Biomedical subjects

M Moreau

Publications and source records attributed to M Moreau.

At least 91 records · Page 5Linked to original sources

PubMed1999

Tissue factor pathway inhibitor is expressed by human monocyte-derived macrophages : relationship to tissue factor induction by cholesterol and oxidized LDL.

Lipid-laden macrophages express tissue factor (TF), which may activate the extrinsic coagulation pathway on rupture of the atherosclerotic plaque. Tissue factor pathway inhibitor (TFPI) is a major regulator of TF-induced coagulation. We evaluated the possibility that monocyte-derived macrophages express this protein, thereby contributing to regulation of TF activity (TFact). Equally, we investigated the effect of cholesterol and of oxidized LDL (Ox-LDL) on the expression of TFPI and TF by human monocyte-derived macrophages (HMDMs). Northern blot analysis of TFPI mRNA from cultured HMDMs revealed a single band at 4.2 kb with weak intensity; this finding was confirmed by reverse transcription-polymerase chain reaction. Gel filtration of HMDM supernatants showed the presence of an active 100-kDa form of TFPI, which was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions; under reducing conditions, however, the immunoblot revealed a 40-kDa form of TFPI. The TFPI in HMDM supernatants possessed heparin-binding affinity, suggesting potential interaction of TFPI with heparan sulfate proteoglycans. Stimulation of foam cell formation by incubation of macrophages for 48 hours with exogenous free cholesterol indicated that neither the biological activity nor the de novo synthesis of TFPI protein was affected. In contrast, cholesterol loading with exogenous free cholesterol induced significant upregulation of total TFact (2.6-fold: 25.0 versus 9.4 mU/mg cell protein, cholesterol-treated versus control cells; P<0. 05); such induction was not correlated with an elevation in TF antigen (8.5 versus 7.8 ng/mg cell protein, cholesterol-treated versus control cells). Similarly, cholesterol-rich Ox-LDL induced an increase in TFact (1.9-fold: 18.9 versus 10.0 mU/mg cell protein, Ox-LDL-treated versus control cells; P<0.05); by contrast, the amount of TF antigen remained unchanged (7.1 versus 7.9 ng/mg cell protein, Ox-LDL-treated versus control cells). Our data indicate that enhancement of the procoagulant activity of TF in macrophage-derived foam cells is not counterbalanced by upregulation of TFPI activity, suggesting that lesion foam cells are in a procoagulant state; they may therefore contribute to thrombus generation on plaque rupture.

Anticoagulants↗

PubMed1999

The effects of melatonin therapy on the development of scoliosis after pinealectomy in the chicken.

The mechanism underlying the development of scoliosis after pinealectomy in young chickens is unknown. However, since the main product of the pineal gland is melatonin, melatonin remains an obvious focus in studies designed to discover this mechanism. One confounding factor is that serum melatonin levels are close to zero after pinealectomy but scoliosis does not develop in all chickens that have had this procedure. Therefore, the role of melatonin in the development of scoliosis in chickens after pinealectomy remains controversial. In the current investigation, two pilot studies demonstrated that a physiological therapeutic dose of melatonin (2.5 milligrams per kilogram of body weight) restored the circadian rhythm of melatonin, as measured by serum assay. In the main study, this dose was administered daily starting either immediately after the pinealectomy or two weeks after it, when scoliosis had developed. Scoliosis was assessed on weekly radiographs, and the Cobb angle was determined for all chickens in which scoliosis developed. Overall, scoliosis developed in only 56 percent (fifty) of the eighty-nine chickens that had had a pinealectomy; this rate was consistent throughout all experimental groups. Scoliosis did not develop in any of the control chickens, which did not have a pinealectomy. On the basis of the average Cobb angles in the chickens in which scoliosis had developed, it was determined that neither the prevalence nor the pattern of the scoliosis was affected by the therapy in any of the experimental groups. It was thus concluded that melatonin therapy after pinealectomy in young chickens has no effect on the development or progression of scoliosis. These results raise doubts regarding the role of melatonin in the development of scoliosis after pinealectomy in the young chicken.

