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At least 793 records · Page 44Linked to original sources
PubMed2006

Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance.

The Fanconi anemia (FA) pathway is a DNA damage-activated signaling pathway which regulates cellular resistance to DNA cross-linking agents. Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event. The cell cycle checkpoint kinase ATR is required for the efficient monoubiquitination of FANCD2, while another checkpoint kinase, ATM, directly phosphorylates FANCD2 and controls the ionizing radiation (IR)-inducible intra-S-phase checkpoint. In the present study, we identify two novel DNA damage-inducible phosphorylation sites on FANCD2, threonine 691 and serine 717. ATR phosphorylates FANCD2 on these two sites, thereby promoting FANCD2 monoubiquitination and enhancing cellular resistance to DNA cross-linking agents. Phosphorylation of the sites is required for establishment of the intra-S-phase checkpoint response. IR-inducible phosphorylation of threonine 691 and serine 717 is also dependent on ATM and is more strongly impaired when both ATM and ATR are knocked down. Threonine 691 is phosphorylated during normal S-phase progression in an ATM-dependent manner. These findings further support the functional connection of ATM/ATR kinases and FANCD2 in the DNA damage response and support a role for the FA pathway in the coordination of the S phase of the cell cycle.

Amino Acid Sequence↗
PubMed2001

Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae.

In eukaryotes, the ATM and ATR family proteins play a critical role in the DNA damage and replication checkpoint controls. These proteins are characterized by a kinase domain related to the phosphatidylinositol 3-kinase, but they have the ability to phosphorylate proteins. In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth. We have isolated the PIE1 gene in a two-hybrid screen for proteins that interact with Mec1, and we show that Pie1 interacts physically with Mec1 in vivo. Like MEC1, PIE1 is essential for cell growth, and deletion of the PIE1 gene causes defects in the DNA damage and replication block checkpoints similar to those observed in mec1Delta mutants. Rad53 hyperphosphorylation following DNA damage and replication block is also decreased in pie1Delta cells, as in mec1Delta cells. Pie1 has a limited homology to fission yeast Rad26, which forms a complex with the ATR family protein Rad3. Mutation of the region in Pie1 homologous to Rad26 results in a phenotype similar to that of the pie1Delta mutation. Mec1 protein kinase activity appears to be essential for checkpoint responses and cell growth. However, Mec1 kinase activity is unaffected by the pie1Delta mutation, suggesting that Pie1 regulates some essential function other than Mec1 kinase activity. Thus, Pie1 is structurally and functionally related to Rad26 and interacts with Mec1 to control checkpoints and cell proliferation.

Amino Acid Sequence↗
PubMed2004

Intra-S-phase checkpoint activation by direct CDK2 inhibition.

To ensure proper progression through a cell cycle, checkpoints have evolved to play a surveillance role in maintaining genomic integrity. In this study, we demonstrate that loss of CDK2 activity activates an intra-S-phase checkpoint. CDK2 inhibition triggers a p53-p21 response via ATM- and ATR-dependent p53 phosphorylation at serine 15. Phosphorylation of other ATM and ATR downstream substrates, such as H2AX, NBS1, CHK1, and CHK2 is also increased. We show that during S phase when CDK2 activity is inhibited, there is an unexpected loading of the minichromosome maintenance complex onto chromatin. In addition, there is an increased number of cells with more than 4N DNA content, detected in the absence of p53, suggesting that rereplication can occur as a result of CDK2 disruption. Our findings identify an important role for CDK2 in the maintenance of genomic stability, acting via an ATM- and ATR-dependent pathway.

Animals↗
PubMed2004

Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation.

Eukaryotic cells have evolved a complex mechanism for sensing DNA damage during genome replication. Activation of this pathway prevents entry into mitosis to allow for either DNA repair or, in the event of irreparable damage, commitment to apoptosis. Under conditions of replication stress, the damage signal is initiated by the ataxia-telangiectasia-mutated and Rad3-related kinase ATR. We recently demonstrated that the human immunodeficiency virus type 1 (HIV-1) gene product viral protein R (Vpr) arrests infected cells in the G(2) phase via the activation of ATR. In the present study, we show that the activation of ATR by Vpr is analogous to activation by certain genotoxic agents, both mechanistically and in its downstream consequences. Specifically, we show a requirement for Rad17 and Hus1 to induce G(2) arrest as well as Vpr-induced phosphorylation of histone 2A variant X (H2AX) and formation of nuclear foci containing H2AX and breast cancer susceptibility protein 1. These results demonstrate that G(2) arrest mediated by the HIV-1 gene product Vpr utilizes the cellular signaling pathway whose physiological function is to recognize replication stress. These findings should contribute to a greater understanding of how HIV-1 manipulates the CD4(+)-lymphocyte cell cycle and apoptosis induction in the progressive CD4(+)-lymphocyte depletion characteristic of HIV-1 pathogenesis.

