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Biomedical subjects

J R Seed

Publications and source records attributed to J R Seed.

At least 55 records · Page 3Linked to original sources
PubMed1984

The ecology of antigenic variation.

A detailed molecular analysis using recombinant DNA technologies is extremely important to our understanding of the phenomena of antigenic variation in the African trypanosomes; however, by itself, it may not completely explain antigenic variation as it occurs in vivo. Several laboratories have demonstrated the ability of one variant population to replace another in vivo as well as the presence of heterogeneous populations of trypanosomes within an individual animal. These two phenomena do not permit us to explain antigen variation solely on the basis of the molecular regulation of variant antigen expression. In addition to studies in molecular biology, it will be necessary to define clearly the differences in growth rates of variant populations and the role of competition between these variants in a single anatomical site. It will also be necessary to determine the influence of various physiological environments on growth rates and the competition between the different variants of a single repertoire. It is concluded that the phenomenon of antigenic variation is a complex problem in ecology and population dynamics as well as molecular regulation. This paper is designated to examine a variety of the ecological parameters presumably involved in antigenic variation.

Animals↗
PubMed1982

Hepatic microsomal alterations during chronic trypanosomiasis in the field vole, Microtus montanus.

The field vole, Microtus montanus, was used as a model system to evaluate the chronic effects of infection by Trypanosoma brucei gambiense on hepatic mixed-function oxidase activity. At day 28 post inoculation there was a 97% increase in liver wet weight per g body weight. A portion of the increase (21%) was accounted for by tissue edema which occurred after day 14 of infection. Total hepatic cytochrome P-450 content and related total tissue mixed-function oxidase activities were decreased to about 60% of control levels at day 28 post inoculation. The decrease in total tissue mixed-function oxidase activity was partly due to a small decrease in microsomal protein per cell, and partly to a large decrease in cytochrome P-450 concentration in the endoplasmic reticulum. Although the decrease in total liver monooxygenase activity in several substrates roughly paralleled the loss in cytochrome P-450 content, several other microsomal enzyme markers not related to cytochrome P-450 monooxygenation were elevated in proportion to total liver microsomal protein content. The results suggest that in M. montanus during trypanosomiasis, there is proliferation of hepatic cells with normal content of endoplasmic reticulum. Furthermore, there appears to be selective toxicity for hepatic cytochrome P-450 and related monooxygenase activities. This may compromise the animals' ability to metabolize and dispose of other drugs to which the animal may be exposed in the course of infection.

Animals↗
PubMed1982

Phenylalanine metabolism in Microtus montanus chronically infected with Trypanosoma brucei gambiense.

1. Alterations in phenylalanine metabolism were observed in Microtus montanus infected with Trypanosoma brucei gambiense. 2. Reductions were found in the incorporation of phenylalanine into free amino acid pools and into proteins of the liver and other organs of infected animals. 3. Increased quantities of phenylpyruvate, 4-hydroxyphenylpyruvate and pyruvate were found in the urine of infected Microtus. 4. There appeared to be very limited conversion of phenylalanine to tyrosine in infected animals. This suggested that either phenylalanine transaminase activity was greatly elevated in proportion to phenylalanine hydroxylase activity; or that phenylalanine hydroxylase activity was actually reduced during the infection.

Animals↗
PubMed1982

Carbon-13 nuclear-magnetic-resonance studies of glucose catabolism by Trypanosoma brucei gambiense.

13C Nuclear magnetic resonance studies have been performed in vivo on Trypanosoma brucei gambiense. The glycolytic pathway has been observed using specifically labelled 13C-enriched glucose and it has been ascertained that there is, under anaerobic conditions, predominant incorporation of C-1 of glucose into glycerol while there is complete randomisation of C-6 of glucose into glycerol and pyruvate. These observations cannot be reconciled by the Embden-Meyerhof glycolytic pathway, purportedly the mechanism by which glucose is catabolised in these organisms, and an alternative pathway must exist. Comparison of whole-cell and acid-lysate 13C nuclear magnetic resonance spectra concludes that pyruvate may be initially formed bound to a macromolecular species. Also, alanine is found to be a major end product of glucose catabolism.

Glucose↗
PubMed1981

Hepatic mixed-function oxidase activity in mice infected with Trypanosoma brucei gambiense or treated with trypanocides.

