Showing papers by "St. Jude Children's Research Hospital published in 1986"
TL;DR: The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptors for macrophage colony stimulating factor (CSF-1).
Abstract: The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptor for macrophage colony stimulating factor (CSF-1). Common structural features include the presence of long sequences that interrupt the tyrosine-specific protein kinase domains of each molecule. The PDGF and CSF-1 receptors also share a characteristic distribution of extracellular cysteine residues. Ubiquitin is covalently bound to the purified PDGF receptor, the human gene for which is on chromosome 5.
1,144 citations
TL;DR: Partial amino acid sequence analysis of a purified lymphocyte homing receptor demonstrates the presence of two amino termini, one of which corresponds precisely to the amino terminus of ubiquitin, leading to a proposed model of the receptor complex as a core polypeptide modified by glycosylation and ubiquitination.
Abstract: Partial amino acid sequence analysis of a purified lymphocyte homing receptor demonstrates the presence of two amino termini, one of which corresponds precisely to the amino terminus of ubiquitin. This observation extends the province of this conserved polypeptide to the cell surface and leads to a proposed model of the receptor complex as a core polypeptide modified by glycosylation and ubiquitination. Independent antibodies to ubiquitin serve to identify additional cell surface species, an indication that ubiquitination of cell surface proteins may be more general. It is proposed that functional binding of lymphocytes to lymph node high endothelial venules might involve the ubiquitinated region of the receptor; if true, cell surface ubiquitin could play a more general role in cell-cell interaction and adhesion.
271 citations
TL;DR: The discovery of EBV shedding in its cell-free infectious form from the uterine cervix raises the possibility of venereal transmission, neonatal infection, and EBV involvement in cervical pathology.
234 citations
TL;DR: The deletion of one or both of these genes may be important in the pathogenesis of myelodysplastic syndromes or of ANLL, and both genes were present on the rearranged chromosome 5.
Abstract: By in situ chromosomal hybridization, the GM-CSF and FMS genes were localized to human chromosome 5 at bands q23 to q31, and at band 5q33, respectively. These genes encode proteins involved in the regulation of hematopoiesis, and are located within a chromosome region frequently deleted in patients with neoplastic myeloid disorders. Both genes were deleted in the 5q-chromosome from bone marrow cells of two patients with refractory anemia and a del(5)(q15q33.3). The GM-CSF gene alone was deleted in a third patient with acute nonlymphocytic leukemia (ANLL) who has a smaller deletion, del(5)(q22q33.1). Leukemia cells from a fourth patient who has ANLL and does not have a del(5q), but who has a rearranged chromosome 5 that is missing bands q31.3 to q33.1 [ins(21;5)(q22;q31.3q33.1)] were used to sublocalize these genes; both genes were present on the rearranged chromosome 5. Thus, the deletion of one or both of these genes may be important in the pathogenesis of myelodysplastic syndromes or of ANLL.
216 citations
TL;DR: Two monoclonal antibodies against different determinants on the EBV/C3d receptor of B cells were shown to react with pharyngeal epithelia in a cell differentiation-dependent manner, raising the possibility of direct virus entry into a naturally exposed epithelium.
175 citations
TL;DR: Terminal deoxynucleotidyl transferase is used to clear the improperly terminated cDNA from these pileup sites, revealing the correct sequence of template RNA's 5'-terminal base.
161 citations
TL;DR: The lymphocyte cell surface receptor for the high endothelial venules (HEV's) of peripheral lymph nodes is specifically recognized by the monoclonal antibody MEL-14, which is likely to reflect control of the expression of the HEV core polypeptide or its level or form of ubiquitination.
Abstract: The lymphocyte cell surface receptor for the high endothelial venules (HEV's) of peripheral lymph nodes is specifically recognized by the monoclonal antibody MEL-14. Three independent complementary DNA (cDNA) clones, each of which encodes the protein ubiquitin, were detected by virtue of the expression of the MEL-14 antigenic determinant on cDNA-beta-galactosidase bacterial fusion proteins. The antigenic determinant defined by MEL-14 resides in the carboxyl terminal 13-amino-acid proteolytic peptide of ubiquitin, but is undetected in intact undenatured ubiquitin and other cellular ubiquitinated proteins. Antisera and monoclonal antibodies to ubiquitin determinants bind to the surface of both HEV-receptor positive and negative cell lines. The MEL-14-identified cDNA clones hydridize to RNA transcripts that encode tandemly repeated ubiquitins. Sequence analysis of these polyubiquitin cDNA's does not identify a leader sequence for export to the cell surface. The expression of the MEL-14 epitope of ubiquitin depends upon its local environment. The steady-state levels of expression of the ubiquitin messenger RNA's do not correlate with either the tissue derivation of the RNA or the expression of the lymphocyte HEV receptor. Regulation of the expression of the HEV receptor is not likely to reflect the transcriptional control of ubiquitin genes, but rather to reflect control of the expression of the HEV core polypeptide or its level or form of ubiquitination.
