Studies on the structure of a novel peptide antibiotic,K-582

A novel peptide antibiotic, K-582, which exhibited significant growth inhibition of Candida, viruses and ascites tumor in mice, was found in the culture medium of a strain of Metarhizium anisopliae by Kondo et al. (J. Antibiotics 33 , 535–542 (1980)]. K-582 consisted of two components, designated K-582 A and K-582 B. Threonine, tyrosine, ornithine, and an unusual amino acid were common in both peptides, but lysine was an extra component of K-582 A. The unusual amino acid was identified to be threo-γ-hydroxy-L-arginine (OHArg) by means of mass, nuclear magnetic resonance and infrared spectrometries of the derivatives and the related compounds. The threonine and the arginine were assigned to be L-configuration, and the ornithine and the tyrosine to be D-configuration in both K-582 A and K-582 B, and the lysine to be L-configuration by comparison of their optical rotatory dispersion spectra with those of standard amino acids. The elucidation of primary structure revealed that they were closely related heptapeptides with the following sequence: K-582 A:H-Arg-OHArg-Orn-Thr-Orn-Lys-Tyr-OH; K-582 B:H-Arg-OHArg-Orn-Thr-Orn-OHArg-Tyr-OH, and had the identical sequence in terms of the configuration of their constituents, namely L-L-D-L-D-L-D.     

Installation of a Neuromate Robot for Stereotactic Surgery: Efforts to Conform to Japanese Specifications and an Approach for Clinical Use—Technical Notes

The neuromate is a commercially available, image-guided robotic system for use in stereotactic surgery and is employed in Europe and North America. In June 2015, this device was approved in accordance with the Pharmaceutical Affairs Law in Japan. The neuromate can be specified to a wide range of stereotactic procedures in Japan. The stereotactic X-ray system, developed by a Japanese manufacturer, is normally attached to the operating table that provides lateral and anteroposterior images to verify the positions of the recording electrodes. The neuromate is designed to be used with the patient in the supine position on a flat operating table. In Japan, deep brain stimulation surgery is widely performed with the patient''s head positioned upward so as to minimize cerebrospinal fluid leakage. The robot base where the patient''s head is fixed has an adaptation for a tilted head position (by 25 degrees) to accommodate the operating table at proper angle to hold the patient''s upper body. After these modifications, the accuracy of neuromate localization was examined on a computed tomography phantom preparation, showing that the root mean square error was 0.12 ± 0.10 mm. In our hospital, robotic surgeries, such as those using the Da Vinci system or neuromate, require operative guidelines directed by the Medical Risk Management Office and Biomedical Research and Innovation Office. These guidelines include directions for use, procedural manuals, and training courses.     

A synthetic peptide derived from staphylokinase enhances plasminogen activation by tissue‐type plasminogen activator

Summary. Background: A synthetic nonadecapeptide (SP; GPYLMVNVTGVDGKGNELL) previously enhanced the activation of plasminogen by the SAK/plasmin complex. Objectives: To identify the binding site for SP on plasminogen and elucidate the effects of SP on plasminogen activation by the tissue‐type plasminogen activator (t‐PA). Methods: The effects of SP on plasminogen activation were estimated using a chromogenic substrate and from the cleavage of plasmin on SDS‐PAGE under reduced conditions. The binding to SP of various peptides derived from the amino acid sequence of plasminogen was analyzed with an IAsys biosensor. The SP‐mediated structural change to plasminogen was analyzed by circular dichroism (CD) spectroscopy. The thrombolytic effects of SP were examined using a mouse model of thrombosis. Results: SP enhanced the activation of plasminogen by t‐PA. The catalytic efficiency (k_cat/K_m) of Glu‐plasminogen activation by t‐PA was 11.4‐fold higher in the presence than absence of SP. The binding of SP to plasminogen was greatly inhibited by a synthetic peptide, FEKDKYILQGVTSWGLG, located close to the C‐terminal of the plasminogen B region. Near‐ultraviolet CD spectra of the complex between SP and Glu‐plasminogen significantly differed from those of Glu‐plasminogen. When SP was administered in a mouse model of thrombosis, early recanalization was observed in a dose‐dependent manner. However, SP did not cause recanalization in t‐PA gene‐deficient mice. Conclusions: SP bound to the B region and promoted the activation of plasminogen by t‐PA, and then induced effective thrombolysis.     

A Randomized Comparison of the Straight Linear Approach with Electrogram Mapping Focal Approach in Selective Slow Pathway Ablation

HAYASHI, M., et al. : A Randomized Comparison of the Straight Linear Approach with Electrogram Mapping Focal Approach in Selective Slow Pathway Ablation. The aim of this study was to evaluate the efficacy and safety of the anatomic linear approach in selective AVN slow pathway ablation, in comparison to the widely used electrogram mapping focal approach. It remains undetermined whether or not anatomic linear ablation has a greater potential for eliminating slow pathway conduction than does focal ablation. Fifty consecutive patients (21 men, 29 women, age  56 ± 14  years) with common type AVNRT were randomly assigned to the linear approach (25 patients) or local electrogram mapping approach (25 patients). A linear lesion was created between the tricuspid annulus, at the midlevel of the coronary sinus (CS) ostium, and the anterior aspect of the CS infundibulum. In 22 (88%) patients in the linear group, the AVNRT was successfully eliminated by  1.5 ± 0.8  linear RF applications without any complications. All 25 patients in the focal group satisfied the endpoint criteria after  3.8 ± 2.4  focal RF deliveries. The success rate did not significantly differ between the two groups. Out of the 22 patients with a successful outcome in the linear group, 17 (77%) attained complete abolition of the slow pathway conduction, whereas this was observed in only eight (32%) patients in the focal group (  P < 0.005  ). The session time was significantly shorter in the linear group. Recurrence of the tachycardia was not documented in any patient during a mean follow-up of  18 ± 8  months except one with residual slow pathway conduction in the focal ablation group. In conclusion, the anatomic linear approach can be performed safely and possesses a greater potential for slow pathway interruption compared to the electrogram mapping focal approach.