Study on the association between sleep disorders versus oral health related variables.

BACKGROUND: To study the association between sleep quality and oral health related variables, which still have conflicts in the literature. MATERIAL AND METHODS: This was a population-based case-control study between subjects with versus without sleep disorders from the Brazilian Public Health System (SUS), city of Maringá (N=1,643). Subjects answered self-reported questionnaires: a) Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), b) Sleep Assessment Questionnaire (SAQ) and c) North York Dental Health Survey (NYDHS). RESULTS: No significant difference was found for gender, marital status, or income; however, non-Caucasians, people with lower levels of education, and those between 20 to 50 years old had worse scores of sleep disorders in the SAQ. Self-perceived oral health, masticatory capacity to eat foods, and gingival bleeding was significantly worse among subjects with self-reported sleep disorders. Self-reported tooth loss, edentulism and use of removable partial dentures (with clasps) or complete dentures showed no significant difference between groups. Self-reported sleep disorder subjects presented significantly higher prevalence of both self-reported tooth and TMJ pain. CONCLUSIONS: It can be concluded that individuals with self-reported sleep disorders presented worse self-perceived oral health for most studied variables.

Gender differences in temporomandibular disorders in adult populational studies: A systematic review and meta-analysis.

The objective of this study was to systematically evaluate gender differences in the prevalence of TMD. A systematic review was performed in PubMed, EMBASE, Web of Science and LILACS in duplicate by two independent reviewers. The inclusion criteria were cross-sectional studies that reported the prevalence of TMD for men and women and that used the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I group diagnostic criteria:(group I = muscle disorders; group II = disc displacements; group III = arthralgias/arthritis/arthrosis).To be eligible for inclusion, studies must include adult individuals (>18 years) from a non-clinical population (ie without pre-diagnosis of TMD); in other words, from population-based studies. There were no restrictions on the year and language of publication. The quality of the articles was assessed by an adapted version of the Newcastle-Ottawa Scale(NOS), and the publication bias was assessed by a funnel plot graph. Data were quantitatively analysed by meta-analysis using odds ratio (OR) as the measure effect. The electronic search retrieved a total of 6104 articles, of which 112 articles were selected for full-text reading according to the eligibility criteria. By means of manual search, one study was retrieved. Five articles were selected for meta-analysis with a combined sample of 2518 subjects. Women had higher prevalence of TMD in all RDC/TMD diagnostic groups. The meta-analysis yielded the following results: (a) OR = 2.24 for global TMD (groups I, II and III combined), (b) OR = 2.09 for group I, (c) OR = 1.6 for group II and (d) OR = 2.08 for group III. The importance of gender in the development of TMD has been demonstrated, with a two times greater risk of women to develop it as compared to men.

Efficacy of a mandibular advancement intraoral appliance (MOA) for the treatment of obstructive sleep apnea syndrome (OSAS) in pediatric patients: A pilot-study.

BACKGROUND: To evaluate the treatment efficacy of a mandibular advancement intraoral appliance (MOA) for treatment of obstructive sleep apnea syndrome (OSAS) in pediatric patients. MATERIAL AND METHODS: Eighteen patients (mean=8.39 years old, women=44.4%) were selected. Sleep disorders, sleep bruxism, and temporomandibular disorders were assessed by the Sleep Disturbance Scale for Children (SDSC), the BiteStrip® (portable SB device), and the Research Diagnostic Criteria for Temporomandibular Disorders, respectively. The clinical diagnosis of OSAS was confirmed with a type 3 portable monitor device (ApneaLinkTM Plus). A silicon-based material MOA was used by patients for 60 days, and the results were compared to baseline. RESULTS: The median RDI was significantly reduced from 10 to 4.5 events/hour. Nadir SpO2 significantly increased from 82.6% to 88.9%. Total snoring events/hour have also significantly decreased from 205.5 to 91.5. Signs and symptoms of TMD remained unaltered. There was also a reduction from moderate to absence of SB in 12 patients. Similarly, all variables measured by the SDSC have had very significant reductions: disorders of initiating and maintaining sleep, sleep disordered breathing, disorders of arousal, nightmares, sleep wake transition disorders, disorders of excessive somnolence, and sleep hyperhidrosis. CONCLUSIONS: In selected cases, OA maybe considered as an alternative for the OSAS treatment.

Pycnogenol® supplementation improves health risk factors in subjects with metabolic syndrome.

