Biomedical subjects

J Liu

Publications and source records attributed to J Liu.

At least 631 records · Page 35Linked to original sources

PubMed2000

Functional CB1 cannabinoid receptors in human vascular endothelial cells.

Cannabinoid CB1 receptor mRNA was detected using reverse transcription-polymerase chain reaction (RT-PCR) in endothelial cells from human aorta and hepatic artery and in the ECV304 cell line derived from human umbilical vein endothelial cells. CB1 receptor-binding sites were detected by the high-affinity antagonist radioligand [(125)I]AM-251. In ECV304 cells, both the highly potent synthetic cannabinoid agonist HU-210 and the endogenous ligand anandamide induce activation of mitogen-activated protein (MAP) kinase, and the effect of HU-210 was completely blocked, whereas the effect of anandamide was partially inhibited by SR141716A, a selective CB1 receptor antagonist. Transfection of ECV304 cells with CB1 receptor antisense, but not sense, oligonucleotides caused the same pattern of inhibition as SR141716A. This provides more definitive evidence for the involvement of CB1 receptors in MAP kinase activation and suggests that anandamide may also activate MAP kinase via an additional, CB1 receptor-independent, SR141716A-resistant mechanism. The MAP kinase activation by anandamide in ECV304 cells requires genistein-sensitive tyrosine kinases and protein kinase C (PKC), and anandamide also activates p38 kinase and c-Jun kinase. These findings indicate that CB1 receptors located in human vascular endothelium are functionally coupled to the MAP kinase cascade. Activation of protein kinase cascades by anandamide may be involved in the modulation of endothelial cell growth and proliferation.

Base Sequence↗

PubMed2000

Cell wall structure of a mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids.

A mutant strain of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids was recently isolated (Liu, J., and Nikaido, H. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 4011-4016). This mutant failed to synthesize full-length mycolic acids and accumulated a series of long chain beta-hydroxymeromycolates. In this work, we provide a detailed characterization of the localization of meromycolates and of the cell wall structure of the mutant. Thin layer chromatography showed that the insoluble cell wall matrix remaining after extraction with chloroform/methanol and SDS still contained a large portion of the total meromycolates. Matrix-assisted laser desorption/ionization and electrospray ionization mass spectroscopy analysis of fragments arising from Smith degradation of the insoluble cell wall matrix revealed that the meromycolates were covalently attached to arabinogalactan at the 5-OH positions of the terminal arabinofuranosyl residues. The arabinogalactan appeared to be normal in the mutant strain, as analyzed by NMR. Analysis of organic phase lipids showed that the mutant cell wall contained some of the extractable lipids but lacked glycopeptidolipids and lipooligosaccharides. Differential scanning calorimetry of the mutant cell wall failed to show the large cooperative thermal transitions typical of intact mycobacterial cell walls. Transmission electron microscopy showed that the mutant cell wall had an abnormal ultrastructure (without the electron-transparent zone associated with the asymmetric mycolate lipid layer). Taken together, these results demonstrate the importance of mycolic acids for the structural and functional integrity of the mycobacterial cell wall. The lack of highly organized lipid domains in the mutant cell wall explains the drug-sensitive and temperature-sensitive phenotypes of the mutant.

Calorimetry, Differential Scanning↗

PubMed2000

Combined LOH/CGH analysis proves the existence of interstitial 3p deletions in renal cell carcinoma.

We have recently developed an allele titration assay (ATA) to assess the sensitivity and influence of normal cell admixture in loss of heterozygosity (LOH) studies based on CA-repeat. The assay showed that these studies are biased by the size-dependent differential sensitivity of allele detection. Based on these data, we have set up new criteria for evaluation of LOH. By combining these new rules with comparative genome hybridization (CGH) we have shown the presence of interstitial deletions in renal cell carcinoma (RCC) biopsies and cell lines. At least three out of 11 analysed RCC cell lines and three out of 37 biopsies contain interstitial deletions on chromosome 3. Our study suggests the presence of several regions on human chromosome 3 that might contribute to tumor development by their loss: (i) 3p25-p26, around the VHL gene (D3S1317); (ii) 3p21. 3-p22 (between D3S1260 and D3S1611); (iii) 3p21.2 (around D3S1235 and D3S1289); (iv) 3p13-p14 (around D3S1312 and D3S1285). For the first time, AP20 region (3p21.3-p22) was carefully tested for LOH in RCC. It was found that the AP20 region is the most frequently affected area. Our data also suggest that another tumor suppressor gene is located near the VHL gene in 3p25-p26.

