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B-type lamins, the major components of the nuclear lamina, are believed to be essential for cell proliferation and survival. We found that mouse embryonic stem cells (ESCs) do not need any lamins for self-renewal and pluripotency. Although genome-wide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in ESCs or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientation in neural progenitor cells and migration of neurons probably cause brain disorganizations found in lamin-B null mice. Thus, our studies not only disprove several prevailing views of lamin-Bs but also establish a foundation for redefining the function of the nuclear lamina in the context of tissue building and homeostasis.

Skeletal muscle tissue provides mechanical force for locomotion of all vertebrate animals. It is prone to damage from acute physical trauma and physiological stress. To cope with this, it possesses a tremendous capacity for rapid and effective repair that is widely held to be accomplished by the satellite cells lying between the muscle fiber plasmalemma and the basement membrane. Cell transplantation and lineage-tracing studies have demonstrated that Pax7-expressing (Pax7(+)) satellite cells can repair damaged muscle tissue repeatedly after several bouts of acute injury. These findings provided evidence that Pax7(+) cells are muscle stem cells. However, stem cells from a variety of other origins are also reported to contribute to myofibers upon engraftment into muscles, questioning whether satellite cells are the only stem cell source for muscle regeneration. Here, we have engineered genetic ablation of Pax7(+) cells to test whether there is any significant contribution to muscle regeneration after acute injury from cells other than this source. We find that such elimination of Pax7(+) cells completely blocks regenerative myogenesis either following injury to the tibialis anterior (TA) muscle or after transplantation of extensor digitorum longus (EDL) muscles into nude mice. As Pax7 is specifically expressed in satellite cells, we conclude that they are essential for acute injury-induced muscle regeneration. It remains to be established whether there is any significant role for stem cells of other origins. The implications of our results for muscle stem cell-based therapy are discussed.

Aim: To observe whether cyclophilin A (CypA)has an effect on macrophage-derived foam cells, and to investigate the involvement of CypA in the development of atherosclerosis., Methods: The foam cell model was established through incubating the human monocyte line (THP-1 cells) with oxidized low density lipoproteins (ox-LDL). The cells were stained with fresh oil red O to study the morphology of the macrophage-derived foam cells. The cell adhesion, invasion and the production of matrix metalloproteinase (MMPs) of the macrophage-derived foam cells were detected by adhesion assay, invasion assay and gelatin zymography respectively both in the absence or presence of different concentrations of purified CypA (50, 100, 200 μg/L). Then the foam cells were respectively pre-treated with CsA, c7b8f10, HAb18 mAb, and dual treatment of c7b8f10 and HAb18 mAb respectively, to investigate the inhibitory effect on macrophage-derived foam cells., Results: The adhesion, invasion and the production of MMP-9 and MMP-2 were enhanced during the differentiation of monocytes into macrophages (P<0.05). CypA, especially in the concentration of 100 ng/mL, significantly promoted the function of macrophage-derived foam cells (P<0.05). CsA, c7b8f10, HAb18 mAb, and c7b8f10- HAb18 mAb combination dramatically inhibited the function of macrophage-derived foam cells both in the absence or presence of CypA (P<0.05). The c7b8f10- HAb18 mAb combination pretreatment had the most obviously suppressive effect on macrophage-derived foam cells (P<0.05)., Conclusion: These findings suggest that CypA up regulates the adhesion, the invasion and the expressions of MMP-2 and MMP-9 in macrophage-derived foam cells. The CypA effect is blocked by the pretreatment of the different antagonists. This research might suggest the correlation between atherosclerosis pathogenesis and the vulnerability of atherosclerotic plaques, and thus give us some good ideas for atherosclerosis therapy in future.

Objective: To establish a simple, fast and accurate double antigen colloidal gold immunochromatographic technique for detecting Mycobacterium tuberculosis antibody from tuberculosis patients., Methods: The fusion protein ESAT-6-16-38 was constructed by using gene cloning technique for the 6, 16 and 38 kDa early secreted antigenic target from Mycobacterium tuberculosis. The ESAT-6-16-38 fusion protein was marked to colloidal gold to establish the double antigen colloidal gold immunochromatographic assay. Serum samples from 163 patients with tuberculosis, including 57 sputum-positive cases, 64 sputum-negative cases, and 42 cases with extrapulmonary tuberculosis, were collected during 2007 and 2009 from the Disease Prevention and Control Center of Deqing County. In addition, 573 controls (224 healthy volunteers, 217 patients with acute pneumonia and bronchitis, 132 patients with paragonimiasis) were recruited for comparison. Mycobacterium tuberculosis specific antibodies were detected by using immunochromatographic and protein chip technique. Detection rate was compared with Chi-square test., Results: Among the 163 tuberculosis patients, the positive rates of immunochromatographic detection and protein chip were 73.0% (120/163) and 72.4% (118/163) respectively; the difference was not statistically significant (χ()2 = 0.062, P > 0.05). Among the 573 controls, the negative rates of immunochromatographic detection and protein chip were 93.9% (538/573) and 92.0% (527/573) respectively; the difference was not statistically significant (χ()2 = 0.635, P > 0.05). There was no cross reaction in the paragonimiasis patients. The positive rate of the immunochromatographic assay was as high as 87.7% (50/57) in the sputum-positive patients., Conclusions: The double antigen immunochromatographic technique is an easy to operate, rapid, highly sensitive, specific, and reproducible method for the detection of Mycobacterium tuberculosis antibodies.

