Showing papers by "St. Jude Children's Research Hospital published in 1976"
TL;DR: This method is useful in detecting simultaneously the position of proteins and sialoglycoproteins in the commonly used SDS polyacrylamide gel electrophoresis.
101 citations
TL;DR: The results suggest that the formation of the enzyme-activator complex is dependent on Ca++, and that adenylate cyclase activityin vivo could be modulated by the cellular flux of Ca++.
89 citations
TL;DR: Silver nitrate irrigations after cystoscopic evacuation of clots stopped intractable hemorrhage from the bladder in 8 of 9 children who had received cyclophosphamide and/or pelvic irradiation for various malignant diseases.
80 citations
TL;DR: Resonance Raman spectra of oxidized hydroperoxidases are examined for shifts in the structure-sensitive, anomalously polarized bands; these are found, respectively, at 1576, 1567 and 1570 cm-1 in the high-spin resting enzymes: horse radish peroxidase, horse blood catalase, and cytochrome c peroxIDase.
80 citations
TL;DR: It is concluded that prevention of CNS leukemia including 2400 rad of cranial irradiation in children with ALL Is effective and destitute of prohibitive toxicity on physical growth and neuropsychlogical competency.
Abstract: Twenty-two children with acute lymphocytic leukemia (ALL) who attained complete remission and received preventive central nervous system (CNS) therapy consisting of 2400 rad cranial irradiation with five doom of intrathecal methotrexate followed by 28–36 months of multiple-agent chemotherapy were uniformly evaluated for potential toxicity upon neuropsychological functioning and somatic growth. Retrospective analysis of CNS signs, symptoms and function as well as head size, height and weight were tabulated at loon of therapy, the following 10 weeks, and at 28–36 months when all treatment was stopped. Sixty months after CNS therapy, a current assessment was performed attempting to identify any resultant neuropsychological aberration and disturbance in growth pattern. Nine of the 22 patients developed nonleukemic pleocytosis or presented headache, backache or leg pain. During the 10 weeks after CNS therapy, 8 of 22 patients developed transitory lethargy or somnolence. During continuation chemotherapy mild cerebro spinal fluid (CSF) pleocytosis was seen in some patents. Two children developed pseudo-tumor cerebri but recovered without sequelae. Neurological examination at 60 months was normal is all patients. Although initial head cicrumference averaged somewhat below normal, growth continued without significant deviation from the normal rate. Linear grow was slower than normal in 12 of the patients, following cessation of therapy only 2 persisted with a slower rhythm of longitudinal growth. Weight pattern was within one standard deviation at 5 years in all but 3 patients. About one-third of patients were rated below average in energy level, motivation, attention span, and concrete-abstract thinking, and one-third to one-ball rated above average in academic interest and approach to problems. We conclude from these results that prevention of CNS leukemia including 2400 rad of cranial irradiation in children with ALL Is effective and destitute of prohibitive toxicity on physical growth and neuropsychlogical competency.
80 citations
TL;DR: The concept that ketosis induced by MCT stems from rapid oxidation of medium-chain fatty acids is supported, as Hyperinsulinemia, hypoglycemia and depressed lipogenesis resulting from MCT feeding appear to potentiate but not initiate ketosis.
Abstract: Medium-chain triglycerides (MCT) induce ketosis in several mammalian species including man To clarify the regulation of this metabolic alteration, we fed rats either MCT or long-chain triglyceride (corn oil) and then attempted to correlate ketosis with changes in (i) concentrations of selected metabolites in plasma and (ii) the synthetic and oxidative capacities of the liver By 1 hour after MCT feeding, plasma levels of total ketone bodies had increased 18-fold, with a maximum value reached 1 hour later By contrast, total plasma ketones in rats fed corn oil were increased only about 2-fold at 2 hours after feeding and did not exceed this value at later intervals Hepatic concentrations of ketone bodies also increased after MCT or corn oil feeding Although plasma concentrations of glucose decreased and insulin increased in rats fed MCT, they were not affected by corn oil feeding MCT-induced ketosis was depressed by glucose administration Neither MCT nor corn oil feeding impaired utilization of glucose by the liver Hepatic lipogenesis was suppressed 50% and 90% by MCT and corn oil feeding, respectively A marked increase of long-chain fatty acids in plasma was observed in rats fed corn oil but not in rats fed MCT The pronounced increase of ketones in MCT-fed rats was closely related to an elevation of octanoate In liver slices of MCT-fed rats, ketogenesis from octanoate was 10-fold higher than from palmitate, and octanoate was oxidized 4 times more rapidly than palmitate The ketosis of MCT-fed rats was depressed by administration of 4-pentenoic acid, a potent inhibitor of fatty acid oxidation These results support the concept that ketosis induced by MCT stems from rapid oxidation of medium-chain fatty acids Hyperinsulinemia, hypoglycemia and depressed lipogenesis resulting from MCT feeding appear to potentiate but not initiate ketosis
74 citations
TL;DR: This annotation presents new data from an analysis of factors influencing haematological remission duration in four consecutive ‘total therapy’ studies of ALL at this hospital and attempts to explain the inferior results in one study.
