, 0.0283 L/kg/h for CL/F, and 2.66 for the absorption rate constant. Of the clinical characteristics evaluated, dapsone CL/F was significantly increased by 50% in children taking rifabutin, by 39% in black children, and by 38% in children younger than 2 years old. Although no significant correlations were found between any dapsone exposure parameter and markers of toxicity, increased AUC was associated with a decreased risk of Pneumocystis carinii pneumonia (PCP). CONCLUSION: Ethnicity, age, and concomitant rifabutin use were associated with dapsone CL/F, with more rapid clearance observed in black children, children younger than 2 years old, and children receiving rifabutin. Dapsone pharmacokinetic parameters were not associated with toxicity, but higher dapsone AUC was associated with decreased risk of PCP. Monitoring of serum dapsone levels may be needed for optimal management of dapsone for PCP prophylaxis in children.

AIDS-Related Opportunistic Infections↗

PubMed2001

Molecular diagnosis of infective endocarditis--a new Duke's criterion.

The molecular approach of PCR amplification of specific gene targets and universal loci for bacteria (16S rRNA) and fungi (18S, 28S and 5.8S rRNA) and subsequent sequencing was used to identify the possible causal microbial agent(s) in blood culture (47 patients) and heart valve material (30 patients) from patients with suspected infective endocarditis (IE). Culture and molecular results were analysed with respect to the patients' clinical background and the Duke Criteria. The findings demonstrated that: (i) all patients who were definite or possible cases were positive by PCR, even patients whose blood culture and valve material were culture-negative; and (ii) all patients who were rejected as having IE were also negative by PCR, with the exception of 1 patient who had bacteraemia from another source and 5 patients whose blood culture material was believed to contain an environmental contaminant. Direct molecular identification of the aetiological agents responsible for IE from blood culture material may enable specific treatment to commence at an earlier stage of the disease and hence reduce the need for valve replacement. Such a molecular approach may aid in the diagnosis of IE and should therefore be included as an additional major criterion in the Duke's classification scheme.

Bartonella↗

PubMed2001

iNOS and nitrotyrosine expression after spinal cord injury.

Secondary tissue damage after spinal cord injury (SCI) may be due to inflammatory mediators. After SCI, the nuclear factor-kappaB (NF-kappaB) transcription factor can activate many pro-inflammatory genes, one of which is inducible nitric oxide synthase (iNOS). iNOS catalyzes the synthesis of nitric oxide (NO), a key inflammatory mediator, which in turn reacts with superoxide to generate peroxynitrite. Peroxynitrite is a strong oxidant that can damage cellular enzymes, membranes, and subcellular organelles through the nitration of tyrosine residues on proteins. The presence of nitrotyrosine (NT) is an indirect chemical indicator of toxic NO and peroxynitrite-induced cellular damage. Using a New York University (NYU) impactor to induce SCI in adult rats, we examined the temporal and cellular expression of iNOS and NT. We observed a progressive increase in iNOS expression in the injured cord starting at day 1 with maximal expression occurring at day 7, as determined by Western blot analysis. iNOS expression corresponded temporally to an increase in iNOS enzyme activity after SCI. In parallel with the progressive increase in iNOS activity, NT expression also increased with time after SCI. The iNOS and NT immunoreactivity was localized in neurons, astrocytes, endothelial cells and ependymal cells at the epicenter and adjacent to the region of spinal cord impact and injury. Results from the present study suggest that increased iNOS and peroxynitrite anion, as reflected by the progressive accumulation of NT in the injured impacted spinal cord, may contribute to the secondary injury process after SCI.

Animals↗

PubMed2001

Cellular localization of tumor necrosis factor-alpha following acute spinal cord injury in adult rats.

Posttraumatic inflammatory reaction may contribute to secondary injury after traumatic spinal cord injury (SCI). Expression of tumor necrosis factor-alpha (TNF-alpha), a key inflammatory mediator, has been demonstrated in the injured cord. However, the specific cell types that are responsible for TNF-alpha expression after SCI remain to be identified. In the present study, cellular sources of TNF-alpha were examined in rats that received a spinal cord impact injury at the 9th thoracic (T9) level. Here we demonstrate that, within hours after SCI, increased TNF-alpha immunoreactivity was localized in neurons, glial cells (including astrocytes, oligodendrocytes, and microglia), and endothelial cells in areas of the spinal cord adjacent to the lesion site. Myelin breakdown was noted in oligodendrocytes that are immunopositive for TNF-alpha. In sham-operated controls, a low level of TNF-alpha immunoreactivity was detected. In antigen-absorption experiments, no TNF-alpha immunoreactivity was detected, indicating the specificity of TNF-alpha immunocytochemistry in the present study. Results suggest that various cell types, including neurons, glial cells, and vascular endothelial cells, contribute to TNF-alpha production in the injured cord.