154 citations
TL;DR: Findings offer an explanation for the majority of early treatment failures in childhood ALL, including those previously attributed to ploidy classification.
148 citations
TL;DR: It is suggested that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12, in children with acute lymphoblastic leukemia whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12.
121 citations
TL;DR: Crosslinking and low temperature studies argue against redistribution of the HA and NA after antibody attachment and indicate that the NA on influenza virus occurs in patches.
115 citations
TL;DR: It is demonstrated that isolates of P. carinii obtained from different species are not antigenically identical, and all six monoclonal antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons.
Abstract: Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.
TL;DR: Flow cytometry provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins as well as detecting platelet membrane defects such as Glanzmann's thrombasthenia.
TL;DR: It is shown that introduction of the v-fms gene into simian virus-40 (SV40)-immortalized, CSF-1 dependent macrophages renders them independent of CSf-1 for growth and tumourigenic in nude mice.
Abstract: The McDonough strain of feline sarcoma virus (SM-FeSV) transforms fibroblast cell lines in culture and produces fibrosarcomas in domestic cats. SM-FeSV does not induce haematopoietic malignancies in spite of the fact that its viral oncogene, v-fms, codes for a glycoprotein related to the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. The v-fms-coded polypeptide includes the complete extracellular domain of the c-fms proto-oncogene product and retains the ability to bind CSF-1 specifically. The two molecules have very similar sequences except at their extreme carboxyl terminal ends where 40 amino acids of the c-fms-coded glycoprotein are replaced by 11 unrelated residues in the v-fms product. Autophosphorylation of the c-fms gene product on tyrosine is enhanced by CSF-1 addition, whereas phosphorylation of the v-fms-coded glycoprotein appears to be constitutive. We now show that introduction of the v-fms gene into simian virus-40 (SV40)-immortalized, CSF-1 dependent macrophages renders them independent of CSF-1 for growth and tumourigenic in nude mice. These factor-independent cell lines express unaltered levels of the c-fms product which is down-modulated in response to either CSF-1 or the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The induction of factor independence by a non-autocrine mechanism suggests that the v-fms product is an unregulated kinase that provides growth stimulatory signals in the absence of ligand.
TL;DR: It is established that a single critical point mutation in the hemagglutinin gene of the avirulent A/Chicken/Pennsylvania/1/83 (H5N2) influenza virus was probably all that was required to produce the highly virulent Chicken/Penn Pennsylvania virus; theAvirulent virus already possessed the other genes necessary for virulence.
TL;DR: The data suggest that childhood ALL of B lineage with more than two mu heavy-chain genes, but without extra copies of chromosome 14, may be more resistant to therapy.
TL;DR: Stark differences between patients in susceptibility to progressive nephrotoxicity were disclosed and persistent increases in urinary N-acetyl-β-D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage.
Abstract: We assessed the acute and chronic effect of multiple courses of cisplatin therapy on renal tubules by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl-β-D-glucosaminidase, and total protein. Urine specimens were obtained before and after doses of cisplatin (90 mg/m2) given to 12 patients. Each dose of cisplatin induced transient increases in enzyme excretion, followed by proteinuria 3–5 days later. Transient enzymuria after the last cisplatin dose was significantly greater than that after the first dose. Moreover, persistent increases in urinary N-acetyl-β-D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage. Our findings disclosed striking differences between patients in susceptibility to progressive nephrotoxicity.
TL;DR: Chloroquine is a modulator of anticancer drug action in the CEM/VLB100 cell line and contains more cytoplasmic vacuoles than their drug-sensitive counter-parts.
TL;DR: Observations suggest that translocation t(10;14)(q24;q11) is specific for T cell neoplasia and that a gene in chromosomal band 10q24, possibly the TdT gene, plays an important role in T cellNeoplasia when its expression or coding sequence is altered by aberrant recombination involving a T cell antigen receptor gene.
TL;DR: Results of studies of the Pediatric Oncology Group (POG) demonstrate that high white blood cell count at diagnosis, very young or older age within childhood, and the presence of a mediastinal mass or central nervous system leukemia predict a poor prognosis within the context of certain therapies.