Animals↗
PubMed2004

Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest.

Bloom's syndrome (BS) is a human genetic disorder associated with cancer predisposition. The BS gene product, BLM, is a member of the RecQ helicase family, which is required for the maintenance of genome stability in all organisms. In budding and fission yeasts, loss of RecQ helicase function confers sensitivity to inhibitors of DNA replication, such as hydroxyurea (HU), by failure to execute normal cell cycle progression following recovery from such an S-phase arrest. We have examined the role of the human BLM protein in recovery from S-phase arrest mediated by HU and have probed whether the stress-activated ATR kinase, which functions in checkpoint signaling during S-phase arrest, plays a role in the regulation of BLM function. We show that, consistent with a role for BLM in protection of human cells against the toxicity associated with arrest of DNA replication, BS cells are hypersensitive to HU. BLM physically associates with ATR (ataxia telangiectasia and rad3(+) related) protein and is phosphorylated on two residues in the N-terminal domain, Thr-99 and Thr-122, by this kinase. Moreover, BS cells ectopically expressing a BLM protein containing phosphorylation-resistant T99A/T122A substitutions fail to adequately recover from an HU-induced replication blockade, and the cells subsequently arrest at a caffeine-sensitive G(2)/M checkpoint. These abnormalities are not associated with a failure of the BLM-T99A/T122A protein to localize to replication foci or to colocalize either with ATR itself or with other proteins that are required for response to DNA damage, such as phosphorylated histone H2AX and RAD51. Our data indicate that RecQ helicases play a conserved role in recovery from perturbations in DNA replication and are consistent with a model in which RecQ helicases act to restore productive DNA replication following S-phase arrest and hence prevent subsequent genomic instability.

Adenosine Triphosphatases↗
PubMed1989

Adipose tissue and skeletal muscle blood flow during mental stress.

Mental stress [a modified Stroop color word conflict test (CWT)] increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

Adipose Tissue↗
PubMed1975

Effects of increased ambient pressure and nitrogen on man's monosynaptic reflexes.

Neurological signs during dives may result from altered excitability of central neurons. The present study assesses the effect of an increase in pressure from 1 to 3 ATA on the excitability of muscle spindles and alpha motoneurons by comparing the EMG amplitudes of the mechanically and electrically elicited monosynaptic reflexes of the gastrocnemius-soleus muscle in 10 normal adults breathing a normoxic oxygen-nitrogen gas mixture. At the surface the amplitude of the electrically elicited H response was matched to that of the mechanically elicited Achilles tendon reflex (ATR), but at depth these amplitudes became significantly different. In every subject the amplitude of the ATR, which depends upon the excitability of both muscle spindles and the alpha motoneurons, was reduced on an average of 38% (with a range of 12-75%). The H response bypasses the muscle spindles and hence, depends primarily upon alpha motoneuron excitability. Its amplitude was unaltered in four, reduced in three, and increased in three subjects. Since the ATR was always depressed despite the direction of change in the H response, we have concluded that an increase in ambient pressure (i.e., pressure per se, or nitrogen, or both) must have decreased the responsiveness of muscle spindles to the tendon tap via a reduction in fusimotor activity.

Achilles Tendon↗
PubMed1993

Influence of autonomic blockade on cardiovascular responses to exercise in rats.

The purposes of this study were to determine the role of the sympathetic and parasympathetic nervous systems in producing the heart rate (HR) response to dynamic exercise in rats and to determine the effect of attenuation of the HR response to exercise on blood flow redistribution. Sprague-Dawley rats (n = 10) were instrumented with arterial and venous catheters and Doppler flow probes. Mean arterial pressure (MAP), HR, mesenteric blood flow (MBF), and iliac blood flow (IBF) were determined during four exercise tests. On 4 consecutive days, rats were treated with saline (SAL, 1 mg/kg iv), atropine methyl nitrate (ATR, 2 mg/kg), timolol maleate (TIM, 0.5 mg/kg), and combined timolol and atropine. One minute of mild exercise (10 m/min) produced an increase in HR of 90 +/- 6 beats/min after SAL treatment, which was significantly less than the increment after ATR (56 +/- 5 beats/min) or TIM (4 +/- 3 beats/min). For the remainder of graded exercise, ATR treatment produced a modest attenuation in the increment in HR and no effect on MAP, IBF, and MBF. At 30 m/min, TIM markedly blunted the exercise-induced increment in HR (SAL, 138 +/- 8 beats/min; TIM, 53 +/- 4 beats/min) and IBF (SAL, 324 +/- 33%; TIM, 197 +/- 33%) with no effect on MAP or MBF. The results suggest that 1) the sympathetic nervous system is an important mediator of exercise-induced tachycardia in rats and 2) exercised-induced hyperemia, but not MAP, is attenuated by nonselective beta-blockade during exercise in rats.

