Showing papers by "St. Jude Children's Research Hospital published in 1972"
TL;DR: It is concluded that one week of intensive chemotherapy does not prolong remission, that 2400 rads craniospinal irradiation early in remission prevents or delays CNS leukemia and prolongs complete remission, and that once CNS leukemia develops, 2400 radS crani Hospitals irradiation is not sufficient to eradicate it.
Abstract: A study was designed to determine whether a one-week course of intensive chemotherapy and 2400 rads craniospinal irradiation prolonged complete remission of acute lymphocytic leukemia (ALL) in children. Of 110 patients entered into the study, 104 (94%) attained complete remission, 94 of whom were available for the 2 randomizations. They were randomly assigned to receive or not receive one week of high-dosage intravenous chemotherapy and, 4 weeks later, were again randomized to receive or not receive 2400 rads cobalt-60 craniospinal irradiation. Patients randomized for no irradiation were to receive identical radiotherapy only if and when central nervous system (CNS) leukemia developed. The one week of intensive chemotherapy had no effect on the duration of remission or on the frequency or site of relapse, but irradiation had a marked effect. Complete remission was terminated by CNS leukemia in only 2 of 45 children who received “prophylactic” craniospinal irradiation compared to 27 of 49 not irradiated. Five of the 25 children who were given “therapeutic” irradiation for demonstrated CNS leukemia have already had recurrences despite continuous hematologic remission. Under the conditions of this study, we conclude that one week of intensive chemotherapy does not prolong remission, that 2400 rads craniospinal irradiation early in remission prevents or delays CNS leukemia and prolongs complete remission, and that once CNS leukemia develops, 2400 rads craniospinal irradiation is not sufficient to eradicate it.
222 citations
TL;DR: With currently available modalities of therapy, the prospects for cure appear bright, and if current trends in these studies continue, the authors can expect a 50% long‐term leukemia‐free remission rate.
Abstract: The ultimate goal of “total therapy” studies has been to establish a significant cure rate for childhood acute lymphocytic leukemia. The principle features of these studies have included administration of maximum tolerated combination chemotherapy and “prophylactic” central nervous system (CNS) irradiation. In the first three studies, a 17% 7-year leukemia-free remission rate was attained. The number of patients in complete remission decreased exponentially until 2 to 3 years, but stabilized thereafter. Complete remission duration was the earliest and most accurate indicator of long-term leukemia-free remission. In Study V, more aggressive CNS therapy was given and over half the patients have been in continuous complete remission for 3 1/2 to 4 years. Similar results are emerging in subsequent studies which also employ aggressive “prophylactic” CNS therapy. Therapy was stopped after 2 or more years of complete remission in 42 patients in “total therapy” studies, and nine have relapsed. Six of the nine had not received “prophylactic” CNS irradiation. If current trends in these studies continue, we can expect a 50% long-term leukemia-free remission rate. Thus, with currently available modalities of therapy, the prospects for cure appear bright.
147 citations
TL;DR: The frequency of remission fatalities at this institution has increased progressively to l6% of all children dying with acute lymphocytic leukemia, which coincides with more aggressive therapy, longer remissions and survival, and a larger patient population at risk.
142 citations
TL;DR: The finding that both enzymes demonstrate stereospecificity in the oxidative coupling reaction for tyrosine isomers is interesting, and results in the production of trityrosine, thyronine and insoluble yellow to brown colored products.
114 citations
TL;DR: Specific antisera to the isolated hemagglutinin subunits of representative A2 influenza viruses were used to examine antigenic variation among influenza A2 viruses and, in particular, the origin of the Hong Kong strain of influenza (A2/Hong Kong/68).
113 citations
TL;DR: Fifteen patients with localized Ewing's sarcoma were treated with 60Co teletherapy in doses of 5000 to 6500 rads and 1 to 2 years of systemic chemotherapy with vincristine and cyclophosphamide and all developed complete remissions of tumor, and 12 are surviving.