Abstract: Although the prognosis of children with ALL has improved markedly, approximately one-half of children continue to relapse. Clinical and biologic features of ALL have been studied at the time of diagnosis and many of these features have been shown to predict the risk of relapse, permitting tailoring of therapy based on relapse hazard. Results of studies of the Pediatric Oncology Group (POG) detailed here demonstrate that high white blood cell (WBC) count at diagnosis, very young or older age within childhood, and the presence of a mediastinal mass or central nervous system leukemia predict a poor prognosis within the context of certain therapies. However, not only age and WBC count, but immunophenotype of ALL as well, were especially predictive of prognosis in these POG studies. The information reviewed here has special importance for the planning of clinical trials for children with ALL.
TL;DR: The use of continuous 24-hour chelation to maintain NTBI at low levels may prevent progressive iron toxicity in patients who first received chelation therapy at an older age or who already have evidence of cardiac damage.
TL;DR: Data derived in tumor cytosols suggested that FdUMP levels in situ were not rate-limiting for formation of covalent ternary complex, but that accumulation of dUMP would retard the rate of complex formation, and inhibition of phosphatase activity did not alter the net rate of dissociation of the Fdump-thymidylate synthase-[6R]-CH2-H4PteGlu complex.
TL;DR: In a multivariate analysis, pseudodiploidy emerged as the strongest factor for predicting relapse in pre-B ALL, which explains, at least in part, the poor treatment outcome reported for children with this subtype of leukemia.
TL;DR: The occurrence of P clusters at different locations on intracellular nucleocapsids indicates that P is a mobile molecule; this suggestion is consistent with P's role in viral RNA synthesis.
TL;DR: Results reveal at least three patterns of production of principal erythrocyte proteins during EP‐mediated terminal differentiation of FVA‐infected erythroid cells.
Abstract: Erythropoietin (EP) controls the terminal phase of differentiation in which proerythroblasts and their precursors, the colony forming units-erythroid (CFU-e), develop into erythrocytes. Biochemical studies of this hormone-directed terminal differentiation have been hindered by the lack of a homogeneous population of erythroid cells at the developmental stages of CFU-e and proerythroblasts that will synchronously differentiate in response to EP. Such a population of cells can be prepared from the spleens of mice with the acute erythroblastosis resulting from infection with anemia-inducing Friend virus (FVA). Using these FVA-infected erythroid cells, which were induced to differentiate with EP, four proteins other than hemoglobin that have key functions in mature erythrocytes were monitored during the 48-hour period of terminal differentiation. Synthesis of spectrin and membrane band 3 proteins were determined by immunoprecipitation and SDS-polyacrylamide gel electrophoresis; accumulation of the cytoskeletal protein band 4.1 was monitored by immunoblotting; carbonic anhydrase activity was measured electrometrically. Band 3 synthesis and band 4.1 accumulation could be detected only after exposure of the cells to EP. Spectrin synthesis was ongoing prior to culture with EP, but it did increase after exposure to the hormone. Carbonic anhydrase-specific activity changed very little throughout the terminal differentiation process. These results reveal at least three patterns of production of principal erythrocyte proteins during EP-mediated terminal differentiation of FVA-infected erythroid cells. Depending on the specific protein examined, de novo synthesis can be induced by EP, an ongoing production can be enhanced by EP, or the production of a protein can be completed at a developmental stage prior to EP-mediated differentiation in these cells.
TL;DR: The threshold for thyrotropin suppression in congenital hypothyroidism and the effect of alterations in the pituitary-thyroid axis on hypothalamic content and in vitro release of somatostatin-like immunoreactivity are identified.
TL;DR: Anti-C antibodies did not inhibit viral RNA synthesis when added to an extract of infected cells, consistent with the conclusion that the C proteins have no direct role in viral transcription, since virions lack C proteins but are transcriptionally active.
TL;DR: It is concluded that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed acute myeloid leukemia.
TL;DR: The presence of these scattered photons leads to only minor dose errors in clinical applications if simple procedures are followed to account for their contribution.
Abstract: When a beam‐modifying filter such as a wedge or a compensator is placed in an x‐ray beam, scatteredphotons are generated in the filter material. The magnitude of the dose contribution from these photons for a 4‐MV x‐ray beam was measured. At a distance of 30 cm from the filter, a copper sheet of 1‐cm thickness produced a dose contribution on the centerline of about 6% of the transmitted primary dose in a 20×20 cm2 field. At the edges of the beam, this contribution was only about one‐half that on the centerline. The presence of these scatteredphotons leads to only minor dose errors in clinical applications if simple procedures are followed to account for their contribution.
TL;DR: The assumption that monoclonal antibodies, which failed to inhibit hemagglutination of the virus yet neutralized viral infectivity, inhibited the fusion step in the viral replication process by interfering with a low pH-induced conformational change in the HA molecule is supported.
TL;DR: Comparison of the deduced amino acid sequences of both proteins revealed a conserved 18 amino acid sequence that may have functional significance, suggesting that the L gene of Sendai virus is polycistronic.