Biomedical subjects

B Wu

Publications and source records attributed to B Wu.

At least 19 recordsLinked to original sources

PubMed2007

A frequent Y chromosome b2/b3 subdeletion shows strong association with male infertility in Han-Chinese population.

BACKGROUND: Azoospermia factor c (AZFc) subdeletions were reported to be significant risk factors for spermatogenesis. In this study, we assessed the occurrence of classical AZF deletions and AZFc subdeletions and their impact on male infertility in a Han-Chinese population. METHODS: This study analysed a population of 699 subjects, including 451 idiopathic infertile patients with a range of fertility disorders and 248 fertile controls, using a retrospective design. Deletions were identified by multiplex PCR. RESULTS: The prevalence and phenotypes of the classical AZF deletions were similar to previous studies. Subdeletions of the AZFc region in patients showed similar overall frequencies in all sperm concentration categories of gr/gr (7.0%) and b2/b3 (8.9%). For controls, these subdeletions were also found with a prevalence of gr/gr (7.7%) and b2/b3 (3.2%). b1/b3 deletions were not found either in the patients or in the controls. CONCLUSION: Our data showed a higher frequency of deletion events in this Han-Chinese population than in populations elsewhere in the world. The classical AZF deletions were the primary genetic factors for spermatogenic failure, while no significant association was found for AZFc subdeletions with sperm concentration. However, the b2/b3 subdeletion was significantly associated with idiopathic male infertility (odds ratio, 2.93; 95% confidence interval 1.34-6.39) (P = 0.005), indicating a potential impairment of male fertility.

Adult↗

PubMed2006

Non-antiepileptic drugs for trigeminal neuralgia.

BACKGROUND: Non-antiepileptic drugs have been used in trigeminal neuralgia management since the 1970s. OBJECTIVES: The objective was to review systematically the efficacy of non-antiepileptic drugs for trigeminal neuralgia. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register, MEDLINE, EMBASE, and LILACS (all to August 2005) and the Chinese Biomedical Retrieval System, the database of the Chinese Cochrane Center (The Cochrane Library, Issue 1 2005), conference paper databases and checked bibliographies. We handsearched ten Chinese journals. SELECTION CRITERIA: We searched for randomized or quasi-randomized controlled trials. DATA COLLECTION AND ANALYSIS: Two authors decided which trials fitted the inclusion criteria and graded methodological quality independently. MAIN RESULTS: Nine trials of different non-antiepileptic drugs involving 223 participants were included. Each trial investigated one non-antiepileptic drug. Two trials tested baclofen. In one, more people gained 50% reduction from baseline than with placebo (relative risk 15.00, 95% CI 0.97 to 231.84, P value = 0.05). In the other, slightly more participants on baclofen had a 75% reduction in attacks on the 10th day compared with carbamazepine (relative risk 2.38, 95% CI 0.83 to 6.85, P value = 0.11). One trial showed no significant difference in reduction in average daily frequency of attacks with L-Baclofen compared with racemic baclofen. Tizanidine was investigated in two trials. In one, the proportion of people with reduction in the average number of paroxysms per day increased with tizanidine compared with placebo (relative risk 8.00, 95% CI 1.21 to 52.69, P value = 0.03). In the other, one of five participants improved in visual analog scale score with tizanidine and four of six with carbamazepine (relative risk 0.30, 95% CI 0.05 to 1.89, P value = 0.20). One study showed that the improvement in mean values of pain scores with tocainide was similar to that of carbamazepine. In one study more participants improved during the pimozide than the carbamazepine period (relative risk 1.78, 95% CI 1.39 to 2.28). In one study, proparacaine hydrochloride 0.5% instillation into the eyes was not significantly different from placebo (relative risk 1.06, 95% CI 0.37 to 2.99, P value = 0.92). In another, there was moderate or marked improvement in seven of nine participants treated with clomipramine and three of nine with amitriptyline after a 12-week treatment (RR 2.33, 95% CI 0.87 to 6.27). AUTHORS' CONCLUSIONS: There is insufficient evidence from randomized controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.

Amitriptyline↗

PubMed2006

A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study.

