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Biomedical subjects

R D Pearson

Publications and source records attributed to R D Pearson.

At least 109 records · Page 6Linked to original sources
PubMed1986

Listeria monocytogenes cerebritis, bacteremia, and cutaneous lesions complicating hairy cell leukemia.

Hairy cell leukemia is a lymphoreticular malignancy characterized by a chronic course and multiple defects in host defense mechanisms. Infections are the major cause of morbidity and mortality in this malignancy. Opportunistic infections due to pathogens normally controlled by cell-mediated immune mechanisms have been increasingly described but have not included listerial infections. This report describes a case of disseminated Listeria monocytogenes infection including the uncommon manifestations of cerebritis and cutaneous lesions in a patient with hairy cell leukemia.

Anti-Bacterial Agents↗
PubMed1986

Evolutionary theory, regeneration and cancer.

Three central problems for biology that remain unsolved are: a complete understanding of macroevolution, the problem of morphogenesis, i.e., the regulation of differentiation during development (related to this is the problem of regeneration), and the sequential maladaptation of these developmental processes, neoplasia. Combined breakthroughs in molecular cytogenetics concerning the "transposable elements" in the evolving genone, and the cellular transforming genes ("oncogenes") implicated in certain neoplastic diseases, add dimension to the discussion about the occurrence of "fetal" or anestral products of anaplastic cells. It is theorized that hormones are a major factor in the non-random regulation of cellular heterochrony in tumourigenesis. What is offered here is a theoretical overview of some current trends in the evolutionary sciences. Some ideas (old and new) on regeneration research will be discussed, and an attempt will be made to integrate those notions underlying hormonal oncology which suggest that there is a common thread woven through these problems, creating the fabric of biological change.

Animals↗
PubMed1986

Susceptibility of Campylobacter jejuni to strain-specific bactericidal activity in sera of infected patients.

Campylobacter jejuni is a common cause of inflammatory enteritis, which in normal hosts is usually self-limited and resolves without antibiotic therapy. C. jejuni bacteremia is very rare. We examined sera for bactericidal activity that might be important in limiting the extent of C. jejuni infection in man. We studied the ability of nonimmune sera and homologous and heterologous immune sera from infected patients to kill different fresh case isolates of C. jejuni in vitro. The reduction of the log10 concentration of viable C. jejuni (log10 killing) by fresh sera from nonimmune donors was only 0.2. Log10 killing by homologous acute sera varied from 0 to 3.8 (mean, 1.8). Convalescent sera showed remarkable log10 killing of only homologous C. jejuni, with values of 2.7 to 4.4 (mean, 3.7). The bactericidal effects of acute and convalescent sera were abrogated by heat and EDTA chelation, indicating mediation by complement. The role of classical complement pathway activation was supported by chelating sera with magnesium EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid] and by reconstitution experiments with heat-inactivated sera, C2-deficient serum, and purified C2. The requirement of specific antibody for the serum bactericidal effect was indicated by the loss of bactericidal activity when immune sera were absorbed with homologous but not heterologous whole C. jejuni isolates. The presence of specific antibodies was further documented by agglutination of only homologous C. jejuni suspensions by heat-inactivated immune sera. Studies with polymorphonuclear leukocytes suggested that ingestion and killing of two C. jejuni strains were modest and variable in the presence of heat-inactivated homologous serum. In summary, the data document a potent serum bactericidal effect that develops rapidly and specifically during C. jejuni enteritis and may be an important factor in host defense against C. jejuni.

Antibodies, Bacterial↗
PubMed1986

Giardia lamblia: a culture method for determining parasite viability.

A simple, quantitative method has been developed to assess the viability of Giardia lamblia trophozoites after exposure to a potentially lethal agent. This method utilizes the ability of trophozoites which remain viable to replicate and multiply. In this study, the percent dead trophozoites after incubation in 20% fresh human serum was determined first by morphologic criteria and then by the ability of parasites to multiply in fresh medium over 48 hr. Using the number of parasites after 48 hr of growth, the original number of dead trophozoites in the serum-exposed samples was determined by extrapolation from a standard growth curve. Ten sera which killed from 7% to 89% of trophozoites by morphologic criteria, killed 8% to 92% using the culture method; these two assays for viability correlated highly (r = 0.96). Use of the culture assay allows the assessment of the lethal effects of serum and can be applied both to the study of other host defense mechanisms on Giardia trophozoites and to antimicrobial susceptibility testing.

Giardia↗
PubMed1985

Interaction of human leukocytes and Entamoeba histolytica. Killing of virulent amebae by the activated macrophage.

Capable effector mechanisms in the human immune response against the cytolytic, protozoan parasite Entamoeba histolytica have not been described. To identify a competent human effector cell, we studied the in vitro interactions of normal human polymorphonuclear neutrophils, peripheral blood mononuclear cells (PBMC), monocytes (MC), and MC-derived macrophages with virulent axenic amebae (strain HMI-IMSS). Amebae killed neutrophils, PBMC, MC, and MC-derived macrophages (P less than 0.001), without loss of parasite viability. The addition of heat-inactivated immune serum did not enable leukocytes to kill amebae, nor did it protect these host cells from amebae. MC-derived macrophages, activated with lymphokine elicited by the mitogens conconavalin A, phytohemagglutinin, or an amebic soluble protein preparation (strain HK9), killed 55% of amebae by 3 h in a trypan blue exclusion assay (P less than 0.001); during this time, 40% of the activated macrophages died. Lysis of amebae was confirmed using 111Indium oxine radiolabeled parasites and was antibody independent. Macrophage death appeared to be due to the deleterious effect of lysed amebae rather than the contact-dependent effector mechanisms of E. histolytica. Adherence between activated macrophages and amebae was greater than that between other leukocytes and amebae (P less than 0.001). Microscopic observations, kinetic analysis of the killing of amebae by activated macrophages, and suspension of amebae with adherent activated macrophages in a 10% dextran solution indicated that contact by activated macrophages was necessary to initiate the killing of amebae. Catalase but not superoxide dismutase inhibited the amebicidal capacity of activated macrophages (P less than 0.001). However, activated macrophages from an individual with chronic granulomatous disease were able to kill amebae, but not as effectively as normal cells (P less than 0.01). In summary, activated MC-derived macrophages killed virulent E. histolytica trophozoites through a contact-dependent, antibody-independent mechanism involving oxidative-dependent and -independent processes.

