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Biomedical subjects

R L Janco

Publications and source records attributed to R L Janco.

28 records · Page 2Linked to original sources

Systemic metastases in primary intracranial germinoma. Case report and literature review.

Systemic metastases from central nervous system germinomas are exceedingly rare, and when they occur lead to fatal outcomes. The authors report the case of a 10-year-old girl who presented with metastatic involvement of the rib and pelvis 2.5 years after surgical resection and radiation therapy for a suprasellar dysgerminoma. After combination chemotherapy, the patient remains disease-free 30 months after relapse. This case provides evidence that chemotherapy can be an effective therapeutic alternative to the use of radiation in the treatment of children with extracranial germinomas.

Bone Neoplasms↗

Selective induction of manganous superoxide dismutase in human monocytes.

Radioimmunoassays for both human copper-zinc and manganous superoxide dismutases (Cu-Zn SOD and Mn SOD, respectively) have been developed, validated, and utilized to measure the concentrations of these enzymes in cultured monocytes. Monocyte Mn SOD increased 4.7-fold over basal during 3 days of culture, an increase that was markedly enhanced by stimulation with bacterial lipopolysaccharide (LPS). Cu-Zn SOD showed a transient decrease over the culture period but was unaffected by LPS. Stimulation with muramyl dipeptide had minimal effect on Mn SOD and no effect on Cu-Zn SOD during culture, even at a concentration capable of activating the monocytes, as defined by zymosan-induced superoxide production.

Acetylmuramyl-Alanyl-Isoglutamine↗

Regulation of monocyte procoagulant by chemoattractants.

Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces a fourfold increase in procoagulant activity (PCA) in cultured human monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses inhibit PCA response. Although nonadherent lymphocytes are not absolutely required for PCA expression, their presence significantly amplifies monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them with FMLP and adherent cells abolishes their ability to amplify PCA. Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA over time whereas high-dose inhibition of PCA generation occurs at various incubation times. Cell viability is unaffected by inhibitory concentrations of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit later expression of PCA by cells exposed to endotoxin. The cellular procoagulant remains cell-bound and exhibits characteristics of thromboplastin (tissue factor), including inhibition by concanavalin A and phospholipase C as well as the ability to shorten the clotting times of factor VIII but not factor VII-deficient substrate plasmas. These results suggest a complex system of lymphoid cell regulation of procoagulant generation by monocytes exposed to various chemotactic peptides in vitro.

Blood Coagulation↗

Serum augments the generation of monocyte procoagulant stimulated by bacterial lipopolysaccharide or chemotactic fragments of C5.

Human serum augments the ability of bacterial lipopolysaccharide (endotoxin) or partially-purified C5-derived chemotactic fragments (C5-fr) to induce the monocyte procoagulant activity (PCA) in vitro. Both autologous and pooled sera induced PCA in the target cell population. Dose response curves revealed a detectable response in PCA with as little as 0.1% serum (v:v) in cell suspensions incubated for 4-6 hours before assay of PCA. Heat-inactivation experiments showed that enhancing activity of serum for both endotoxin and C5-fr induced-PCA could be destroyed by heating at 56 degrees C, with the greater part of the activity lost during the first 30 minutes of heating. The enhancing serums studied contained no endotoxin as measured by the Limulus amebocyte lysate assay and these serums failed to induce aggregation of neutrophils, a sensitive measure for the presence of complement-derived chemotactic fragments such as C5a. Serum without endotoxin or C5-fr also induced a variable increase in PCA and this inducing activity could also be abolished by heating, whereas the ability of endotoxin alone (10 micrograms/ml) to induce PCA was unaffected by similar heat-treatment. The procoagulant appeared to function as tissue factor in one-stage clotting assays using deficient substrate plasmas. Lymphocytes stimulated by serum and later washed failed to amplify monocyte tissue factor whereas lymphocytes exposed to endotoxin retained the ability to amplify monocyte tissue factor. These results suggest a role for serum in the modulation in vitro of monocyte procoagulant.

Adult↗

Neutrophil labeling with indium-111: tropolone vs. oxine.

