Cultivation of Leishmania braziliensis braziliensis from skin ulcers in man under field conditions.
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Brazil↗
Biomedical subjects
J L Costa
Publications and source records attributed to J L Costa.
Limited dermal ossification: clinical features and natural history.
For 9 years we have observed a girl who has ossification in the dermis with a strikingly limited distribution. Recently a second girl with similar dermal ossification restricted to a single extremity was identified. The ectopic bone is histologically identical to normal membranous bone. These two patients have no obvious underlying cause for soft tissue bone formation, and no disorder of calcium or phosphate metabolism. Ossification first involved the dermal and subcutaneous connective tissue, and with time advanced locally in the affected areas to bridge joints and limit mobility. The ossification has now extended to involve muscle fascia but has not involved the muscle itself. This disease appears to represent a heretofore unrecognized disorder of mesenchymal differentiation.
Bone and Bones↗
Apparent cure of a difficult treatment problem in a patient with mucosal leishmaniasis.
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Amphotericin B↗
Leishmania braziliensis braziliensis infection of the nipple.
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Adult↗
Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures.
Neuropsychological and neurochemical effects of zimeldine, a relatively specific serotonin reuptake blocker, were examined in four patients with clinically diagnosed Alzheimer's disease, in a double-blind, placebo-controlled, crossover study. Individualized doses of zimeldine were administered to achieve target plasma zimeldine concentrations of approximately 50 (low) to 100 (high) ng/mL. Overall, there was no significant effect of zimeldine on memory or reaction time measures as compared with placebo. The drug significantly reduced (by up to 38%) 5-hydroxyindoleacetic acid concentrations in the cereobrospinal fluid and almost abolished (90% reduction) platelet serotonin uptake. Cerebrospinal fluid concentrations of 3-methoxy-4-hydroxy-phenylglycol, a major metabolite of norepinephrine, and homovanillic acid, the major metabolite of dopamine, were not altered. Our findings indicate that alterations in central and peripheral serotoninergic function by a serotonin reuptake blocker (zimeldine) are unaccompanied by measurable changes in memory and/or reaction time in patients presumed to have Alzheimer's disease.
Aged↗
High continuous antimony therapy in two patients with unresponsive mucosal leishmaniasis.
The treatment of two patients with severe mucosal leishmaniasis due to Leishmania braziliensis braziliensis is described. Both patients had received much prior antimonial therapy and one had relapsed after a total dose of 2.5 g of Amphotericin B. Both patients responded to prolonged continuous Pentostam therapy at a daily dose of 20 mg Sbv/kg/day for 62 days in one case and for 85 days in the other. Pentavalent antimonials can be curative in such protracted courses in selected patients unresponsive to standard chemotherapy.
Adult↗
Antidepressant drugs suppress growth of the human pathogenic protozoan Giardia lamblia.
The tricyclic antidepressant drug chlorimipramine, some of its congeners, and its mammalian metabolites inhibited the growth in vitro of the human intestinal pathogen Giardia lamblia. The inhibitory action may reside in their ability to inhibit the membrane-associated ATPase characteristic of eukaryotes. Synthesis of other compounds of the tricyclic class may produce drugs of potential therapeutic use in the treatment of giardiasis and possibly other protozoal diseases.
Animals↗
Cell mediated immunity in American cutaneous and mucosal leishmaniasis.
