Infusion of Cryopreserved Autologous Marrow in the Treatment of Acute Leukemia: A Preliminary Report

Autologous marrow was collected from patients with acute leukemiaduring their first remission, and cryopreserved. In relapse,four of the patients were treated with remission-induction chemotherapymore intensive than the previous treatment, followed by infusionof the cryopreserved autologous marrow. Autologous marrow infusioncaused relatively rapid hematological recovery from the bonemarrow depression induced by high-dose chemotherapy. All fourpatients achieved a second complete remission, but with no maintenancetherapy leukemic relapses were observed in three of them. Onepatient survived without leukemic relapse for 19 months, 13months longer than the previous remission period. Another effectof autoinfusion was reduction in blood products required duringthe bone marrow depression. These observations suggest thatcryopreserved autologous marrow may retain its hemopoietic activityand autologous marrow infusion may be effective in providingearly recovery or rescue from bone marrow failure.     

Current status and future prospects of human gene therapy

Gene therapy is defined as the treatment of diseases by the transfer of genes into patients. Clinical trials of gene therapy became feasible as a result of the development of retroviral mediated gene transfer techniques. The first trial was begun in September 1990 at the National Institutes of Health when a four year old girl was treated for adenosine deaminase deficiency. Currently, more than 500 patients are being treated by this innovative therapeutic strategy. In the present review article, the basic concepts and present status of human gene therapy are summarized.     

STRUCTURAL STUDIES ON STEM BROMELAIN

Stem bromelain was cleaved with cyanogen bromide, and the products were fractionated with and without prior maleylation and sulfitolysis. The fragments that corresponded to the carboxyl-terminal half of the molecule were isolated and nearly completely sequenced. This portion of the enzyme molecule contained one disulfide linkage. A specific cleavage at the amino peptide bonds of that cystine residue by reduction, modification into S-cyano derivatives and exposure to alkali gave important information of the amino terminal sequence. By combining the present data with the previously known partial sequence of the parent molecule, 101 amino acid residues were aligned down to the carboxyl terminus and compared with those of papain. The sequence homology between carboxyl-terminal halves of these two thiol proteases of plant origin was found to be 34.7%.     

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.     

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.     

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.     

Primary Adrenocortical Carcinoma and Ganglioneuroblastoma Followed by Rhabdomyosarcoma in a Child: A Case Report

We report a case of a young child affected by triple cancerswho developed a pleomorphic rhabdomyosarcoma of the retroperitoneumfollowing prophylactic chemotherapy after surgery for doubleprimary adrenocortical carcinoma and ganglioneuroblastoma. It is suggested that genetic susceptibility and chemotherapymight be responsible for the development of rhabdomyosarcomaas the second malignant neoplasm.