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Objective: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barre syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). Methods: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. Results: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. Conclusions: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. Significance: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.(c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

CAPE is the major active component of propolis, a widely available, safe, honeybee natural product with anti-inflammatory, antioxidant, and antitumor properties. We have previously shown diverse effects of CAPE in breast cancer. We postulated that CAPE may be useful in chemoprevention for women at high risk for triple-negative breast cancers (TNBC) and evaluated this in a radiation chimera mouse model in which the tumor spectrum is shifted to TNBC. The radiation chimera model consists of surgically clearing the mammary epithelium from the inguinal glands of 3-week old BALB/c mice, the mice were irradiated with 1 Gy or sham irradiated at 10–12 weeks of age, and bilaterally transplanted 3 days later with syngeneic Trp53 null mammary fragments. Mice were placed on a CAPE diet or a control diet at 1 month post transplantation that was maintained for the course of the experiment. Mammary tumor development was monitored by palpation for up to 18 months. The first tumor was resected at 1cm3 and mice monitored for tumor recurrence or second tumor formation. Tumors were immunostained for estrogen receptor (ER) status and ER negative tumors were selected from all the groups for RNA sequencing. No difference in body weight or tumor incidence was observed between mice on the CAPE versus control diet. Host irradiation significantly accelerated tumor growth rate compared to the control sham irradiated mice. CAPE treatment blocked this effect, but did not affect the control tumor growth rate. Resected tumors in CAPE treated mice recurred at significantly longer intervals (average of 40 days in the control group versus 90 days with CAPE treatment) and much less frequently than tumors from mice on a control diet. Mean expression analysis showed that CAPE induces a distinct gene expression pattern in ER negative tumors from irradiated mice. As previously described, the transcriptional profile of ER negative tumors was enriched in immune response genes in tumors from nonirradiated mice on a control diet, while irradiation suppresses these genes. Interestingly, this difference was abrogated in mice on the CAPE diet where we found that CAPE reverses the suppression of immune response genes in the ER negative tumors from the irradiated mice. These findings support the potential use of CAPE to modify the aggressive behavior of TNBC. This may be due to effects on the immune system in which CAPE acts to re-establish anti tumor immunity. Thus, CAPE may be useful in chemoprevention both for women at high risk for TNBC and to prevent or delay TNBC breast cancer recurrence. Citation Format: Omene C, Patel M, Illa Bochaca I, Barcellos-Hoff MH. Modification and reversal of the aggressive behavior of triple negative breast cancer by caffeic acid phenethyl ester (CAPE) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-06-04.

La Tordera, al seu pas per la vila a què dona nom, ha estat l’eix sobre el qual ha girat bona part de la vida dels torderencs. El riu ha aportat l’aigua de boca i de rec, l’energia per a moure moles farineres, per a generar electricitat o crear negocis com l’aigua embotellada, per exemple. Però també ha estat el malson quan s’ha sortit de mare o quan s’ha convertit en el camí que ha portat enemics vinguts del mar. En la nostra comunicació repassarem els usos i les incidències del riu que, al llarg de la història, han marcat el pols vital del poble.

The government of Catalonia has developed a planning framework that seeks to establish the provision of cultural facilities throughout the country. The Cultural Facilities Plan of Catalonia (PECCAT) is based on an analysis of historical gaps and establishes a minimum spatial scheme. The plan responds to problems associated with the absence of a former similar instrument, which has led to an inconsistent and inappropriate cultural infrastructure that fails to fulfill its fundamental mission of securing the cultural rights of the population. The paper sets forth the aims of this policy and describes the objectives and basic characteristics of the plan and the expected outcomes. With the plan, the government of Catalonia seeks to rebalance the infrastructure within the territory and to ensure universal access to basic cultural services, while avoiding a logic of standardization and taking local communities into account. With the development of local plans in the municipalities, local governments encourage community participation processes to adapt and decide on priorities for action based on needs assessments and cultural opportunities for local sustainable development. The local plans focus on local cultural strengths, take advantage of opportunities, and aim to realize the cultural dynamics of a place through establishing an infrastructure that can best respond to the needs and cultural demands of the local communities, taking into account economic, social, and environmental sustainability.