Animals↗

PubMed1999

[A new vaccine concept: polysaccharide conjugate vaccines].

Polysaccharide-based vaccines such as the vaccines against Neisseiria meningitidis group A and C or Streptococcus pneumoniae have proved their efficacy in children and adults. Nevertheless they induce B cell mediated immunological response and therefore fail to protect infants. In the eighties appeared a new concept of Polysaccharide based vaccine for infants: Polysaccharide conjugate vaccines. Coupling polysaccharide to carrier protein transforms the T-independent antigen into T-dependant antigen. The first conjugate vaccines for the prevention of infections caused by Haemophilus influenzae type b were a success, with a 95% efficacy. A worldwide vaccination program might lead to the eradication of that bacterial disease. New vaccines are currently under development, the next conjugate vaccine should be one against Streptococcus pneumoniae. First published clinical data are very promising and confirmed the potential of the polysaccharide conjugate vaccine approach against bacterial infections.

Animals↗

PubMed1998

Changes in serum melatonin levels in response to pinealectomy in the chicken and its correlation with development of scoliosis.

STUDY DESIGN: Normal, sham, and groups of chickens subjected to pinealectomy from which serum melatonin levels were measured and correlated with scoliosis development in a period of 5 weeks. OBJECTIVES: To measure serum melatonin levels in chickens subjected to pinealectomy and control chickens and correlate findings with development of scoliosis. SUMMARY OF BACKGROUND DATA: In a previous study by others, scoliosis developed in 100% of chickens subjected to pinealectomy, and serum melatonin levels were found to be reduced. Previous results in a study by the authors showed scoliosis developing in only approximately 55% of chickens that underwent pinealectomy. METHODS: Young chickens were subjected to pinealectomy. Control groups consisted of sham operation and normal groups. Radiographs and blood samples were taken at weekly intervals to monitor scoliosis development and measure serum melatonin levels using radioimmunoassay techniques. RESULTS: Scoliosis developed in only 52% of chickens that underwent pinealectomy, but all had low levels of serum melatonin and no circadian rhythm. The chickens in the two control groups maintained normal serum melatonin levels and rhythms. CONCLUSIONS: Pinealectomy in young chickens reduces serum melatonin levels and eliminates the melatonin circadian rhythm. It can also produce scoliosis, but low levels of serum melatonin are a poor predictor of development of scoliosis.

Animals↗

PubMed1998

Plasma membrane depolarization-activated calcium channels, stimulated by microtubule-depolymerizing drugs in wild-type Arabidopsis thaliana protoplasts, display constitutively large activities and a longer half-life in ton 2 mutant cells affected in the organization of cortical microtubules.

Depolarization-activated plasma membrane calcium channels have been suggested to play prominent roles in signal perception and transduction processes during growth and development of higher plants. The existence of such channels has recently been established in higher plant cells. However, patch-clamp experiments have shown that their activity is very low and decreases very rapidly after the establishment of the whole-cell configuration, due most probably to protein-protein interactions involving microtubules. The present study takes advantage of the existence of Arabidopsis thaliana mutants referred to as ton 2 mutants reported to be affected in their microtubule organization, to address the physiological relevance of such a hypothesis based on a pharmacological approach. Patch-clamp studies showed that depolarization-activated calcium channel activities in ton 2 protoplasts were 10-fold higher and their relative half-life three-times longer than in wild-type protoplasts. In addition, oryzalin and colchicine, which disrupt the microtubule organization, stimulated and stabilized calcium channel activities in wild-type but remained ineffective on ton 2 protoplasts. However, although the microtubules appeared important in the regulation of calcium channels in A. thaliana, immunocytological staining of tubulin demonstrated that there was no visible difference in the general organization of microtubule networks or in the amount of microtubules bound to the plasma membrane in ton 2 and wild-type protoplasts. It is suggested that the down-regulation of calcium channels implicating microtubules involves additional component(s) corresponding probably to gene product(s) defective in ton 2 mutant cells.

