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Biomedical subjects

R D Pearson

Publications and source records attributed to R D Pearson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Common-source outbreak of trichinosis associated with eating raw home-butchered pork.

Four patients had trichinosis after consuming raw home-butchered pork. The patients had fever, myalgias, periorbital edema, and conjunctivitis. All of the patients had nausea, vomiting, or diarrhea (corresponding to the intestinal phase of the infection) seven to ten days before the onset of fever and myalgias. Laboratory findings included eosinophilia, elevated serum CPK and aldolase values, and seroconversion of Trichinella serology one month after onset of myalgias. The patients were treated with mebendazole and prednisone and recovered uneventfully.

Adult↗
PubMed1988

Identification of leishmanial antigens in the sera of patients with American visceral leishmaniasis.

Circulating immune complexes are present in the sera of patients with visceral leishmaniasis caused by Leishmania donovani chagasi. In order to determine whether these complexes contain parasite antigens, sera were collected from Brazilian patients with visceral leishmaniasis and from hospitalized control subjects with other diagnoses. High-molecular-weight complexes were precipitated from pooled sera with 2.5% polyethylene glycol. Approximately 140-fold-more protein was precipitated from patient sera than from control sera; 12% of the total patient serum protein was precipitated. Patient serum precipitates contained immunoglobulins G (525 mg/dl), M (27 mg/dl), and A (8 mg/dl). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the patient serum precipitates revealed multiple bands, including a prominent band at 70 kilodaltons, that were not seen in precipitates of control sera. The 70-kilodalton band was recognized by human and hamster sera with antileishmanial antibodies, but not by control sera. Finally, immunization of BALB/c mice with the high-molecular-weight precipitates from patients elicited antileishmanial antibodies against L. donovani chagasi antigens as detected by enzyme-linked immunosorbent assay and Western blot (immunoblot) assay. In summary, sera of patients with American visceral leishmaniasis were found to have high-molecular-weight complexes that contained one or more parasite antigens. These complexes may play a role in the immunology of the disease, and detection of circulating parasite antigens has potential diagnostic importance.

Antigen-Antibody Complex↗
PubMed1988

Roles of CR3 and mannose receptors in the attachment and ingestion of Leishmania donovani by human mononuclear phagocytes.

Leishmania donovani is an obligate intracellular parasite of mammalian macrophages. Two macrophage receptors, the mannose-fucose receptor (MFR) and the receptor for complement component C3bi, CR3, were examined for their roles in the attachment and ingestion of L. donovani by human monocyte-derived macrophages. Two monoclonal antibodies which bind to the human CR3, anti-Mo1 and anti-Mac-1, inhibited both attachment and ingestion of L. donovani promastigotes after preincubation with human monocyte-derived macrophages; attachment was inhibited by 40 and 62% by anti-Mo1 and anti-Mac-1, respectively, and ingestion was inhibited by 34 and 51% by anti-Mo1 and anti-Mac-1, respectively. The interaction between promastigotes and CR3 may not have involved the C3bi-binding site on CR3, however, because a monoclonal antibody which exhibits specificity for this site, OKM10, inhibited promastigote attachment by only 18%. In contrast, OKM1, which is believed to react with the alternate lectinlike binding site on CR3, inhibited ingestion by 65%. MFR activity was inhibited using the soluble MFR ligands, mannan and mannosylated bovine serum albumin, which also inhibited promastigote attachment by 40 and 37%, respectively. The simultaneous inhibition of both CR3 (by anti-Mac-1) and the MFR (by either mannan or mannosylated bovine serum albumin) resulted in a greater decrease in promastigote attachment than inhibition of either receptor alone. Additionally, the reduction of MFR activity by allowing macrophages to adhere to a mannan-coated surface followed by the addition of anti-CR3 antibodies resulted in an 81% inhibition of promastigote ingestion, a greater decrease than was obtained by manipulation of either receptor alone. The results suggest that the MFR and CR3 independently participate in the attachment and ingestion of L. donovani promastigotes by human macrophages.

Animals↗
PubMed1988

Effects of a chronic wasting infection on skeletal muscle size and contractile properties.

To evaluate the effects of chronic infection on skeletal muscle dimensions and contractile properties, we used a hamster model of visceral leishmaniasis, a parasitic infection of the reticuloendothelial system produced by Leishmania donovani (LD). To distinguish between effects of reduced caloric intake and infection per se, we also studied healthy control animals and noninfected animals subjected to caloric restriction. Three muscles were tested in vitro: plantaris, soleus, and diaphragm. Both caloric restriction and LD infection caused loss of body weight and reduced muscle cross-sectional areas and wet weights. The interventions had variable effects on in vitro contractile properties, the most pronounced being reduction in peak tension in response to tetanic stimulation. Tension loss was 35-45%, except for a loss of 65% in plantaris of LD-infected animals. We conclude that chronic LD infection affects skeletal muscles in both indirect and direct ways. 1) Reduced caloric intake due to anorexia decreases muscle size and active tension. Disuse probably enhances this effect in limb muscles. 2) Infection produces profound weakness of inactive fast-twitch muscle by unknown mechanisms.

