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Biomedical subjects

J B Wilson

Publications and source records attributed to J B Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1989

Cytoplasmic interaction between pp60c-src and a truncated polyoma virus middle T antigen.

We have investigated the subcellular localization, transforming capacity and cellular protein binding properties of a mutant middle T antigen, 82JF3. This mutant lacks the carboxyterminal 86 amino acids of middle T and, as expected, failed to associate with cellular membranes. Like other cytoplasmic mutants, it also failed to transform. Nevertheless, 82JF3 middle T antigen associated with pp60c-src and increased its tyrosine kinase activity. The associated pp60c-src was also cytoplasmic, raising interesting questions about the nature and formation of the complex. This soluble complex also contained very reduced levels both of the p81 protein and of associated phosphatidylinositol (PI) kinase activity. These results are consistent with the hypothesis that p81 is a component of PI kinase.

Animals↗
PubMed1988

Hb natal or alpha 2(minus Tyr-Arg) beta 2: a high oxygen affinity alpha chain variant with a deleted carboxy-terminus resulting from a TAC----TAA (Tyr----terminating codon) mutation in codon alpha 140.

The discovery is reported of a fast-moving alpha chain variant (Hb Natal) which is characterized by a shortened alpha polypeptide chain because of the deletion of the Tyr-Arg carboxy-terminal residues. Through amplification of appropriate segments of DNA and hybridization with synthetic oligonucleotide probes, it was possible to detect a C----A mutation in codon 140 of the alpha 2 globin gene, which causes a change in the codon for tyrosine to a terminating codon. Hb Natal or alpha 2 (minus Tyr-Arg) beta 2 has a high affinity for oxygen without a Bohr effect and heme-heme interaction. These results provide direct evidence for the importance of the tyrosine residue at alpha 140 in the oxygenation-deoxygenation process.

Amino Acid Sequence↗
PubMed1988

Hb Duan [alpha 75(EF4)Asp----Ala], Hb Westmead [alpha 122(H5)His----Gln], and alpha-thalassemia-2 (-4.2 Kb deletion) in a Chinese family.

Detailed data are presented concerning the relative amounts of Hb A and two alpha chain variants (Hb Duan with alpha 75 Asp----Ala, and Hb Westmead with alpha 122 His----Gln), and the occurrence of an alpha-thalassemia-2 heterozygosity in five members of a small Chinese family. The three children who have the three abnormalities inherited the alpha-Duan and alpha-thalassemia-2 heterozygosities from their father, and the alpha-Westmead heterozygosity from their mother. The base substitution which leads to the synthesis of the alpha-Duan chain occurred at codon 75 of the alpha 1 globin gene of the chromosome which also carried the alpha-thalassemia-2 deletion; the concentration of alpha-Duan (37% of total alpha) is similar to that observed for other alpha chain variants, linked to an alpha-thalassemia-2 condition.

Adolescent↗
PubMed1988

Some rare hemoglobin variants with altered oxygen affinities; Hb linkoping [beta 36(C2)Pro----Thr], Hb Caribbean [beta 91(F7)Leu----Arg], and Hb Sunnybrook [beta 36(C2)Pro----Arg].

A few rare hemoglobin variants with altered functional properties have been observed in Canadian subjects with either an erythrocytosis or mild anemia. These variants were Hb Alberta [beta 101(G3)Glu----Gly], Hb Linkoping [beta 36(C2)Pro----Thr], a new variant Hb Sunnybrook [beta 36(C2)Pro----Arg], and Hb Caribbean [beta 91(F7)Leu----Arg]. Short clinical descriptions of the subjects are given, the characterization of the variants is described in detail (except for Hb Alberta), while data from some functional analyses are provided. Comparisons with previously published data have been made and the unusual chromatographic property of two abnormal beta chains in a reversed phase high performance liquid chromatographic system is reviewed.

Aged↗
PubMed1988

Hb Las Palmas or alpha 2 beta 2(49)(CD8)Ser----Phe, a mildly unstable hemoglobin variant.

A new hemoglobin variant with a Ser----Phe substitution at position beta 49(CD8) was discovered in two members of a family living in the Canary Islands, Spain. Detection was by polyacrylamide gel electrophoresis and by reversed phase high performance liquid chromatography. The variant, which constituted 43% and 45%, respectively, in the two heterozygotes, was slightly unstable. Its presence did not affect hematological values though there was a mild reticulocytosis.

Adult↗
PubMed1988

Inclusion body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta 114.

We have analyzed the sequence of the beta globin gene of a chromosome that is linked to the occurrence of an inclusion body beta-thalassemia characterized in the heterozygote by moderate anemia, severe red cell abnormalities, splenomegaly, inclusion body formation, elevated Hb A2 levels, and an increased in vitro alpha/beta chain synthetic ratio. The data indicate a change in codon 114 from CTG (Leu) to -GG that resulted in a frameshift and the presumed synthesis of an abnormal beta chain that is 156 residues long with a completely different C-terminal amino acid sequence. The change in codon 114 gives a -GGGCCC- sequence that creates a new ApaI site; the resulting 2.6-kilobase fragment has been observed in all subjects with this thalassemia condition. Protein structural analyses failed to demonstrate any trace of the abnormal beta chain, even in reticulocytes and nucleated red cells that were isolated by density gradient centrifugation. The inclusion bodies appear to contain mainly normal alpha chains. It is assumed that the structure of the beta-Geneva chain prevents it from combining with normal alpha chains; this results in a rapid breakdown of the abnormal protein during the early stages of red cell maturation and an accumulation of free alpha chains.