OBJECTIVE: The superiority of risperidone long-acting injection (RLAI) over oral typical and atypical antipsychotics demonstrated in previous studies may be related to the improved drug compliance. The aim of the 12-week randomized, single-blind study was to test whether the superiority of RLAI remained among hospitalized patients that drug compliance could be optimally controlled. METHODS: Fifty hospitalized stable schizophrenic patients, who had maintained on oral risperidone for more than 3 months, were randomized to the RLAI and oral risperidone group. Finally 49 patients (98 %) completed the study, and no dose change of oral risperidone, or RLAI was noted among all patients. RESULTS: The RLAI group showed significantly increased positive score of Positive and Negative Syndrome Scale (PANSS) than the risperidone group (0.72 +/- 3.52 vs. -1.24 +/- 3.81, p = 0.022), but without significance difference for the PANSS total, negative and general psychopathology scores. The RLAI group also showed a significantly improved Udvalg for Kliniske Undersogelser (UKU) Scale (p = 0.037), social life domains of Short-Form Health Survey (SF-36) (p = 0.011), and reduced prolactin level (p = 0.001). CONCLUSION: The results indicated that with optimal controlling of drug compliance among hospitalized patients, RLAI showed no benefit of efficacy over oral risperidone, but with advantages of improved side-effect profiles, social life ratings, and reduced prolactin levels.

Administration, Oral↗

PubMed2005

Direct electrodeposition of highly dense Bi/Sb superlattice nanowire arrays.

Ordered arrays of Bi/Sb superlattice nanowires with diameters of about 50 nm have been produced by pulsed electrodeposition technique into the pores of anodic alumina membrane (AAM). The structure of Bi/Sb superlattice nanowire can be modulated by controlling the electrodeposition conditions.

Journal Article↗

PubMed2005

ABACUS, a direct method for protein NMR structure computation via assembly of fragments.

The ABACUS algorithm obtains the protein NMR structure from unassigned NOESY distance restraints. ABACUS works as an integrated approach that uses the complete set of available NMR experimental information in parallel and yields spin system typing, NOE spin pair identities, sequence specific resonance assignments, and protein structure, all at once. The protocol starts from unassigned molecular fragments (including single amino acid spin systems) derived from triple-resonance (1)H/(13)C/(15)N NMR experiments. Identifications of connected spin systems and NOEs precede the full sequence specific resonance assignments. The latter are obtained iteratively via Monte Carlo-Metropolis and/or probabilistic sequence selections, molecular dynamics structure computation and BACUS filtering (A. Grishaev and M. Llinás, J Biomol NMR 2004;28:1-10). ABACUS starts from scratch, without the requirement of an initial approximate structure, and improves iteratively the NOE identities in a self-consistent fashion. The procedure was run as a blind test on data recorded on mth1743, a 70-amino acid genomic protein from M. thermoautotrophicum. It converges to a structure in ca. 15 cycles of computation on a 3-GHz processor PC. The calculated structures are very similar to the ones obtained via conventional methods (1.22 A backbone RMSD). The success of ABACUS on mth1743 further validates BACUS as a NOESY identification protocol.

Algorithms↗

PubMed2005

Tumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in mice.

BACKGROUND: Collagen induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) amenable to immunotherapy directed against tumour necrosis factor alpha (TNFalpha). OBJECTIVE: To evaluate whether local TNF receptor (TNF-R) gene therapy in DBA/1 mice exerts an influence beyond anti-inflammatory effects. Two measures of CIA pathogenesis were investigated-namely, immunity to collagen II (CII) 245-270 peptide (the major immunodominant epitope within bovine CII) and the preferential activation of T cell Vbeta8.2 variable region receptors in arthritic DBA/1 mice. METHODS: DBA/1 mice received single periarticular injections of media or retroviral vectors containing LacZ or human TNF-R into affected arthritic paws at disease onset. Disease severity was monitored, immune responses towards the immunodominant bovine CII 245-270 and subdominant CII 334-360 peptide epitopes were assessed by ELISA, and T cell Vbeta usage was analysed by real time polymerase chain reaction for the LacZ transduced, TNF-R, and viral-free media treated control animals. The therapeutic influence of TNF-R gene transduction was compared with other groups at different times after treatment. RESULTS: Reduced disease severity was seen 15-35 days after treatment, with a concomitant increase in immunity towards the subdominant CII 334-360 peptide epitope rather than the immunodominant CII 245-270 peptide in TNF-R treated animals. Early in the disease, TNF-R treated animals demonstrated a reduction of bias towards the otherwise predominant Vbeta8.2 T cell subset. CONCLUSIONS: TNF-R gene therapy influences cellular immunity in CIA, leading to overall disease amelioration, thus suggesting that TNF inhibition may have therapeutic potential beyond the control of inflammation in RA.

