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Biomedical subjects

R D Pearson

Publications and source records attributed to R D Pearson.

At least 145 records · Page 8Linked to original sources
PubMed1981

Tumourigenesis: the subterfuge of selection.

Variation of rearrangement of regulatory genes is responsible for cellular malignant change. These types of chromosomal variations also produce heterochrony or paedomorphic evolution at the organismal level. Analogously, neoplasia represents a cellular 'macroevolutionary' event, and a tumour can be said to be an evolved population of cells. To understand this cellular evolution to malignancy, it may be necessary to go beyond a 'clonal selection' (adaptationist) explanation of neoplastic alteration. In the pericellular environment 'natural selection' consists of the organizational restraints of surrounding cells as well as the host's immunological surveillance and non-specific monocyte-macrophage systems. Indirect evidence suggests that success for the neoplasm depends not upon 'clonal selection', but solely upon a genetic methodology-the function of which is to elude selection. The author has coined the term 'cellular heterochrony' to illustrate analogic similarities in the molecular modes of speciation between anaplastic cancer cells and the heterochronic evolution of organisms. By reverting to juvenile (embryonic) repertoire of cellular behaviour a tumour secures its own tenure or niche by usurping the host's armamentarium of selection forces, employing many of the same or similar methods by which implanting and invading tissues of the mammalian embryo forestall maternal detection and rejection. A number of ways by which the tumour blocks, subverts or evades selection are discussed.

Biological Evolution↗
PubMed1981

Interaction of Leishmania donovani promastigotes with human monocyte-derived macrophages: parasite entry, intracellular survival, and multiplication.

Leishmania donovani promastigotes were incubated with human monocyte-derived macrophages in vitro to assess the role of macrophages in the early stage of visceral leishmaniasis. Adherent mononuclear cells, obtained from nonimmune human donors, were cultivated on glass cover slips for 5 days and then incubated with axenically grown promastigotes in the presence of heat-inactivated autologous serum. Promastigotes attached to macrophages with either their flagellar or aflagellar ends, and macrophage pseudopodia formed around them. Intracellular parasites were identified within phagocytic vacuoles by electron microscopy, and the parasites assumed a form similar to that of amastigotes obtained from infected hamster spleens. Initially, 67 +/- 5% of the macrophages were infected with a mean of 4.2 +/- 0.7 parasites per infected cell. After 6 days of incubation, 79 +/- 7% of the macrophages were infected with 15.9 +/- 3.2 parasites per infected cell. The total number of parasites per monolayer increased from 4.8 +/- 0.8 x 10(5) to 1.8 +/- 0.4 x 10(6) (P less than 0.05). Dividing parasites were identified in macrophage vacuoles by electron microscopy. Human monocyte-derived macrophage vacuoles by electron microscopy. Human monocyte-derived macrophages can phagocytize promastigotes, allow the conversion of promastigotes to an amastigote-like state, and support intracellular multiplication.

Cell Division↗
PubMed1981

Lectin binding by Giardia lamblia.

Surface carbohydrates of Giardia lamblia were examined using six plant lectins chosen because of their specificity for major carbohydrates moieties. The binding to axenically grown G. lamblia trophozoites was assessed in both a quantitative microagglutination assay and a fluorescence assay. Of the six lectins tested, wheat germ agglutinin (WGA) agglutinated the highest percentage (22.9 +/- 3.7%) of live trophozoites, and fluorescein-labeled WGA (100 micrograms/ml) bound to 98 +/- 5% of them. Since the carbohydrate specificity of WGA includes both N-acetyl-D-glucosamine (GlcNAc) and sialic acid, inhibition experiments were performed. GlcNAc inhibited he binding of WGA to G. lamblia in both assays to a greater extent than did sialic acid. Binding of WGA was not altered by prior treatment of trophozoites with neuraminidase, suggesting that WGA was binding to GlcNAc moieties on G. lamblia and not to sialic acid. The remaining five lectins either bound nonspecifically or exhibited low percentages of binding. The apparent presence of GlcNAc but not sialic acid or other exposed surface carbohydrates may be important in the interaction of G. lamblia with its human host.

Agglutination↗
PubMed1981

Coagulopathy associated with hematin treatment for acute intermittent porphyria.

Hematin has been shown to be effective therapy for acute intermittent porphyria. Few complications have been found. We cared for a patient who developed a markedly prolonged prothrombin time, partial thromboplastin time, thrombocytopenia, mild hypofibrinogenemia, mild elevation of fibrin split products, and a 10% fall in hematocrit while receiving hematin. No other cause for the coagulopathy could be found. The abnormal coagulation variables returned to normal when hematin was discontinued. Patients receiving hematin for acute intermittent porphyria should be closely observed for signs of coagulopathy.

Acute Disease↗
PubMed1981

Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes.