Adult↗
PubMed1985

The interaction of Leishmania donovani promastigotes and human fibroblasts in vitro.

Leishmania donovani promastigotes derived from infected hamster spleens, in either log phase or stationary phase growth, associated with human foreskin fibroblasts in vitro and assumed the morphological characteristics of amastigotes. This apparent conversion was noted within hours at 26 degrees C, 32 degrees C or 37 degrees C; in the continued presence of promastigotes, increasing numbers of amastigote-like forms were seen for 2 weeks at 26 degrees C or 32 degrees C. At 37 degrees C amastigote-like forms declined sharply after 6 days. Multiplication of amastigote-like forms was not observed at any temperature, this was also true of freshly isolated amastigotes from hamster spleens which associated with fibroblasts but did not multiply. Approximately 0.1% of promastigotes appeared to convert per day. Amastigote-like forms were seen within fibroblasts by transmission electron microscopy, surrounded by a closely applied host membrane. Scanning electron microscopy showed promastigotes with their flagellae under or within fibroblasts, but phagocytosis was not observed. These experiments suggest that the conditions required for promastigote-to-amastigote conversion may be different than those required for amastigote multiplication, and the mammalian core body temperature may not be required for promastigote conversion.

Animals↗
PubMed1985

Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases.

Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.

Amidines↗
PubMed1985

Bordetella extracytoplasmic adenylate cyclase: actions as a bacterial toxin.

Virulent Bordetella organisms produce an adenylate cyclase which is extracytoplasmic in location, activated by the eukaryotic regulatory protein, calmodulin, and able to act as a toxin, promoting cyclic AMP accumulation in target mammalian cells. Initial steps in purification of this novel adenylate cyclase toxin reveal two forms: one which possesses only enzymatic adenylate cyclase activity, but has no effect on intact target cells; and the other which has both enzymatic and intoxicating activity. These data suggest that this toxin may conform to the A/B model for bacterial toxins. A variety of mammalian cell types can be affected by the adenylate cyclase toxin, including neutrophils, macrophages, monocytes, lymphocytes, lymphoma cells, and pituitary cells. Although the consequence of intoxication in many cells is inhibition of normal function, the enhancement of pituitary hormone secretion by this toxin suggests that its biological effects are the result of cAMP accumulation. These data confirm the hypothesis that Bordetella adenylate cyclase is, indeed, a toxin and illustrate its role as a novel research probe.

Adenylyl Cyclases↗
PubMed1985

American visceral leishmaniasis (kala-azar).

Visceral leishmaniasis (kala-azar) is an important cause of morbidity and mortality in widely scattered areas of the world. To better characterize the South American form of the disease, the clinical and laboratory manifestations of 29 patients admitted to hospital (18 male and 11 female patients, mean age 4.9 years), were assessed in an endemic area in northeastern Brazil. Fever, weight loss, pronounced splenomegaly, hepatomegaly, anemia, thrombocytopenia, relative neutropenia, hypoalbuminemia and hypergammaglobulinemia were found in the majority of patients. Symptoms were often present for two or more months before diagnosis. Secondary infections complicated many cases; there were ten cases of pneumonia and half of the patients had one or more intestinal parasites. The average length of hospital stay was 27 days; all patients were treated with meglumine antimoniate (Glucantime). The mortality rate was 3%. American visceral leishmaniasis remains an important disease among children living in endemic areas.

Brazil↗
PubMed1984

Antileishmanial activity of chlorpromazine.

The antiprotozoal activity of chlorpromazine against the pathogenic protozoan Leishmania donovani, in both its amastigote and promastigote stages, was characterized. Chlorpromazine at concentrations greater than or equal to 3.12 micrograms/ml (9.8 X 10(-6) M) produced a significant reduction in viable promastigotes. The minimal protozoacidal concentration for promastigotes, defined as that concentration which produced greater than or equal to 90% reduction in viable parasites after 18 h, was 13.8 micrograms/ml. The results were similar when promastigote viability was assessed by flagellar motility or by the ability of drug-exposed or control promastigotes to incorporate [3H]uridine and [3H]leucine. Exposure of promastigotes to 50 micrograms of chlorpromazine per ml reduced O2 consumption by 87% within 30 min and immobilized 97% of parasites. Morphological disruption of promastigotes was observed by electron microscopy. The mean minimal protozoacidal concentration of chlorpromazine for amastigotes was 13.2 micrograms/ml. Chlorpromazine given orally (20 mg/kg per day for 14 days) reduced the parasite burden in L. donovani-infected hamsters by 64.2% (P less than 0.01) as measured by the number of amastigotes in touch preparations of livers and by 67.9% (P = 0.03) as measured by the number of promastigotes derived from homogenates of spleens. This dose is ca. 10-fold greater than that tolerated by patients being treated for psychiatric illness. Although chlorpromazine will probably not be useful in the treatment of human visceral leishmaniasis, the data suggest that less-toxic phenothiazines might prove to be effective.

Animals↗