Abstract: Modern therapy for acute 1 ymphocytic leukaemia (ALL) induces remission and prevents evident central nervous system (CNS) leukaemia in over 90% of children (Simone, 1974). The quality and duration of remission has so improved that therapy may be stopped safely in a significant proportion of patients (Aur et al , 1974). Despite these advances, the current treatment of ALL leaves much to be desired. Modern therapy is complex, costly and largely empirical; it has side effects ranging from merely annoying to life-threatening ; it is potentially carcinogenic and may have latent functional effects on organs such as the gonads, liver, nervous system and heart. The most serious immediate problem facing modern therapy, however, is its inability to prevent haematological relapse in one-third to two-thirds of patients. When haematological relapse occurs in patients receiving chemotherapy at the time, the chance for survival is virtually eliminated. Although the ideal therapy for preventing or delaying haematological relapse is unknown, useful guidelines have been developed. Studies have clearly established the necessity of continuing therapy during remission (Freireich et al, 1964), the superiority of intermittent over daily methotrexate administration (Acute Leukemia Group B, 1965) and the value of giving maximum-tolerated doses of chemotherapy (Pinkel et al , 1971). While methotrexate and mercaptopurine have been the most effective agents for prolonging haematological remission, controlled studies failed to establish the substantial superiority of simultaneous, sequential or cyclic combinations (Frei et al , 1961; Australian Study Group, 1968; Krivit et al , 1968). The addition of other chemotherapeutic agents prolonged remission in some studies (Holland & Glidewell, 1972; Leikin et al , 1969; Pinkel, 1971; Haghbin et al, 1974) and not in others (Aur et a l , 1972; Sackman Muriel et al , 1974; Simone et al , 197~a, b). However, since no regimen has emerged with sufficient efficacy to become standard, the composition of therapy during remission requires periodic re-examination (Simone, I 974). This annotation presents new data from an analysis of factors influencing haematological remission duration in four consecutive ‘total therapy’ studies of ALL at this hospital and attempts to explain the inferior results in one study. As shown in Table I, all studies employed multiple-agent therapy and, after Study V (Aur et a/, 1971a), a series of modifications was tested by randomization in Studies VI (Aur et al, 1972), VII (Aur et a!, 1973) and VIII (S’ imone, 1974; Simone et al, 1975a, b). All patients who attained haematological remission are included in the comparisons between studies except the 20 patients in study VIII randomized to receive methotrexate alone; excessive neurotoxicity required early termination of this limb (Simone et al, 197sa). To quantify the haematological relapse rate for each study and subgroup, the regression coefficient was derived by the least squares method from the proportion of patients remaining in haematological remission at 6 month intervals. Analysis is limited to 24 months in Studies V-VII because most relapses occur during this time and the slopes subsequently become
73 citations
TL;DR: Thrombin binds tightly to human platelets and the platelet receptor recognizes that part of the thrombin molecule on its surface which is blocked by hirudin, and binding studies with serotonin loaded platelets showed a close correlation between Thrombin binding and the release reaction.