Background: Mesencephalic dopaminergic neurons (mDA) and serotonergic (5-HT) neurons are clinically important ventral neuronal populations. Degeneration of mDA is associated with Parkinson's disease; defects in the serotonergic system are related to depression, obsessive-compulsive disorder, and schizophrenia. Although these neuronal subpopulations reveal positional and developmental relationships, the developmental cascades that govern specification and differentiation of mDA or 5-HT neurons reveal missing determinants and are not yet understood., Methodology: We investigated the impact of the transcription factor Sim1 in the differentiation of mDA and rostral 5-HT neurons in vivo using Sim1-/- mouse embryos and newborn pups, and in vitro by gain- and loss-of-function approaches., Principal Findings: We show a selective significant reduction in the number of dorsal raphe nucleus (DRN) 5-HT neurons in Sim1-/- newborn mice. In contrast, 5-HT neurons of other raphe nuclei as well as dopaminergic neurons were not affected. Analysis of the underlying molecular mechanism revealed that tryptophan hydroxylase 2 (Tph2) and the transcription factor Pet1 are regulated by Sim1. Moreover, the transcription factor Lhx8 and the modulator of 5-HT(1A)-mediated neurotransmitter release, Rgs4, exhibit significant higher expression in ventral hindbrain, compared to midbrain and are target genes of Sim1., Conclusions: The results demonstrate for the first time a selective transcription factor dependence of the 5-HT cell groups, and introduce Sim1 as a regulator of DRN specification acting upstream of Pet1 and Tph2. Moreover, Sim1 may act to modulate serotonin release via regulating RGS4. Our study underscores that subpopulations of a common neurotransmitter phenotype use distinct combinations of transcription factors to control the expression of shared properties.

Context:  Scutellaria baicalensis Georgi (Labiatae) (SbG), one of the fifty fundamental herbs of Chinese herbology, has been reported to have anti-asthmatic, antifungal, antioxidative, and anti-inflammatory activities., Objective:  This study was designed to determine the protective effects of the extract of SbG against the acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells (HUVEC)., Materials and Methods:  The MTT reduction assay was employed to determine cell viability. The total cellular glutathione (GSH) level was detected using a colorimetric GSH assay kit. Cellular GSH production was conducted by detecting the mRNA expression levels of γ-glutamylcysteine ligase catalytic subunit and modifier subunit., Results:  Concentration-dependent cytotoxic effects of acrolein were observed while SbG could effectively protect the acrolein-induced oxidative damage. The protective mechanism was investigated, showing that the increased GSH content in the SbG-incubated HUVE cells was associated with the protective effects of SbG-treated cells. Further RT-PCR data confirmed the elevated mRNA expressions of GSH synthesis enzymes., Discussion and Conclusion:  The current study strongly indicated that SbG could be a potential antioxidant against oxidative stress in treating cardiovascular diseases.

Objective: Based on previous experience from surgical surveillance, risk-adjusted cumulative sum (CUSUM)-type charts were applied to monitor out-of-hospital cardiac arrest (OHCA) patient mortality., Materials and Methods: Data from 2356 OHCA patients were collected by the Taipei County Fire Bureau from June 2006 to November 2007. Logistic regression analysis was applied to create a risk-adjusted model. Next, a risk-adjusted CUSUM chart, a risk-adjusted resetting sequential probability ratio test chart and a cumulative risk-adjusted mortality with prediction limits chart were used to detect excess deaths of the OHCA patients rescued by the emergency medical service (EMS) system., Results: The overall mortality rate, defined as having no return of spontaneous circulation, was 79.3%. These three charts signalled an increase in the death rate at similar sites, and also suggested a small process shift., Conclusion: A visual approach to EMS systems monitoring that combines the risk-adjusted cumulative sum, Risk-adjusted resetting sequential probability ratio test and cumulative risk-adjusted mortality with prediction limits charts was established. It was found that this approach can be effectively used by the EMS community to monitor OHCA outcomes in real time., (© 2010 Blackwell Publishing Ltd.)

Purpose: To evaluate the clinical effectiveness and safety of uterine artery embolization (UAE) in the treatment of primary postpartum hemorrhage (PPH), secondary PPH, and PPH associated with cesarean section., Materials and Methods: All women who underwent UAE for obstetric-related hemorrhage during a 52-month period culminating in April 2009 were included. Clinical success was defined as obviation of hysterectomy. Blood product requirements before and after UAE were calculated. Statistically significant associations between subject characteristics and clinical success were evaluated. The two subgroups of women with uterine artery pseudoaneurysms and women who underwent cesarean section were examined separately as well., Results: Sixty-six women (mean age, 33 years; range, 17-47 y) underwent UAE, with an overall clinical success rate of 95% (98% for primary PPH, 88% for secondary PPH, and 94% for PPH associated with cesarean section) and an overall complication rate of 4.5%. Mean pre- and postembolization transfusion requirements were 3.1 U and 0.4 U of packed red blood cells, respectively. The only significant characteristic identified for the cases that necessitated hysterectomy was an increased transfusion requirement after UAE (increase of 1.0 U ± 0.5; P = .02). Uterine artery pseudoaneurysms were associated with secondary PPH (P = .01) and cesarean section (P = .03)., Conclusions: The threshold for UAE in women with PPH should be low, as it is associated with a high clinical effectiveness rate and a low complication rate. Uterine artery pseudoaneurysms should be suspected in women presenting with secondary PPH after cesarean section., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the clinical characteristics and prognosis of Chinese patients with apical hypertrophic cardiomyopathy (AHCM)., Methods: A total of 188 patients with AHCM diagnosed at Fuwai Hospital were included in this retrospective study. Clinical characteristics, mortality and cardiovascular morbidity were analyzed. A multiple logistic regression was performed to adjust for potential confounding factors., Results: Males predominated with a number of 139 (73.9%) in this cohort. Patient's age ranged from 15 to 81 (51.9 ± 12.6) years. There were 120 patients (63.8%) with "pure" type and 68 patients (36.2%) with "mixed" type of AHCM, 171 patients were followed up for (5.0 ± 3.0) years, cardiovascular mortality was 1.2%, 28 patients (16.4%) experienced one or more cardiovascular events., Conclusion: The prevalence of AHCM is high in Chinese HCM patients, pure type AHCM is more common, and AHCM patients have a benign clinical course.

