October 2008 >
Research on Biology of Acupuncture has Met the Gold Standard of
Research on Biology of Acupuncture has Met the
Gold Standard of Science
Charles Shang, MD
Confirmed Predictions on Acupuncture
One corollary from the growth control
model is that acupuncture has extensive growth control effects which
have been confirmed: Acupuncture has been shown to regulate various
growth factors and growth control genes. It can induce vascular
endothelial growth factor82 and basic fibroblast growth
factor83 during brain ischemia. It also induces glial cell
line-derived neurotrophic factor84 and expression of the c-fos
proto-oncogene.85, 86 Acupuncture regulates the expression of
Bcl-2,87 Bax, fas and FasL proteins which are involved in
apoptosis signaling. Acupuncture inhibits the apoptosis of intestinal
epithelial cells in inflammatory bowel disease of rats88 and
enhances proliferation of CD8+ lymphocytes,89 reduces nerve
growth factor in polycystic ovaries,90, 91reduces IL-6
expression and proliferation of osteoclasts.92 The
neuro-humoral factors induced by acupuncture such as endorphins, nitric
oxide and serotonin also have growth-control effects.92, 98, 94
In RCTs, acupuncture has shown efficacy in treating growth control
related disorders including spinal cord injuries38 and low
sperm quality.95, 96
Growth Control System as Foundation of
A growth control system originates from a
network of organizers.97 In embryogenesis, the development of
organizers precedes the development of other physiological systems.18,64
The formation, maintenance and regulation of all the physiological
systems are dependent on the activity of the growth control system.
Growth control is a primary function of all multi-cellular organisms.
The evolutionary origin of the growth control system likely preceded all
the other physiological systems. Its genetic blueprint served as a
template from which the newer systems evolved. Consequently, it overlaps
and interacts with other systems but is not merely part of the nervous
system, immune system or circulatory system. The growth control signal
transduction is embedded in the activity of the function-based
physiological systems: The regulation of many neural, circulatory,
immune processes and related disorders are mediated through growth
control mechanisms such as hypertrophy, hyperplasia, atrophy, apoptosis
with shared messenger molecules including morphogens98, 99, 77,81
and common signal transduction pathways involving growth control genes
such as proto-oncogenes.100, 101, 102
The Nonspecific Stimulation and the
Long Term Effects of Acupuncture
Based on the growth control model,
acupuncture points and organizers are singular points and therefore
prone to nonspecific perturbation. The long lasting systemic effects of
acupuncture can be achieved by nonspecific stimuli as mentioned above.
Similarly, long lasting growth control activities of organizers have
been induced by various stimuli such as mechanical injury and injection
of nonspecific chemicals.67 Based on the growth control
model, acupuncture effect is a byproduct of the growth control network.
Stimulating organizers – acupuncture points can not only cause transient
modulation of neurotransmission, but also alter the growth control
signal transduction in various systems - leading to long term effects.18
The Distribution of Acupuncture Points
Organizers are at the extreme points of
curvature on the body surface such as the locally most convex points
(e.g., apical ectodermal ridge and other growth tips) or concave or
saddle points (e.g., zone of polarizing activity).103, 18
Similarly, almost all the extreme points of the body surface curvature
are acupuncture points. For example, the convex points include EX-UE11
Shixuan (finger tips), EX-LE12 Qiduan (toe tips), ST17 Ruzhong (tip of
nipple), ST42 Chongyang, (the convex, palpable point of arteria dorsalis
pedis), GV25 Suliao (nose tip) ... The concave points include TE3
Zhongzhu (the concave point between the 4th and 5th metacarpal), KI1
Yongquan (at the concave point of the sole), GB20 Fengchi (the concave
point below occipital bone, between upper ends of sternocleidomastoid
and trapezius), BL40 Weizhong (midpoint of the transverse crease of the
popliteal fossa), HT1 Jiquan (the most concave point of axilla), BL1
Jingming (at the concave point above medial canthus), CV8 Shenque
(navel)... Based on growth control model, the extreme points of surface
curvature are associated with organizers – acupuncture points. The
auricle obviously has the most convoluted surface morphology of the
human body. Therefore it has the highest density of extreme points of
surface curvature and is expected to have the highest density of
organizers - acupuncture points. Auricle exemplifies the interconnection
of growth control: Auricular morphology is a sentinel of malformation in
other organs. Auricular malformation has been observed in numerous
malformation syndromes. It is recommended in a standard textbook of
pediatrics that any auricular anomaly should initiate a search for
malformations in other parts of the body.104
The Origin of Meridians
The growth control model suggests that
the discontinuity or abrupt transition in growth control not only exists