Animals↗

PubMed2005

Detection of porcine circovirus type 2, porcine parvovirus and porcine pseudorabies virus from pigs with postweaning multisystemic wasting syndrome by multiplex PCR.

Multiplex PCR was established to detect porcine circovirus type 2 (PCV-2), porcine parvovirus (PPV) and porcine pseudorabies virus (PRV) and applied to samples from 137 piglets exhibiting clinical signs of postweaning multisystemic wasting syndrome (PMWS). PCV-2 DNA was detected from all samples. Moreover, 43 samples were positive for PPV but negative for PRV; 11 samples were positive for PRV but negative for PPV; and 35 samples were positive both for PPV and PRV. These results suggests that PCV-2 co-infection with PRV and PPV may play an important role in PMWS. Also, multiplex PCR is an appropriate candidate method for diagnosis of PCV-2, PRV and PPV simultaneously in field cases.

Animals↗

PubMed2005

Amino acid sensing by Ssy1.

Saccharomyces cerevisiae senses extracellular amino acids using two members of the family of amino acid transporters, Gap1 or Ssy1; aspects of the latter are reviewed here. Despite resemblance with bona fide transporters, Ssy1 appears unable to facilitate transport. Exposure of yeast to amino acids results in Ssy1-dependent transcriptional induction of several genes, in particular some encoding amino acid transporters. Amino acids differ strongly in their potency, leucine being the most potent one known. Using a selection system in which potassium uptake was made dependent on amino acid signalling, our laboratory has obtained and described gain-of-function mutations in SSY1. Some alleles conferred inducer-independent signalling; others increased apparent affinity for inducers. These results revealed that amino acid transport is not required for signalling and support the notion that sensing by Ssy1 occurs via its direct interaction with extracellular amino acids. Current work includes development of quantitative assays of sensing. We use the finding by Per Ljungdahl's laboratory that the signal transduction from Ssy1 involves proteolytic removal of an inhibitory part of the transcriptional activator Stp1. Protein-A Z-domain fused to the C-terminus of Stp1 and Western analysis using antibody against horseradish peroxidase allow quantification of sensing.

Amino Acids↗

PubMed2005

The Oral Fluid MEMS/NEMS Chip (OFMNC): diagnostic and translational applications.

The ability to monitor health status, disease onset and progression, and treatment outcome through non-invasive means is a most desirable goal in health-care promotion and delivery. There are three prerequisites for this goal to be realized: specific biomarkers associated with a health or disease state, a non-invasive approach to detect and monitor the biomarkers, and the technologies to discriminate between and among the biomarkers. We present a roadmap to achieve these goals using oral fluids as the diagnostic medium to scrutinize the health and/or disease status of individuals. This is an ideal opportunity to bridge state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral fluid for diagnostic applications. As the "mirror of body", oral fluid is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous.

Biomarkers↗

PubMed2004

Dan Shen agents for acute ischaemic stroke.