Cellular immune responses were studied in 35 Brazilian patients with either active cutaneous leishmaniasis (CL), active mucosal leishmaniasis (ML), or healed cutaneous leishmaniasis. The mean age and duration of illness in the two groups were as follows: 14 CL patients, age 28 +/- 13 yr, disease 5 +/- mo; and 16 ML patients, age 34 +/- 15 yr, disease 86 +/- 117 mo. Patients with CL and ML responded well to leishmania antigen in blastogenesis assays. However, the response of ML patients was over three times greater than the response of CL patients. There was a significant correlation between the magnitude of the lymphoproliferative response and the duration of disease activity. There were no significant differences between CL and ML patients in terms of the following parameters: lymphoproliferative responsiveness to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen) and peripheral blood lymphocyte subpopulations (T and B cells, oKT8+ and OKT4+ cells, OKT4:OKT8 ratio). Peripheral blood mononuclear cells from ML patients also generated interferon-gamma containing lymphokine in response to stimulation with leishmania antigen. This lymphokine was capable of inducing macrophages from ML patients to inhibit the intracellular multiplication of leishmania in vitro. These studies have determined that the parameters of lymphocyte and macrophage functions evaluated in ML and CL patients are comparable, except for an enhanced lymphoproliferative response, with leishmania antigen in ML patients. This later finding may be a function of the long duration of active disease in this population and unrelated to the pathogenesis of their mucosal lesions.
Adolescent↗
Comparison of serotonin uptake by dense bodies inside and outside human platelets.
A technique has been developed for quantitating the absolute number of dense bodies present in solution following isolation from human platelets. The amount of [3H]-5HT accumulated per dense body was measured following either sonication alone or sonication plus isolation utilizing a Metrizamide density gradient; the dense bodies in each case were washed and resuspended in sodium or potassium-rich buffer. Uptake per dense body following removal from the cell was less than 10% of the amount of uptake per dense body by intact platelets. It thus seems possible that residence of dense bodies inside intact platelets is required for 5HT transport into dense bodies to proceed at a maximal rate.
Blood Platelets↗
Purified -SH-activated toxins (streptolysin O, alveolysin): new tools for determination of platelet enzyme activities.
The purpose of this study was to examine the lytic effect on human platelet preparations (washed, gel-filtered and dextran-isolated) of two sulfhydryl-activated bacterial protein toxins, streptolysin 0 and and alveolysin, and to compare their efficacy with that of other disruptive procedures (freezing and thawing, ultrasonic, mechanical, or nystatin-toluene treatment) as a method for the determination of various platelet enzyme activities. The enzymes assayed were alkaline and acid phosphatases, monoamine oxidase, phenolsulfotransferase, N-acetyltransferase, hydroxyindole-O-methyltransferase, glutathione peroxidase and lactate dehydrogenase. In all cases, the lowest activities were found after freezing and thawing and/or ultrasonic disruption. The highest activities were always observed in the platelet lysates obtained after toxin, and in some instances after nystatin-toluene treatment. Intermediate values were obtained for mechanical disruption. The -SH-activated cytolysins thus appear to be appropriate and gentle tools for the assay of platelet enzymes when compared to the physical or chemical procedures generally employed.
Bacterial Proteins↗
Calcium phosphate formation in aqueous suspensions of multilamellar liposomes.
The present study examined calcium phosphate precipitation in aqueous suspensions of multilamellar liposomes as a possible in vitro model for matrix vesicle mineralization. Liposomes were prepared by dispersing CHCl3-evaporated thin films of 7:2:1 and 7:1:1 molar mixtures of phosphatidylcholine, dicetyl phosphate, and cholesterol in aqueous solutions containing 0, 25, or 50 mM PO4 and 0 or 0.8 mM Mg. After removal of unencapsulated PO4 by gel filtration, the liposomes were suspended in 1.33 mM Ca/0.8 mM Mg solutions and made permeable to these cations by the addition of the ionophore X-537A. All experiments were carried out at pH 7.4, 22 degrees C, and 240 mOsm. In the absence of entrapped PO4, Ca2+ taken up by the liposomes was largely bound to inner membrane surfaces. With PO4 present, Ca2+ uptake increased as much as sixfold with maximum accumulations well above values sufficient for solid formation. Precipitated solids appeared to be located predominantly in the aqueous intermembranous spaces of the liposomes. Amorphous calcium phosphate (ACP) precipitated initially in the presence of entrapped Mg2+, then subsequently converted to apatite intermixed with some octacalcium phosphate. The stability of the liposomal ACP was somewhat greater than that observed in bulk solutions under comparable conditions of pH, temperature, and electrolyte makeup. In time, the mineral deposits caused entrapped PO4 to leak from the liposomes. These findings suggest that the precipitation within liposomes is similar to that which occurs in macro-volume synthetic systems but that the precipitated solid eventually impairs the integrity of the surrounding intermembranous space.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcification, Physiologic↗
Flash X-ray microscopy with a gas jet plasma source.