This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome. Pycnogenol® was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose. Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol® was administered for 6 months. A group of 66 equivalent subjects were followed up as controls. In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects. Pycnogenol lowered fasting glucose from baseline 123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls). Men's waist circumference decreased with Pycnogenol from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months. Women's waist decreased from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months. Both genders waist circumference reduction was significant as compared to controls at both time points. In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34.6%; p < 0.05). In conclusion, this study indicates a role for Pycnogenol® for improving health risk factors in subjects with metabolic syndrome.

Fear of cancer recurrence in young women with a history of early-stage breast cancer: a cross-sectional study of prevalence and association with health behaviours.

PURPOSE: Fear of cancer recurrence (FCR) is common and associated with younger age. This study aimed to explore the prevalence and correlates of FCR amongst younger survivors of early breast cancer. SUBJECTS: A total of 218 women aged 18-45 were diagnosed with stage 0-2 breast cancer at least 1 year earlier. METHODS: The participants completed a web-based survey including a validated measure of FCR and items exploring medical surveillance practices and health care use. RESULTS: A total of 70% of participants reported clinical levels of FCR. Higher FCR was associated with higher frequency of unscheduled visits to the GP, higher frequency of breast self-examination and other forms of self-examination for cancer, not having mammograms or ultrasounds or other forms of cancer screening in the past year, more complementary therapy use and the use of counselling and support groups. CONCLUSIONS: Young women with breast cancer are particularly vulnerable to FCR. The present study provides preliminary evidence that FCR is associated with higher health costs and lower surveillance rates which may compromise health outcomes. Routine screening for FCR in follow-up care is recommended.

Indocyanine green enhanced subthreshold diode-laser micropulse photocoagulation treatment of chronic central serous chorioretinopathy.

PURPOSE: To assess the efficacy and safety of indocyanine green (ICG) dye-enhanced subthreshold diode-laser micropulse (SDM) photocoagulation in patients with chronic central serous chorioretinopathy (CCSC) with no spontaneous resolution 6 months after the onset of the disease. STUDY DESIGN: Interventional prospective non-comparative case series of seven patients presenting with CCSC with well-defined active leaking sites (ALS) suitable for laser treatment and with serous neuroepithelial detachment persisting for 6 or more months. METHODS: SDM treatment was performed 15 minutes after the injection of 25 mg of ICG in 2 cc of 5% glucose solution. ALS were treated with a series of 50 500-ms exposures separated by 500-ms pauses. Each 500-ms exposure delivered a train of 250 micropulses at 10% duty cycle and 500 mW power. ICG angiographic images were taken after the treatment without new ICG injection, to check for the presence of laser-induced spots of background hypofluorescence at the treated leakage sites. RESULTS: Within 7-14 days after treatment, all the patients showed improved visual acuity and reduction of serous neuroepithelial detachment on OCT. No signs of laser lesions were visible at fundus examination and on fluorescein angiography. In a period ranging from 4 to 8 weeks, the neuroepithelial detachment was completely resolved in five patients and reduced in two patients. At the 12-month follow-up visits, no recurrence had occurred in the patients, with resolution of the serous neuro-epithelial detachment, and no worsening of the serous detachment or of VA was noted in the patients with incomplete recovery. CONCLUSIONS: These preliminary results suggest that ICG dye-enhanced SMD photocoagulation appears to be an effective treatment, and can represent a viable approach for the management of CSCC with persistent serous neuroepithelial detachment. Post-treatment ICG angiography, without new ICG dye injection, can be used to verify the placement of the SDM laser applications.

Detection of microbial concentration in ice-cream using the impedance technique.

The detection of microbial concentration, essential for safe and high quality food products, is traditionally made with the plate count technique, that is reliable, but also slow and not easily realized in the automatic form, as required for direct use in industrial machines. To this purpose, the method based on impedance measurements represents an attractive alternative since it can produce results in about 10h, instead of the 24-48h needed by standard plate counts and can be easily realized in automatic form. In this paper such a method has been experimentally studied in the case of ice-cream products. In particular, all main ice-cream compositions of real interest have been considered and no nutrient media has been used to dilute the samples. A measurement set-up has been realized using benchtop instruments for impedance measurements on samples whose bacteria concentration was independently measured by means of standard plate counts. The obtained results clearly indicate that impedance measurement represents a feasible and reliable technique to detect total microbial concentration in ice-cream, suitable to be implemented as an embedded system for industrial machines.

Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients.

This study was conducted with the aim of showing the effects of Pycnogenol on controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7 days starting 2 days prior to the flight was used. The study was divided into two separate parts. In study 1 the most common complaints of patients with jet-lag were evaluated with a rating scale consisting in of a scoring system. In study 2 a brain CT scan was performed after the flight in order to assess minimal brain edema (MBE) in association with typical signs and symptoms, observed in previous published flight studies. Study one included 38 subjects treated with Pycnogenol and 30 controls. The symptomatic jet-lag related total score was significantly lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average duration of any jet lag symptom following the flight was significantly reduced from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol and 31 controls. The main observation was the brain CT scan performed within 28 hours after the end of the flight. The difference between the Pycnogenol and the control groups was statistically significant (P<0.05) for all items assessed including the cerebral edema score obtained by CT scan. The short-term memory was significantly altered in the control group and associated to edema and swelling of the lower limbs. The score (and the level of edema) was comparatively higher in a subgroup of hypertensive subjects in the control group. Minor alterations of cardiac function were observed in association with de-stabilisation of blood pressure. Fatigue was also significantly higher in the control group in comparison with the Pycnogenol group. A number of spontaneously reported symptoms was also scored and there was a statistically significant difference (P<0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

LINFAVENIX: improvement of signs and symptoms of chronic venous insufficiency and microangiopathy.

The aim of this independent study was to demonstrate the rapidity of the efficacy of an oral venotropic compound (Linfavenix, including natural elements) in patients with chronic venous insufficiency (CVI). Two groups of patients with chronic venous insufficiency (CVI) ankle swelling) were treated with Linfavenix or with below-knee elastic compression. The average ambulatory venous pressure (AVP) at inclusion (both groups)was 56.2 (range 48-55) with a refilling time (RT) shorter than 10 seconds. These parameters indicated a severe level of venous hypertension. There were no significant differences in AVP and RT between the two groups. The two groups of subjects with CVI were comparable; in the Linfavenix group there were 14 patients (age 44.5; sd 4; range 34-55; 7 females); in the elastic compression group there were 12 patients (45.4;5; range 36-56; 7 females). The clinical picture and microcirculatory parameters at inclusion were comparable. RF was comparable at inclusion in the two groups. At two weeks, the differences in RF (between goups) were not significant (the flux decreased in both groups, indicating improvement) while at 4 weeks the difference was larger (but non significant between the two groups) with a significant decrease in RF in the Linfavenix group. The RAS was also comparable at inclusion. Both groups had a significant decrease at 2 and 4 weeks. The decrease produced by Linfavenix after 4 weeks in RF was larger and significant (p<0.05) in comparison with the elastic compression group. Also the differences observed in ASLS were significant in both groups with an important, significant difference in favour of Linfavenix at 4 weeks (op<0.05) visibile as edema reduction. The decrease in edema was relevant in both groups at 2 (p<0.05) and 4 weeks (p<0.05) with a minimal but significant difference (p<0.05) between the Linfavenix and the elastic compression group. These variations in microcirculatory parameters indicate that the treatment with Linfavenix is, in its microcirculatory efficacy, at least comparable than elastic compression with is considered a standard therapeutic option in these patients. A significant level of improvement was reached with Linfavenix, in most patients (10/14) at 2 weeks for RF, at 7 days for the RAS and also at 2 weeks in almost all patients (13/14) considering ASLS and edema. No side effects due to treatment were observed. Compliance and tolerability were very good (no patient had to stop treatment; there were no drop-outs). In conclusion venous microangiopathy and edema were improved by the treatment with Linfavenix (better in comparison with compression) in a few days.

[NPT (near patient test) in the pharmacy: document and practice guidelines 2008]. / Screening nelle farmacia: documento e linee guida 2008.