Three days after mice were inoculated with Trypanosoma brucei gambiense, total hepatic cytochrome P-450 levels were decreased 14% from control values, while the specific mixed-function oxidase activity (per nmole of cytochrome P-450) was inhibited almost 40% in infected animals. Furthermore, drugs used to treat trypanosomiasis (Suramin and Melarsoprol B) are themselves potent in vitro inhibitors of hepatic mixed-function oxidase activity. These two trypanocides also produced a decrease in mixed-function oxidations and an increase in pentobarbital sleeping time when administered intraperitoneally in vivo. These results demonstrate that mice with trypanosomiasis or undergoing trypanosome chemotherapy have a significantly impaired capacity to metabolize foreign compounds.

Animals↗
PubMed1981

Further studies on difluoromethylornithine in African trypanosomes.

DL-alpha-Difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC) was previously shown to cure mice infected with Trypanosoma brucei brucei, a parasite of game and cattle in Africa and Trypanosoma brucei rhodesiense, a human African Sleeping Sickness pathogen. Our studies now indicate that DFMO blocks ornithine decarboxylase and lowers trypanosome polyamine levels in vivo. Polyamine uptake in T.b. brucei also resembles that previously described for mammalian cells. The therapeutic potential of DFMO can now also be extended to another human pathogen, Trypanosoma brucei gambiense. Finally, DFMO acts synergistically with another drug, bleomycin, to cure acute trypanosome infections, and furthermore, this same drug combination provides a new approach to the treatment of trypanosomal infections of the central nervous system.

Acute Disease↗
PubMed1978

Competition among serologically different clones of Trypanosoma brucei gambiense in vivo.

When different antigenic variant clones are injected in equal numbers into white mice one variant clone always replaces the other. This phenomenon appears to be a predictable one, even under conditions analogous to a chronic infection. It is hypothesized that a constant ratio is approached between the number of cells of different antigenic serotypes present in a single population, in such a manner that there is always a major antigenic variant and minor populations of different antigenic variants. It is further suggested that these ratios can undergo rapid changes in response to changes in the environment, e.g. nutritional status of the host, changes in body temperature, antibody synthesis, etc. The changes in these ratios are discussed in relation to the mechanism(s) of antigenic variation.

Agglutination Tests↗
PubMed1977

Alteration of free serum amino acids in voles infected with Trypanosoma brucei gambiense.

Free serum amino acid pools of field voles, Microtus montanus, were determined over a 24 hr period, and compared to values obtained from voles infected with Trypanosoma brucei gambiense. The majority of amino acids in the control animals demonstrated a diurnal variation, peaking predominantly during the dark portion of the photoperiod. This trend was not evident in the infected animals. In addition, infected voles possessed an apparent state of hypoaminoacidemia, with levels of threonine, serine, valine, isoleucine, leucine, tryosine, and tryptophan typically below uninfected values. Alanine and proline, in contrast, were markedly increased at certain time points. Tyrosine (reduced by approximately 50%) and tryptophan (reduced to levels below detection) underwent the most pronounced drop in trypanosome-infected animals, indicating the possibility of a related alteration in pools of derivative biogenic amines in other tissues. This suggests a role for the latter 2 amino acids in the neuropsychiatric syndromes of African trypanosomiasis.

Alanine↗
PubMed1977

Evidence for adsorption of heterospecific host immunoglobulin on the tegument of Schistosoma mansoni.

Mice infected with Schistosoma mansoni were immunized against human type B Rh-positive (B+) RBC, bovine serum albumin, or horseradish peroxidase. Adult parasites, recovered by perfusion, extensively washed, and incubated in their respective antigens, selectively bound to their tegumental surfaces only those antigens to which their murine host had been immunized. All controls supported the specificity of those reactions leading to the conclusion that adult S. mansoni in mice have the ability to adsorb heterospecific antibody onto their tegumental surfaces. These surface immunoglobulins were lost within 10 min when complexed with theri antigens or within 2.5 hr when incubated at 37 degrees C. Parasites that had lost their tegumental immunoglobulins regained them when incubated in normal mouse or rat anti-human type B Rh-negative (B-) RBC serum. Those parasites that had their surface immunoglobulins reconstituted with rat anti-human B- serum specifically bound human B- RBC, suggesting the possible presence of Fc receptors on adult S. mansoni.

ABO Blood-Group System↗