The role of polymorphonuclear leukocytes (PMN) in host defense against Leishmania donovani, the protozoan that causes visceral leishmaniasis, is unknown. To assess the ability of PMN to ingest and kill the infecting promastigote stage of the organism, cytocentrifuge preparations were made from tumbled suspensions of 5 X 10(6) PMN, an equal number of promastigotes, and fresh human serum deficient in the 6th component of complement. 53 +/- 9% PMN were found to have 1 or more associated promastigotes, and 81 +/- 14 promastigotes were found per 100 PMN after 15 min at 37 degrees C. There was a corresponding decrease in extracellular promastigotes from 5 x 10(6) ml to 2.7 X 10(4)/ml. Superoxide anion was generated during phagocytosis. Ingetion was saturable with respect to promastigote concentration, required heat labile factors, and was minimal when suspensions were incubated in ice water. Intracellular killing of promastigotes was indicated by a decline in cell-associated organisms without a concomitant increase in extracellular promastigotes. Light and electron microscopy showed disintegration of intracellular promastigotes. Oxidative killing mechanisms appear to be required for PMN killing of this protozoan organism, since there was no decline in intracellular organisms in PMN from a donor with chronic granulomatous disease. Promastigotes studied in a phagocyte-free system were susceptible to H2O2 generated from glucose by glucose oxidase or added directly at greater than or equal to 10(-5) M. Killing was enhanced by the addition of lactoperoxidase (50 mU/ml) with KI (0.05 mM) and inhibited by fresh, but not boiled catalase in the glucose-glucose oxidase system. These studies demonstrate that human PMN can ingest and kill L. donovani by the H2O2-peroxidase-halide system and may be capable of providing host defense against the invading, promastigote stage of this pathogen.

Humans↗
PubMed1981

Paragonimus westermani: a cause of cavitary lung disease in an Indochinese refugee.

A Laotian immigrant with persistent cough and hemoptysis was found to have multiple small cavities on chest roentgenogram. Ova of the lung fluke Paragonimus westermani were found in the sputum, and the patient responded to bithionol therapy. Pulmonary paragonimiasis should be considered in the differential diagnosis of cavitary lung disease in Indochinese refugees entering the United States.

Adult↗
PubMed1980

Clostridium perfringens wound infection associated with elastic bandages.

Clostridium perfringens wound infections were associated with the use of nonsterile elastic outer bandages in diabetic patients who had undergone lower extremity amputation for vascular insufficiency. In each case a second surgical procedure was required. Elastic bandages similar to those used in these procedures were found to contain C perfringens and other clostridial species. This report illustrates the need for maintenance of a sterile, nonpermeable inner barrier to prevent transudation of bacteria into the wound and the potential benefit of using sterile elastic outer bandages after amputation for vascular insufficiency.

Aged↗
PubMed1980

Immunodetente and the 'see-saw'.

The materno-fetal relationship is governed by critical levels of progesterone (P) and prostaglandin F2 alpha (PGF2 alpha). The 'see-saw' in concentration of these molecules maintain and terminate pregnancy in placental mammals. Apart from the enhancement or suppression of uterine contractility by PGF2 alpha and P respectively, the hypothesis in these pages is that the initiating event of parturition is a maternal immunologic repudiation of the feto-placental unit. This immunoregulative theory of parturition is not in contradiction to other physico-endocrinologic theories of labour; but is here presented to further explain some, heretofore, puzzling empirical data witnessed in complications of pregnancy and induced abortion, when Pgs are employed as abortifacients.

Abortifacient Agents↗
PubMed1980

Aborting solid tumours: a possible role for PGF2alpha.

As well as being an efficacious abortifacient agent, PGF2alpha is known to be an endogenous mediator of parturition. It is the hypothesis of this paper that PGF2 alpha may also be an effective macrophage tumouricidal activator; if correct, PGF2alpha may be said to 'abort' tumour cell mass. Indirect evidence for such a mechanism of action, as well as a theory as to the mode of action itself, is presented.

Animals↗
PubMed1980

Method of reliable determination of minimal lethal antibiotic concentrations.

The lack of a standardized, statistically reliable method for in vitro determinations of the minimal lethal or bactericidal concentrations of antibiotics has complicated analyses of isolates of Staphylococcus aureus which appear to be inhibited but not killed by the usual concentrations of cell wall-active antibiotics. We describe a method which identifies some of the covariants involved in determinations of minimal lethal concentrations. Lethality was defined as a 99.9% reduction in the initial inoculum of bacteria after 24 h of incubation. We limited the sample volume to 0.01 ml to minimize the inhibitory effect of antibiotic and corresponding rejection values, which detected lethality with a high degree of sensitivity and specificity. When the number of colonies on subculture was equal to or less than the rejection value, the antibiotic was considered lethal for the test organism. Rejection values encompassed initial inocula from 10(5) to 10(7) colony-forming units per ml for single and duplicate samples and allowed for 1 or 5% variability in pipette volumes and errors in initial inoculum determinations. This method was used to determine the minimal lethal concentrations of semi-synthetic penicillins for S. aureau isolates, one of which was tolerant to the killing action of penicillin.

Anti-Bacterial Agents↗
PubMed1980

Diffuse pneumonitis due to adenovirus type 21 in a civilian.

