Modelling and simulation of the intervertebral movements of the lumbar spine using an inverse kinematic algorithm.

An inverse kinematic model is presented that was employed to determine the optimum intervertebral joint configuration for a given forward-bending posture of the human trunk. The lumbar spine was modelled as an open-end, kinematic chain of five links that represented the five vertebrae (L 1-L5). An optimisation equation with physiological constraints was employed to determine the intervertebral joint configuration. Intervertebral movements were measured from sagittal X-ray films of 22 subjects. The mean difference between the X-ray measurements of intervertebral rotations in the sagittal plane and the values predicted by the kinematic model was less than 1.6 degrees. Pearson product-moment correlation R was used to measure the relationship between the measured and predicted values. The R-values were found to be high, ranging from 0.83 to 0.97, for prediction of intervertebral rotation, but poor for intervertebral translation (R= 0.08-0.67). It is concluded that the inverse kinematic model will be clinically useful for predicting intervertebral rotation when X-ray or invasive measurements are undesirable. It will also be useful to biomechanical modelling, which requires accurate kinematic information as model input data.

Applications of the pulsatile flow versatile ECLS: in vivo studies.

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.

Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway.

C. elegans insulin-like signaling regulates metabolism, development, and life span. This signaling pathway negatively regulates the activity of the forkhead transcription factor DAF-16. daf-16 encodes multiple isoforms that are expressed in distinct tissue types and are probable orthologs of human FKHRL1, FKHR, and AFX. We show that human FKHRL1 can partially replace DAF-16, proving the orthology. In mammalian cells, insulin and insulin-like growth factor signaling activate AKT/PKB kinase to negatively regulate the nuclear localization of DAF-16 homologs (reviewed in ). We show that the absence of AKT consensus sites on DAF-16 is sufficient to cause dauer arrest in daf-2(+) animals, proving that daf-16 is the major output of insulin signaling in C. elegans. FKHR, FKRHL1, and AFX may similarly be the major outputs of mammalian insulin signaling. daf-2 insulin signaling, via AKT kinases, negatively regulates DAF-16 by controlling its nuclear localization. Surprisingly, we find that daf-7 TGF-beta signaling also regulates DAF-16 nuclear localization specifically at the time when the animal makes the commitment between diapause and reproductive development. daf-16 function is supported by the combined action of two distinct promoter/enhancer elements, whereas the coding sequences of two major DAF-16 isoforms are interchangeable. Together, these observations suggest that the combined effects of transcriptional and posttranslational regulation of daf-16 transduce insulin-like signals in C. elegans and perhaps more generally.

Loads in the lumbar spine during traction therapy.

The purpose of the present study was to determine the loads acting on the lumbar spine when traction therapy was given in the Fowler's position. The study had two parts: a theoretical analysis which showed that traction produced a flexion moment on the spine as well as axial distraction; and an experimental study which measured the flexion moment induced by the adoption of the Fowler's position. The Fowler's position is clinically essential in that it flexes the spine and takes up the slack of the posterior tissues before the traction force is applied. Hence the axial tension and flexion moment generated by the traction force are more effective in stretching the posterior tissues. The angle of pull on the traction harness influences the friction between the body and the couch. However, this consideration is not necessary if a split traction table is used. The mechanical effects of traction are compared with those produced by postero-anterior mobilisation. The relative magnitude and direction of loads produced, and their variation with segmental level should be considered by therapists when choosing a technique for treating low back pain.

Time course of stress relaxation and recovery in human ankles.