at organizers but also along boundaries.18,61 The growth
control boundaries or folds between different structures are also called
separatrices in mathematics and often connect singular points -
organizers. The model predicted that growth control boundaries have high
electric conductance and high density of gap junctions – just as the
meridians in acupuncture which likely originate from growth control
boundaries. These predictions have been confirmed: As embryogenesis
progresses, high density gap junctions become restricted at discrete
boundaries, leading to the subdivision of the embryo into communication
compartment domains.105, 106 Increasing or decreasing the gap
junctions can cause various developmental defects107 such as
spina bifida.108 These high electric conductance boundaries
are likely major pathways of bioelectric currents. Organizers are known
to locate at boundaries between different structures.109 The
growth control model suggests that meridians originate from separatrices
– boundaries in growth control and form an undifferentiated,18,61
interconnected cellular network that regulates growth and physiology. In
consistence with the prediction of under-differentiation of the meridian
system and growth control system, it has been observed that the most
apical part of folds of embryo remain undifferentiated in morphogenesis,110
including organizers such as apical ectodermal ridge.111 As
predicted by the growth control model, singular point and separatrix
have important roles in morphogenesis.112, 113 Growth control
boundaries/separatrices are similar to organizers in controlling growth
and pattern formation with morphogen gradient.114 Many
acupuncture points are located at boundaries between different body
domains or muscles, coinciding with the connective tissue planes which
connect adjacent body domains or muscles.17, 37, 115
Current acupuncture research suggests a
convergence of the neurophysiology model, the connective tissue model
and the growth control model. The growth control model of acupuncture
set the first example of a biological model in integrative medicine with
significant prediction power across multiple disciplines. It is the
first theory in basic acupuncture research which has met the gold
standard in testing scientific theory. The following predictions of the
growth control model have been independently confirmed by research
results in both acupuncture and conventional biomedical sciences: 1.
Acupuncture has extensive growth control effects. 2. Singular point and
separatrix have important roles in morphogenesis. 3. Organizers have
high electric conductance, high current density and high density of gap
junctions. 4. A high density of gap junctions is distributed as
separatrices or boundaries at body surface after early embryogenesis. 5.
Many acupuncture points are located at transition points or boundaries
between different body domains or muscles, coinciding with the
connective tissue planes. 6. Some morphogens and organizers continue to
function after embryogenesis. The growth control model has also shed
light on several puzzling phenomena of acupuncture such as the
distribution of auricular acupuncture points, the long term effects of
acupuncture and the effect of multimodal nonspecific stimulation at
- The structure and cell
differentiation at acupuncture points as well as the neurophysiology
and growth control signal transduction involved in different
modalities of acupuncture should be further delineated.
- Manipulating the singular points -
organizers of the growth control system may be a convenient way of
activating intrinsic stem cells as evident from the improvement of
sperm quality after acupuncture.95, 96
- As the growth control model predicts
the growth control activity at acupuncture points/extreme points of
surface (or interface) curvature after embryogenesis, residual
morphogen gradient may still exist at these points and may be
detectable by probing morphogen candidates such as Hedgehog, Wnt and
TGF-beta families. Certain morphogen gradient distributes along
boundaries.116 This pattern may persist after
embryogenesis into adulthood and coincides with meridians.
- Mapping of the growth control system
and the dynamics of its electromagnetic field with high resolution
techniques such as the superconducting quantum interference device
(SQUID) and atomic magnetometer :117 The growth control
model predicts that the singular points and separatrices of the
bioelectric field in growth control correlate with the acupuncture
points and meridians respectively.
- The growth control model suggests
that techniques involving the stimulation of the growth control
system such as acupuncture can activate the growth control activity
of an organism and improve its structure and function at a more
fundamental level than symptomatic relief.18 In growth
control, the change in electric field precedes morphologic change
and manipulation of the electric field can affect the change.70,
118 Development of the techniques of detecting and
manipulating the electric field may enable the diagnosis and
treatment of a pathologic process at the early signal transduction
stage prior to the anatomical or morphological change.