Objective: To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring., Methods: In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis., Results: The randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001)., Conclusions: The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

We have generated a mouse strain carrying a Cre-ER(T2) knock-in allele at the Pax7 locus, the Pax7(CE) allele (Lepper et al., 2009, Nature 460:627-631). Combining Pax7(CE) and the R26R(LacZ) Cre reporter allele, here we describe temporal-specific tamoxifen (tmx)-inducible lineage tracing of embryonic Pax7-expressing cells. In particular, we focus on the somitic lineage. Tmx-inducible Cre activity directed by the Pax7(CE) allele is similar to the endogenous Pax7 expression pattern. The somitic Pax7-expressing cells selectively marked at embryonic day 9.5 (E9.5) give rise to dorsal dermis and brown adipose tissue, in addition to dorsal aspects of trunk muscles and the diaphragm muscle. However, they do not contribute to ventral body wall and limb muscles. After E12.5, marked Pax7-expressing cells become lineage restricted to muscles. Descendants of these early marked Pax7-expressing cells begin to occupy sublaminal positions associated with the myofibers around E16.5, characteristic of embryonic satellite cells. Furthermore, they contribute to adult myofibers and regeneration competent satellite cells in the tibialis anterior muscle, providing evidence that some adult satellite cells are of embryonic origin., ((c) 2010 Wiley-Liss, Inc.)

Stem cell differentiation is accompanied by a gradual cellular morphogenesis and transcriptional changes. Identification of morphological regulators that control cell behavior during differentiation could shed light on how cell morphogenesis is coupled to transcriptional changes during development. By analyzing cellular behavior during differentiation of mouse embryonic stem cells (ESCs), we uncover a role of Borg5 (binder of Rho guanosine 5'-triphosphatase 5) in regulating trophectoderm (TE) cell morphogenesis. We report that differentiation of ESCs toward TE is accompanied by enhanced actin protrusion and cell motility that require upregulation of Borg5. Borg5 interacts with both Cdc42 and atypical protein kinase C (aPKC) and functions downstream of Cdc42 to enhance TE cell motility. Borg5 is required for the sorting of differentiating TE to the outside of ESCs in vitro. In developing embryos, Borg5 protein localizes to cell-cell contacts and the cytoplasm after compaction. It exhibits higher levels of expression in outer cells than in inner cells in morula and blastocysts. Reduction of Borg5 disrupts aPKC localization and inhibits blastocyst formation. Since Cdx2 and Borg5 facilitate each other's expression as ESCs differentiate toward TE, we propose that cell morphogenesis is coupled with transcriptional changes to regulate TE differentiation. Our studies also demonstrate the utility of ESCs in identifying morphological regulators important for development.

In art and literature, originals are revered and copies frowned upon. But do men use germline stem cell copies to pass traits to their children? In Science, Nakagawa et al. (2010) show that new stem cell copies regularly arise in mouse testes by fragmentation of downstream germ cell clusters.

Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.

Holoprosencephaly (HPE) is a common birth defect predominantly affecting the forebrain and face and has been linked to mutations in the sonic hedgehog (SHH) gene. HPE is genetically heterogeneous, and clinical presentation represents a spectrum of phenotypes. We have previously shown that Gas1 encodes a cell-autonomous Hedgehog signaling enhancer. Combining cell surface binding, in vitro activity, and explant culture assays, we provide evidence that SHH contains a previously unknown unique binding surface for its interaction with GAS1 and that this surface is also important for maximal signaling activity. Within this surface, the Asn-115 residue of human SHH has been documented to associate with HPE when mutated to lysine (N115K). We provide evidence that HPE associated with this mutation can be mechanistically explained by a severely reduced binding of SHH to GAS1, and we predict a similar result if a mutation were to occur at Tyr-80. Our data should encourage future searches for mutations in GAS1 as possible modifiers contributing to the wide spectrum of HPE.

Aim: To ascertain the effect of CyPA and IL-8 in chemotaxis of neutrophil and the level of IL-8 from the CyPA effecting of peripheral blood from RA patients., Methods: 12 RA patients matched 4 healthy people were studied. Chemotaxis of IL-8 was measured by Boyden chamber on neutrophil of RA patients and that of 4 normal healthy people controls were studied; the level of IL-8 on neutrophil of RA patients peripheral blood after the effecting of CyPA was assessed by ELISA. Correlations between CyPA and IL-8 were observed in RA., Results: The chemotaxis of neutrophil which IL-8 mixed with CyPA antibody was lower than IL-8(P<0.05); The secretion of RA peripheral blood in IL-8 was higher than normal people, as well as the secretion of RA peripheral blood in IL-8 after effecting of CyPA was higher than before (P<0.05), but the level of IL-8 after blocking CyPA was not changed., Conclusion: CyPA could affect the chemotaxis of IL-8 in the neutrophil of RA patients' peripheral blood. The secretion of IL-8 is accelerated by CyPA on neutrophil of RA patients'peripheral blood.