Alleles↗

PubMed2000

Ring constrained analogues of beta-alanine-containing GPIIb/IIIa receptor antagonists.

A series of ring constrained analogues of the GPIIb/IIIa receptor antagonist XR299 (1) was investigated as potential inhibitors of glycoprotein IIb/IIIa, a platelet receptor that plays a key role in platelet aggregation and platelet adhesion. Ring size was found to have a large effect on in vitro potency. Selected compounds showed good in vitro activity, a preference for binding to activated platelets, and modest duration of action when dosed i.v. as a racemate in a canine model.

Humans↗

PubMed2000

Loss of FBP function arrests cellular proliferation and extinguishes c-myc expression.

The c-myc regulatory region includes binding sites for a large set of transcription factors. The present studies demonstrate that in the absence of FBP [far upstream element (FUSE)-binding protein], which binds to the single-stranded FUSE, the remainder of the set fails to sustain endogenous c-myc expression. A dominant-negative FBP DNA-binding domain lacking effector activity or an antisense FBP RNA, expressed via replication-defective adenovirus vectors, arrested cellular proliferation and extinguished native c-myc transcription from the P1 and P2 promoters. The dominant-negative FBP initially augmented the single-stranded character of FUSE; however, once c-myc expression was abolished, melting at FUSE could no longer be supported. In contrast, with antisense FBP RNA, the single-stranded character of FUSE decreased monotonically as the transcription of endogenous c-myc declined. Because transcription is the major source of super-coiling in vivo, we propose that by binding torsionally strained DNA, FBP measures promoter activity directly. We also show that FUSE is predicted to behave as a torsion-regulated switch poised to regulate c-myc and to confer a higher order regulation on a large repertoire of factors.

Animals↗

PubMed2000

Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein.

Mammalian RAD51 protein plays essential roles in DNA homologous recombination, DNA repair and cell proliferation. RAD51 activities are regulated by its associated proteins. It was previously reported that a ubiquitin-like protein, UBL1, associates with RAD51 in the yeast two-hybrid system. One function of UBL1 is to covalently conjugate with target proteins and thus modify their function. In the present study we found that non-conjugated UBL1 forms a complex with RAD51 and RAD52 proteins in human cells. Overexpression of UBL1 down-regulates DNA double-strand break-induced homologous recombination in CHO cells and reduces cellular resistance to ionizing radiation in HT1080 cells. With or without overexpressed UBL1, most homologous recombination products arise by gene conversion. However, overexpression of UBL1 reduces the fraction of bidirectional gene conversion tracts. Overexpression of a mutant UBL1 that is incapable of being conjugated retains the ability to inhibit homologous recombination. These results suggest a regulatory role for UBL1 in homologous recombination.

Animals↗

PubMed2000

Cyclic peptide formation catalyzed by an antibody ligase.