- The growth control model suggests
that apparently unrelated acupuncture points are not exactly
‘placebo’ points. The more acupuncture points are used as placebo
points in a RCT, the more likely that some systemic effects will be
resulted from the ‘placebo’ treatment. The self-regulatory effect of
acupuncture will be difficult to predict when the patients have
multiple comorbidities and many acupuncture points are used. Subtle,
‘sham’ stimulation at acupuncture points can be effective due to the
response of the acupuncture points to nonspecific stimuli. These
reasons may contribute to the mixed results in RCTs on acupuncture.
This model also suggests that acupuncture is mostly likely to
demonstrate its efficacy and advantage in a patient population with
few comorbidities, relatively good general health and
Vitality and a
regimen with efficient use of acupoints.
- The growth control model suggests
that the distribution of growth control system is related to both
internal and external structures. Acupuncture points which are not
at obvious extreme points of surface curvature or meridians which
are not at obvious surface boundaries may be vestigial or related to
interface between internal structures such as muscles and bones.
Intrinsic stem cells are likely part of the undifferentiated growth
control network. The germ cell is one of the least differentiated
cells and also a type of stem cell – similar to the embryonic stem
cell in its ability to differentiate into all three germ layers. The
distribution pattern of intrinsic germ cells can be deduced based on
the fact that the distribution pattern of primary tumors reflects
the distribution of their normal counterpart. The primary germ cell
tumors119 have a midline and para-axial distribution
pattern which spans from the sacrococcygeal region to pineal gland.
It appears to concentrate at 7 locations: sacrococcygeal region,
gonads, retroperitoneum, thymus, thyroid,120 suprasellar
region, and pineal gland. This pattern reflects the distribution
pattern of intrinsic germ cells which are likely to be highly
inter-connected in a normal state (e.g. via gap junctions121
) and provide important regulatory functions.122, 56 This
also suggests a hierarchy in the degree of cell differentiation and
function in the growth control system.
I thank Steven K.H. Aung, Zang-Hee Cho,
Yuenan Cui, Li Dingzhong, Maria do Desterro Leiros, Michael Levin,
Vitaly Napadow, Richard Nuccitelli, Stig Ollmar, Rosa N. Schnyer, San
Wan, Peter Wayne, Raimond Wong, Seung-Schik Yoo for their input.
- World Health Organization. 2002.
Acupuncture: Review and analysis of reports on controlled clinical
trials. WHO Geneva.
- World Health Organization. 1991. A
proposed standard international acupuncture nomenclature: report of
a WHO scientific group. World Health Organization, Geneva.
- Osiri M, Welch V, Brosseau L, Shea
B, McGowan J, Tugwell P, Wells G. 2004. Transcutaneous electrical
nerve stimulation for knee osteoarthritis. Cochrane Database of
Systematic Reviews. 3.
- Kwon YD, Pittler MH, Ernst E.
Acupuncture for peripheral joint osteoarthritis: a systematic review
and meta-analysis. Rheumatology. 2006;45:1331-7.
- Berman BM, Lao L, Langenberg P, Lee
WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as
adjunctive therapy in osteoarthritis of the knee: a randomized,
controlled trial. Ann Intern Med. 2004;141:901-10.
- Young G, Jewell D. 2004.
Interventions for preventing and treating pelvic and back pain in
pregnancy. Cochrane Database of Systematic Reviews. 3.
- Trinh K, Graham N, Gross A,
Goldsmith Ch, et al. Acupuncture for neck disorders. Cochrane
Database Syst Rev, 2006; 3: CD004870.
- Vincent CA. 1989. A controlled trial
of the treatment of migraine by acupuncture. Clin J Pain 5: 305-12.
- Vickers AJ. Rees RW. Zollman CE.
McCarney R. Smith CM. Ellis N. Fisher P. Van Haselen R. 2004.
Acupuncture for chronic headache in primary care: large, pragmatic,
randomised trial. BMJ 328:744-747.
- Vickers AJ. Can acupuncture have
specific effects on health? A systematic review of acupuncture
antiemesis trials. J R Soc Med 1996;89:303-11.
- Joos S, Brinkhaus B, Maluche C,
Maupai N, Kohnen R, et al. 2004. Acupuncture and moxibustion in the
treatment of active Crohn's disease: a randomized controlled study.
Digestion 69: 131-9.
- White PF. Electroanalgesia: does it
have a place in the routine management of acute and chronic pain?
