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Biomedical subjects

L Christian

Publications and source records attributed to L Christian.

At least 19 recordsLinked to original sources

Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation.

Exogenously administered opiates are recognized as rewarding and the involvement of dopamine systems in mediating their apparent pleasurable effects is contentious. The aversive response to naloxone administration observed in animal studies suggests the presence of an endogenous opioid tone regulating hedonic state. We sought evidence for the requirement for dopamine systems in mediating this action of endogenous opioids by determining whether mice deficient in dopamine D-1 or D-2 receptors were able to display conditioned place aversion to naloxone. Mice received saline in the morning in one chamber and either saline or naloxone (10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon. Similar to their wild-type littermates, D-1 and D-2 receptor knockout mice receiving naloxone in the afternoon spent significantly less time on the test day in the compartment in which they previously received naloxone, compared with animals receiving saline in the afternoon. The persistence of naloxone-conditioned place aversion in D-1 and D-2 knockout mice suggests that endogenous opioid peptides maintain a basal level of positive affect that is not dependent on downstream activation of dopamine systems involving D-1 or D-2 receptors.

Affect↗

Effects of cocaine and morphine under mixed-ratio schedules of food delivery: support for a behavioral momentum analysis.

Previous studies have shown that ratio size influenced the development of tolerance under simple and multiple schedules, but not under progressive-ratio (PR) schedules. PR schedules share certain features with mixed-ratio (MR) schedules, and pilot data suggested that ratio size fails to modulate tolerance to cocaine or morphine under MR schedules. The present study examined more comprehensively the pre- and postchronic effects of cocaine and (in separate birds) morphine under MR schedules with fixed-ratio (FR) 5 and FR 95, FR 25 and FR 75, and FR 50 and FR 50 components. Acute doses of cocaine and morphine initially were given in an ascending series (beginning with 0.56 mg/kg) until responding was reduced to near-zero levels. Chronic (daily) dosing with a dose that reduced, but did not eliminate, responding then occurred until response rates stabilized. Finally, postchronic dose-response determinations were conducted. Both cocaine and morphine reduced response rates at all FR values. Tolerance was consistently observed to the effects of morphine, but not to those of cocaine. With both drugs the degree of tolerance observed did not vary as a function of FR value. These findings, like those obtained under PR schedules, indicate that ratio size does not always modulate drug tolerance. A behavioral momentum analysis of drug action appears to account for whether or not ratio size modulates tolerance, and such an analysis is provided.

Animals↗

Flow cytometric assessment of human peripheral blood mononuclear cells in response to a coccidioidal antigen.

The in vitro responses of peripheral blood mononuclear cells (PBMC) from healthy immune and non-immune donors were assessed by flow cytometry after incubation with the coccidioidal antigen toluene spherule lysate (TSL). After 120 h of incubation with 100 microg ml(-1) of TSL, expression of the activation markers CD69, CD25 and human leukocyte antigen-DR were all significantly increased in CD3+ lymphocytes from immune donors compared to non-immune donors (P < 0.03 for all). No differences in the surface expression of the costimulatory molecules CD28, CD152 or CD154 was seen between immune and non-immune donors after either 24 or 120 h of TSL incubation, nor were differences detected in the expression of the B7 ligands CD80 or CD86 on CD14+ monocytes. The percent of CD3+ lymphocytes expressing intracellular interferon-gamma (IFN-gamma) was significantly increased in immune compared to non-immune donors and was further increased by the addition of 10 ng ml(-1) of human recombinant interleukin (IL)-12 (P < 0.05 for both). Both CD4+ and CD8+ lymphocytes contributed to IFN-gamma production. These data indicate that coccidioidal antigen stimulation of lymphocytes from healthy immune donors leads to specific expression of activation molecules and production of intracellular IFN-gamma. Addition of IL-12 leads to a significant recruitment of cells producing IFN-gamma among immune donors.

Abatacept↗

A major cell surface antigen of Coccidioides immitis which elicits both humoral and cellular immune responses.

Multinucleate parasitic cells (spherules) of Coccidioides immitis isolates produce a membranous outer wall component (SOW) in vitro which has been reported to be reactive with antibody from patients with coccidioidal infection, elicits a potent proliferative response of murine immune T cells, and has immunoprotective capacity in a murine model of coccidioidomycosis. To identify the antigenic components of SOW, the crude wall material was first subjected to Triton X-114 extraction, and a water-soluble fraction derived from this treatment was examined for protein composition and reactivity in humoral and cellular immunoassays. Protein electrophoresis revealed that the aqueous fraction of three different isolates of C. immitis each contained one or two major glycoproteins (SOWgps), distinguished by their molecular sizes, which ranged from 58 to 82 kDa. The SOWgps, however, showed identical N-terminal amino acid sequences, and each was recognized by sera from patients with C. immitis infection. Antibody raised against the purified 58-kDa glycoprotein (SOWgp58) of the Silveira isolate was used for Western blot and immunolocalization analyses. Expression of SOWgp was shown to be parasitic phase specific, and the antigen was localized to the membranous SOW. The water-soluble fraction of SOW and the purified SOWgp58 were tested for the ability to stimulate proliferation of human peripheral monocytic cells (PBMC). The latter were obtained from healthy volunteers with positive skin test reaction to spherulin, a parasitic-phase antigen of C. immitis, and from volunteers who showed no skin test reaction to the same antigen. The SOW preparations stimulated proliferation of PBMC from skin test-positive but not skin test-negative donors, and the activated cells secreted gamma interferon, which is indicative of a T helper 1 pathway of immune response. Results of this study suggest that SOWgp is a major parasitic cell surface-expressed antigen that elicits both humoral and cellular immune responses in patients with coccidioidal infection.

