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Biomedical subjects

L Hall

Publications and source records attributed to L Hall.

At least 181 records · Page 10Linked to original sources
PubMed1986

On the mechanism of Hb F elevations in the baboon by erythropoietic stress and pharmacologic manipulation.

Maximal fetal hemoglobin (Hb F) elevations in the baboon subsequent to phenyl hydrazine-induced hemolytic anemia, bleeding, bleeding plus hydroxyurea (HU), or cytosine arabinoside were two to three times lower than those achieved with bleeding plus 5-azacytidine (azaC). Because, in the baboon, maximal elevations in F cell numbers occurred with bleeding alone, changes in the levels of Hb F in hemolysates and in Hb F per F cell could be considered to be due to the administered drugs. Erythropoietic toxicity of azaC was minimal, making it unlikely that the marked elevations of Hb F were due to shifts in the population of erythroid progenitors and precursors and more likely that they were related to a biochemical effect of the drug on DNA. The data indicate marked DNA hypomethylation. This was also found to be associated, but to a much lesser extent, with the modest Hb F elevations after bleeding, hemolysis, and treatment with HU. This drug had greater erythroid toxicity than azaC, and it appeared that the Hb F elevations occurred mainly on the rebound from the early cytotoxicity. The explanation of the molecular DNA changes with this drug and in erythropoietic stress alone remains unknown.

Anemia, Hemolytic↗
PubMed1986

Changes in gene expression in established human mammary tumor cell lines when compared with normal breast and breast tumor tissue.

RNA complexity analyses of total cellular polyadenylate-containing RNA isolated from lactating human breast tissue, human breast tumor tissue, and a mixture of established cell lines of mammary origin demonstrate extensive homology between the tissue RNA populations but suggest a decrease in the complexity of cell line nuclear RNA populations, with the exception of an early-passage MCF-7 cell line. Cell-free protein synthesis and two-dimensional gel electrophoresis also show quantitative and qualitative differences in gene expression between human mammary tumor tissue and reduction mammoplasty or established mammary cell lines of early and late passage number. The results demonstrate a major role for transcriptional and posttranscriptional mechanisms in the regulation of gene expression in the human mammary gland and show that studies on mammary gland gene expression using established cell lines of mammary origin reflect only in part gene expression in normal lactating human breast or breast tumor tissues.

Breast↗
PubMed1985

Tetrahydrouridine, cytidine analogues, and hemoglobin F.

5-Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5-azauridine, made it possible to reduce the amount of azaC and also of 2-deoxy-5-azacytidine (d-azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5-azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5-azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d-azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d-azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of gamma globin chain production.

Agranulocytosis↗
PubMed1985

The effects of dietary fibre in a liquid diet on bowel function of mentally retarded individuals.

A soy polysaccharide at a level of 20-22.3 g/day was added to a liquid formula diet provided to constipated, tube-fed, nonambulant, severely or profoundly mentally retarded individuals. This amount of polysaccharide contained 15.6-17.4 g of dietary fibre or 4.9-5.5 g of neutral detergent fibre. The fibre formula was well tolerated by the subjects and increased stool size and improved stool consistency. At these levels of fibre and short duration of the study, defecation rate and need for elimination aids were unaffected. Transit times of 5 to 6 days were unchanged but mean daily stool weights increased to a level equivalent to low normal values for healthy adults on a low fibre intake.

Adolescent↗
PubMed1985

An accurate assessment of the prevalence ratio of epilepsy adequately adjusted by influencing factors.

The prevalence of epilepsy was estimated by defining an initial prevalence ratio based on a population study and modifying this figure on the basis of various factors which influenced it. The definition required 3 seizures diagnosed by a doctor and the influencing factors included false-negative responses (where the diagnosis was confirmed), false reporting (where the diagnosis had not been established) and falsely low seizure counts (where therapy had reduced the number of seizure below the mandatory 3). As a result of these calculations the figure of approximately 1 in 50 was offered as a reliable and reasonable estimate of the true prevalence ratio of epilepsy within a well-defined Australian population.

Anticonvulsants↗
PubMed1984

Effect of a zinc phosphate suspension of a long-acting somatostatin analog on postprandial plasma glucose, triglyceride and glucagon concentrations in alloxan diabetic dogs.

The effects of a zinc phosphate suspension of a long-acting, reportedly selective somatostatin analog, Des-Ala1,Gly2 [His4,5,D-Try]-somatostatin (100 micrograms/kg) on postprandial plasma glucose, glucagon, xylose and triglyceride levels were evaluated in alloxan diabetic dogs. Compared to the analog in aqueous solution, the zinc phosphate suspension had a more gradual onset of action in suppressing plasma glucose and xylose levels but a similar onset of action on suppression of plasma triglyceride and glucagon responses. On all these responses, the zinc suspension had a duration of action (greater than 6 hrs) at least three times as long as the aqueous solution. We conclude that such a somatostatin analog in zinc phosphate suspension may have a sufficient duration of action to be useful as an adjunct to insulin in the treatment of diabetes mellitus.

Animals↗
PubMed1984

Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat alpha s1 caseins and conservation of the non-coding regions of the mRNA.