Arabidopsis↗

PubMed1997

HgCl2-induced interleukin-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels.

Mercuric chloride (HgCl2) induces T helper 2 (Th2) autoreactive anti-class II T cells in Brown Norway rats. These cells produce interleukin (IL)-4 and induce a B cell polyclonal activation that is responsible for autoimmune disease. In Brown Norway rats, HgCl2 triggers early IL-4 mRNA expression both in vivo and in vitro by T cells, which may explain why autoreactive anti-class II T cells acquire a Th2 phenotype. The aim of this study was to explore the transduction pathways by which this chemical operates. By using two murine T cell hybridomas that express IL-4 mRNA upon stimulation with HgCl2, we demonstrate that: 1) HgCl2 acts at the transcriptional level without requiring de novo protein synthesis; 2) HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels; 3) calcium/calcineurin-dependent pathway and protein kinase C activation are both implicated in HgCl2-induced IL-4 gene expression; and 4) HgCl2 can activate directly protein kinase C, which might be one of the main intracellular target for HgCl2. These data are in agreement with an effect of HgCl2 which is independent of antigen-specific recognition. It may explain the T cell polyclonal activation in the mercury model and the expansion of pathogenic autoreactive anti-class II Th2 cells in this context.

Animals↗

PubMed1997

Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans.

STUDY DESIGN: The characteristics of the scoliosis that develops after pinealectomy in young chickens were determined from weekly posteroanterior radiographs. These data were compared with similar data collected from human patients with adolescent idiopathic scoliosis. OBJECTIVES: To characterize the scoliosis produced in young chickens after pinealectomy and to compare these characteristics with those seen in human patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although it has been recognized that pinealectomy produces scoliosis in chickens, the characteristics of these curves have never been well described other than by simple visual descriptions. METHODS: The characteristics of the scoliosis produced in chickens after pinealectomy done 3 days after hatching were measured from radiographs taken at weekly intervals. These characteristics were compared with similar data collected from human patients with adolescent idiopathic scoliosis. RESULTS: Similarities included development of single and double curves, degree of curvature, stability of the curve, numbers of vertebrae involved, direction of rotation, and progression characteristics. Differences included wedged vertebrae in the chickens, in conjunction with curve development and increased variability in vertebrae involved. CONCLUSIONS: There are many similarities in the development of scoliosis in young chickens after pinealectomy and in children with adolescent idiopathic scoliosis. The few differences might be related to the different biomechanical properties associated with the spine in the two species.

Adolescent↗

PubMed1997

Heteronuclear NMR studies of E. coli translation initiation factor IF3. Evidence that the inter-domain region is disordered in solution.

Initiation factor IF3 from Escherichia coli plays a critical role in the selection of the correct initiation codon. This protein is composed of two domains, connected by a lysin-rich hydrophilic linker. The conformation of native IF3 was investigated by heteronuclear NMR spectroscopy. The two domains are independent and show little or no interaction. Heteronuclear relaxation studies of a sample selectively labelled on lysine residues demonstrates that the inter-domain linker is highly flexible, exhibiting increased 15N T2 values and negative 1H[15N] nuclear Overhause effects over a length of at least eight residues. Analysis of the rotational correlation times further shows that the motions of the two domains are most likely uncorrelated. The inter-domain linker thus displays almost totally unrestricted motions. Accordingly, the amide protons in the central region are shown to be in fast exchange with water. Such a high degree of flexibility of the inter-domain linker might be required for IF3 domains to interact with distant regions of the ribosome.

Bacterial Proteins↗

PubMed1997

Identification of the location, extent, and pathway of sensory neurologic feedback after mechanical stimulation of a lateral spinal ligament in chickens.