Amino Acid Sequence↗

Direct service staff and their perceptions of psychotropic medication in non-institutional settings for people with intellectual disability.

Previous studies have surveyed a variety of service providers in school and institutional settings, and reported a pervasive lack of education and training with regard to the use of psychotropic medication in people with intellectual disability. Because an increasing number of people with intellectual disability are living in the community and since many of these people receive psychotropic medications, the present study extended research in this area by surveying direct service staff to determine their perceptions, knowledge and opinions with regard to the use of psychotropic medication in non-institutional settings for individuals with developmental disabilities. Consistent with the findings of previous studies, a majority of the 334 respondents in the present study reported that they had not received adequate training in the area of drug treatment The knowledge and skills deficits of direct service staff appear to represent a significant barrier to the appropriate monitoring and management of pharmacotherapy for individuals with intellectual disability. Therefore, a systematic training programme to educate direct service staff about psychotropic medication needs to be designed, implemented and disseminated on a broad scale.

Attitude of Health Personnel↗

In vitro modulation of proliferation and cytokine production by human peripheral blood mononuclear cells from subjects with various forms of coccidioidomycosis.

Using peripheral blood mononuclear cells (PBMC) from individuals with or without coccidioidal delayed-type hypersensitivity (DTH), we examined and attempted to modulate the in vitro responses of PBMC from various donors to the coccidioidal antigen toluene spherule lysate (TSL). Among healthy DTH-positive donors, 100 ng of human recombinant interleukin-10 (IL-10) per ml suppressed both PBMC proliferation (P = 0.01) and gamma interferon (IFN-gamma) and IL-12 production (for both, P < 0.05). In vitro proliferation and production of IFN-gamma and IL-12 by PBMC were significantly higher in DTH-positive donors with active coccidioidomycosis than in healthy, nonimmune controls (P < 0.05) but not in active DTH-negative donors with or without human immunodeficiency virus infection (for both, P > 0.05). Human recombinant IL-12 increased IFN-gamma production by PBMC from active, DTH-positive donors (P = 0.01) but not by PBMC from DTH-negative groups. For healthy DTH-positive donors, the median antigen-reactive cell frequency per 10(5) PBMC was 3.7, compared to 1.7 in DTH-negative donors with active coccidioidomycosis (P = 0.03). These data indicate that the in vitro TSL response is highly dependent on coccidioidal DTH. Not only do PBMC from individuals with DTH appear to respond to TSL, but their response can be modulated in vitro with either IL-10 or IL-12. On the other hand, PBMC from DTH-negative individuals do not respond in vitro to TSL and their response is not modulable, suggesting a lack of antigen response.

Adult↗

Drug abuse in persons with mental retardation: a review.

The literature on drug abuse by people with mental retardation, a real, but largely ignored problem, was reviewed. Topics addressed were (a) the prevalence of drug use, (b) the drug-related problems characteristically encountered by this population, (c) the special vulnerabilities of people with mental retardation, (d) the treatment programs used with (and appropriate for) people with mental retardation, and (e) the status of drug abuse prevention and drug education for this population. Controlled research dealing with the genesis, treatment, and prevention of drug abuse among people with mental retardation is essentially nonexistent, but badly needed.

Alcoholics Anonymous↗

Using self-management procedures to improve the productivity of adults with developmental disabilities in a competitive employment setting.

This study describes the use of self-management procedures, similar to those proposed by Lagomarcino, Hughes, and Rusch (1989), to improve the productivity of 2 women with mild mental retardation who worked in restaurants. Substantial improvements were observed as a function of treatment, and the procedures were deemed acceptable by the participants, their coworkers, and their supervisors.

Adult↗

[Patient knowledge concerning anesthesia general practice and the responsibilities of the anesthetist].

In two Austrian university hospitals 104 patients were interviewed on the basis of questionnaires about their knowledge of the role of anaesthetists. Although 93% of the Patients considered anaesthesists to be physicians, major deficits were found regarding the knowledge about the spheres of activities of anaesthetists. 60% of the respondents confined the anaesthetist to the operating theatre. Only 55% considered the anaesthetist responsible for their safe recovery from anaesthesia. Previous anaesthesia showed to have no influence on the knowledge of anaesthesia practice and the role of anaesthetists. To current practice of informing the patient calls for improvement and new approaches. In addition to this further evaluation work on the influence of the mass media and public knowledge about anaesthesia and the anaesthetists' role should be undertaken.

Adolescent↗

Cytokine production by peripheral blood mononuclear cells in human coccidioidomycosis.

The production and mRNA expression of the cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-4, -10, and -12 by peripheral blood mononuclear cells (PBMC) after incubation with the coccidioidal antigen toluene spherule lysate (TSL) from various subjects were measured. The IFN-gamma concentration in PBMC supernatants incubated for 72 h from 8 subjects with disseminated coccidioidomycosis was significantly less than that from 7 healthy, coccidioidal-immune subjects (P = .015). No differences were seen among the subject groups in the concentrations of IL-4, -10, or -12. By use of competitive polymerase chain reaction, PBMC from subjects with disseminated coccidioidomycosis also expressed less mRNA for IFN-gamma and IL-12 than did cells from healthy, immune subjects. These data suggest that patients with disseminated coccidioidomycosis have a diminished T helper lymphocyte type 1 response.

Base Sequence↗