Anesth Analg. 2004;98:1197-8.
- Han JS. Acupuncture: neuropeptide
release produced by electrical stimulation of different frequencies.
Trends Neurosci. 2003;26: 17-22.
- Pomeranz B. Acupuncture analgesia –
basic research. In Clinical Acupuncture: Scientific Basis. edited by
G. Stux and R. Hammerschlag, Berlin: Springer-Verlag; 2000;p1-29.
- Han JS. Opioid and antiopioid
peptides: A model of Yin-Yang balance in acupuncture mechanism of
pain modulation. In Clinical Acupuncture: Scientific Basis. edited
by G. Stux and R. Hammerschlag, Berlin: Springer-Verlag;
- Crisostomo MM, Li P, Tjen-A-Looi SC,
Longhurst JC. Nociceptin in rVLM mediates electroacupuncture
inhibition of cardiovascular reflex excitatory response in rats. J
Appl Physiol. 2005;98:2056-2063.
- Langevin HM, Churchill DL, Wu J,
Badger GJ, Yandow JA, Fox JR, Krag MH. Evidence of connective tissue
involvement in acupuncture. FASEB J 2002;16: 872-4.
- Shang C. Electrophysiology of growth
control and acupuncture. Life Sci 2001;68:1333-1342.
- Pomeranz B, Chiu D. Naloxone blocks
acupuncture analgesia and causes hyperalgesia: endorphin is
implicated. Life Sci 1976;19:1757-1762.
- Mayer DJ, Price DD, Raffii A.
Antagonism of acupuncture analgesia in man by the narcotic
antagonist naloxone. Brain Res 1977;121:368-72.
- Bowsher D. Mechanisms of
acupuncture. In: Filshie J, White A, editors. Medical Acupuncture.
Edinburgh: Churchill Livingston, 1998;p69-80.
- Chiang CY, Chang CT. Peripheral
afferent pathway for acupuncture analgesia. Scientia Sinica
- Xu GS, Wang ZJ, Zhu SL, Chen QZ,
Zhang DQ. Nitric oxide participates in protective effect of
acupuncture on gastric mucosal damages in rats. World J
- Comunetti A, Laage S, Schiessl N,
Kistler A. Characterisation of human skin conductance at acupuncture
points. Experientia 1995;51:328-31.
- Saku K, Mukaino Y, Ying H, Arakawa
K. Characteristics of reactive electropermeable points on the
auricles of coronary heart disease patients. Clin Cardiol
- Oleson TD, Kroenig RJ, Bresler DE.
An experimental evaluation of auricular diagnosis: The somatotopic
mapping of musculoskeletal pain at acupuncture points. Pain 1980;8:
- Martinsen OG, Grimnes S, Morkrid L,
Hareide M. Line patterns in the mosaic electrical properties of
human skin--a cross-correlation study. IEEE Trans Biomed Eng.
- Shiraishi T, Onoe M, Kageyama T,
Sameshima Y, Kojima T, Konishi S, Yoshimatsu H, Sakata T. Effects of
auricular acupuncture stimulation on nonobese, healthy volunteer
subjects. Obes Res 1995;3: 667S-673S.
- Mashanskii VF, Markov IuV, Shpunt
VKh, Li SE, Mirkin AS. Topography of the gap junctions in the human
skin and their possible role in the non-neural signal transduction.
Arkh Anat Gistol Embriol 1983;84:53-60.
- Cui H-M. Meridian system -
specialized embryonic epithelial conduction system. Shanghai J
Acupunct 1988;3: 44-45.
- Fan JY. 1990. The role of gap
junctions in determining skin conductance and their possible
relationship to acupuncture points and meridians. Am J Acupunct
- Zheng CH, Huang GY, Zhang MM, Xiao
YL. [Experimental study on expression of connexin 43 in meridians of
rats] Zhongguo Zhen Jiu. 2005; 25:629-32.
- Ma SX. Enhanced nitric oxide
concentrations and expression of nitric oxide synthase in
acupuncture points/meridians. J Altern Complement Med 2003;9:
- Chang HC, Xie YK, Wen YY, Zhang SY,
Qu JH, Lu WJ. Further investigation on the hypothesis of
meridian-cortex-viscera interrelationship. Am J Chin Med 1983.
- Ulett GA. Beyond Yin and Yang: How
Acupuncture Really Works. Warren H. Green, Inc. St. Louis, MO; 1992.