STUDY DESIGN: This study traced the location, extent, and pathway of sensory feedback after the mechanical stretching of a lateral spinal ligament in young chickens. The pathway was traced by locating the sites of Fos protein production in neuronal cell bodies at various sites in the nervous system. OBJECTIVES: To trace the location, extent, and pathway of sensory feedback after the mechanical stretching of a lateral spinal ligament in young chickens. SUMMARY OF BACKGROUND DATA: The innervation of ligaments is thought to form part of a protective feedback mechanism to provide stability for joints. The precise pathway and extent of the feedback for spinal ligaments is currently unknown. Such information would provide a clear focus for future studies, especially for diseases such as scoliosis where it has been suggested that there is abnormality in perception of sensory feedback. METHODS: The intertransverse ligament on the right side at T3-T4 in 4-week-old chickens was exposed by blunt dissection. After Fos production resulting from the surgery had been stopped, the ligament was stretched mechanically and repeatedly for 60 minutes using a 300-g weight. Various areas of the nervous system then were sectioned and processed immunohistochemically to identify areas of Fos production in nerve cell bodies. The presence of Fos indicated neurons that had been stimulated by the stretching the ligament, including interneurons along the feedback pathway. RESULTS: Fos protein was identified in nerve cell bodies in the dorsal root ganglia and intermediate gray matter of the spinal cord at the level of stimulation as well as at several spinal cord levels above and below the site of stimulation. Identification was made on the ipsilateral and the contralateral sides, although the extent of Fos production was less on the contralateral side. Fos presence also was identified in sympathetic ganglia at these sites. Nerve cell bodies in the combined nucleus cuneatus and gracilis in the medulla oblongata, the vestibular nuclei, and the thalamus also contained Fos-positive particles. CONCLUSIONS: Stretching a single lateral ligament of the spine produces a barrage of sensory feedback from several spinal cord levels on both sides of the spinal cord. This sensory information also is transferred to higher levels in the brain, including the nucleus gracilis and cuneatus, the vestibular nuclei, and the thalamus. These sites of Fos production suggest the locations of pathways for this sensory information, which include the dorsal columns and the spinocerebellar tracts. The information obtained from this study provides a clear focus for future studies in this area, particularly for diseases such as scoliosis where it is thought that incorrect perception of sensory information from the ligaments might be a major contributing factor.

Animals↗

PubMed1997

Organization of cytoskeleton controls the changes in cytosolic calcium of cold-shocked Nicotiana plumbaginifolia protoplasts.

Using Nicotiana plumbaginifolia constitutively expressing the recombinant bioluminescent calcium indicator, aequorin, it has been previously demonstrated that plant cells react to cold-shock by an immediate rise in cytosolic calcium. Such an opportune system has been exploited to address the regulatory pathway involved in the calcium response. For this purpose, we have used protoplasts derived from N. plumbaginifolia leaves that behave as the whole plant but with a better reproducibility. By both immunodetecting cytoskeletal components on membrane ghosts and measuring the relative change in cytosolic calcium, we demonstrate that the organization of the cytoskeleton has profound influences on the calcium response. The disruption of the microtubule meshwork by various active drugs, such as colchicin, oryzalin and vinblastin, leads to an important increase in the cytosolic calcium (up to 400 nM) in cold-shocked protoplasts over control. beta-Lumicolchicin, an inactive analogue of colchicin, is ineffective either on cytoplasmic calcium increase or on microtubule organization. A microfilament disrupting drug, cytochalasin D, exerts a slight stimulatory effect, whereas the simultaneous disruption of microtubule and microfilament meshworks results in a dramatic increase in the calcium response to cold-shock. The results described in the present paper illustrate the role of the intracellular organization and, more specifically, the role of cytoskeleton in controlling the intensity of calcium response to an extracellular stimulus.

Actin Cytoskeleton↗

PubMed1997

L-type calcium channel activation controls the in vivo transduction of the neuralizing signal in the amphibian embryos.