Adult↗
PubMed1987

Detection of the embryonic zeta chain in blood from newborn babies by reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) using the large-pore Vydac C4 column has been used to detect and quantitate the embryonic zeta chain in blood samples of normal babies and of newborns with varying degrees of alpha chain deficiencies. The zeta chain eluted at the end of the chromatogram at about 130 min using a modified and extended gradient. Its identity was confirmed by structural analysis of zeta chain isolated from a blood sample of a fetus without active alpha globin genes, i.e. with hydrops fetalis (--/--). The quantity of zeta in normal babies is less than 0.7% [% of (alpha + zeta)] and is dependent upon the maturity of the baby as it was only present in babies with low levels of beta chain or hemoglobin (Hb) A. The presence of a zeta globin gene deletion [A. E. Felice et al., Hum. Genet., 73 (1986) 221; and P. Winichagoon et al., Nucleic Acids Res., 10 (1982) 5853] did not affect the level of zeta in the newborn. All babies with an alpha-thalassemia-2 heterozygosity, i.e. with three active alpha globin genes or -alpha/alpha alpha, had zeta in a range of 0.1-0.9%; again the level showed a negative correlation with that of the beta chain. Newborns with an alpha-thalassemia-2 homozygosity or -alpha/-alpha had a varying level of zeta of 0.3-2.3%, which did not correlate with the level of beta, suggesting that zeta chain production persists after birth in this condition. Macrochromatographic analyses in combination with RP-HPLC indicated that the zeta chain is present as zeta 2 gamma 2 or Hb Portland-I, as expected.

Alpha-Globulins↗
PubMed1987

The M gamma chain of human fetal hemoglobin; its identification and occurrence.

High-performance liquid chromatographic procedures have been used in the detection and identification of a new gamma chain of human fetal hemoglobin (Hb). This M gamma chain is characterized by a Leu----Met replacement at position gamma 141; no other structural variations have been observed. The M gamma chain has been detected in red cell lysates of subjects with a heterozygosity for one of many types of so-called hereditary persistence of fetal hemoglobin conditions, which are characterized by an increased level of Hb F in adult life, in sickle cell anemia, and in a few cord blood samples. At present it is not possible to definitely identify the genetic cause of this newly discovered heterogeneity; an infidelity in translation or the existence of an unrecognized gamma globin gene should be considered.

Amino Acids↗
PubMed1987

HB Q-Thailand-HB H disease in a Chinese living in Geneva, Switzerland: characterization of the variant and identification of the two alpha-thalassemic chromosomes.

Data on a 24-year-old Chinese male with Hb Q-Thailand-Hb H disease are presented. The hemoglobin variant was characterized by fast microprocedures, mainly by reverse-phase high-performance liquid chromatography. Gene mapping analyses identified the alpha-thalassemia-2, which is associated with the alpha-Q chain, as caused by a 4.2-kb deletion involving the alpha 2 globin gene, while the alpha-thalassemia-1 anomaly was the common Southeast Asian type in which part of the psi zeta, the psi alpha, and the alpha 2 and alpha 1 globin genes are deleted.

Adult↗
PubMed1987

Characterization of chromosomes with hybrid genes for Hb Lepore-Washington, Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya.

This study concerns the characterization of chromosomes with hybrid genes for Hb Lepore-Washington (44 chromosomes), for Hb Lepore-Baltimore (5 chromosomes), for Hb P-Nilotic (8 chromosomes), and for Hb Kenya (7 chromosomes) by determining a relatively large number of restriction enzyme polymorphism. Two, and possibly three, different Hb Lepore-Washington chromosomes were identified by specific haplotypes, while the haplotype of the Hb Lepore-Baltimore chromosome had its own characteristic pattern. A likely conclusion is that the crossovers leading to the formation of these chromosomes have occurred as independent events within the populations. Chromosomes with the delta beta-Lepore-Washington hybrid gene maintained specific characteristics (such as increased Hb F levels in heterozygotes, and high or low G gamma values in this Hb F) which have been observed in normal individuals with chromosomes having comparable haplotypes. Only one haplotype was observed for each of the chromosomes carrying either the beta delta-P-Nilotic hybrid gene or the A gamma beta hybrid gene of Hb Kenya.

Chromosome Mapping↗
PubMed1987

Hb F-Xin-Su or A gamma I73(E17)Asp----His: a new slow-moving fetal hemoglobin variant.

A slow-moving gamma chain variant was discovered in the cord blood of an infant born to parents of the Han nationality from Jiangsu. The variant, which migrated electrophoretically at alkaline pH between Hb A and Hb D, was characterized by an Asp----His substitution at gamma 73, while residues gamma 75 and gamma 136 were occupied by Ile and Ala, respectively. As the A gamma T-chain was also present, this baby has two types of abnormal gamma-chain. The variant was named Hb F-Xin-Su.

Amino Acid Sequence↗