- Mann F. A new system of acupuncture.
In: Filshie J, White A, editors. Medical Acupuncture. Edinburgh:
Churchill Livingston; 1998:63.
- Langevin HM, Yandow JA. Relationship
of acupuncture points and meridians to connective tissue planes.
Anat Rec (New Anat) 2002;269: 257 – 265.
- Barker R, Kober A, Hoerauf K, Latzke
D, Adel S, Kain ZN, Wang SM. Out-of-hospital auricular acupressure
in elder patients with hip fracture: a randomized double-blinded
trial. Acad Emerg Med. 2006;13:19-23.
- Usichenko TI, Dinse M, Hermsen M,
Witstruck T, Pavlovic D, Lehmann Ch. Auricular acupuncture for pain
relief after total hip arthroplasty - a randomized controlled study.
- Sator-Katzenschlager SM, Scharbert
G, Kozek-Langenecker SA, Szeles JC, Finster G, Schiesser AW, Heinze
G, Kress HG. The short- and long-term benefit in chronic low back
pain through adjuvant electrical versus manual auricular
acupuncture. Anesth Analg. 2004;98:1359-64.
- Ricci L, Minardi D, Romoli M, Galosi
AB, Muzzonigro G. Acupuncture reflexotherapy in the treatment of
sensory urgency that persists after transurethral resection of the
prostate: a preliminary report. Neurourol Urodyn. 2004;23:58-62.
- Wong AM, Leong CP, Su TY, Yu SW,
Tsai WC, Chen CP. Clinical trial of acupuncture for patients with
spinal cord injuries. Am J Phys Med Rehabil. 2003;82:21-7.
- Bier ID, Wilson J, Studt P,
Shakleton M. Auricular acupuncture, education, and smoking
cessation: a randomized, sham-controlled trial. Am J Public Health.
- Jarvis D, MacIver MB, Tanelian DL.
Electrophysiologic recording and thermodynamic modeling demonstrate
that helium-neon laser irradiation does not affect peripheral Adelta-
or C-fiber nociceptors. Pain 1990;43:235-42.
- Whittaker P. Laser acupuncture:
past, present, and future. Lasers Med Sci 2004;19:69-80.
- Yu HS, Wu CS, Yu CL, Kao YH, Chiou
MH. Helium-neon laser irradiation stimulates migration and
proliferation in melanocytes and induces repigmentation in
segmental-type vitiligo. J Invest Dermatol. 2003;120:56-64.
- Foley KM, Kourides IA, Inturrisi CE,
Kaiko RF, Zaroulis CG, Posner JB, Houde RW, Li CH. Endorphin:
Analgesic and hormonal effects in humans. Proc Natl Acad Sci U S A.
- Guerra de Hoyos JA, Andres Martin
Mdel C, Bassas y Baena de Leon E, Vigara Lopez M, Molina Lopez T,
Verdugo Morilla FA, Gonzalez Moreno MJ. Randomised trial of long
term effect of acupuncture for shoulder pain. Pain. 2004;112:289-98.
- Sator-Katzenschlager SM. Scharbert
G. Kozek-Langenecker SA. Szeles JC. Finster G. Schiesser AW. Heinze
G. Kress HG. The short- and long-term benefit in chronic low back
pain through adjuvant electrical versus manual auricular
acupuncture. Anesth Analg. 2004;98:1359-1364.
- Carlsson CP, Sjölund BH. Acupuncture
for chronic low back pain: a randomized placebo-controlled study
with long-term follow-up. Clin J Pain 2001;17: 296-305.
- Helms JM. Acupuncture for the
management of primary dysmenorrhea. Obstet Gynecol. 1987;69:51-6.
- Witt CM, Jena S, Brinkhaus B,
Liecker B, Wegscheider K, Willich SN. Acupuncture in patients with
osteoarthritis of the knee or hip: a randomized, controlled trial
with an additional nonrandomized arm. Arthritis Rheum.
- Stener-Victorin E. Kruse-Smidje C.
Jung K. Comparison Between Electro-Acupuncture and Hydrotherapy,
Both in Combination With Patient Education and Patient Education
Alone, on the Symptomatic Treatment of Osteoarthritis of the Hip.
Clin J Pain 2004;20:179-185.
