Tollefsen, md, phD (1980. Evan Sadler, md, phD (1984 lee ratner, md, phD (1985 timothy. Ley, md (1986 and Stanley. Korsmeyer, md (1986 all of whom went on to have distinguished careers in academic medicine. In 1973, most oncology patients at Barnes Hospital and The jewish Hospital. Louis were cared for by private physicians; among them was Virgil Bud loeb,., md, who served on the board of directors of the American Society of Clinical Oncology in 1970 and later as president of the American Cancer Society.
Thalassemia - anemia associated with impaired globin synthesis
Brown, md, led the division from 19His research focused on several aspects of iron metabolism, including the function of transferrin and the role of chelating agents in argumentative the treatment of iron overload. Continued Focus on Basic Research. Kornfeld, md, and Philip. Majerus, md, joined the faculty in 1966, each having completed two years of residency in internal medicine and two to three years of research training at the national Institutes of health (NIH). In 1973, they became co-directors of the newly designated division of Hematology-Oncology. Kornfelds laboratory elucidated the mechanism by which lysosomal enzymes are transported from their site of synthesis in the rough endoplasmic reticulum to their final destination in lysosomes. Majeruss laboratory discovered how aspirin inhibits platelet function and characterized many of the enzymes involved in inositol phosphate metabolism. In little more than a decade, they recruited Robert. Allen, md (1973 Thomas. Deuel, md (1977 george. Broze,., md (1980 douglas.
Early Scientific Achievements, other notable achievements during the first two decades of the division included demonstration that febrile transfusion reactions are caused by sensitivity to donor leukocytes and platelets (Thomas. Brittingham and Hugh Chaplin,., pdf md successful treatment of polycythemia vera with radioactive phosphorus (Edward. Reinhard, md, and colleagues and identification of hemoglobin E (Virginia minnich). Moore hired Virginia minnich, who had a masters degree in food science, in 1939 as his technician at a starting salary of 75 per month; she retired in 1984 as a full professor of medicine, the first person with neither an md nor a phD. She was an expert morphologist who trained several generations of hematology fellows in this area. After moore was appointed chairman of the department of Medicine in 1955, harrington became chief of the hematology division. A few years earlier, at the age of 28, harrington had become the youngest member ever elected to the American Society for Clinical Investigation. He continued to investigate the pathogenesis and treatment of immune thrombocytopenia, and he studied the effects of high-dose glucocorticoids in patients with lymphocytic leukemia and lymphoma. In 1964, harrington moved to the University of miami, where he became chairman of the department of Medicine.
According to Oliver. Lowry, md, phd, moore belonged to a new breed of clinicians who thought that basic medical science is too important to be left to the preclinicians (from a biographical memoir published by the national Academy of Sciences in 1994). His laboratory, which became a leading training center for hematologists during the 1940s, made fundamental contributions to our understanding of iron absorption, transport and storage. In a remarkable series of clinical investigations with William. Harrington, md, in the early 1950s, they established that thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP) is caused by a stable factor in the globulin fraction of plasma. These studies involved intravenous injection of plasma from patients with itp into normal volunteers - among them moore and Harrington. In similar studies, moore and his colleagues elucidated the mechanism of quinine-induced thrombocytopenia.
For the synthesis of haemoglobin
However, at longer incubation periods, the rate of globin synthesis with poly(A)-free mrna is considerably lower than with native mRNA. Similar differences in the template activity of the two mrna preparations were found with a cell-free extract of Krebs ii ascites tumor. It is concluded that the presence of the 3tex"right poly(A)-rich sequence in mrna is required to ensure high functional stability., keywords system *Protein biosynthesis, Adenine nucleotides metabolism, Animals, Anura, carcinoma, krebs 2/metabolism, cell-Free system, Chromatography, gel, female, globins biosynthesis, half-Life, hemoglobins/biosynthesis, histidine/metabolism, ovum/metabolism, polynucleotides metabolism, rabbits. Gov/pubmed/4528715, author huez,. The cartilage-hair hypoplasia anauxetic dysplasia (chh-ad) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (mdwh). Chh-ad spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis.
