Racemization studies in peptide synthesis through the separation of protected epimeric peptides by reversed-phase high performance liquid chromatography

Separation of protected epimeric peptides, Z-Gly-Xaa-Xbb-OMe (where Xaa and Xbb = chiral amino acid residues), by reversed-phase HPLC was utilized for studying racemization in peptide synthesis. Thus, the following factors which might affect the extent of racemization during the coupling by the carbodiimide method were investigated: the combination of amino acid residues to be coupled, coexisting tertiary amine salts, and the relative configuration of the amino acid residues. The following points were revealed: the combination of bulky residues at the coupling site results in extensive racemization in a polar solvent such as DMF, the amine hydrochlorides cause less racemization than the p-toluenesulfonates in DMF, and the influence of relative configuration differs depending on the solvent and the individuality of the amino components. Furthermore, the racemization-suppressing effect of some additives in the carbodiimide method was reevaluated by employing the same procedure.     

Long-Term Evaluation of the Ventricular Defibrillation Energy Requirement

Defibrillation Energy Requirements. Introduction : Defibrillation energy requirements in patients with nonthoracotomy defibrillators may increase within several months after implantation. However, the stability of the defibrillation energy requirement beyond 1 year has not been reported. The purpose of this study was to characterize the defibrillation energy requirement during 2 years of clinical follow-up.
Methods and Results : Thirty-one consecutive patients with a biphasic nonthoracotomy defibrillation system underwent defibrillation energy requirement testing using a step-down technique (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, and 1 J) during defibrillator implantation, and then 24 hours, 2 months, 1 year, and 2 years after implantation. The mean defibrillation energy requirement during these evaluations was 10.9 ± 5.5 J, 12.3 ± 7.3 J, 11.7 ± 5.6 J, 10.2 ± 4.0 J, and 11.7 ± 7.4 J, respectively ( P = 0.4). The defibrillation energy requirement was noted to have increased by 10 J or more after 2 years of follow-up in five patients. In one of these patients, the defibrillation energy requirement was no longer associated with an adequate safety margin, necessitating revision of the defibrillation system. There were no identifiable clinical characteristics that distinguished patients who did and did not develop a 10-J or more increase in the defibrillation energy requirement.
Conclusion : The mean defibrillation energy requirement does not change significantly after 2 years of biphasic nonthoracotomy defibrillator system implantation. However, approximately 15% of patients develop a 10-J or greater elevation in the defibrillation energy requirement, and 3% may require a defibrillation system revision. Therefore, a yearly evaluation of the defibrillation energy requirement may he appropriate.     

Anti-neutrophil cytoplasmic antibody for proteinase 3 in a child with polyarteritis nodosa

We report a case of a 15 year old boy with polyarteritis nodosa associated with antineutrophil cytoplasmic antibody (ANCA) against proteinase 3 (PR3). After months of steroid and immunosuppressant therapy, the symptoms subsided and the polyaneurysms almost disappeared. The levels of anti-PR3 antibody and of cytokines also decreased. The results indicate that ANCA is a good indicator of this disease activity, and may play some pathogenic role in the disease.     

Selective Eradication of Erythropoiesis by Actinomycin D as the Result of Interference with Hormonally Controlled Effector Pathway of Cell Differentiation

Daily injections of 60 µg. actinomycin D per Kg. mouse caused cessation oferythropoiesis due to complete disappearance of erythroid marrow elements,and the mice were absolutely refractory to erythropoietin. No decrease inmyelo-, lympho-, or megakaryocytopoiesis was found during more than 3weeks of daily administration of the drug. Observations on the effect of thedrug on a cohort of erythroid cells, induced by erythropoietin in polycythemicmice, gave no evidence of its destructive or inhibitory action on early or latenormoblasts. A critical reduction in the number of integer stem cells waslikewise ruled out as the cause of eradication of erythropoiesis. The latter isattributed to a specific interference of actinomycin D in the effector pathwayof erythropoietin controlled transformation (differentiation) of stem cells intoearly pronormoblasts. The findings indicate this process to be contingent onformation of new types of mRNA rather than on activation of templatesalready present in erythropoietin-sensitive stem cells.

Submitted on September 2, 1965 Accepted on November 13, 1965     

β-PLEATED SHEETS IN OLIGOPEPTIDE CRYSTALS

Many oligopeptide crystals show the β-pleated sheet structures. Both parallel and antiparallel chain pleated sheets are found, and also both ideal (flat) and heavily twisted sheets are found. The structural parameters, such as the T (NCα-C') angles, the torsion angles (φ and ø), the fiber axis periods, the hydrogen bond lengths, and the interchain spacings, are studied. Some of them deviate signifi cantly from those proposed by Pauling & Corey (Proc. Natl. Acad. Sci. US (1953), 39, 253–256). In the heavily twisted sheets, the twists are larger than those in the globular proteins, and each two neighboring chains are almost per pendicular with each other, preserving the β-sheet type hydrogen bond system. The torsion angles in the twisted sheets are rather close to those of the poly (L-proline) II helix. It also is discussed that the (NCαC) angles sometimes deviate by almost 5° from the standard value depending on the structures of the main and side chains.     

Concentrations of Human Atrial Natriuretic Peptide in the Cord Blood and the Plasma of the Newborn

ABSTRACT. Concentrations of human atrial natriuretic peptide (hANP) in the cord blood and the plasma were measured in 25 newborns. The level of hANP in 0 to 1 post-natal days (212.8±118.1 pg/ml; mean±SD) was significantly higher than that in cord blood (69.7±53.2 pg/ml) ( p < 0.005). There were no significant differences in the levels of hANP at the ages of 0 to 1, 4 and 6 post-natal days. The level of hANP did not show any significant correlation with urinary excretion of Na, urinary Na/Cr or Na/K ratios. Further evaluations should be made in order to clarify the role of hANP during the early post-natal period.     

A Preliminary Report on Autologous Bone Marrow Transplantation for the Treatment of Advanced Non-Hodgkin's Lymphoma

Four patients with advanced non-Hodgkin's lymphoma of unfavorablehistology were treated with marrow-lethal doses of cyclophosphamide(CY) and total body irradiation (TB1) followed by the infusionof cryopreserved autologous marrow. All four patients showedengraftment after autologous bone marrow transplantation andachieved complete remission (CR). Three of them, however, developedrelapse in 1.7, 12.9 and 14.5 mo respectively after the transplantation.The other patient has survived in drug-free CR for more than16.6 mo. There was no treatment-related death although therewere some tolerable complications. These data suggest that theCY-TBI regimen may be effective in inducing CR in patients withadvanced non-Hodgkin's disease but it does not contribute topreventing relapse.