Animals↗
PubMed2005

Hedamycin, a DNA alkylator, induces (gamma)H2AX and chromosome aberrations: involvement of phosphatidylinositol 3-kinase-related kinases and DNA replication fork movement.

Genotoxic treatments, such as UV light, camptothecin, and adozelesin, stall DNA replication and subsequently generate DNA strand breaks. Typically, DNA breaks are reflected by an increase in ataxia and Rad-related kinase (ATR)-regulated phosphorylation of H2AX (gammaH2AX) and require replication fork movement. This study examined the potential of the monofunctional DNA alkylating agent hedamycin, a powerful inhibitor of DNA replication, to induce DNA strand breaks, phosphorylated H2AX (gammaH2AX) foci, and chromosome aberrations. Hedamycin treatment of HCT116 carcinoma cells resulted in a rapid induction of DNA strand breaks accompanied by increasing H2AX phosphorylation and focalization. Unlike many other treatments that also stall replication, such as UV, camptothecin, and adozelesin, gammaH2AX formation was not suppressed in ATR-compromised cells but actually increased. Similarly, hedamycin induction of gammaH2AX is not dependent on ataxia telangiectasia mutated or DNA-protein kinase, and pretreatment of cells with the phosphatidylinositol 3-kinase-related kinase inhibitor caffeine did not substantially reduce induction of H2AX phosphorylation by hedamycin. Furthermore, the DNA replication inhibitor aphidicolin only modestly depressed hedamycin-induced gammaH2AX formation, indicating that hedamycin-induced DNA double-strand breaks are not dependent on fork progression. In contrast, camptothecin- and adozelesin-induced gammaH2AX was strongly suppressed by aphidicolin. Moreover, after 24 hours following a short-term hedamycin treatment, cells displayed high levels of breaks in interphase nuclear DNA and misjoined chromosomes in metaphase cells. Finally, focalization of a tightly bound form of Ku80 was observed in interphase cells, consistent with the subsequent appearance of chromosomal aberrations via abnormal nonhomologous end joining. Overall, this study has revealed a disparate type of DNA damage response to stalled replication induced by a bulky DNA adduct inducer, hedamycin, that seems not to be highly dependent on ATR or DNA replication.

Anthraquinones↗
PubMed2004

Renin-angiotensin system gene polymorphisms: its impact on IgAN and its progression to end-stage renal failure among Chinese in Singapore.

BACKGROUND: Gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasian and Japanese had reported contradicting results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess their clinical impact. METHODS: Genotyping was performed with DNA from peripheral leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes digestion, separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Among controls, genotype distributions were in Hardy-Weinberg equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar whereas there was significant increase in the ACE DD genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF) and without (IgAN-nonESRF), there was no difference in any of the three gene polymorphisms. But in contrast, there were significant differences in higher male prevalence (p < 0.05), increased serum creatinine at presentation (p < 0.05), more sclerosis (p < 0.01) and higher tubulointerstitial lesion score (p < 0.001) in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in our Chinese population. In contrast to clinical and histological risk factors, these genetic variations showed no impact on disease progression to ESRF. It is unlikely that genotyping more patients will prove these genes useful. Nevertheless, preclinically determined genetic markers are very useful as risk factors for disease occurrence and as prognostic indices for disease progression. Therefore, continuing efforts should be made to look at other genes to find those with significance.

Adult↗
PubMed1980

Growth kinetics of ataxia telangiectasia lymphoblastoid cells. Evidence for a prolonged S period.

Growth rates were investigated in long-term lymphoblastoid cell lines derived from normal individuals and patients with ataxia telangiectasia (ATR). By a cell doubling method, sister chromatid exchanges, and autoradiography, the ATR cells showed a significantly longer total generation time. Autoradiography demonstrated that the difference in cell cycle was due to a specific lengthening of the S period in the ATR lymphoblasts.

Adult↗
PubMed1976

Influence of cholinergic receptor blockade on drug-induced prolactin release in the monkey.