BACKGROUND: Based mainly on experimental data which indicates improvement to the cerebral microcirculation, Dan Shen, a form of herbal medicine, is widely used in the treatment of acute ischaemic stroke in China. We aimed to assess the evidence from randomised controlled trials of their effects. OBJECTIVES: To review the randomised or quasi-randomised controlled trials of Dan Shen agents for acute ischaemic stroke. The primary objective was to determine whether Dan Shen agents improve functional outcome without causing undue harm in patients with acute ischaemic stroke. Secondary objectives were to assess the effect of Dan Shen agents on impairment and on quality of life. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2003), the register of the Cochrane Complementary Field (last searched September 2003) and the Chinese Stroke Trials Register (last searched September 2003). In addition we searched the following bibliographic databases: The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (1996 to December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002), AMED (1985 to December 2002) and China Biological Medicine Database (CBM-disc 1979 to December 2002). We handsearched 10 Chinese journals, searched clinical trials and research databases, scanned reference lists and contacted the pharmaceutical company manufacturing Dan Shen. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing Dan Shen agents with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Eight potentially eligible trials were identified, of which three trials (304 patients) were included. Two trials were excluded and three trials are awaiting assessment. Numbers of deaths and dependent patients at the end of follow-up of at least three months were not reported in the three included trials. Only one trial reported adverse events. Three trials measured the outcome "significant improvement in neurological deficit at the end of treatment". Compound Dan Shen agents were associated with a significant increase in the number of patients with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence Interval (CI) 1.10 to 6.72). No deaths were reported within the first two weeks of treatment or during the whole follow-up period (21 to 28 days). The trials did not include any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were too few patients and outcome events to draw reliable conclusions from the present data. The methodological qualities of all included studies were poor. Further high-quality randomised controlled trials should be performed.

Acute Disease↗

PubMed2004

Acupuncture for Bell's palsy.

BACKGROUND: Bell's palsy or idiopathic facial palsy is an acute facial paralysis due to inflammation of the facial nerve. A number of studies published in China have suggested acupuncture is beneficial for facial palsy. OBJECTIVES: The objective of this review was to examine the efficacy of acupuncture in hastening recovery and reducing long-term morbidity from Bell's palsy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register, MEDLINE (January 1966 to December 2002), EMBASE (January 1980 to December 2002), LILACS (from January 1982 to December 2002) and the Chinese Biomedical Retrieval System (January 1978 to December 2002) for randomised controlled trials using 'Bell's palsy' and its synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms including 'acupuncture'. Chinese journals in which we thought we might find randomised controlled trials or controlled clinical trials relevant to our study were handsearched. We reviewed the bibliographies of the randomised trials and contacted the authors and known experts in the field to identify additional published or unpublished data. SELECTION CRITERIA: We included all randomised or quasi-randomised controlled trials involving acupuncture in the treatment of Bell's palsy irrespective of any language restrictions. DATA COLLECTION AND ANALYSIS: Two reviewers identified potential articles from the literature search and extracted data independently using a data extraction form. The assessment of methodological quality included allocation concealment, patient blinding, differences at baseline of the experimental groups and completeness of follow-up. Two reviewers assessed quality independently. All disagreements were resolved by discussion between the reviewers. MAIN RESULTS: Three studies including a total of 238 patients met the inclusion criteria. Two of them used acupuncture while the third used acupuncture combined with drugs. No trials reported on the outcomes specified for this review. Three included studies showed that the therapeutic effect of acupuncture alone was superior to that of medication or that acupuncture combined with medication was better than medication alone. Harmful side-effects were not reported in any of the trials. Flaws in study design or reporting (particularly uncertain allocation concealment and substantial loss to follow-up) and clinical differences between trials prevented a meta-analysis. REVIEWER'S CONCLUSIONS: The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture. More research with high quality trials is needed.

Acupuncture Therapy↗

PubMed2004

Protective effects of IL-1Ra or vIL-10 gene transfer on a murine model of wear debris-induced osteolysis.

The current study evaluated the protective effects of anti-inflammatory cytokine gene transfer on osteolysis provoked by orthopedic biomaterial particles using a murine model of inflammatory bone loss. A section of bone was surgically implanted into an air pouch established on a syngeneic recipient mouse. Inflammation was provoked by introduction of ultra-high-molecular-weight polyethylene (UHMWPE) particles into the pouch, and retroviruses encoding for interleukin-1 receptor antagonist (hIL-1Ra), viral interleukin-10 (vIL-10), or LacZ genes were injected. Pouch fluid and tissue were harvested 7 days later for histological and molecular analyses. The results indicated that IL-1Ra or vIL-10 gene transfer significantly inhibited IL-1beta and tumor necrosis factor (TNF) expression at both mRNA and protein levels. There were significantly lower mRNA expressions of calcitonin receptor and cathepsin K in RNA isolated from hIL-1Ra- or vIL-10-transduced pouches than LacZ-transduced and virus-free controls. Both anti-inflammatory cytokine gene transfers significantly reduced the mRNA expression of M-CSF (70-90%) and RANK (>65%) in comparison with LacZ- and virus-free controls. Histological examination showed that hIL-1Ra or vIL-10 gene transfer dramatically abolished UHMWPE-induced inflammatory cellular infiltration and bone pit erosion compared to LacZ-transduced and virus-free controls. Histochemical staining revealed significantly fewer osteoclast-like cells in samples treated with IL-1Ra or vIL-10 gene transfer. In addition, bone collagen content was markedly preserved in the groups with anti-inflammatory cytokine gene transfers compared with the other two groups. Overall, retrovirus-mediated hIL-1Ra or vIL-10 gene transfer effectively protected against UHMWPE-particle-induced bone resorption, probably due to the inhibition of IL-1/TNF-induced M-CSF production and the consequent osteoclast recruitment and maturation.

