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Glutathione depletion potentiates 12-O-tetradecanoyl phorbol-13-acetate(TPA)-induced inhibition of gap junctional intercellular communication in WB-F344 rat liver epithelial cells: relationship to intracellular oxidative stress.

Treatment of WB-F344 liver epithelial cells with buthionine sulfoximine (BSO, 100 microM) for 24 h caused a greater than 95% depletion in cellular glutathione (GSH) and potentiated the ability of 12-O-tetradecanoyl phorbol-13-acetate (TPA) to inhibit gap junctional intercellular communication (GJIC) between the cells (IC50 shifted from 5 microM to 2 microM). Similarly, acute depletion of GSH by up to 30%, either with the thiol oxidant diamide or with BSO, also potentiated the inhibitory effect of the phorbol ester on GJIC. The treatment of the control cells with TPA caused a concomitant increase in the accumulation of oxidation products of 2',7'-dichlorofluorescein (DCF), indicating elevated production of oxidants in the cells during the blockade of GJIC. The depletion of GSH over a 24 h period with BSO itself increased the flux of oxidants in the cells but did not inhibit GJIC. Treatment of these GSH-depleted cells with TPA caused an additive elevation in the accumulation of oxidised DCF metabolites. Direct application of H2O2 (25-200 microM) or benzoyl peroxide (25-150 microM) to the control cells for 60 min caused weak, dose-dependent inhibitions of gap junctional communication in these cells but these responses were accompanied by the induction of acute, sub-lethal cytotoxicity. The depletion of GSH from the cells did not potentiate these responses to the peroxides but did facilitate synergistic inhibition of gap junctional communication in response to both TPA and sub-toxic doses of either peroxide. The results of the above studies indicate that oxidants are produced in WB-F344 cells in response to TPA and that these function in a co-operative manner with other cellular responses to the phorbol ester in the inhibition of gap junctional communication. This may explain why priming the cells for the induction of oxidative stress by the depletion of GSH potentiates the inhibitory activity of TPA on gap junctional communication.

Animals↗

Communication disturbances in schizophrenia: a two-process formulation.

We hypothesized that communication disturbances in the form of unclear linguistic references in schizophrenia are associated with excess-related pathophysiologic processes in some individuals and deficit-related processes in others. We divided a sample of 28 acutely ill schizophrenic inpatients into two groups: those with negative symptoms and those without. We analyzed audiotaped speech samples from each subject, and found that the two groups did not differ significantly on overall level of communication disturbance. In patients without negative symptoms, level of communication disturbance was associated with severity of positive symptoms (r = .62, P < .02) and with neuroleptic responsiveness (r = .52, P < .06 [trend]). In those with negative symptoms, level of communication disturbance did not correlate with severity of positive symptoms (r = .09, NS), and correlated negatively with medication responsiveness (r = -.66, P < .01). These findings support a two-process hypothesis of schizophrenic communication disturbance.

Acute Disease↗

Tumour promoter-mediated reversible inhibition of cell-cell communication (electrical coupling). Relationship with phorbol ester binding and de novo macromolecule synthesis.

A tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), reversibly inhibits the onset and maintenance of cell-cell communication measured by electrophysiological method. We have now studied the mechanism by which TPA inhibits communication of human cells (FL) in culture. Using [3H]phorbol-12,13-dibutyrate [( 3H]PDBu), we found a class of specific, high-affinity, saturable binding sites in intact FL cells; they have a dissociation constant of 15.4 nM, and at saturation about 3 X 10(5) PDBu molecules were bound to each cell. The binding of [3H]PDBu to FL cells was inhibited by TPA, phorbol-12-13-didecanoate and mezerein, whereas phorbol and 4 alpha-phorbol-12-13-didecanoate had no effect. There is a close correlation between the ability of the former compounds to inhibit [3H]PDBu binding and their capacity to inhibit cell-cell communication. When FL cells are dispersed with EDTA and plated onto a culture dish, they start to couple electrically within 2 h; such cell coupling was not affected by the presence of cycloheximide or actinomycin D. TPA inhibits the formation of electrical cell coupling as well as its maintenance, even in the presence of cycloheximide; the recovery of cell-cell communication after the removal of TPA was not significantly affected by the addition of cycloheximide or actinomycin D. Taken together, these results suggest that TPA-mediated reversible inhibition of intercellular communication is mediated by specific binding of TPA to cellular receptors and that macromolecular synthesis is not necessary.