Acute Disease↗

PubMed2001

Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects.

Heavy metal-tungsten alloys (HMTAs) are dense heavy metal composite materials used primarily in military applications. HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%) and either cobalt (2-4%) or iron (2-4%) particles. Like the heavy metal depleted uranium (DU), the use of HMTAs in military munitions could result in their internalization in humans. Limited data exist, however, regarding the long-term health effects of internalized HMTAs in humans. We used an immortalized, non-tumorigenic, human osteoblast-like cell line (HOS) to study the tumorigenic transforming potential of reconstituted mixtures of tungsten, nickel and cobalt (rWNiCo) and tungsten, nickel and iron (rWNiFe). We report the ability of rWNiCo and rWNiFe to transform immortalized HOS cells to the tumorigenic phenotype. These HMTA transformants are characterized by anchorage-independent growth, tumor formation in nude mice and high level expression of the K-ras oncogene. Cellular exposure to rWNiCo and rWNiFe resulted in 8.90 +/- 0.93- and 9.50 +/- 0.91-fold increases in transformation frequency, respectively, compared with the frequency in untreated cells. In comparison, an equivalent dose of crystalline NiS resulted in a 7.7 +/- 0.73-fold increase in transformation frequency. The inert metal tantalum oxide did not enhance HOS transformation frequency above untreated levels. The mechanism by which rWNiCo and rWNiFe induce cell transformation in vitro appears to involve, at least partially, direct damage to the genetic material, manifested as increased DNA breakage or chromosomal aberrations (i.e. micronuclei). This is the first report showing that HMTA mixtures of W, Ni and Co or Fe cause human cell transformation to the neoplastic phenotype. While additional studies are needed to determine if protracted HMTA exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized HMTAs exposure may be comparable with the risk from other biologically reactive and insoluble carcinogenic heavy metal compounds (e.g. nickel subsulfide and nickel oxide).

Alloys↗

PubMed2001

Development of cloned embryos from adult rabbit fibroblasts: effect of activation treatment and donor cell preparation.

This research was to study the in vitro and in vivo development of cloned embryos derived from adult rabbit fibroblasts following various activation protocols. Effects of serum starvation and passage number of donor cells on the efficiency of cloning were also examined. In experiment I, oocytes were activated either by electric pulses or by electric pulses followed by culture with 6-dimethylaminopurin (DMAP). For experiment II, the best activation protocol from experiment I was employed for cloning using adult rabbit fibroblasts that were cultured for 0-15 passages. In experiment III, the effect of serum starvation of the donor cells on cloning was examined. Finally, in experiment IV, embryo transfers were conducted. These experiments showed that combined electrical pulse and DMAP treatment resulted in superior parthenogenetic blastocyst development (up to 29%), and that activation of the cytoplast before versus after fusion was not different in supporting the in vitro development of nuclear transferred embryos (16%-18% blastocysts). Adult fibroblasts derived from nonpassaged cells were less capable of developing into blastocysts than passaged cells (6% vs. 17%). Serum starvation of donor cells improved cleavage (up to 71%) but did not improve blastocyst development (13%), and no progeny was obtained, irrespective of the treatment. Cell-cycle analysis of adult rabbit fibroblast cells showed that passage 6 and 12 cells were more likely to be in G(0)/G(1) than passage 0 cells, which agrees with the improved embryo development in the passaged-cell groups.

Adenine↗

PubMed2001

Telomerase activity in early bovine embryos derived from parthenogenetic activation and nuclear transfer.