Animals↗

PubMed2003

Cervical lymphadenitis caused by Candida albicans.

Cervical lymphadenitis caused by Candida albicans developed in an 8-year-old Chinese child. There was no evidence of disseminated infection. The infection apparently confined to a lymph node was interpreted as a stage of fungal invasion. The child showed lymphopenia with a proportionate decrease in T-helper and T-suppressor cells. The child was successfully treated intravenously with fluconazole.

Antifungal Agents↗

PubMed2003

Effects of antioxidative agents on apoptosis induced by ischaemia-reperfusion in rat intestinal mucosa.

BACKGROUND AND AIM: We have previously demonstrated that ischaemia-reperfusion induces apoptosis in the intestinal mucosa. To evaluate that reactive oxygen species enhanced intestinal apoptosis after ischaemia-reperfusion, we examined whether antioxidants reduced apoptosis. METHODS: Rats were infused through a duodenal tube with antioxidative agents, glutathione, rebamipide and dymethylsulfoxide during 2 h before an ischaemic insult. The superior mesenteric artery was occluded for 60 min, followed by 60 min reperfusion. Apoptosis was evaluated by percentage fragmented DNA (fragmented DNA/total DNA) and immunochemical staining. RESULTS: Increase in apoptosis in the intestinal mucosa after ischaemia-reperfusion was attenuated by intraduodenal infusion of antioxidative agents, but was not completely abolished. CONCLUSION: Scavenging effects of the antioxidative agents attenuated increases in intestinal apoptosis, indicating that oxidative stress after ischaemia-reperfusion plays an important role in induction of apoptosis in the intestinal mucosa.

Alanine↗

PubMed2003

IFNgamma deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor Vbeta6 and Vbeta8 in arthritic joints.

BACKGROUND: Transgenic deficiency in interferon gamma (IFNgamma) or IFNgamma receptor makes resistant strains of mice bearing H-2(b) or H-2(d) susceptible to collagen induced arthritis (CIA). OBJECTIVE: To determine whether the escape from regulation of disease susceptibility at the major histocompatibility complex level involves a new use of autoimmune T cells expressing T cell receptor (TCR) Vbeta that vary from the cell populations previously identified within arthritic joints. METHODS: Arthritis was induced by a standard protocol with type II bovine collagen (CII) in complete Freund's adjuvant. Clinical features, histopathology, immunological responses, and TCR profile in arthritic joints in IFNgamma knockout C57BL/6 (B6.IFNgamma KO) mice (H-2(b)) were compared directly with those in DBA/1 mice (H-2(q)). RESULTS: 60-80% of B6.IFNgamma KO mice developed a progressive arthritis with a similar clinical course to classical CIA in DBA/1 mice. The affected joints in B6.IFNgamma KO mice had an erosive form of arthritis with similar features to joint disease in DBA/1 mice. B6.IFNgamma KO mice produced significantly higher levels of IgG2b and IgG1 autoantibodies to murine CII and showed increased proliferative response to CII compared with B6 mice. Comparable levels of interleukin 1beta and tumour necrosis factor alpha expression were detected in arthritic joints from beta6.IFNgamma KO and DBA/1 mice. B6.IFNgammaKO mice used predominantly TCR Vbeta6 and Vbeta8 in arthritic joints. This TCR Vbeta profile is similar to that found in DBA/1 mice with CIA. CONCLUSIONS: C57BL/6 mice deficient in IFNgamma production can develop arthritis that resembles classical CIA. These data suggest that IFNgamma is a key factor mediating susceptibility to CIA.