Nucleotide sequence analysis of cloned guinea-pig casein B cDNA sequences has identified two casein B variants related to the bovine and rat alpha s1 caseins. Amino acid homology was largely confined to the known bovine or predicted rat phosphorylation sites and within the 'signal' precursor sequence. Comparison of the deduced nucleotide sequence of the guinea-pig and rat alpha s1 casein mRNA species showed greater sequence conservation in the non-coding than in the coding regions, suggesting a functional and possibly regulatory role for the non-coding regions of casein mRNA. The results provide insight into the evolution of the casein genes, and raise questions as to the role of conserved nucleotide sequences within the non-coding regions of mRNA species.

Amino Acid Sequence↗
PubMed1984

Guinea-pig casein A cDNA. Nucleotide sequence analysis and comparison of the deduced protein sequence with that of bovine alpha s2 casein.

The nucleotide sequence (1036 bases) of guinea-pig casein A mRNA has been determined. Two cDNA recombinant plasmids contained a total of 993 base pairs, including part of the 5' noncoding region, and the complete coding and 3' noncoding region. The remaining 5' noncoding sequence was obtained by primer extension. The deduced 223-amino-acid-coding sequence of guinea-pig pre-casein A exhibited 30% homology with bovine alpha s2 casein, the most striking similarities being in the locations of potential phosphorylation sites.

Amino Acid Sequence↗
PubMed1984

Speciation in the baboon and its relation to gamma-chain heterogeneity and to the response to induction of HbF by 5-azacytidine.

In the baboon (Papio species), the two nonallelic gamma-genes produce gamma-chains that differ at a minimum at residue 75, where isoleucine (I gamma-chain) or valine (V gamma) may be present. This situation obtains in baboons that are sometimes designated as Papio anubis, Papio hamadryas, and Papio papio. However, in Papio cynocephalus, although the I gamma-chains are identical with those in the above mentioned types, the V gamma-chains have the substitutions ala----gly at residue 9 and ala----val at residue 23. The V gamma-chains of P. cynocephalus are called V gamma C to distinguish them from the V gamma A-chains of P. anubis, etc. A single cynocephalus animal has been found to have only normal I gamma-chains and I gamma C-chains (that is, glycine in residue 9, valine in 23, and isoleucine in 75). When HbF is produced in response to stress with 5-azacytidine, P. anubis baboons respond with greater production than do P. cynocephalus, and hybrids fall between. Minimal data on P. hamadryas and P. papio suggest an even lower response than P. cynocephalus. As HbF increases under stress, the ratio of I gamma to V gamma-chains changes from the value in the adult or juvenile baboon toward the ratio in the newborn baboon. However, it does not attain the newborn value. The V gamma A and V gamma C-genes respond differently to stress. In hybrids, the production of V gamma A-chains exceeds that of V gamma C-chains. A controlling factor in cis apparently is present and may be responsible for the species-related extent of total HbF production. It may be concluded that the more primitive the cell in the erythroid maturation series that has been subjected to 5-azacytidine, the more active is the I gamma-gene.

Amino Acid Sequence↗
PubMed1983

Changes in the gamma chain heterogeneity of hemoglobin F of the baboon (Papio cynocephalus) postnatally and after partial switching to hemoglobin F production by various stimuli.

The postnatal switch from hemoglobin (Hb) F to Hb A in the baboon (Papio cynocephalus) occurs somewhat more rapidly than in humans. Minor components which are related to Hb F and Hb A are also present and show reciprocal rise and fall. The baboon produces two types of gamma chain presumably from nonallelic genes. These have either an isoleucyl (I gamma) or a valyl (V gamma) residue in position 75. As in the human case with G gamma and A gamma chains, the ratio I gamma to V gamma chains changes during the postnatal switch. Production of Hb F in the baboon may be stimulated by phenylhydrazine or more effectively by 5-azacytidine. With phenylhydrazine, the ratio of I gamma to V gamma chains in the Hb F is the same as in the traces of Hb F in the juvenile or adult baboon. However, with 5-azacytidine, at least some of the Hb F that is produced probably has been synthesized with an I gamma to V gamma ratio that is present prenatally and in the newborn baboon.

Aging↗
PubMed1982

Comparison of the nucleotide sequence of cloned human and guinea-pig pre-alpha-lactalbumin cDNA with that of chick pre-lysozyme cDNA suggests evolution from a common ancestral gene.

Nucleotide sequence analyses of essentially full-length copies of human and guinea-pig pre-alpha-lactalbumin cDNAs contained within recombinant plasmids, (i) confirm the presence of 19 amino acid hydrophobic amino terminal peptide extensions encoded within each mRNA; and (ii) provides evidence for the existence of a minor variant of guinea-pig alpha-lactalbumin mRNA encoding a protein with a 36 residue carboxyl-terminal extension. Comparison of the nucleotide sequence within the coding region of the human, and the predominant guinea-pig pre-alpha-lactalbumin mRNAs, with the analogous region of hen pre-lysozyme mRNA provides compelling evidence that all have evolved from a common ancestral gene.

Amino Acid Sequence↗