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Biomedical subjects

M Keane

Publications and source records attributed to M Keane.

At least 19 recordsLinked to original sources
PubMed1993

Neuropsychopharmacological profile in rodents of SR 57746A, a new, potent 5-HT1A receptor agonist.

The effect of the 5-HT1A agonist SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl))-1,2,5,6 tetrahydropyridine hydrochloride), was evaluated in a variety of psychopharmacological tests in rodents. In the approach-avoidance conflict test in rats, orally administered SR 57746A significantly increased punished responding at doses as low as 3 mg/kg, while unpunished responding was only reduced at 30 mg/kg. SR 57746A was active for at least 4 hours in this test. SR 57746A significantly antagonised the lithium-induced taste aversion in rats at doses of 3 and 10 mg/kg po. In staircase test in mice, SR 57746A reduced rearing at doses which did not reduce the number of steps climbed. In the two-compartment exploratory model in mice, SR 57746A increased the latency to the first entry into the dark compartment (at 2 to 8 mg/kg po), and reduced the time spent in the dark compartment (at 8 mg/kg po), but had no effect on the total number of transitions. SR 57746A potently reduced aggressive behaviour in isolated mice, the dose of 1 mg/kg po produced over 80% inhibition of fighting in this test. SR 57746A was also active in the behavioural despair test of depression in mice and rats, and reversed learned helpless behaviour in rats. SR 57746A was also active in the behavioural despair test of depression in mice and rats, and reversed learned helpless behaviour in rats. SR 57746A dose-dependently generalised to the cue produced by 8-OH-DPAT in rats, but produced only a very weak serotonergic syndrome. Like 8-OH-DPAT and ipsapirone, SR 57746A reduced body temperature in mice, but only at a high dose (10 mg/kg po). SR 57746A reversed haloperidol-induced catalepsy in rats with an ED50 of 3.85 mg/kg po, but was unable to antagonise the stereotypy induced by apomorphine in this species. SR 57746A was inactive or only very weakly active in a series of tests typical of benzodiazepine-like activity, including antagonism of pentetrazol-induced seizures, reduction of muscle tone and locomotor activity, impairment of motor co-ordination, and potentiation of the effects of centrally-acting sedative-hypnotics. SR 57746A was also inactive as an analgesic in the PBQ writhing test. Thus, SR 57746A is active in a number of tests indicative of 5-HT1A receptor stimulation in vivo, and, more particularly, in a number of tests predictive of anxiolytic, anti-aggressive and antidepressant activities. SR 57746A is as potent as diazepam in anxiolytic tests, and more potent than imipramine in antidepressant tests, whereas it is devoid of neuroleptic potential. In view of this profile of activity, SR 57746A merits evaluation as a potential anxiolytic and antidepressant in humans.

Aggression↗
PubMed1992

Oral etoposide in small cell lung cancer.

Small cell lung cancer (SCLC) accounts for 25% of all cases of lung cancer diagnosed in the United States. The sensitivity of SCLC to chemotherapy offers good prospects for prolonged remission and long-term survival. Over the last decade, however, the overall response rate and median survival in SCLC patients have remained essentially unchanged. Single-agent intravenous (IV) etoposide has proven to be among the most active drugs for the treatment of SCLC. Oral or oral plus intravenous etoposide has been used in many combination chemotherapies. Studies demonstrating the schedule dependency of etoposide suggest that optimum results would be achieved if the total were administered over a minimum of 5 days. Given in such a schedule, oral etoposide has been shown to be effective in unfit or elderly (> 70 years of age) patients with SCLC, who represent 25% to 30% of the total SCLC population. Prolonged etoposide administration has achieved efficacy comparable with that attained in 5-day schedules, but with notable toxicity. Moreover, the value of dose intensity in single-agent and combination regimens employing etoposide has recently been questioned. New therapeutic strategies are clearly needed to increase the response rate, to prolong survival, and to improve quality of life in SCLC patients.

Administration, Oral↗
PubMed1991

Acceptance vs. rejection: nursing students' attitudes about mental illness.

The influence of a psychiatric nursing course on BSN students' attitudes toward mental illness was the subject of quasi-experimental research. Attitude theory was the conceptual framework for the study. The Opinion about Mental Illness (OMI) questionnaire was given to a group of nursing students before and after an eight-week course. Half of the students took the course, the other half served as a comparison group. Nursing students taking the course changed more than the control group on authoritarianism and interpersonal etiology but expressed higher stereotypical attitudes.

