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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 343 records · Page 19Linked to original sources
PubMed1984

Fusion of intracellular membrane pools with cell surfaces of macrophages stimulated by phorbol esters and calcium ionophores.

Mouse tumor macrophages (J774) exposed to phorbol myristate acetate (PMA) exhibited a marked increase in cell spreading. Correlated with this phenomenon was an increase in the number of cell surface transferrin (Tf) receptors and a corresponding decrease in the number of Tf receptors located intracellularly in membrane-bound endosomes. Similar effects were noted when J774 cells were exposed to the calcium ionophore A23187. Rabbit alveolar macrophages did not respond to PMA but did respond to A23187 by increasing cell spreading, which was accompanied by increases on the cell surface of four different receptors. These results demonstrate that phorbol esters and calcium ionophores can induce a redistribution of cellular receptors.

Animals↗
PubMed1984

Epidermal growth factor rapidly induces a redistribution of transferrin receptor pools in human fibroblasts.

Treatment of human fibroblasts with epidermal growth factor (EGF) results in a rapid increase (less than 5 min) in the ability of the cells to bind 125I-labeled transferrin to surface receptors. Scatchard analyses of EGF-treated cells indicate that this increase was due to an increase in the number of transferrin receptors at the cell surface rather than to alterations in ligand-receptor affinity. The EGF-induced increase in transferrin receptors was transient, reaching a peak by 5 min and then declining back to near basal levels by 45 min. Increases in transferrin receptor number were observed when approximately equal to 1% of the EGF receptors were occupied and were maximal at 16% occupancy. EGF treatment accelerated the rate at which previously internalized 125I-labeled transferrin-receptor complexes were returned to the cell surface. The kinetics and magnitude of the loss of intracellular transferrin receptors was sufficient to account for the increase in surface transferrin receptors. We conclude from these studies that one of the earliest effects of EGF treatment is the induced translocation of an intracellular compartment to the cell surface. This intracellular compartment contains transferrin receptors and may be part of the pathway involved in the normal recycling of cell surface proteins.

Cells, Cultured↗
PubMed1984

Ultrastructural localization of specific gonococcal macromolecules with antibody-gold sphere immunological probes.

In an effort to determine the ultrastructural location of specific macromolecules on the surface of intact microorganisms and in experimentally infected tissues, a new method of rapidly conjugating antibodies to gold spheres via a staphylococcal protein A intermediary has been developed. This new technique provides the excellent density of marking and versatility of sphere size provided by existing gold methods, but decreases preparation time, decreases the chance of bacterial contamination of antibody reagents, and increases specificity of marking. Staphylococcal protein A-coated gold spheres were conjugated with antibodies from rabbits immunized with purified gonococcal pili. The resulting gold-antibody conjugates allowed demonstration of antibody binding to pilus structures of the same gonococcal strain whose pili were used to raise the antibody and demonstration of the lack of antibody recognition of pilus structures on two other gonococcal strains. The failure of gold spheres to attach to isogenic nonpiliated clones of the homologous gonococcus indicated the absence of pilus antigens on the surface of these organisms. The use of a double label--small gold spheres conjugated to anti-pilus antibody and larger gold spheres conjugated to anti-protein I antibody--allowed the simultaneous localization of two gonococcal antigens.

Antibodies, Bacterial↗
PubMed1984

Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions.

Immunologic abnormalities qualitatively similar to those seen in acquired immunodeficiency syndrome (AIDS), including a low helper/suppressor lymphocyte ratio and low natural killer (NK) activity, have been observed in many hemophiliacs receiving clotting factor concentrates. To determine whether these changes also occur after repeated blood transfusion, we measured helper/suppressor (T4/T8) ratios and NK activity in four groups of test subjects: (A) 30 subjects with sickle cell anemia (SCA) receiving monthly transfusions, (B) 30 nontransfused sickle cell anemia subjects, (C) 87 individuals with hemophilia or severe von Willebrand's disease, and (D) 30 normal controls. Like the hemophiliacs, transfused SCA subjects had low T4/T8 ratios and low NK activity compared to controls. Nontransfused SCA subjects had normal values. These findings suggest that a modest decrease in T4/T8 ratio and NK activity may be part of the normal immune response to repeated transfusion.

Adolescent↗
PubMed1984

Transferrin receptor function in hereditary hemochromatosis.

