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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 307 records · Page 17Linked to original sources
PubMed1987

Characterization of endocytic compartments using the horseradish peroxidase-diaminobenzidine density shift technique.

We have employed a modification of the horseradish peroxidase (HRP)-diaminobenzidine density shift technique of Courtoy et al. (J. Cell Biol., 1984, 98:870-876) to examine the biochemical properties of the endosome. This organelle is involved in receptor recycling and the sorting of internalized receptor ligand complexes. Transferrin covalently bound to HRP was used to place peroxidase activity specifically within the endosome. The peroxidase-catalyzed polymerization of diaminobenzidine within these vesicles causes an increase in buoyant density, thus allowing them to be separated from other membranes. Using this technique we demonstrate that 125I-low density lipoprotein, 131I-epidermal growth factor, and Tf-HRP are internalized into the same endosome. We discovered that the diaminobenzidine reaction product "cross-links" the lumen of the vesicle, rendering vesicular components detergent insoluble. Furthermore, the reaction inactivates enzymatic activities associated with the endosome. Thus, the diaminobenzidine density shift procedure has limited usefulness in studies designed to isolate endosomal constituents. Nonetheless, we have found that the inactivation of enzymatic activities is confined to those endosomes that contain peroxidase. This selectivity allows us to define endosome-specific activities.

Biological Transport↗
PubMed1987

Depression, parkinsonian symptoms, and negative symptoms in schizophrenics treated with neuroleptics.

To determine whether depression and neuroleptic-induced parkinsonism confound the clinical assessment of negative symptoms in schizophrenics, we evaluated 45 outpatient schizophrenics for depression, parkinsonian symptoms, and negative symptoms using standard clinical rating scales. Neuroleptic and anticholinergic dose and plasma activity were also determined. Associations between negative symptoms and these clinical and drug variables were examined using a multivariate statistical model. Negative symptoms were significantly correlated with several parkinsonian symptoms, some vegetative features of depression, and with anticholinergic dose. No significant correlations were found between negative symptoms and cognitive features of depression, or neuroleptic and anticholinergic plasma activity. These findings suggest that assessment criteria for negative symptoms, depression, and drug-induced parkinsonism overlap in treated schizophrenics. Strategies for differentiating these clinical syndromes are discussed.

Adult↗
PubMed1987

[Genetic counseling and prenatal diagnosis in Duchenne myopathy: yesterday, today and tomorrow].

The coming of molecular biology has greatly modified the concept of genetic counselling and prenatal diagnosis of Duchenne muscular dystrophy. The most important stages of the genetic counselling are reported: estimate of the risk and carrier detection. This heterozygote detection is now possible in a few cases owing to polymorphic DNA markers recently identified that are genetically linked to the DMD gene locus and detected with probes. An analysis of foetal DNA is also possible and allows us to consider prenatal diagnosis of this affection. This study is yet limited by two impediments: on one hand low rate of informative families, on the other hand use of markers that are not very closely linked to DMD involving recombinations and risks of errors. The solution of these problems is in the use of linked DNA markers with the best polymorphism flanking the Duchenne muscular dystrophy locus. Finally the authors report the necessity of strict collaboration systems between clinical experts, geneticists, biologists and informaticians.

Female↗
PubMed1987

Source of iron in neutrophil-mediated killing of endothelial cells.

Recently we have shown that human neutrophils activated with phorbol ester are cytotoxic for cultured bovine pulmonary artery endothelial cells in an iron-dependent manner. By using the ferric iron chelator deferoxamine mesylate, we have now investigated the source of the iron. Pretreatment of neutrophils with deferoxamine mesylate affected neither their production of O2- nor their cytotoxicity for endothelial cells after addition of phorbol ester. However, similar pretreatment of endothelial cells with deferoxamine mesylate, followed by washing of the cells, resulted in a persistent presence of chelator associated with the endothelial cells and high degrees of protection of endothelial cells from cytotoxicity. The protection was dependent on the amount of chelator used and on the duration of exposure of the endothelial cells to the chelator. These data suggest that iron, which plays an important role in oxygen radical-mediated killing of endothelial cells by neutrophils, is derived from the target (endothelial) cells.