- Janknegt RA, Janknegt RA, Hassouna
MM, Hassouna MM, Siegel SW, Siegel SW, Oleson KA, et al. Long-term
effectiveness of sacral nerve stimulation for refractory urge
incontinence. Eur Urol 2001;39:101-106.
- Schachter SC. Vagus nerve
stimulation therapy summary: five years after FDA approval.
- Qian L, Peters LJ, Chen JD. Effects
of electroacupuncture on gastric migrating myoelectrical complex in
dogs. Dig Dis Sci. 1999;44:56-62.
- Lipton P. Testing hypotheses:
prediction and prejudice. Science. 2005;307:219-21.
- Desbiens NA. More support for
- Carlsson C. Acupuncture mechanisms
for clinically relevant long-term effects--reconsideration and a
hypothesis. Acupunct Med. 2002;20:82-99.
- Kim HW, Roh DH, Yoon SY, Kang SY,
Kwon YB, Han HJ, Lee HJ, Choi SM, Ryu YH, Beitz AJ, Lee JH. The
anti-inflammatory effects of low- and high-frequency
electroacupuncture are mediated by peripheral opioids in a mouse air
pouch inflammation model. J Altern Complement Med. 2006;12:39-44.
- Shang C. Singular Point, organizing
center and acupuncture point. Am J Chin Med 1989;17:119-127.
- Shang C. Prospective Tests on
Biological Models of Acupuncture. Evidence-based Complementary and
Alternative Medicine 2007; doi: 10.1093/ecam/nem122
- Bryant PJ, Simpson P. Intrinsic and
Extrinsic Control of Growth in Developing Organs. Quart Rev Biol
- Meinhardt H. Models of Biological
Pattern Formation London: Academic; 1982:20.
- Niehrs C. Regionally specific
induction by the Spemann-Mangold organizer.
Nat Rev Genet. 2004;5:425-34.
- Winfree AT. The Geometry of
biological time. New York: Springer-Verlag. 1980: 71.
- Toivonen S. Regionalization of the
embryo. In: Organizer – A milestone of a half- century from Spemann.
Nakamura O, Toivonen S. editors. Amsterdam: Elsevier; 1978: 132.
- McCaig CD. Zhao M. Physiological
electrical fields modify cell behaviour. Bioessays 1997;19:819-26.
- Marx JL. Electric currents may guide
development. Science 1981;211:1147-9.
- Huttenlocher A, Horwitz AR. Wound
healing with electric potential. N Engl J Med. 2007;356:303-4.
- Erickson CA. Morphogenesis of the
neural crest. In: Browder LW, editor. Developmental Biology. New
York: Plenum; 1985;2:528.
- Hotary KB, Robinson KR. Endogenous
electrical currents and voltage gradients in Xenopus embryos and the
consequences of their disruption. Dev Biol 1994;166:797.
- Laird DW, Yancey SB, Bugga L, Revel
JP. Connexin expression and gap junction communication compartments
in the developing mouse limb. Dev Dyn 1992;195: 153-61.
- Yancey SB, Biswal S, Revel JP.
Spatial and temporal patterns of distribution of the gap junction
protein connexin43 during mouse gastrulation and organogenesis.
Development 1992;114: 203-12.
- Coelho CN, Kosher RA. A gradient of
gap junctional communication along the anterior-posterior axis of
the developing chick limb bud. Dev Biol 1991;148: 529-35.
- Meyer RA, Cohen MF, Recalde S, et
al. Developmental regulation and asymmetric expression of the gene
encoding Cx43 gap junctions in the mouse limb bud. Dev Genet
- Rosendahl A, Pardali E, Speletas M,
Ten Dijke P et al. Activation of bone morphogenetic protein/Smad
signaling in bronchial epithelial cells during airway inflammation.
Am J Respir Cell Mol Biol. 2002;27:160-9.
- Maden M. The role of retinoic acid
in embryonic and post-embryonic development. Proc Nutr Soc.
- Farquharson C, Jefferies D,
Seawright E, Houston B. Regulation of chondrocyte terminal
differentiation in the postembryonic growth plate: the role of the
PTHrP-Indian hedgehog axis. Endocrinology. 2001;142:4131-40.
- Kishimoto J, Burgeson RE, Morgan BA.
Wnt signaling maintains the hair-inducing activity of the dermal
papilla. Genes Dev. 2000;14:1181-5.
- Miano JM, Topouzis S, Majesky M,
Olson EN. Retinoid receptor expression and all-trans retinoic
acid-mediated growth inhibition in vascular smooth muscle cells.