La construccion de sistemas de informacion cultural y la representacion de sus contenidos mediante recursos cartograficos se inicio en Espana a principios de los anos 90. La realizacion de atlas y mapas de recursos culturales exigieron en su momento esfuerzos de sistematizacion y taxonomia que les confirieron un valor cultural intrinseco. En una primera etapa, la realizacion de mapas culturales se vio muy condicionada por la dificultad asociada a la obtencion, estructuracion, y sobre todo, a la actualizacion de la informacion de base. La introduccion de las tecnologias de informacion geografica (TIG) permitio dar un salto adelante aportando una dimension dinamica y facilitando la actualizacion, el analisis y la representacion simultanea de la informacion y tambien su tratamiento en la web. Esta dimension se vio aun mas potenciada con la introduccion de los instrumentos geoweb que facilitan las rutinas de geolocalizacion, y muy especialmente los procesos colaborativos propios de la web 2.0. Pero cuando hablamos de cartografias culturales podemos establecer marcos de accion que van mas alla de la aplicacion de la ars cartografica al sector cultural, podemos hablar de unas cartografias con un nivel de “profundidad” o “intensidad” cultural que desborda la simple asociacion instrumental. Por un lado, cabe contemplar la relacion de la cartografia con el arte, relacion fructifera y secular. Por otro lado, cabe destacar una dimension mucho mas reciente, pero no menos intensa y sumamente interesante: la esencia cartografica de determinados proyectos culturales y creativos.

Introduction - In amyotrophic lateral sclerosis (ALS), symptoms apparently spread following regional rules, and depending on the site of onset. We examined if respiratory function deterioration appears earlier or is more severe in patients with upper-limb onset. Material & methods-We compared the results of various pulmonary function tests (PFT) obtained at diagnosis depending on the site of onset in 49 ALS patients. In a longitudinal study, we compared the deterioration of forced vital capacity (FVC) in relation to the site of onset, and analyzed the time elapsed to reach values below 80% of predicted according to site of onset, and we compared the survival depending on the site of onset. Results - No significant differences in PFT were found in the upper-limb onset group in any of the analysis performed. No differences in survival were detected in any disease onset group. Conclusion - Pulmonary function deterioration does not appear to be time-linked to arm onset in ALS.

We report a Spanish family with muscle glycogen phosphorylase (PYGM) deficiency (McArdle's disease) harbouring a novel compound genotype (A659D/L586P). Four individuals who had the same genotype for PYGM, showed a wide variability in the presentation of the clinical phenotype, including one patient with a restrictive respiratory pattern, which is unusual in McArdle's disease. Moreover, these patients were studied for the insertion/deletion (I/D) trait in the angiotensin converting enzyme (ACE) which has been suggested to be a strong modulator of severity in McArdle's disease. Our results indicate no association of the I/D ACE trait in this family, suggesting that other factors would be more relevant in determining the severity of the clinical presentation.

Los trastornos inmunologicos pueden estar implicados en neuropatias adquiridas. Se repasan las entidades mas relevantes y el valor de la determinacion de diversos anticuerpos.

The reported prevalence of myasthenia gravis ranges between 5 and 24 cases per 100,000, and people over 65years account for less than 50% of all cases. The prevalence and clinical characteristics of myasthenia gravis in the county of Osona were studied in patients younger and older than 65.The study draws from the county-based prospective myasthenia gravis register implemented by the Neurology Department at Hospital General de Vic in 1991.The prevalence of myasthenia gravis was 32.89×10These figures show the highest prevalence rate reported to date. This high prevalence is due to the rate observed among patients older than 65. These results provide a new warning that myasthenia gravis may be underdiagnosed in the elderly population.