NPT tests in the pharmacy. Blood testing can be made with NPT (near patient testing) directly in the pharmacy. Most tests can be made with a single drop of blood (i.e. from a finger) and results are comparable with results from blood test obtained with standard vein blood samples. NPT is basically used for: 1 - evaluating the risk of a disease. 2 evaluating or confirming the presence of a disease. 3 to manage and monitor treatments. The social role of the pharmacy in NPT (particularly in cardiovascular screening) is very important as the pharmacy is an institution with capillary diffusion in the territory. The pharmacy often constitutes an important, first-level consultancy point for the population, particularly where health institutions are far away (small villages) or not easily accessible. Rules for NPT. Guidelines for NPT testing in the pharmacy have been proposed and discussed in a consensus meeting (Spoleto, 2007). NPT guidelines suggest operating management and technical procedures and indicate prospective lines of action defining new roles for the pharmacy. Coagulation tests can be now made in the pharmacy at a very low cost and with an efficacy comparable to blood tests obtained with a vein sample. Results can be read in seconds. This test is also available for personal use and home testing. NPT: The Clinical Study. The evaluation of the results of a clinical study (patients with venous thrombosis/pulmonary embolisation, patients with fibrillation and patients with artificial cardiac valves) indicates that costing is very favourable for NPT which may reduce costs and improve management of many clinical conditions and their monitoring. Training and control systems help NPT testing to be reliable and useful to screen and manage most clinical and risk conditions. The clinical study also shows the positive correlation between NPT tests and standard' tests. In conclusion NPT tests are now very reliable and cost-effective and can be used for screening, diagnosis and to monitor treatments.

Management of uncomplicated ankle sprains with topical or oral ketoprofen treatment. A registry study.

Ankle sprains mainly caused by accidents or strenuous sport activities can often be quite painful and impair motility. If not treated immediately and correctly, sprains may lead to severe complications. The aim of the present study was to compare the efficacy and safety of topically applied ketoprofen versus orally administered ketoprofen in 20 patients with grade I ankle sprain and 34 patients with grade II sprain. The patients were divide into in two treatment groups and received either topically applied ketoprofen treatment (ketoprofen 10% spray-gel; Prontoflex; 360 mg/die) or orally administered ketoprofen treatment (ketoprofen tablets; 3x50 mg/die). Treatment duration was one week. After 3 and 7 days of treatment, reduction of spontaneous pain and pain on active movement in the Prontoflex group was significantly bigger greater in the oral treatment group, irrespective of sprain severity. Regarding secondary parameters as mobility impairment and ankle swelling topically applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, Prontoflex was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients. The good efficacy in pain reduction and absence of side effects in the present study distinguished the topically applied ketoprofen as a favorable treatment for patients with accidental or sport soft tissue injuries.

BK virus-plasmid expression vector that persists episomally in human cells and shuttles into Escherichia coli.

We describe a novel expression vector, pBK TK-1, that persists episomally in human cells that can be shuttled into bacteria. This vector includes sequences from BK virus (BKV), the thymidine kinase (TK) gene of herpes simplex virus type 1, and plasmid pML-1. TK+-transformed HeLa and 143 B cells contained predominantly full-length episomes. There were typically 20 to 40 (HeLa) and 75 to 120 143 B vector copies per cell, although some 143 B transformants contained hundreds. Low-molecular-weight DNA from TK+-transformed cells introduced into Escherichia coli were recovered as plasmids that were indistinguishable from the input vector. Removal of selective pressure had no apparent effect upon the episomal status of pBK TK-1 molecules in TK+-transformed cells. BKV T antigen may play a role in episomal replication of pBK TK-1 since this viral protein was expressed in TK+ transformants and since a plasmid that contained only the BKV origin of replication was highly amplified in BKV-transformed human cells that synthesize BKV T antigen.

Topical heparin: new observations.

Topical effects of heparins on the skin need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (a) the anticoagulant action, (b) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (c) the 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively in both experimental and clinical conditions. Recent experimental studies demonstrate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have promising answers. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis (SVT) can focus on locally applied heparin. SVT is an important clinical condition considering its frequency and the potentially heavy use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.

Cytotoxic necrotizing factor 1 hinders skeletal muscle differentiation in vitro by perturbing the activation/deactivation balance of Rho GTPases.

The current knowledge assigns a crucial role to the Rho GTPases family (Rho, Rac, Cdc42) in the complex transductive pathway leading to skeletal muscle cell differentiation. Their exact function in myogenesis, however, remains largely undefined. The protein toxin CNF1 was herein employed as a tool to activate Rho, Rac and Cdc42 in the myogenic cell line C2C12. We demonstrated that CNF1 impaired myogenesis by affecting the muscle regulatory factors MyoD and myogenin and the structural protein MHC expressions. This was principally driven by Rac/Cdc42 activation whereas Rho apparently controlled only the fusion process. More importantly, we proved that a controlled balance between Rho and Rac/Cdc42 activation/deactivation state was crucial for the correct execution of the differentiation program, thus providing a novel view for the role of Rho GTPases in muscle cell differentiation. Also, the use of Rho hijacking toxins can represent a new strategy to pharmacologically influence the differentiative process.