Aims: To evaluate HAb18G/CD147 as a cancer-associated biomarker using its monoclonal antibody HAb18., Methods and Results: On immunohistochemical analysis of 28 tissue microarrays and pathological sections of 1117 breast tissue samples, HAb18G/CD147 was expressed in carcinoma with an overall positivity rate of 67.76%, which was significantly higher than that in sarcomas (27.34%, P < 0.0001) and normal epithelial (5.18%, P < 0.0001) and fetal (2.67%, P < 0.0001) tissues. In epithelial tissues from 14 organs, the difference in HAb18G/CD147 expression between normal epithelium and the corresponding carcinoma was also significant (P < 0.05 for each pair). This expression in carcinoma was also found at the mRNA level, suggesting transcriptional level regulation of HAb18G/CD147 expression. In a retrospective study of 106 patients with infiltrating ductal carcinoma of the breast, the level of HAb18G/CD147 expression was positively correlated with tumour recurrence/metastasis (P = 0.0003) and negatively correlated with survival of breast cancer patients (P = 0.002). Multivariable Cox regression analysis showed that HAb18G/CD147 was an independent prognostic factor., Conclusions: HAb18G/CD147 is significantly expressed in various cancers and appears to have prognostic significance, rendering it a possible cancer-associated biomarker for pathological diagnosis, prognostic evaluation, targeted therapy and radioimmunoimaging of a broad range of cancer types.

Objectives: This before-after study investigated the association between an audit program and door-to-balloon times in patients with acute ST-elevation myocardial infarction (STEMI) and explored other factors associated with the door-to-balloon time., Methods: An audit program that collected time data for essential time intervals in acute STEMI was developed with data feedback to both the Department of Emergency Medicine and the Department of Cardiology. The door-to-balloon times for 76 consecutive acute STEMI patients were collected from February 16, 2007, through October 31, 2007, after the implementation of the audit program, as the intervention group. The control group was defined by 104 consecutive acute STEMI patients presenting from April 1, 2006, through February 15, 2007, before the audit was applied. A multivariate linear regression model was used for analysis of factors associated with the door-to-balloon time., Results: The geometric mean 95% CI of the door-to-balloon time decreased from 164.9 (150.3, 180.9) minutes to 141.9 (127.4, 158.2) minutes (p = 0.039) in the intervention phase. The median door-to-balloon time was 147.5 minutes in the control group and 136.0 minutes in the intervention group (p = 0.09). In the multivariate regression model, the audit program was associated with a shortening of the door-to-balloon time by 35.5 minutes (160.4 minutes vs. 195.9 minutes, p = 0.004); female gender was associated with a mean delay of 58.4 minutes (208.9 minutes vs. 150.5 minutes; p = 0.001); posterolateral wall infarction was associated with a mean delay of 70.5 minutes compared to anterior wall infarction (215.4 minutes vs. 144.9 minutes; p = 0.037) and a mean delay of 69.5 minutes compared to inferior wall infarction (215.4 minutes vs. 145.9 minutes; p = 0.044). The use of a glycoprotein IIb/IIIa inhibitor was associated with a 46.1 minutes mean shortening of door-to-balloon time (155.7 minutes vs. 201.8 minutes; p < 0.001)., Conclusions: The implementation of an audit program was associated with a significant reduction in door-to-balloon times among patients with acute STEMI. In addition, female patients, posterolateral wall infarction territory, and nonuse of glycoprotein IIb/IIIa inhibitor were associated with longer door-to-balloon times.

Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

The hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) contain neuroendocrine cells that modulate pituitary secretion to maintain homeostasis. These two nuclei have a common developmental origin but they eventually form at locations distant from each other. Little is known about the molecular cues that direct the segregation of PVN and SON. As a means to identify potential factors, we have documented expression patterns of genes with known guidance roles in neural migration. Here, we focus on two groups of ligand/receptor families classified to mediate chemo-repulsion of neurons and their axons: the Slit/Robo and the Semaphorin/Plexin/Neuropilin families. Their dynamic expression patterns within and around the common PVN/SON progenitor as well as the mature PVN and SON may provide a framework for understanding the formation of these two important nuclei.

Aim: To ascertain the effect of etanercept treatment on the T-helper cells subsets (including Th1, Th2, Th17) in rheumatoid arthritis (RA)., Methods: 20 RA patients and 10 age-matched healthy people were studied. The expression of IL-4, IFN-gamma and IL-17 on lymphocyte(CD4(+)) of RA patients peripheral blood were assessed by flow cytometry; Production of IFN-gamma, IL-4 and IL-17 were measured by enzyme-linked immunosorbent assay(ELISA)in RA sera pre- and post-12 weeks of therapy and that of 10 normal health controls were studied; correlations between percentage of IFN-gamma Th1, IL-17(+)Th17, value of Th1/Th2 and clinical factors were observed in RA., Results: The percentage of Th1 and Th17, intensity of Th17 and value of Th1/Th2 were higher than the healthy controls (P<0.05); After etanercept treatment the percentage and intensity of Th17 were significantly decreased (P<0.01), as well as the percentage of Th1 and value of Th1/Th2 (P<0.05), level of IL-17 decreased significantly but IFN-gamma, IL-4 had no significant difference; The percentage of IL-17(+)Th17 on CD4(+) T cells correlate positively to CRP and DAS28., Conclusion: Th17 cells may play a role in the pathogenesis of RA, the down regulation of Th17 and Th1/Th2 is significant for the evaluation of the curative effect of etanercept.

Staphylococcal enterotoxins (SEs) are superantigenic toxins. They are five major classical types, i.e., SEA, SEB, SEC, SED, SEE, and new SEs or SE-like superantigens, such as SEG to SEU. Only the staphylococcal superantigens (SAgs) that induce emesis following oral administration in a monkey model are designated as SEs while other related toxins are called SE-like (SEl) superantigens. To survey the enterotoxin genotypes for S. aureus strains isolated from food-poisoning cases in Taiwan, we developed PCR primers specific for SEN, SEO, SEP, SEQ, SER, and SEU genes. The complete SE sequences and their expression potential for strains positive to sen, seo, sep, seq, ser, and seu specific primers were also determined. These strains were used as reference strains. With the PCR primers specific for all SEs or SAgs, including toxic shock syndrome toxin I (TSST-1), we assayed the genotypes of 147 S. aureus strains isolated from patients associated with staphylococcal food-poisoning outbreaks occurred during 2001-2003. For these 147 strains, 135 (91.8%) were found positive for one or more SE or SAg genes. For classical enterotoxin and TSST-1 types, the major one was tsst-1 (59.1%) following by sea (29.2%), seb (19.7%), sec (6.8%), and sed (2.0%). For new SE and SAg types, the major one was sei (29.9%) and sep (27.9%) followed by, sek (16.3%), seo (14.3%), seu (14.2%), sem (11.6%), sen (10.9%), seq (10.9%), seh (8.2%), sel (6.8%), and ser (5.4%) etc. This report reveals the whole SE and SAg genotypes for S. aureus strains isolated from staphylococcal food-poisoning cases in Taiwan.

