Prevalence of TTN mutations in patients with dilated cardiomyopathy : A meta-analysis.

A meta-analysis was performed to assess the prevalence of TTN mutations in patients with dilated cardiomyopathy (DCM). Prevalence point estimates and 95% confidence intervals were computed using the logit transformation formula. The prevalence of TTN mutations in patient with DCM, familial dilated cardiomyopathy (FDCM), and sporadic dilated cardiomyopathy (SDCM) was 0.17 (95% CI: 0.14-0.19), 0.23 (95% CI: 0.20-0.26), and 0.16 (95% CI: 0.12-0.21), respectively. No individual study had a marked influence on the pooled prevalence in the meta-analysis. Meta-regression analysis between the logit event for prevalence and sample size explained 32% of between-study variance (p < 0.05). Cumulative meta-analysis confirmed the influence of sample size on the reported prevalence among the different studies. In conclusion, the present analysis suggests that TTN mutations are familial in DCM patients. More attention should be paid to TTN mutations in clinical examinations.

[The relationship between mental stimulation level of life events and suicide attempt of rural residents in Shandong Province].

Objective: To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods: A 1:1 matched case-control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results: The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low-medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values <0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low-medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion: Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.

A Practical Review of Functional MRI Anatomy of the Language and Motor Systems.

Functional MR imaging is being performed with increasing frequency in the typical neuroradiology practice; however, many readers of these studies have only a limited knowledge of the functional anatomy of the brain. This text will delineate the locations, anatomic boundaries, and functions of the cortical regions of the brain most commonly encountered in clinical practice-specifically, the regions involved in movement and language.

Posterior glottic stenosis with a calcified interarytenoid scar band: CT and laryngoscopic correlation.

A 52-year-old man with burn injuries and prolonged intubation developed PGS with hoarseness, dyspnea, and bilateral vocal cord immobility. On CT, a calcified interarytenoid scar band was identified, corresponding to an interarytenoid scar on laryngoscopy. Endoscopic laser lysis of the calcified scar band relieved the symptoms. We present laryngoscopic and CT findings of PGS with interarytenoid calcification along with the postlysis findings. The classification, clinical findings, imaging, and management of PGS are reviewed.

Percutaneous transosseous translaminar approach for thecal sac access in advanced ankylosing spondylitis with instrumented posterior spinal fusion.

A novel transosseous approach for percutaneous access of the lumbar subarachnoid space is described in a patient with advanced ankylosing spondylitis (AS) and instrumented spinal fusion who presented for myelography. Use of a coaxial threaded bone biopsy system to provide transosseous access to the thecal sac, imaging findings, and outcome are discussed. This technique provided access to an otherwise inaccessible subarachnoid space and is an alternative approach in the setting of advanced AS or posterior spinal fusion.

Tangutorine induces p21 expression and abnormal mitosis in human colon cancer HT-29 cells.

A novel beta-carboline alkaloid, tangutorine (benz[f]indolo[2,3-a]quinolizidine) was isolated from the leaves of Nitraria tangutorum L. [Duan JA, Williams ID, Che CT, Zhou RH, Zhao RH, Tangutorine: a novel beta-carboline alkaloid from Nitraria tangutorum. Tetrahedron Lett 1999;40:2593-6], and its unique structural characters led us to initiate a study of its potential anti-proliferation activity. The in vitro treatment with low doses of tangutorine slightly stimulated the proliferation of human colon cancer HT29 cells until at concentrations higher than 6.25 microg/ml when the cell numbers, cellular MTT reduction, and cell proliferation by 3H-thymidine incorporation decreased in a dose-dependent manner (IC50=15 microg/ml=48 microM). Morphological studies of cells by fluorescence and electron microscopy did not show features for apoptosis but only large vacuoles, swollen mitochondria and dense cytoskeletal filaments bunching in the cytoplasm. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of topoisomerase II expression at 25 microg/ml tangutorine, thereby impeding cell progression from S to G2/M phase. Cells accumulated at G1 phase of the cell cycle at concentrations > or =50 microg/ml tangutorine. Interestingly, some cells escaped from prolonged growth arrest without cell division and resulted in binucleated and polyploid G1 cells. Taken all results together, tangutorine induced a p21 suppression of all cyclins and their associated kinases, such as the topoisomerase II, and thus inhibited normal DNA replication and mitosis.

Wheat germ lectin induces G2/M arrest in mouse L929 fibroblasts.