Binding Sites↗

Patterns of junctional communication in skin: studies on cultured keratinocytes.

Junctional communication has long been suggested to play a role in coordinating the development of multicellular tissues. A better understanding of the patterns of communication between cells in such tissues is important for the identification of areas where this process may have a role. We have investigated the patterns of communication in cultures of human epidermal keratinocytes by iontophoretic injection of Lucifer Yellow CH, using involucrin expression as a marker of cells undergoing terminal differentiation. Cells that lack involucrin (i.e., the basal, proliferating cells) transfer dye preferentially to other involucrin-negative cells, whereas involucrin-positive cells either are not coupled or transfer dye with similar frequency to involucrin-positive and involucrin-negative neighbors. This decrease in communication associated with terminal differentiation was observed in both the presence and the absence of assembled desmosomes. Our observations lead us to speculate that loss of junctional communication may influence the commitment of basal keratinocytes to terminal differentiation.

Cell Communication↗

Vitamin D influences gap junctional communication in C3H/10T 1/2 murine fibroblast cells.

Vitamin D3, cholecalciferol, induces cell-cell communication via gap junctions in murine fibroblasts (C3H/10T 1/2 cells) at concentrations between 0.01 and 1.0 microM, as assayed by the dye transfer method using Lucifer yellow CH. The extent of induction is similar to that obtained with the positive controls, canthaxanthin or retinoic acid, applied at 10 and 1 microM, respectively. Vitamin D2 also induces cell-cell communication. At elevated concentrations of vitamin D3 (5 microM) there is a suppression of gap junctional communication, reversible upon exposure to all-trans retinoic acid (1 microM) after removal of vitamin D3 from the medium. Conversely, communication between cells prestimulated with retinoic acid (1 microM) rapidly decreases when the retinoid is replaced by vitamin D3 (5 microM). The data demonstrate a role for vitamin D in the regulation of intercellular communication. This novel property of vitamin D may contribute to the antiproliferative effects of vitamin D exhibited in some types of cancer.

Animals↗

Communication and decision-making in a study of a multidisciplinary team conference with the registered nurse as conference chairman.

It was decided that the medical and nursing staff had to communicate verbally concerning the patient's need for information and to make decisions concerning steps to be taken when satisfying the patient's need for information. The aim of this study was, accordingly, to investigate if a training programme for registered nurses as chairperson of the multidisciplinary team conference (MTC) changed the communication and decision pattern during the neurological ward conference. The training material provided instructions and a scheme for the chairperson of the MTC. The training was carried through with the help of patient case reports and role play. Data were collected through tape recordings of the communication at ten MTCs before the training and ten MTCs after the training. The strictly medical communication was less illuminated, while the patient's psychological needs, especially concerning the patient's need for information, were better illuminated than before the training. After the training 42 information problems were reported and two before. For half of them, decisions were made on the steps to be taken in order to fulfil the patient's need. For the other half, the discussion concerning the patient's need for information was communicated between the staff. Only the decision-making was missed.

Communication↗

Communicative effectiveness in Broca's aphasia.

The purpose of this study was to investigate communicative effectiveness in aphasia. Five patients with Broca's aphasia and five neurologically normal subjects participated in referential communication and spontaneous conversation tasks. Performance on the referential tasks was used to derive measures of communication success, learning, and efficiency. A representative sample of utterances from the referential tasks and 100 utterances from the spontaneous conversation task also were analyzed to determine the frequency of operationally defined errors in speech, lexical access, grammar, content, discourse, and use. Results suggest that patients with Broca's aphasia retain communicative effectiveness in the presence of significant speech and language deficits and experimentally imposed constraints on the use of visual and gestural communication modalities.

Adult↗

Symbolic play and early communication development in hearing-impaired children.

This study investigated the relationship between symbolic play and language performance for young hearing-impaired children. Subjects included 20 hearing-impaired youngsters ranging in age from 38 months to 69 months. The children were placed in two ordinal communication groups. Placement in one of the communication levels was dependent upon information concerning the number of spontaneous expressive communication units the child produced. The experimental task consisted of three predetermined play themes in which the child previously displayed functional play. A nonconventional item was then included, and the play behaviors were observed for the occurrence of symbolic play under a spontaneous or modeled condition. The results indicate a significant difference in symbolic play between the two ordinal communication levels. Additionally, there was a strong positive relationship observed between the variables of symbolic play and early communication development.

Child, Preschool↗

Speech intelligibility of two voice output communication aids.

