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G C Mills

Publications and source records attributed to G C Mills.

12 recordsLinked to original sources
PubMed1991

Cytochrome c: gene structure, homology and ancestral relationships.

In this paper, the author notes the recommended definition of the word "homology" (i.e., indicating an ancestral relationship) and the recommended stipulation that "evidence for homology should be explicitly laid out". The postulated homology for somatic and testes-specific isozymes of cytochrome c is then examined, using recent data obtained from the study of cytochrome c genes. Consideration is also given to some newer findings of molecular biology and possibilities are considered for various types of change in the genome of an organism. Possible roles of introns, pseudogenes and multigene families are considered. The relationship of testes-specific cytochrome c to somatic cytochrome c is carefully considered from data obtained in experimental studies of genes of these two isozymes. If one assumes that these isozymes arose as a consequence of a gene duplication, data from rat and mouse genes indicate that the testes-specific isozyme has incorporated more amino acid changes than the somatic isozyme since the time of their divergence. However, when the 15 amino acid differences (testes-specific vs. somatic isozyme) are considered, there is virtually no similarity in these 15 positions of the testes-specific isozyme with any of the hypothetical ancestral sequences of the somatic isozyme. Nucleotide differences in cytochrome c genes have been evaluated by comparing genes for the two rodent cytochrome c isozymes to cytochrome c genes of fruit flies, chickens and humans. Comparisons of nucleotide substitution rates in genes for the two cytochrome c isozymes in rodents confirm the conclusions from amino acid sequence comparisons; namely, that more rapid nucleotide changes have occurred in the testes-specific cytochrome c gene, than in the somatic cytochrome c gene. Possible explanations for these findings are considered.

Amino Acid Sequence↗
PubMed1979

Cytosine and orotic acid in urine of immunodeficient children.

We describe procedures for determining cytosine and orotic acid in urine. We determine cytosine by cation-exchange analysis with either HCl or pH 5.2 buffer as eluent. Orotic acid is first separated by an anion-exchange separative procedure; after lyophilization, the product is subjected to "high-pressure" liquid chromatography for further separation and detection. We analyzed urine from normal subjects and from immunodeficient children. Three children with severe combined immunodeficiency had increased levels of cytosine in urine (23-160 mmol/mol creatinine); one child with severe combined immunodeficiency and two children with other immunodeficiencies had normal urinary levels (less than 2 mmol/mol creatinine). Orotic acid excretion in urine was normal (1-5 mmol/mol creatinine) in all of th immunodeficient children. We discuss the possible significance of the increased cytosine excretion in the three children with severe combined immunodeficiency.

Child↗
PubMed1978

Limited effect of erythrocyte and plasma infusions in adenosine deaminase deficiency.

A 10-month-old child with a profound deficiency of adenosine deaminase and severe combined immunodeficiency was treated for a period of 17 months with red cell and plasma transfusions containing normal amounts of the deficient enzyme. Following each transfusion, the plasma adenosine, red cell and lymphocyte ATP, urinary adenine, and urinary deoxyadenosine decreased transiently. During this period, the absolute blood lymphocyte count rose and a limited increased in the response of the lymphocytes to PHA-P was observed. Delayed hypersensitivity skin tests remained negative during the transfusion periods. A quantitative elevation of serum immunoglobulins occurred, but specific antibody formation was not elicited. In contrast to a previous report of successful therapy of ADA deficiency with red cell and plasma infusions, this patient responded poorly to enzyme replacement therapy. The difference may be related to a more profound enzyme deficiency in our patient.

Adenine↗
PubMed1977

Increased purine nucleotides in adenosine deaminase-deficient lymphocytes.

It was found that ATP and cyclic AMP were greatly increased in human blood lymphocytes which were deficient in ADA. Certain other purine and pyrimidine nucleotides were elevated but to a lesser degree. Energy production in these cells may be inhibited by the increase in nucleotides since the ATP:ADP ratio was significantly below normal. Thus it appears that the immunologic deficiency in human ADA deficiency is related to increased nucleotide concentrations in the lymphocytes.

Adenosine Deaminase↗
PubMed1976

Purine metabolism in adenosine deaminase deficiency.

Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides.

Adenine↗