Wheat germ lectin (WGA) is a cytotoxic lectin for many cell lines [Wang et al., 2000], but its underlying mechanism is not clear. In this report, we found that incubation of synchronized mouse L929 fibroblasts with WGA resulted in a dose-dependent reduction of intracellular incorporation of 3H-thymidine and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)-conversion activity (IC50 congruent with 0.4 microM). Fluorescein-conjugated WGA was demonstrated to transport from the cell surface into the paranuclear region of cultured L929 cells within 30 min, and subsequently evoked lipid peroxidation of plasma membrane and vacuolation in the cytoplasm of these cells. Studies with tritiated thymidine incorporation, immunofluorescence microscopy, immunoblotting analysis and flow cytometry revealed that WGA inhibited cell cycle progression after one replication, resulting in G2/M arrest and alteration of cell cycle regulatory proteins, particularly activation of p21Cip1/WAF1 and suppression of cyclin B and cdc 2. Although there was an increase of cytosolic caspase 3 and bax protein expression, no apoptotic bodies were observed by both fluorescence and transmission electron microscopy. These results suggest that WGA arrested L929 proliferation after one cell cycle in the G2/M phase through activation of the p21Cip1/WAF1 and suppression of Cyclin B-Cdc2.

Semaphorin-mediated axonal guidance via Rho-related G proteins.

For many growing axons, interaction with an extracelluar Semaphorin signal leads to growth cone collapse and axon repulsion. Semaphorin receptors composed of Neuropilins and Plexins transduce extracellular cues into changes in the growth cone actin cytoskeleton. The data implicating Rho family G proteins in Semaphorin signaling and in other axon guidance events are considered here. Recent work makes it clear that Rac1 is required for this process. In particular, there is intriguing new evidence that the Plexin receptors communicate directly with members of the Rho family GTPases, although uncertainties remain concerning how Plexins alter Rac1 function. The CRMP (collapsin response mediator protein) family is also required for Plexin-based Semaphorin signaling, and new data demonstrate direct links to Rho and Rac1-based signaling.

Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not beta1 integrins.

The Rho family of GTPases plays a major role in the organization of the actin cytoskeleton. These G proteins are activated by guanine nucleotide exchange factors that stimulate the exchange of bound GDP for GTP. In their GTP-bound state, these G proteins interact with downstream effectors. Vav2 is an exchange factor for Rho family GTPases. It is a ubiquitously expressed homologue of Vav1, and like Vav1, it has previously been shown to be activated by tyrosine phosphorylation. Because Vav1 becomes tyrosine phosphorylated and activated following integrin engagement in hematopoietic cells, we investigated the tyrosine phosphorylation of Vav2 in response to integrin-mediated adhesion in fibroblasts and epithelial cells. However, no tyrosine phosphorylation of Vav2 was detected in response to integrin engagement. In contrast, treating cells with either epidermal growth factor or platelet-derived growth factor stimulated tyrosine phosphorylation of Vav2. We have examined the effects of overexpressing either wild-type or amino-terminally truncated (constitutively active) forms of Vav2 as fusion proteins with green fluorescent protein. Overexpression of either wild-type or constitutively active Vav2 resulted in prominent membrane ruffles and enhanced stress fibers. These cells revealed elevated rates of cell migration that were inhibited by expression of dominant negative forms of Rac1 and Cdc42. Using a binding assay to measure the activity of Rac1, Cdc42, and RhoA, we found that overexpression of Vav2 resulted in increased activity of each of these G proteins. Expression of a carboxy-terminal fragment of Vav2 decreased the elevation of Rac1 activity induced by epidermal growth factor, consistent with Vav2 mediating activation of Rac1 downstream from growth factor receptors.

p120 catenin regulates the actin cytoskeleton via Rho family GTPases.

Cadherins are calcium-dependent adhesion molecules responsible for the establishment of tight cell-cell contacts. p120 catenin (p120ctn) binds to the cytoplasmic domain of cadherins in the juxtamembrane region, which has been implicated in regulating cell motility. It has previously been shown that overexpression of p120ctn induces a dendritic morphology in fibroblasts (Reynolds, A.B. , J. Daniel, Y. Mo, J. Wu, and Z. Zhang. 1996. Exp. Cell Res. 225:328-337.). We show here that this phenotype is suppressed by coexpression of cadherin constructs that contain the juxtamembrane region, but not by constructs lacking this domain. Overexpression of p120ctn disrupts stress fibers and focal adhesions and results in a decrease in RhoA activity. The p120ctn-induced phenotype is blocked by dominant negative Cdc42 and Rac1 and by constitutively active Rho-kinase, but is enhanced by dominant negative RhoA. p120ctn overexpression increased the activity of endogenous Cdc42 and Rac1. Exploring how p120ctn may regulate Rho family GTPases, we find that p120ctn binds the Rho family exchange factor Vav2. The behavior of p120ctn suggests that it is a vehicle for cross-talk between cell-cell junctions and the motile machinery of cells. We propose a model in which p120ctn can shuttle between a cadherin-bound state and a cytoplasmic pool in which it can interact with regulators of Rho family GTPases. Factors that perturb cell-cell junctions, such that the cytoplasmic pool of p120ctn is increased, are predicted to decrease RhoA activity but to elevate active Rac1 and Cdc42, thereby promoting cell migration.

Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts.

Microtubules are involved in actin-based protrusion at the leading-edge lamellipodia of migrating fibroblasts. Here we show that the growth of microtubules induced in fibroblasts by removal of the microtubule destabilizer nocodazole activates Rac1 GTPase, leading to the polymerization of actin in lamellipodial protrusions. Lamellipodial protrusions are also activated by the rapid growth of a disorganized array of very short microtubules induced by the microtubule-stabilizing drug taxol. Thus, neither microtubule shortening nor long-range microtubule-based intracellular transport is required for activating protrusion. We suggest that the growth phase of microtubule dynamic instability at leading-edge lamellipodia locally activates Rac1 to drive actin polymerization and lamellipodial protrusion required for cell migration.

Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho.

Microtubule depolymerization has multiple consequences that include actin stress fiber and focal adhesion assembly, increased tyrosine phosphorylation and DNA synthesis. Similar effects induced by serum, or agents such as lysophosphatidic acid, have previously been shown to be mediated by the GTP-binding protein Rho. We have investigated whether the effects of microtubule depolymerization are similarly mediated by Rho and show that they are blocked by the specific Rho inhibitor, C3 transferase. Because microtubule depolymerization induces these effects in quiescent cells, in which Rho is largely inactive, we conclude that microtubule depolymerization leads to activation of Rho. The activation of Rho in response to microtubule depolymerization and the consequent stimulation of contractility suggest a mechanism by which microtubules may regulate microfilament function in various motile phenomena. These range from growth cone extension to the development of the contractile ring during cytokinesis, in which there are interactions between the microtubule and microfilament systems.

Clinical evidence of genetic anticipation in adult-onset idiopathic dystonia.

Idiopathic dystonia occurs in both hereditary and sporadic forms. In this report, we studied the age of onset and family history of 260 patients (probands) with idiopathic adult-onset dystonia (IAD), cranial or cervical. The mean age at onset of these patients was (45.71 +/- 15.85) years. Forty-nine probands had a positive family history of dystonia or tremor in first- and second-degree relatives, and 7 had affected siblings only. The significance of tremor as a part of clinical manifestation of dystonia was evidenced by a high frequency of postural or action tremor in patients and relatives. Retrospectively, we examined the age of onset of dystonia (cervical or cranial) on successive generations in 49 families. Age of onset of clinical symptoms was earlier, by an average of 21.25 years, in the second generation than in the first generation. The mean age at onset of affected family members differed significantly between successive generations in these 49 families (p = 1.11 x 10(-8)). Our results suggest a tendency for earlier onset of dystonia and worsening of disease phenotype in succeeding generations in the same family. These findings are most compatible with genetic anticipation and suggest that an unstable trinucleotide repeat is most likely involved in adult-onset primary cranial or cervical dystonia. In addition, tremor as an integral part of dystonia needs further evaluation by molecular genetic studies.

[Effects of combined therapy of traditional Chinese and Western medicine on C-reactive protein in post-debridement patients].

Closely monitoring whether the secondary infection in the patients of post-debridement occurred or not and appropriately treating these patients were the important ways to reduce the incidence of infection. Through estimating the level of the serum C-reactive protein (CRP) as the monitoring index of infection, dynamically observed the effect of the combined traditional Chinese and Western medicine therapy (TCM-WM) on CRP after debridement, as was compared with the effect of the Western medicine therapy (WM) group in which only the WM was administrated. The result showed that the levels of CRP decreased in both TCM-WM and WM group on 4th day after the operation, but the level of CRP in former group was lower than that in latter one, the difference was very significant (P < 0.001). So that, it was assumed that TCM-WM significantly excelled the WM on affecting the level of CRP and reducing the incidence of infection. It was suggested that CRP could be used as an effective and objective index to determine whether the secondary infection has happened and to assess the efficacy of some drugs.