Cyclic hexapeptides represent a class of compounds with important, diverse biological activities. We report herein that the antibody 16G3 catalyzes the cyclization of d-Trp-Gly-Pal-Pro-Gly-Phe small middle dotp-nitrophenyl ester (8a) to give c-(d-Trp-Gly-Pal-Pro-Gly-l-Phe) (11a). The antibody does not, however, catalyze either epimerization or hydrolysis. The resulting rate enhancement of the cyclization by 16G3 (22-fold) was sufficient to form the desired product in greater than 90% yield. In absolute rate terms, the turnover of 16G3 is estimated to be 2 min(-1). The background rate of epimerization of 8a was reduced from 10 to 1% and hydrolysis from 50 to 4% in the presence of 16G3. As expected, the catalytic effects of 16G3 were blocked by the addition of an amount of the hapten equal to twice the antibody concentration. We also synthesized three diastereomers of 8a: the d-Trp(1)-d-Phe(6) (8b), l-Trp(1)-l-Phe(6) (8c), and l-Trp(1)-d-Phe(6) (8d) hexapeptides as well as d-Trp'-l-Trp(6) (12) and d-Phe'-l-Phe(6) (13). As expected, the rate enhancement by 16G3 was greatest for 8a, because the stereochemistry of Trp(1) and Phe(6) matches that of the corresponding residues on the hapten used to induce the biosynthesis of 16G3. A model of the variable domain of 16G3 was generated from the primary sequence using the antibody structural database to guide the model construction. The resulting model provided support for some previously proposed interpretations of the kinetic data, while providing valuable new insights for others.

Antibodies, Catalytic↗

PubMed2000

Novel ligands lacking a positive charge for the delta- and mu-opioid receptors.

Recently we reported using minilibraries to replace Lys(9) [somatostatin (SRIF) numbering] of the potent somatostatin agonist L-363,301 (c[-Pro-Phe-D-Trp-Lys-Thr-Phe-]) to generate the potent neurokinin receptor (NK-1) antagonist c[-Pro-Phe-D-Trp-p-F-Phe-Thr-Phe-]. This novel cyclic hexapeptide did not bind the SRIF receptor. Thus, a single mutation converted L-363,301, a SRIF agonist with potency ca. 2-8 times the potency of SRIF in laboratory animals,(24) into a selective NK-1 receptor antagonist with an IC(50) of 2 nM in vitro. During the screening of the same libraries for ligands of the delta-opioid receptor, we identified four compounds (1-4) which represent a new class of delta-opioid antagonists, some of which were also NK-1 receptor antagonists. The most potent delta-opioid antagonist, c[-Pro-1-Nal-D-Trp-Tyr-Thr-Phe-] (2), showed a K(e) value of 128 nM in the mouse vas deferens assay and a delta-receptor binding affinity constant of 152 nM in the rat brain membrane binding assay. These results are of interest because they represent a novel class of delta-opioid antagonists and, like two previously reported delta-opioid antagonists, they lack a positive charge. To examine further the requirement for a positive charge in the delta-opioid ligands, we prepared two analogues of the beta-casomorphin-derived mixed mu-agonist/delta-antagonist, H-Dmt-c[-D-Orn-2-Nal-D-Pro-Gly-] (7), in which we eliminated the positive charge either through formylation of the primary amino group (5) or by the deletion of this N-terminal amino group (6). These latter compounds proved to be delta-opioid antagonists with K(e) values in the 16-120 nM range, as well as fairly potent mu-opioid antagonists (K(e) approximately 200 nM). These six compounds provide the most convincing evidence to date that there is no requirement for a positive charge in mu- and delta-opioid receptor antagonists. In addition, cyclic hexapeptide 4 lacks a phenolic hydroxyl group. Taken together, these data suggest that the prevailing assumptions about delta- and mu-opioid receptor binding need revision and that the receptors for these opioid ligands have much in common with the NK-1 and somatostatin receptors.

Animals↗

PubMed2000

Helical interactions in the HIV-1 gp41 core reveal structural basis for the inhibitory activity of gp41 peptides.

