Showing papers by "St. Jude Children's Research Hospital published in 1973"

The central nervous system in childhood leukemia: I. The arachnoid

Abstract: A histopathologic study was performed to evaluate the distribution and extension of intracranial leukemic infiltrates and their relationship to other morphological disturbances of the central nervous system (CNS) in childhood acute lymphocytic leukemia Of 126 brains examined, 70 had arachnoid leukemia at the time of autopsy The earliest evidence of leukemia was seen in the walls of superficial arachnoid veins With more advanced arachnoid leukemia, the disease was seen to extend into the deep arachnoid surrounding blood vessels as they course through the brain The arachnoid leukemia followed a predictable expanding pattern to eventual invasion of brain parenchyma with destruction of the pia-glial membrane Leukemic infiltrate at the capillary-neural tissue interface was present only following destruction of pia-glial membrane secondary to deep arachnoid leukemia Arachnoid fibrosis and certain brain parenchymatous lesions were found in association with arachnoid leukemia The brain lesions included gliosis, necrosis, cerebral hemorrhage, and nonhemorrhagic degenerative encephalopathy This study demonstrates that CNS leukemia is primarily an arachnoid disease Disturbances of brain parenchyma apparently result from leukemic extension through pia-glial membrane or interference with local perfusion due to constriction of blood vessels by perivascular arachnoid leukemia

Prevention of central nervous system leukemia by irradiation.

Abstract: During the past 10 years, 1962 to 1972, we have administered irradiation to the central nervous system (CNS) during the first few weeks of remission of acute lymphocytic leukemia (ALL) as an integral part of a treatment plan aimed at cure of ALL. Its purpose has been to eradicate residual leukemia in the CNS and thus prevent CNS relapse. The results indicate that craniospinal irradiation alone, 2400 rads, or cranial irradiation, 2400 rads, with simultaneous intrathecal methotrexate is effective in -preventing CNS relapse. This results in marked improvement in complete remission duration and a 50% frequency of long-term leukemia-free survival and possible cure. Although intermittent intrathecal methotrexate during remission is said to reduce the incidence of CNS relapse by one half, a 15-fold reduction results from adequate preventive CNS irradiation. Until a better method is found, all children with ALL should receive adequate CNS irradiation early during remission in order to prevent CNS relapse and to prolong complete remission.

Comparison of Methods for Identification of Pneumocystis carinii in Pulmonary Aspirates

Abstract: Specimens obtained by percutaneous pulmonary needle aspiration from patients suspected of having Pneumocystis carinii pneumonitis were examined by five staining methods for the presence of Pneumocystis carinii . With polychrome methylene blue (Hema-Tek), Wright, and Giemsa stains, Pneumocystis carinii could unequivocally be identified in three developmental stages: “cyst,” “sporozoite,” and “trophozoite.” Although the contrast of organism against host tissue cells was not outstanding, the simplicity, consistency, and rapidity of the methods were the major advantages. Toluidine blue O stain and methenamine silver nitrate stains provided easy recognition of the organisms, with marked contrast between the organisms and host cells. However, the intracystic structures and trophozoites could not be identified with these stains. It is suggested that the clinical specimen be stained first with the more rapid and simple stains, and if the organism is not found, the methenamine silver stain should be used to arrive at a final conclusion.

Infection during induction of remission in acute lymphocytic leukemia

Abstract: The effects of infectious diseases during the transition from untreated acute lymphocytic leukemia to induction of remission were studied in 100 children enrolled consecutively into a standardized protocol for chemotherapy. During the initial 6 weeks of therapy, 30 patients had no evidence of infection; 19 had episodes of fever without other evidence of infection, and 51 had one or more episodes of infectious diseases. Most of the infections and febrile episodes occurred prior to and during the first week of therapy. Bacterial sepsis or meningitis and systemic candidiasis accounted for the serious infections. The incidence was inversely related to the absolute neutrophil count. Immunoglobulin values were normal. The occurrence of infection during the initial 6 weeks of anticancer therapy had no relation to success or failure of induction and continuation of complete remission of the leukemia.

Mycoflora in cystic fibrosis: some ecologic aspects of Pseudomonas aeruginosa and Candida albicans.

Abstract: The mycotic and bacterial flora of 65 patients with cystic fibrosis was studied.C. albicans andP. aeruginosa were present in 33% and 43% of sputa samples, respectively; only 6.5% harbored both organisms. The mycotic flora of the nasopharynx, rectum and skin of the cystic fibrosis patients was similar to that of children with other chronic lung diseases and to that of normal children.In vitro studies clearly revealed inhibition ofC. albicans byP. aeruginosa. It is suggested thatP. aeruginosa, so prevalent with cystic fibrosis, has an inhibitory effect onC. albicans and that this interaction is effective to some extent in preventing candidal infection.

