Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

SYNOPSISLiving cationic polymerization of alkoxyethyl vinyl ether [ CH, = CHOCH,CH,OR R CH, (MOVE), C2H5 (EOVE) ] and related vinyl ethers with oxyethylene units in the pendant was achieved by 1-(isobutoxy)ethyl acetate ( 1)/Etl.5AlC1,.5 initiating system in the presence of an added base (ethyl acetate or T H F ) in toluene at 0°C. The polymers had a very narrow molecular weight distribution (A?,,,/A?,, = 1.1-1.2) and the M,, proportionally increased with the progress of the polymerization reaction. On the other hand, the polymerization by 1/EtA1C12 initiating system in the presence of ethyl acetate, which produces living polymer of isobutyl vinyl ether, yielded the nonliving polymer. When an aqueous solution of the polymers thus obtained was heated, the phase separation phenomenon was clearly observed in each polymer at a definite critical temperature ( T p s ) .For example, Tps was 70°C for poly(MOVE), and 20°C for poly(E0VE) (1 wt % aqueous solution, M n -2 X l o 4 ) . The phase separation for each case was quite sensitive (AT,, = 0.3-05°C) and reversible on heating and cooling. The T,, or AT,, was clearly dependent not only on the structure of polymer side chains (oxyethylene chain length and w-alkyl group), but also on the molecular weight (A?,, = 5 X lo3-7 X lo4) and its distribution. 0

Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods:The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione-or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results:The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)-fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161-174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions:The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.

Figure 6. a) Galvanostatic charge/discharge curves, and b) cycle stability of Na 2 Mn 3 O 7 between 1.5 and 4.7 V at a rate of C/20.

BackgroundBecause circulating antibodies against a variety of antigens have been detected in patients with coronary heart disease, carotid atherosclerosis and those who have suffered a stroke, it is suspected that immune response may be one of the mechanisms of atherogenesis The objective of this study is to identify novel antibodies in ischemic stroke patients by screening the expressed recombinant proteins using a human cDNA library (SEREX).MethodsTo identify the candidate antigens, cDNA library was screened by SEREX using plasma from ten patients with ischemic stroke. Subsequently, via ELISA using recombinant proteins and synthetic peptides, the serum antibody levels were measured in two independent patient/healthy donor (HD) cohorts (142 and 78 in the 2nd screening and a validation cohort, respectively).ResultsThe initial screening resulted in the identification of six candidate antigens. Of these antigens, replication protein A2 (RPA2) was determined to be the antigen associated with stroke (P < 0.05) by ELISA with 2nd screening and validation cohort. Multifactorial logistic regression analysis showed that the increased levels of the RPA2 antibodies (RPA2-Abs) associated with stroke independent of other risk factors for stroke (P < 0.05). Receiver operating curve analysis demonstrated that the area under the curve from ELISA using GST fusion RPA2 and synthetic peptides (bRPA2-132) were 0.867 (95% CI: 0.798-0.936) and 0.971 (95% CI: 0.940-1.00), respectively. If the cut-off value of the bRPA2-132-Ab level was determined to be 0.334, the sensitivity and specificity of the antibody level as the diagnostic marker for stroke were 0.323 (95% CI: 0.209-0.453) and 1.00 (95% CI: 0.713-1.00), respectively.ConclusionsSEREX identified RPA2 as the antigen associated with ischemic stroke and serum auto-antibodies against RPA2 elevates in stroke patients. RPA2-Abs could become a biomarker for the evaluation of ischemic stroke at risk.

The occurrence of rebleeding a long time after the first hemorrhagic episode was not uncommon. Furthermore, the change in which hemisphere and the type of bleeding that occurred after the first episode suggested the difficulty encountered in the prevention of repeated hemorrhage.

Objective: To evaluate the safety and efficacy of removing large acoustic neurinomas (>3 cm) by the retrosigmoid approach. Methods: Large acoustic neurinomas (mean (SD), 4.1 (0.6) cm) were removed from 50 consecutive patients by the retrosigmoid suboccipital approach while monitoring the facial nerve using a facial stimulator-monitor. Excision began with the large extrameatal portion of the tumour, followed by removal of the intrameatal tumour, and then removal of the residual tumour in the extrameatal region just outside the porus acusticus. The last pieces of tumour were removed by sharp dissection from the facial nerve bidirectionally, and resected cautiously in a piecemeal fashion. Results: There were no postoperative deaths. The tumour was removed completely in 43 of 50 patients (86%). The facial nerve was anatomically preserved in 92% of the patients and 84% had excellent facial nerve function (House-Brackmann grade 1/2). One patient recovered useful hearing after tumour removal. Cerebrospinal fluid leak occurred in 4%, but there were no cases of meningitis. All but two patients (96%) had a good functional outcome. Conclusions: The method resulted in a high rate of functional facial nerve preservation, a low incidence of complications, and good functional outcomes, with no mortality and minimal morbidity. Very favourable results can be obtained using the retrosigmoid approach for the removal of large acoustic neurinomas.

Conservative management, gamma-knife (GK) radiosurgery, and microsurgery are therapeutic options for acoustic neurinomas (ANs). To determine the outcomes and risks of these methods this systematic review analyzed data from 903 patients with conservative management, 1475 with GK radiosurgery, and 5005 with microsurgery from 38 studies identified in MEDLINE searches. Conservative management over a 3.1-year period showed that 51% of ANs showed a tumor growth, an average tumor growth rate was 1.87 mm year-1, 20% of ANs ultimately required surgical intervention, and a third of the patients lost useful hearing. GK radiosurgery significantly reduced the percentage of ANs that enlarged, to 8%, and reduced the percentage that underwent microsurgery to 4.6% over a 3.8-year period. Microsurgery removed 96% of ANs totally, with tumor recurrence, mortality, and major disability rates of 1.8%, 0.63%, and 2.9%, respectively. The majority of ANs grow slowly, but ultimately require intervention. Carrying the risk of hearing loss, conservative management should be supplemented with close follow-up. With a low rate of morbidity, GK radiosurgery suppresses tumor growth and provides good tumor control. Microsurgery provides the best tumor control, although mortality and morbidity are not completely eliminated.