In this overview, new and existent material on the organization and composition of the thoracolumbar fascia (TLF) will be evaluated in respect to its anatomy, innervation biomechanics and clinical ...relevance. The integration of the passive connective tissues of the TLF and active muscular structures surrounding this structure are discussed, and the relevance of their mutual interactions in relation to low back and pelvic pain reviewed. The TLF is a girdling structure consisting of several aponeurotic and fascial layers that separates the paraspinal muscles from the muscles of the posterior abdominal wall. The superficial lamina of the posterior layer of the TLF (PLF) is dominated by the aponeuroses of the latissimus dorsi and the serratus posterior inferior. The deeper lamina of the PLF forms an encapsulating retinacular sheath around the paraspinal muscles. The middle layer of the TLF (MLF) appears to derive from an intermuscular septum that developmentally separates the epaxial from the hypaxial musculature. This septum forms during the fifth and sixth weeks of gestation. The paraspinal retinacular sheath (PRS) is in a key position to act as a ‘hydraulic amplifier’, assisting the paraspinal muscles in supporting the lumbosacral spine. This sheath forms a lumbar interfascial triangle (LIFT) with the MLF and PLF. Along the lateral border of the PRS, a raphe forms where the sheath meets the aponeurosis of the transversus abdominis. This lateral raphe is a thickened complex of dense connective tissue marked by the presence of the LIFT, and represents the junction of the hypaxial myofascial compartment (the abdominal muscles) with the paraspinal sheath of the epaxial muscles. The lateral raphe is in a position to distribute tension from the surrounding hypaxial and extremity muscles into the layers of the TLF. At the base of the lumbar spine all of the layers of the TLF fuse together into a thick composite that attaches firmly to the posterior superior iliac spine and the sacrotuberous ligament. This thoracolumbar composite (TLC) is in a position to assist in maintaining the integrity of the lower lumbar spine and the sacroiliac joint. The three‐dimensional structure of the TLF and its caudally positioned composite will be analyzed in light of recent studies concerning the cellular organization of fascia, as well as its innervation. Finally, the concept of a TLC will be used to reassess biomechanical models of lumbopelvic stability, static posture and movement.
Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can ...be assessed by exhaled breath metabolomics. Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed. Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p < 0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p < 0.01; eNose breathprint r = 0.84, p = 0.002) (MPO: four compounds, p < 0.01; eNose r = 0.72, p = 0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD. Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.
This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the ...spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure.
The thoracolumbar fascia (TLF) consists of aponeurotic and fascial layers that interweave the paraspinal and abdominal muscles into a complex matrix stabilizing the lumbosacral spine. To better ...understand low back pain, it is essential to appreciate how these muscles cooperate to influence lumbopelvic stability. This study tested the following hypotheses: (i) pressure within the TLF's paraspinal muscular compartment (PMC) alters load transfer between the TLF's posterior and middle layers (PLF and MLF); and (ii) with increased tension of the common tendon of the transversus abdominis (CTrA) and internal oblique muscles and incremental PMC pressure, fascial tension is primarily transferred to the PLF. In cadaveric axial sections, paraspinal muscles were replaced with inflatable tubes to simulate paraspinal muscle contraction. At each inflation increment, tension was created in the CTrA to simulate contraction of the deep abdominal muscles. Fluoroscopic images and load cells captured changes in the size, shape and tension of the PMC due to inflation, with and without tension to the CTrA. In the absence of PMC pressure, increasing tension on the CTrA resulted in anterior and lateral movement of the PMC. PMC inflation in the absence of tension to the CTrA resulted in a small increase in the PMC perimeter and a larger posterior displacement. Combining PMC inflation and tension to the CTrA resulted in an incremental increase in PLF tension without significantly altering tension in the MLF. Paraspinal muscle contraction leads to posterior displacement of the PLF. When expansion is combined with abdominal muscle contraction, the CTrA and internal oblique transfers tension almost exclusively to the PLF, thereby girdling the paraspinal muscles. The lateral border of the PMC is restrained from displacement to maintain integrity. Posterior movement of the PMC represents an increase of the PLF extension moment arm. Dysfunctional paraspinal muscles would reduce the posterior displacement of the PLF and increase the compliance of the lateral border. The resulting change in PMC geometry could diminish any effects of increased tension of the CTrA. This study reveals a co‐dependent mechanism involving balanced tension between deep abdominal and lumbar spinal muscles, which are linked through the aponeurotic components of the TLF. This implies the existence of a point of equal tension between the paraspinal muscles and the transversus abdominis and internal oblique muscles, acting through the CTrA.
The definition of centromeres of human chromosomes requires a complete genomic understanding of these regions. Toward this end, we report integration of physical mapping, genetic, and functional ...approaches, together with sequencing of selected regions, to define the centromere of the human X chromosome and to explore the evolution of sequences responsible for chromosome segregation. The transitional region between expressed sequences on the short arm of the X and the chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is satellite-rich. At the junction between this satellite region and canonical DXZ1 repeats, diverged repeat units provide direct evidence of unequal crossover as the homogenizing force of these arrays. Results from deletion analysis of mitotically stable chromosome rearrangements and from a human artificial chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function. Evolutionary studies indicate that, while alpha satellite DNA present throughout the pericentromeric region of the X chromosome appears to be a descendant of an ancestral primate centromere, the current functional centromere based on DXZ1 sequences is the product of the much more recent concerted evolution of this satellite DNA.