A novel flash X-ray source, the gas jet plasma source, has been used for contact X-ray microscopy. Using a wavelength range of 2-7 nm a resolution of the order of 30 nm can be obtained. The gas jet plasma source provides a new and unique tool which should allow future imaging of wet live cells.
Blood Platelets↗
Elemental composition of bacterial metachromatic inclusions determined by electron microprobe X-ray analysis.
Electron microscopy and microprobe X-ray analysis were used to study metachromatic inclusions of Spirillum itersonii , Corynebacterium diphtheriae, and Micrococcus luteus. In situ metachromatic inclusions were electron dense and contained phosphorus and divalent cations. Metachromatic inclusions isolated by anion-exchange column chromatography and by isoosmolar Metrizamide density gradient centrifugation were similar in composition to in situ inclusions.
Calcium↗
Exploration of mechanisms of amine storage in the dense bodies of human platelets.
Storage of 5-hydroxytryptamine (5HT) in membrane-bound vesicles (dense bodies) of platelets has been proposed to occur as a result of the formation of macromolecular complexes between nucleotides and 5HT, or because of the existence of an electrochemical proton gradient (delta mu H+) across the vesicle membrane. Tests of the applicability of these hypotheses to 5HT storage in the dense bodies of human platelets have been made by examining the disposition of quinacrine and 5HT in these organelles following varying treatments. Binding seems unlikely, since solid analogues of the dense body core (calcium, adenine nucleotides, and pyrophosphate) do not significantly bind 5HT or quinacrine. Incubation of platelets with substances which disrupt delta mu H+ releases a large percentage of the intra-platelet quinacrine. A much smaller fraction of the total platelet 5HT is released by similar treatment, suggesting that the delta mu H+ may not be required for 5HT storage. Because inhibition of the de novo uptake of 5HT into dense bodies fails to cause the significant loss of the 5HT stored in this compartment, 5HT stores do not appear to be maintained by active 5HT uptake. Several substances which enter the dense bodies equally well at 0 degrees C and 37 degrees C cause release of 5HT at 37 degrees C but not at 0 degrees C. The release observed at 37 degrees C thus cannot be attributable to collapse of delta mu H+ or to the displacement of 5HT from intra-granular binding sites, but may be related to increased membrane permeability to 5HT at 37 degrees C. Based on these observations, it appears as if 5HT taken up into the dense bodies of human platelets is retained because the dense body membrane has a very low passive permeability for 5HT, and that many compounds which cause 5HT release at 37 degrees C may act by increasing this permeability.
Amines↗
Heterogeneity of human whole blood platelet subpopulations. III. Density-dependent differences in subcellular constituents.
Structurally intact platelet cohorts of differing densities can be isolated from normal subjects by the use of isosmolar arabinogalactan density gradients. Using platelets separated in this fashion, we have studied the density-dependent distribution of four subcellular organelles: mitochondria, lysosomes, dense bodies, and alpha granules. Mitochondria, which are not secreted during platelet release, demonstrate a slow decline in monoamine oxidase activity within the gradient. Lysosomal beta-glucuronidase does not vary significantly with platelet density. In contrast, dense body number and endogenous serotonin content decrease significantly with decreasing platelet density, primarily as the result of differences in the number of storage organelles. Platelet factor 4 content declines rapidly in comparison to lysosomal activities (P less than .001 from bottom to top of the gradient); but beta-thromboglobulin, also an alpha granule component, exhibits considerably less change than platelet factor 4 (P less than .001). Thus, specific platelet subcellular constituents have different density distributions. We postulate that these density differences may be due to differential in vivo loss of selective biochemical constituents from unique subcellular compartments.
