Showing papers by "St. Jude Children's Research Hospital published in 1978"
TL;DR: The susceptibility of ducks to infection with human and avian strains of influenza virus and the possibility of transmission to animal species through the water supply suggests that ducks may be important in the ecology of influenza viruses.
646 citations
TL;DR: These studies indicate that subclinical P. carinii infection is highly prevalent in normal children, analogous to other opportunistic infections where active disease is manifest predominantly in the compromised host.
Abstract: Using Pneumocystis carinii organisms propagated through three passages in embryonic chick epithelial lung cultures, specific antigens and antisera were prepared for use in counterimmunoelectrophoresis and indirect immunofluorescent antibody techniques. These methods proved to be specific and sensitive for the detection of P. carinii antigen and antibody, respectively, in sera, and were applied to the study of cancer patients with P. carinii pneumonitis (PCP), cancer patients without pneumonitis, and normal children. Antigenemia was detected in 95% of patients with PCP, in 15% of cancer patients without pneumonitis, and in none of the normal children tested. In cross-sectional and longitudinal studies of normal infants and children, acquisition of serum antibody to P. carinii was demonstrated to occur progressively with increase in age. By 4 years of age two thirds of the normal children were found to have antibody to P. carinii in titers of 1:16 or greater. These studies indicate that subclinical P. carinii infection is highly prevalent in normal children, analogous to other opportunistic infections where active disease is manifest predominantly in the compromised host.
390 citations
TL;DR: Serological and virological surveillance of swine during 1976-77 showed that Hsw1N1 influenza viruses were prevalent throughout the swine population of the U.S., particularly in the northern states.
221 citations
TL;DR: This study shows that TMP-SMZ is as effective as pentamidine in the treatment of PCP, and that it offers the advantages of minimal adverse effects, oral administration, and ready availability.
201 citations
TL;DR: This controlled study of children with ALL was designed to test the efficacy and toxicity of one‐, two‐, three‐ and four‐drug therapy during remission and whether more aggressive therapy in the first eight weeks prolongs remission in patients with features associated with a particularly poor prognosis.
Abstract: This controlled study of children with ALL was designed to test the efficacy and toxicity of one-, two-, three- and four-drug therapy during remission and whether more aggressive therapy in the first eight weeks prolongs remission in patients with features associated with a particularly poor prognosis. After inducing remission with prednisone, vincristine and asparaginase, patients received cranial irradiation and IT methotrexate and were randomized to receive: 1--methotrexate alone; 2--methotrexate plus mercaptopurine; 3--same as in group 2 plus cyclophosphamide; and 4--same as in group 3 plus arabinosyl cytosine. Patients with CNS leukemia at diagnosis received IT methotrexate weekly during the induction period and a higher dose of CNS irradiation. Patients with anterior mediastinal enlargement at diagnosis received radiotherapy to the mass during the induction period. Patients who failed to attain bone marrow remission after four weeks of therapy were given daunorubicin and prednisone for 2--4 additional weeks. Of the 282 patients entering this study between January 1972 and November 1975, 268 (95%) attained complete remission and 228 (85%) were randomized to receive continuation chemotherapy with 1, 2, 3 or 4 drugs. In Group 1 (methotrexate alone), 14 of 20 patients relapsed and 9 developed leukoencephalopathy without antecedent CNS leukemia apparently due to higher doses of intravenous methotrexate; in Groups 2, 3 and 4 the results were equivalent, but without leukoencephalopathy in initial CR. The addition of cyclophosphamide and arabinosyl cytosine increased toxicity and complications without demonstrably increasing the leukemocidal effect. In the 40 patients given additional early therapy, the modalties employed in this study did not prolong remission.
165 citations
TL;DR: Analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation had induced the degenerative process, and Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor.
Abstract: We determined the prevalence, histopathologic features, and clinical correlations of a distinctive vascular lesion within the central nervous system (CNS) of children who died with acute lymphoblastic leukemia (ALL). Of 163 brains examined at autopsy, 28 (17%) had a noninflammatory mineralizing microangiopathy, usually accompanied by varying amounts of necrosis and calcification in adjacent neural tissue. The lesion always involved the lenticular nucleus with or without additional involvement of cerebral cortex. It was not the cause of death in any patient. An analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation, in doses as low as 1500 rad, had induced the degenerative process. Survival beyond 10 months from the time of irradiation and multiple postirradiation CNS leukemic relapses, both had significant influences on the development of the lesion. Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor. Patients at greatest risk for developing microangiopathy are those under 10 years of age at the time of cranial irradiation, who then live more than 10 months and develop multiple CNS leukemic relapses.