Animals↗
PubMed1986

Natural killer cell regulation of age-related and type-specific variations in antibody responses to pneumococcal polysaccharides.

Pretreatment of mice with anti-asialo GM1, which has been shown to deplete NK cytolytic activity without affecting cytotoxic T cells or macrophages, increased the weak anti-PPS 6 responses of adult mice to levels similar to that of their anti-PPS 3 responses, and increased the weak-to-absent anti-PPS 3 and anti-PPS 6 responses of weanling mice to the same levels as achieved by adult mice. By contrast, pretreatment with poly(IC), which augments NK activity, resulted in a 14-fold reduction in the anti-PPS 3 responses of adult mice. The enhancement of anti-PPS responses in mice treated with anti-asialo GM1 was due to inactivation or depletion of NK cells, and not T suppressor cells, since this enhancement occurred in athymic nude mice as well as in euthymic mice. In addition, strains of mice with low or absent endogenous NK activity were found to have considerably stronger anti-PPS responses than strains of mice with normal NK activity. NK depletion enhanced anti-PPS 6 IgM but not IgG response, and resulted in a true increase in antibody production rather than an alteration in the time course of the response. These findings indicate that NK cells physiologically downregulate anti-PPS responses, and that age-dependent and type-specific variations in these responses are primarily determined by NK regulatory effects.

Age Factors↗
PubMed1986

Mitogenic agents induce redistribution of transferrin receptors from internal pools to the cell surface.

Incubation of serum-growth HeLa cells in serum-free medium causes a rapid (t1/2 3 min) 30-60% decrease in the binding of 125I-diferric transferrin to the cell surface. Addition of fetal bovine serum to cells in serum-free medium results in a rapid (t1/2 3 min) and concentration-dependent increase in binding activity. The loss or gain in ligand binding is a result of changes in surface receptor number rather than an alteration in ligand-receptor affinity. A variety of hormones (insulin, insulin-like growth factor, interleukin 1 and platelet-derived factor) were found to mimic the effect of serum on receptor number. The alteration in surface receptor number was found to be calcium-dependent. Changes in surface receptor number were independent of either receptor biosynthetic rate or the absolute cellular content of receptors. The effect of insulin or serum on Hela cell transferrin receptor distribution was unaffected by the presence of transferrin, demonstrating that receptor distribution in this cell type is ligand-independent. The ability of serum or insulin to modify surface transferrin receptor number was also observed in mouse L-cells, human skin fibroblasts, and J774 macrophage tumour cells. However, transferrin receptors on K562 and Epstein-Barr virus-transformed human lymphoblasts were unaltered by these agents. The quantities of receptors whose distribution is predominantly on the surface (i.e. epidermal growth factor or low density lipoprotein receptor) were unaltered by addition of the mitogenic agents. These results extend our previous studies [H.S. Wiley & J. Kaplan (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 7456-7460] demonstrating that mitogenic agents can induce redistribution of receptor pools in selected cell types.

Blood↗
PubMed1986

T-cell acute lymphoblastic leukemia with natural killer cell phenotype.

To determine the type and proportion of cases within that type of acute lymphoblastic leukemia (ALL) that has a natural killer (NK) cell phenotype, we examined leukemic blasts from 31 children with ALL (14 with T-ALL, 17 with non-T-ALL) for expression of antigens detected by NK-specific monoclonal antibodies Leu 11b, Leu 7, and 1G2 (an antibody we have developed that cross-reacts with Leu 7). None of the patients had leukemic blasts that reacted with Leu 11b. However, leukemic blasts from four T-ALL patients were 1G2+ and/or Leu 7+. Blasts from two of these had spontaneous lytic activity against standard NK target cell line K562; blasts from one killed K562 only when incubated with interferon; blasts from the other had no lytic activity against K562 but did manifest antibody-dependent cell-mediated cytotoxicity against antibody-coated cells from NK-resistant cell line SB. Blasts from all four Leu 7+ patients had L2 morphology. In one, the leukemic blasts had azurophilic cytoplasmic granules similar to those found in NK-enriched normal populations of large granular lymphocytes. These findings suggest that a significant proportion of T-cell acute lymphoblastic leukemias may be malignancies of NK cell origin.