OBJECTIVE: To characterise the time course of stress relaxation and recovery from stress relaxation in human ankles. DESIGN: Two experiments were conducted. The first used a randomised within-subjects design, and the second used a randomised between-subjects regression design. BACKGROUND: Several studies have described the time course of stress relaxation in human joints, but most have looked only at the effects of short durations of stretch. The time course of recovery from stretch in human ankles has not been documented. METHODS: In the first experiment, one ankle of each of eight subjects was stretched to a fixed dorsiflexion angle for 20 min. The ankle was then released for 2 min (during which time subjects either remained relaxed or performed isometric contractions), then stretched again. In a second experiment, on 24 subjects, the ankle was stretched for 20 min, then released between 0 and 20 min, then stretched again. In both experiments, subjects remain relaxed and ankle torque was measured continuously. RESULTS: When a constant-angle stretch was applied to the ankle, torque declined bi-exponentially towards an asymptote that was 58% of the initial torque. Nearly 5 min of stretch were required to obtain half of the maximal possible stress relaxation. Torque had recovered by 43% within 2 min of the release of stretch, but the degree of recovery did not appear to depend on whether subjects remained relaxed or performed isometric contractions. The time course of recovery was similar to the time course of stress relaxation. CONCLUSIONS: Long duration stretches are required to produce a large proportion of the maximal possible stress relaxation. Recovery is initially rapid when the stretch is released. RELEVANCE: These data provide a description of the time course of the effects of stretch, and of the subsequent relief of stretch, on mechanical properties of human ankles.

Kinematics of rotational mobilisation of the lumbar spine.

OBJECTIVE: The purposes of this study were to measure the movements of the lumbar spine produced by rotational mobilisation, and to study the effects of different grades of mobilisation on the movements produced. DESIGN: Kinematics of rotational mobilisation was assessed with an electromagnetic tracking device. BACKGROUND: Rotational mobilisation is frequently used in the treatment of back pain, but there was no information on its mechanical effects. METHODS: Movements of the lumbar spine were measured in 14 healthy volunteers when they were subjected to grades I to IV left rotational mobilisation. RESULTS: In the starting positions, the spines were found to be flexed, axially rotated to the left and laterally bent to the right. As the mobilisation grade increased, the spine was axially rotated further into the range. Rotational mobilisation was found to produce oscillatory movements of the lumbar spine in all three anatomical planes. It produced axial rotation which was accompanied by lateral bending in the opposite direction and sagittal rotation. The mean frequency of the oscillatory movements was 1.4 Hz. The amplitude of the oscillations was small, and was found to be increased in grades II and III mobilisation. CONCLUSION: Rotational mobilisation may be able to restore lost movements of the lumbar spine in any of the three anatomical planes.

Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo.

Many human breast tumors are driven by high intratumor concentrations of 17beta-estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequately assessed and remains unclear. To evaluate the role of STS further, we transduced estrogen-dependent MCF-7 human breast cancer cells with a retroviral vector directing the constitutive expression of the human STS gene. Gene integration was confirmed by Southern hybridization, production of the appropriately sized messenger RNA by Northern hybridization, and expression of functional protein by metabolism of [(3)H]estrone sulfate to [(3)H]estrone. Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg protein.h in STS-transduced cells (STS Clone 20), levels comparable to those seen in some human breast tumors. Lower levels of endogenous activity are seen in MCF-7 cells (13.0 pmol estrone/mg protein.h) and in cells transduced with vector lacking the STS gene (Vector 3 cells; 12.0 pmol estrone/mg protein.h). 17beta-Estradiol sulfate induces expression of the progesterone receptor messenger RNA only in STS Clone 20 cells, whereas estrone sulfate produces the greatest stimulation of anchorage-independent growth in these cells. STS Clone 20 cells retain responsiveness to antiestrogens, which block the ability of estrogen sulfate to increase the proportion of cells in both the S and G(2)/M phases of the cell cycle. Consistent with these in vitro observations, only STS Clone 20 cells exhibit a significant increase in the proportion of proliferating tumors in nude ovariectomized mice supplemented with 17beta-estradiol sulfate. The primary activity in vivo appears to be from intratumor STS, rather than hepatic STS. Surprisingly, 17beta-estradiol sulfate appears more effective than 17beta-estradiol when both are administered at comparable concentrations. This effect, which is seen only in STS Clone 20 cells, may reflect differences in the cellular pharmacology of exogenous estrogens compared with those released by the activity of intracellular STS. These studies directly demonstrate that intratumor STS activity can support estrogen-dependent tumorigenicity in an experimental model and may contribute to the promotion of human breast tumors.

