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Biomedical subjects

C G Johnson

Publications and source records attributed to C G Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Starting patients on clozapine in a partial hospitalization program.

OBJECTIVE: The authors' aim was to assess the safety and efficacy of starting clozapine in a structured, long-term, partial hospitalization program that included protocols for detecting and managing side effects and adverse reactions to the drug as well as therapeutic programming to enhance patients' reintegration into community life. METHODS: Medical records of 47 patients with schizophrenia or schizoaffective disorder who were started on clozapine in the partial hospitalization program were analyzed. Data on incidence and management of adverse reactions, number of hospitalizations, status of symptoms, and changes in patients' social functioning for periods up to 12 months after initiation of clozapine were collected. RESULTS: Although adverse reactions were common in the first weeks of treatment, they were managed with dosing strategies, monitoring, and concomitant medication so that no patient had to discontinue the medication. Psychotic symptoms and symptoms of tardive dyskinesia decreased significantly during the study period. At 12-month follow-up, most patients were able to attend school, hold paying or volunteer jobs, and live independently. CONCLUSIONS: Clozapine can be safely initiated outside an inpatient setting. Partial hospitalization programs can enhance patients' reintegration into the community through a combination of treatment with clozapine and rehabilitative and psychotherapeutic programming.

Adolescent↗
PubMed1993

Substance P regulation of glutamate and cystine transport in human astrocytoma cells.

UC11 human astrocytoma cells transported glutamate by at least two distinct systems which appeared to be very similar to the Na(+)-dependent XAG- system (glutamate and aspartate are preferred substrates) and the Na(+)-independent xc- system (glutamate and cystine are preferred substrates) described in other cells, including primary cultures of rat astrocytes. The xc- system accounted for about 80% of the total glutamate influx. In a Na(+)-free buffer, the average Km and Vmax values for glutamate influx in UC11 cells were 167 +/- 15 microM and 0.82 +/- 0.04 nmoles/min/mg protein. Substance P, acting via an NK1 receptor, caused half maximal inhibition of glutamate and cystine transport at a peptide concentration of approximately 3 nM. Maximal inhibition was usually in the range of 60-80% and was noncompetitive in nature. Substance P also induced a significant increase in the release of endogenous glutamate. These effects of Substance P may be of pathophysiological significance in the CNS: first, a combination of inhibition of glutamate influx and stimulation of glutamate efflux from astrocytes is potentially toxic with respect to nearby neurons; second, an inhibition of cystine influx could result in a depletion of intracellular glutathione, resulting in increased sensitivity to oxidative stress.

Astrocytoma↗
PubMed1992

Characterization of receptors for substance P in human astrocytoma cells: radioligand binding and inositol phosphate formation.

UC11 cells, derived from a human astrocytoma, have a high density of functional substance P receptors. Radioligand binding studies were conducted with the highly selective neurokinin-1 receptor ligand [3H][Sar9,Met(O2)11]-substance P. Kinetic binding experiments conducted at 4 degrees C yielded an association rate constant k1 of 1.86 x 10(7) M-1 min-1, a dissociation rate constant k-1 of 0.00478 min-1, and a calculated kinetic KD of 257 pM. Saturation binding experiments yielded average values of KD = 447 +/- 103 pM, Bmax = 862 +/- 93 fmol/mg of protein. This Bmax corresponds to more than 150,000 binding sites/cell. Competition binding experiments with unlabeled [Sar9,Met(O2)11]-substance P yielded average values of KD = 491 +/- 48 pM and Bmax = 912 +/- 67 fmol/mg of protein. In [3H]inositol-labeled cells, substance P induced a robust inositol phosphate formation. Inositol trisphosphate levels increased as much as 20-fold within approximately 15 s of addition of substance P. This inositol trisphosphate formation was transient and had returned to baseline within the first 60-120 s. Inositol monophosphate formation, however, was linear for at least 2 h. Structure activity data on binding and inositol monophosphate formation confirmed the presence of a neurokinin-1 receptor subtype in these cells. Thus, the UC11 cell should be a useful model cell for delineating the physiological role of substance P receptors in astrocytes.

Astrocytoma↗
PubMed1991

Tumor necrosis factor and interleukin-1 down-regulate receptors for substance P in human astrocytoma cells.

This study examined the influence of cytokines on substance P (SP) receptors (NK1 subtype) in the human astrocytoma cell line UC11. Following trypsinization and passage, the density of SP receptors in these cells was rather low but gradually increased several fold over the course of a few days in culture. Frequent replacement of the growth medium enhanced the density of receptors even more, suggesting that growth factors in the culture medium may determine the levels of receptor. Exposure of the cells to sub-nanomolar concentrations of tumor necrosis factor (TNF alpha) or interleukin-1 beta (IL1 beta), but not interleukin-2 or interleukin-6, decreased the density of SP receptors. This was accompanied by a decrease in the ability of SP to stimulate inositolphosphate formation. The ability of histamine to activate inositolphosphate formation was not influenced by the cytokines. The decrease in SP receptor density was readily reversible on washout of the cytokines. The EC50 for TNF alpha was approximately 0.5 ng/ml, the EC50 for IL1 beta was approximately 0.1 ng/ml. Radioligand binding studies with [125I]TNF alpha indicated the presence of a low density of high affinity binding sites for this ligand: Kd = 2.5 +/- 0.6 ng/ml, Bmax = 14.8 +/- 2.7 fmol bound/mg protein (assuming trimeric form of ligand bound). The most likely explanation for the cytokine effect is an inhibition of the synthesis of new receptors.