A patient with severe pneumonitis due to adenovirus type 21 responded to oxygen delivered by continuous positive airway pressure through a face mask. Pulmonary function studies over ten months demonstrated resolving, restrictive lung disease. The prognosis of severe adenovirus pneumonia may be better than expected based on previous reports.

Adenoviridae Infections↗
PubMed1980

Mechanism of lethal effect of human serum upon Leishmania donovani.

In order to gain greater understanding of potential host defense mechanisms against Leishmania donovani, we examined the effect of nonimmune, human serum upon promastigotes and amastigotes. Fresh sera were found to be lethal for promastigotes, but had no detectable effect on amastigotes. Serum exposed promastigotes became immotile, did not take up neutral red dye, appeared to be disrupted, and failed to recover after further incubation in fresh media. Heat labile components were required for promastigote killing since heat-inactivated serum (56 degrees C, 30 min) agglutinated but did not kill them. Sera that lacked either the 5th or 6th complement (C) component had no effect when used alone, but when used together, were lethal, indicating that activation of the membrane attack complex (C5b-C9) ws necessary for the lethal effect. The mode of C activation was determined by using serum with complete, selective, deficiency of C2, and normal serum chelated with Mg-EGTA. The C2-deficient serum killed promastigotes only after the addition of purified C2, and Mg-EGTA chelated serum had no detectable lethal effect. Thus, promastigotes appeared to activate C through the classical pathway. Human IgG and IgM, detected with 125I-anti-human antibody, bound to promastigotes. Removal of antibody from serum by absorption with promastigotes eliminated the lethal effect. The effect was restored by addition of heat-inactivated serum to absorbed serum. We conclude that promastigotes bind antibody and are killed by activation of the membrane attack complex of C through the classical pathway.

Animals↗
PubMed1979

Immunogenicity, parturition and the prostaglandins.

Immunologists have long suspected that maintenance of pregnancy (viable placentation) is contingent upon the suppressed maternal immune response. Curiously, it has never been suggested that the termination of pregnancy at term might in some way be triggered by the un-blocking of this maternal immune suppression. It is the hypothesis of this paper that maintenance and termination of pregnancy are contravening expressions of a maternal-fetal immunologic regulatory response. The role of the prostaglandins in parturition, and the immune response, is discussed.

Abortifacient Agents↗
PubMed1979

Increased heparin binding in cystic fibrosis: a reflection of altered glycoprotein biosynthesis?

Some of the serum proteins which bind to heparin and contribute to the pH 5.57 "heparin binding capacity" of human serum are glycoproteins; those from cystic fibrosis serum were found to be 27% higher in fucose (methylpentose) content, 27% lower in sialic acid content, and 31% lower in hexose content when compared to heparin-precipitated serum glycoproteins from normal control subjects. Hexosamine content of the heparin-precipitated serum glycoproteins was the same. Results of this preliminary investigation indicate that altered carbohydrate composition in serum glycoproteins may affect significantly their heparin binding capacity.

Adolescent↗
PubMed1978

A simple method for estimating a 'heparin binding capacity' of human serum.

A method for estimating a 'heparin binding capacity' of human serum is described. When human serum is diluted with a low ionic strength, heparin-containing buffer at pH 5.5, protein-heparin electrostatic complexes form in solution with subsequent formation of insoluble aggregates which can be collected by centrifugation. Quantitative determination of the relative amounts by weight of protein and heparin in the insoluble heparin-protein aggregates permits estimation of a combining ratio at which serum proteins bind with heparin to precipitate from solution. This weight combining ratio of protein and heparin is a quantitative measure of the total affinity for heparin of all proteins in serum which bind heparin at pH 5.57 to form an insoluble complex. An unusually high affinity for heparin by an abnormal serum protein or an increase in amount of a normally-occuring, high heparin-affinity, serum protein would alter the average protein: heparin combining ratio and increase the 'heparin-binding capacity' of human serum. The converse would be true for serum proteins having a low affinity for heparin, lowering the 'heparin-binding capacity' of human serum. The described method was used to evaluate the 'heparin-binding capacity' of serum proteins in normal individuals and in persons with cystic fibrosis.

Adolescent↗
PubMed1977

Convulsions in the first three years of life.

A prospective study of convulsions in 5803 consecutive newborn infants from an Australian city is described; 535 children were lost to study, leaving 90.9% of the original sample. Of the remaining 5268, 325 had at least one convulsive episode during the first three years of life--an incidence of 61.7 per thousand. Convulsions following breath-holding attacks were experienced by 8.1 per thousand, while a further 4.0 per thousand had simple breath-holding attacks associated with transient loss of consciousness, but no convulsion. Convulsions associated with fever were experienced by 39.9 per thousand. In addition, 8.2 per thousand had idiopathic convulsions, 2.8 per thousand had neonatal convulsions and 2.7 per thousand had convulsions of mixed aetiology. Factors relating to the convulsion are described in detail. Pregnancy and birth data are compared with those of a control group taken from the study.

Australia↗