In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

No abstract

To determine whether a link exists between reproductive seasonality and the structure of the gene for melatonin receptor Mel(1a), the latter was studied in two groups of Mérinos d'Arles (MA) ewes previously chosen for their genetic value, which took into account their own out-of-season ovulatory activity adjusted by environmental parameters and that of their relatives. The genomic DNA of 36 ewes found regularly cycling in spring (group H) and that of 35 ewes never cycling in spring (group L) during the 2-3 yr before the present study was prepared, and the cDNA corresponding to almost all exon II was amplified and checked for the presence of MnlI restriction sites. The presence (+) or absence (-) of an MnlI site at position 605 led to genotypes "++", "+-", and "--", whose frequencies differed significantly (P < 0.001) between the H and L groups: 52.8%, 47.2%, and 0% vs. 28.5%, 42.9%, and 28.5%, respectively. Sequencing of exon II cDNA in group L ewes with genotype -- showed the presence of only one allele - with 4 mutations, while that in ewes with genotype ++ showed different types of alleles unrelated to the H or L groups. These + alleles exhibited a combination of 1 to 7 of the 8 mutations recorded in the part of exon II studied. The genotyping of 29 ewes from the more seasonal Ile-de-France breed indicated that 38% of animals had a -- genotype and exhibited the same mutations as in the MA ewes. Finally, a comparison of (125)I-melatonin binding to membrane preparations of pars tuberalis showed a lower number of binding sites (P < 0. 0005) in MA ewes with genotype ++ than in those with genotype -- (43. 2 +/- 4.4 vs. 75.4 +/- 8.4 fmol/mg protein in genotype ++ and genotype --, respectively). In conclusion, the data show an association between genotype -- for site MnlI at position 605 and seasonal anovulatory activity in MA ewes.

Additions, corrections, comments and nomenclatural novelties for the volumes 7 and 8 of the Catalogue of Palaearctic Coleoptera are provided. For the exact authorship of these check the text. One new species is described: Mecinus tavaresi Caldara & Fogato, sp. nov. from Portugal and Spain. New synonymies are: Compsapoderus (Compsapoderus) erythropterus (Gmelin, 1790) = Attelabus intermedius Hellwig, 1795, syn. nov.; Paroplapoderus (Erycapoderus) angulipennis (Kolbe, 1886) = Paroplapoderus (Erycapoderus) angulipennis shaanxinsis Legalov, 2004, syn. nov.

Plasma prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassay in groups of eight gilts sampled every 20 min for 6 h at about 2-wk intervals between 15 and 192 d of age. The PRL levels were high at 15 and 28 d, declined at 40 d just after weaning and then rose slowly until 192 d of age. The number of LH pulses during 6 h was higher between 83 and 125 d than at the other periods. Magnitude of LH pulses was highest at 15 d, constant from 54 to 125 d, fell at 137 d and remained low until 192 d. Plasma FSH was high from 15 to 125 d, with a maximum at 54 d. It declined slowly until 168 d and did not change thereafter. Estrogen excretion was estimated from urine excretion of estrone (E1; conjugated plus nonconjugated E1) per 24 h from 40 d until puberty in three gilts and at 156 and 174 d in two other animals. The E1 excretion increased with age and four levels were described before peak values with the onset of first estrus. The first increase in E1 excretion occurred between 68 and 110 d, when antral follicles appeared in the ovaries. It was subsequent to the highest levels of FSH and concomitant with the increased frequency of LH pulses. The drop in levels of both gonadotropins after 125 d probably corresponded to the development of the negative feedback as a result of greater ovarian activity in these gilts.