Objectives: The objective of this study is to review the basics of laser and established tissue response patterns to thermal injury, with specific reference to endovenous laser ablation (EVLA). This study also reviews the current theories and supporting aspects for the mechanism of action of EVLA in the treatment of superficial venous reflux., Methods: The method involves the review of published literature and original investigation of histological effects of 810 nm and 980 nm wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro system., Results: The existing histological reports confirm that EVLA produces a transmural vein wall injury, typically associated with perforations and carbonization. The pattern of injury is eccentrically distributed, with maximum injury occurring along the path of laser contact. Intravenous temperature monitoring studies during EVLA have confirmed that the peak temperatures at the fibre tip exceed 1000 degrees C, and continuous temperatures of at least 300 degrees C are maintained in the firing zone for the majority of the procedure. Steam production during EVLA, which occurs early in the photothermolytic process when temperatures reach 100 degrees C, accounts for only 2% of applied energy dose, and is therefore unlikely to be the primary mechanism of action of thermal injury during the procedure., Conclusion: EVLA causes permanent vein closure through a high-temperature photothermolytic process at the point of contact between the vein and the laser.

Objective: To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM)., Methods: Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker. Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography., Results: After 12-month arotinolol treatment, there was a significant improvement in left ventricular systolic function. Left ventricular end-systolic dimension significantly decreased from 59.52 +/- 8.83 mm to 50.89 +/- 8.17 mm (P < 0.001). Left ventricular ejection fraction significantly increased from 27.39% +/- 7.94% to 41.13% +/- 9.45% ( P < 0.001). Left ventricular mass index decreased from 150.47 +/- 42.42 g/m2 to 141.58 +/- 34.36 g/m2 (P < 0.01). No adverse events leading to premature discontinuation of study drug occurred., Conclusion: In this preliminary study, 12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM, and it is safe and well tolerated.

Staphylococcus aureus may cause foodborne disease outbreaks and staphylococcal infections and is one of the major causes of mastitis. Rapid and reliable methods for detection of this microorganism in milk and other foods are needed. In this study, we designed a primer set from the sequence of the heat shock protein gene htrA, a gene coding for high-temperature-requirement A (HtrA) protein, and used it for real-time PCR detection of S. aureus isolates: 16 reference strains and 40 strains isolated from food-poisoning cases. All strains tested generated positive results. Bacterial strains other than S. aureus, including strains of other Staphylococcus species, did not produce positive results. When this primer set was used for the real-time PCR detection of S. aureus in milk and meat samples without the preenrichment step, samples with target cell numbers greater than 10(3) CFU/ml or CFU/g could be detected, indicating the potential quantitative ability of this real-time PCR assay. With a 10-h preenrichment step, however, a detection limit of 1 CFU/ml or CFU/g could be obtained.

PWS is caused by the loss of expression of a set of maternally imprinted genes including NECDIN (NDN). NDN is expressed in post-mitotic neurons and plays an essential role in PWS as mouse models lacking only the Ndn gene mimic aspects of this disease. Patients haploid for SIM1 develop a PW-like syndrome. Here, we report that NDN directly interacts with ARNT2, a bHLH-PAS protein and dimer partner for SIM1. We also found that NDN can interact with HIF1alpha. We showed that NDN can repress transcriptional activation mediated by ARNT2:SIM1 as well as ARNT2:HIF1alpha. The N-terminal 115 residues of NDN are sufficient for interaction with the bHLH domains of ARNT2 or HIF1alpha but not for transcriptional repression. Using GAL4-NDN fusion proteins, we determined that NDN possesses multiple repression domains. We thus propose that NDN regulates neuronal function and hypoxic response by regulating the activities of the ARNT2:SIM1 and ARNT2:HIF1alpha dimers, respectively.

Growth Arrest Specific Gene 1 (Gas1) has long been regarded as a cell cycle inhibitor of the G(0) to S phase transition. How GAS1, a GPI-anchored plasma membrane protein, directs intracellular changes without an extracellular ligand or a transmembrane protein partner has been puzzling. A recent series of biochemical and molecular genetic studies assigned the mammalian Hedgehog (HH) growth factor to be a ligand for GAS1 in vitro and in vivo. HH has enjoyed considerable attention for its profound role in embryonic patterning as a classic morphogen, i.e. inducing various cell types in a concentration-dependent manner. GAS1 appears to help transform the HH concentration gradient into its morphogenic activity gradient by acting cooperatively with the HH receptor, the 12-transmembrane protein Patched 1 (PTC1). These findings provoke intriguing thoughts on how HH and GAS1 may coordinate cell proliferation and differentiation to create biological patterns. The role of HH extends to human genetic diseases, stem cell renewal, and cancer growth, and we consider the possibility of GAS1's involvement in these processes as well.

Purpose: To describe the pathophysiology, identification and management of inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion has been reported., Review Findings: These aneurysms are thought to arise due to increased flow through the pancreaticoduodenal arcades. The arcades first enlarge, and then form focal aneurysms which may rupture. The aneurysms can be treated through endovascular techniques or by surgery, though the former is a preferred approach.

Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. As growth arrest-specific 1 (Gas1) encodes a membrane glycoprotein previously identified as a Shh antagonist in the somite, we analyzed the craniofacial phenotype of mice harboring a targeted Gas1 deletion. Gas1(-/-) mice exhibited microform HPE, including midfacial hypoplasia, premaxillary incisor fusion, and cleft palate, in addition to severe ear defects; however, gross integrity of the forebrain remained intact. These defects were associated with partial loss of Shh signaling in cells at a distance from the source of transcription, suggesting that Gas1 can potentiate hedgehog signaling in the early face. Loss of a single Shh allele in a Gas1(-/-) background significantly exacerbated the midline craniofacial phenotype, providing genetic evidence that Shh and Gas1 interact. As human GAS1 maps to chromosome 9q21.3-q22, a region previously associated with nonsyndromic cleft palate and congenital deafness, our results establish GAS1 as a potential locus for several human craniofacial malformations.

Cellular signaling initiated by Hedgehog binding to Patched1 has profound importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts as a morphogen to specify distinctive cell fates using different concentration thresholds, but our knowledge of how the concentration gradient is interpreted into the activity gradient is incomplete. The membrane protein Growth Arrest-Specific Gene 1 (GAS1) was thought to be a negative regulator of the Hedgehog concentration gradient. Here, we report unexpected genetic evidence that Gas1 positively regulates Hedgehog signaling in multiple developmental contexts, an effect particularly noticeable at regions where Hedgehog acts at low concentration. Using a combination of in vitro cell culture and in ovo electroporation assays, we demonstrate that GAS1 acts cooperatively with Patched1 for Hedgehog binding and enhances signaling activity in a cell-autonomous manner. Our data support a model in which GAS1 helps transform the Hedgehog protein gradient into the observed activity gradient. We propose that Gas1 is an evolutionarily novel, vertebrate-specific Hedgehog pathway regulator.

Aim: To observe the correlation between vascular endothelial growth factor (VEGF) and CD147 expressed in the rheumatoid synovium and to investigate the effect of CD147 of cultured rheumatoid fibroblast-like synoviocytes (FLS) on the production of VEGF., Methods: The presence of CD147 and VEGF in the rheumatoid synovium derived from 15 patients with RA and 4 patients with osteoarthritis (OA) was detected by streptavidin/peroxidase (SP) immunostaining. FLS were cultured by enzymatic digestion of synovial tissues and incubated in 24-well plates. Then different concentration of LY294002, PD98059, SP600125, SB203580 and HAb18G mAb was added to each well. VEGF in the culture supernatant was measured by sandwich ELISA., Results: CD147 and VEGF in synovium from 15 patients with RA showed high expression, while CD147 and VEGF in synovium from 4 patients with OA showed low expression. Macrophages, fibroblast-like synovial cells and lymphocytes were demonstrated to express CD147 while synovial lining cells, fibroblasts surrounding microvessels and vascular smooth muscle cells were demonstrated to express VEGF. Statistic analysis indicates that VEGF production was correlated with the levels of CD147 expression. VEGFproduction was suppressed when CD147 expression was inhibited by LY294002 or HAb18G mAb., Conclusion: CD147 can regulate the angiogenesis in rheumatoid arthritis by VEGF. The low levels of CD147 expressed by FLS cells decrease the production of VEGF via the PI3K-Akt signaling pathway. These findings further highlight the importance of CD147 in pannus formation and angiogenesis.

SIM1 is a transcription factor essential for the developmental expression of the endocrine hormone genes, e.g. vasopressin (Vp) and oxytocin (Ot), in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Mice mutant for Sim1 lack structural PVN and SON, attributed in previous studies to the death of the PVN/SON progenitor cells. Here, we use a tau-LacZ knock-in allele at the Sim1 locus to trace Sim1 mutant cells and show that they are generated normally and survive to birth, contrasting to the previous proposal. Mutant cells adopt neuronal characteristics and maintain their PVN/SON identity as they continue to express PVN/SON progenitor markers. However, they occupy an ectopic position between the normal PVN and SON, indicating a defect in neuronal migration. To explore candidate molecular cues that contribute to PVN/SON neuronal migration, we focused on the Plexin family of genes. We found that PlexinA1 is expressed in regions surrounding the PVN and SON, whereas PlexinC1 is expressed within the PVN and SON. PlexinA1 expression becomes up-regulated in Sim1 mutant cells, whereas PlexinC1 expression is down-regulated. Finally, the PlexinC1 mutant has a selective defect in partitioning the VP and OT neurons coherently into the PVN and SON. Together, our results uncover a transcriptional regulation of neuronal migration cues initiated by Sim1 that contribute to the organization of the PVN and SON.

Aim: To explore the percentages of CD4(+) CD25(high) regulatory T cells in peripheral blood or synovial fluid from patients with rheumatoid arthritis (RA) on different stages, and to study their correlations with the activity of the disease., Methods: Peripheral blood lymphocytes were obtained from the patients with active RA who had received no previous disease modifying (DMARDs) therapy(n=11), from individuals with stable, well-controlled RA (n=12), from subjects whose disease were poorly improved after DMARDs therapy(n=9), and from healthy controls(n=8). The frequencies of CD4(+) CD25(high) T cells were quantified by using flow cytometry(FCM). Meanwhile, the correlations between the percentage of CD4(+) CD25(high) T cells and the level of Anti-CCP antibody, CRP, ESR and RF were also investigated. Paired blood and synovial fluid was analysed in a small group of RA and other patients., Results: There was a smaller proportion of CD4(+) CD25(high) T cells in the peripheral blood of the active RA patients(mean 5.24%) and poorly-improved RA patients(mean 6.43%) than in patients with stable well-controlled RA or in healthy controls(mean 11.79% and 17.17%, respectively, P<0.01 in each case). The frequency of CD4(+) CD25(high) T cells from RA was negatively associated with Anti-CCP antibody(58.0 Ru/mL), ESR(38.8 mm/h) and CRP(2.73 mug/L), (P<0.05 for each). On contrast, The frequency of CD4(+) CD25(high) T cells from healthy controls was not significantly correlated with the level of Anti-CCP antibody(<5.0 Ru/mL), ESR(4.67 mm/h), CRP(0.15 mug/L) and RF(1.37) (all P>0.1). The percentage of CD4(+) CD25(high) regulatory T cells from synovial fluid of RA patients (24.32%) was significantly lower than that of AS patients(30.24%) (P<0.05)., Conclusion: The results demonstrate a smaller CD4(+) CD25(high) regulatory T cell population in peripheral blood of individuals with active RA prior to disease modifying treatment and with poorly-improved RA, and this is negatively associated with the activity of the disease.