The HIV-1 gp41 envelope protein mediates membrane fusion that leads to virus entry into the cell. The core structure of fusion-active gp41 is a six-helix bundle in which an N-terminal three-stranded coiled coil is surrounded by a sheath of antiparallel C-terminal helices. A conserved glutamine (Gln 652) buried in this helical interface replaced by leucine increases HIV-1 infectivity. To define the basis for this enhanced membrane fusion activity, we investigate the role of the Gln 652 to Leu substitution on the conformation, stability, and biological activity of the N34(L6)C28 model of the gp41 ectodomain core. The 2.0 A resolution crystal structure of the mutant molecule shows that the Leu 652 side chains make prominent contacts with hydrophobic grooves on the surface of the central coiled coil. The Gln 652 to Leu mutation leads to a marginal stabilization of the six-helix bundle by -0.8 kcal/mol, evaluated from thermal unfolding experiments. Strikingly, the mutant N34(L6)C28 peptide is a potent inhibitor of HIV-1 infection, with 10-fold greater activity than the wild-type molecule. This inhibitory potency can be traced to the corresponding C-terminal mutant peptide that likely has greater potential to interact with the coiled-coil trimer. These results provide strong evidence that conserved interhelical packing interactions in the gp41 core are important determinants of HIV-1 entry and its inhibition. These interactions also offer a test-bed for the development of more potent analogues of gp41 peptide inhibitors.

Amino Acid Sequence↗

PubMed2000

Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter.

The cytokine oncostatin M (OM) activates human low density lipoprotein receptor (LDLR) gene transcription through a sterol-independent mechanism. Previous studies conducted in our laboratory have narrowed the OM-responsive element to promoter region -52 to +13, which contains the repeat 3 and two TATA-like sequences. We now identify LDLR promoter region -17 to -1 as a sterol-independent regulatory element (SIRE) that is critically involved in OM-, transcription factor CCAAT/enhancer-binding protein (C/EBP)-, and second messenger cAMP-mediated activation of LDLR transcription. The SIRE sequence overlaps the previously described TATA-like element and consists of an active C/EBP-binding site (-17 to -9) and a functional cAMP-responsive element (CRE) (-8 to -1). We demonstrate that (a) mutations within either the C/EBP or CRE site have no impact on basal or cholesterol-mediated repression of LDLR transcription, but they completely abolish OM-mediated activation of LDLR transcription; (b) replacing the repeat 3 sequence that contains the Sp1-binding site with a yeast transcription factor GAL4-binding site in the LDLR promoter construct does not affect OM inducibility, thereby demonstrating that OM induction is mediated through the SIRE sequence in conjunction with a strong activator bound to the repeat 3 sequence; (c) electrophoretic mobility shift and supershift assays confirm the specific binding of transcription factors C/EBP and cAMP-responsive element-binding protein to the SIRE; (d) cotransfection of a human C/EBPbeta expression vector (pEF-NFIL6) with the LDLR promoter construct pLDLR234 increases LDLR promoter activity; and (e) OM and dibutyryl cAMP synergistically activate LDLR transcription through this regulatory element. This study identifies, for the first time, a cis-acting regulatory element in the LDLR promoter that is responsible for sterol-independent regulation of LDLR transcription.

Base Sequence↗

PubMed2000

Ly49I NK cell receptor transgene inhibition of rejection of H2b mouse bone marrow transplants.

The Ly49 family of genes encode NK cell receptors that bind class I MHC Ags and transmit negative signals if the cytoplasmic domains have immunoregulatory tyrosine-based inhibitory motifs (ITIMs). 5E6 mAbs recognize Ly49C and Ly49I receptors and depletion of 5E6+ NK cells prevents rejection of allogeneic or parental-strain H2d bone marrow cell (BMC) grafts. To determine the function of the Ly49I gene in the rejection of BMC grafts, we transfected fertilized eggs of FVB mice with a vector containing DNA for B6 strain Ly49I (Ly49IB6). Ly49IB6 is ITIM+ and is recognized by 5E6 as well as Ly49I-specific 8H7 mAbs. Normal FVB H2q mice reject H2b but not H2d BMC allografts, and the rejection of H2b BMC was inhibited partially by anti-NK1.1 and completely by anti-asialo GM1, but not by anti-CD8, Abs. In FVB mice, NK1.1 is expressed on only 60% NK cells. FVB. Ly49IB6 hosts failed to reject H2d or H2b BMC, but did reject class I-deficient TAP-1-/- BMC, indicating that NK cells were functional. Nondepleting doses of anti-Ly49I Abs reversed the acceptance of H2b BMC by FVB.Ly49IB6 mice. FVB.Ly49IB6+/- mice were crossed and back-crossed with 129 mice-H2b, 5E6-, poor responders to H2d BMC grafts. While transgene-negative H2b/q F1 or first-generation back-crossed mice rejected H2b marrow grafts (hybrid resistance), transgene-positive mice did not. Thus B6 strain Ly49I receptors transmit inhibitory signals from H2b MHC class I molecules. Moreover, Ly49IB6 has no positive influence on the rejection of H2d allografts.