We describe a patient with a pure motor chronic demyelinating polyneuropathy with an IgM monoclonal component showing w Ž. x anti-GM2, GalNAc-GD1a and GalNAc-GM1b reactivity whose common epitope appears to be - GalNAcb1-4Gal 3-2a NeuAc b 1. We used intracellular recording to study how IgM from this patient affected neurotransmitter release in the mouse diaphragm in vitro. Ž. Adding serum and specifically, the purified monoclonal IgM component blocked the nerve-evoked response in both quantal content Ž. and evoked endplate potential EPP amplitude in a complement-independent and reversible manner. The IgM increased the frequency of Ž. spontaneous miniature endplate potentials MEPPs in a complement-dependent and reversible manner but had no effect on MEPP amplitude. q 2001 Elsevier Science B.V. All rights reserved.

Distal myopathies are classified according to clinical, histopathological, and genetic patterns into the following: late adult onset type 1, or Welander myopathy, the first recognized distal myopathy with autosomal dominant inheritance and very recently linked to chromosome 2p; late adult onset type 2, or Markesbery-Griggs/Udd myopathy, autosomal dominant with linkage to chromosome 2q; early adult onset type 1, or Nonaka myopathy, an autosomal recessive disease linked to 9p1-q1 and considered indistinguishable from hereditary inclusion body myopathy; early adult onset type 2, or Miyoshi myopathy, with autosomal recessive inheritance linked to chromosome 2p12-p14; and early adult onset type 3, or Laing myopathy, autosomal dominant with linkage to chromosome 14. Very recently, dysferlin, a novel skeletal muscle gene, has been found mutated in Miyoshi myopathy and also in the limb girdle muscular dystrophy 2B, a disease with a completely different phenotype. This indicates that the classification of the distal and other genetically determined muscle diseases will probably change when these myopathies are understood at the molecular level. For example, it would be reasonable to use the term dysferlinopathies to describe all the diseases due to dysferlin mutations.

Serial evaluation of forced vital capacity (FVC) were performed in 34 patients with amyotrophic lateral sclerosis, 28 of whom were followed until death. Successive evaluation of FVC in the same patient did not show a linear progression. An inflexion point was detected in most patients followed to death (81%) with initial normal FVC values. The decline was more rapid and survival time was less than 1 year in most patients after the inflexion point. Significant changes in FVC were characteristic of the second half of the course of the disease. FVC results are useful for determining the presence and degree of respiratory system involvement, but our results suggest that FVC alone cannot serve as a quantitative test in clinical trials, since most patients show a curvilinear slope in FVC deterioration instead of a linear slope.

Before 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appear.

Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited neuropathy. In accordance with the inheritance pattern and degree of slowing of motor conduction velocity (MCV) of the median nerve, CMT encompasses five main forms: CMT1 (autosomal dominant [AD] or X-linked transmission and MCV38 m/s); CMT2 (AD or X-linked transmission and MCV38 m/s); CMT4 (autosomal recessive [AR] and severe slowing of MCV); AR-CMT2 (AR transmission and MCV38 m/s); and DI-CMT (intermediate form with AD transmission and MCV between 30 and 40 m/s). In spite of its stereotyped semiological repertoire (basically, symptoms and signs of sensory-motor polyneuropathy and pes cavus), CMT seems to be one of the most complex hereditary neurodegenerative syndromes, 31 causative genes having been cloned.This paper is aimed at performing a nosological review of the disease, emphasising the guidelines for its molecular diagnosis. Genetic epidemiological studies and genotypes reported in Spanish patients are revised.In the great majority of CMT cases, mutations involve a reduced number of genes, namely: for CMT1, PMP22, GJB1 and MPZ; for CMT2, MFN2 and GJB1; for CMT4, GDAP1, and NDRG1, HK1 and SH3TC2 (gypsies); for AR-CMT2, GDAP1; and for DI-CMT, GJB1 and MPZ. Given their low prevalence, mutations in other pathogenic genes should be investigated after discarding the previous ones. There is no place for the indiscriminate use of diagnostic CMT genetic panels.