Animals↗

PubMed2003

TNF receptor gene therapy results in suppression of IgG2a anticollagen antibody in collagen induced arthritis.

BACKGROUND: Therapeutic strategies to block tumour necrosis factor alpha (TNFalpha) activity in experimental autoimmune arthritis models and rheumatoid arthritis (RA) have proved highly successful, and provide sustained beneficial effects. OBJECTIVE: To examine whether TNFalpha inhibition has immunological activity beyond the reduction of inflammation in collagen induced arthritis (CIA), an established experimental model of RA. METHODS: Arthritic DBA/1 mice received single periarticular injections of retroviral constructs encoding human TNF receptor (TNF-R) into the affected arthritic paw, at the onset of arthritis. Severity of arthritis, antibodies to collagen type II (CII), and extent of pathological joint damage of arthritic paws were compared between TNF-R and media treated (control) animals 3, 7, 14, 21, and 49 days after disease onset. RESULTS: Severity of CIA was significantly decreased in TNF-R treated animals compared with controls, 14-34 days after disease onset. Joint destruction was reduced in TNF-R injected joints and in the uninjected contralateral and ipsilateral paws of TNF-R treated animals. Seven days after disease onset, TNF-R treated mice had lower levels of inflammatory Th1 driven IgG2a antibodies to CII (p<0.05) than controls. This altered the anticollagen IgG2a:IgG1 ratio towards Th2 driven IgG1. CONCLUSIONS: Local TNF-R gene therapy in CIA appears to have systemic effects on the anti-CII antibodies. The overall influence of TNF-R gene therapy is that it inhibits the progression of CIA mainly by suppressing the inflammatory Th1 response rather than by stimulating a Th2 response. Therefore, periarticular TNF-R gene therapy may have excellent therapeutic potential in RA.

Animals↗

PubMed2003

Specific immunotherapy of experimental myasthenia by genetically engineered APCs: the "guided missile" strategy.

Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell-dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR-specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen-presenting cells (APCs) to "guided missiles" that target AChR-specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen-specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a "warhead" of Fas ligand (FasL) to eliminate the activated AChR-specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR-specific T cells by the Fas/FasL pathway, while sparing T cells of other specificities.

Animals↗

PubMed2003

Zinc accumulation in N-methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered expression of ZnT-1 and metallothionein.

Zinc is essential for cell proliferation. Several human studies have shown that in breast cancer tissues, zinc concentration expressed on a per tissue weight basis is higher than that in normal breast tissues. However, the mechanisms involved are unknown. N-methyl-N-nitrosourea (MNU)-induced rat mammary tumorigenesis is one of the most widely used rodent mammary tumorigenesis models for studying human breast cancer due to their similarities in hormone dependency, pathogenesis, histological classification, and immunocytochemical markers. This study was to establish if there was an accumulation of zinc in MNU-induced rat mammary tumors and, if there was, to explore the possible mechanisms involved. Sprague-Dawley rats were sham-treated or MNU-treated (50 mg/kg; n = 12) for 100 days. In MNU-induced mammary tumors (mammary tumors), zinc concentration expressed on a per dry weight basis was 12 times of that in normal mammary glands. Moreover, the mRNA level of ZnT-1 (a transporter involved in zinc efflux) in mammary tumors was reduced by 55% as compared with that in normal mammary glands. The mRNA level of Nramp2 (a divalent cation importer) and ZnT-4 (another transporter involved in zinc efflux) was unaffected by MNU-induced mammary tumorigenesis. The mRNA and protein levels of metallothionein (a putative zinc storage protein) in mammary tumors were 1.3 and 3.5 times of that in normal mammary glands, respectively. Collectively, our observations showed that zinc is accumulated in MNU-induced rat mammary tumors and this accumulation is accompanied by an altered expression of ZnT-1 and metallothionein, suggesting that zinc homeostasis might be altered in MNU-induced rat mammary tumorigenesis. Because zinc is essential to cell proliferation and cell proliferation is increased in mammary tumors, zinc accumulation is likely a part of an integrated effort to ensure sufficient zinc supply to sustain tumor growth.

Animals↗