Inducible expression of FGF2 by a rat oligodendrocyte precursor cell line promotes CNS myelination in vitro

Transplantation of glial cells into the central nervous system (CNS) may be a promising approach for the treatment of myelin disorders such as multiple sclerosis (MS). Myelination by transplantation of oligodendrocyte precursors has been obtained in different animal models of demyelination. A strategy to favor CNS remyelination is to enrich the lesioned areas in growth factors to stimulate the quiescent population of oligodendrocyte precursors. In this context, we have developed a genetically modified CG4 cell line (CG4-FGF2), which are able to release significant amounts of fibroblast growth factor 2 (FGF2) in a controlable fashion in vitro. The data presented here demonstrate that upon induction with Dox, CG4-FGF2 cells retain their capacity to differentiate in vitro. Additionally, we provide evidence that FGF2 release by engineered cells enhance proliferation and migration of cells of the oligodendrocyte lineage without preventing them to differentiate and myelinate axons in vitro.     

Reduced thrombus cohesion in an ex vivo human model of arterial thrombosis induced by clopidogrel treatment: kinetics of the effect and influence of single and double loading-dose regimens

OBJECTIVE: To compare the effects of clopidogrel on ex vivo thrombogenesis with those on ADP-dependent platelet aggregation, and to compare single and double loading-dose regimens. METHODS AND RESULTS: Step 1: Volunteers (n=12) received clopidogrel 75 mg/day for 8 days. ADP-induced platelet aggregation was measured in platelet-rich plasma (PRP). Thrombogenesis was measured in an ex vivo model. Clopidogrel produced rapid platelet inhibition, increasing up to day 5. Maximal intensity of platelet aggregation correlated with density of platelet thrombus, surface of collagen covered by platelets and thrombus cross-sectional surface (p<0.001). Step 2: On day 1, volunteers (n=60) randomly received clopidogrel 75 mg, a single 300-mg loading dose or two 300-mg loading doses separated by a 12-h interval. On day 2, all volunteers received clopidogrel 75 mg. Both loading dose regimens enhanced platelet inhibition at all time points (p<0.03 vs. clopidogrel 75 mg). After 3 h, the antiplatelet effect of a loading dose was substantial, and the mean decrease in dense thrombus surface was greater in the loading-dose groups than in the 75 mg group (p=0.041 for the single loading dose). Ex vivo, there were no significant differences between loading-dose groups. CONCLUSIONS: Clopidogrel reduces arterial thrombus cohesion by an effect that correlates with inhibition of ADP-induced platelet aggregation. A single 300-mg loading dose provides a rapid onset of such an antithrombotic effect, which was more significant at 24 h with the double loading dose.     

A 1-Mb resolution radiation hybrid map of the canine genome

The purebred dog population consists of >300 partially inbred genetic isolates or breeds. Restriction of gene flow between breeds, together with strong selection for traits, has led to the establishment of a unique resource for dissecting the genetic basis of simple and complex mammalian traits. Toward this end, we present a comprehensive radiation hybrid map of the canine genome composed of 3,270 markers including 1,596 microsatellite-based markers, 900 cloned gene sequences and ESTs, 668 canine-specific bacterial artificial chromosome (BAC) ends, and 106 sequence-tagged sites. The map was constructed by using the RHDF5000-2 whole-genome radiation hybrid panel and computed by using MULTIMAP and TSP/CONCORDE. The 3,270 markers map to 3,021 unique positions and define an average intermarker distance corresponding to 1 Mb. We also define a minimal screening set of 325 highly informative well spaced markers, to be used in the initiation of genome-wide scans. The well defined synteny between the dog and human genomes, established in part as a function of this work by the identification of 85 conserved fragments, will allow follow-up of initial findings of linkage by selection of candidate genes from the human genome sequence. This work continues to define the canine system as the method of choice in the pursuit of the genes causing mammalian variation and disease.     

Abridged version of the severe impairment battery (SIB)