Changes in accessibility of plasma membrane protein as the result of tryptic hydrolysis.

Abstract: IT is now known that the plasma membrane is not a simple, inert envelope enclosing the cell but plays an important role in the regulation of cellular functions. The transformation of a normal cell into a cancer cell, for example, is correlated with alterations of the plasma membrane2–4, which have been detected using plant lectins which bind to specific carbohydrate residues5. When the glycoprotein on the surface of the plasma membrane is properly orientated, the polyvalent lectins bind to the carbohydrate residue, thus cross-linking cells and inducing agglutination.

Naloxone reveral of non - narcotic induced apnea

Abstract: A 46-year-old woman was treated for unexplained coma with intravenous lactated Ringer's solution, intravenous glucose, and a gastric lavage. During therapy respiratory depression progressed to apnea. Naloxone hydrochloride was administered intravenously, in three doses, each of 0.4 mg, over a period of ten minutes. Normal breathing and a lightening of coma occurred within minutes, and consciousness returned within four hours. Laboratory studies on blood, urine and lavage returns confirmed the history of ingestion of barbiturate, diazepam and alcohol. No narcotics were detected.

Chronic subdural hematoma in childhood acute leukemia

Abstract: Chronic subdural hematomas were present at necropsy in 13 of 126 children with acute lymphocytic leukemia (10.3%), and were absent in other types of acute leukemia. Thrombocytopenia, which was usually associated with acute subdural bleeding, was thought to have an insignificant role in the pathogenesis of chronic subdural hematoma. Clinically, the frequent coexistence of meningeal leukemia and chronic subdural hematoma made diagnosis difficult. We believe that chronic subdural hematoma should be suspected in children with acute lymphocytic leukemia and neurologic symptoms who have no pleocytosis or blast cells in the cerebrospinal fluid, seizures, focal neurologic signs, or poor clinical response to therapy for meningeal leukemia. In view of the improving prognosis of acute lymphocytic leukemia, an aggressive diagnostic and therapeutic approach is advocated.

Cell-Free Translation of Paramyxovirus Messenger RNA

Abstract: Polypeptides corresponding in electrophoretic mobility to virion polypeptides 1, 3, and 5 were made in a reticulocyte cell-free system to which 18S RNA from Sendai virus-infected cells was added. Immune precipitation was used to select relevant polypeptides from endogenous products. The cell-free product corresponding to virion polypeptide 3 (the nucleocapsid structure unit) was the most abundant; its tryptic peptides comigrated electrophoretically with tryptic peptides of polypeptide 3 isolated from virions. Other sedimenting classes of RNA from infected cells were tested; only the 28S fraction showed slight activity. Virion 50S RNA was inactive. These findings support the hypothesis that complementary RNA transcripts of paramyxovirion RNA are the templates for viral proteins.

Molecular Morphology of Ribosomes

Abstract: The effect of chain initiation factor 3 (IF-3) and ribosomal protein S1 on ribosome conformation was measured by alterations in the reactivity of individual ribosomal proteins to lactoperoxidasecatalyzed iodination. Escherichia coli ribosomes, under ionic conditions conducive to the binding of IF-3 and S1, were enzymatically iodinated in the presence and absence of IF-3 and/or S1. Our results demonstrate that the binding of ribosomal protein S1 to isolated 30-S subunits induces a conformational change in the small subunit as reflected by the altered reactivity of proteins S3, S7, S12, S19 and S21 to enzymatic iodination. We have also previously shown [FEBS Lett. 71, 347–350 (1976)] that the binding of IF-3 to isolated 30-S subunits alters the reactivity of ribosomal proteins S2, S5, S8, S11 and S17. These data suggest that the factor does not influence 30-S subunit conformation in the same manner as ribosomal protein S1. The binding of IF-3 or S1 to 70-S ribosomes results in the same conformational change to 30-S subunits as that obtained with isolated 30-S subunits. This effect is additive when both proteins are bound to the 70-S particle. Ribosomal protein S1 does not appear to influence 50-S conformation. However, the binding of IF-3 to 50-S and 70-S particles results in the altered reactivity of several 50-S ribosomal proteins, the most prominent of which is L10. Our results suggest that IF-3 interacts with 30-S, 50-S and 70-S particles, and that part of the 70-S binding site of the factor is in the region of L7/L12 on the 50-S subunit.