We have analyzed the transduction pathways involved in the triggering of neural induction, in amphibian embryos, in vivo. Using a plasmid construction, we have targetted the bioluminescent calcium probe aequorin to the plasma membrane of ectoderm cells of the amphibian Pleurodeles waltl before gastrulation. We have demonstrated that the in vivo triggering of neural induction depends on the activation of calcium-dependent pathways and involves L-type calcium channels. Furthermore, on excised ectoderm taken at the gastrula stage, we show that noggin, a protein currently considered as one of the natural inducers, also activates L-type calcium channels. This activation represents the first necessary event to determine cells of the dorsal ectoderm toward the neural pathway.

Aequorin↗

PubMed1997

X-ray imaging technique for in vitro tissue composition measurements using saline/iodine displacement: technique optimization.

An in vitro radiographic technique which uses saline/iodine displacement has been developed to study the thickness of bone-equivalent and soft-tissue-equivalent materials within atherosclerotic plaques in arterial specimens which have been cut open longitudinally and laid flat. Results concerning the optimization of the imaging parameters are presented and discussed. The technique consists of imaging arterial specimens under two different conditions: (1) when it is immersed in an isotonic saline solution, to estimate the calcium content, and (2) when it is immersed in a concentrated iodine solution, to estimate the total thickness of the specimen. Calibration step wedges made out of bone-mimicking and soft-tissue-mimicking materials are imaged simultaneously to generate calibration curves which are used to convert the radiographs into bone-equivalent and soft-tissue-equivalent thickness images. The optimal spectral parameters were determined to be 45 and 100 kVp for the saline and the iodine images, respectively, with a significant amount of added filtration for both images. Inherent systematic inaccuracies due to (1) the nonidealities due to linear attenuation coefficient mismatch between tissue and calibration materials and (2) beam hardening due to heel effect are determined theoretically, and can be used to correct a set of bone-equivalent and the soft-tissue-equivalent images to within +/- 6 microns with an ideal, noise-free imaging system.

Angiography↗

PubMed1997

Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII: correction of image intensifier distortion.

X-ray image intensifiers (XRIIs) have many applications in diagnostic imaging including acquisition of near-real-time projection images of the intracranial and coronary vasculature. Recently, there has been some interest in using this projection data to generate three-dimensional (3-D) computed tomographic (CT) reconstructions. The XRII and x-ray tube are rotated around the object, acquiring sufficient data for the simultaneous reconstruction of many transverse slices. Three-dimensional reconstructions are compromised, however, if the projection data is geometrically distorted in any way. Previous studies have shown the distortion in XRIIs to be substantial and to be highly angular dependent. In this paper, we present a global correction technique which provides a table of correction coefficients for an image acquired at any arbitrary angle about the patient. The coefficients are generated using a linear least-squares fit between the detected and known locations of a grid of small steel beads which is attached to the XRII (27 cm nominal diameter). We have performed corrections on 100 images obtained during rotation of the gantry through 200 degrees and find that a fifth-order polynomial provides optimum image distortion reduction (mean residual distortion of 0.07 pixels), however, fourth-order polynomials provide sufficient distortion reduction for our application (mean residual displacement of 0.1 pixels). Using sixth-order polynomials does not provide a statistically significant reduction in image distortion. The spatial distribution of residual distortion did not demonstrate any particular pattern over the face of the XRII. Image angle and coefficient angle must be known to within +/- 2 degrees in order to keep the mean residual distortion be approximately 0.5 pixels.

Humans↗

PubMed1997

X-ray imaging technique for in vitro tissue composition measurements using saline/iodine displacement: experimental verification.