Attitude↗
PubMed1991

Beliefs about mental illness in a culturally diverse nursing student population: implications for education and practice.

The effects of a psychiatric nursing curriculum on a culturally diverse nursing student population was investigated using Cohen and Streuning's factor analyzed Opinions About Mental Illness questionnaire. Statistical analysis revealed that the experimental subjects (N = 118) showed change on four out of five selected attitude dimensions. Cultural variables (ethnic group, length of time in the US and political affiliations) corresponded with mental illness attitudes. Length of time in the US had a significant effect on two factors--Authoritarianism and Stereotyping.

Attitude to Health↗
PubMed1989

Growth factor production and requirements during the proliferative response of human T lymphocytes to anti-CD3 monoclonal antibody.

Anti-CD3 was administered with three different accessory stimuli to purified populations of human T cells. Sepharose conjugated anti-CD3, monocytes, and PMA each could induce the p55 component of the IL-2R as well as responsiveness to exogenous IL-2. Sepharose anti-CD3 did not induce IL-2, although the levels of IL-2 protein and mRNA were 10 to 30 times higher with PMA than with monocytes. Despite these differences in IL-2 production, the amount of DNA synthesis and the number of lymphoblasts were comparable when monocytes or PMA were used as the accessory stimulus, and the responses were equally sensitive to inhibition by an anti-IL-2R antibody. To pursue the functional relevance of the "supraoptimal" levels of IL-2 that are induced by PMA, anti-CD3-induced lymphoblasts were isolated free of monocytes and challenged with lymphokines. It could be shown that 1) the small amounts of IL-2 in the monocyte-T cell conditioned medium would drive DNA synthesis, but that 2) higher levels of IL-2 (20 to 100 U/ml) were needed to induce IFN-gamma, as well as the mRNA for IL-4 and the p55 IL-2R. We suggest that the capacity to produce high levels of IL-2, as seen with PMA, is required under physiologic conditions for two reasons: to up-regulate the IL-2R when small amounts of Ag rather than large amounts of anti-CD3 are ligands for the T cell, or to induce the release of lymphokines like IL-4 and IFN-gamma from sensitized lymphoblasts.

Antibodies, Monoclonal↗
PubMed1989

Bronchoalveolar lavage plasmacytosis in a patient with a plasma cell dyscrasia.

A patient with serum monoclonal gammopathy, Bence-Jones proteinuria, and bone marrow plasmacytosis underwent fiberoptic bronchoscopic study for evaluation of interstitial lung disease. Bronchoalveolar lavage fluid contained 47 percent plasma cells, which were monoclonal by immunoperoxidase staining. This is the first time BAL plasmacytosis has been demonstrated in a patient with a plasma cell dyscrasia.

Aged↗
PubMed1988

Evidence that cyclosporine inhibits cell-mediated immunity primarily at the level of the T lymphocyte rather than the accessory cell.

The inhibitory effects of CsA in cell-mediated immunity are well known. There is controversy about whether CsA directly inhibits the function of accessory cells as well as T lymphocytes. We have used northern blotting to compare the effects of CsA on several human monocyte and T cell mRNAs, and we have performed "CsA-pulsing" experiments to separately evaluate the effect of the drug on accessory and T cells during lymphocyte mitogenesis. CsA blocked the induction of several lymphokine mRNAs in stimulated T cells including IL-2, IFN-gamma, and IL-4. CsF, an analog that is ten times less active than CsA as an immunosuppressant, was some ten times less active in inhibiting lymphokine gene expression in culture. CsA and CsF had little effect on the mRNA for the 55 KD low-affinity IL-2 receptor, but there was decreased expression of the TAC antigen. Exogenous IL-2 reversed the CsA-mediated suppression of cell proliferation and TAC expression. This indicates that the primary block with cyclosporines is at the level of lymphokines rather than lymphokine receptors. CsA did not reduce the levels of several monocyte mRNAs, however. These included c-myc and Il-1 alpha/beta mRNAs, induced by PMA plus Con A, as well as HLA-DR alpha and gamma-Ip10 mRNAs in monocytes treated with IFN-gamma. When monocytes were pulsed with CsA, there was no reduction in their subsequent accessory function for anti-CD3 and lectin responses. T lymphoblasts pulsed with CsA, however, did not proliferate or release growth factor. Likewise in the primary MLR between dendritic cells and T cells, dendritic cells were not impaired following pulsing with CsA, whereas treated T cells made 70% less IL-2. The primary site of action of CsA therefore seems to be the production of lymphokines by T lymphocytes.