158 citations
TL;DR: Throbin-activated human platelets cause agglutination of trypsinized, formalinized bovine erythrocytes and it appears that a membrane surface component that has lectin activity mediates platelet aggregation.
Abstract: Throbin-activated human platelets cause agglutination of trypsinized, formalinized bovine erythrocytes. This lectin activity of stimulated platelets was blocked by galactosamine, glucosamine, mannosamine, lysine, and arginine, but not by N-acetylated sugars, other neutral sugars, or other amino acids. Inhibitors of the thrombin-induced lectin activity also blocked thrombin-induced platelet aggregation. It appears that a membrane surface component that has lectin activity mediates platelet aggregation.
104 citations
TL;DR: Analysis of viral DNA and RNA synthesis in infected cells by electron microscopic autoradiography and biochemical techniques supports the conclusion that FV 3 DNA synthesis is initiated in the nucleus and completed in the cytoplasm.
86 citations
TL;DR: The kinetics of methotrexate were followed in a patient given two 6‐hr infusions of 400 mg/kg in the presence and absence of a pleural effusion to indicate that the increased risk of toxicity following high‐dose metotrexate in patients with Pleural effusions is due to changes in methotRexate kinetics resulting in delayed excretion.
Abstract: The kinetics of methotrexate were followed in a patient given two 6-hr infusions of 400 mg/kg in the presence and absence of a pleural effusion. Although the decline in serum concentrations during the first 30 hr after the infusion was similar for the two treatment courses, the half-life beginning 30 hr after the infusion was 6.7 hr without the pleural effusion and 14.4 hr with the pleural effusion. Comparison of the intercompartment distribution rate constants indicated slower movement of the drug back into the central compartment from the peripheral compartment when a pleural effusion was present. Pleural fluid methotrexate concentrations were consistently higher than serum concentrations. These data indicate that the increased risk of toxicity following high-dose methotrexate in patients with pleural effusions is due to changes in methotrexate kinetics resulting in delayed excretion.
81 citations
TL;DR: Patients who developed varicella while being treated for malignancy received human leukocyte interferon in a randomized double-blind placebo-controlled trial andInterferon was tolerated without significant side effects.
Abstract: Eighteen patients who developed varicella while being treated for malignancy received human leukocyte interferon in a randomized double-blind placebo-controlled trial. Complications of varicella occurred in six of nine placebo recipients, but in only two of nine interferon recipients. Interferon was tolerated without significant side effects.
71 citations
TL;DR: Another brain factor was described which inhibited both brain adenylate cyclase and phosphodiesterase in vitro in vitro and appeared to be a protein; it was inactivated by incubation with trypsin, but not with ribonuclease or deoxyrib onuclease.
TL;DR: In this article, an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multi-agent chemotherapy, would be successful in prolonging durations of complete remission.
Abstract: In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved.
TL;DR: The hematologic recovery pattern and degree of rebound marrow lymphocytosis after cessation of therapy did not correlate with the frequency of subsequent relapse and the adequacy of therapy, especially CNS prophylaxis, was a positive factor.
Abstract: Therapy was stopped in 140 children with acute lymphocytic leukemia after 2–3 years of complete remission (CR) Of the 108 children who had received preventive central nervous system (CNS) therapy and were in initial CR when therapy was stopped, 85 (79%) remain in CR for a median time of 93 months (66–166) and have been off therapy for a median time of 58 months (36–128) The 23 relapses involved the bone marrow in all but four patients who had isolated testicular relapse Six of seven children who were in initial CR, but had received no CNS therapy, relapsed after cessation of therapy; five relapses involved the CNS Twenty-five children had at least one extramedullary relapse, usually in the CNS, with subsequent CR for 2–3 years before therapy was stopped; 18 of 25 (72%) remain in CR for a median time of 86 months (56–141) and have been off therapy for a median time of 56 months (33–103) Six of the seven relapses involved the marrow No feature present at the time of diagnosis could be correlated with the frequency of relapse after cessation of therapy except for the significantly greater frequency among boys (25/75) than girls (11/67) The adequacy of therapy, especially CNS prophylaxis, was a positive factor The hematologic recovery pattern and degree of rebound marrow lymphocytosis after cessation of therapy did not correlate with the frequency of subsequent relapse Of the 36 patients who relapsed after cessation of therapy, all attained CR again and six are off therapy a second time for 3–21 months
TL;DR: It is concluded that, while reinduction of a second remission in ALL is comparatively easy, effective maintenance treatment for these remissions remains a difficult therapeutic problem.