The purpose of the study was to investigate the intelligibility of two voice output communication aids. Twenty words and 20 sentences, synthesized with the Personal Communicator and with the SpeechPAC, were presented to 20 listeners. Listener transcriptions of the stimuli were used to compare the intelligibility of the two communication aids. Analysis of variance revealed significantly higher intelligibility scores for the Personal Communicator compared to the SpeechPAC and higher scores for sentences than for words. The implications of these findings for selection of augmentative communication devices is discussed.

Adult↗

Inhibition of intercellular junctional communication in human fibroblasts by triphenylmethane, triphenylmethylchloride, tetraphenylboron and related compounds.

Intercellular junctional communication was measured using [14C]citrulline incorporation in co-cultures of argininosuccinate synthetase-deficient and argininosuccinate lyase-deficient human fibroblasts. Triphenylmethane, triphenylmethylchloride and tetraphenylboron inhibited communication at concentrations at least 12-fold lower than cytotoxic concentrations. This inhibition was of rapid onset and was rapidly reversible by washing the co-cultures. Refractoriness to inhibition did not develop after prolonged exposure. Several other compounds also induced communication inhibition, but only at concentrations slightly below cytotoxic concentrations. Treatment of co-cultures with calcium ionophore A23187 or cycloheximide did not cause communication inhibition. It is suggested that triphenylmethane, triphenylchloride and tetraphenylboron may be useful inhibitors for studying the roles of intercellular junctional communication in some biological systems.

Argininosuccinate Lyase↗

Effect of various polybrominated biphenyls on cell-cell communication in cultured human teratocarcinoma cells.

Firemaster BP-6 (FM), a mixture of polybrominated biphenyls (PBB), and the congeners 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB), 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB), and 3,3',4,4'-tetrabromobiphenyl (34-TBB) were tested for their ability to inhibit cell-cell communication between human teratocarcinoma cells in culture. Both FM and 245-HBB were capable of inhibiting cell-cell communication in these cells, with only slight effects on cell survival. 345-HBB was highly cytotoxic, but did not show the ability to interrupt cell-cell communication. 34-TBB was moderately cytotoxic and was also ineffective at blocking cell-cell communication. The results agree with previously published findings in Chinese hamster V79 cells, and are in accordance with proposed structure-activity relationships for these compounds. Inhibition of cell-cell communication, either directly (FM and 245-HBB) or indirectly through necrosis-induced compensatory hyperplasia (345-HBB), may be involved in the promotion of hepatocellular neoplasms by these compounds.

Cell Communication↗

Dieldrin inhibition of gap junctional intercellular communication in rat glial cells as measured by the fluorescence photobleaching and scrape loading/dye transfer assays.

Application of the fluorescence-recovery after photobleaching (FRAP analysis) technique and scrape loading/dye transfer assay was made to measure the presence of gap junctional communication in primary rat glial cells in vitro in the presence and absence of the neurotoxicant and tumor promoter dieldrin, a chlorinated insecticide. Results demonstrate that primary rat glial cells are able to exhibit gap junctional intercellular communication and that dieldrin at noncytotoxic concentrations can modulate gap junctional communication as early as 10 min after exposure to the chemical and that the effect is reversible after 4 hr recovery from the dieldrin exposure. Both the FRAP analysis and the scrape loading/dye transfer assay have validated the observation that dieldrin inhibits gap junctional communication in other cell types using different techniques to measure gap junction function. These results were interpreted as an indication that inhibition of gap junctional communication might contribute to the cellular mechanism of dieldrin's neurotoxicity.

Animals↗

Antioxidant prevention of tumor promoter induced inhibition of mouse hepatocyte intercellular communication.

The liver tumor promoters, phenobarbital (20-500 micrograms/ml), lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer; 0.1-5.0 micrograms/ml), and DDT (1,1-bis[4-chlorophenyl]-2,2,2-trichloroethane; 0.5-10.0 micrograms/ml), and the hydrogen peroxide-generating enzyme, glucose oxidase (0.01-0.10 units/ml) inhibited gap junctional intercellular communication between B6C3F1 mouse hepatocytes in primary culture. Addition of the antioxidants, superoxide dismutase (100 units/ml), DPPD (N,N'-diphenyl-1,4-phenylenediamine; 25 microM), and vitamin E (DL-alpha-tocopherol acetate; 100 microM), to tumor promoter-treated cultures prevented the inhibition of hepatocyte intercellular communication. DPPD and vitamin E, prevented the inhibition of hepatocyte intercellular communication by glucose oxidase. Superoxide dismutase had no effect on the inhibition of intercellular communication caused by glucose oxidase. These results suggest that activated oxygen species are produced during liver tumor promoter treatment of cultured mouse hepatocytes and are responsible for the inhibition of mouse hepatocyte intercellular communication by the promoters.

