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R D Pearson

Publications and source records attributed to R D Pearson.

At least 127 records · Page 7Linked to original sources
PubMed1984

Stage-specific variations in lectin binding to Leishmania donovani.

Visceral leishmaniasis is caused by the dimorphic protozoan Leishmania donovani, which exists as an aflagellar amastigote within mammalian mononuclear phagocytes and as a flagellated extracellular promastigote in its sandfly vector. We have identified four plant lectins that bind to the L. donovani surface, and through these we have documented stage-specific differences in exposed surface carbohydrates. Concanavalin A bound to both promastigotes and amastigotes; binding was inhibited by mannose or alpha-methyl-mannoside, implying a mannose-containing residue on the surface of both parasite stages. Ricinus communis agglutinin, which binds to galactose-containing residues, also bound to both stages and was inhibited by lactose, implying a galactose-containing glycoconjugate on the parasite surface. Two other lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), exhibited stage specificity in their binding characteristics. Amastigotes bound WGA but not PNA. During the process of conversion from the amastigote to the promastigote stage, the WGA-binding glycoconjugate was lost, and a PNA-binding residue was newly displayed. WGA binding was inhibited by N-acetyl-D-glucosamine and was not altered by neuraminidase treatment, suggesting the presence of an exposed N-acetyl-D-glucosamine moiety on the amastigote surface. The PNA binding site is known to accommodate the oligosaccharide beta-D-galactose-(1----3)-N-acetyl-D-galactosamine; in our system, PNA may have identified an internal rather than a terminal galactose on the promastigote surface. Localized binding of WGA and PNA to the surface of intermediate phases of the parasite suggested inhomogeneous and changing surface characteristics during conversion from amastigote to promastigote stages. This evolution of L. donovani surface glycoconjugates may be important in the adaptation of the organism to its divergent mammalian host and arthropod vector environments.

Age Factors↗
PubMed1984

The relationship of American visceral leishmaniasis to ABO blood group type.

It has been hypothesized that the Leishmania use a system of camouflage or mimicry of human ABO blood group antigens to evade host defense mechanisms. In order to test this hypothesis, the distribution of ABO blood groups among healthy control donors and among patients with visceral leishmaniasis in northeastern Brazil was compared. No significant differences were found between patients with American visceral leishmaniasis and controls, indicating that ABO blood group type is not an important determinant in the development of clinically apparent visceral leishmaniasis in that area. The findings raise doubt about the validity of the original hypothesis.

ABO Blood-Group System↗
PubMed1984

Susceptibility of Giardia lamblia trophozoites to the lethal effect of human serum.

To define the potential role of complement and antibody in host defense against Giardia lamblia, the effect of human serum on axenically cultured G. lamblia trophozoites was studied. Sera from patients without a history of giardiasis and with no detectable antibody by an indirect immunofluorescence antibody (IFA) assay (IFA titers less than 1:2) killed from 8 to 76% of trophozoites (n = 23 sera). Whereas less than 10% of parasites incubated in phosphate-buffered saline alone were killed, 16 sera killed from 10 to 25% and six sera killed from 25 to 75%. One serum with an anti-G lamblia antibody titer of 1:128 killed greater than 98% of the parasites. The complement dependency of killing was demonstrated by abrogation of the lethal effect when serum was chelated with EDTA (7 mM) or was heat-inactivated (56 degrees C, 30 min), and, in an immunofluorescence assay, by detection of C3 on parasites killed by normal serum. When the classical complement pathway was selectively blocked by using serum chelated with Mg+2 (2 mM)-EGTA (8 mM), or serum congenitally deficient for the second component of complement, there was no killing; thus, killing was dependent on the presence of an intact classical pathway. In each of three sera from donors with negative IFA titers, an absorbable factor specific for G. lamblia, possibly antibody not detected by IFA, was required for classical pathway activation. To determine if alteration of the surface of G. lamblia would render it an activator of the alternative pathway of complement, trophozoites were studied after cell death or after treatment with neuraminidase or trypsin. In MgEGTA-chelated serum, dead trophozoites activated the alternative pathway as determined by consumption of Factor B and deposition of C3 on their surface. In contrast, untreated or enzyme-treated living parasites did not activate the alternative pathway.

Adult↗
PubMed1983

Giardia lamblia infection of suckling mice.

Axenically cultured Giardia lamblia trophozoites (2 x 10(5)) were inoculated by gavage into suckling mice. All mice three, seven, and 14 days old became infected, with the peak trophozoite count in the small bowel of 5.3 +/- 1.1 x 10(6) occurring seven days after inoculation of three-day-old mice. In addition to infecting each of 65 challenged mice, G. lamblia was able to complete its life cycle by encysting and, as cysts, to infect previously unchallenged animals. Control mice given culture medium alone, mice challenged with trophozoites when older than 14 days of age, and mothers of infected mice did not become infected. There was no difference in body weight between infected mice and control mice, nor were histopathologic changes in the small bowel noted at the time of peak infection. Infection was cleared in all mice by 17-21 days. Thus, axenically cultured G. lamblia trophozoites are capable of infecting and completing their life cycle in suckling mice. The susceptibility of mice to infection is remarkably age specific, and the infection is apparently without adverse effects on the murine host.

Aging↗
PubMed1983

Susceptibility of Bordetella species to growth inhibition and killing by chlorpromazine.

