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Biomedical subjects

R A Popp

Publications and source records attributed to R A Popp.

At least 55 records · Page 3Linked to original sources
PubMed1981

Mouse alpha-globin genes and alpha-globin-like pseudogenes are not syntenic.

A genetic polymorphism for a Bgl I endonuclease site near the alpha-globin-like pseudogene alpha-4 of C57BL/6 and C3H/HeN mice was used to show that alpha-4 was not affected by three independent mutations in which the adult globin genes alpha-1 and alpha-2 were deleted. These results indicated that alpha-4 might not be located adjacent to the adult alpha-globin genes on chromosome 11. Restriction endonuclease analysis of DNA of a primary clone of a Chinese hamster--mouse somatic cell hybrid that had lost mouse chromosomes 11 and 18 showed that this clone lacked the adult murine globin genes alpha-1 and alpha-2 but it did contain the alpha-globin-like pseudogenes alpha-3 and alpha-4. These results indicated that the adult alpha-globin genes and alpha-globin-like pseudogenes are not located on the same chromosome. Similar analyses of several other Chinese hamster--mouse somatic cell hybrids that had segregated other mouse chromosomes indicated that the alpha-globin-like pseudogenes alpha-3 and alpha-4 are located on mouse chromosomes 15 and 17, respectively. These data explain why alpha-3 and alpha-4 were not affected by the three independently induced deletion-type mutations that cause alpha-thalassemia in the mouse.

Animals↗
PubMed1981

Deletions in the alpha-globin gene complex in alpha-thalassemic mice.

Three induced, heritable mutations in the mouse cause alpha-thalassemias. The adult alpha-globin genes on each mutant chromosome are no longer expressed. Embryos heterozygous for one normal and any of the three mutant chromosomes also seem to be deficient in embryonic alpha-globin-like x-globin, suggesting that the x-globin gene is nearby and also inactivated. A normal genetic polymorphism for a specific EcoRI site in or around the mouse alpha-globin gene complex has been used here to show that each of the three mutated chromosomes has a deletion that includes the segment of a 12-kilobase EcoRI band which normally carries one of the two adult alpha-globin genes. The deletion of the comparable part of the second alpha-globin gene site is also inferred. Nonetheless, a 4.7-kilobase EcoRI segment which carries a characterized alpha-globin-like pseudogene is still present in each mutant. These mutations were recovered after triethylenemelamine or x-ray treatments.

Animals↗
PubMed1981

Three mouse models of human thalassemia.

Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes.

Animals↗
PubMed1981

Preschool children's understanding of children with orthopedic disabilities and their expectations.

The present study investigated whether preschool children (N = 121) had a realistic understanding of the limitations imposed by various orthopedic disabilities. The results have indicated that the preschoolers were aware that orthopedic disabilities may impose some physical limitations. Ss tended to perceive able-bodied children more capable in performing various tasks than disabled children. This evaluative judgment does not necessarily mean that the preschoolers were discriminating against the disabled children, but it may be a reflection of a sense of realism that the able-bodied children have less trouble in doing these tasks than their disabled counterpart. It was suggested that, with increased understanding of the realistic limitations imposed by orthopedic disabilities, children may be come less biased toward their disabled peers. This change in attitude would have significant impact on the self-concepts of disabled children.

Attitude↗
PubMed1980

Differential association of transfer RNAs with the genomes of murine, feline and primate retroviruses.

The tRNAs that are bound to the genomic RNAs of several murine, feline, and primate retroviruses have been identified. Transfer RNAs were divided into those loosely bound and those tightly bound by stepwise thermal dissociation of the 70 S RNA. They were then identified and semiquantitated by aminoacylation. Proline tRNA is the most tenaciously bound tRNA in several strains of murine leukemia virus, two strains of feline leukemia virus, and the primate viruses simian sarcoma, baboon endogenous, and gibbon ape lymphoma. In the feline xenotropic virus, RD-114, tRNAGly is enriched in the most tightly bound fraction. In Mason-Pfizer monkey virus, as in the murine mammary tumor virus, tRNALys is the tRNA most tenaciously bound to its genomic RNA. Besides the most tightly associated tRNA, one or more different tRNAs are found in relatively large amounts in association with the 70 S RNA. (For convenience, we refer to the largest RNA ccomplex (50-70 S) isolated from any of the retroviruses studies as '70 S' RNA.) These tRNAs can be distinguished from the most tightly bound tRNA by the fact that they can be dissociated at lower temperatures. However, they occur in the same relative abundance as the tightly bound tRNA.

Genes, Viral↗
PubMed1980

Species comparison of protein synthesis accuracy.