Animals↗
PubMed1988

Health advice for international travel.

Travel to the developing world by U.S. citizens has been increasing. Exposure to illnesses such as travelers' diarrhea, malaria, and vaccine-preventable diseases challenges the internist to provide pre-travel advice. Each traveler's itinerary, duration of stay and medical history, including previous immunizations, should be reviewed. Immunizations that may be required by individual countries, such as yellow fever and cholera, may then be administered. Immunizations for diseases such as hepatitis, typhoid fever, and meningococcal disease can be given according to the type of exposure within each country. Restricting a traveler's diet to cooked foods and purified, carbonated, or heated beverages may prevent travelers' diarrhea and other enteric infections. Most travelers will want to carry medications to treat diarrhea promptly. Malaria is prevented by avoiding mosquitos, taking safe and appropriate anti-malarials and treating malaria if it occurs. Preparation before travel may prevent medical complications.

Adult↗
PubMed1987

Inhibition of monocyte oxidative responses by Bordetella pertussis adenylate cyclase toxin.

Bordetella pertussis and the other Bordetella species produce a novel adenylate cyclase toxin which enters target cells to catalyze the production of supraphysiologic levels of intracellular cyclic adenosine monophosphate (cAMP). In these studies, dialyzed extracts from B. pertussis containing the adenylate cyclase toxin, a partially purified preparation of adenylate cyclase toxin, and extracts from transposon Tn5 mutants of B. pertussis lacking the adenylate cyclase toxin, were used to assess the effects of adenylate cyclase toxin on human peripheral blood monocyte activities. Luminol-enhanced chemiluminescence of monocytes stimulated with opsonized zymosan was inhibited greater than 96% by exposure to adenylate cyclase toxin-containing extract, but not by extracts from adenylate cyclase toxin-deficient mutants. The chemiluminescence responses to particulate (opsonized zymosan, Leishmania donovani, and Staphylococcus aureus) and soluble (phorbol myristate acetate) stimuli were inhibited equivalently. The superoxide anion generation elicited by opsonized zymosan was inhibited 92% whereas that produced by phorbol myristate acetate was inhibited only 32% by B. pertussis extract. Inhibition of oxidative activity was associated with a greater than 500-fold increase in monocyte cAMP levels, but treated monocytes remained viable as assessed by their ability to exclude trypan blue and continued to ingest particulate stimuli. The major role of the adenylate cyclase toxin in the inhibition of monocyte oxidative responses was demonstrated by: 1) little or no inhibition by extracts from B. pertussis mutants lacking adenylate cyclase toxin; 2) high level inhibition with extract from B. parapertussis, a related species lacking pertussis toxin; and 3) a reciprocal relationship between monocyte cAMP levels and inhibition of opsonized zymosan-induced chemiluminescence using both crude extract and partially purified adenylate cyclase toxin. Pertussis toxin, which has been shown to inhibit phagocyte responses to some stimuli by a cAMP-independent mechanism, had only a small (less than 20%) inhibitory effect when added at concentrations up to 100-fold in excess of those present in B. pertussis extract. These data provide strong support for the hypothesis that B. pertussis adenylate cyclase toxin can increase cAMP levels in monocytes without compromising target cell viability or impairing ingestion of particles and that the resultant accumulated cAMP is responsible for the inhibition of oxidative responses to a variety of stimuli.

Adenylate Cyclase Toxin↗
PubMed1987

Upper extremity swelling and hyperpigmentation due to onchocerciasis in an American.

An American woman who had lived in Equatorial Guinea was seen in the United States with intermittent swelling, pruritus, hyperpigmentation, and mild cutaneous atrophy of the right arm. Filarial diseases were considered in the differential diagnosis; skin snips subsequently revealed Onchocerca volvulus microfilariae. There was no evidence of ocular involvement. The case illustrates the importance of obtaining a history of international travel, the need to consider "exotic" parasitic diseases in travelers returning from the tropics, and several of the presenting features of onchocerciasis. In the past, onchocerciasis was treated with diethylcarbamazine and suramin, both of which have appreciable toxicity. A major recent advance has been the introduction of ivermectin, which appears to be more effective and less toxic, and is currently undergoing clinical evaluation in the United States and abroad.