Until recently, severe dementia has received little attention on the part of clinicians and researchers. Yet, it represents a major problem from the point of view of Public Health because it is always accompanied by marked functional impairment with, in addition, frequent psychiatric and behavioural problems. These deficits are associated with impairment in activities of daily living that result in marked loss of autonomy and lead inevitably to the need to seek outside assistance, at least on a part-time basis. The arrival of new drugs with a potential to palliate some of the symptoms makes the assessment of severe dementia even more important. The Severe Impairment Battery (SIB) has been proposed in 1990 in order to evaluate the cognitive abilities of patients for whom standard cognitive measures are no longer adapted. Its purpose was to analyze different cognitive domains, based on the residual capacities of these patients. It evaluates the following domains: social interaction, orientation, attention, language, memory, praxis, constructional abilities and visuo spatial functions. The original SIB consisted of 51 items with a maximum score of 152. The battery was later shortened with a score of 133 and later 100. The latter version, which included 40 items, has been validated and published in France by Boller et al. However, clinical experience suggests that even this version is too long and includes some redundancies. We have therefore prepared an abridged version, which only includes 26 items with a maximum score of 50. It can be administered in 10 to 15 minutes. The selection was based mainly on clinical experience. We wanted to keep all of the domains included in the original version. Finally the selection was justified by a factorial analysis. The present version is based on a consensus reached by an US and Italian research group, in addition to ours.     

A new scale for measuring dynamic patterns of sexual partnership and concurrency: application to three French Caribbean regions

BACKGROUND: Quantitative assessment of multiple sexual partnerships and concurrency may help to elucidate the large observed differences in the prevalence of AIDS among population subgroups and countries. GOAL: The goals of the study were (1) to develop a global scale of dynamic patterns of sexual partnerships, including concurrency with new partners and stable concurrency; (2) to apply this scale to three Caribbean regions characterized by different cumulative rates of incidence of AIDS; and (3) to compare the concurrency rates given by this scale with those of other published methods. STUDY DESIGN: We defined an individual scale based on 6 patterns of sexual behavior over the previous 12-month period, by using a simple algorithm to combine 7 variables. We then applied this scale to cross-sectional data collected from men living in three French Caribbean regions: Guadeloupe, Martinique, and Guyana. RESULTS: We found that all adults of all age classes in the three regions studied frequently had multiple (>2) and concurrent partnerships. The patterns of sexual behavior in the three regions were consistent with the respective cumulative incidence rates of AIDS, and a lower rate of concurrency with new partners and a higher rate of stable partnership concurrency were noted in Martinique, especially among 45- to 59-year-olds. The rate of concurrent partnerships was found to depend on the criteria used to define them and on the observation period (a given moment, or a defined period). Our definition gave a higher rate of concurrency than previously published indicators. CONCLUSION: The proposed scale can be applied to easy-to-collect data in cross-sectional population surveys and takes into account a wide variety of behaviors, including different types of concurrency.     

Granulomatous slack skin: treatment with extensive surgery and review of the literature

We report an 11-year follow-up of a case of granulomatous slack skin. The patient was first treated surgically followed by a rapid relapse. Then he was treated by alpha-interferon during 15 months. When this treatment was stopped, the disease relapsed again. Extensive surgery was undertaken. Recently, a new relapse has occurred which was again treated by extensive surgery. No other manifestation of a lymphoproliferative disorder appeared. The clinical, histological, immunohistochemical, ultrastructural, molecular biological and genetic studies with a review of 39 other cases described in the literature are presented.     

Trabecular alveolar bone in the human mandible: a dual-energy x-ray absorptiometry study

OBJECTIVE: The purpose of this study was to evaluate the potential use of dual energy x-ray absorptiometry for the assessment of bone mineral content and bone mineral density before implant placement. MATERIALS AND METHODS: The material examined consisted of 63 mandibular bone specimens cut from 21 fresh cadavers (11 men; 10 women). Three specimens were cut per cadaver in the incisal, premolar, and molar regions. Three regions of interest (G, R1, and R2) were delineated. The global bone specimen (G) consisted of the whole specimen (ie, both cortical and trabecular bone). R1 and R2 were delineated in the trabecular bone of the alveolar process. RESULTS: In all subjects, the combined bone mineral content of the whole mandible specimens (global bone mineral content) was significantly correlated with age. The difference between the mean bone mineral densities of the male and female mandibles was found to be significant for G (P = .009). The mean bone mineral densities of dentate and edentulous specimens were also found to be significantly different for G and R1, respectively (P = .001 and P = .02), but not for R2. A positive correlation could be detected among the mean bone mineral density of G and R1, G and R2, and R1 and R2 of (1) male and female specimens, (2) dentate and edentulous specimens, and (3) incisal, premolar, and molar specimens. CONCLUSIONS: The intra-alveolar trabecular bone of these 21 mandibles is affected by the same local and systemic influences as cortical bone, whereas the infra-alveolar trabecular bone is mostly sensitive to dental status. The cortical and trabecular bone of the 10 mandibles from women is more sensitive to systemic influences, whereas that from men is more sensitive to local influences. This is somewhat in agreement with some studies that found an association between osteoporosis and oral bone loss, which is a metric measure.