- Wang SJ. Omori N. Li F. Jin G.
Hamakawa Y. Sato K. Nagano I. Shoji M. Abe K. Functional improvement
by electro-acupuncture after transient middle cerebral artery
occlusion in rats. Neurol Res 2003;25:516-21,
- Ou YW. Han L. Da CD. Huang YL. Cheng
JS. Influence of acupuncture upon expressing levels of basic
fibroblast growth factor in rat brain following focal cerebral
ischemia--evaluated by time-resolved fluorescence immunoassay.
Neurol Res 2001;23:47-50.
- Liang XB. Luo Y. Liu XY. Lu J. Li FQ.
Wang Q. Wang XM. Han JS. Electro-acupuncture improves behavior and
upregulates GDNF mRNA in MFB transected rats. Neuroreport
- Pan B, Castro-Lopes JM, Coimbra A.
Activation of anterior lobe corticotrophs by electroacupuncture or
noxious stimulation in the anaesthetized rat, as shown by
colocalization of Fos protein with ACTH and beta-endorphin and
increased hormone release. Brain Res Bull 1996;40:175-82.
- Lee JH, Beitz AJ. The distribution
of brain-stem and spinal cord nuclei associated with different
frequencies of electroacupuncture analgesia. Pain 1993;52:11-28.
- Zhang Y, Wu GC, He QZ, Cao XD.
Effect of morphine and electro-acupuncture (EA) on apoptosis of
thymocytes. Acupunct Electrother Res 2000;25:17-26.
- Wu HG, Gong X, Yao LQ, Zhang W, Shi
Y, Liu HR, Gong YJ, Zhou LB, Zhu Y. Mechanisms of acupuncture and
moxibustion in regulation of epithelial cell apoptosis in rat
ulcerative colitis. World J Gastroenterol 2004;10: 682-8.
- Chen Y, Zhao C, Chen H, et al.
Effects of "moxibustion serum" on proliferation and phenotypes of
tumor infiltrating lymphocytes. J Tradit Chin Med 2003;23: 225-9.
- Stener-Victorin E. Lundeberg T.
Waldenstrom U. Manni L. Aloe L. Gunnarsson S. Janson PO. Effects of
electro-acupuncture on nerve growth factor and ovarian morphology in
rats with experimentally induced polycystic ovaries. Biol Reprod
- Bai YH, Lim SC, Song CH, et al.
Electro-acupuncture reverses nerve growth factor abundance in
experimental polycystic ovaries in the rat. Gynecol Obstet Invest
- Liu X, Shen L, Wu M, Wu B, Gao L, Hu
W, Zhang A. Effects of acupuncture on myelogenic osteoclastogenesis
and IL-6 mRNA expression. J Tradit Chin Med 2004;24:144-8.
- Kishi H, Mishima HK, Sakamoto I,
Yamashita U. Stimulation of retinal pigment epithelial cell growth
by neuropeptides in vitro. Curr Eye Res 1996;15:708-13.
- Pakala R, Benedict CR. Effect of
serotonin and thromboxane A2 on endothelial cell proliferation:
effect of specific receptor antagonists. J Lab Clin Med
- Siterman S, Eltes F, Wolfson V,
Zabludovsky N, Bartoov B. Effect of acupuncture on sperm parameters
of males suffering from subfertility related to low sperm quality.
Arch Androl 1997;39:155-161.21
- Pei J, Strehler E, Noss U, Abt M,
Piomboni P, Baccetti B, Sterzik K. Quantitative evaluation of
spermatozoa ultrastructure after acupuncture treatment for
idiopathic male infertility. Fertil Steril. 2005;84:141-7.
- Rives AW, Galitski T. Modular
organization of cellular networks. Proc Natl Acad Sci U S A.
- Voelker CA, Miller MJ, Zhang XJ,
Eloby-Childress S, Clark DA, Pierce MR. Perinatal nitric oxide
synthase inhibition retards neonatal growth by inducing hypertrophic
pyloric stenosis in rats. Pediatr Res 1995;38:768-74.
- Lee CH, Whiteman AL, Murphy CJ,
Barney NP, Taylor PB, Reid TW. Substance P, insulin like growth
factor 1, and surface healing. Arch Ophthalmol 2002;120:215-7.