Metastatic involvement of the heart in childhood rhabdomyosarcoma

Abstract: Eight of 23 patients who succumbed with childhood rhabdomyosarcoma had metastases to the heart. Each of these eight patients had metastatic tumor in the visceral pericardium, and seven patients had metastases in the myocardium. These eight patients exhibited extensive involvement of the skull, long bones, lungs, lymph nodes, and bone marrow. In two of these eight patients, cardiac tumor with intractable congestive heart failure contributed to death. Three additional patients had pericardial effusions secondary to neoplasm. The presence of rhabdomyosarcoma cells in antemortem bone marrow aspirates was noted in each case associated with postmortem findings of extensive metastatic tumor, including metastases to the heart. Although the endocardium was frequently infiltrated by tumor, the conduction tissue was spared and ventricular activation usually occurred in a normal manner.

Stimulation of Sendai Virion Transcriptase by Polyanions

Abstract: Exogenous polyribonucleotides stimulated the ribonucleic acid (RNA) transcriptase in Sendai virions. Added yeast RNA, polyadenylic acid, or polycytidylic acid increased incorporation of 3H-guanosine monophosphate as much as fivefold. The products of stimulated reactions were virus-specific as determined by hybridization with Sendai virion RNA, but they sedimented more slowly (13s) than the product of an unstimulated reaction (16s). The stimulating activity was nondialyzable and heat stable, but was abolished by alkaline hydrolysis. Nucleoside monophosphates, individually or in combination, were ineffective, confirming the requirement for a polymer. Among other substances tested for effects on Sendai virion transcriptase, polyaspartic acid and polyglutamic acid stimulated the enzyme; polyinosinic acid, polyuridylic acid, and polyamines had no effect; and dextran sulfate and polyvinyl sulfate were inhibitory.

Thermophilic fungi in the mycoflora of man and environmental air

Abstract: The objective of this study was to determine if thermophilic fungi exist in the mycoflora of man and in the aeroflora of his environment.Humicola lanuginosa andHumicola grisea were isolated from 5 of 55 samples of outside air. Three thousand cultures were taken from the nasal mucosae, skin surfaces and recta of 570 children. Cultures were incubated at 50°C. Thermophilic fungi were isolated from 6 of 287 children receiving immunosuppressive therapy for malignancies and from 1 of 283 normal children.H. lanuginosa was recovered from the skin of one, the rectum of one and the nasal mucosae of three patients.Mucor pusillus was isolated from the nasopharynges of two patients.

Thyroid peroxidase-catalyzed iodination and coupling reactions and their control.

Abstract: The biosynthetic pathway of the important hormone thyroxine, or triiodothyronine, may be divided into a number of steps. The aspects of this biosynthetic path that are most unique to the thyroid are the steps involved in the metabolism of iodide. There is evidence that tissues other than the thyroid can concentrate iodine and incorporate it into protein.',' The thyroid, however, is the site of most of the anabolic metabolism of iodide in the mammals. FIGURE 1 shows the metabolic steps that are unique to the thyroid. The first of these unique steps is the iodination of the tyrosine residues of thyroglobulin to yield monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues. The second step is the oxidative coupling of two residues of DIT to yield thyroxine residue. The thyroglobulin then passes out of the cell into the colloid. Finally, the iodinated thyroglobulin is returned to the cell, where it is hydrolyzed to yield free thyroxine. The first two reactions, iodination and oxidative coupling, are depicted as being catalyzed by a peroxidase. The hydrolysis catalyzed by a thyroid protease has been considered to be unrelated to the peroxidase-catalyzed reactions. The data presented here demonstrate that there is an interrelationship between these reactions and the possible control of peroxidase-catalyzed reactions that is provided by the hydrolytic step.

Carbohydrate metabolism during differentiation (sclerotization) of the myxomycete Physarum flavicomum.

Abstract: The metabolism of carbohydrates during differentiation (sclerotization) of Physarum flavicomum was studied using the radiorespirometric technique. After about 36 h in a sclerotization (starvation) medium the metabolism declined to a level characteristic of the dormant state. Sclerotia incubated in complete growth medium quickly reverted to a metabolically active state and by 9 h they regained about 50% of their metabolic potential.

Bleomycin in xeroderma pigmentosum.

Abstract: A child with multiple squamous cell carcinomas associated with xeroderma pigmentosum (XP) was treated with Bleomycin on a twice weekly schedule utilizing a dosage of 30 mg/m2. Satisfactory clinical responses of facial and scalp lesions were observed. A total cumulative dose of 441 mg (630 mg/m2) was administered before fatal pulmonary toxicity occurred after 18 weeks of therapy. Postmortem examination revealed a diffuse pulmonary disease consisting of atypical desquamative alveolitis and interstitial inflammatory changes with varying degrees of fibrosis.