A novel in vitro radiographic technique using saline/iodine displacement, which can be used to study the bone-equivalent and soft-tissue-equivalent thicknesses within vessel walls, was applied to imaging of arterial specimens. Results concerning the accuracy and precision of the bone-equivalent and soft-tissue-equivalent thickness measurements obtained with this technique are reported and discussed. Planar radiographs of a phantom were obtained under two different conditions: (1) when it is immersed in an isotonic saline solution using a 45-kVp spectrum with no added filtration, and (2) when it is immersed in a concentrated iodine solution using a 100-kVp spectrum with 12.5-mm aluminum-added filtration. Calibration step wedges made out of bone-mimicking and soft-tissue-mimicking materials are imaged simultaneously to generate calibration curves that are used to convert the radiographs into bone-equivalent and total-thickness images. A soft-tissue-thickness image is obtained from the subtraction of the bone-equivalent image from the total-thickness image. Thickness measurements obtained from these images yielded average accuracies of +/- 110 microns for both the bone-equivalent and the soft-tissue-equivalent images. The precision (one standard deviation) of the thickness measurements was +/- 60 and +/- 90 microns for the bone-equivalent and the soft-tissue-equivalent images, respectively. In conclusion, since calcified plaque can become as thick as 3-4 mm, the saline/iodine displacement technique has the potential to be a very useful technique for ex vivo studies of the progression of atherosclerosis because of its high accuracy and precision.

Angiography↗

PubMed1997

A comparison of the innervation characteristics of the lateral spinal ligaments between normal subjects and patients with adolescent idiopathic scoliosis.

Evidence is rapidly accumulating to suggest that general proprioceptive dysfunction might be a major contributing factor in the development of adolescent idiopathic scoliosis (AIS). The innervation of appropriate ligaments which has been shown to be involved in proprioceptive feedback mechanisms, has also been suggested to play a part in this sensory dysfunction. Accordingly, this study compared the innervation characteristics of lateral spinal ligaments from patients with AIS to similar measurements from control subjects. Using an antibody to neurofilament protein, Ruffini corpuscles, small and large nerve bundles, and free nerve endings were identified and their numbers and distribution patterns compared. In the control group, the innervation was found to be symmetrical between left and right sides but was more concentrated in the ventral portion of each ligament. No apparent morphological defect of the innervation was found in the lateral spinal ligaments of the scoliosis patients but the innervation densities of Ruffini corpuscles, single nerve fibres and total neural elements were significantly lower (p<0.01) than those found in normal subjects. These results suggest a possible mechanism for the production of AIS and warrant further study.

Adolescent↗

PubMed1997

Impact of a combination of a calcium antagonist and a beta-blocker on cell- and copper-mediated oxidation of LDL and on the accumulation and efflux of cholesterol in human macrophages and murine J774 cells.

Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. In the absence of data pertaining to the potential cardioprotective action of an association of such agents, we have investigated the impact of nifedipine and atenolol, alone or in combination, on the capacity of monocyte-macrophages (ex vivo) and copper ions (in vitro) to oxidize LDL and on intracellular metabolism and efflux of free and esterified forms of cholesterol in human macrophages and foam cells. At concentrations up to 100 micromol/L, atenolol had no effect on the oxidative resistance of LDL; on the contrary, nifedipine displayed a significant dose-dependent capacity to protect LDL during copper-mediated oxidation (100 micromol/L; P<.001). Using a DPPH radical generating system, nifedipine was shown to exert free radical-trapping activity (molar ratio of scavenging activity, nifedipine:alpha-tocopherol, 1:114). The addition of atenolol to nifedipine was without effect on the antioxidant activity of the calcium antagonist. In experiments in which oxidative modification was mediated by monocyte-macrophages, nifedipine but not atenolol conserved its antioxidant capacity. Furthermore, we demonstrated that association of atenolol with nifedipine did not modify the antioxidant properties of nifedipine itself. Using a human monocyte-derived macrophage culture system, nifedipine, atenolol, or a combination of the two drugs was ineffective in inhibiting foam cell formation induced by acetylated LDL or oxidized LDL. However, atenolol (100 micromol/L) increased cellular accumulation of cholesteryl ester (+17%; P<.05), whereas nifedipine (100 micromol/L) decreased total cholesterol (-37.4%; P<.05) accumulation induced by acetylated LDL in the mouse macrophage cell line J774. A combination of the two drugs neutralized these antagonistic effects. None of these results were reproduced during the oxidized LDL-induced transformation of murine J774 cells into foam cells. Furthermore, cholesterol efflux from preloaded human macrophages was equally unaffected by the addition of the drugs alone or in combination. It therefore seems unlikely that the beneficial effect of atenolol on coronary heart disease is mediated by changes in either LDL oxidizability or cholesterol metabolism in human macrophages and foam cells. Our findings with nifedipine suggest, however, that this calcium antagonist may potentially exert antiatherosclerotic properties via a reduction of the oxidative modification of LDL, thereby affecting a reduction in foam cell formation and in the pathophysiological cellular activities of oxidized lipids, rather than by inducing a direct reduction in cholesterol accumulation in human foam cells of macrophage origin.