The most severe phenotype, ad, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations plan of the chh-ad spectrum disorders are variable, even within the same family. Origins of the hematology division, the hematology division was founded in 1938 by carl. Moore, md, a native. Louisan and graduate of Washington University School of Medicine.
Ti - a previously undetected pseudogene in the human alpha globin gene cluster. Ab - the sequence of the dna between two pseudogenes in the human alpha-like globin gene cluster has been determined. Comparison of this sequence with sequences from other alpha-like globin gene clusters revealed another pseudogene, psi alpha 2, between the previously recognized pseudogenes zeta 1 and psi alpha. Therefore, the human alpha-like globin gene family is organized 5'-zeta 2-zeta 1-psi alpha 2-psi alpha 1-alpha 2-alpha 1-3'. The new pseudogene psi alpha 2 is very close to zeta 1, beginning only 65 base pairs 3' to the polyadenylation site of zeta. The first exon and the first intron of psi alpha 2 are interrupted by large inserts which are flanked by short (6 to 8 base pairs) direct repeats.
The pseudogene psi alpha 2 lacks a promoter for transcription by rna polymerase ii, the first exon is highly divergent, one splice site is mutated, and five different frameshift mutations have occurred in the coding regions. Thus psi alpha 2 cannot encode a globin polypeptide. This pseudogene was not recognized in previous hybridization analyses of the human alpha-like globin gene cluster, and our discovery of it by sequence analysis suggests that divergent copies of a large number of genes may comprise a substantial fraction of the slowly renaturing dna. Mh - base sequence ; Comparative study ; Genes ; Globin genetics ; Human ; Linkage (Genetics) ; Nucleic Acid Hybridization ; Sequence homology, nucleic Acid ; Support,. So - nucleic Acids Res 1986 Feb 25;14(4 1903-11. @article 3119, title role of the polyadenylate segment in the translation of globin messenger rna in Xenopus oocytes, journal Proc Natl Acad Sci, volume 71, number 8, year 1974, note huez, gmarbaix, ghubert, eleclercq, mnudel, usoreq, hsalomon, rlebleu, brevel, mlittauer, u zproc Natl Acad Sci. 1974 Aug;71(8 3143-6., month aug, pages 3143-6, edition 1974/08/01, abstract The translations of native messenger rna for rabbit globin and that of poly(A)-free globin messenger rna have been compared after injection into xenopus oocytes. The initial rate of translation of poly(A)-free mrna is close to that found with intact mRNA.
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Ab - we previously hypothesized that a 2 nucleotide deletion, causing a a-greater than C change at position -3 essay preceding the atg initiation codon of alpha globin gene, reduced translation efficiency of alpha globin mrna and was responsible for a form of alpha thalassemia displayed. We presently show that this deletion leads to a 30-45 reduction in translation efficiency of synthetic alpha globin mrna in rabbit reticulocyte lysate. In other experiments, we constructed alpha/G gamma hybrid globin genes in which the 3' end of normal or mutated alpha globin genes downstream to the atg initiation codon was substituted by the 3' part of a g gamma globin gene. Cos cells transfected with either of these 2 hybrid genes were shown to synthesize a similar amount of alpha/G gamma hybrid mRNAs but 50 less G gamma globin when transfected with the alpha/G gamma hybrid gene carrying the deletion. These results definitively establish that the 2 nucleotide deletion reduces translation efficiency by 30-50. This contrasts with the 93 reduction induced by a similar A-greater than C change at position -3 in the different nucleotide context preceding the atg codon of the rat preproinsulin gene. Mh - base sequence ; *Chromosome deletion ; *Codon ; *Genes, Structural ; Globin genetics/isolation purification ; Human ; Macromolecular Systems ; *Peptide Chain Initiation ; *rna, messenger ; Support, non-U. Gov't ; Templates ; Thalassemia familial genetic ; Transcription, genetic ; Translation, genetic. So - nucleic Acids Res 1986 Apr 25;14(8 3279-92 5, ui, friend au - hardison rc ; Sawada i ; Cheng jf ; Shen ck ; Schmid.