Oral antigen is an attractive approach for the treatment of autoimmune and inflammatory diseases. Establishment of immune markers and methods in evaluating the effects of antigen-specific cellular and humoral immune responses will help the application of oral tolerance in the treatment of human diseases. The present article observed the effects of chicken collagen II (CII), the recombinant polymerized human collagen II 250-270 (rhCII 250-270) peptide and synthesized human CII 250-270 (syCII 250-270) peptide on the induction of antigen-specific autoimmune response in rheumatoid arthritis (RA) peripheral blood mononuclear cells (PBMC) and on the specific cellular and humoral immune response in collagen-induced arthritis (CIA) and mice fed with CII (250-270) prior to immunization with CII. In the study, proliferation, activation and intracellular cytokine production of antigen-specific T lymphocytes were simultaneously analyzed by bromodeoxyuridine (BrdU) incorporation and flow cytometry at the single-cell level. The antigen-specific antibody and antibody-forming cells were detected by ELISA and ELISPOT, respectively. CII (250-270) was found to have stimulated the response of specific lymphocytes in PBMC from RA patients, including the increase expression of surface activation antigen marker CD69 and CD25, and DNA synthesis. Mice, fed with CII (250-270) before CII immunization, had significantly lower arthritic scores than the mice immunized with CII alone, and the body weight of the former increased during the study period. Furthermore, the specific T cell activity, proliferation and secretion of interferon (IFN)-gamma in spleen cells were actively suppressed in CII (250-270)-fed mice, and the serum anti-CII, anti-CII (250-270) antibody activities and the frequency of specific antibody-forming spleen cells were significantly lower in CII (250-270)-fed mice than in mice immunized with CII alone. These observations suggest that oral administration of CII (250-270) can suppress the cellular and humoral immune response in collagen-induced arthritis, and the simultaneous analysis of antigen-specific cellular and humoral immune responses at single-cell level will help the understanding of the oral tolerance mechanisms in CIA and the development of innovative therapeutic intervention for RA.

We report the case of a 48-year-old woman presenting with recurrent uterine leiomyosarcoma (LMS) associated with right iliac vein and inferior vena cava (IVC) invasion and left lower lobe pulmonary tumor embolus. Because the prognosis and treatment differ from that of thrombotic pulmonary emboli, the differentiating imaging characteristics of intravascular tumor embolism are reviewed. To our knowledge, only two other cases of intravenous uterine leiomyosarcomatosis have been described in the existing literature, and this is the first reported case of the entity with associated intravascular tumor embolism.

Aim: To investigate the modulation of rhC II 250-270 peptide on special humoral immune response in the course of oral administration., Methods: ELISA was used to determine antigen-specific antibodies in mice sera. The frequency of anti-C II and anti-C II (250-270) antibody-forming spleen cells was measured by ELISPOT., Results: The level of C II- and C II (250-270)- specific IgG in serum from the mice fed with rhC II (250-270) were (0.82+/-0.02) and (0.84+/-0.04) respectively, and lower significantly than those of collagen-induced arthritis (CIA) control group. The anti-C II (250-270) antibody responses were suppressed obviously (P<0.01). The frequency of antibody-forming cells in the spleen from rhC II (250-270)-fed mice were (158+/-9 counts/well) and (181+/-10 counts/well) respectively, and also were reduced significantly when compared with that in CIA control group (247+/-16 counts/well)(P<0.05)., Conclusion: Oral rhC II (250-270) could induce specific suppression of humoral responds in CIA. These findings together with a better understanding of the mechanisms of oral tolerance and regulation of humoral immune response in CIA, will help the development of innovative therapeutic intervention for rheumatoid arthritis.

The purpose of the study was to assess the clinical safety and efficacy of the "Recovery(TM)" (Bard) inferior vena cava (IVC) filter. We retrospectively evaluated the clinical and imaging data of patients who had a "Recovery(TM)" IVC filter placed between January 2003 and December 2004 in our institution. The clinical presentation, indications, and procedure-related complications during placement and retrieval were evaluated. Follow-up computed tomography (CT) examinations of the abdomen and chest were evaluated for filter-related complications and pulmonary embolism (PE), respectively. "Recovery" filters were placed in 96 patients (72 males and 24 females; age range: 16-87 years; mean: 46 years). Twenty-four patients presented with PE, 13 with deep vein thrombosis (DVT) and 2 with both PE and DVT. The remaining 57 patients had no symptoms of thromboembolism. Indications for filter placement included contraindication to anticoagulation (n = 27), complication of anticoagulation (n = 3), failure of anticoagulation (n = 5), and prophylaxis (n = 61). The device was successfully deployed in the infrarenal (n = 95) or suprarenal (n = 1) IVC through a femoral vein approach. Retrieval was attempted in 11 patients after a mean period of 117 days (range: 24-426). The filter was successfully removed in nine patients (82%). Failure of retrieval was due to technical difficulty (n = 1) and the presence of thrombus in the filter (n = 1). One of the nine patients who had the filter removed developed IVC thrombus after retrieval and another had an intimal tear of the IVC. Follow-up abdominal CT (n = 40) at a mean of 80 days (range: 1-513) showed penetration of the IVC by the filter arms in 11, of which 3 had fracture of filter components. In one patient, a broken arm migrated into the pancreas. Asymmetric deployment of the filter legs was seen in 12 patients and thrombus within the filter in 2 patients. No filter migration or caval occlusion was encountered. Follow-up chest CT (n = 27) at a mean of 63 days (range: 1-386) showed PE in one patient (3%). During clinical follow-up, 12 of 96 patients developed symptoms of PE and only 1 of the 12 had PE on CT. There was no fatal pulmonary embolism in our group of patients following "Recovery" filter placement. However, the current version of the filter is associated with structure weakness, a high incidence of IVC wall penetration, and asymmetric deployment of the filter legs.