Adolescent↗
PubMed1986

Possible associations among plasma prolactin levels, tardive dyskinesia, and paranoia in treated male schizophrenics.

To determine whether there is an association between prolactin (PRL) levels and psychopathology or tardive dyskinesia during neuroleptic treatment, we measured plasma prolactin levels and neuroleptic activity (NA) in 33 chronically treated male schizophrenics. Neuroleptic dose, plasma NA, and PRL were significantly intercorrelated. Plasma PRL levels were also measured in 8 male schizophrenics recently withdrawn from neuroleptics and in 18 normal male controls. In treated patients, but not in controls, PRL levels decreased with age and duration of illness, two variables that we interpreted as indirect measures of neuroleptic exposure. PRL levels in patients recently withdrawn from neuroleptics were lower than in treated patients or controls, which was suggestive of rebound hypoprolactinemia. A prolactin index, calculated as the ratio of PRL levels to NA, was inversely correlated with paranoid symptoms and tardive dyskinesia in younger treated patients. These results lead to speculation that tuberoinfundibular dopaminergic supersensitivity develops in chronically treated schizophrenics and that it is associated with nigrostriatal supersensitivity, manifested by tardive dyskinesia, and paranoid symptoms, which may reflect mesolimbic supersensitivity.

Adult↗
PubMed1986

Intracellular pools of transferrin receptors result from constitutive internalization of unoccupied receptors.

In HeLa cells the majority of transferrin (Tf) receptors are found within the endocytic apparatus, with only 20% of receptors exposed at the cell surface. Receptor distribution is unaltered by the presence or absence of Tf. The mechanism responsible for the cellular distribution of receptors was explored by selectively inactivating receptors within the endocytic apparatus. This was accomplished by employing Tf-horseradish peroxidase conjugates. Peroxidase-catalyzed oxidation of diaminobenzidine within an endosome destroys Tf receptor activity. Using such conjugates, we have demonstrated that the majority of internal Tf receptors could be inactivated when less than 6.0% of receptors were occupied by the conjugate at steady state. This result indicates that occupied and unoccupied receptors are in the same compartment. Furthermore, horseradish peroxidase that was internalized by fluid-phase pinocytosis inactivated intracellular Tf receptors in the absence of Tf; this indicates that the presence of internal receptors is ligand independent. Following exposure of cells to the conjugate, receptor inactivation was proportional to the percentage of the endocytic cycle traversed by the conjugate--that is, the rate of ligand accumulation was the same as the rate of endosomal Tf receptor inactivation. When the Tf-horseradish peroxidase conjugate and 125I-labeled Tf were internalized simultaneously, both ligands were found in the same compartment. However, if the two ligands were administered as separate pulses and the period between pulses was as short as 1 min, the ligands remained separate within the cell. Together these results demonstrate that the intracellular pool of Tf receptors reflects the constitutive internalization of unoccupied Tf receptors, which, once internalized, remain segregated.

Cell Compartmentation↗
PubMed1986

Legal deterrents.

Explore the source record for details and available documents.

Capital Punishment↗
PubMed1986

Revaccination with polyvalent pneumococcal vaccine in children with sickle cell anemia.

To determine if revaccination improves levels of antibodies to pneumococcal polysaccharide types 6A, 14, and 19, 86 subjects with sickle cell anemia between 4 and 23 years old were given a booster injection of a polyvalent pneumococcal vaccine 37 to 53 months after primary immunization. Most subjects had mild local reactions similar to those seen after primary immunization. Only two subjects, both young adults, had severe local and systemic reactions. The percentages of subjects with protective antibody levels to types 6A, 14, and 19 increased from 74%, 44%, and 79% respectively before boosting, to 92%, 66%, and 92% respectively after boosting. Revaccination of children and young adults with sickle cell anemia appears to result in increased protective levels of antibody, and is associated with a low prevalence of severe reactions.

Adolescent↗
PubMed1986

[The genetics of collagen diseases].

Heritable disorders of collagen include Ehler-Danlos syndromes (11 types are actually known), Larsen syndrome and osteogenesis imperfecta. Their clinical, genetic and biochemical features are reviewed. Marfan syndrome is closely related to heritable disorders of collagen.

Abnormalities, Multiple↗