Antigen-Presenting Cells↗
PubMed1985

A new device for delayed hypersensitivity skin testing.

A new device for assessment of delayed cutaneous hypersensitivity using seven standardized antigens (Multitest CMI) was compared to conventional intradermal testing with two recall antigens in 83 patients referred for nutritional support. Sixteen patients (19.3%) were anergic to Multitest CMI while four (4.8%) were anergic to conventional testing. Patients anergic to Multitest CMI had a higher complication (intraabdominal abscess, prolonged ileus, sepsis, pneumonia) than those who were immunocompetent by this test suggesting a group at greater risk. This interpretation is consistent with an increased specificity of Multitest CMI over conventional testing in the identification of clinically important anergy.

Adult↗
PubMed1982

Fetal cytotoxic antibodies to maternal T-lymphocytes: a possible mechanisms for maternal tolerance of the fetal allograft.

The absolute numbers of B lymphocytes and of total and "active" T lymphocytes in peripheral venous blood (Mv) from 15 females at the time of normal term deliveries were found to be significantly less (p less than 0.001) than in the fetal umbilical vein (Uv) or artery (Ua) or in the peripheral blood of 75 normal nonpregnant controls (Cv), suggesting that maternal cellular immunity at term is lowered. In 19 umbilical artery samples, titers of lymphocytotoxic antibodies (Cyt), expressed as the mean log of reciprocal titer values, were significantly higher (p less than 0.01 in each case)( than in matched maternal samples, against the following cell types: Maternal T cells (7.1 in Ua vs 1.21 in Mv sera); maternal B cells (3.23 vs 1.58); T cells (4.41 vs 1.38) but not B cells from other females at delivery; autologous T cells (2.9 vs 1.0); autologous B cells (1.88 vs 0.69); T (5.39 vs 0.81) and B (2.80 vs 1.25) cells from the paired Uv; T (3.78 vs 0.62) and B (2.64 vs 0.77) cells from the Uv of other newborn infants; and T (4.19 vs 2.0) but not B cells from controls (Cv). The highest Cyt titers in the umbilical artery samples were against maternal T lymphocytes. Immunofluorescence studies indicated that the Cyt antibodies were primarily IgG. Absorption of 13 other Ua sera with maternal T cells eliminated with Cyt activity against both Mv and Cv T cells; absorption with Cv T cells eliminated the reaction against Cv T while reducing cyt titres to Mv T lymphocytes. We conclude that the fetus produces lymphocytotoxic antibody specifically directed against maternal T lymphocytes, in addition to antibody against T lymphocytes of other adults.

Adult↗
PubMed1980

Immunological studies of human placentae: complement components in immature and mature chorionic villi.

The localization and distribution of complement components in term and pre-term normal human placentae have been studied by using haemadsorption and immunofluorescence experiments. The components Clq, C4, C5, C6 and C9 were identified in characteristic locations. Receptors for C3 and C4 were not found. Complement was associated with certain stromal cells, areas of fibrinoid necrosis within the trophoblastic mantle, and in the walls and endothelia of foetal stem vessels. Activation of the complement system on trophoblastic basement membranes (TBM) did not appear to involve the early reacting components of the classical pathway of complement activation, because C1q, C4 and C2 could not be identified on TBM. The C6 component was identified within cytoplasmic granules of foetal stem vessel endothelia, suggesting that it may be synthesized by these cells. These findings put forward the possibility that complement may play an immunobiological role in the materno-foetal relationship during normal human pregnancy.

Basement Membrane↗
PubMed1977

Proficiency testing for the radioimmunoassay of carcinoembryonic antigen. A one-year report.

Forty-three laboratories participated in an interlaboratory testing program offered by the College of American Pathologists for the radioimmunoassay (RIA) of carcinoembryonic antigen (CEA). Thirty correctly reported a sample with 1.9 ng of endogenous CEA per ml as less than 2.5 ng. For samples with added exogenous CEA at the 5.4 ng/ml level, 24 laboratories reported too low and six too high (more than 2 SD beyond the targe value). At the 8.9 ng/ml concentration, three laboratories underestimated the CEA, while 18 overestimated the sample's concentration. A similar proportion of the laboratories performed in the same manner when estimating CEA at a target concentration of 15.9 ng/ml (five underestimating and 27 overestimating the concentration). Although individual variations were large, the majority of participating laboratories can reliably distinguish normal concentrations of CEA from moderate, intermediate and large elevations.

Carcinoembryonic Antigen↗
PubMed1974

"New horizons".

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Economics, Nursing↗