Abstract: SUMMARY Thrombin binds tightly to human platelets. The binding reaction is dependent on the thrombin concentration used. At a physiologically significant thrombin concentration, there are about 500 binding sites per platelet with an apparent dissociation constant of 0.02 u/ml. Autoradiography studies of platelets treated with labelled thrombin showed that the thrombin was located on the platelet surface. Separation of the subcellular fractions of platelets treated with labelled thrombin by density gradient centrifugation revealed that the membrane area contained over 80% of the radioactivity initially applied. Furthermore, isolated platelet membranes bind thrombin similar to intact platelets. These data suggest that the receptors for thrombin are located on the platelet membrane. Cytochalasin A, cytochalasin B or prostaglandin E1 did not have any effect on thrombin binding although these agents inhibited platelet aggregation. Thus, binding of thrombin is not sufficient for aggregation of platelets and other steps are involved. These agents do not affect the induction of stimulation but interfere at a later step in the thrombin-platelet interaction. On the other hand, hirudin completely inhibited binding of thrombin to platelets. It appears that the platelet receptor recognizes that part of the thrombin molecule on its surface which is blocked by hirudin. Binding studies with serotonin loaded platelets showed a close correlation between thrombin binding and the release reaction.
69 citations
TL;DR: The initial features, response to therapy, complications, cause of death, and prognostic factors of 171 consecutive children with ANLL are described and compated to historical data for adults with ANll and for children with ALL.
Abstract: The initial features, response to therapy, complications, cause of death, and prognostic factors of 171 consecutive children with ANLL are described and compared to historical data for adults with ANLL and for children with ALL. Major differences between children and adults with ANLL include a higher frequency of CNS leukemia and a lower frequency of early deaths in the children. The most important differences between children with ANLL and ALL are the absence of a peak age of incidence in ANLL and the far better response to therapy in ALL. Among features present at 100,000/mm3 or above, and no palpable hepatomegaly had significantly longer survivals, while patients with platelet counts below 10,000/mm3 had significantly shorter survivals. The frequency and duration of remission were significantly better with three protocols used since 1968 than previously. However, even with these protocols, the results were far from satisfactory, with a complete remission frequency of 66%, a median duration of hematological remission of 6 months, and a median duration of survival of 10 months. The striking contrast of these results in childhood ANLL with current results in childhood ALL underscores the need for novel, imaginative therapeutic approaches for ANLL.
66 citations
TL;DR: Vaccines containing hemagglutinin and neuraminidase subunits were as effective as intact inactivated virus in eliciting a late primary antibody response when injected in saline into rabbits and in hamsters, but the immune response to the subunits could be potentiated by the simultaneous injection of an intact heterologous influenza A or B virus.
64 citations
TL;DR: Perhaps one of the most important lessons to be learned from a review of the developing treatment of acute lymphoblastic leukemia is the importance of the proper design of regimens and their critical factors since these principles can be applied to the treatment of other forms of cancer.
TL;DR: The results reported here suggest that hystovaginectomy and oophorectomy coordinated with chemotherapy and irradiation is an acceptable alternative to pelvic exenteration in patients with sarcoma botryoides of the vagina or uterus.
Abstract: Three children with rhabdomyosarcoma (sarcoma botryoides) of the vagina or uterus were managed by modified radical resection combined with pre- and/or postoperative chemotherapy and high-dose irradiation. This plan of therapy contrasts sharply with the conventional approach: i.e., pelvic exenteration consisting of cystectomy, hystovaginectomy, and oophorectomy, with urinary diversion by ureteroileostomy or ureterosigmoidostomy. Two patients had complete regressions of tumor following preoperative chemotherapy and irradiation. The third patient received no preoperative therapy, but was given postoperative radium implantation, irradiation, and chemotherapy. The surgical approach consisted of hystovaginectomy and oophorectomy without urinary diversion. These patients are free of tumor for 32, 44, and 54 months, respectively. There were no serious toxic reactions to the drugs, nor any significant postoperative urinary tract problems. The results reported here suggest that hystovaginectomy and oophorectomy coordinated with chemotherapy and irradiation is an acceptable alternative to pelvic exenteration in patients with sarcoma botryoides of the vagina or uterus.
TL;DR: It was concluded that newly synthesized P associates rapidly with intracellularucleocapsids and then departs into an unavailable pool, consistent with a transient function of P in nucleocapsid assembly or in RNA synthesis, and suggests a control device to insure that at least half of the nucleocapids produced can never exit as components of virions, but must remain within the cell to serve as RNA-synthesizing complexes.