The binding of 125I-diferric transferrin to cultured skin fibroblasts and phytohemagglutinin-stimulated lymphocytes was studied in cells derived from individuals homozygous for hereditary hemochromatosis and from normal individuals. Receptors with a high affinity for diferric transferrin were present on all cells. Transferrin receptor number decreased by more than 50% when fibroblasts from both normal and hemochromatotic subjects were maintained in iron-supplemented medium. The number of transferrin receptors expressed by normal and hemochromatotic lymphocytes after mitogen stimulation in iron-supplemented media was less than 50% that of lymphocytes which were mitogen stimulated in standard medium. No change in the affinity of the receptors for diferric transferrin was seen in cells maintained in iron-supplemented medium. Competition experiments in the presence of deferoxamine suggested that the transferrin receptors of fibroblasts and mitogen-stimulated lymphocytes have a 70- to 100-fold higher affinity for diferric transferrin than for apotransferrin. No differences in the properties of transferrin receptors were found between patients with hereditary hemochromatosis and normal individuals. Although transferrin binding decreases when cells are exposed to high levels of iron in the medium, the failure to totally abolish transferrin binding to the receptor suggests that the concentration of diferric transferrin to which cells are exposed may be a major determinant of cellular iron loading in hereditary hemochromatosis.

Cells, Cultured↗
PubMed1984

[Oto-palato-digital type II syndrome].

A new case of the recently described oto-palato-digital type II is reported. The authors insist on the characteristic anomalies, the facial dysmorphism, the overlapping and deviation of the digits, the proximal implantation and hypoplasia of the big toe, and the deafness. Radiologically, the massive appearance of the bones, their incurvation, their defective modeling are characteristic of the syndrome. Life expectancy is often reduced. X-linked inheritance with minor stigmata in the heterozygous females is well established.

Abnormalities, Multiple↗
PubMed1984

[The impact of genetic counseling on the fertility of couples].

The authors from two independent patterns, genetic counselling on the one hand, familial study on the other hand show that the procreation rate of parents with affected children with spina bifida, digestive malformations and autosomal recessive diseases depend especially on the motherhood eagerness, on the mothers' age, on the family composition and on the possibilities of prenatal diagnosis effort to severely suffered parents before.

Adult↗
PubMed1984

[Malformation uropathies and multiple malformation syndromes].

The authors, from their experience emphasize the associated malformations' frequency in major congenital urinary tract malformations (26,9%). It is essential to recognize in these multiple defects some certified syndromes - inherited or not. The most associations are still unknown, nevertheless the genetic counselling require an accurate diagnosis.

Abnormalities, Multiple↗
PubMed1983

Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.

We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption. Four were severely disabled; all improved after withdrawal. Weakness was not a feature of this condition, and the central nervous system was clinically spared. Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin.

Adult↗
PubMed1983

Internalization and subcellular localization of transferrin and transferrin receptors in HeLa cells.

The subcellular location of radiolabeled transferrin (125I-Tf), internalized during cellular iron uptake, and the cellular distribution of transferrin (Tf) receptors were studied in cultured HeLa cells. Cells were incubated at 37 degrees C with 125I-Tf(Fe)2. Forty per cent of the labeled ligand was associated with cell surface receptors. The remaining 60% was internalized as shown by the inability to dissociate 125I-Tf from cells by competition with excess Tf(Fe)2 or treatment of cells with 0.2 M acetic acid containing 0.5 M NaCl. Subcellular fractionation studies using sucrose density gradients indicated that internalized Tf was localized in a membranous vesicle distinct from lysosomes, Golgi apparatus, endoplasmic reticulum, or plasma membranes. The subcellular distribution of Tf receptors was studied using an assay for detergent solubilized receptors. Even without preincubation with ligand, the majority of cellular Tf receptors were localized intracellularly in a vesicle with the same buoyant density as the vesicle containing internalized 125I-Tf. Using an assay for occupied receptors, we demonstrated that the same vesicle contained both internal receptors and internalized ligand. A portion (20%) of the intracellular receptor pool was insensitive to trypsin treatment of whole cells at 37 degrees C suggesting that during the experimental time period (20-30 min) this portion did not recycle to the cell surface. We propose that during cellular iron uptake, Tf receptor-ligand complexes are internalized and directed to a nonlysosomal compartment where iron is released, followed by recycling to the cell surface of an intact Tf receptor-apo-Tf complex.

Biological Transport↗
PubMed1983

Serum neuroleptic activity, prolactin, and tardive dyskinesia in schizophrenic outpatients.

The authors measured serum neuroleptic activity and serum prolactin levels in 26 schizophrenic outpatients on prolonged neuroleptic therapy. Of the 24 patients, 11 had moderate to severe tardive dyskinesia, as assessed by the Abnormal Involuntary Movement Scale (AIMS). AIMS scores were positively correlated with age, duration of illness, and negative schizophrenic symptoms, but not with variables of neuroleptic exposure, current serum levels of neuroleptic activity, or serum prolactin levels. Neuroleptic activity and prolactin levels were positively correlated, and both variables also correlated with the current daily dose of neuroleptics.