The influence of varying doses of perphenazine, thyrotropin-releasing hormone (TRH) and serotonin on prolactin release was examined in two species of monkeys: rhesus (Macaca mulatta) and crab-eating (Macaca fascicularis). The intravenous administration of 0.33 mg/kg body weight of perphenazine or 1.0 mug/kg body weight of TRH gave a greater release of prolactin than higher doses of perphenazine (1.0 mg/kg) or TRH) (3.4 mug/kg), respectively. Prolactin release induced by serotonin at doses of 1, 5 and 10 mug/kg was similar. Both atropine sulfate (Atr-SO4) and atropine methyl nitrate (Atr-MN) at a similar base level potentiated the prolactin releasing action of the high dose of perphenazine suggesting that high doses of perphenazine activate a cholinergic inhibitory component present in the pituitary. Atropine sulfate had no potentiating action on the TRH-induced prolactin release, while Atr-MN appeared to prolong the response of TRH without potentiating it. Neither form of atropine had any influence on serotonin-induced prolactin release. The data indicated that the lower prolactin response to high doses of perphenazine and TRH were brought about by different mechanisms, and that the mechanism for perphenazine appeared to be mediated through a pituitary cholinergic system.

Animals↗
PubMed2006

High-dose atorvastatin improves hypercholesterolemic coronary endothelial dysfunction without improving the angiogenic response.

BACKGROUND: Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) can restore endothelial function in coronary disease, in vitro and murine studies have shown their effects on myocardial angiogenesis to be biphasic and dose dependent. We investigated the functional and molecular effects of high-dose atorvastatin on the endogenous angiogenic response to chronic myocardial ischemia in hypercholesterolemic swine. METHODS AND RESULTS: Yucatan pigs were fed either a normal (NORM group; n=7) or high-cholesterol diet, with (CHOL-ATR group; n=7) or without (CHOL group; n=6) atorvastatin (3 mg/kg per day) for 13 weeks. Chronic ischemia was induced by ameroid constrictor placement around the circumflex artery. Seven weeks later, microvessel relaxation responses, myocardial perfusion, and myocardial protein expression were assessed. The CHOL group demonstrated impaired microvessel relaxation to adenosine diphosphate (29+/-3% versus 61+/-6%, CHOL versus NORM; P<0.05), which was normalized in the CHOL-ATR group (67+/-2%; P=NS versus NORM). Collateral-dependent myocardial perfusion, adjusted for baseline, was significantly reduced in the CHOL group (-0.27+/-0.07 mL/min per gram versus NORM; P<0.001) as well as the CHOL-ATR group (-0.35+/-0.07 mL/min per gram versus NORM; P<0.001). Atorvastatin treatment was associated with increased phosphorylation of Akt (5.7-fold increase versus NORM; P=0.001), decreased vascular endothelial growth factor expression (-68+/-8%; P<0.001 versus NORM), and increased expression of the antiangiogenic protein endostatin (210+/-48%; P=0.004 versus NORM). CONCLUSIONS: Atorvastatin improves hypercholesterolemia-induced endothelial dysfunction without appreciable changes in collateral-dependent perfusion. Increased myocardial expression of endostatin, decreased expression of vascular endothelial growth factor, and chronic Akt activation associated with atorvastatin treatment may account for the diminished angiogenic response.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: influence of the phase separation on protein adsorption patterns.

Octadecyltrichlorosilane (OTS) and [2-(perfluorooctyl)ethyl]trichlorosilane (FOETS) monolayers and their mixed monolayer were polymerized on a water subphase and subsequently immobilized onto a silicon wafer surface by covalent bonding. Atomic force microscopic (AFM) observation of the mixed (OTS/FOETS) monolayer revealed the formation of a phase-separated structure. Protein-adsorption behavior onto the monolayers was investigated in situ on the basis of an attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopic flow cell method and the morphology of the monolayer surface-adsorbed bovine serum albumin (BSA) was observed by AFM. Protein adsorption behavior observed by ATR-FT-IR flow cell method revealed that the amount of BSA adsorption onto the OTS and FOETS monolayers increased remarkably at an initial experimental stage and attained a steady state within a few minutes at pH 7.5. The amount of steady state adsorption was c. 0.18-0.2 microgcm(-2). AFM observation of the monolayer after exposure to BSA solution suggested that BSA adsorbed in the end-on adsorption state on OTS monolayer and side-on one in the FOETS monolayer, respectively. However, in the case of the mixed (OTS/FOETS) monolayer, ATR-FT-IR flow cell experiment revealed that the amount of steady state adsorption of BSA was suppressed. Also, AFM observation revealed that at pH 7.5, BSA preferentially adsorbed onto the FOETS phase of the mixed (OTS/FOETS) monolayer, which had a higher interfacial free energy against water. On the other hand, BSA adsorbed homogeneously onto the OTS and FOETS phases at the isoelectric point of BSA (pH 4.7). These results indicate that the preferential adsorption of BSA onto the FOETS phase in the mixed (OTS/FOETS) monolayer system is due to: (1) the minimization of the interfacial free energy between a monolayer surface and an aqueous solution; and (2) the electrostatic repulsion between BSA molecules bearing negative charges.