Adult↗
PubMed1987

Ingestion of Giardia lamblia trophozoites by human mononuclear phagocytes.

Mononuclear phagocytes may be important effector cells against Giardia lamblia. Human monocyte-derived macrophages were incubated with G. lamblia trophozoites in 13% heat-inactivated autologous serum. At a G. lamblia/macrophage ratio of 1:1, the number of trophozoites ingested per 100 macrophages ranged from 1 to 12 at 0.5 h and increased for all donors (n = 6) to 10 to 92 at 8 h. Ingestion was confirmed by electron microscopy. Increasing the parasite/phagocyte ratio to 5:1 increased the percentage of macrophages with adherent but not ingested trophozoites. Incubating Giardia cells and macrophages with 20% immune serum increased ingestion of parasites eightfold, indicating that anti-G. lamblia antibody can enhance ingestion. Both phase-contrast microscopy and electron microscopy documented trophozoite destruction within macrophages. Ingestion of parasites elicited an oxidative burst as measured by luminol-enhanced chemiluminescence. In vitro, Giardia trophozoites were killed by greater than or equal to 5 X 10(-5) M H2O2. Fusion of lysosomes with parasite-containing phagosomes was suggested by acridine orange-stained preparations. Human macrophages have the capacity to ingest Giardia trophozoites and to kill intracellular parasites, possibly by oxidative microbicidal mechanisms.

Animals↗
PubMed1987

Use of pyrimethamine-sulfadoxine (Fansidar) in prophylaxis against chloroquine-resistant Plasmodium falciparum and Pneumocystis carinii.

The widespread emergence of chloroquine-resistant Plasmodium falciparum led to the formulation of an effective, fixed combination of two antimalarial agents, pyrimethamine and the long-acting sulfonamide sulfadoxine, for prophylaxis and treatment. These drugs act at sequential steps to inhibit the formation of tetrahydrofolate in the parasite. Recently, their use for malaria prophylaxis has been associated with severe, at times fatal, cutaneous reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. These reactions have necessitated a major reassessment of the indications for pyrimethamine-sulfadoxine use and increased the search for pharmacologic, immunologic and behavioral approaches to the prophylaxis and treatment of infection with P. falciparum. Pyrimethamine-sulfadoxine may be effective in preventing recurrent pneumonia caused by Pneumocystis carinii in patients with the acquired immunodeficiency syndrome, but life-threatening cutaneous reactions have also been reported in this setting.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Early histopathology of experimental infection with Leishmania donovani in hamsters.

The extracellular promastigote stage of Leishmania donovani is inoculated by a phlebotomine sandfly into the skin of a susceptible host, after which visceral dissemination and clinical disease may ensue. Using a hamster model we examined the histopathology of early infection with L. donovani after intradermal inoculation of cultured promastigotes. The initial response was a mixed polymorphonuclear (PMN)-mononuclear phagocyte infiltrate, noted between 1 and 24 hr after inoculation, which became primarily mononuclear by 48 hr. Parasites were initially found intracellularly in both PMN's and mononuclear phagocytes, but by 48 hr they had assumed amastigote-like morphology and were found exclusively in macrophages. The number of parasites per infected macrophage increased during the first week after inoculation, suggesting that intracellular replication of the organism was taking place. This was followed by the formation of granulomas between 4 and 6 wk. By 8 wk intracellular parasites were largely gone. The histologic response was consistent with early destruction of parasites in PMN's, and survival and replication of L. donovani in macrophages. Cutaneous infection with the parasite was eventually controlled locally, coincident with granuloma formation. Despite these local responses, the organism was able to disseminate and eventually produce typical visceral leishmaniasis.

Animals↗
PubMed1986

Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism.

The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extra-cellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. We have found remarkable similarities between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands. Mannan (2.5 mg/ml) decreased ingestion by 63.7% (p less than 0.001), and the neoglycoproteins mannose-BSA and fucose-BSA (20 micrograms/ml) inhibited parasite ingestion by 46.5% and 39.6%, respectively (p less than 0.04). In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. These results are consistent with reports that MFR activity is present in monocyte-derived macrophages but not in monocytes. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4% (p less than 0.006). Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion (p less than 0.006). Additionally NH4Cl, a weak lysosomotropic base that impairs MFR recycling, decreased macrophage ingestion of promastigotes by 38.2% (p less than 0.03, 30 mM NH4Cl). Subinhibitory concentrations of NH4Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parasite ingestion by 76.4% (p less than 0.002). These studies suggest that L. donovani promastigotes may utilize a receptor system on human monocyte-derived macrophages, the MFR, to efficiently parasitize the human host.

Adult↗