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Biomedical subjects

J J Marr

Publications and source records attributed to J J Marr.

At least 73 records · Page 4Linked to original sources
PubMed1980

Pyrazolopyrimidine metabolism in African trypanosomes: metabolic similarities to Trypanosoma cruzi and Leishmania spp.

Growth inhibition and radioisotope incorporation studies with allopurinol (4-hydroxypyrazolo(3,4-d)pyrimidine) have shown that the African trypanosomes are biologically and biochemically similar to Leishmania spp. and Trypanosoma cruzi with respect to their response to this compound. These organisms, as a group, share the unique ability to convert allopurinol sequentially to its ribonucleoside monophosphate and 4-aminopyrazolo(3,4-d)pyrimidine ribonucleoside mono-, di- and triphosphates.

Allopurinol↗
PubMed1980

Prevention of transfusion-induced Chagas' disease by amphotericin B.

Amphotericin B, a polyene antibiotic effective against eukaryotic cells, can eliminate the trypomastigote form of Trypanosoma cruzi from blood stored at 4 degrees C. This antitrypanosomal effect can be achieved with a concentration of 3 micrograms/ml within 48 hours. This concentration of amphotericin B does not produce hemolysis over a period of 3 weeks. Amphotericin B methyl ester and nystatin are not effective. Amphotericin B may be considered as a replacement for crystal violet in blood bank blood to prevent transfusion-induced Chagas' disease.

Amphotericin B↗
PubMed1979

Metabolism of pyrazolo(3,4-d)pyrimidines in Leishmania braziliensis and Leishmania donovani. Allopurinol, oxipurinol, and 4-aminopyrazolo(3,4-d)pyrimidine.

Leishmania donovani and Leishmania braziliensis grown in culture formed millimolar concentrations of allopurinol ribonucleoside 5'-monophosphate from [6-14C]allopurinol. In addition, allopurinol 1-ribonucleoside, oxipurinol riboside 5'-monophosphate, and three new metabolites of allopurinol, namely, 4-aminopyrazolo(3,4-d)pyrimidine ribonucleoside 5'-monophosphate and the corresponding di- and triphosphates (1-ribosyl 4-aminopyrazolo(3,4-d)pyrimidine 5'-diphosphate and 1-ribosyl 4-aminopyrazolo(3,4-d)pyrimidine 5'-triphosphate) were identified in the parasitic cells. They were formed via a unique amination reaction from 1-ribosyl allopurinol 5'-phosphate, analogous to the conversion of IMP to AMP. [6-14C]Allopurinol was incorporated into RNA of L. donovani in the form of 4-aminopyrazolo(3,4-d)pyrimidine. Adenine reversed the growth inhibition of allopurinol and prevented its metabolism to all of the ribonucleotide metabolites. L. donovani was 2- to 4-fold more active in its metabolism of allopurinol to ribonucleotides than L. braziliensis. 4-Aminopyrazolo(3,4-d)pyrimidine inhibited cell growth and resulted in high intracellular levels of 1-ribosyl allopurinol 5'-phosphate and smaller amounts of the 4-aminopyrazolo(3,4-d)pyrimidine ribonucleotides. The metabolism of allopurinol to 4-aminopyrazolo(3,4-d)pyrimidine ribonucleotides and its resultant cytotoxicity occurs in these parasitic protozoans, but not in mammalian cells.

Adenine↗
PubMed1979

Comparative metabolism of a new antileishmanial agent, allopurinol riboside, in the parasite and the host cell.

HPP-Rib is a potent antileishmanial agent, which has been useful in defining new and unusual purine metabolizing pathways in leishmaniae, in comparison with those in the host. The ribosyl linkage both in the parasite and in the host is resistant to cleavage. In the parasite there is a selective and marked conversion of HPP-Rib to HPP-Rib-5'-P and 4-APP ribonucleotides as well as incorporation into RNA, which does not occur in the host. These findings with HPP-Rib suggest a new chemotherapeutic approach which may be exploited in the treatment of leishmaniasis.

Allopurinol↗
PubMed1979

Cardiobacterium hominis endocarditis.

A case of Cardiobacterium hominis endocarditis involving a prosthetic heart valve is reported, and 12 previously reported cases are reviewed. This gram-negative rod grows slowly in blood cultures and is readily suppressed for long periods of time by token antibiotic administration. It should be considered as a causative agent in culture-negative cases of endocarditis and also when a gram-negative rod is isolated which is sensitive to all antibiotics. The treatment of choice is penicillin.