Adult↗
PubMed1983

Phenotypic change of acute monocytic leukemia to acute lymphoblastic leukemia on therapy.

Acute nonlymphocytic leukemias comprise most of the therapy-linked leukemias in cancer patients. We report here the unusual occurrence of acute lymphoblastic leukemia in a patient while on therapy for acute monocytic leukemia. The morphologic and histochemical studies were distinctly different between the initial presentation and the subsequent "relapse". At "relapse," the Philadelphia chromosome was not present, ruling out chronic myelogenous leukemia presenting in two morphologically different blastic phases. Cytogenetic and histochemical studies both at original presentation and at the time of relapse would be helpful in establishing the occurrence of a new leukemia.

Child↗
PubMed1983

Inhibition of a Langerhans cell-mediated immune response by treatment modalities useful in psoriasis.

Neither the pathogenesis of psoriasis nor the mechanism whereby seemingly diverse therapies alter the disease is understood. In this study, several antipsoriatic agents were tested for their effects on the skin cell lymphocyte reaction (SLR), an immunologic assay in which HLA-DR antigens on Langerhans cells (LC) stimulate proliferation of allogeneic lymphocytes. Every agent tested (cortisol, methotrexate, hyperthermia, anthralin) inhibited the SLR at therapeutic dose levels. By contrast, a variety of antibiotics, an anti-inflammatory agent, and lithium carbonate and propranolol, two drugs known to be ineffective in psoriasis, failed to inhibit the SLR. Finally, we have shown that hyperthermia and anthralin treatments are toxic for LC whereas they have little or no effect on keratinocyte viability. These results suggest that antipsoriatic agents may act in psoriasis by alteration or killing of LC.

Anthralin↗
PubMed1983

Studies on the physiology of macrophage receptors for alpha-macroglobulin X protease complexes.

Alveolar macrophages exhibit high-affinity receptors that effect the binding and internalization of alpha-macroglobulin X protease complexes (alpha M X P). Studies were designed to probe the mechanism of internalization of alpha M X P complexes. Macrophages also exhibit receptors capable of clearing other injurious agents such as mannose-terminal glycoproteins. We have demonstrated that uptake of mannose-terminal glycoproteins does not affect the rate of internalization of alpha M X P complexes, suggesting that "scavenger" receptors function independently, and that the machinery for endocytosis is not rate limiting. We have also demonstrated that the rate of internalization of receptor-bound alpha M X P is independent of receptor occupancy. During the internalization of alpha M X P there is a decrease in the number of surface receptors consistent with the internalization of ligand-receptor complexes. Using photoaffinity-labeled alpha M X P to inactivate surface receptors, we have demonstrated that even in the absence of ligand accumulation, pools of intracellular receptors exist which are capable of being exteriorized to the cell surface. These results suggest that concomitant with internalization of occupied receptors is the appearance of unoccupied receptors on the cell surface from an internal pool.

Animals↗
PubMed1983

Flow-volume curves and sleep-disordered breathing: therapeutic implications.

To assess the relationship of abnormal flow-volume curves during awake periods to the clinical severity of sleep-disordered breathing and the need for surgical treatment of obstructive sleep apnoea, flow-volume curves were measured in 72 adults with obstructive apnoea. Patients in whom surgery was recommended for standard clinical indications had significantly lower inspiratory flow rates (p less than 0.01) and a higher incidence of flow-volume curves indicating extrathoracic airway obstruction (p less than 0.01) than did non-surgical patients. These abnormal flow-volume curves correlated with an increased severity of nocturnal oxygen desaturation (p less than 0.01). Furthermore, increases in inspiratory flow rates measured serially in 22 patients were related to improvement in their polysomnography (p less than 0.05), suggesting that alterations of airway function during awake periods correlate with changes in the severity of sleep apnoea.

Female↗
PubMed1983

Production of pharmacologic monodisperse aerosols.

Monodisperse aerosols containing a range of chemical material, including pharmacologically active substances, were produced by using a modified Sinclair-LaMer condensation generator. Instead of the usual hot-wire technique, an ultrasonic nebulizer was used to suspend nuclei in the gas phase as an aqueous polydisperse aerosol. This technique allowed the generation of monodisperse oil (sebacate) aerosols containing nuclei of sodium chloride, histamine, methacholine, antigen, iron oxide, methylene blue, uranine, radioactive technetium pertechnetate, and technetium-labeled human serum albumin. Quantitative agonist activity was demonstrated for each active nucleus. Particle sizes ranged from 0.65 to 3 microns, with a geometric standard deviation of 1.1-1.2. This system can produce a stable, monodisperse, biologically active radiolabeled aerosol for a period of several hours.

Aerosols↗