Astrocytoma↗
PubMed1990

Inhibition of human skin fibroblast proliferation by histamine and phorbol esters is mediated by protein kinase C.

The proliferation of human skin fibroblasts in culture was examined using a [3H]thymidine incorporation assay. Histamine inhibited thymidine incorporation with an IC50 of about 0.2 microM. This effect was blocked by the H1 receptor antagonist mepyramine but not by the H2 receptor antagonist cimetidine. Protein kinase C activators, including several phorbol esters and mezerine, also inhibited thymidine incorporation. The IC50 for beta-phorbol 12,13-didecanoate was less than 0.1 nM. The alpha-isomer of this compound was inactive. Long-term treatment of cells with the beta-isomer eliminated the ability of both histamine and phorbol ester to inhibit thymidine incorporation, presumably due to downregulation of protein kinase C. Our results suggest that histamine H1 receptors are linked to activation of protein kinase C and that activation of this enzyme leads to an inhibition of cell proliferation.

Blood↗
PubMed1990

Histamine receptors in human fibroblasts: inositol phosphates, Ca2+, and cell growth.

Histamine stimulated inositol phosphate formation by human skin fibroblasts. The effect of histamine was reduced but still readily apparent in the absence of extracellular Ca2+. Histamine caused a transient increase in intracellular free Ca2+ as detected by indo-1 and fura-2 fluorescence studies on cell populations and on individual cells. Similar increases were observed in the absence of extracellular Ca2+, indicating that the effect was primarily due to mobilization of Ca2+ from intracellular stores, presumably by inositol trisphosphate (IP3). The effects of histamine on phosphoinositide metabolism and intracellular Ca2+ were inhibited by pretreatment of the cells with phorbol esters, suggesting that the histamine receptor in fibroblasts is subject to feedback regulation by protein kinase C. Histamine inhibited the incorporation of [3H]-thymidine into DNA. The effects of histamine on inositol phosphate formation, intracellular Ca2+, and thymidine incorporation were blocked by the H1 receptor antagonist mepyramine. Our results indicate that human skin fibroblasts have H1 receptors coupled to the formation of inositol phosphates and mobilization of intracellular Ca2+. We suggest that this H1 receptor also mediates a block of the cell cycle and that histamine may play a physiological role in the regulation of fibroblast proliferation.

Aminopyridines↗
PubMed1989

Women and autonomy: using structural analysis of social behavior to find autonomy within connections.

In their work to construct psychological theories about women's development, Carol Gilligan and Jean Baker Miller both highlight the centrality of interpersonal connections in women's lives. As they describe how women's senses of self and morality are organized around relationships, Gilligan and Miller tend to contrast affiliation with autonomy. The message that readers often take from this view is that autonomy has no meaning for women--is somehow beneath them, beyond them, or unnatural to them. Although Miller and Gilligan dichotomize affiliation and autonomy, they also provide numerous examples in which women's feelings of worth, ability, and self-consideration enhance relatedness. We argue that autonomy can be understood as a sense of freedom and personal integrity that encompasses these same characteristics, and we use the Structural Analysis of Social Behavior to clarify how autonomy makes critical contributions to interpersonal connections.

Female↗
PubMed1986

Impacts of labeling and competence on peers' perceptions: mentally retarded versus nonretarded perceivers.

In an attempt to determine whether educably mentally retarded children hold the same attitudes towards members of their group that nonretarded children hold, regular-class and special-education class students in junior high school indicated their trait perceptions of and willingness to interact with same-sex target children who were either competent or incompetent spellers and who were labeled as either regular-class or special-class students. Although both groups perceived competent peers more positively than incompetent peers, only nonretarded students perceived peers labeled as special-education students more negatively than they perceived unlabeled peers. Neither group expressed any unwillingness to interact socially with either an incompetent or a special-class student. Thus, within the context of this study, there was no evidence that special-education students internalize prevailing negative attitudes toward their group.

Achievement↗
PubMed1978

Acid-etch repair of hereditary type 4 enamel hypoplasia.

Defects of the enamel include hypoplasia and hypomineralization. The cause can be local, systemic, or hereditary. A 14-year-old boy had type 4 hereditary hypoplastic enamel. The Nuva-Seal, Nuva-Fil acid-etch technique was used to restore the defect.

Acid Etching, Dental↗