The role of spinal tissues in resisting posteroanterior forces applied to the lumbar spine.

OBJECTIVE: To determine the effects of the dissection of spinal tissues on the mechanical behavior of motion segments under the application of posteroanterior forces. DESIGN: A cadaveric motion segment study. SETTING: A tissue mechanics research laboratory. PROCEDURE: Anterior shear and extension moment were applied to 10 motion segments to simulate the clinical situation when posteroanterior forces were applied to the spine. The movements of the specimens in the sagittal plane were studied by a camera. Spinal tissues were dissected sequentially, and the mechanical testing was repeated after the dissection of each tissue. RESULTS: The most significant movements produced were extension and superior translation of the anteroinferior corner of the superior vertebral body. Translational movements in the other directions were small. The dissection of the posterior ligaments and zygapophyseal joints did not lead to significant changes in the movements. CONCLUSIONS: Injuries of the posterior ligaments are unlikely to alter the mechanical response of the spine to posteroanterior forces. However, these posterior tissues are pain sensitive and may be subjected to large strains and elicit symptoms.

Fatigue of abdominal and paraspinal muscles during sustained loading of the trunk in the coronal plane.

OBJECTIVE: To measure fatigue-related changes in the electromyographic signals of trunk muscles during lateral bend loading, and to determine the effects of load magnitude, gender, and contraction time on these changes. DESIGN: A factorial experimental design. SETTING: A research laboratory. PARTICIPANTS: Twenty-four healthy volunteers (12 men, 12 women; mean age +/- SD, 22.9 +/- 3.1 yrs). INTERVENTION: Subjects sustained lateral bend loads at 20%, 40%, and 60% of their maximal exertion. OUTCOME MEASURES: Median frequency and total power of the power spectrum of the electromyographic signals. RESULTS: Trunk muscles' median frequency signals decreased and their total power increased as contraction time increased. These changes became more pronounced as the magnitude of loading increased. Men and women showed a similar rate of median frequency decline, but the total power of signals in men was larger than that in women. All muscles showed signs of fatigue, except that at 20% of maximal exertion only thoracic erector spinae fatigued significantly. CONCLUSIONS: Endurance training of paraspinal and abdominal muscles may be useful in preventing low back pain associated with lateral bend loading. The risk of back pain is similar in both genders and is higher with larger load magnitude and longer contraction time.

Passive moment about the hip in straight leg raising.

OBJECTIVE: The purpose of this examine is to study the load-deformation characteristics of the hip in straight leg raising. DESIGN: An experimental study in which passive moment about the hip was determined as a function of hip angle. BACKGROUND: Straight leg raising is widely employed in clinical examination, and there is little information on its mechanical characteristics. METHODS: Fourteen healthy volunteers were recruited for this study. Three trials of straight leg raise tests were performed while subjects lay supine on a plinth that was fitted with load cells. An electrogoniometer was employed to measure hip flexion during the test. Resistive moment at the hip was determined using a dynamic biomechanical model. RESULTS: The present experimental method was shown to be highly reliable. The moment-angle curves of all subjects were shown to follow an exponential function. CONCLUSION: Stiffness and strain energy of posterior hip tissues could be derived from the moment-angle curves. Evaluation of such elastic properties is clinically important as they may be altered with injuries of the tissues. RELEVANCE: Clinically, contracture of hamstring muscles and other posterior hip tissues is evaluated by measuring the available range of hip flexion in straight leg raising. However, this does not provide any information on the elastic properties of the tissues. The present study reports a reliable method of evaluating such properties.

Are dental anomalies risk factors for apical root resorption in orthodontic patients?

