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Biomedical subjects

M Borgers

Publications and source records attributed to M Borgers.

At least 199 records · Page 11Linked to original sources

Promotion of pseudomycelium formation of Candida albicans in culture: a morphological study of the effects of miconazole and ketoconazole.

The effects of miconazole and its new derivative ketoconazole on Candida albicans have been evaluated by light and electron microscopy. The growth characteristics and morphology of C. albicans in culture for various periods of time in a solution consisting of Eagle's minimum essential medium supplemented with amino acids and fetal calf serum are emphasized. This medium, normally used for culturing mammalian cells, promotes a rather fast growth of C. albicans and favours the development of pseudomycelium. The obvious interest in using such culture conditions for drug evaluation is the prevalence of pseudomycelium, which in vivo is the predominant pathological form of C. albicans. Suppression of pseudomycelium formation is found in the 10-9 to 10-7 M concentration range of the imidazoles. Growth retardation and the destruction of both yeast and pseudomycelial forms brought about by incubating the cells with 10-9 to 10-4 M of the drugs are reported. At low doses these changes include the alteration of cell division, an increase in cell volume and a progressive deterioration of subcellular organelles at the cell periphery. At higher doses the involvement of all other organelles is observed finally leading to complete cell necrosis.

Candida albicans↗

Purine nucleoside phosphorylase in lymphocytes of various mammalian species.

The distribution of purine nucleoside phosphorylase has been assessed by light and electron microscopy in peripheral lymphocytes of man, the rabbit, rat, mouse, guinea-pig, pig and dog. The enzyme activity was detected in the cytosol of the majority of lymphocytes in all species. The amount of reaction product was high in the rabbit, man, guinea-pig and dog, mpderate in the rat and very low in the pig and mouse. Other blood cell types are reactive as well, although there is a variation between species. A possible relationship of purine nucleoside phosphorylase with particular subpopulations of lymphocytes is suggested.

Animals↗

Alkaline phosphatase activity in human polymorphonuclear leukocytes.

Alkaline phosphatase has been localized ultracytochemically in PMN of man with normal and elevated levels of this enzyme. Contrary to guinea-pig PMN, no activity appears to be present in the specific granules. Instead, the plasma membrane and the membrane of the endocytic vacuoles show a strong staining. However, the demonstration of this activity depends on the preparatory procedure employed for PMN isolation. The use of dextran and Ficoll-Hypaque in the isolation procedure induces a marked increase in alkaline phosphatase staining of the PMN plasma membrane. Strongly increased activity at this site has been found in PMN from cancer patients. In most of them, additional staining has been observed in atypical vesicles and sometimes in the Golgi apparatus. These findings are discussed in the light of some previously reported controversial biochemical and cytochemical data on the distribution of alkaline phosphatase in human PMN.

Alkaline Phosphatase↗

Oxatomide protects Trichinella spiralis infected mice from lethal anaphylaxis.

Infection with Trichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active anti-allergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice. The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.

Anaphylaxis↗

Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL).

Purine nucleoside phosphorylase (PNP), the enzyme schematically next to adenosine deaminase in the purine salvage pathway, has been demonstrated cytochemically in peripheral blood lymphocytes of healthy subjects and chronic lymphocytic leukemia (CLL) patients. The enzyme activity is confined to the cytosol. In healthy subjects the majority of lymphocytes are strongly reactive for PNP, whereas the rest are devoid of cytochemically demonstrable activity. The percentage of PNP-positive cells largely corresponds to the number of E rosette-forming cells and is inversely proportional to the number of Ig-bearing cells. In six of seven CLL patients studied only a minor percentage of the lymphocytes showed strong PNP activity, whereas the large majority (88%--98%) possessed trace activity. Such patients have a high number of Ig-bearing cells and a low number of E rosette-forming cells. A different pattern of markers was found in the lymphocytes of the seventh CLL patient: 66% were strongly reactive for PNP, an important number formed E rosettes, and a minor percentage were Ig bearing. These data indicate that PNP can be useful as a "nonmembrane" marker in the differentiation of the B and T cell origin in CLL and deserves to be studied in other lymphoproliferative disorders.

Histocytochemistry↗

Scanning electron microscopic observations of Cysticercus fasciolaris (=Taenia taeniaeformis) after treatment of mice with mebendazole.

The time-related topographical changes in mature cysticerci of Taenia taeniaformis induced after medication of infected mice with 250 ppm of mebendazole are described. The changes included the gradual disappearance of microtriches and progressive degeneration of the tegment resulting in an irregular surface with grooves, holes, and craterlike structures. Host cells adhered to the altered areas and the number of these cells increased when more severe changes became apparent. Finally the necrotized cysticerci, which lost their tegument completely, were almost entirely covered with adhesive host cells. A difference in the time sequence of the reported changes occurred between the scolex, the pseudoproglottids, and the bladder. This difference in susceptibility towards the drug between the three parts of the parasite in relation to the morphology of their microtrichous covering is discussed.

Animals↗

Oxatomide, a new orally active drug which inhibits both the release and the effects of allergic mediators.

Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogensous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical application different from classical antihistaminics and from cromoglycate.

Administration, Oral↗

Purine nucleoside phosphorylase, a possible histochemical marker for T-cells in man.

