Unanticipated Insights into Biomedicine from the Study of Acupuncture.

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain.

A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis.

Manual and electrical needle stimulation in acupuncture research: pitfalls and challenges of heterogeneity.

In the field of acupuncture research there is an implicit yet unexplored assumption that the evidence on manual and electrical stimulation techniques, derived from basic science studies, clinical trials, systematic reviews, and meta-analyses, is generally interchangeable. Such interchangeability would justify a bidirectional approach to acupuncture research, where basic science studies and clinical trials each inform the other. This article examines the validity of this fundamental assumption by critically reviewing the literature and comparing manual to electrical acupuncture in basic science studies, clinical trials, and meta-analyses.

AcuTrials®: an online database of randomized controlled trials and systematic reviews of acupuncture.

Background: The growing quantity of Complementary and Alternative Medicine literature requires databases enabled with increasingly powerful search capabilities. To address this need in the area of acupuncture research, a bibliographic database of randomized controlled trials (RCTs) and systematic reviews called AcuTrials® has been developed by the Oregon College of Oriental Medicine. AcuTrials® introduces a comprehensive keyword thesaurus that categorizes details of treatment protocols and research design to an extent not currently available in MEDLINE or other databases.

A prospective patient-centered data collection program at an acupuncture and oriental medicine teaching clinic.

Objective: Large-scale patient-reported outcomes research investigating the role of acupuncture and Oriental medicine (AOM) in general practice is limited, despite the growing use of AOM in the United States. This article describes the development and refinement of a prospective, patient-centered outcomes data collection program at an Oriental medicine college and presents demographic and clinical data.

Setting/location: Individualized acupuncture treatment at the Oregon College of Oriental Medicine teaching clinic in Portland, Oregon.

Paradoxes in acupuncture research: strategies for moving forward.

In November 2007, the Society for Acupuncture Research (SAR) held an international symposium to mark the 10th anniversary of the 1997 NIH Consensus Development Conference on Acupuncture. The symposium presentations revealed the considerable maturation of the field of acupuncture research, yet two provocative paradoxes emerged. First, a number of well-designed clinical trials have reported that true acupuncture is superior to usual care, but does not significantly outperform sham acupuncture, findings apparently at odds with traditional theories regarding acupuncture point specificity.

Randomized Controlled Trials of Acupuncture (1997-2007): An Assessment of Reporting Quality with a CONSORT- and STRICTA-Based Instrument.

The present study describes the development of a comprehensive quality of reporting assessment tool and its application to acupuncture RCTs from 1997-2007. This Oregon CONSORT STRICTA Instrument (OCSI) is based on the revised CONSORT guidelines as modified by the STRICTA recommendations for acupuncture trials. Each of the resulting 27 OCSI items were applied to English language prospective RCTs that compared acupuncture, using manual and/or electro-stimulation, to no treatment, a sham procedure, or usual biomedical care.

Modulation of immunogenicity and allergenicity by controlling the number of immunostimulatory oligonucleotides linked to Amb a 1.

Background: Immunostimulatory DNA sequences (ISS) are potent immunomodulators that can drive T(H)1 responses to antigens or allergens. This effect can be dramatically enhanced by direct linkage of ISS to the protein.

Objective: Evaluate the effects of the number of ISS bound to the major ragweed allergen Amb a 1 on immunogenicity and allergenicity.

Targeted inhibition of V(D)J recombination by a histone methyltransferase.

The tissue- and stage-specific assembly of antigen receptor genes by V(D)J recombination is regulated by changes in the chromatin accessibility of target gene segments. This dynamic remodeling process is coordinated by cis-acting promoters and enhancers, which function as accessibility control elements. The basic epigenetic mechanisms that activate or repress chromatin accessibility to V(D)J recombinase remain unclear.

Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy.

Background: Recent studies have demonstrated that bacterially derived immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate immune system and promote the development of T(H)1 cells. Promotion of T(H)1 immunity by means of immunotherapy in allergic patients has led to the alleviation of symptoms that result from allergen-specific T(H)2 responses.

Objective: Our purpose was to investigate whether the T(H)1-enhancing properties of ISSs could be used to alter the T(H)2-dominated immune response of allergic PBMCs in vitro.

Disulfide linkages in the in vitro refolded intermediates of recombinant human macrophage-colony-stimulating factor: analysis of the sulfhydryl alkylation of free cysteine residues by fast-atom bombardment mass spectrometry.

Fast-atom bombardment mass spectrometry was used to follow the time course of disulfide bond formation during in vitro refolding of recombinant human macrophage-colony-stimulating factor. The content of iodoacetamide-alkylated half-cystines in proteolytic peptides of trapped refolding intermediates collected at 0, 6, 17, 24, and 72 hr was determined under reducing conditions. Size-exclusion high-performance liquid chromatography analyses of the collected alkylated samples indicate that aggregated monomer proceeded through a nonaggregated monomer to an intermediate dimer and finally to the fully folded and active dimer.

Transformation of human mammary epithelial cells by oncogenic retroviruses.

We have introduced viral oncogenes into human mammary epithelial cells through the use of murine retroviruses. A continuous cell line (184A1N4) derived from benzo(a)pyrene treatment of normal breast epithelial cells was used as a recipient for the ras, mos, and T-antigen oncogenes. Each of these oncogenes enabled the 184A1N4 cells to grow in a selective medium, thus demonstrating the potential utility of these cells for oncogene detection and isolation.

Functional properties of proteins coded by three human alpha-interferon genes and a pseudogene.

We have characterized the functional properties of four highly purified recombinant human class I alpha-interferon subtypes whose biological activities have not been described previously. We selected biological and biochemical activities that may discriminate between different functions of these molecules. We found that the alpha subtypes could be discriminated only by antiviral-host range specificity and natural killer cell activation.

Biochemical and biological properties of the human N-ras p21 protein.

We characterized the normal (Gly-12) and two mutant (Asp-12 and Val-12) forms of human N-ras proteins produced by Escherichia coli. No significant differences were found between normal and mutant p21 proteins in their affinities for GTP or GDP. Examination of GTPase activities revealed significant differences between the mutant p21s: the Val-12 mutant retained 12% of wild-type GTPase activity, whereas the Asp-12 mutant retained 43%.

Inhibition of cell surface ruffling and fluid-phase pinocytosis by microinjection of anti-ras antibodies into living cells.

Fibroblasts transformed by ras oncogenes display enhanced cell surface ruffling and fluid-phase pinocytotic activities. Microinjection of antibodies that specifically bind the ras proteins into these cells results in the inhibition of these two surface activities. The possible underlying biochemical basis of the influence of the ras proteins on membrane ruffling and pinocytosis and the potential relationship of these two biological activities to membrane signal transduction are discussed.

Transient reversion of ras oncogene-induced cell transformation by antibodies specific for amino acid 12 of ras protein.

The proteins encoded by the ras oncogene are thought to trigger expression of the transformed phenotype in some types of cancer cells. In human cells, the ras protein family consists of several members including normal (proto-oncogene) and mutant (oncogene) forms. In general, the proto-oncogene forms are thought to be involved in the normal growth control of cells, while the mutant forms (which apparently result from somatic mutation of the normal ras genes) appear to be responsible, in part, for the loss of normal growth control.