Animals↗

PubMed2000

Mutations of the serine phosphorylated in the protein phosphatase-1-binding motif in the skeletal muscle glycogen-targeting subunit.

Cellular functions of protein phosphatase-1 (PP1) are determined by regulatory subunits that contain the consensus PP1-binding motif, RVXF. This motif was first identified as the site of phosphorylation by cAMP-dependent protein kinase (PKA) in a skeletal muscle glycogen-targeting subunit (G(M)). We reported previously that a recombinant fusion protein of glutathione S-transferase (GST) and the N-terminal domain of G(M) [GST-G(M)-(1-240)] bound PP1 in a pull down assay, and phosphorylation by PKA prevented PP1 binding. Here we report that substitution of either Ala or Val for Ser-67 in the RVS(67)F motif in GST-G(M)-(1-240) essentially eliminated PP1 binding. This was unexpected because other glycogen-targeting subunits have a Val residue at the position corresponding to Ser-67. In contrast, a mutation of Ser-67 to Thr (S67T) in GST-G(M)(1-240) gave a protein that bound PP1 the same as wild type and was unaffected by PKA phosphorylation. Full length G(M) tagged with the epitope sequence DYKDDDDK (FLAG) expressed in COS7 cells bound PP1 that was recovered by co-immunoprecipitation, but this association was prevented by treatment of the cells with forskolin. By comparison, PP1 binding with FLAG-G(M)(S67T) was not disrupted by forskolin treatment. Neither FLAG-G(M)(S67A) nor FLAG-G(M)(S67V) formed stable complexes with PP1 in COS7 cells. These results emphasise the unique contribution of Ser-67 in PP1 binding to G(M). The constitutive PP1-binding activity shown by G(M)(S67T) opens the way for studying the role of G(M) multisite phosphorylation in hormonal control of glycogen metabolism.

Amino Acid Motifs↗

PubMed2000

The selectivity of the occipitotemporal M170 for faces.

Evidence from fMRI, ERPs and intracranial recordings suggests the existence of face-specific mechanisms in the primate occipitotemporal cortex. The present study used a 64-channel MEG system to monitor neural activity while normal subjects viewed a sequence of grayscale photographs of a variety of unfamiliar faces and non-face stimuli. In 14 of 15 subjects, face stimuli evoked a larger response than non-face stimuli at a latency of 160 ms after stimulus onset at bilateral occipitotemporal sensors. Inverted face stimuli elicited responses that were no different in amplitude but 13 ms later in latency than upright faces. The profile of this M170 response across stimulus conditions is largely consistent with prior results using scalp and subdural ERPs.

Acoustic Stimulation↗

PubMed2000

Anti-sense oligonucleotide of p21(waf1/cip1) prevents interleukin 4-mediated elevation of p27(kip1) in low grade astrocytoma cells.

Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.

Astrocytoma↗

PubMed2000

[Effects of microwave radiation on lipid peroxidation and the content of neurotransmitters in mice].