Purpose: To evaluate the effect of verteporfin therapy (Visudyne) on age-related macular degeneration (AMD) in Chinese patients. The baseline characteristic and the visual outcome will be compared with the treatment of AMD with photodynamic therapy study (TAP) and verteporfin in photodynamic therapy study (VIP)., Design: Retrospective comparative case series., Method: We recruited patients >50 years old, with best-corrected visual acuity >20/200 and fluorescein angiography documenting subfoveal either predominantly classic with greatest linear dimension <5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We applied non-thermal laser to the lesion 15 min after visudyne infusion as described in TAP study. Patients were followed up with fluorescein angiography every 3 months. Additional treatment would be offered if there was evidence of recurrence of CNV., Outcome Measure: Baseline characteristic and visual outcome., Result: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002 to June 2003. They comprised 11 eyes with predominantly classic lesions and 35 eyes with pure occult lesion. The mean number of treatment sessions given was 2.9 in the first year. At the 12-month examination, there were 63 and 29% of patients showing visual improvement in predominantly classic and occult groups, respectively, while there were only 16% of patients in the TAP study and 12% of patients in the VIP study showing visual improvement in the same period., Conclusion: Verteporfin therapy for subfoveal CNV is beneficial to Chinese patients with AMD at first year. The visual result seems to be better than that observed in Caucasian patients.

Aim: To investigate the expression of CD147 both on cellular membrane and in culture supernatant of in vitro cultured THP-1 cells and monocytes of RA patients before and after stimulation with phorbol myristate acetate (PMA)., Methods: Human peripheral blood monocytes (HPBMs) were segregated from RA patients by adherent culture method. After the HPBMs and THP-1 cells were stimulated with PMA, the expression rate and expression intensity of CD147 on THP-1 cells and HPBMs of RA patients were determined by flow cytometry. The soluble CD147 levels in culture supernatant of in vitro cultured THP-1 cells and HPBMs were quantified by double antibody Sandwich ELISA., Results: The soluble CD147 in the supernatant of cultured THP-1 cells and HPBMs was detectable before PMA stimulation. Both cells showed high CD147 expression. After PMA stimulation, soluble CD147 level in the supernatant of THP-1 cells increased. CD147 expression on THP-1 cells firstly increased then decreased and kept stable for several days. CD147 expression on HPBMs of RA patients decreased, but CD147 level in the culture supernatant of HPBMs of RA patients increased and kept stable for 2 days., Conclusion: CD147 molecule can be shed from the membrane of THP-1 cells and HPBMs of RA patients, or it can be directly secreted into the culture supernatant from the two kinds of cells. PMA can up-regulate the level of soluble CD147.

Chronic venous insufficiency and varicose veins are among the most prevalent medical problems in the adult population. Historically, our understanding of venous reflux disease focused upon the anatomical mechanisms of valvular incompetence. More recent investigations into the cellular and molecular aspects of venous insufficiency have shown that the disease is a complex multifactorial process reflecting both systemic abnormalities of connective tissue synthesis and cellular inflammatory reaction. New minimally invasive endovenous treatments for primary lower extremity venous insufficiency have spurred growing clinical interest in this disease. The intent of this review article is to discuss the prevalence, epidemiological risk factors, and current theories of the pathophysiology of primary venous insufficiency.

The 4554 ORFs of Agrobacterium tumefaciens C58 Cereon were used for the prediction of signal peptides by the network tools, such as SignalP3.0, LipoP1.0, TMHMM2.0 and TargetP1.01. Total 203 signal peptides with conserved amino residues are found, among them, 158 are secretary types, 9 are RR-motif types, 28 are SignalPase II types and 8 are bacteriocin-pheromone types. However, only two signal peptides from the secreted proteins, AGR-C-1878p and AGR-C-1880p have the same amino sequences, showing the signal peptides of the strain are highly variable.

We report here a novel approach to direct gene expression in the mouse somite based on the combined application of adenovirus-mediated gene delivery and whole embryo ex vivo culture. As proof of principle, we show functional analysis of somites microinjected with an engineered virus expressing an activated form of Smoothened, the signaling receptor for Sonic Hedgehog (SHH). As adenovirus can infect many embryonic tissues in the mouse, this method may provide an effective alternative to conventional transgenesis for targeted spatial and temporal gene expression., ((c) 2005 Wiley-Liss, Inc.)

Select members of the Wnt family of secreted glycoproteins have been implicated in inducing the myogenic determinant genes Pax3, MyoD and Myf5 during mammalian embryogenesis, but the mechanism of induction has not been defined. We describe an unexpected role for protein kinase A (PKA) signalling via CREB in this induction. Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for Wnt-directed myogenic gene expression. Wnt proteins can also stimulate CREB-mediated transcription, providing evidence for a Wnt signalling pathway involving PKA and CREB. Our findings raise the possibility that PKA/CREB signalling may also contribute to other Wnt-regulated processes in embryonic patterning, stem cell renewal and cancer.