Abstract: Fifteen patients with localized Ewing's sarcoma were treated with 60Co teletherapy in doses of 5000 to 6500 rads and 1 to 2 years of systemic chemotherapy with vincristine and cyclophosphamide. All developed complete remissions of tumor, and 12 are surviving. Ten of the 12 have been continuously free of tumor since initial treatment for 91+, 84+, 67+, 31+, 21+, 19+, 17+, 12+, 11+, and 4+ months from diagnosis. The results suggest that this treatment is superior to other treatment methods with regard to extended tumor-free remission and survival.
106 citations
TL;DR: It is postulate that the number of long-lived, drug-resistant, memory lymphocytes increases in peripheral blood as a function of age and antigenic stimulation and an increase of bone marrow lymphocytes above 40% in children with ALL in whom chemotherapy has been stopped does not indicate relapse but may be a manifestation of immunologic recovery.
101 citations
TL;DR: The results suggest that the hemagglutinin subunits of Hong Kong influenza were not derived by mutation from a preexisting human A 2 strain: it is thought that a more reasonable explanation for their origin is that they came, probably by genetic recombination, from an animal or avian influenza virus.
76 citations
TL;DR: Black children with acute lymphocytic leukemia should be considered separately in designing and evaluating chemotherapy programs because of the difference in response.
Abstract: This study of 334 children with acute lymphocytic leukemia was undertaken to compare the clinical course and response to chemotherapy of Negro children with those of Caucasian children. An initial hematologic remission was attained in 34 of 46 Negro children (74%) with a median duration of the first hematologic remission of 4.9 months and median survival of 14 months. In Caucasian children, a remission occurred in 265 of 288 (92%) with a median duration of 13.1 months and a median survival of 23 months. The poor prognosis in Negro children was related to advanced disease and poverty. However, the natural history of leukemia in the Negro children suggested that other factors related to race also influence host-disease interaction. Because of the difference in response, Negro children should be considered separately in designing and evaluating chemotherapy programs.
70 citations
66 citations
TL;DR: The buoyant density, chemical composition, and electron microscopic appearance of the transcriptive complex indicate a structure like that of viral nucleocapsids.
Abstract: A Sendai virus-induced transcriptase-template complex was isolated from the cytoplasm of infected cells by combined sedimentation and isopycnic centrifugation. This transcriptive complex banded at 1.27 g/cm(3) in D(2)O-sucrose gradients. It contained two polypeptides, the viral nucleocapsid structure unit (molecular weight, 60,000) and the largest virion polypeptide (molecular weight, 75,000). The buoyant density, chemical composition, and electron microscopic appearance of the transcriptive complex indicate a structure like that of viral nucleocapsids.
TL;DR: Two kinds of antigenic variation occur in influenza viruses, antigenic drift and major antigenic shifts; both involve changes in the hemagglutinin and neuraminidase antigens on the surface of the virus.
Abstract: Influenza continues to be one of the major epidemic diseases of man and is, in fact, his only remaining pandemic disease (Beveridge, 1969). This is largely because influenza virus undergoes extreme antigenic variation, the mechanism of which is still poorly understood. Two kinds of antigenic variation occur in influenza viruses, antigenic drift and major antigenic shifts; both involve changes in the hemagglutinin and neuraminidase antigens on the surface of the virus.
TL;DR: Rat and human strains of Pneumocystis carinii were found to be identical in morphology of all the developmental stages, including cysts and trophozoite forms identified by Giemsa staining fluoresced by IFA method.
Abstract: SummaryRat and human strains of Pneumocystis carinii were found to be identical in morphology of all the developmental stages. “Trophozoites” varied greatly in size and had paired nuclei located eccentrically. Transitional forms were also observed in addition to “cyst” forms with eight “sporozoites” which have been described previously. By these observations, life cycle of P. carinii inside the pulmonary alveoli was proposed. Uninfected rats were immunized with the rat strains of P. carinii. The pooled rat antisera contained specific antibody to homologous P. carinii through dilution of 1:2048 as detected by indirect fluorescent antibody (IFA) method. Eight rat and five human strains of P. carinii were then studied by IFA method. All of the rat strains fluoresced while none of human strains gave fluorescence which suggested antigenic dissimilarity between these two strains. Both cysts and trophozoite forms identified by Giemsa staining fluoresced by IFA method.