Centromeres are
cis-acting chromosomal domains that direct kinetochore formation, enabling faithful chromosome segregation. Centromeric regions of higher eukaryotes are structurally complex, ...consisting of various epigenetically modified chromatin types including specialized chromatin at the kinetochore itself, pericentromeric heterochromatin, and flanking euchromatin. Although the features necessary for the establishment and maintenance of discrete chromatin domains remain poorly understood, two models have been proposed based either on the passive convergence of competing activities involved in individual domain formation or, alternatively, on the action of specific genomic sequences and associated proteins to actively block the propagation of one chromatin type into another.
Functional analysis of centromeric sequences located at the intersection of
Schizosaccharomyces pombe central core chromatin and outer repeat heterochromatin identified a chromatin barrier that contains a transfer RNA (tRNA) gene. Deletion or modification of the barrier sequences result in the propagation of pericentromeric heterochromatin beyond its normal boundary. The tRNA gene is transcriptionally active, and barrier activity requires sequences necessary for RNA polymerase III transcription. Moreover, absence of the barrier results in abnormal meiotic chromosome segregation.
The identification of DNA sequences with chromatin barrier activity at the fission yeast centromere provides a model for establishment of centromeric chromatin domains in higher eukaryotes.
Movement and stability of the lumbosacral region is contingent on the balance of forces distributed through the myofascial planes associated with the thoracolumbar fascia (TLF). This structure is ...located at the common intersection of several extremity muscles (e.g. latissimus dorsi and gluteus maximus), as well as hypaxial (e.g. ventral trunk muscles) and epaxial (paraspinal) muscles. The mechanical properties of the fascial constituents establish the parameters guiding the dynamic interaction of muscle groups that stabilize the lumbosacral spine. Understanding the construction of this complex myofascial junction is fundamental to biomechanical analysis and implementation of effective rehabilitation in individuals with low back and pelvic girdle pain. Therefore, the main objectives of this study were to describe the anatomy of the lateral margin of the TLF, and specifically the interface between the fascial sheath surrounding the paraspinal muscles and the aponeurosis of the transversus abdominis (TA) and internal oblique (IO) muscles. The lateral margin of the TLF was exposed via serial reduction dissections from anterior and posterior approaches. Axial sections (cadaveric and magnetic resonance imaging) were examined to characterize the region between the TA and IO aponeurosis and the paraspinal muscles. It is confirmed that the paraspinal muscles are enveloped by a continuous paraspinal retinacular sheath (PRS), formed by the deep lamina of the posterior layer of the TLF. The PRS extends from the spinous process to transverse process, and is distinct from both the superficial lamina of the posterior layer and middle layer of the TLF. As the aponeurosis approaches the lateral border of the PRS, it appears to separate into two distinct laminae, which join the anterior and posterior walls of the PRS. This configuration creates a previously undescribed fat‐filled lumbar interfascial triangle situated along the lateral border of the paraspinal muscles from the 12th rib to the iliac crest. This triangle results in the unification of different fascial sheaths along the lateral border of the TLF, creating a ridged‐union of dense connective tissue that has been termed the lateral raphe (Spine, 9,1984, 163). This triangle may function in the distribution of laterally mediated tension to balance different viscoelastic moduli, along either the middle or posterior layers of the TLF.
In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation. However, some genes escape X-inactivation and are expressed from both the active and inactive ...X chromosome. Such genes are potential contributors to sexually dimorphic traits, to phenotypic variability among females heterozygous for X-linked conditions, and to clinical abnormalities in patients with abnormal X chromosomes. Here, we present a comprehensive X-inactivation profile of the human X chromosome, representing an estimated 95% of assayable genes in fibroblast-based test systems. In total, about 15% of X-linked genes escape inactivation to some degree, and the proportion of genes escaping inactivation differs dramatically between different regions of the X chromosome, reflecting the evolutionary history of the sex chromosomes. An additional 10% of X-linked genes show variable patterns of inactivation and are expressed to different extents from some inactive X chromosomes. This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females.
We have combined long synthetic arrays of alpha satellite DNA with telomeric DNA and genomic DNA to generate artificial chromosomes in human HT1080 cells. The resulting linear microchromosomes ...contain exogenous alpha satellite DNA, are mitotically and cytogenetically stable in the absence of selection for up to six months in culture, bind centromere proteins specific for active centromeres, and are estimated to be 6-10 megabases in size, approximately one-fifth to one-tenth the size of endogenous human chromosomes. We conclude that this strategy results in the formation of de novo centromere activity and that the microchromosomes so generated contain all of the sequence elements required for stable mitotic chromosome segregation and maintenance. This first-generation system for the construction of human artificial chromosomes should be suitable for dissecting the sequence requirements of human centromeres, as well as developing constructs useful for therapeutic applications.
Some deleterious X-linked mutations may result in a growth disadvantage for those cells in which the mutation, when on the active X chromosome, affects cell proliferation or viability. To explore the ...relationship between skewed X-chromosome inactivation and X-linked mental retardation (XLMR) disorders, we used the androgen receptor X-inactivation assay to determine X-inactivation patterns in 155 female subjects from 24 families segregating 20 distinct XLMR disorders. Among XLMR carriers, ∼50% demonstrate markedly skewed X inactivation (i.e., patterns ⩾80:20), compared with only ∼10% of female control subjects (
P<.001). Thus, skewed X inactivation is a relatively common feature of XLMR disorders. Of the 20 distinct XLMR disorders, 4 demonstrate a strong association with skewed X inactivation, since all carriers of these mutations demonstrate X-inactivation patterns ⩾80:20. The XLMR mutations are present on the preferentially inactive X chromosome in all 20 informative female subjects from these families, indicating that skewing is due to selection against those cells in which the XLMR mutation is on the active X chromosome.