Male LACA mice were exposed to 900 MHz microwaves at the power densities of 0,1,2 and 5 mW/cm2. The resulting specific absorption rates(SARs) were 0, 0.22, 0.44 and 1.10 W/kg respectively. Animals were exposed at the dosage of 1 hour a day for 35 days. The results showed that the activity of glutathione peroxidase (GSH-Px) increased and the concentration of malondialdehyde (MDA) decreased in blood, and the concentration of noradrenaline (NE) increased in brains in the microwave exposed groups at 1 mW/cm2 compared with the sham-exposed group. But no significant changes were found in the microwave exposed groups at 2 and 5 mW/cm2. No significant changes of the concentrations of 5-hydroxytryptamine(5-HT), 5-hydroxyindole acetic acid(5-HIAA) and dopamie(DA) in brains were found.

Animals↗

PubMed2000

Changes of free fatty acids and acyl-CoAs in rat brain hippocampal slice with tetraethylammonium-induced long-term potentiation.

We investigated the role of acyl-CoAs during induction and maintenance of long-term potentiation in rat brain hippocampus. Changes of acyl-CoA and free fatty acids (FFA) in hippocampus were measured during tetraethylammonium (TEA)-induced LTP. Results indicated that concentrations of acyl-CoAs and FFAs in slices were changed during TEA-induced LTP and 16:0-CoA and 18:0-CoA were increased in the early phase of stimulation, whereas free fatty acids in this phase were rather decreased. The increase of 20:4-CoA was delayed more than saturated acyl-CoAs. To examine the role of acyl-CoA in LTP of evoked transmitter release, we measured the glutamate release from hippocampal slice with the addition of acyl-CoA using glutamate electrode. Acyl-CoA (16:0-, 18:1-, and 20:4-CoA) could enhance glutamate release in hippocampal slice. It is suggested that saturated acyl-CoAs may play a functional role in the early phase of LTP.

Acyl Coenzyme A↗

PubMed2000

Transforming growth factor beta2, but not beta1 and beta3, is critical for early rat lung branching.

Mesenchymal-epithelial tissue interactions are critical for lung branching morphogenesis, and polypeptide growth factors are likely involved in these tissue interactions. Transforming growth factorbetas (TGFbetas) have been implicated in lung development, but their involvement in early lung branching morphogenesis is unclear. In the present study, we investigated the role of the three mammalian TGFbeta subtypes (beta1, beta2, and beta3) and their receptors (type III (TbetaR-III), type II (TbetaR-II), and two types I (TbetaR-I), ALK-1 and ALK-5) in early rat lung organogenesis by using an embryonic rat lung explant culture. Transcripts and proteins for all three TGFbetas and their receptors were detected during the embryonic period of fetal rat lung development. Inhibition of TGFbeta2, but not beta1 and beta3, with antisense oligonucleotides and neutralizing antibodies resulted in significant inhibition of early lung branching in culture. Addition of minute amounts (</=1 ng/ml) of exogenous TGFbeta2, but not beta1 and beta3, restored the branching of TGFbeta2 antisense-treated explants. Higher concentrations of TGFbeta2 were inhibitory. BrdU labeling of lung explants was not altered by antisense TGFbeta2 treatment, but low concentrations of TGFbeta2 increased thymidine uptake by isolated epithelial cells. Fibronectin and metallogelatinase activities of embryonic lung cells were not affected by any TGFbeta isoform but TGFbeta2 specifically decreased mesenchymal hyaluronan synthesis. Antisense inhibition of ALK-5 and TbetaR-II showed a similar reduction in early lung branching as observed with antisense TGFbeta2. Incubation of lung explants with soluble TbetaR-II receptors also abrogated lung branching. ALK-1 antisense treatment did not affect early branching. Administration of neither activin A, which can act via ALK-1, nor follistatin, the natural inhibitor of activin, to the explants cultures had any significant effect on lung branching. Antisense inhibition of the activin receptor-II (Act-RII) also did not affect lung branching. These results are consistent with TGFbeta2, but not beta1 and beta3, regulating pattern formation during early rat lung organogenesis. This TGFbeta signaling in rat lung branching in vitro appears to be predominantly mediated via the TbetaR-I(ALK-5)/TbetaR-II heteromeric complex.

Activin Receptors, Type I↗

PubMed2000

Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects.

Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.

Acupuncture Therapy↗