This study was undertaken to compare tropolone with oxine (8-hydroxy-quinoline) for labeling human neutrophils with In-111. Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis. In contrast, no impairment of neutrophil chemotaxis was observed using In-111 oxine. Labeling efficiencies obtained with In-111 tropolone under optimal conditions were consistently less than those obtained with In-111 oxine. We evaluated cells labeled by the two methods using chemotaxis radioassay to assess the chemotatic potential of labeled cells. The results led to the conclusion that the oxine technique is preferable to tropolone for labeling human neutrophils with In-111.

Chemotaxis, Leukocyte↗

Regulation of monocyte oxidative metabolism: chemotactic factor enhancement of superoxide release, hydroxyl radical generation, and chemiluminescence.

Human peripheral blood mononuclear cells exposed to the synthetic chemotactic factor n-formyl-methionyl-leucyl-phenylalanine (FMLP) were enhanced in their ability to generate superoxide anion (O-2), hydroxyl radical (OH.), and chemiluminescence when later exposed to phorbol myristate acetate (PMA). When compared to oxidative responses of cells treated with PMA alone, the degree of enhancement by pretreatment with FMLP was 1.85-fold for O-2 generation, 1.73-fold for OH. production, and 1.34-fold for chemiluminescence. Similarly, pretreatment of mononuclear leukocytes with 5% zymosan-activated serum also enhanced subsequent oxidative responses of cells exposed to PMA. FMLP did not enhance subsequent O-2 release or chemiluminescence by mononuclear leukocytes stimulated by opsonized zymosan or 20 mM sodium fluoride (F-), demonstrating that the O-2 generating system of monocytes stimulated by phagocytosis or F- is not susceptible to chemotactic factor regulation in a manner similar to the system stimulated by PMA. The latter system, like that of neutrophils, is susceptible to regulation by cellular processes activated during an initial encounter with chemoattractants. These processes may provide a mechanism to amplify oxidative responses at sites of infection or inflammation, leading to enhanced efficiency of microbicidal activity or increased tissue damage in vivo.

Adult↗

Perfluorochemical blood substitutes differentially alter human monocyte procoagulant generation and oxidative metabolism.

Human blood mononuclear leukocytes exposed in vitro to perfluorochemical blood substitutes (Fluosol-DA and FC-43) generated increased procoagulant activity that was time dependent. Mononuclear leukocytes incubated with 10 percent Fluosol-DA for 4 hours generated 3.43-fold more procoagulant activity than control cells. At 24 hours of incubation with 10 percent Fluosol-DA, cells generated 10.49-fold more procoagulant than control. Cells incubated with 10 or 20 percent FC-43 generated 2.5- or 3.4-fold greater procoagulant than controls, respectively. The perfluorochemical emulsifier (Pluronic F68) also stimulated 3.4-fold more activity than control cells. Stimulated oxidative metabolism (superoxide anion generation) was significantly impaired by Fluosol-DA but not by FC-43 or Pluronic F68. No significant perfluorochemical-induced cytotoxicity was measured by trypan blue dye exclusion or lactate dehydrogenase release. Electron microscopic analysis showed progressive uptake of the perfluorochemicals by monocytes but not by lymphocytes. Thus, perfluorochemicals may differentially activate cellular initiators of coagulation while impairing other metabolic responses of mononuclear phagocytes. Patients receiving perfluorochemical preparations should be monitored for abnormalities of hemostasis and for disorders of the mononuclear phagocyte system.

Blood Coagulation Factors↗

MR imaging of hemophiliac arthropathy.

Magnetic resonance (MR) imaging of the knee was performed in 10 patients with hemophilia. The periarticular and subchondral abnormalities were classified according to the signal intensity from these regions on T1- and T2-weighted pulse sequences. Periarticular abnormalities were detected in 50% of the hemophiliac joints, and fibrous changes were noted in 57% of all the areas of subchondral abnormality. Magnetic resonance imaging identifies periarticular and subchondral abnormalities in patients with hemophilia and may help in monitoring the progress of the disease process.

Adolescent↗