Blood Platelets↗
Effects of osmotic dehydration on the nucleotides of isolated chromaffin granules: evaluation by 31p nuclear magnetic resonance.
The 31P nuclear magnetic resonance spectrum of chromaffin granules isolated from bovine adrenal medulla, when examined at 30 degrees C in 0.3 M sucrose, shows sharply defined gamma, alpha, and beta nucleotide resonances with linewidths of 141, 58 and 90 Hz respectively. These are essentially unchanged when examined at 4 degrees C. When the granules are resuspended in 1.6 M sucrose, the linewidths of 161, 117 and 162 Hz seen at 30 degrees C reversibly broaden to greater than 1000 Hz at 4 degrees C. Addition of quinacrine produces no discernable change in the nucleotide linewidths of either preparation. The broadening at high osmolarity and low temperature appears to be due to ATP:catecholamine complex formation rather than to increased viscosity. Since purification of chromaffin granules is often performed utilizing sucrose gradients, the present results raise the question of whether dehydration may alter the structure of the granule core.
Adrenal Medulla↗
Quinacrine and basic amines in human platelets: subcellular compartmentation and effects on serotonin.
Human platelets appear to accumulate quinacrine both in a thrombin-releasable compartment (dense bodies or amine storage vesicles) and in another compartment from which it is released by agents known to collapse pH gradients (possibly lysosomes with an acidic interior). Approximately 61% of the total amount of quinacrine present in human platelets resides in dense bodies and 14+ in lysosomes, with the remainder probably present in the cytoplasm. Other basic amines are accumulated in the three compartments to widely varying extents, suggesting that several factors besides the existence of pH gradients act to determine the distribution of these substances within the cell. The fluorescence emission of quinacrine excited with 420 nm light is completely quenched for quinacrine inside both dense bodies and lysosomes, and the absorption of 440 nm light is decreased by approximately 25%. Quinacrine added to dense bodies at 37 degrees C induces the efflux of 5-hydroxytryptamine (5HT) from the bodies. There is, however, no 5HT loss following quinacrine entry at 0 degree C, and the relationship between the two types of amine movement varies according to incubation time at 0 degree C and 37 degrees C. This action of quinacrine therefore does not appear to be associated with stoichiometric exchange of 5HT and quinacrine, but rather to modulation of the passive permeability of the dense body membrane for 5HT.
Amines↗
Effects of media of low osmolarity on the dense bodies of human platelets.
Exposure of human platelets to buffer at 30 milliosmoles (mOs) caused marked swelling of the cells (a volume increase of almost 300% as estimated from electronic sizing) without a statistically significant loss of dense bodies or a change in the measured diameter of the dense-body core (as examined electron-microscopically in air-dried whole mounts). Even biochemically isolated dense bodies maintained the integrity of their electron-opaque cores in 30 mOs buffer. However, exposure of platelets to 30 mOs buffer reduced the platelet content of cytoplasmic 14C-labeled nucleotides and the vesicular content of [3H]5-hydroxytryptamine (5-HT) by 90%. It thus seems likely that the dense-body membrane displays a sufficiently low permeability to water to prevent swelling and dissolution of the core, but that exposure to hypotonic media allows stored 5-HT to cross the vesicular membrane. Impermeability of this membrane to 5-HT under normal conditions may, therefore, play an important role in the maintenance of vesicular 5-HT stores, rather than the presence of an intact dense-body core. The data also suggest that an "osmotic lysis" or "chemiosmotic" model of secretion may not account for the exocytotic release of human platelet dense bodies.
Blood Platelets↗