A protein, which facilitates assembly of a nucleosome-like structure in vitro, was previously partially purified from mouse FM3A cells [Ishimi, Y. et al. (1 983) J . Biochem. (Tokyo) 94,735 -7441. The protein has been purified to approximately 80 from FM3A cells by using histone-Sepharose column chromatography. It sedimented at 4.6 S and had a molecular mass of 53kDa. A preincubation of core histones with the 53-kDa peptide before DNA addition was necessary for the nucleosome assembly. The 53-kDa peptide bound to core histones and formed a 12-S complex. This complex contained stoichiometrical amounts of the 53-kDa peptide and core histones, and the core histones in this complex were composed of equal amounts of H2A, H2B, H3 and H4 histones. The nucleosomes were assembled by adding pBR322 DNA to the 12-S complex. When mononucleosome DNA and core histones were mixed in the presence of the 53-kDa peptide, formation of a 10.5-S complex was observed. The complex contained DNA and core histones in equal amounts, while no 53-kDa peptide was detected in the complex.From above results it is suggested that the 53-kDa peptide facilitates nucleosome assembly by mediating formation of histone octarner and transferring it to DNA. Rat antibody against the 53-kDa peptide did not bind to nucleoplasmin from Xenopus eggs. The relationship between the 53-kDa peptide and nucleoplasmin is discussed.In eukaryotic cells, chromatin consists of a repeating unit called a 'nucleosome', which contains about 200 base-pairs of DNA, two molecules each of H2A, H2B, H3 and H4 histones, and one molecule of HI histone [1,2]. In many mammalian cells almost all core histones (H2A, H2B, H3, H4) are synthesized at S phase and their synthesis is coupled with DNA synthesis [3 -51. However, basal histone synthesis is observed also at GI phase in some cells [6], and mouse lymphoma cell synthesizes core histones at G I phase at the same level as S phase [7,8].As to the mode of deposition of newly synthesized histone on DNA, several confusing results have been presented. From the observation of the group of Weintraub [9-111, it is suggested that new histones are bound to the lagging strand of replicated DNA and they are assembled conservatively into an octamer. On the other hand, Jackson et al. [12,13] indicated that new H3 and H4 histones were bound to replicating DNA, while new H2A and H2B histones were deposited on nonreplicating DNA rather than the replicating DNA. There are several reports indicating that new histones are distributed equally to both daughter strands [14,15]. In any case it is not well examined whether new histones are bound to DNA by a single step as an octamer or by multiple steps.There are several factors which facilitatc nucleosome assembly in t'itro at physiological ionic strength. Nucleoplasmin (29 kDa), which has been discovered in Xenopus eggs by Laskey et al. [I 6,171, facilitate nucleosome assembly by the interaction with core histones. Experiments using its fluorescent antibody suggested that it exists in mammalian cells [...

Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. To clarify the current situation in treatment, a multicenter study was carried out to obtain information on the results of CPT treatment. The objective of this study was to propose appropriate treatment guidelines for CPT. Records of 73 patients with CPT who underwent surgical treatment were collected from 32 hospitals. The modality of the treatment was 26 with Ilizarov technique, 25 with free vascularized fibular graft, 7 with a combination of the two techniques, 6 with intramedullary nailing with free bone grafting, 5 plating with free bone grafting, and 4 with other treatments. Fifty-four procedures resulted in union, 7 resulted in delayed union, 7 were left un-united, 1 underwent amputation, and the results were unknown in 4. According to the results of this study, the most acceptable methods of treatment of CPT are the Ilizarov method and the vascularized fibular graft.

E nhancement of functional recovery during the subacute and chronic phases of stroke represents a major therapeutic goal because a significant proportion of patients have persisting neurological deficits, even with optimal acute care and conventional rehabilitation. Preclinical in vivo models suggest that a time-limited window of neuroplasticity opens after stroke.1 New therapeutic approaches that stimulate these repair mechanisms may be able to exploit this opportunity, and a range of these is currently under investigation, including small molecules that target specific processes, small molecules that have a general stimulatory effect that may aid rehabilitation, growth factors, cell therapies, and physical modulation of neuronal networks.2 The σ-1 receptor chaperone protein (Sig-1R) mediated functional recovery in a model of neuronal plasticity relevant to stroke.3 Sig-1Rs mainly reside in the endoplasmic reticulum and are enriched in the mitochondriaassociated endoplasmic reticulum membrane but can change their intracellular location in response to cellular stress. 4 The biochemical function of the Sig-1R is that of a molecular chaperone, stabilizing proteins in response to cellular stress 5 Background and Purpose-The σ-1 receptor (Sig-1R) agonist cutamesine (SA4503) enhanced functional recovery after experimental stroke with a treatment initiation window of 48 hours and chronic treatment for 28 days. We conducted a phase 2 clinical trial exploring the safety, tolerability, dose range, and functional effects of cutamesine in patients with ischemic stroke. Methods-Subjects were randomized between 48 and 72 hours after stroke to receive cutamesine 1 mg/d, 3 mg/d, or placebo for 28 days. Effects on safety and function were assessed at baseline, at end of treatment (day 28), and at end of followup (day 56). Results-In 60 patients, treatment with both cutamesine dosages was safe and well tolerated without significant differences in numbers of treatment emergent or serious adverse events. No significant effect was observed on the primary efficacy measure (change in National Institutes of Health Stroke Scale from baseline to day 56) or modified Rankin Scale and Barthel Index scores. Post hoc analysis of moderately and severely affected patients (baseline National Institutes of Health Stroke Scale, ≥7 and ≥10) showed greater National Institutes of Health Stroke Scale improvements in the 3 mg/d cutamesine group when compared with placebo (P=0.034 and P=0.038, respectively). A trend toward a higher proportion being able to complete a 10m timed walk was observed for cutamesine-treated subjects. Conclusions-Cutamesine was safe and well tolerated at both dosage levels. Although no significant effects on functional end points were seen in the population as a whole, greater improvement in National Institutes of Health Stroke Scale scores among patients with greater pretreatment deficits seen in post hoc analysis warrants further investigation. Additional studies should focus on the patient population with moderate-to-severe...