Adrenergic beta-Antagonists↗

PubMed1996

Activation of plasma membrane voltage-dependent calcium-permeable channels by disruption of microtubules in carrot cells.

Plasma membrane-bound voltage-dependent calcium channels may couple the perception of an initial stimulus to a regulated pathway for calcium influx. The activities of these channels have been shown to be very low and highly unstable but may be recruited by large-predepolarizing pulses, according to a process referred to as recruitment. By combining pharmacological and electrophysiological approaches, we demonstrate in the present paper that the cytoskeleton plays an important role in the regulation of the activity and stability of voltage-dependent calcium channels during whole-cell patch-clamp experiments on carrot protoplasts. Whereas drugs affecting the organization of the microfilament network have no measurable effect, the manipulation of the microtubule network elicits important changes. Thus, the addition of colchicine or oryzalin, which are known to disrupt microtubule organization, leads to a 6-10-fold increase in calcium channel activities and half-life. In contrast, stabilization of the microtubules by taxol has no effect on any of these parameters. The data obtained suggest that interactions of microtubules and voltage-dependent calcium channels by either direct or indirect mechanisms inhibit channel activities and decrease their half-life. In contrast, the disruption of the network overcomes such an inhibitory effect and allows the activation of calcium channels. It is speculated that under normal physiological conditions these protein-protein interactions may work in a reversible manner and contribute to signal transduction in higher plants.

Calcium Channels↗

PubMed1996

Melatonin levels in idiopathic scoliosis. Diurnal and nocturnal serum melatonin levels in girls with adolescent idiopathic scoliosis.

STUDY DESIGN: Matched pairs of adolescent girls were used to compare serum melatonin levels in adolescent patients and control subjects with idiopathic scoliosis during the day and in the middle of the night. OBJECTIVES: To compare serum melatonin levels in patients with adolescent idiopathic scoliosis and matched control subjects during the day and in the middle of the night. SUMMARY OF BACKGROUND DATA: Recent studies using the chick as the animal model have suggested that the pineal gland and its main product, melatonin, might be involved in the cause of scoliosis. There have been no studies of melatonin levels in patients with adolescent idiopathic scoliosis. METHODS: Blood was collected from seven adolescent girls with idiopathic scoliosis and a group of seven age-matched control subjects. Two samples were collected, one in the middle of the day and one in the middle of the night, to examine the diurnal variation of melatonin production. Serum melatonin levels were measured using a radioimmunoassay technique. RESULTS: No significant differences were found in serum melatonin levels between experimental and control groups either during the day, when melatonin levels were low, or during the night, when melatonin levels were high. CONCLUSIONS: Whereas pinealectomy in young chickens leads to reduced melatonin levels and the development of scoliosis, the results of this study suggest that melatonin levels in mature patients who already have severe scoliosis do not differ from healthy subjects. Whether melatonin levels differ in humans between healthy subjects and patients with scoliosis at the time of onset of the disease remains to be seen.

Adolescent↗