Ab - a method is described for directly cloning enzymatically amplified segments of genomic dna into an M13 vector for sequence analysis. A 110-base pair fragment of the human beta-globin gene and a 242-base pair fragment of the human leukocyte antigen dq alpha locus were amplified by the polymerase chain reaction method, a procedure based on repeated cycles of denaturation, primer annealing, and extension by dna polymerase. Oligonucleotide primers with restriction endonuclease sites added to their 5' ends were used to facilitate the cloning of the amplified dna. The analysis of cloned products allowed the quantitative evaluation of the amplification method's specificity and fidelity. Given the low frequency of sequence errors observed, this approach promises to be a rapid method for obtaining reliable genomic sequences from nanogram amounts of dna. Mh - antigens, Immune response genetics ; Base sequence ; Cloning, molecular/ *methods ; Coliphages genetics ; dna polymerase I/metabolism ; Gene Amplification ; *Genetic Vectors ; Globin genetics ; Human ; In Vitro ; Polymorphism (Genetics). So - science 1986 Sep 5;233(4768 1076-8 4, ui, au - morle f ; Starck j ; Godet. Ti - alpha-thalassemia due to the deletion of nucleotides -2 and -3 preceding the aug initiation codon affects translation efficiency both in vitro and in vivo.
differs considerably (70-450) from one allele to another. The sequence of the 17-bp repeats is highly conserved within and between alleles. Furthermore, this sequence identifies a core oligonucleotide 5'-gngggg(N)acag-3' that is common to three previously characterised hypervariable regions. At reduced stringency, a probe to the 3' hvr detects a new family of multiallelic loci that will be of value in the study of human genetics. Mh - alleles ; Base sequence ; Cloning, molecular ; dna restriction Enzymes ; evolution ; *Genes, Structural ; Globin genetics ; Human ; Nucleic Acid Hybridization ; Repetitive sequences, nucleic Acid ; Support, non-U. Gov't ; *Variation (Genetics). So - embo j 1986 Aug;5(8 1857-63 3, ui, au - scharf sj ; Horn gt ; Erlich. Ti - direct cloning and sequence analysis of enzymatically amplified genomic sequences.
The relative distribution of alpha-. Beta-globin mrna is consistent with more efficient beta-globin translation. In contrast, the parallel distributions of alpha 1- and alpha 2-globin mRNAs suggests they are translated with equal efficiencies. Considering the relative concentrations of the two alpha-globin mRNAs in normal reticulocytes, this result predicts a dominant role for the alpha 2-globin locus in human alpha-globin expression. Mh - base sequence ; paper Gene Expression Regulation ; Globin genetics ; Human ; Polyribosomes/metabolism ; Reticulocytes metabolism ; rna, messenger/ *metabolism ; Support,. So - j clin Invest 1986 Oct;78(4 1125-9 2, ui, au - jarman ap ; Nicholls rd ; weatherall dj ; Clegg jb ; Higgs. Ti - molecular characterisation of a hypervariable region downstream of the human alpha-globin gene cluster.
Translation glossary: english : - flowers - proZ
I want the sequence for exon 2 in the alpha-2 coding region of human alpha guaranteed globin. 1, ui, au - shakin sh ; liebhaber. Ti - translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes. Ab - in human reticulocytes, the critical balancing of alpha- and beta-globin synthesis may be controlled in part by differential translation of the three major adult globin messenger rnas (mRNAs alpha 1, alpha 2, and beta. In this study, we determined, as a parameter of translational efficiency, the relative ribosome loading of these three mRNAs. Using oligonucleotide probes specific for the alpha 1- and alpha 2-globin mRNAs, we find that these two mRNAs have identical translational profiles. Their distribution contrasts with that of beta-globin mrna, which is present on heavier polyribosomes and is less prevalent in pre-80S messenger ribonucleoprotein fractions.