A procedure is described for the histochemical detection of purine nucleoside phosphorylase (PNP) activity in circulating lymphocytes of man. The number of PNP-positive cells, as evaluated on smears of Ficoll--Hypaque purified cells, correlated well with the number of E-rosette-forming cells of the same blood samples of healthy and diseased people with normal or abnormal numbers of E-rosettes. In healthy people, the number of PNP-positive cells was within the range of 70-80% of the total lymphocyte population, whilst the corresponding E-rosette-forming cells were scored between 60-75%. Patients with unusually low or high E-rosettes had equally low or high numbers of PNP-reactive cells. More substantial evidence for the presence of PNP activity in T-cells and not in B cells was gathered from experiments in which PNP activity and surface membrane immunoglobulins (SMIg) were simultaneously demonstrated on the same preparation. These results showed, on the one hand, that the bulk of lymphocytes that are reactive for PNP do not reveal SMIg and, on the other hand, that most Ig-bearing cells were unreactive for PNP.

Histocytochemistry↗

Cytochemical and biochemical studies of yeasts after in vitro exposure to miconazole.

Yeast cells exposed to different doses of the antimycotic agent miconazole revealed important cytochemical changes in the topographic distribution of the phosphatases. A strong effect was observed on the behavior of oxidative and peroxidative enzymes. Decreased cytochrome c oxidase and peroxidase activity and increased catalase activity were seen after treatment with a fungistatic dose of miconazole, whereas a complete disappearance of these enzymes was observed after treatment with a minimal fungicidal dose of miconazole. This was in complete agreement with the quantitative biochemical data. A hypothesis is advanced concerning the possible involvement of peroxidase and catalase in the mechanism of action of this drug.

Acid Phosphatase↗

Cytochemical localization of NADH oxidase in Candida albicans.

The application of a recently published technique to localize reduced nicotinamide adenine dinucleotide oxidase activity is described in glutaraldehyde-fixed Candida albicans. The reaction product appears as a finely granular precipitate on the mitochondrial cristae and on the central vacuolar membrane, and, if present, on the vacuolar contents. Fixation should be kept to a minimum and prolonged incubation times up to 2 hr are necessary to show these reactive sites. The reaction appears to be strongly substrate-dependent and not affected by cyanide. Exposure of C. albicans cells to the antimycotic miconazole resulted in a strong increase in reduced nicotinamide, adenine dinucleotide and oxidase activity. The hypothesis is put forward that this enzyme, together with peroxidative and catalatic enzymes, may be implicated in the mechanism by which miconazole exerts its lethal effect on C. albicans.

Candida albicans↗

Intranuclear microtubules in lung mast cells of guinea pigs in anaphylactic shock.

Intranuclear microtubules were found in lung mast cells during anaphylactic shock following ovalbumin challenge of guinea pigs passively sensitized with homocytotropic antibodies. Simultaneously, such cells showed mitochondrial swelling with a clear matrix and partially disrupted cristae. Although a decreased number of mast cell granules generally accompanied these observations, the degree of degranulation and the morphologic appearance of the granules are less reliable criteria to indicate the immediate participation of a cell in the anaphylactic phenomenon. The cells that presented intranuclear microtubules were mainly found in the vicinity of the bronchiolar smooth muscle. The distribution of cations has been investigated in these tissues with a combined oxalate-pyroantimonate method. Whereas in controls the reaction product is located mainly in the nucleus and the mitochondria of mast cells, these sites become almost completely devoid of precipitate during the anaphylactic reaction. A hypothetical link between histamine release, intracellular distribution of cations, possibly calcium, and the appearance of intranuclear microtubules in mast cells is proposed.

Anaphylaxis↗

The effects of miconazole on the ultrastructure of Candida albicans.

Ultrastructural changes in Candida albicans induced by increasing concentrations of miconazole in vitro are described. Fungistatic concentrations (10(-8) to 10(-7) M) induced minimal morphologic changes at the cell periphery. At 10(-6) M cell volume increased and peroxisomes became numerous in the cell interior. The minimal fungicidal dose of 10(-5) M caused severe damage to most of the cell population and a total fungicidal dose of 10(-4) M caused total internal cellular necrosis even when cell walls remained intact. It is suggested that miconazole inhibits the peroxidative enzymes cytochrome c-peroxidase and catalase. Cell necrosis then results from peroxide accumulation.

Candida albicans↗

Further characterization of phosphatase activities using non-specific substrates.

The demonstration of non-lysosomal acid phosphatase has been the subject of a number of recent investigations. In the present study we compared the enzyme activities in rat liver and kidney that are revealed after incubation in the presence of either beta-glycerophosphate, p-nitrophenylphosphate or phenylphosphate at varying pH. As seen by others, the activity towards p-nitrophenylphosphate at pH 5-6 was confined to lysosomes, Golgi apparatus, endoplasmic reticulum (ER), nuclear envelope and plasmalemma. The reactivity of the plasmalemma and the ER was increased at pH 7. The TER of Küpffer cells in the liver stained intensely in contrast to the ER of the parenchymal cells, which stained only weakly. In the presence of NaF, all sites except the plasmalemma became negative. Addition of a levamisole-analogue, L-p-bromotetramisole, which is a specific inhibitor of alkaline phosphatase, resulted in the disappearance of the plasmalemmal activity whereas the activity at the other sites appeared unaltered. The rather unusual locations of activities with so-called non-specific substrates were further compared with those obtained with specific substrates such as glucose-6-phosphate and thiamine pyrophospate. The possible implication of these data in relation to the specificity of marker-enzymes for subcellular organelles is discussed.

Animals↗