TL;DR: The therapeutic value of peri toneal dialysis for removing mercury from blood and tissues in young infants, even if associated with a chelating agent, is questionable and remains to be demonstrated.
TL;DR: It appears that ultraviolet-irradiated (but not X-ray irradiated) DNA contains damaged bases that are lost spontaneously after irradiation.
TL;DR: In this article, the frequency and severity of urinary-bladder toxicity were determined retrospectively in a large series of childhood cancer patients treated with either pelvic irradiation and simultaneous cyclophosphamide or cylclophosamide with extrapelvic irradiation.
Abstract: The frequency and severity of urinary-bladder toxicity were determined retrospectively in a large series of childhood cancer patients treated with either pelvic irradiation and simultaneous cyclophosphamide or cylclophosphamide with extrapelvic irradiation. Of 50 patients who received the first combination, 17 (34%) developed urinary-bladder toxicity. Eight of the 17 had transient hematuria and dysuria with complete clearing clinically after cessation of treatment; nine had chronic or intermittent hematuria which persisted after treatment was stopped and often resulted in demonstrable fibrosis and telangiectasia of the bladder. By contrast, of 60 children who received cyclophosphamide and radiotherapy outside the pelvic region, only five (8%) developed hematuria and in all instances it was transient. This comparative study demonstrates a significantly increased frequency and severity of urinary-bladder toxicity in cancer patients receiving pelvic irradiation with simultaneous cyclophosphamide.
TL;DR: Although the rate and duration of induced remissions were notably high, 9 of the 17 patients who relapsed off therapy have again developed recurrent leukemia, indicating that more therapy is needed.
Abstract: A unique population of patients--children who developed recurrent acute lymphocytic leukemia (ALL) following cessation of initial prolonged therapy--was studied. During a 2-year period, 17 such children were admitted to a planned combination chemotherapy program. Complete bone-marrow remissions were achieved in 16 patients, and the median duration of second hematologic remissions was 216 days. These responses were significantly better than those obtained in seven patients who relapsed during the administration of continuation chemotherapy. Although the rate and duration of induced remissions were notably high, 9 of the 17 patients who relapsed off therapy have again developed recurrent leukemia. This result, together with the moderate toxicity encountered during treatment, indicates that more therapy is needed. The equal proportion of bone marrow and meningeal relapses was interpreted to mean that a secon course of preventive central nervous system therapy early in remission may be especially useful.
TL;DR: The data suggest that a limited availability of insulin permits a high rat of ketogenesis and hence induced ketosis in newborn and suckling rats, and the energy requirements of suckling Rats can be met with a reduced risk of hypoglycemia.
Abstract: Extract: A possible regulatory role of insulin in the development of ketosis in newborn and suckling rats was inrestigated. The average plasma concentration of total ketone bodies measured at birth was 0.414 ± 0.037 μmol/ml. Within 24 hr after birth the level of ketones had increased to 4 times its initial value. The 3-to 4-fold increase in plasma ketones was maintained during the first 5 days of life but started to decline thereafter. Plasma insulin of newborn rats at birth (62 ± 8 μU/ml) was comparable to that of fed adult rats (85 ± 10 μU/ml). The levels decreased to 28 μU/ml on the first day of life and stayed low throughout the suckling period despite a tendency to increase at the time close to weaning. The capacities for ketone production in liver homogenates of suckling rats were inversely related to the levels of insulin. Administration of insulin (0.125 mU/g body weight, im) and glucose (1.75 mg/g body weight, ip) both suppressed plasma ketone bodies in suckling rats. Insulin administration increased plasma insulin but failed to decrease plasma glucose. Injection of glucose increased plasma insulin and glucose. Neither insulin nor glucose treatment changed the plasma levels of free fatty acids. These data suggest that a limited availability of insulin permits a high rat of ketogenesis and hence induced ketosis in newborn and suckling rats. Speculation: Developing rats suckled by their dams derive most of their energy from the high fat and low carbohydrate content of milk. The low concentration of insulin in suckling rats not only minimizes utilization of glucose by insulin-dependent tissues but permits a rapid synthesis of ketone bodies that then serve as energy sources for extrahepatic tissues, particularly the brain. Consequently, the energy requirements of suckling rats can be met with a reduced risk of hypoglycemia. Further studies on the effect of insulin on lipolysis, fatty acid oxidation, and ketone synthesis in vitro could add to our understanding of the action of insulin in reversing ketosis of suckling rats.