This study examined the telomerase activity in preimplantation bovine embryos derived from either parthenogenetic activation or nuclear transfer. Telomeres are the DNA-protein structures located at the ends of eukaryotic chromosomes. Telomerase is the ribonuclear enzyme that helps to restore telomere length by synthesizing telomeric DNA repeat (5'-TTAGGG-3') from its own RNA template. Without telomerase activity, telomeres shorten with each cell division through conventional DNA replication. In most mammalian species, telomerase activity is present in germ cells but not in somatic cells. Previously, we reported the dynamics of telomerase activity in bovine in vitro fertilized (IVF) embryos. In the present study, we examined the telomerase activity in bovine embryos derived either from parthenogenetic activation or somatic cell nuclear transfer (i.e., cloning). Embryos from both sources were harvested at different stages, from zygote to blastocyst. Telomerase activity in embryos derived from parthenogenetic activation and nuclear transfer showed a dynamic profile similar to that of those derived from IVF. Telomerase activity was detected in embryos at all stages examined, with the highest level in the blastocyst stage, regardless of the method of embryo production.

Animals↗

PubMed2001

P504S: a new molecular marker for the detection of prostate carcinoma.

The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

Antibodies, Monoclonal↗

PubMed2001

Amyloid beta peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation.

Amyloid beta peptide (A beta), a 39 to 43 amino acid fragment of the beta-amyloid precursor protein (betaAPP), forms insoluble fibrillar accumulation in neurofibrillary tangles and vascular plaques. A beta has been implicated in neuronal and vascular degeneration in brain regions susceptible to plaque formation because of its cytotoxic effect on neurons and endothelial cells (ECs). The authors used a murine cerebral endothelial cell (CEC) line and primary cultures of bovine CECs to explore the cytotoxic mechanism of A beta. A beta 1-40 and A beta 25-35 peptides caused cell death in a dose-dependent and time-dependent manner. Exposure to either A beta 25-35 or A beta 1-40 at 10 micromol/L for 48 hours caused at least 40% cell death. Cerebral endothelial cell death was characterized by nuclear condensation, mitochondrial dysfunction, and nuclear and mitochondrial DNA damage. A beta 25-35 activated both caspase-8 and caspase-3 in murine CECs. zVAD-fmk, a broad-spectrum caspase inhibitor, prevented A beta 25-35-induced increase in caspase-3 activity and CEC death. N-acetyl-cysteine, an antioxidant, also prevented A beta-induced cell death. Together, these findings indicate that A beta-mediated CEC death is an apoptotic process that is characterized by increased oxidative stress, caspase activation, mitochondrial dysfunction, and nuclear and mitochondrial DNA damage.

Acetylcysteine↗

PubMed2001

Alternative valuations of work loss and productivity.

In this article, we examine the indirect costs (i.e., work loss and productivity costs) of employee illness from the employer's perspective. We provide a conceptual framework to help employers consider alternative views with regard to assessing indirect costs and valuing the health care they purchase. First, we discuss the matter of perspective and how an employer should view and assess indirect costs. We briefly review current models of measuring indirect costs, and we critique these models. Then we introduce a simple, conceptual framework based on the ideas of health capital and labor productivity, and we lay out the effects of health investment on indirect costs while considering what employees desire and employers can provide. Finally, we offer an agenda for further research.

Absenteeism↗

PubMed2001

The role of radiographic phase-contrast imaging in the development of intracochlear electrode arrays.

OBJECTIVE: This study describes the application of a new radiographic imaging modality, phase-contrast radiography, to in vitro human temporal bone imaging and investigates its use in the development of new electrode arrays for cochlear implants. BACKGROUND: The development of perimodiolar electrode arrays for cochlear implants requires detailed information from postoperative radiologic assessment on the position of the array in relation to the cochlear structures. Current standard radiographic techniques provide only limited details. MATERIALS AND METHODS: Nucleus standard electrode arrays and perimodiolar Contour electrode arrays were implanted into the scala tympani of 11 human temporal bones. Both conventional and phase-contrast radiographs were taken of each temporal bone for comparative purposes. RESULTS: Phase-contrast imaging provides better visualization of anatomic details of the inner ear and of the structure of the intracochlear electrode array, and better definition of electrode location in relation to cochlear walls. CONCLUSION: Phase-contrast radiography offers significant improvement over conventional radiography in images of in vitro human temporal bones. It seems to be a valuable tool in the development of intracochlear electrode arrays and cochlear implant research. However, this new radiographic technique still requires certain computational and physics challenges to be addressed before its clinical use can be established.

Cochlea↗