Ependymomas, malignant tumors of pancreatic islets, and osteosarcomas induced in hamsters by BK virus, a human papovavirus.

BK virus (BKV), a human papovavirus, was inoculated iv into 3-week-old Syrian golden hamsters. Between 2 1/2 and 9 months after inoculation, 82% of the animals developed tumors. The induced neoplasms were ependymoma, carcinoma of the pancreatic islets, osteosarcoma, adenocarcinoma, angiosarcoma, angioma, lymphoma, and seminoma. Hypersecretion of insulin, glucagon, C-peptide, and calcitonin was detected in tumors of pancreatic islets. BKV etiology of tumors was supported by the following evidence: 1) No tumors with BKV-specific markers appeared in animals given injections of buffer, animals inoculated with BKV neutralized by anti-BKV-specific serum, or uninoculated controls; 2) BKV tumor (T) antigen was detected by immunofluorescence and complement fixation tests in tumors of animals inoculated with infectious BKV and in transplanted tumors; 3) antibodies to BKV T-antigen were detected in sera of animals bearing primary or transplanted tumors; 4) BKV could be activated by Sendai virus-mediated fusion of neoplastic cells with susceptible Vero cells; and 5) no endogenous hamster oncornaviruses were found in tumors.

NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.

A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.

v-jun oncogene prevents terminal differentiation and suppresses muscle-specific gene expression in ASV-17-infected muscle cells.

Infection of replicating quail myoblasts with avian sarcoma virus 17 (ASV-17) results in the inhibition of terminal differentiation into multinucleated myotubes and in the acquisition of anchorage-independent proliferation. Expression of v-jun, the ASV-17 oncogene, concomitantly leads to the accumulation of the gag-jun polyprotein P65 in the nucleus and to the lack of expression of typical differentiation-specific genes such as myosin heavy chain (MHC) and alpha-actinin. Surprisingly, expression of desmin, the muscle-specific subunit of intermediate filaments, is conserved in ASV-17-transformed myoblasts. Analysis of clonal strains of transformed myoblasts suggests that (i) suppression of morphological and biochemical differentiation depends on the absence of muscle-specific gene transcripts; (ii) inhibition of muscle differentiation by v-jun does not depend on the transcriptional silencing of MyoD, a muscle-specific regulatory gene; (iii) expression of desmin is compatible with proliferation of ASV-17-transformed cells and is independent of v-jun and MyoD levels of expression. The present data suggest that nuclear localization of v-jun prevents terminal differentiation in myoblasts and selectively down-regulates muscle-specific genes in terminally differentiated myotubes. In this respect, the behaviour of v-jun is quite different from that of v-myc, thus suggesting that these two oncogenes, although both encoding nuclear proteins, may have different mechanisms of action.

Transcriptional down-regulation of myogenin expression is associated with v-ras-induced block of differentiation in unestablished quail muscle cells.

Unestablished quail myoblasts were infected with a retroviral vector encoding the oncogenic form of H-Ras in order to investigate the mechanism by which this oncoprotein interferes with terminal differentiation. Primary quail myogenic cells exhibit the simultaneous expression of the muscle regulatory genes myf-5, MyoD and myogenin in proliferative conditions. v-ras-transformed myoblasts displayed an altered growth control and lost the competence for terminal differentiation. When expression of myogenic regulatory genes was analysed, it was immediately apparent that the difference between normal and v-ras-transformed cells was limited to a severely decreased level of myogenin expression. Forced expression of exogenous myogenin in v-ras-transformed quail myoblasts led to a striking recovery of the competence for terminal differentiation. The present data show that: (i) repression of myogenin expression is linked to the differentiation defective phenotype of quail myoblasts transformed by v-ras as well as other retroviral oncogenes; (ii) correction of the differentiation-defective phenotype of v-ras-transformed myoblasts by exogenous myogenin entailed reactivation of endogenous myogenin and of the E-box-dependent transactivating function. These results strongly indicate that myogenin expression plays a central role in regulating the transition into the terminally differentiated state and that its transcriptional down-regulation represents a nodal step in v-ras-induced block of differentiation.