The average accuracy of protein synthesis in reticulocytes from several mammalian species does not correlate with longevity potential from 13 to 90 years. Isoleucine incorporation into highly purified hemoglobin chains which contain no genetically coded isoleucine was used as a direct test of protein synthesis accuracy. Since isoleucine can be incorporated into these molecules by mutations in a few cells as well as errors in most cells, the constant level of isoleucine substitution may also show that the mutation rates are not dramatically different among these species. Isoleucine substitutions in hemoglobin can be used to estimate mutations only above the level of errors, which may be as low as 1/1,000,000, but the probability of seeing a few mutant clones at any time is dependent on the number of stem cells producing reticulocytes. The number of stem cells being expressed is a reflection of the number of cell divisions per clone. If the number of cell divisions per clone is 30 or less, then isoleucine substitutions would increase when the mutation accumulation rose above 30 per million for the mutation to isoleucine at any position in the alpha or beta chain.

Aging↗
PubMed1979

Hemopoietic stem cell heterogeneity: use of cell cycle-specific drugs to look for age-associated alterations.

Hemopoietic tissue is vulnerable to perturbations, and data show that it is an appropriate tissue in which to look for age-associated alterations. This tissue has a high regenerative capacity, is composed of a heterogeneous population of stem cells that are capable of self renewal or differentiation, or both, and is sustained by a pool of resting cells. The heterogeneity of bone marrow has made characterization of the cellular elements difficult. Techniques commonly used to identify and quantify the various maturation levels of hemopoietic stem cells and the limitations of these techniques are discussed. Most techniques used to assay age-associated changes in bone marrow have not differentiated between specific cellular alterations or shifts in the distribution of the cellular elements. In particular, it has been difficult to determine the stability of the non-dividing stem cell because of the low incidence of this cell (6 per 1000) and the lack of a specific assay for this important cell type. The use of cell cycle-specific drugs has provided quantitative information on specific subpopulations of hemopoietic stem cells and seems to be the most promising approach towards determining qualitative and quantitative differences in the hemopoietic stem cells of young and old individuals.

Aging↗
PubMed1979

Amino acid substitution: its use in detection and analysis of genetic variants.

Techniques of chemical analysis, amino acid sequencing and autoradiography are being used to study the frequency of incorporation of normally noncoded amino acids into hemoglobins and seminal fluid proteins. We are studying, by the sequencing of radiolabeled proteins followed by the recovery of [3H]isoleucine phenylthiohydantoin by high-performance liquid chromatography, the frequency at which normally noncoded isoleucine is incorporated into hemoglobin because of base-substitution mutations versus translational errors. Irradiation increases the isoleucine content of human hemoglobin and the frequency of substitution of isoleucine for specific amino acids in rabbit hemoglobin. Studies to date indicate that these techniques have been developed sufficiently for initial analysis of the potential of drugs and environmental pollutants to induce base-substitution mutations in mammalian somatic cells.

Amino Acid Sequence↗
PubMed1978

Amino acid sequence of a progesterone-binding protein.

The amino acid sequence of blastokinin, also called uteroglobin, has been determined by a combined study of both the intact native molecule and the peptide fragments resulting from tryptic and chymotryptic digestions. Sequence analyses performed by automated methods and by sequential digestion with leucine aminopeptidase and carboxypeptidase Y demonstrate that blastokinin is a dimer of identical 69-amino acid subunits held together in parallel orientation by two disulfide bridges at positions 3 and 68. The polypeptide chains are further characterized by the absence of tryptophan residues and by single residues of histidine and tyrosine at positions 8 and 21, respectively. Six of eight amino acids, positions 17--24, near the progesterone binding site of blastokinin contain a hydroxyl group. Knowledge of the chemistry of this receptor site should allow better perspectives of the chemistry of molecules in normal tissues that are dependent on progesterone for growth and development, as well as compounds that could act as cancer antagonists for endocrine therapy of hormone-dependent tumors.

Amino Acid Sequence↗
PubMed1977

Radiation-induced alpha-thalassemia in mice.

The clinical hematologic change in 2 groups of progeny from mice carrying radiation-induced strain SEC alpha-chain deficiencies was found to be similar to the hematologic alterations in persons with alpha-thalassemia. The heterozygous deletion or inactivation of the alpha-chain gene in mice caused an anemia similar to alpha-thalassemina minor in persons. The alpha-chain deficiency in mice created an erythrocytosis, reticulocytosis, and microcytic, hypochromic anemia comparable with the changes in human alpha-thalassemia minor resulting from deletion of the alpha-chain gene. These mouse mutants are the only known animal models of human thalassemia. A comparison of hematologic values obtained from progeny possessing an alpha-chain gene deficiency and from progeny possessing a beta-chain duplication suggested that the deficiency of alpha-chain synthesis, rather than a simple imbalance between the amounts of alpha- and beta-chains produced, was primarily responsible for the altered hematologic characteristics in these alpha-thalassemic mice.

Animals↗