TL;DR: The combination of 6‐azauridine, 6‐mercaptopurine, and vincristine was effective for remission induction of acute myelocytic leukemia in children.
Abstract: Seventeen children with acute myelocytic leukemia were treated with a combination of 6-azauridine, 6-mercaptopurine, and vincristine. Twelve attained complete bone marrow remission, and 2 achieved good partial remissions. For maintenance therapy, patients who attained remission were randomized into 2 groups: one received 6-mercaptopurine alone; the other received a combination of 6-mercaptopurine, 6-azauridine, and vincristine. The median duration of hematologic remission in these groups was 7 and 6 months, respectively. Meningeal leukemia developed in 8 of 15 patients. The overall median survival time was 8 months; for those who attained remission it was 10.5 months. The combination of 6-azauridine, 6-mercaptopurine, and vincristine was effective for remission induction of acute myelocytic leukemia in children.
TL;DR: It is concluded that neuraminidase alters the platelet membrane resulting in its rapid and permanent removal by the reticuloendothelial system.
Abstract: Summary. The purpose of this study was to elucidate the effect of neuraminidase on circulating platelets in rats and the pathogenesis of this effect. Injection of bacterial, purified bacterial and viral neuraminidase caused thrombocytopenia of various degrees. Thrombocytopenia was less pronounced in rats given viral neuraminidase and in splenectomized animals. A dose-response effect was seen only with purified bacterial neuraminidase injected intravenously. Ultrastructural studies of blood platelets were performed after injection of neuraminidase. Fifteen minutes after injecting neuraminidase, before a definite fall in the count, platelets showed evidence of structural damage such as irregular shapes, centripetal migration and fusion of granules and bleb formation. The structural alterations were progressive, reaching a maximum at about 2–4 hr. At no time were large platelet aggregates observed in the circulating blood. Four hours after injection of neuraminidase, when the platelet count dropped significantly, many platelets had normal ultrastructurc. By 24 hr, the majority of circulating platelets appeared normal; however, the splenic sinusoids and macrophages contained platelets with the same structural abnormalities seen in the circulation 15 min to 2 hr after injection of neuraminidase. We conclude that neuraminidase alters the platelet membrane resulting in its rapid and permanent removal by the reticuloendothelial system.
TL;DR: The model for this repair process envisions initial endonucleolytic cleavages in the DNA strand, close to the damage, followed by excision of a short oligonucleotide containing the lesion, and the resulting gap is then filled and sealed by polymerase and ligase enzymes.
Abstract: THE capacity of an organism to maintain the integrity of the genetic information in its DNA is of critical importance to its survival and the survival of its progeny. Some damage to the DNA is inevitable and it seems that most organisms possess mechanisms for the correction of such damage. There is evidence for one such mechanism, excision-patch repair, in both microorganisms1 and mammalian cells2. The model for this repair process envisions initial endonucleolytic cleavages in the DNA strand, close to the damage, followed by excision of a short oligonucleotide containing the lesion. The resulting gap is then filled and sealed by polymerase and ligase enzymes.
TL;DR: Partially ribonuclease-resistant RNA complexes elicited by Sendai virus infection were separated by rate zonal centrifugation and their metabolic and chemical properties were examined, finding that they may be predominantly transcriptive intermediates specified by the 19 and 24 S RNA species in incomplete virions.
TL;DR: In this article, the authors demonstrate that recombinant influenza A viruses can be selected in vivo using recombinant viruses and recombinant recombinant antigenic hybrids of different influenza A virus types.
TL;DR: Improved pediatric surgical techniques, supervoltage radiotherapy, and the availability of effective chemotherapeutic agents have all contributed to better results in the treatment of malignant tumors.
TL;DR: It is pointed out that spectrophotometric assays for iodination of tyrosine may not distinguish between oxidative coupling and iodination, and the converse appears to be true in the case of glutamic acid containing dipeptides.
TL;DR: Virus-specific complementary ribonucleic acid from cells infected with Sendai virus was isolated by a procedure involving hybridization with virion RNA and isopycnic centrifugation of the RNA hybrids.