The government of Catalonia has developed a planning framework that seeks to establish the provision of cultural facilities throughout the country. The Cultural Facilities Plan of Catalonia (PECCAT) is based on an analysis of historical gaps and establishes a minimum spatial scheme. The plan responds to problems associated with the absence of a former similar instrument, which has led to an inconsistent and inappropriate cultural infrastructure that fails to fulfill its fundamental mission of securing the cultural rights of the population. The paper sets forth the aims of this policy and describes the objectives and basic characteristics of the plan and the expected outcomes. With the plan, the government of Catalonia seeks to rebalance the infrastructure within the territory and to ensure universal access to basic cultural services, while avoiding a logic of standardization and taking local communities into account. With the development of local plans in the municipalities, local governments encourage community participation processes to adapt and decide on priorities for action based on needs assessments and cultural opportunities for local sustainable development. The local plans focus on local cultural strengths, take advantage of opportunities, and aim to realize the cultural dynamics of a place through establishing an infrastructure that can best respond to the needs and cultural demands of the local communities, taking into account economic, social, and environmental sustainability.

Background Chronic inflammatory demyelinating polyradiculoneuropathy is a chronic progressive or relapsing and remitting disease with a prevalence of up to 8.9 per 100,000.

Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs' syndrome).To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts.Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non-thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long-term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4-Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short-term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).

Objective: To describe the clinical phenotype of an autosomal-dominant pedigree with myotilinopathy. Methods: Two symptomatic patients and six asymptomatic gene mutation carriers were examined. We performed serum chemistry, electrophysiological assessments, magnetic resonance imaging (MRI) of lower limb musculature, histochemical and immunohistochemical studies of a muscle biopsy and mutation analysis of the myotilin gene. Results: Both symptomatic patients, aged 76 and 61 years, presented with late-onset, distal lower-limb weakness involving the ankle and toe flexo-extensor muscles extending up to the thigh muscles; there was mild weakness of the intrinsic hand musculature in the eldest patient. Electromyography revealed a myopathic pattern. Serum creatine kinase levels were slightly elevated. Muscle biopsy revealed myopathic changes with myotilin- and desmin-positive aggregates. Gene sequencing identified a myotilin S55F mutation. In both patients, MRI showed moderate to severe fatty atrophy of all four leg muscle compartments, extending up to the thigh musculature, mainly involving the biceps, femoris, semimembranosus, vasti and glutei muscles; intrinsic foot musculature was involved but to a lesser degree. In all six gene mutation carriers, aged from 21 to 63 years, clinical examinations showed no myopathic signs. MRI was normal in the youngest individual, whereas in the remaining five individuals the outstanding finding was fatty infiltration of the soleus muscles. Conclusions: Myotilin S55F mutations may cause a clinically distinct autosomal-dominant late-onset and lower-limb distal myopathic syndrome involving all four leg muscle compartments. MRI helps to reliably depict the topography of fatty muscle atrophy and to detect early leg muscle changes in asymptomatic gene mutation carriers.