Aged↗
PubMed1978

Purine metabolism in Leishmania donovani and Leishmania braziliensis.

We have studied purine metabolism in the culture forms of Leishmania donovani and Leishmania braziliensis. These organisms are incapable of synthesizing purines de novo from glycine, serine, or formate and require an exogenous purine for growth. This requirement is better satisfied by adenosine or hypoxanthine than by guanosine. Both adenine and inosine are converted to a common intermediate, hypoxanthine, before transformation to nucleotides. This is due to the activity of an adenine aminohydrolase ((EC 3.5.4.2), a rather unusual finding in a eukaryotic cell. There is a preferential synthesis of adenine nucleotides, even when guanine or xanthine are used as precursors. The pathways of purine nucleotide interconversions in these Leishmania resemble those found in mammalian cells except for the absence of de novo purine biosynthesis and the presence of an adenine-deaminating activiting.

Formates↗
PubMed1978

Antitrypanosomal effect of allopurinol: conversion in vivo to aminopyrazolopyrimidine nucleotides by Trypanosoma curzi.

The parasite Trypanosoma cruzi metabolizes allopurinol by a sequential conversion to allopurinol mononucleotide and aminopurinol mononucleotide. The latter is incorporated into RNA. This transformation of a widely used innocuous agent, allopurinol, into a toxic adenine analog appears to account for the antiprotozoan effect of allopurinol. These unique enzymatic activities appear to occur only in T. cruzi and the pathogenic lesihaminae. Allopurinol may serve as a model for the synthesis of similar antiprotozoan agents.

Adenine↗
PubMed1978

Effect of atypical antibiotic resistance on microorganism identification by pattern recognition.

We classified microorganisms from the clinical laboratory by using information provided by the Gram stain and antibiotic sensitivity profiles obtained with the Bauer-Kirby technique. Approximately 4,000 microorganisms, routinely identified and tested for antibiotic sensitivities in a large hospital microbiology laboratory, were used as a data set for several pattern recognition classification methods: K--nearest-neighbor analysis, statistical isolinear multicomponent analysis, Bayesian inference, and linear discriminant analysis. K--nearest-neighbor analysis yielded the highest prospective classification accuracy for gram-negative organisms, 90%. When those organisms displaying an atypical antibiotic resistance pattern were excluded from the data, the gram-negative classification accuracy improved to 95%. These results are inferior to currently accepted biochemical identification methods. Microorganisms with atypical antibiotic resistance patterns are likely to be misidentified and are common enough (17% of our isolates) to limit the feasibility of routine identification of microorganisms from their antibiotic sensitivities.

Anti-Bacterial Agents↗
PubMed1978

A comparative study of tuberculous and other mycobacterial infections and their associations with malignancy.

We reviewed 162 cases of bacteriologically proved mycobacterial disease. Nontuberculous acid-fast bacilli were responsible for 27 per cent of the infections, a higher frequency than has previously been reported, and Mycobacterium kansasii and Mycobacterium avium-intracellulare were isolated with equal frequency. This indicates that Mycobacterium avium-intracellulare may be a significant agent of disease in the Midwest as well as the Southeast. There are no useful clinical, radiographic, or laboratory features to distinguish between tuberculous and other mycobacterial infections. Mycobacteria act as opportunistic pathogens in persons with malignant diseases. The attack rate was 607 of 100,000 persons verus 95 of 100,000 persons in our general hospital population. Mycobacterium tuberculosis and the nontuberculous mycobacteria were of equal virulence in this regard.

Adolescent↗
PubMed1978

Atypical mycobacteria and the xenograft valve.

During a 4 month interval, cultures taken at the time of porcine xenograft valve implantation grew a fastidious atypical mycobacterium, Mycobacterium chelonei (Runyon's groups IV), in eight of 20 patients. Initial growth occurred at 2 to 3 weeks in thioglycollate broth only; detailed biochemical and bacteriologic evaluation demonstrates altered catalase activity accounting for its initial slow growth. Only one patient has manifested clinical evidence of infection 5 months after mitral valve replacement. A large pericardial effusion required pericardiectomy. Pericardial tissue and fluid have grown M. chelonei with the same growth characteristics as the initial valve culture. It is recommended that manufacturers of xenograft valve bioprostheses maintain a quarantine of 6 weeks until cultures, smears of culture broth, and microscopic evaluation of aortic wall coupons are negative. Users of these prostheses should keep cultures for a minimum of 3 weeks. Should positive cultures result, antimicrobial therapy should be considered only with clinical evidence of infection.

Animals↗