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11.
Craig D. Wegner Bobbie Ann Mount Christine M. Colvis 《CTS Clinical and Translational Science》2022,15(7):1581
Launched in May 2012 as part of the New Therapeutic Uses program, the National Center for Advancing Translational Sciences (NCATS)’ National Institutes of Health (NIH)‐Industry Partnerships initiative fostered collaboration between pharmaceutical companies and the biomedical research community to advance therapeutic development. Over the 10‐year life of the initiative, the industry partners included: AstraZeneca; AbbVie (formerly Abbott); Bristol‐Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Janssen Pharmaceutical Research & Development, L.L.C.; Pfizer; Sanofi; and Mereo (out licensed assets). The initiative provided researchers at academic medical centers with a rare opportunity to propose clinical trials to test ideas for new therapeutic uses for a selection of clinic‐ready and often previously proprietary experimental pharmaceutical assets that were provided by industry partners. Here, we describe the process by which collaborations between pharmaceutical companies with viable experimental assets and academic researchers with ideas for new uses of those assets were established; and how NCATS/NIH funding supported not only phase I and II clinical trials as well as any nonclinical studies needed before testing in a new patient population, it also provided an opportunity for testing innovative outcome measures for proof‐of‐concept trials. Although the program did not demonstrate improved success rates for phase II clinical trials, this collaboration model leverages the strengths of each party and with a focus toward evaluating an innovative outcome measure, could be used to reduce patient burden and trial costs, and improve patient engagement. 相似文献
12.
Caldwell LL Smith EA Collins LM Graham JW Lai M Wegner L Vergnani T Matthews C Jacobs J 《Child & youth care forum》2012,41(2):119-136
Background
HealthWise South Africa: Life Skills for Adolescents (HW) is an evidence-based substance use and sexual risk prevention program that emphasizes the positive use of leisure time. Since 2000, this program has evolved from pilot testing through an efficacy trial involving over 7,000 youth in the Cape Town area. Beginning in 2011, through 2015, we are undertaking a new study that expands HW to all schools in the Metro South Education District. 相似文献13.
Lundberg K Kinloch A Fisher BA Wegner N Wait R Charles P Mikuls TR Venables PJ 《Arthritis and rheumatism》2008,58(10):3009-3019
OBJECTIVE: To map the antibody response to human citrullinated alpha-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase. METHODS: Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated alpha-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting. RESULTS: An immunodominant peptide, citrullinated alpha-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37-62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated alpha-enolase peptide 1 correlated with the levels of antibodies to the bacterial peptide (r2=0.803, P<0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase. CONCLUSION: We have identified an immunodominant epitope in citrullinated alpha-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA. 相似文献
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Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: implication for therapy and new epidemiological associations. 总被引:12,自引:0,他引:12
D Lucey M J Dolan C W Moss M Garcia D G Hollis S Wegner G Morgan R Almeida D Leong K S Greisen 《Clinical infectious diseases》1992,14(3):683-688
Two previously healthy, immunocompetent men had persistent Rochalimaea henselae bacteremia with clinical relapses after courses of antibiotics to which the isolates were ultimately demonstrated susceptible in vitro. Both had sustained tick bites prior to their illnesses, thus demonstrating an association not previously identified, although suspected. The first patient had relapsing fever, constitutional symptoms, and an episode of aseptic meningitis despite therapy with amoxicillin, then with doxycycline, and then with ceftriaxone. Thereafter, he spontaneously became asymptomatic during a span of 2 months of persistent bacteremia. Finally, after 2 weeks of therapy with ceftriaxone plus gentamicin, followed by 4 weeks of therapy with oral ciprofloxacin, his bacteremia was cured. The second man had relapsing fever and constitutional symptoms after courses of tetracycline, then of chloramphenicol, and then of doxycycline. He became permanently asymptomatic after serial 2-week courses of chloramphenicol and erythromycin. The greater efficacy of lysis-centrifugation blood cultures in the recovery of R. henselae was noted. 相似文献
16.
C. Mueller-Eckhardt G. Mueller-Eckhardt W. Kayser R.M. Voss J. Wegner and E. Küenzlen 《British journal of haematology》1982,52(1):49-58
S ummary . Platelet-associated IgG (PAIgG), platelet mean life span (MLS), and platelet sequestration sites were studied in 69 patients with immune (ITP) and presumed nonimmune thrombocytopenias (NTP). A shortened MLS was associated with elevated PAIgG (N=46), and with normal PAIgG (N=15), Four patients had a normal MLS, but elevated PAIgG, four patients were normal for both parameters. The highest PAIgG values occurred in ITP patients with a very short MLS. Nine NTP patients had also elevated PAIgG, but a normal or slightly shortened MLS. There was a significant double log correlation between PAIgG and MLS for ITP, but not for NTP patients. Judged from the coefficient of determination, only 10% of PAIgG were directly related to a shortened MLS.
70% of patients (N= 63) had exclusively splenic and 30% hepatosplenic sequestration. PAIgG was elevated in 29/44 patients with splenic (66%) and in 16/19 patients with hepatosplenic sequestration (84%). In ITP, PAIgG-positive cases were observed in 69% of splenic v 82% of hepatosplenic sequestration, while in NTP the corresponding figures were 6/11 and 2/2. No significant correlation between PAIgG and either sequestration type was demonstrable.
We conclude that in immunologically mediated thrombocytopenia only a small portion of PAIgG accounts for a decreased MLS, and that the concentration of PAIgG per se does not determine the platelet sequestration type. 相似文献
70% of patients (N= 63) had exclusively splenic and 30% hepatosplenic sequestration. PAIgG was elevated in 29/44 patients with splenic (66%) and in 16/19 patients with hepatosplenic sequestration (84%). In ITP, PAIgG-positive cases were observed in 69% of splenic v 82% of hepatosplenic sequestration, while in NTP the corresponding figures were 6/11 and 2/2. No significant correlation between PAIgG and either sequestration type was demonstrable.
We conclude that in immunologically mediated thrombocytopenia only a small portion of PAIgG accounts for a decreased MLS, and that the concentration of PAIgG per se does not determine the platelet sequestration type. 相似文献
17.
Bodo B. Beck Jennifer B. Phillips Malte P. Bartram Jeremy Wegner Michaela Thoenes Andrea Pannes Josephina Sampson Raoul Heller Heike Göbel Friederike Koerber Antje Neugebauer Andrea Hedergott Gudrun Nürnberg Peter Nürnberg Holger Thiele Janine Altmüller Mohammad R. Toliat Simon Staubach Kym M. Boycott Enza Maria Valente Andreas R. Janecke Tobias Eisenberger Carsten Bergmann Lars Tebbe Yang Wang Yundong Wu Andrew M. Fry Monte Westerfield Uwe Wolfrum Hanno J. Bolz 《Human mutation》2014,35(10):1153-1162
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD. 相似文献
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