Regression analyses suggest a weak prediction power of identified risk factors for apical root resorption in orthodontic patients, indicating the presence of etiologic or causative factors that have not yet been disclosed. To investigate the possible significance of dental anomalies as risk factors, pretreatment and posttreatment periapical radiographs of 84 patients with presence of at least one dental anomaly and of 84 patients without such anomalies were compared. The patients in the two groups were matched according to age, gender, Angle Class, extraction therapy, overbite, and treatment time. Apical root resorption was calculated by subtracting posttreatment tooth length measurements from the corresponding pretreatment measurements. Two sample t tests revealed no differences in mean root resorption between the patients in the two groups (P = .88). Stepwise regression analyses did not identify any of the individual anomalies as risk factors. In addition, patients with more than one anomaly did not appear to be at increased risk.

EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in caenorhabditis elegans.

The Caenorhabditis elegans gene eat-4 affects multiple glutamatergic neurotransmission pathways. We find that eat-4 encodes a protein similar in sequence to a mammalian brain-specific sodium-dependent inorganic phosphate cotransporter I (BNPI). Like BNPI in the rat CNS, eat-4 is expressed predominantly in a specific subset of neurons, including several proposed to be glutamatergic. Loss-of-function mutations in eat-4 cause defective glutamatergic chemical transmission but appear to have little effect on other functions of neurons. Our data suggest that phosphate ions imported into glutamatergic neurons through transporters such as EAT-4 and BNPI are required specifically for glutamatergic neurotransmission.

Mutations in the alpha1 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans.

The control of excitable cell action potentials is central to animal behavior. We show that the egl-19 gene plays a pivotal role in regulating muscle excitation and contraction in the nematode Caenorhabditis elegans and encodes the alphal subunit of a homologue of vertebrate L-type voltage-activated Ca2+ channels. Semi-dominant, gain-of-function mutations in egl-19 cause myotonia: mutant muscle action potentials are prolonged and the relaxation delayed. Partial loss-of-function mutations cause slow muscle depolarization and feeble contraction. The most severe loss-of-function mutants lack muscle contraction and die as embryos. We localized two myotonic mutations in the sixth membrane-spanning domain of the first repeat (IS6) region, which has been shown to be responsible for voltage-dependent inactivation. A third myotonic mutation implicates IIIS4, a region involved in sensing plasma-membrane voltage change, in the inactivation process.

Compartment-selective sensitivity of cardiovascular morphogenesis to combinations of retinoic acid receptor gene mutations.

Several aspects of normal cardiovascular development require signaling by the vitamin A metabolite retinoic acid. We have previously established germ-line mutations in mice in the genes that encode the RAR alpha 1, RAR beta, and RXR alpha retinoic acid receptors as a means of studying the function of these receptors in vivo. Although mutation of RXR alpha results in fetal ventricular defects, the RAR alpha 1 and RAR beta mutations are apparently nonphenotypic in the heart and elsewhere. In this study, we have established and analyzed combinations of these receptor gene mutations. Malformations of the ventricular chamber (chamber hypoplasia and muscular ventricular septal defects), conotruncus (double-outlet right ventricle, transposition, and membranous ventricular septal defects), aortic sac (persistent truncus arteriosus and aorticopulmonary window), and aortic arch-derived arteries were recovered in various combinations of the RAR alpha 1, RAR beta, and RXR alpha gene mutations. Depending on the combination of receptor mutations, selective defects were obtained in specific cardiovascular compartments, suggestive of differential expression or function of each receptor within domains of the developing heart.

The relation of prosocial and antisocial behavior to personality and peer relationships of Hong Kong Chinese adolescents.