Abstract: Fifty-six children with acute lymphocytic leukemic (ALL) who had initial marrow relapses during continuation chemotherapy were retreated with vincristine and prednisone. By one month, 36 of 56 (64%) were again in hematologic remission. Twelve of the remaining 20 achieved marrow remissions with additional therapy. Thus, 48 of 56 patients (85%) achieved second marrow remissions. Continuation therapy consisted of weekly cytosine arabinoside (Ara-C), 150 mg/m2, and methotrexate (MTX), 40 mg/m2. Patients were randomly selected to receive the drugs simultaneously or sequentially (48 hours apart) to evaluate the theoretical advantage of scheduling Ara-C before MTX. In 13 children, drug-induced changes in DNA-synthetic activity were documented before reinduction of remission by determining tritiated thymidine and deoxyuridine labeling indices, autoradiographically, in marrow samples obtained at 0, 4, 24, 48 and 72 hours after a dose of Ara-C and MTX. Neither clinical nor cytokinetic results supported the sequential schedule. The duration of second remissions among 25 patients treated with simultaneous Ara-C and MTX (median = 56 days) did not differ significantly from that of 22 sequentially treated patients (median = 65 days). Moreover, there was no convincing cytokinetic evidence for partial synchronization of the mitotic cycle of leukemia blasts following Ara-C administration. Instead, the labeling indices showed extensive variability from patient to patient, and, in the simultaneously treated group, the drug-induced suppression of lymphoblast labeling was unexpectedly brief, possibly due to relative drug resistance. We conclude that, while reinduction of a second remission in ALL is comparatively easy, effective maintenance treatment for these remissions remains a difficult therapeutic problem. Combinations of Ara-C and MTX, under the conditions of this study, failed to interfere effectively with leukemic cell replication as evidenced by both cytokinetic studies and end results. Cancer 42:2521–2528, 1978.
TL;DR: The treatment effect was significant, even after adjustments were made for the important covariates, and non-Caucasian patients did poorly on all regimens with a response rate of only 31% compared to 62% for Caucasian patients.
Abstract: Identification of important prognostic factors with respect to the patient's initial response to therapy was made from a set of 25 covariates available on 281 patients with advanced breast cancer. Since the patients studied were all participants in a randomized clinical trial that involved three different treatment regimens (repeated weekly treatment of a combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; intermittent treatment of the same preceding five drugs given in 5-day courses every 4 weeks; or treatment every 3 weeks with adriamycin as a single agent), the effect of these treatments on the selection of important covariates was assessed. Although some evidence indicated that the set of important covariates differed by treatment, the differences were not strong enough to be of practical importance. Non-Caucasian patients did poorly on all regimens with a response rate of only 31% compared to 62% for Caucasian patients. The covariates of major prognostic importance for Caucasians were: disease-free interval, liver involvement, and performance status. Ambulatory patients with long disease-free intervals and no liver involvement had the best prognosis. After adjustments were made for these three covariates, the remaining covariates (such as menopausal status, bone involvement, number of metastatic sites, and duration of metastatic disease) were not significantly related to response. As reported earlier, the treatment effect was significant, even after adjustments were made for the important covariates.
TL;DR: Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions, leading to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy as mentioned in this paper.
Abstract: Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy
TL;DR: It is shown that early frog virus 3 (FV3) RNA can be subdivided into two sequentially synthesized classes: immediate early, which took place in the absence of protein synthesis (cycloheximide), and “delayed early,” which occurred under conditions of restrictedprotein synthesis (FPA).
TL;DR: Results indicated that antimicrobial activity was due to peroxidase-catalyzed oxidation of I− to I2, followed by I2 oxidation of cell components, and there was a direct relationship between sulfhydryl oxidation and antimicrobial action.
Abstract: The chemical modification of bacterial components was studied following incubation of Escherichia coli with the peroxidase-hydrogen peroxide (H(2)O(2))-iodide (I(-)) antimicrobial system or with iodine (I(2)). The oxidation of cell sulfhydryls and the iodination of cell components were measured. Both the peroxidase system and I(2) oxidized sulfhydryls. When the I(-) concentration in the peroxidase system was greater than 100 muM, the peroxidase system and I(2) were equivalent. That is, sulfhydryl oxidation or killing per mole of H(2)O(2) equaled that per mole of I(2). These results were consistent with peroxidase-catalyzed oxidation of I(-) to yield 1 mol of I(2) per mol of H(2)O(2). Sulfhydryls were oxidized to yield sulfenic acids and free I(-). With I(-) concentrations in the range of 10 to 100 muM, the amount of sulfhydryls oxidized by the peroxidase system could exceed the amount of I(-). Because the oxidation of sulfhydryls to sulfenic acids did not consume I(-), one I(-) ion could participate in the oxidation of many sulfhydryls. With I(-) concentrations lower than 10 muM, complete oxidation of sulfhydryls was not obtained. Incorporation of I(-) into iodinated derivatives of bacterial components partly depleted the system of I(-) and limited the formation of I(2). These results indicated that antimicrobial activity was due to peroxidase-catalyzed oxidation of I(-) to I(2), followed by I(2) oxidation of cell components. There was a direct relationship between sulfhydryl oxidation and antimicrobial action. Although iodination of bacterial components accompanied sulfhydryl oxidation, the amount of I(-) incorporation was not directly related to antimicrobial action. Also, incorporation of I(-) interfered with antimicrobial action at low I(-) concentrations.