SUMMARYWe have studied the influence of variations in dietary protein (P) and digestible carbohydrate (C), the quantity of food eaten, and insect age during the fifth instar on the expression of the proliferating cell nuclear antigen(PCNA) in the epithelial cells of the midgut (with special reference to the midgut caeca) in the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA-immunostained cells was used as an indirect measure of the levels of expression of PCNA, and a PCNA cellular index(PCNA-I) was obtained. Measurements of the DNA content of the cells have also been carried out by means of microdensitometry of Feulgen-stained, thick sections of midgut. A comparison between the PCNA nuclear level and the DNA content was performed. The PCNA levels were significantly different among the cells of the five regions studied: caeca, anterior ventricle, medial ventricle, posterior ventricle and ampullae of the Malpighian tubules. We have studied in more detail the region with highest PCNA-I, i.e. the caeca. The quality and the quantity of food eaten under ad libitum conditions were highly correlated with both the PCNA and DNA levels in the caeca cells. Locusts fed a diet with a close to optimal P:C content (P 21%, C 21%) showed the highest PCNA and DNA content. In locusts fed a food that also contained a 1:1 ratio of P to C but was diluted three-fold by addition of indigestible cellulose (P 7%, C 7%), a compensatory increase in consumption was critical to maintaining PCNA levels. Our measurements also showed that the nuclear DNA content of the mature and differentiated epithelial cells was several-fold higher than the levels in the undifferentiated stem cells of the regenerative nests. These results, combined with the low number of mitotic figures found in the regenerative nests of the caeca and the marked variation in PCNA levels among groups, suggest that some type of DNA endoreduplication process may be taking place. Our data also indicate that the DNA synthetic activity in the midgut is related to feeding in locusts. The possible dietary and nutritional regulatory mechanisms and the significance of the differences found are discussed.

Neuromuscular disorders alone can account for up to 62% of the cases of ventilatory dependency in intensive care unit (ICU) patients with no other apparent causes of failure to wean, and they may be a contributing factor in up to 86% of these patients (Spitzer et al. 1992). In addition, neuromuscular abnormalities can be detected in up to 95% of patients who stay in the ICU for a period of more than 7 days (Coakley et al. 1993). Among the neuromuscular disorders, critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) have become two of the most common underlying diagnoses associated with an otherwise unexplained need for prolonged ventilatory support. Although in the earliest reports on CIP and CIM most patients had sepsis and multiple organ failure or were given neuromuscular blocking agents or high doses of corticosteroids, respectively, it is now well accepted that the spectrum of primary medical diseases in these patients is much broader than initially suspected and that the above-mentioned pharmacological precedent is not a constant feature (Berek et al. 1996; Coakley et al. 1993). In this chapter, we describe the epidemiological, clinical, electrophysiological, and pathological characteristics of both entities and summarize the relevant findings related to their pathogenesis.

This is a document prepared by the Spanish Society of Neurology (SEN), which was given to the President of Spain (Mr. José María Aznar) last September with the main aim of examining the current situation of Neurology in our country. It analyses the present and future of Neurology in clinical assistance, teaching and research. To prepare this document the criteria of patients' associations has been considered, including the Declaration of Madrid which has been subscribed by thirty of these associations. In spite of its relevant development in the previous decades, the current situation of Neurology in Spain is far from the ideal. To reach the recommendable menber of 3 or 4 neurologists per 100,000 inhabitants it is necessary to duplicate the present number of neurologists which has been estimated around 2/100,000; this situation is especially urgent in some Autonomous Communities. The most important problems in neurological assistance are: inadequate follow-up of the chronic outpatients, low numbers of neurological beds and of duties of Neurology, as well as of neurological case of patients with urgent neurological disorders. It is also necessary to increase the number of professors of Neurology to adequately cover pregraduate teaching; again there are important differences in teaching positions among Autonomous Communities. Neurology residence should be prolonged from 4 to 5 years. Finally, it is necessary to support the appearance of superespecialised units and to promote a coordinated research with other close specialities including basic neuroscience.

To study the presence of anti-GQ1b antibodies as a tool for the diagnosis of Miller-Fisher syndrome (MFS).We studied 54 patients with probable diagnosis of MFS and 10 patients diagnosed as Guillain-Barré syndrome plus ophthalmoplegia (1 case), Bickerstaff's encephalitis (1 case), relapsing ophthalmoplegia (7 cases) and relapsing diplopia (1 case). Results were compared with 130 patients with other disimmune neuropathies. Antibodies were detected by ELISA and checked by thin layer chromatography. Campylobacter jejuni serology was studied using a complement fixation test.Diagnosis of MFS was confirmed in 38 patients. A 97.3% were positive for GQ1b, being all negative for Campylobacter jejuni serology. A second test after 4-5 weeks of nadir was negative in 84.2% (16/19), concomitant with clinical recovery.Anti-GQ1b antibodies are useful markers for the differential diagnosis of MFS, specially with some acute brainstem disorders. Testing must be performed during the first four weeks of clinical course. This correlation between the triad ataxia, arreflexia and ophthalmoplegia and anti-GQ1b antibodies confirms that they are highly specific of MFS.