TL;DR: The sialoglycoproteins of the human erythrocyte membrane can be separated into at least eight periodic acid Schiff-positive components using sodium dodecyl sulfate gel electrophoresis in the discontinuous buffer system of Laemmli.
TL;DR: In this article, a laryngeal sarcoidosis was observed in the absence of other systemic manifestations of the disease and the vocal cords were rarely abnormal, which explains why airway obstruction rather than vocal changes usually occurs.
TL;DR: Most of the virus-specific RNA molecules isolated from the cytoplasm of BHK-21 cells infected with frog virus 3 did not contain poly(A) tracts of sufficient length to permit the RNA to bind to oligo(dT) cellulose, and the bound RNA was representative of the whole spectrum of vaccinia virus RNA size classes.
TL;DR: Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pneum onitis and leukemia, and cure was achieved with a second course of chloramphenicol therapy.
TL;DR: It is demonstrated that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.
Abstract: Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.
TL;DR: The data indicate that transcription in FV3-infected cells is regulated at two levels—qualitative, which depends on viral DNA synthesis, and quantitative, which does not.
TL;DR: Exposure of rabbit spleen cell cultures to i- RNA isolated from T2 phage-exposed rabbit peritoneal exudate cells induces the synthesis of antigen and allotype specific 19S proteins even in the presence of actinomycin D, indicating that i-RNA functions as mRNA and contains the information required to code forThe synthesis of IgM antibodies.
01 Jan 1976
TL;DR: Hypotrichous ciliates (e.g., Euplotes, Oxytricha, Stylonychia), like most other ciliated protozoans, possess two morphologically and functionally distinct nuclei, macron nuclei and micronuclei.
Abstract: Hypotrichous ciliates (e.g., Euplotes, Oxytricha, Stylonychia), like most other ciliated protozoans, possess two morphologically and functionally distinct nuclei, macronuclei and micronuclei. The macronuclei are large, divide amitotically, and function as somatic nuclei with distinct nucleoli and active ribonucleic acid (RNA) synthesis. Micronuclei are small, divide by mitosis, and have little or no RNA synthesis. The primary function of a micronucleus is to give rise to a new macronucleus each time the cells undergo conjugation.
TL;DR: This is the first reported evidence implicating porphyrin a as a precursor of the heme of cytochrome c oxidase in copper-deficient yeast cells, and demonstrates that a porph Kyrin precursor of heme a is synthesized and integrated into the apo-oxidase.
TL;DR: Results suggest that the adenosine activation of concanavalin A agglutination of intact human erythrocytes is mediated through a metabolic conversion ofAdenosine to a rapidly turned over metabolite which participates directly in the activation of agglUTination.
TL;DR: For the patients in this study, filtration of intravenous fluids with a 5-mum mesh filter appeared to be a feasible and effective means of reducing postinfusion complications.
Abstract: A double-blind study was conducted to determine the effectiveness of 5-mum final filtration in preventing phlebitis secondary to intravenous fluid administration. An experimental administration set which contained distal portion of the tubing was used for patients randomly assigned to receive filtered intravenous solutions. An identical administration set minus the filter was used in the control group to allow double-blind evaluation of the injection site. Data were collected on 49 patients whose average age was eight years and one month. Most patients had a primary diagnosis of acute lymphocytic or myelocytic leukemia or solid tumor. The patients' injection sites were evaluated daily for clinical findings of phlebitis (erythema, induration, heat, erythematous-streak and discomfort). The incidence of phlebitis was significantly lower (p less than 0.01) in patients receiving filtered intravenous solutions. For the patients in this study, filtration of intravenous fluids with a 5-mum mesh filter appeared to be a feasible and effective means of reducing postinfusion complications.
TL;DR: Prevention and treatment of complications are essential to the optimal outcome in the child with a malignant neoplasm.