Adsorption↗
PubMed2005

Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation.

Iron is critical for cell growth and proliferation. Iron chelators are being explored for a number of clinical applications, including the treatment of neurodegenerative disorders, heart disease, and cancer. To uncover mechanisms of action of tachpyridine, a chelator currently undergoing preclinical evaluation as an anticancer agent, cell-cycle analysis was performed. Tachpyridine arrested cells at G2, a radiosensitive phase of the cell cycle, and enhanced the sensitivity of cancer cells but not nontransformed cells to ionizing radiation. G2 arrest was p53 independent and was accompanied by activation of the checkpoint kinases CHK1 and CHK2. G2 arrest was blocked by UCN-01, a CHK1 inhibitor, but proceeded in CHK2 knock-out cells, indicating a critical role for CHK1 in G2 arrest. Tachpyridine-induced cell-cycle arrest was abrogated in cells treated with caffeine, an inhibitor of the ataxia-telangiectasia mutated/ataxia-telangiectasia-mutated and Rad3-related (ATM/ATR) kinases. Further, G2 arrest proceeded in ATM-deficient cells but was blocked in ATR-deficient cells, implicating ATR as the proximal kinase in tachpyridine-mediated G2 arrest. Collectively, our results suggest that iron chelators may function as antitumor and radioenhancing agents and uncover a previously unexplored activity of iron chelators in activation of ATR and checkpoint kinases.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2006

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model.

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E2) serum concentrations during the estrous cycle. The results indicate that ULO effects on E2 concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E2 serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E2 serum concentrations.ULO of the right ovary (left ovary in situ) resulted in significantly higher E2 concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E2 serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E2 secretion response; when the right ovary remained in situ an increase in E2 was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E2 from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E2 secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E2 secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E2 secretion.

Anesthesia↗
PubMed2006

Clinical improvement and radiological progression in a girl with early onset scoliosis (EOS) treated conservatively--a case report.

BACKGROUND: Chêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60 degrees showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently. METHODS: The patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60 degrees thoracic and 59 degrees lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13 degrees thoracic and 13 degrees lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche. RESULTS: After a treatment time of 27 Month the Cobb angle increased to 74 degrees thoracic and 65 degrees lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26 degrees thoracic and 28 degrees lumbar to 30 degrees thoracic and 28 degrees lumbar. The ATR improved to 12 degrees thoracic and 5 degrees lumbar while Lateral deviation improved from 22.4 mm to 4.6 mm and average surface rotation improved from 10.6 degrees to 6 degrees. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result. CONCLUSION: Conservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60 degrees when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement.

Journal Article↗
PubMed2006

Study of trunk asymmetry in normal children and adolescents.

The scoliometer readings in both standing and sitting position of 2071 children and adolescents (1099 boys and 972 girls) aged from 5 to 18 years old were studied. The angle of trunk rotation (ATR) was measured, in order to quantify the existing trunk asymmetry. Children and adolescents were divided in two groups according to the severity of trunk asymmetry. In the first group asymmetry was 1 to 6 degrees and in the second group was 7 or more degrees. Radiographic and leg length inequality evaluation were also performed in a number of children. The mean frequency of symmetric (ATR = 0 degrees) boys and girls was 67.06% and 65.01% for the standing screening position and 76.5% and 75.1% for the sitting position, respectively. The mean difference of frequency of asymmetry (ATR > 0 degrees) at standing minus sitting forward bending position for boys and girls was 10.22% and 9.37%, respectively. The mean frequency of asymmetry of 7 or more degrees was 3.23% for boys and 3.92% for girls at the standing forward bending position and 1.62% and 2.21% at the sitting, respectively. Girls are found to express higher frequency of asymmetry than boys. Right trunk asymmetry was more common than left. The sitting position is the preferred screening position for examining the rib or loin hump during school screening as it demonstrates the best correlation with the spinal deformity exposing the real trunk asymmetry.

Journal Article↗