Search

RA-III acetate was treated with Lawesson's reagent to afford [Tyr-3-Ψ(CS-NH)-Ala-4]RA-III acetate. Treatment of this product with Hg(OAc) 2 /Li 2 CO 3 and then methanol gave an oxazole intermediate. Acid-catalyzed arylation of the methylene carbon atom on the oxazole ring and subsequent partial hydrolysis of the oxazole ring in the resultant compounds afforded RA-VII analogues having an aromatic amino acid at residue 2. [5-Fluoro-d-Trp-2]RA-VII showed IC 50 values of 0.038 and 0.077 μM against the HL-60 and HCT-116 cell lines, respectively.

An immunoassay system was established for the estimation of the quantity of an antitumor cyclohexapeptide, deoxybouvardin (RA-V) from Bouvardia ternifolia (Cav.) Schlecht, Rubia cordifolia L., and R. akane Nakai (Rubiaceae). First, RA-V was converted into a protein conjugate to make it an effective antigen. In the conjugate the molecular ratio between RA-V and the carrier protein was 5.9:1. The splenocytes from the mouse immunized with the conjugate were then fused with mouse myeloma cells to produce hybridoma, secreting monoclonal antibodies (MAbs) against RA-V. Two clones were isolated, one producing MAb IgG(1) and the other MAb IgG(2b), both having a κ light chain. The resultant MAbs were evaluated for their sensitivity and cross-reactivity.

In order to compare the long-term clinical and angiographic outcomes after sirolimus-eluting stent (SES) and bare-metal stent (BMS) placement in severely calcified lesions using a rotablator under the widespread indication of SES, a nonrandomized examination of 312 consecutive lesions after successful implantation of a BMS (99 lesions in 84 patients; from January 2003) or SES (213 in 167; from September 2004) using a rotablator was conducted. The lesion-based primary endpoints (cardiac death and nonfatal recurrent myocardial infarction) and the secondary endpoint [binary restenosis (BR) (diameter stenosis > 50%) at follow-up angiography] were retrospectively determined in August 2010. The incidence of primary endpoint in the SES group (2.3%; mean follow-up period of 1289 ± 526 days) was significantly lower than that in the BMS group (7.1%; P = 0.043; 1803 ± 887 days), although the several variables related to the endpoints were present in the SES group. Cox proportional hazard model analysis revealed that SES was not significantly related to a primary endpoint [hazard ratio of 0.42 (95% CI, 0.073-2.42; P = 0.33)]. The incidence of BR in the SES group (21.3%) was not significantly different from that in the BMS group (27.1%) (P = 0.33). Multivariate logistic regression analysis revealed that SES was not a significant predictor of BR [Odds ratio of 0.78 (95% CI, 0.41-1.51; P = 0.47)]. Thus, although the results of the present retrospective nonrandomized study demonstrate the long-term safety of SES for calcified lesions using a rotablator in daily practice, SES did not show a benefit for the angiographic outcomes compared to BMS.

Background: Outcomes after sirolimus-eluting stent (SES: Cypher) implantation remained to be elucidated in Japan., Methods and Results: Among 1,070 consecutive angiographic follow-up lesions, 99 lesions underwent target lesion revascularization (TLR) with in-stent restenosis (ISR). Retrospective estimation by multivariate analysis including 50 variables showed that the ostiums of right coronary and left circumflex arteries, hemodialysis, calcification, non-direct stenting, ISR of SES, and non-eccentric lesion were the predictors of TLR. There was no documented late stent thrombosis (LST) among 2,166 lesions and very LST (VLST) among 1,423 lesions., Conclusion: Further revises are needed to implant SES to these predictive lesions. LST and VLST were very rare.

Three analogues of RA-VII (1), an antitumor bicyclic hexapeptide from Rubia plants, were synthesized. Three analogues, [Gly-1]RA-VII (4), [Gly-2]RA-VII (5), and [Gly-4]RA-VII (6), in which one of the three alanine residues in 1 was replaced by a glycine residue, were prepared by linking of the cycloisodityrosine unit, obtained by degradation of 1, to three different glycine-containing tetrapeptides followed by macrocyclization. Of these three analogues, analogue 4 showed the highest cytotoxic activity. The NMR study revealed that in solution the conformer structures and their ratios of analogue 4 were very similar to those of natural peptide 1, suggesting that the methyl groups at Ala-2 and Ala-4 should be essential for producing the bioactive conformation, whereas that at D-Ala-1 is not essential.

Background: Dihydropyridines (DHPs), a type of calcium channel blocker (CCB), are commonly prescribed for the treatment of hypertension and angina pectoris. DHPs act mainly on L-type calcium channels, essentially causing reflex tachycardia (elevated heart rate [HR]), which negatively affects cardiac function. Because T-type calcium channels in the sinoatrial node attenuate reflex tachycardia, a dual L- and T-type CCB (eg, efonidipine hydrochloride) may favorably affect cardiac pacing, thereby reducing reflex tachycardia. The effect of efonidipine as a DHP on HR deserves special consideration with regard to reflex tachycardia., Objective: The aim of this study was to determine whether the L- and T-type CCB efonidipine can decrease the elevated HR induced by prior treatment using traditional DHPs., Methods: This uncontrolled, open-label pilot study was conducted at the Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine (Tokyo, Japan). Patients aged 48 to 80 years with mild to severe hypertension and angina pectoris and who were receiving therapy with a DHP other than efonidipine were eligible. During an 8-week observation period, patients continued therapy with their DHP. After those 8 weeks, therapy was switched to oral efonidipine (40-mg tablet once daily) in patients whose blood pressure (BP) was stable and well controlled and whose HR was >80 bpm. BP and HR were monitored every 4 weeks of treatment with efonidipine., Results: Eighteen patients (12 men, 6 women; mean [SD] age, 62.6 [12] years) were enrolled. After the switch to efonidipine, mean (SD) HR decreased significantly, from 94 (7) bpm to 86 (11) bpm at 12 weeks (P<0.05). The antihypertensive effect of efonidipine was similar to that of the DHPs used before the switch to efonidipine therapy, and reflex tachycardia was attenuated., Conclusion: In this study of a small sample of patients with mild to severe essential hypertension and angina pectoris, efonidipine was as effective as other DHPs. Moreover, the drug attenuated the reflex tachycardia that occurred with traditional DHPs.

The three-dimensional structure of the N-terminal SH3 domain (residues 583-660) of murine Vav, which contains a tetra-proline sequence (Pro 607-Pro 610), was determined by NMR. The solution structure of the SH3 domain shows a typical SH3 fold, but it exists in two conformations due to cis-trans isomerization at the Gly614-Pro615 bond. The NMR structure of the P615G mutant, where Pro615 is replaced by glycine, reveals that the tetra-proline region is inserted into the RT-loop and binds to its own SH3 structure. The C-terminal SH3 domain of Grb2 specifically binds to the trans form of the N-terminal SH3 domain of Vav. The surface of Vav N-terminal SH3 which binds to Grb2 C-terminal SH3 was elucidated by chemical shift mapping experiments using NMR. The surface does not involve the tetra-proline region but involves the region comprising the n-src loop, the N-terminal and the C-terminal regions. This surface is located opposite to the tetra-proline containing region, consistent with that of our previous mutagenesis studies.