The etiology of neuromuscular diseases varies widely as does their treatment. This study reports the treatment of patients with neuromuscular disease of autoimmune origin in addition to the therapy of muscular dystrophies. The mechanisms of action of the immunosuppressive drugs (glucocorticoids, azathiaprin, cyclosporin, methotrexate, chlorambucil, cyclophosphamide) and immunomodulators (plasmapheresis, Ig ev) currently used are analyzed, as are their indications, management and the methods which allow the control of therapeutic efficacy. The immunotherapies presently in experimental phases are also reviewed (oral tolerance, inhibition of cytokines, chemokines, etc.). Both molecular therapy (myoblast transplantation, genetic therapy, gentamycin) and anabolizing drugs administered after the favorable results of clinical trials (glucocorticoids, oxandrolone) and undergoing controlled clinical studies (albuterol, creation, etc.) on the treatment of muscular dystrophies are evaluated. Lastly, symptomatic treatments which improve the quality of life of patients with muscular dystrophy are analyzed.

Anti-Hu antibodies (Hu-Abs) were positive in 40 patients with paraneoplastic sensory neuropathy (PSN) and in 1 patient with idiopathic sensory neuropathy in a series of 126 patients who presented with clinical features suggestive of PSN. The specificity of Hu-Abs was 99% and the sensitivity was 82%. Nine (18%) PSN patients were Hu-Ab-negative, and their sera did not harbor other specific anti-neuronal or anti-ganglioside antibodies. Small cell lung carcinoma (SCLC) was the leading neoplasm in the Hu-Ab-positive (79%) and Hu-Ab-negative (44%) groups. This study confirms the value of Hu-Abs for the diagnosis of PSN and SCLC and also emphasizes that in patients with possible PSN, the absence of Hu-Abs does not exclude cancer, particularly in those patients with risk factors for SCLC.

Insulin-like growth factors (IGFs) are potent stimulators of muscle differentiation, and phosphatidylinositol 3-kinase (PI 3-kinase) is an essential second messenger in this process. Little is known about the downstream effectors of the IGF/PI 3-kinase myogenic cascade, and contradictory observations have been reported concerning the involvement of p70 S6 kinase. In an attempt to clarify the role of p70 S6 kinase in myogenesis, here we have studied the effect of rapamycin on rat, mouse, and human skeletal muscle cell differentiation. Both insulin and IGF-II activated p70 S6 kinase in rat L6E9 and mouse Sol8 myoblasts, which was markedly inhibited at 1 ng/ml rapamycin concentrations. Consistent with previous observations in a variety of cell lines, rapamycin exerted a potent inhibitory effect on L6E9 and Sol8 serum-induced myoblast proliferation. In contrast, even at high concentrations (20 ng/ml), rapamycin had no effect on IGF-II-induced proliferation or differentiation. Indeed, neither the morphological differentiation, as assessed by myotube formation, nor the expression of muscle-specific markers such as myogenin, myosin heavy chain, or GLUT4 (glucose transporter-4) glucose carriers was altered by rapamycin. Moreover, here we extended our studies on IGF-II-induced myogenesis to human myoblasts derived from skeletal muscle biopsies. We show that, as observed for rat and mouse muscle cells, human myoblasts can be induced to form multinucleated myotubes in the presence of exogenous IGF-II. Moreover, IGF-II-induced human myotube formation was totally blocked by LY294002, a specific PI 3-kinase inhibitor, but remained unaffected in the presence of rapamycin.