Animals↗

Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters.

The effect of the liver tumor promoters phenobarbital (PB), 1,1-bis(4-chlorophenyl)-2,2,2-trichlorethane (DDT), and dieldrin on gap junction-mediated intercellular communication between primary cultured hepatocytes from male mice (B6C3F1), C3H, C57BL, and Balb/c strains) and male F344 rats was determined. Intercellular communication was detected autoradiographically as the passage and incorporation of [5-3H]uridine nucleotides from prelabelled donor hepatocytes to donor-contacting recipient hepatocytes. At non-toxic concentrations, PB (20-500 micrograms/ml) inhibited intercellular communication between B6C3F1, C3H, and Balb/c mouse hepatocytes and F344 rat hepatocytes, but not between C57BL mouse hepatocytes. DDT (1-10 micrograms/ml) inhibited intercellular communication between hepatocytes from all 4 strains of mice and the F344 rat. Dieldrin (1-10 micrograms/ml) inhibited intercellular communication between hepatocytes from the 4 strains of mice but not between rat hepatocytes. These findings showed a good correlation with the in vivo liver tumor promoting/hepatocarcinogenic actions of PB, DDT and dieldrin in the 4 mouse strains and the F344 rat strain.

Animals↗

Women and health care communication.

Research bearing on the issue of gender differences in patient-provider communication is discussed, and recommendations for future research and for patient education and counseling are offered. Based on limited available evidence, women appear to receive more health care communications and more health information than men, possibly due to women's superior general communication skills. Provider gender may also affect the communication process, and congruence between patient and provider gender could produce more effective communication under some circumstances.

Communication↗

Health risk communication--a view from within industry.

Health risk communication is discussed in respect to four principles of biomedical ethics: (1) autonomy, the need to protect confidentiality and provide decision-making information; (2) beneficence, an obligation to inform and to develop trust; (3) non-maleficence, not covering up study findings, not over- or underinterpreting data; and (4) justice, helping place risk in proper perspective. The epidemiologist's role in risk communication includes responsible interpretation of data, balanced and non-judgemental risk communication and careful attention to the biologic and population significance of study findings. Potential problem areas for epidemiologists which are discussed include deciding when risk is significant, working for an agency which does not want a communication to take place and the occasional need to violate confidentiality for overriding societal goals. The paper concludes with an example risk communication which illustrates some of the principles covered in the paper.

Communication↗

Communication with dying patients in coronary care units.

There now seems to be a much greater willingness among hospital staff to disclose a terminal prognosis to a patient. The paper starts with a review of the changing attitudes towards disclosure and then considers communication with dying patients in Coronary Care Units. After considering general factors influencing nurse communication with dying patients sources of difficulty in such communication are considered. Characteristics of patients and relatives, of nurses, and features of the work environment may all contribute to communicational difficulties. The paper closes with a brief overview of basic communicative requirements.

Cardiovascular Diseases↗

The communication process with ventilator patients in the ICU as perceived by the nursing staff.

Intensive care unit (ICU) nurses (n = 27) were interviewed about their experiences and opinions of the communication process with ventilator treated patients. Nurses with limited ICU experience considered the initial contact with a new critically ill ventilated patient more frustrating than experienced nurses. The nurses thought that the content of the communication commonly requested by a patient was dominated by factors related to the clinical condition, prognosis and reassurance that the situation was under control. Factors considered to limit the communication and to create feelings of uncertainty and stress for nurses with an ICU experience of less than 5 years were: work overload, unstable condition of the patient, impaired communication with the patient, and their own personal problems or worries. For nurses with an ICU experience of more than 5 years stress was more commonly evoked by the presence of worried and anxious spouses/relatives, and by the feeling that something was wrong with the patient but they were unable to identify the problem. Failure to understand a ventilated patient could induce feelings of incompetence, stress and sometimes even despair. The present small scale study shows that there are many factors, in addition to ICU experience, that may influence the ability of an ICU nurse to establish and maintain a well functioning communication with ventilated patients and the likelihood of doing so.

Adult↗