- Baldwin AS Jr. The NF-kappa B and I
kappa B proteins: new discoveries and insights. Annu Rev Immunol
- Bailey CH, Bartsch D, Kandel ER.
Toward a molecular definition of long-term memory storage. Proc Natl
Acad Sci USA 1996;93:13445-52.
- Tanaka H, Samuel CE. Mechanism of
interferon action: structure of the mouse PKR gene encoding the
interferon-inducible RNA-dependent protein kinase. Proc Natl Acad
Sci USA 1994;91:7995-9.
- Winfree AT. A continuity principle
for regeneration. In: Malacinski GM, editor. Pattern formation. New
York: Macmillan; 1984: 106-7.
- Cotton RT. The ear, nose, oropharynx
and larynx. In: Rudolph AM, Hoffman JIE, Rudolph CD, editors.
Rudolph’s Pediatrics. Stamford: Appleton & Lange; 1996: 945.
- Lo CW. The role of gap junction
membrane channels in development. J Bioenerg Biomembr
- Levin M. Isolation and community: a
review of the role of gap-junctional communication in embryonic
patterning. J Membr Biol 2002;185: 177-92.
- Ewart JL, Cohen MF, Meyer RA, Huang
GY, Wessels A, Gourdie RG, Chin A, Park SMJ, Lazatin BO, Villabon S,
Lo CW. Heart and neural tube defects in transgenic mice
overexpressing the Cx43 gap junction gene. Development 1997;124:
- Becker DL, McGonnell I, Makarenkova
HP, Patel K, Tickle C, Lorimer J, Green CR. Roles for 1 connexin in
morphogenesis of chick embryos revealed using a novel antisense
approach. Dev Genet 1999;24: 33-42.
- Chi CL, Martinez S, Wurst W, Martin
GR. The isthmic organizer signal FGF8 is required for cell survival
in the prospective midbrain and cerebellum.
- Toivonen S. Regionalization of the
embryo. In: Organizer – A milestone of a half- century from Spemann.
Nakamura O, Toivonen S. editors. Amsterdam: Elsevier; 1978: 124.
- Carlson MR. Bryant SV. Gardiner DM.
Expression of Msx-2 during development, regeneration, and wound
healing in axolotl limbs. J Experimental Zool 1998;282:715-23.
- Lee D, Malpeli JG. Global form and
singularity: modeling the blind spot's role in lateral geniculate
morphogenesis. Science 1994;263:1292-4.
- Sawai S, Thomason PA, Cox EC. An
autoregulatory circuit for long-range self-organization in
Dictyostelium cell populations. Nature 2005;433, 323-326.
- Diaz-Benjumea FJ, Cohen SM.
Interaction between dorsal and ventral cells in the imaginal disc
directs wing development in Drosophila. Cell. 1993;75:741-52.
- Baldry P. Trigger point acupuncture.
In: Filshie J, White A, editors. Medical Acupuncture. Edinburgh:
Churchill Livingston. 1998: 35.
- Neumann CJ, Cohen SM. Long-range
action of Wingless organizes the dorsal-ventral axis of the
Drosophila wing. Development. 1997;124:871-80.
- Xia H, Ben-Amar Baranga A, Hoffman
D, Romalis MV. Magnetoencephalography with an atomic magnetometer.
Appl Phys Lett 2006;89:211104.
- McCaig CD, Rajnicek AM, Song B, Zhao
M. Controlling cell behavior electrically: current views and future
potential. Physiol Rev. 2005;85:943-978.
- Azizkhan RG, Caty MG. Teratomas in
childhood. Curr Opin Pediatr 1996;8:287-92.
- Gonzalez-Crussi F. Extragonadal
teratomas. Washington, D.C.: Armed Forces Institute of Pathology.
- Francis RJ, Lo CW. Primordial germ
cell deficiency in the connexin 43 knockout mouse arises from
apoptosis associated with abnormal p53 activation. Development.
- Nichols CR, Timmerman R, Foster RS,
Roth BJ, Einhorn LH. Neoplasms of the testis. In: Cancer Medicine.
Holland JF, Basst RC, Jr. Morton DL, Frei E III, Kufe DW,
Weichselbaum RR, editors. 4th ed. Baltimore: Williams & Wilkins;
Charles Shang, MD
Department of Medicine
New England Baptist Hospital
Harvard Medical School
125 Parker Hill Ave.
Boston, MA 02120