Abstract: Virus-specific complementary ribonucleic acid (RNA) from cells infected with Sendai virus was isolated by a procedure involving hybridization with virion RNA and isopycnic centrifugation of the RNA hybrids. The complementary RNA contained adenylate-rich sequences which sedimented at about 4S.
TL;DR: These experiments indicate that cyclic AMP bound to the binding protein is not susceptible to the action of phosphodiesterase and is hydrolyzed only when dissociated from the protein, and the rate of dissociation appears to be the limiting factor.
TL;DR: The results suggest that children with ALL who experience relapse have an opportunity for a prolonged subsequent remission.
Abstract: The objective of this study was to determine in children with acute lymphocytic leukemia (ALL) whether prolonged remission could be attained following relapse from prior chemotherapy. Multiple agent chemotherapy and central nervous system radiotherapy were administered to 16 children who had had one or more relapses. With prednisone, vincristine, and daunomycin, 14 of 16 patients attained complete remission in a median time of 31 days. The median duration of complete remission for the 14 children was 12 months. Drug toxicity and morbidity secondary to therapy included pancytopenia, oral ulcerations, nausea, vomiting, diarrhea, abdominal pain, and potentially fatal infections. Five of the 14 who achieved remission developed Pneumocystis carinii pneumonia. Patients who had relapsed during prior unmaintained remission had superior responses to therapy. After 46 to 50 months in this study, three patients remain in continuous complete remission and two others remain in continuous hematologic remission. Therapy was stopped in four children after 36 months of continuous hematologic remission. These results suggest that children with ALL who experience relapse have an opportunity for a prolonged subsequent remission.
TL;DR: It is found that early death from streptococcal infection was prevented with one injection of MTX, whereas comparable dosage in milligrams of penicillin G failed to protect the animals, indicating that MTX therapy likely influences the incidence of Group A beta hemolytic strePTococci and the occurrence of streptitiscal infections.
Abstract: The incidence of Group A beta hemolytic streptococci and streptococcal infections was lower in children with leukemia than those with no malignancy. Cancer chemotherapy agents were suspected of having some effect on the microbial flora, and methotrexate was investigated. In vitro, methotrexate (MTX) was found to inhibit Group A beta hemolytic streptococci in concentrations of 7.8 μg/ml and less, whereas P. aeruginosa, E. coli, S. aureus, S. marcescens, C. albicans, and Klebsiella‐Enterobacter sp. were resistant to 250 μg/ml. In mice, early death from streptococcal infection was prevented with one injection of MTX, whereas comparable dosage in milligrams of penicillin G failed to protect the animals. These findings indicate that MTX therapy likely influences the incidence of Group A beta hemolytic streptococci and the occurrence of streptococcal infections.
TL;DR: Radioautographic studies performed on samples taken at the same post-injection times gave even more convincing evidence concerning the localization of 125 I-labeled bovine growth hormone in or on mitochondria.
TL;DR: By morphological criteria, these viruses are rhabdoviruses with dimensions and ultrastructural features similar to vesicular stomatitis virus.
Abstract: The morphology and ultrastructure of three North American salmonid pathogens, Oregon sockeye salmon, chinook salmon and infectious hematopoietic necrosis viruses, were examined by thin sectioning and negative staining after growth in fathead minnow cells at 10 ° C. The viruses matured at the plasma membrane of these cells. They were approximately 170 nm in length, 70 nm in width and had internal striations with a periodicity of 5.5nm. They were rounded on one end and planar on the other (i.e., bullet shaped). By morphological criteria, these viruses are rhabdoviruses with dimensions and ultrastructural features similar to vesicular stomatitis virus.
TL;DR: The presence of sickle cell trait did not appear to influence the median age of onset, the median survival time, or the quality of survival in black children with acute leukemia.
Abstract: Among 58 black children with leukemia, seven had sickle cell trait and one was homozygous for Hb-S. Both of these rates are similar to those for the black population of the United States in general. The presence of sickle cell trait did not appear to influence the median age of onset, the median survival time, or the quality of survival in black children with acute leukemia. The single patient with sickle cell ane mia died a sudden, unexpected death with massive intravascular eryth rocytic sickling secondary to viremia while in a leukemic remission.