Chlorpromazine, the prototype phenothiazine tranquilizer, inhibited the growth and killed organisms of the genus Bordetella. There were striking differences, however, among the three Bordetella species. Bordetella pertussis was most susceptible, with some inhibition of growth at greater than or equal to 4 micrograms/ml and killing at 16 micrograms of chlorpromazine per ml. Bordetella parapertussis and Bordetella bronchiseptica were less susceptible, with killing at 32 and 256 micrograms/ml, respectively. Although the phenothiazines were inhibitory for Bordetella extracytoplasmic adenylate cyclase, the lethal effect occurred at a lower concentration and did not appear to involve modification of the enzyme activity. Exposure of B. pertussis to combinations of chlorpromazine and erythromycin resulted in impaired growth at concentrations lower than that of either drug alone, but there was no evidence that the two drugs interacted either synergistically or antagonistically.

Adenylyl Cyclase Inhibitors↗
PubMed1983

Interaction of Leishmania donovani promastigotes with human phagocytes.

Leishmania donovani is an important intracellular protozoal pathogen of humans, which resides solely within mononuclear phagocytes. Phase-contrast microscopy and cinemicroscopy were used to examine the interaction of L. donovani promastigotes with human phagocytes to characterize and quantitate the sequence of events that results in leishmanial infection.

Animals↗
PubMed1983

Praziquantel: a major advance in anthelminthic therapy.

Praziquantel recently has been approved in the United States for use against a broad range of trematodes and cestodes. The drug is highly effective against all Schistosoma species that infect humans as well as other flukes and tapeworms, including the larval stage of Taenia solium, which causes cysticercosis. In addition, praziquantel is relatively nontoxic, well accepted by patients, and can be given orally in one dose or several doses in a single day. Praziquantel lowers or abolishes the threshold for treating persons with these infections, and, if costs can be contained, may help in the global control of serious systemic helminthic infections.

Animals↗
PubMed1983

Differential survival of Leishmania donovani amastigotes in human monocytes.

Leishmania donovani is an important intracellular protozoal pathogen of man; it is found solely within macrophages in its amastigote stage in humans, and exists in its extracellular, flagellated promastigote stage in the sandfly, its arthropod vector. To determine if either stage of L. donovani was capable of surviving within monocytes--the oxidatively active precursors of tissue macrophages--interactions of the parasite with human monocytes were studied in vitro. Amastigotes and promastigotes were ingested to a comparable degree by monocytes; whereas 79% of promastigotes were killed within 48 hr, however, amastigotes survived and multiplied threefold over 5 days. Promastigotes, which have been shown to be sensitive to hydrogen peroxide-peroxidase-halide microbicidal mechanisms, elicited a phagocytic oxidative burst that was 49% of the response to serum-opsonized zymosan, as assessed by luminol-enhanced chemiluminescence. NBT was reduced to formazan in 71% of monocytes exposed to promastigotes. The death of promastigotes within monocytes could be attributed at least in part to oxidative microbicidal mechanisms because there was no significant decrease in the number of cell-associated parasites in monocytes from donors with chronic granulomatous disease of childhood. In contrast to promastigotes, amastigotes survived within monocytes, despite eliciting an oxidative response that was 27% of the response produced by serum-opsonized zymosan; this response was not significantly different from that produced by promastigotes. In a phagocyte-free system, amastigotes were found to be sevenfold more resistant than were promastigotes to the lethal effects of hydrogen peroxide. The survival of L. donovani in human monocytes is thus dependent on the parasite stage; promastigotes are ingested, they elicit an oxidative burst, and the majority are killed by oxidative microbicidal mechanisms, whereas amastigotes are ingested and survive to parasitize human monocytes successfully, despite eliciting a phagocytic oxidative burst.

Adult↗
PubMed1982

Lethal effect of phenothiazine neuroleptics on the pathogenic protozoan Leishmania donovani.

Phenothiazine drugs, which are widely used for their antipsychotic, antianxiety, and antiemetic effects, have been found to have protozoacidal effects on the human pathogen Leishmania donovani. These compounds are lethal to both the extracellular stage of the organism, which is inoculated into humans by the sand fly, and the intracellular stage, which is found solely in human macrophages during established infection.

Animals↗
PubMed1982

Cellular heterochrony and neoplasia.

Neoplastic change in a cell represents a cellular "macroevolutionary' event. Through variation or rearrangement of regulatory genes, neoplastic cells reiterate the expression of normally quiescent ancestral, juvenile, or embryonic traits and behavior at an inappropriate stage in their ontogeny. The author has coined the term 'cellular heterochrony' to illustrate analogic similarities in the molecular modes of evolutionary change of both anaplastic cancer cells and the heterochronic, paedomorphic evolution of organisms. In these pages, anaplasia is considered to be part of a larger biological phenomenon. A theory regarding the role of prolactin and thyroxine in tumourigenesis is presented to explain the atavistic or heterochronic development and possible metamorphosis of retrodifferentiated malignant cells.

Animals↗
PubMed1982

Susceptibility of Shigella species to erythromycin.

Two of the most common causes of inflammatory enteritis are Campylobacter fetus subsp. jejuni and Shigella species. No single antimicrobial agent is recommended for treatment of both diseases. Erythromycin is used to treat C. fetus subsp. jejuni infections but has not been studied in shigellosis. For this reason, we determined the susceptibility of 22 strains of Shigella to erythromycin and found that Shigella species are susceptible to concentrations of erythromycin which are obtainable in stool.

Dose-Response Relationship, Drug↗