The prosocial and antisocial behaviors of 2,862 Hong Kong Chinese adolescents were investigated. The major findings were as follows: (a) boys were more antisocial than girls: (b) negative peer influences were significantly stronger in boys than in girls, whereas positive peer influences were significantly stronger in girls than in boys; (c) antisocial adolescents tended to perceive their best friend as antisocial and exerting more negative influences on them, whereas prosocial adolescents tended to perceive their best friend as prosocial and exerting more positive influences on them; (d) antisocial behavior was positively associated with psychoticism and neuroticism; and (e) academic achievement tended to have a positive relation with prosocial behavior and a negative relation with antisocial behavior.

eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling.

The Drosophila melanogaster genes Passover and l(1)ogre and the Caenorhabditis elegans gene unc-7 define a gene family whose function is not known. We have isolated and characterized the C. elegans gene eat-5, which is required for synchronized pharyngeal muscle contractions, and find that it is a new member of this family. Simultaneous electrical and video recordings reveal that in eat-5 mutants, action potentials of muscles in the anterior and posterior pharynx are unsynchronized. Injection of carboxyfluorescein into muscles of the posterior pharynx demonstrates that all pharyngeal muscles are dye-coupled in wild-type animals; in eat-5 mutants, however, muscles of the anterior pharynx are no longer dye-coupled to posterior pharyngeal muscles. We show that a gene fusion of eat-5 to the green fluorescent protein is expressed in pharyngeal muscles. unc-7 and eat-5 are two of at least sixteen members of this family in C. elegans as determined by database searches and PCR-based screens. The amino acid sequences of five of these members in C. elegans have been deduced from cDNA sequences. Polypeptides of the family are predicted to have four transmembrane domains with cytoplasmic amino and carboxyl termini. We have constructed fusions of one of these polypeptides with beta-galactosidase and with green fluorescent protein. The fusion proteins appear to be localized in a punctate pattern at or near plasma membranes. We speculate that this gene family is required for the formation of gap junctions.

Expression of prokaryotic HhaI DNA methyltransferase is transforming and lethal to NIH 3T3 cells.

In neoplastic cells, levels of DNA methyltransferase activity are often increased, and evidence is accruing to suggest an important role for this event in tumorigenesis. To evaluate this possibility further, and to investigate the contribution of increasing de novo, as opposed to maintenance, DNA methylation in mammalian cells, we expressed the bacterial HhaI methyltransferase in cultured murine fibroblasts. This enzyme is a pure de novo DNA methyltransferase that methylates the internal C in the sequence GCGC. We find that both constitutive and induced expression of the wild-type HhaI results, primarily, in lethality to the cells. However, surviving cell clones that express low levels of M. HhaI demonstrate increased tumorigenicity as assessed by soft agar cloning efficiency (8.6% for sense HhaI-transduced PA 317 cells versus 0.4% for antisense controls; 1.7% for sense HhaI-transfected NIH 3T3 cells versus 0% for a mutant HhaI control) and tumorigenicity in nude mouse heterotransplants (75% for sense HhaI-transduced PA 317 cells versus 18.5% for antisense controls). DNA isolated from the clonogenic sense HhaI clones, versus clones expressing the mutant HhaI gene, has no increase in overall CpG methylation but an average of 27% (range, 16.7-38.9) increase in methylcytosine content at GCGC sites. These findings suggest that eukaryotic cells tolerate a narrow window of increase de novo DNA methylating capacity, above which cell death occurs and within cell transformation results. Our results further emphasize the potential role of increased DNA methyltransferase activity in the evolution of cancer.

The molecular genetics of retinoic acid receptors: cardiovascular and limb development.

The vitamin A metabolite retinoic acid (RA) is utilized as a signalling molecule in wide variety of developmental processes, defined by defects which occur after nutritional vitamin A deficiency or after exposure to excess vitamin A. We have initiated a genetic analysis of RA function through the establishment of lines of mice which carry germline mutations in the genes which encode retinoid receptors. Defects which result from developmental RA deficiency or excess have been recovered in embryos which are deficient in various combinations of retinoid receptors. In this chapter, our current understanding of the role of RA and retinoid receptors in cardiovascular and limb development are described, as for these our level of understanding is most advanced.