TL;DR: The data indicate that Sendai virus nucleocapsid assembly occurs in two steps: condensation of NP with viral genomic RNA followed by addition of P (and probably L) to the structure, which explains, in part, why newly synthesized P is rapidly incorporated into virions.
TL;DR: It is proposed that peroxidase-catalyzed oxidation of I− yields I2, which reacts with bacterial components to yield the oxidized components and I−, which can be reoxidized and participate again in the oxidation of bacterial components.
Abstract: The mechanism of antimicrobial activity of the peroxidase-hydrogen peroxide (H(2)O(2))-iodide (I(-)) system was investigated. Inhibition of respiration and loss of viability of Escherichia coli were used as measures of antimicrobial activity. Because the bacteria destroyed H(2)O(2), peroxidase antimicrobial action depended on the competition for H(2)O(2) between the bacteria and the peroxidase. Utilization of H(2)O(2) by the peroxidase was favored by (i) increasing either the peroxidase or the I(-) concentration, so as to increase the rate of oxidation of I(-), (ii) lowering the temperature to lower the rate of destruction of H(2)O(2) by the bacteria, and (iii) adding H(2)O(2) in small increments so as to avoid a large excess of H(2)O(2) relative to I(-). When utilization of H(2)O(2) by the peroxidase system was favored, the peroxidase system and iodine (I(2)) were equivalent. That is, antimicrobial action per mole of H(2)O(2) equaled that per mole of I(2). Also, identical antimicrobial action was obtained either by incubating the bacteria directly with the peroxidase system or by preincubating the peroxidase system so as to form I(2) and then adding the bacteria. On the other hand, peroxidase antimicrobial action could be obtained at low I(-) concentrations. These I(-) concentrations were lower than the concentration of I(2) that was required for antimicrobial action. It is proposed that peroxidase-catalyzed oxidation of I(-) yields I(2), which reacts with bacterial components to yield the oxidized components and I(-). The I(-) that is released can be reoxidized and participate again in the oxidation of bacterial components. In this way, I(-) acts as a cofactor in the peroxidase-catalyzed oxidation of bacterial components.
TL;DR: Peritoneal exudate cells from immunized and nonimmunized animals were separated into subpopulations by centrifugation on discontinuous bovine serum albumin (BSA) density gradients and cytotoxic activity against syngeneic and xenogeneic tumor cells was tested.
TL;DR: Assessment of the metabolism, structure, or composition of bacterial cells can greatly increase their susceptibility to peroxidase bactericidal action, and mild reducing agents did partly reverse bactericidal activity when added after exposure of cells to the per oxidase systems.
Abstract: The bactericidal action that results from lactoperoxidase-catalyzed oxidation of iodide or thiocyanate was studied, using Escherichia coli as the test organism. The susceptibility of intact cells to bactericidal action was compared with that of cells with altered cell envelopes. Exposure to ethylenediaminetetraacetic acid, to lysozyme and ethylenediaminetetraacetic acid, or to osmotic shock were used to alter the cell envelope. Bactericidal action was greatly increased when the cells were exposed to the lactoperoxidase-peroxide-iodide system at low temperatures, low cell density, or after alteration of the cell envelope. When thiocyanate was substituted for iodide, bactericidal activity was observed only at low cell density or after osmotic shock. Low temperature and low cell density lowered the rate of destruction of peroxide by the bacteria. Therefore, competition for peroxide between the bacteria and lactoperoxidase may influence the extent of bactericidal action. Alteration of the cell envelope had only a small effect on the rate of destruction of peroxide. Instead, the increased susceptibility of these altered cells suggested that bactericidal action required permeation of a reagent through the cell envelope. In addition to altering the cell envelope, these procedures partly depleted cells of oxidizable substrates and sulfhydryl components. Adding an oxidizable substrate did not decrease the susceptibility of the altered cells. On the other hand, mild reducing agents such as sulfhydryl compounds did partly reverse bactericidal action when added after exposure of cells to the peroxidase systems. These studies indicate that alteration of the metabolism, structure, or composition of bacterial cells can greatly increase their susceptibility to peroxidase bactericidal action.
TL;DR: Fundamental similarities between reports of ultrastructural studies of malignant histiocytoma of soft tissues suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the offspring cell is capable of differentiation in both Histiocytic and fibroblastic directions.
TL;DR: Patients and parents had overall high levels of hospital-related anxiety and depression which varied with the patient's chronologic age, and parents of preschool children had more negative opinions toward peninsula isolation than did parents of older children.
TL;DR: A possible relationship between content of amino sugars (other than NANA) and charge heterogeneity was suggested by the finding that the amount of radioactive glucosamine incorporated biosynthetically into G of VSV and HN of Sendai virus was greater in the more electropositive species.
TL;DR: The results suggest that the platelet dysfunction in myeloid leukaemia is partially due to a membrane defect involving the thrombin receptors which leads to an impaired induction of the initial stimulation.
Abstract: Platelets from patients with myeloid leukaemia showed reduced aggregation with collagen or thrombin. These platelets also had a lower capacity to bind thrombin. This lower thrombin binding is due to a decrease in the total quantity of receptors available and not because of a change in the affinity. In the presence of the patients' plasma, the aggregation behaviour of normal platelets induced by thrombin as well as the clotting time of fibrinogen remained unchanged. The results suggest that the platelet dysfunction in myeloid leukaemia is partially due to a membrane defect involving the thrombin receptors which leads to an impaired induction of the initial stimulation.
TL;DR: Clinically, the affected patients seem to recover completely soon after the anoxia, but after two to ten days that may exhibit strange behavior, irritability, agitation, and confusion or they may become very withdrawn and uncommunicative.
TL;DR: The results show clearly that feeding either LCT or MCT will enhance hyperketonemia in suckling rats and in the livers of all animals, regardless of age, the capacity for incorporation of [1-14C] octanoate into CO2 and acetoacetate far exceeded that for [ 1- 14C] palmitate.
Abstract: The potential of medium chain triglyceride (MCT) and long chain triglyceride (LCT) as sources of plasma ketones was investigated in suckling rats. Initially high concentrations of plasma ketones in 6-, 10-, and 17-day-old rats increased 2- to 3-fold after acute feeding of MCT. This feeding had the same effect in fed or fasted adult rats. Corn oil (as a source of LCT) induced a large increase in the plasma ketone concentration of suckling rats and a relatively small but significant increase in fasted adult rats. The LCT treatment did not affect plasma ketone levels in fed adult rats. The results show clearly that feeding either LCT or MCT will enhance hyperketonemia in suckling rats. In the livers of all animals, regardless of age, the capacity for incorporation of [1-14C] octanoate into CO2 and acetoacetate far exceeded that for [1-14C] palmitate. The hyperketonemic action of LCT in suckling rats was accompanied by an increased activity of carnitine palmityltransferase and increased level of carnitine.
TL;DR: It is concluded that SCL and ESR, even when age corrected and consecutively followed, are not useful as indicators of disease activity in children with Hodgkin's disease.
Abstract: Initial and serial serum copper levels (SCL) and erythrocyte sedimentation rates (ESR) of 29 children with Hodgkin's disease were reviewed to determine the relationship of these features to disease activity. Only six of 10 patients who relapsed had SCL greater than adult upper normal levels. Although correction for age increased this to 7, it also increased the number of patients with false positive results to 9 of 19. Although 9 of the 10 patients at relapse had an increase in SCL over the preceding value, almost one-fifth of patients in remission had increases in consecutive SCL greater than the average increase of patients who relapsed. We conclude that SCL, even when age corrected and consecutively followed, are not useful as indicators of disease activity in children with Hodgkin's disease. Although the ESR increased to >20 mm/hour in 9 of 10 patients who relapsed, this determination could not be considered a useful early indicator of disease recurrence since it was so frequently elevated in patients who were free of disease (62 of 109 determinations). The extremely nonspecific nature of SCL and ESR in childhood renders these tests unreliable, particularly in the individual child. Cancer 42:1929–1935, 1978.
TL;DR: Pyridoxal phosphate exerted a concentration-dependent inhibition of epinephrine-induced platelet aggregation, in vitro, and appears to be due to its specific binding to these platelet-surface proteins which may be involved in various platelet functions.